5^th Hellenic Congress of Oncology

Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of “liquid biopsy” and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy.

The aim of this study was to investigate the feasibility of ctNA analysis in everyday practice, using a sensitive NGS approach in patients with NSCLC. The plasma mutation distribution was calculated in newly diagnosed patients as well as in patients at progression on treatment with EGFR TKIs.

Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms.

At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p. T790M mutation, with NGS being able to detect this mutation in three 3 additional patients.

This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.

NENs are rare tumors and can grow in almost all tissues. Regardlesshistological, molecular and imaging characteristicsthat are indicative of the primary origin, a significant percentage remain of unknownprimary.

A prospective observational study was conducted by HeSMOin Oncology Departments to register patients with histologically confirmed NEN. Inclusion criteria were: a) residencyin Greece, b) treatment by medical Oncologist in Greece, c) Age > 14 years and d) signed informed consent.

169 patients (pts) diagnosed with NENs were enrolled of 6 centers from 1/2012to 12/2018. The female to maleratio (90/79) was 1.1 and the age range was 19–89 years (ys). The higher incidence concerned the age range 60–69 ys (30.1%; 51 pts), followed by 70–79 ys (21.8%; 37pts) and 50–59 ys (20.7%; 35pts). The most frequently primary sites were lung (28.4%; 48 pts), pancreas (15.95%; 27pts) and stomach (15.38%; 26 pts). Less frequent were ileum/small intestine (6.5%;11 pts), cecum (4.73%; 8pts), colon (2.36%; 4pts), rectum (1.77%; 3pts) and duodenum (0.6%; 1pt). Less common primary sites were in 20.11% (34 pts) whereasin4.13% (7pts) they were unknown primary tumors. The distribution of stages at diagnosis, were early stage in 20%, locally advanced in 48% and metastatic in 32% pts. Results regarding histology and treatments will be presented as well.

These are preliminary results from the largest prospective NEN registries in Greece. Due to the increased training of NEN specialists in pathology and the improved imaging methods, NENs are increasingly recognized. However, a large percentage of pts are diagnosed in locally advanced or metastatic stages. It is necessary to improve the rates of early diagnosis and identification of NENs.

Cell-free DNA levels are distinctly increased in most patients with prostate cancer (PCA). It is established that a small fraction of the DNA is derived from the tumor itself and epigenetic (DNA methylation) alterations are regularly detected in patients with PCA. The detection of increased DNA levels and tumor-specific DNA methylated sequences may provide diagnostic and prognostic information.

The aim of the present study was to analyze the cfDNA concentrations at different time points and to detect DNA methylation profile of APC and RASSF1A genes, in order to assess the value of these biomarkers for prognosis.

Plasma samples were obtained from 50 patients with metastatic prostate cancer, at the beginning of the first-line treatment (baseline), one month and two months later. Cell-free circulating DNA was isolated from 500 μL of plasma, using a commercially available kit and quantified using a fluorometer. Plasma from 25 healthy individuals was collected and used as a control group. The extracted DNAs were subjected to a sodium bisulfite conversion reaction. Real time methylation specific PCR for each gene was performed.

The median levels of cfDNA in the baseline samples of PCA patients (n = 50) were higher than controls (n=25) but tend to diminish during the different time points. At the baseline APC was found to be methylated at 29/50 (58%) and RASSF1A 32/50 (64%), but no significant alteration at the methylation levels of these two genes was observed at the following time points. In the survival analysis, the group with baseline methylated APC and RASSF1A tend to not reach the median survival point. Furthermore, there were strong positive correlations between Gleeson score APC and RASSF1A methylation (P values <0.04).

These results are promising and further studies in a larger cohort of patients are required to explore the prognostic significance of these markers in metastatic prostate cancer.

The analysis of the molecular profile of tumors is now becoming a reality, mainly due to next-generation sequencing technology (NGS) and can be used to personalize the therapeutic approach in cancer patients.

The present study aimed to investigate the molecular profile results obtained by using a pancancer NGS panel for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1) was also explored.

NGS analysis was conducted using a panel of 161 genes in tumor tissues from 451 cancer patients. Furthermore, analysis of Microsatellite Instability, Tumor mutational burden (TMB) and PD-L1 expression analysis was performed in 201 cases.

451 patients with various types of cancer were analyzed, such as pancreas, lung, breast, colon, ovary, prostate, brain, and others. A total of 594 pathogenic mutations in 91 genes were detected in 76.5% of the patients analyzed. 7.10% of the patients harbored a mutation in a gene of homologous recombination, which could be used as a predictive biomarker of response to treatment with PARP inhibitors. 33.37% of patients had a mutation in a gene associated with on label or off label treatment, while 42.13% of the findings could give them access to a clinical trial. Regarding immunotherapy markers, microsatellite instability was detected in 3.89% and PDL1 positivity in 30.49% of patients. TMB showed a significant variation between patients, with a minimum value of 1.9 and a maximum of 82.8 mutations/MB. In addition, as expected, the median TMB value varied among cancers with the lowest value being observed in sarcomas and the highest in NSCLC.

The multigene NGS analysis allowed the simultaneous analysis of predictive biomarkers in both targeted therapies and immunotherapy, identifying a clinically important finding in 75.5% of patients tested.

Extramammary Paget's disease (EMPD) is a rare intraepithelial carcinoma and accounts for only 6.5% of Paget's disease. It appears as an erythematous plaque and it is usually associated with carcinoma of the apocrine sweat glands (primary) or colorectal and urogenital cancer (secondary). Although it usually develops slowly, in 20% of cases it can progress into invasive carcinoma and give lymph node and distant metastases. To date, various chemotherapeutic regimens have been tested in metastatic EMPD, as well as drug combinations including trastuzumab in HER2 (+) tumors, but the prognosis generally remains poor, with a median survival of approximately 1.5 years.

The description of a rare case of metastatic EMPD and the review of bibliographic data concerning the therapeutic approach.

A 67-year-old woman was diagnosed with non-invasive perineal Paget's disease 10 years ago. Due to local recurrence, she underwent vaginectomy 4 years ago and since then follow-up biopsies were performed every 6 months because of positive surgical margins. 1.5 years ago, she developed swelling and redness of the lower left extremity related to lymphedema. Diagnostic imaging showed a solitary liver metastasis and pathologically enlarged inguinal, iliac and paraaortic lymph nodes. An inguinal lymph node biopsy revealed a poorly differentiated adenocarcinoma CK7 and CK20 positive, CDX2, PAX8, uropladin, TTF1, P63, HER2 negative, consistent with the known Paget's disease. Further staging with mammography, breast MRI, cystoscopy and colonoscopy did not reveal any pathological findings. Eventually the patient began chemotherapy with docetaxel and carboplatin based on data showing docetaxel activity as monotherapy or in combination with S-1. Serial imaging tests after 8 cycles of treatment showed an ongoing response with reduction in the size of the liver lesion, disappearance of the enlarged lymph nodes and improvement of the lymphedema. Since the last 3 months the patient has been taking a treatment break and she remains in good clinical condition.

Metastatic EMPD is a carcinoma with a poor prognosis and very few data exist on its treatment. The case of our patient shows that the combination of docetaxel/carboplatin could be added to the therapeutic quiver for this rare disease.

The purpose of this prospective multicenter observational study was to describe the clinicopathological and treatment characteristics of patients (pts) with pancreatic adenocarcinoma (PC) in Greece. Secondarily, the study aimed to collect data about the effectiveness of the local and systemic therapies in terms of survival parameters.

Clinicopathological and treatment data were prospectively collected from 2/2016 to 2/2018 from the files of 200 pts in 20 participating centers. Disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method.

Median age at PC diagnosis was 65 years (range 17–84) and male-to-female ratio was 1.2. Median body mass index was 23.8 (range 14.2–37.8). PS(ECOG) was 0 in 88 (44%) pts. Baseline median serum CA19-9 levels were 370 U/mL (range 0.6–1,000,000). Rare histological subtypes were acinar cell carcinoma in 3 (1.5%) pts, adenosquamous carcinoma in 3 (1.5%), squamous cell carcinoma in 1 (0.5%) and mucinous carcinoma in 1 (0.5%). Seven pts (3.5%) were diagnosed with stage I, 11 (5.5%) with stage IIA and 35 (17.5%) with stage IIB. Of them, 41 (77.4%) pts received adjuvant and 2 (3.8%) neoadjuvant chemotherapy. Median DFS was 24.9 months (95%CI, 16.9–33.0) and median OS 40 months (95%CI, 25.3–54.6). Also, 24 pts (12%) were initially diagnosed with stage III and 119 (59.5%) with stage IV. Eighty pts with stage IV disease had liver (67.2%), 22 had distant lymph node (18.5%) and 18 had peritoneal metastases/ascites (15.1%), while 49 (41.2%) had metastases in other organs. Of pts with stage III/IV disease, 88 (61.5%) received nab-paclitaxel/gemcitabine, 24 (16.7%) received FOLFIRINOX/XELOXIRI, 16 (11.2%) gemcitabine monotherapy and 13 (9.1%) other regimens. Median PFS was 7.8 months (95%CI 6.5–9.2) for stage III and 7.1 months (95%CI 5.2 – 9.0) for stage IV pts. Median OS was 14.2 months (95%CI 9.2 – 19.2) for stage III and 13.5 months(95%CI 11.5 – 15.4) for stage IV pts.

In this study, we described the status of care of pancreatic cancer in Greece in an attempt to improve the therapeutic standards.

In 2019, European Working Group on Sarcopenia in Older People (EWGSOP2) revised the consensus criteria on definition and diagnosis for sarcopenia.

To estimate the prevalence of sarcopenia by applying the recently revised definition criteria in a sample of newly diagnosed elderly patients with metastatic tumors prior to treatment initiation.

Patients >65 years old, referred for induction/first line therapy were eligible. Handgrip Strength (HGS) was used to estimate muscle strength and skeletal muscle index (SMI) from computed tomography in the 3rd lumbar vertebra (L3) was used to estimate muscle mass (muscle quantity). Gait Speed Test (GST) was used to assess physical performance status for the assessment of sarcopenia severity.

In total 45 patients (69% men) with mean age [± Standard Deviation (SD)] 77.4 years (± 6.8 years) were evaluated. 42.2% of the patients (n=19) were classified as sarcopenic. Sarcopenia severity was estimated for 34 patients for whom gait speed test was available, with 23,5% of the sample (n=8) being severe sarcopenic. Patients mean values (±SD) for HGS, SMI and GST was 25,6 kg (± 9.3), 42,9 cm²/m² (± 6.9) and 0.87 m/sec (± 0.3) respectively. From the confounding factors that were analyzed, older age significantly affected the prevalence of sarcopenia (p value =0.002). Survival analysis showed that non-sarcopenic patients achieved a significantly higher overall survival compared with sarcopenic patients (12.9 months vs 6.0 months), p = 0.02. Based on multivariate cox regression analysis presence of sarcopenia increased the risk of death by 68% after adjustment for age and tumor site (HR 0.32 95% CI 0.12–0.87, p = 0.02).

Prevalence of sarcopenia, using the international consensus definition criteria according to EWGSOP2, is high in elderly patients with metastatic cancer already at the time of the diagnosis. Presence of sarcopenia is independently associated with shorter overall survival.

CAT is the 2^nd leading cause of death in oncology patients and there is need for thrombosis management across the natural history of cancer because of its dynamic nature. Anticoagulant therapy is the cornerstone of prevention and treatment, since thrombosis interferes with cancer treatment, increases health care resource utilization, imposes emotional and economic burden.

A prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high risk for thrombosis, active cancer patients who received thromboprophylaxis are enrolled after signing informed consent.

Preliminary results are collected from 17 oncology departments. From the 272 enrolled patients, 176 (64.7%) have completed second visit (3–4 cycles of anticancer treatment). Primary cancers included: lung 31.3%, pancreas 26.1%, colorectal 13.6%, gynecological cancers 10.2%, stomach 7.8%, bladder 6.3%, and others. 75.6% of the patients had metastatic disease. 1/3 of the patients were smokers or ex-smokers and 33% underwent surgery. Most of patients (65.9%) were at 1^st line treatment and 17.6% at 2^nd line. The vast majority (90.3%) were treated with High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as cisplatin etc. Regarding Khorana score, 65.1% of patients had ≥2. In particular, 86.7% of patients with Khorana score ≤1 received HRTCAs while 95.4% of patients with score=2. All patients received thromboprophylaxis, specifically: 93.0% tinzaparin, 5.2% fondaparinux and 1.8% other (enoxaparin, bemiparin) with average duration 5.3±3.1 months. 67.1% of patients received higher than standard prophylactic doses.3 patients (1.7%) experienced thrombotic events (2DVT and 1 PE). These 3 patients had metastases and were treated with HRTCAs. Five grade 1 bleeding events were reported (2.8%).

Thromboprophylaxis of CAT is both safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs along with drug-drug interactions, increase the LMWHs usage often in higher than prophylactic doses in CAT management.

The aim of the current study was to examine the prognostic significance of inflammatory biomarkers in patients with locally advanced or metastatic pancreatic adenocarcinoma undergoing first-line chemotherapy with nab-paclitaxel and gemcitabine.

To investigate the prognostic role of infiammatory biomarkers in patients with advanced pancreatic adenocarcinoma undergoing first-line chemotherapy.

In the current cohort study data from 57 patients were retrospectively collected. All patients had histologically or cytologically confirmed pancreatic locally advanced or metastatic adenocarcinoma and were treated with first-line nab-paclitaxel and gemcitabine from July 2014 to February 2020. White cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH), monocyte (MONO) and platelet (PLT) blood levels during the last two days before the start of the first cycle of chemotherapy were measured. Median neutrophil to lymphocyte ratio (NLR), median monocyte to lymphocyte ratio (MLR), median systemic inflammatory response index (SIRI=NEUT × MONO/LYMPH) and median platelet-to-lymphocyte ratio PLR were calculated.

Median age was 67 years (range, 43–81), while 29 (50.9%) male and 28 (49.1%) female patients were included in the study. PS (ECOG) was zero in 32 (56.2%) patients, one in 21 (36.8%) and two in 4 (7.0%) patients. Forty seven (82.5%) patients had stage IV and 10 (17.5%) had stage III disease. After a median follow-up of 20.6 months (range, 1.1–37.3), 48 (84.2%) developed progressive disease and 41 (71.9%) died of disease. Median progression-free survival (PFS) was 5.1 months (95%CI, 3.6–6.6) and median overall survival (OS) was 9.9 months (95%CI, 6.2–13.6). Patients with stage III had median PFS 9.2 months (95% CI 3.0–15.4), while stage IV patients had median PFS 5.1 months (95% CI 3.3–6.9), with statistically significant difference (p=0.011). Increasing NLR levels were correlated with poorer PFS (HR 1.10, 95% CI 1.01–1.20, p=0.033) but not with OS (HR 1.07, 95% CI 0.98–1.18, p=0.139). Cox proportional hazard models confirmed that higher NLR levels were independently associated with poorer PFS (HR 1.14, 95% CI 1.03–1.25, p=0.009) and poorer OS (HR 1.11, 95% CI 1.01–1.23, p=0.037). Also, PS ECOG 1–2 (compared to PS 0) showed independent prognostic significance for PFS (HR 2.51, 95% CI 1.34–4.69, p=0.004) and OS (HR 3.00, 95% CI 1.53–5.76, p=0.001). In contrast, tumor stage did not demonstrate independent prognostic significance. Exploratory analysis examined the prognostic significance of different NLR cutoffs (by increasing the NLR value by 0.5) for PFS and OS. The best cutoff was NLR ≥4 vs. <4. Median PFS of patients with NLR ≥4 was significantly shorter compared to NLR <4 (3.1 vs. 6.0, respectively, p=0.005). Also, median OS of patients with NLR ≥4 was significantly shorter compared to NLR <4 (5.7 vs. 11.5, respectively, p=0.025). Subgroup analysis showed that patients with PS ECOG 0 and NLR <4 had the longest median PFS compared to the group with PS ECOG 1–2 or NLR ≥4 and the group with PS ECOG 1–2 and NLR ≥4 (7.1 vs. 5.1 vs. 2.0, respectively, p<0.001) and longest median OS compared to the group with PS ECOG 1–2 and NLR ≥4 (14.0 vs. 8.2 vs. 5.7, respectively, p<0.001).

The present retrospective analysis revealed clinically meaningful subgroups with distinct prognoses according to inflammatory biomarkers and performance status, irrespective of tumor stage, in patients with advanced pancreatic adenocarcinoma treated with first-line nab-paclitaxel – gemcitabine.

Cutaneous squamous cell carcinomas (SCC) with distant metastases are rare, yet more common than metastatic basal cell carcinomas. The average risk of distant metastatic disease is only 0,4%, risk of lymph node metastasis is 3,7%, and risk of disease-specific death is 2,1%. There is no standard treatment, and unfortunately, evidence regarding systemic therapy is limited.

We aim to present a patient with metastatic SCSC that was treated with cemiplimab, a new monoclonal antibody that targets checkpoint inhibitor PD-1.

A 59-year-old female patient was diagnosed in December 2018 with SCSC of the right sole, on a site-specific sunburn during childhood. PET-CT revealed enlarged inguinal lymph nodes but no other sign of distant metastasis. The patient underwent wide local excision of the primary tumour and regional lymph node dissection. The pathology revealed a T3N2bG1-high risk SCC (40mm in max diameter, high mitotic rate, Breslow 12 mm, Clark IV, R0, ulceration and 2/11 lymph nodes were positive < 3cm). She was treated with 50Gy of adjuvant radiotherapy (25fr × 2Gy). One month later, the CT scans showed multiple pulmonary metastases, and she received first-line platinum-based treatment (carboplatin/5FU/paclitaxel). The best response was stable disease, which lasted four months. Subsequently, she presented with local recurrence on her right calf, on a previously irradiated area. The new lesion was excised with clear margins (SCSC 17mm, gr. II, Breslow 5,9mm, Clark IV, high mitotic rate). Due to concurrent disease progression in lung metastases, we started second-line treatment with cemiplimab 350mg q21d. After three cycles, the patient was hospitalized with pneumonitis gr. III that required oxygen supply and steroids intravenously. After recovery, we restarted cemiplimab at the initial dose, and recent imaging revealed partial response to treatment (PR).

Metastatic SCSC are rare conditions, and evidence from prospective phase III studies regarding systemic therapy is limited. This case is in concordance with early phase clinical trials showed that treatment with cemiplimab is feasible with potentially positive results.

Michael R. Migden et al, PD-1 blockade with Cemiplimab in Advanced Cutaneous Squamous Cell Cancer, NEJM, 26 July 2018

SCSC: squamous cell skin cancer, PD-1: programmed death 1, PR: partial response

Samarium-153 is a radionuclide that is selectively bone bound to the skeleton and especially in areas with intense osteoblastic activity. The result is effective relief of bone pain in patients with multiple painful osteoblastic skeletal metastases. Intermediate response to pain is reported in 80% of patients with breast cancer and 56–74% with prostate cancer.

The investigation of possible antineoplastic activity of ¹⁵³Sm EDTMP in bone metastases.

Patients with painful bone metastatic disease for at least 3 months, without having received bone targeted therapy or radiotherapy. Analgesic treatment concerned standard analgesic regimens and / or NSAIDs. Thereafter, values shall be recorded before and after each application of the ¹⁵³Sm EDTMP (1mCi/kg) of the following osteoblastic markers, P1CP collagen type I carboxyellate propeptide and P1NP aminofinal collagen type I propeptide. Measurements shall be performed by the ELISA method. To date, seven patients aged 40 to 80 years, ECOG performance status 0–1 with multiple painful bone metastases, have been introduced in the study. Three from Prostate cancer and four from breast cancer.

A comparison of markers of bone metabolism and osteoblastic activity, before and after administration of 153Sm EDTMP, shows in the majority of cases a significant increase in markers indicating repair of bone damage through increased osteoblastic activity.

Despite the small number of patients in this ongoing study, the results suggest an effect of ¹⁵³Sm EDTMP on osteoblasts as well as on cancer cells.

Dysbiosis has been associated with diseases and is of a major public health importance. Can lead to the passage of viable bacteria, their products or their fragments from the intestinal lumen through the mesenteric lymph nodes and other sites, known as bacterial translocation.

To determine if microbial translocation occurs in stage II/III–IV colorectal cancer (CRC) patients and evaluate the usefulness of blood PCR for diagnosis of such translocation. Also to correlate the presence of Toll-Like Receptor and Vitamin D Receptor polymorphisms with the detection of microbial DNA fragments in the blood of CRC patients.

Peripheral blood was obtained from 397 CRC patients (adjuvant n=202 and metastatic n=195) and 32 healthy indviduals. DNA from all subjects was analyzed using PCR for amplification of genomic DNA encoding 16S rRNA, β-galactosidase gene of E. coli, Glutamine synthase gene of B. fragilis and 5.8S rRNA found in C. albicans.

Significantly higher rates of 16S rRNA, β-galactosidase, Glutamine synthase and 5.8S rRNA detection was observed in the pool of CRC patients than the controls (p<0.001). All microbial DNA fragments detected were also significantly associated with the metastatic disease (p<0.001) leading to shorter survival rates (p<0.001). Moreover, individuals with the homozygous mutant alleles of either TLR or VDR gene polymorphisms had significantly higher detection rates of microbial DNA fragments.

The detection of microbial DNA fragments in patients with CRC highlights the role of these microbes in cancer development, progression and therefore in patients’ survival.

Late rectal bleeding has a negative impact to the quality of life of patients with prostate cancer who have received 3D conformal radiation therapy treatment(3D-CRT).

Our aim was to investigate the incidence of rectal bleeding due to radiation therapy for prostate cancer and to correlate rectal bleeding with dosimetric and other factors as treatment with anticoagulants agents.

Sixty-four patients with intermediate and high risk prostate cancer were investigated retrospectively. All received 3D-CRT to a total dose of 7000 cGy in 35 daily fractions. Most of the patients (81.7%) received neoadjuvant and concurrent hormone therapy. Late rectal bleeding toxicity was defined according to EORTC criteria for adverse events (Common Terminology Criteria for Adverse Events v4.0). Clinical factors investigated were the administration of anticoagulants agents and hormone therapy. Dosimetric factors taken into consideration were the V50 and V60 of rectum.

Median time for the appearance of rectal bleeding was 17.4 months with range 9–49 months. From 64 patients, 16 suffered from Grade 1 bleeding which was treated with local administration of sterinoids. Ten patients presented Grade 2 bleeding and only one patient had serious bleeding of Grade 3. All were treated with argon plasma laser coagulation therapy (APC). Eight patients(61,5%) from the eleven with Grade 2 and 3 bleeding had also a second session of APC. None of the patients developed important bleeding after the second session. Four patients that developed grade 2 toxicity were under treatment with anticoagulants agents. During the retrospective analysis of dose volume histograms(DVH)we discovered important differences to the mean value of V60 and V10 between toxicities grades of 0–1 and 2–3. To the 13 patients with rectal bleeding of grade 2 and 3 V50 was between 45–50% and V60 was >35%.

Our results are consistent with international publications and indicate the possible association of grade 2 or 3 rectal bleeding with the intake of anticoagulants agents and radiation dose that rectum receives during treatment(V50–V60.). Hormone therapy was not associated with late toxicity as rectal bleeding.

Paclitaxel induced interstitial pneumonitis is a well-defined hypersensitivity reaction that has been mostly described in cancers of breast and lung. A great percentage of these cases are associated with either concurrent or previous irradiation of the chest, with the latter known as radiation recall pneumonitis.

We present the case of a middle-aged, chemotherapy- and radiotherapy- naïve patient with locally advanced penile cancer, who developed severe pneumonitis shortly during the first course of paclitaxel, ifosfamide and cisplatin administration. We emphasize on the particular “crazy – paving” appearance of pneumonitis on chest CT and the rapid clinical and imaging improvement with high dose steroids.

A 50 year–old male with a recent diagnosis of locally advanced penile squamous cell carcinoma was referred to our department as a candidate for neoadjuvant chemotherapy. After the appropriate premedication dose of dexamethasone, the patient was started on chemotherapy by receiving paclitaxel 175 mg/m² on day 1, ifosfamide 1200 mg/m² and cisplatin 20 mg/m² from day 1 to day 3. However, during the 2^nd day of treatment the patient presented acute dyspnea and nonproductive cough, leading to treatment discontinuation. The symptoms along with hypoxemia were suggestive of rapidly worsening respiratory function, while physical examination revealed bilateral fine crackles. Urgent computed tomography of the chest uncovered a combination of ground glass opacity with superimposed septal thickening, mainly in the upper fields of both lungs. The appearance of these findings is characteristically described under the term “crazy – paving pattern” and accounts for a less common imaging manifestation of drug–induced pneumonitis. Based on other reports and the temporal relationship of onset of symptoms (approximately 24 hours after paclitaxel infusion) paclitaxel was considered as the most likely culprit for interstitial pneumonitis. Prompt administration of high dose corticosteroids (methylprednisolone 2 mg/kg) resulted in quick significant recovery. Indeed, clinical improvement was reflected to the comparative CT scan, 5 days later, that showed remarkable radiological improvement with complete resolution of lesions.

To our knowledge, this is the first report of interstitial pneumonitis attributable to TIP chemotherapy regimen. Clinicians should be aware of the potentially life-threatening pulmonary toxicity following this regimen. Early administration of high-dose steroids seems critical in the successful management of this emergency situation.

Bladder cancer consists the commonest malignancy involving the urinary system with urothelial carcinoma to be the predominant histologic type. It is recorded as the second most common urinary tract malignancy in men and is responsible for more than 80,000 new cases and almost 18,000 deaths yearly. 10–15% of patients appear to have metastatic disease during diagnosis. Bone metastases are not frequent and usually follow other systemic metastases.

The first patient is a 56-year-old male that underwent radical cystectomy. The histological examination revealed a pT4aN0 low differentiated urothelial carcinoma and adjuvant chemotherapy with cisplatin/gemcitabine was administered. Four years later, an histologically confirmed solitary bone metastasis in left ankle was found. The patient received radiotherapy and remained progression free for 3 years before the appearance of new bone metastases in the middle of left tibia and lumbar vertebrae. The second patient is a 58-year-old male with an histological examination obtained after radical cystectomy representing a low differentiated pT3bN0 urothelial carcinoma. According to the new imaging examination performed a month after cystectomy because of continuous left tibia pain, a lytic bone lesion in the middle of the left tibia was discovered and therefore the patient underwent preventive static intramedullary nailing of tibia. The biopsy of this lesion revealed metastatic invasion of bladder cancer while the rest imaging testing remained negative. 1^st line chemotherapy with cisplatin/gemcitabine was administered in combination with lesion radiotherapy with a progression free interval of six months.

According to recent studies, the incidence of bone metastases in patients with bladder cancer is about 5,5%. Nevertheless, it is not clear if searching bone metastases in asymptomatic patients consists a cost effective approach.

Transcribed Ultra-Conserved Regions (T-UCRs) Uc160, Uc283 and Uc346 have been shown that undergo CpG island methylation in their promoter regions, which results in their transcriptional silencing in colorectal cancer (CRC), while they are transcribed in the adjacent non-malignant tissues.

The present study explores the possible alterations in methylation levels of Uc160, Uc283 and Uc346 during CRC development and progression and their clinical significance for CRC patients’ survival.

Promoter methylation of Uc160, Uc283 and Uc346 was detected using methylation-on-beads and real-time quantitative Methylation Specific PCR (qMSP) in 137 CRC and 49 adenoma tissues, as well as in 35 infiltrated lymph nodes and 11 liver and lung metastatic lesions. Their transcription was assessed in representative sample tissues using in situ hybridization. Moreover, T-UCRs mRNA levels were assessed in the colon cancer cell line HT-29 before and after resistance to chemotherapeutics 5-fluorouracil (5-FU) and oxaliplatin.

A gradual increase in methylation levels was observed from hyperplastic polyps to adenomas and in situ carcinomas, while a gradual decrease was observed in infiltrating and metastatic carcinomas (p<0.001 for Uc160 and Uc283, p=0.018 for Uc346). Moreover, methylation levels of Uc160 and Uc283 were positively associated with grade of dysplasia (p=0.034 and p=0.019, respectively). Higher methylation levels of Uc160 were associated with longer overall survival of advanced stage CRC patients, in univariate (p=0.009, HR=0.366) and multivariate analysis (p=0.005, HR=0.240). Similarly, higher methylation levels of Uc283 were associated with longer overall survival (p=0.030) and disease-free survival (p=0.038). Finally, mRNA levels were significantly lower in colon cancer cells resistant to oxaliplatin (p<0.001 for all three T-UCRs).

The present study suggests that methylation levels of T-UCRs Uc160, Uc283 and Uc346 differ during CRC development and progression and Uc160 and Uc283 methylation is prognostic for CRC.

Rhabdomyosarcoma (RMS) is a rare neoplasm, however the most common pediatric soft tissue sarcoma. The histological subtypes include the embryonal (ERMS), alveolar (ARMS), spindle-cell and pleomorphic rhabdomyosarcoma. ARMS has the worse overall prognosis and is characterized by specific cytogenetic alterations. These alterations display a recurrent translocation between genes encoding for transcription factor FKHR with either PAX3/PAX7. As a result, the chimeric genes encode transcription factors that promote tumorigenesis.

The presentation of a rare ARMS case report, which was diagnosed and studied with FISH analysis in our Hospital.

Histopathological examination, subsequent FISH analysis and literature review in PubMed/MEDLINE.

A 12-year-old female patient, with no significant medical history, attended the emergency department, with dull inguinal pain symptoms. An abdomen CT scan revealed a 4cm pelvic mass. Since there were no metastases and the lesion did not infiltrate any regional structures, the patient was submitted to a local mass excision and pelvic lymph node dissection. Histologically are mentioned: R0 excision, absence of infiltrated lymph nodes and round, usually multinucleated tumor cells with mitotic figures. Paternless sheets of discohesive tumor cells with fibrovascular septae were also identified. Immunohistochemistry showed positivity for desmin, vimentin, myogenin and MyoD1. Therefore, the diagnosis of ARMS was suggested. FISH analysis for FKHR alterations, revealed one normal fusion signal, two split signals for the telomeric region of FKHR and multiple split signals for the centromeric region of FKHR. These results indicate gene translocation of FKHR3 region with simultaneous gene amplification and aneuploidy. The patient received postoperative adjuvant chemotherapy and radiotherapy. There was no recurrence at 6 months follow-up.

The uniqueness of the case is based on the simultaneously observed amplification, translocation and deletion of FKHR3 gene; a cytogenetic profile mentioned for the first time in the literature. In conclusion, FISH analysis contributes to the histological diagnosis of sarcomas. Additionally, the detection of unusual ARMS genetic subtypes is possible. The prominence of cytogenetic heterogeneity offers useful information for further histological classification of this rare tumor, with possible therapeutic and prognostic extensions.

Pancreatic cancer is a disease with very high mortality and minimal therapeutic progress in last decades. It's the fourth leading cause of cancer death overall and the average life expectancy of patients does not exceed 1.5 years. There is very little research on the unmet needs of these patients in relation to other types of cancer.

Exploring the views of healthcare professionals about the providing care and their unsatisfied needs.

The study involved doctors and nurses of a cancer hospital. All participants had to work for at least one year in a clinic that carries patients with pancreatic cancer undergoing chemotherapy. The maximum variation was used as a sampling strategy. Eleven semi-structured interviews were conducted and recorded in mp3 format and then transcribed verbatim on MS Word. Qualitative thematic analysis was the selected method of analysis. The introduction of new participants into the study stopped when it reached the point of theoretical saturation and the interviews did not offer new concepts or contributed to the existence of the already recorded ones.

Pain management is the main need of patients with pancreatic cancer undergoing chemotherapy. Psychological support is important for the majority of patients, even at the time of diagnosis. A number of non-physical symptoms are identified that are related to and affect the daily lives and quality of life of these patients. Dissatisfaction is expressed in the absence of palliative care structures and services. Finally, the participants addressed the need for an interdisciplinary approach to improve the quality of care of these patients.

In the present study, health professionals report a wide range of unsatisfied needs of patients with pancreatic cancer, with the majority expressing their concerns about the complete lack of patient support in the last stages of their lives.

Brachytherapy is an essential part of treatment in endometrium cancer.

The study of our experience during last three years in the management of endometrium cancer. It refers to the effectiveness and toxicity of this treatment approach.

From April 2018 to February 2020, 156 patients received 3D conformal HDR brachytherapy (range of age : 36–90 years). Only 2 patients were inoperable. Intravaginal cylinders were applied to operated patients and a wide variety of fractionation was followed. Patients who didn’t receive adjuvant external beam radiotherapy, followed these fractionation schemes : 4 fractions × 7Gy/fr (31 patients) and 3 fractions × 7Gy/fr (41 patients). Patients who received adjuvant external beam radiotherapy, followed these fractionation schemes: 2 fractions × 7Gy/fr (38 patients), 3 fractions × 6 Gy/fr (19 patients), 2 fractions × 6 Gy/fr (18 patients). One patient didn’t complete the brachytherapy protocol. Tandem of different curvature was applied to inoperable patients in conjunction to intravaginal cylinder. The curvature was decided based on the anatomical position of uterus. It is worth to refer that an intravaginal ultrasonography was very helpful to the estimation of uterus cavity length.

Early toxicity of treatments was recorded. The most common side effects were related to mild enteritis (45%), especially when it was combined with EBRT, inflammation of vagina was quite common in the completion of treatment (30%), radiation cystitis with dysuria and frequent urination (most common to elderly patients). In terms of late toxicities, abnormalities to intestine habits (25%) and dyspareunia – dryness of vagina (35%) were recorded to patients younger than 50 years old. The most severe late effect was the sigmoid stenosis – early obstructive ileus in 2 patients (an operation was mandatory to one patient).

Three dimensional planning of brachytherapy treatment has minimized late side effects while early side effects are manageable and don’t cause treatment interruption or extension of treatment time.

In recent years, the relationship between DNA methylation and cancer has been intensively studied. New biomarkers are emerging, which can be used to detect the primary tumor, recurrence, metastasis, and patient response to treatment. Aiming mainly at early disease, the detection of molecular markers of methylation, characteristics of malignant mutation and metastasis, may have been indicative of more intensive investigation or more regular follow-up.

The aim of the present study is to detect the methylation status of tumor suppressor genes BRCA1 and BRCA2 in the free-circulating DNA (cell-free DNA) of patients with early gastric cancer (n = 70). An additional objective of the study is to determine the concentration of cfDNA in plasma.

We used the real-time QUBIT fluorometer and real-time PCR (qReal Time PCR) specific for repeated ALU sequences, compared the above two methodologies and correlated the concentration of cfDNA with the clinical and pathological characteristics of patients.

The BRCA1 and BRCA2 genes were found to be hypermethylated in the cfDNA of patients at 56.6% and 42.1%, respectively. A survival analysis showed that patients with non-methylated genes had a longer progression free survival (PFS) than those with methylated genes (p <0.009 and p = 0.013, respectively). The overall survival (OS) was also higher for patients with non-methylated BRCA1 and BRCA2 genes (p = 0.012, and p = 0.001, respectively). Finally, it was shown that tumors located in the body of the stomach, showed a higher percentage of methylation of the BRCA2 gene, compared to tumors located in the antrum (p = 0.006).

Hypermethylation of tumor suppressor genes is an early event during carcinogenesis and remains during metastatic transformation. Methylation of the above genes appears to be a sufficient prognostic indicator of survival, however its value should be validated and confirmed in an even larger number of patients.

Head and neck cancer is the 6^th most common cancer globally with numbers still rising in developing countries. Developments in treatment management have led to progression of free and overall survival. Metastatic disease usually appears in lungs, bones and liver following regional recurrence.

A 60-year-old male patient is diagnosed with stage IVa squamous cell carcinoma of left pyriform sinus and was treated with neoadjuvant chemotherapy with cisplatin, docetaxel and 5-fluorouracil followed by concomitant chemoradiotherapy. While being disease free, this patient was urgently hospitalized because of hypercalcemia and deteriorated respiratory function. There was no evidence of regional recurrence or metastatic disease according to the imaging tests, except for bilateral pleural effusions with the cytology obtained to be negative for malignancy. As the symptoms insisted, a new imaging scan was performed forty days later revealing a new intense bilateral nodular pleural thickness, tangential irregular swelling of diaphragm domes (mostly considering the left dome) and enlarged lymph nodes close to diaphragm. A pleural biopsy revealed moderately differentiated squamous cell carcinoma. Subsiquently, two cycles of chemotherapy with cisplatin, 5-fluorouracil and cetuximab were administered with poor outcome.

Distal metastatic disease in squamous cell carcinoma of head and neck is rare, especially without evidence of local recurrence. More specifically, metastasis in pleura and diaphragm is considered extremely rare and referring to this case report, no other is reported in published literature till date.

Three dimensional conformal brachytherapy is a very important part of radical treatment in cervix cancer.

The recording and the study of our experience during last three years in the management of cervix cancer, refers to the control of effectiveness of this treatment approach and to the research of related toxicity.

During last three years, we offer treatment in 82 patients (range of age : 25–86 years). Twenty of them were operated. Sixty two patients had local advanced disease and were inoperable. The first group of patients received adjuvant brachytherapy with intravaginal cylinders following different fractionation schemes. Specifically, 7 patients received 3 fractions of 7 Gy each, 5 patients received 2 fractions of 6 Gy each. All the others follow different schemes. Only one patient with inoperable disease denied to receive all the fractions of brachytherapy. In inoperable patients, tandems of different curvature were used based on anatomical position of uterus. Before the application, an intravaginal ultrasonography took place estimating the length of uterus cavity. Most of the patients, 45 totally, with inoperable disease received 4 fractions of brachytherapy with 7 Gy per fraction.

Early toxicity of treatments was recorded in detail. The most common side effects were related to mild enteritis (15%), inflammation of vagina that was presented at the end of the treatment (45%), radiation cystitis with dysuria and frequent urination (most common to elderly patients). As late effects, abnormalities to intestine habits (10%) and dyspareunia – dryness of vagina were recorded.

Our team prescribes weekly cisplatin concomitantly with external beam radiotherapy. We have the opportunity to plan the applications of brachytherapy in ideal intervals in relation to external beam radiotherapy. To summarize, following these rules, we manage to optimize the total treatment time for cervix cancer minimizing the toxicity at the same time.

Neuroendocrine Neoplasms (NENs) are considered to be rare neoplasms. They are epithelial tumors with predominant neuroendocrine differentiation and can be developed in all types of tissues. Their histological, molecular and imaging characteristics aremostly indicative for their site of origin, but to a small extent it is difficult to find the primary site.

83-year-old woman presented with a history of one year diarrhea, weakness, fatigue and anorexia. She also suffered from coronary disease, hypertension and hemorrhoids. Clinical examination revealed traces of blood in the digital anal examination as well as reduction of respiratory wheezing on the right lung. The laboratory tests showed abnormal values for CEA, CA-125, NSE and chromogranin A. Imaging tests showed enlarged mediastinal and axillary lymph nodes as well as hepatomegaly, ascites and enlarged mesenteric and paraortic lymph nodes. Patient underwent colonoscopy that showed diverticulosis and rectal polyps with central ulceration and hemorrhagic lesion. The histology revealed a well differentiated, grade 3 (NETG3 WHO,2–4MF/10HPF, Ki67>20%), chromogranin(−), synaptophysin locally positive. She underwent gastroscopy that showed gastric polyps with central ulceration. The histology revealed infiltration of a well differentiated NET, grade 3 (NETG3 WHO, 2–4MF/10HPF, Ki67>20% ~35–40%) chromogranin(−), synaptophysin locally positive. The octreoscan showed diffused bone marrow infiltration in the whole skeleton and visceral infiltration at the lower lobe of the right lung, liver and abdominal area. She underwent a bone marrow aspiration due to thrombocytopenia that showed diffused infiltration by epithelial origin malignancy, with strong positivity in oestrogen and progesterone receptors. A breast ultrasound showed a solid lesion at the left breast and histology of the lesion confirmed ductal carcinoma of the breast with positive hormone receptors and Her-2 negative. Review of all histologies tested revealed metastatic breast cancer. For this reason, patient received treatment with lanreotide 120mg and aromatase inhibitor with remarkable clinical improvement.

Neuroendocrine neoplasms usually present characteristics that lead us to the primary site, but sometimes it is difficult to conclude. These characteristics are not always indicative of the primary site as in our case in which diagnosis was achieved by bone marrow aspiration and has been confirmed by histology of the breast lesion.

Clostridium Difficile Infection (CDI) has been increasing dramatically in the last decade. The most important risk factor in the general population patients is antibiotic use such as -lactam, quinolones and clindamycin. Literature data on CDI risk factors in oncologic patients are contradictory.

To investigate the prevalence, characteristics and possible risk factors of CDI in hospitalized oncologic patients.

Data of hospitalized patients in our department who were on or had discontinued their anti-neoplastic treatment and presented diarrhea from March 2018 to January 2020 were analyzed. Their medical history was studied and a stool sample was sent for CD toxin investigation.

79 oncologic patients (29 A, mean age 64 years, 35–87) were studied. 48.1% had a recent history of chemotherapy, 51.9% were on antibiotic therapy, 68.3% were using PPIs, 29.1% had a history of gastrointestinal surgery and 11.4% had undergone appendicectomy. A total of 10 patients (12.7%) presented CDI. Of these, 70% had a recent chemotherapy treatment, 60% were on antibiotic therapy, 60% were using PPIs, 30% had a history of gastrointestinal surgery, and 1 (10%) had undergone appendicectomy. The vast majority presented with an intermediate severity CDI (40%) while 1 (10%) patient presented with a severe infection. 1 (1.26%) patient died without his death being associated with the CDI. Statistical analysis of epidemiological and clinical parameters of patients who presented compared with those who did not present CDI showed a statistically significant relationship between CDI, PPIs use (p = 0.040) and the history of gastrointestinal surgery (p = 0.016).

In our study the prevalence of CDI is 12.7%. Statistically significant risk factors associated with CDI are the use of PPIs and a history of gastrointestinal surgery. Chemotherapy was not statistically associated with CDI.

The 25^th HCCO “Unfolding the thread of Ariadne…for each of our patients” was organized by the Hellenic Society of Medical Oncology (HeSMO) in collaboration with the Hellenic Society of Radiation Oncology, the Hellenic Society of Surgical Oncology and the Hellenic Oncology Nursing Society and took place under the auspices of the European Society of Medical Oncology (ESMO). In particular, the 25^th HCCO was held on April 18–20, 2019 in Athens and 560 delegates attended(315 oncologists, 85 doctors of other specialties, 68 nurses and 92 students) while 159 abstracts were submitted.

All participants in the 25^th ESCO were asked to complete an online evaluation form consisting of 23 questions (general, satisfaction, open).

Received responses from 148 delegates with the following characteristics: men 59%, age: 36–45 40% and 46–55 30%, medical oncology 59%, radiationoncology 3%, surgical 1%, nursing 10% and other 22%, trainees 13% and specialists 70%, university hospital 26%, public 30%, private 17%, pharmaceutical company 9% and students 3%, Attica 58% and Thessaloniki 13%, members of HeSMO 53% and HeGYO 25%. Information for 25^th HCCO: internet 51%, colleagues 35% and announcements 30%. Main reasons to attend 25^th HCCO: participation as president-speaker-commentator-member of committees60%, scientific program 55% and review-update 47%. Participation at 25^th HCCO: attendance 40%, speaker 28% and president 20%. Way of attendance: physical presence 90%, physical presence and live streaming 9% and live streaming only 1%. At what rate did you attend the 25^th HCCO: 41–60% 39%, 21–40% 26% and 61–80% 20%. Participation in the opening ceremony 62%, closing ceremony 52%, HeSMO elections 48%, scientific event of HeGYO 32%, general meeting of HeSMO26% and scientific event of W4O 22%. The majority of delegates expressed overall satisfaction in various important dimensions. Indicatively, topics of conference (89%), duration of lectures (85%), interest of topics (90%), way of presenting the topics (85%), relativity of topics with work-specialty (91) %), expansion of scientific knowledge (85%), balance of program (89%), books of HeGYO / HeSMO (90%), awardfor best abstracts (82%), publication of abstracts in journal FCO of HeSMO (91%), pre-conference meeting (90%), conference website (88%), conference secretariat (95%), conference updates (91%), conference space (95%) and exhibition space (89%). Finally, an important element of satisfaction is that the 82% of the delegates would attend the next HeSMO conference while 18% are unsure.

The annual conference of HeSMO is the biggest oncology conference in Greece and it is now well known, recognized and well attended by the Greek Oncology Community.

Small Cell Lung Cancer has worse prognosis in comparison with other types of lung cancer due to its biological characteristics. Prophylactic Cranial Irradiation, in those patients that is recommended, delays the occurrence of metastasis to the brain and increases overall survival.

The goal of this study is, through an experienced medical centre for the study and treatment of lung cancer, to review the role of Prophylactic Cranial Irradiation, in association with certain variables, in brain metastasis free survival and overall survival of patients with Small Cell Lung Cancer.

A review of 439 medical records of patients diagnosed with Small Cell Lung Cancer in Oncology Department of Sotiria General Hospital in Athens was performed. There were 66 patients among them who had undergone Prophylactic Cranial Irradiation (PCI). Statistical analysis of Overall Survival and Brain Metastasis Free Survival of these patients was done, in association with sex, age, performance status, method of diagnosis, plan of therapy, dose of irradiation, time since 1^st chemotherapy and end of it till PCI.

According to this study the possibility of Brain Metastasis Free Survival in patients with Small Cell Lung Cancer is 83% on 1^st year, 54% 2-year survival and 48% 5-year survival. The possibility rate of Overall Survival for 1 year is 82% and 20% for 5-year survival. The only statistically significant variable for worse overall survival is poorer performance status after PCI.

Small Cell Lung Cancer patients have high probability to develop brain metastases affecting their quality of life and cause worse prognosis. Further research is needed, to effectively evaluate any possible association of Prophylactic Cranial Irradiation with other possible variables with aim to prolong overall survival.

Oncology patients represent an important population and a group with high sensitivity to infections. Solid tumors are a negative prognostic factor considering the infection incidence, hospitalization necessity and patients’ mortality. Literature evidence proves that influenza and pneumococcal immunization is necessary for this population.

Recording the immunization of oncology patients and their compliance with updated guidelines for influenza and pneumococcal pneumonia prevention.

A prospective recording study of 380 patients with solid tumors under systemic therapy respectively with immunization towards influenza and pneumoniococcus and the appearance of related infection.

Recorded patients were of median age of 64,1±11,9 years and were divided in 182 (47,9%) men and 198 (52,1%) women. Between them 284 (74,7%) were receiving chemotherapy, 34 (8,9%) immunotherapy, 56 (14,7%) hormonotherapy and 6 (1,6%) concurrent chemo-immunotherapy. Considering immunization, 42,3% had received influenza vaccine, 15,5% pneumococcal vaccine and only 12,1% were immunized for both. For patients receiving chemotherapy regimen, 118 (41,8%) underwent influenza immunization and 47 (16,7%) pneumococcal immunization while the percentages for those receiving immunotherapy were 35% and 15% respectively. Remarkably, 170 (44,7%) of patients were over 65 years of age and nevertheless only 38 (17,6%) of those were pneumococcal immunized. Finally, 8 cases of influenza-like illness were recorded but only half of them have been vaccinated.

Considering these results it is clear that vaccination of oncology patients towards influenza and pneumoniococcus remains low. Subsequently, queries about patients’ compliance and health professionals’ education are emerging.

Mesothelioma is a rare but really aggressive neoplasm with poor prognosis, originating from the mesothelial cells of the serosal membrane lining the pleural, peritoneal and pericardial cavities, and the tunica vaginalis. Peritoneal mesothelioma is rare and it accounts for ~10% of all mesotheliomas. It is associated with exposure to asbestos fibers in a subset of patients, typically with a long latency (median ~32 years) but the association seems to be weaker than in pleural mesothelioma. The disease typically presents with non-specific features and tumor nodules of variable size located diffusely throughout the peritoneal cavity, with massive malignant ascites and rare distant metastases.

The presentation of a rare case of peritoneal mesothelioma diagnosed by cytology of ascitic fluid.

A 55-year-old male presented with malaise and weight loss since 2 months. Clinical examination and CT demonstrated ascites and multiple peritoneal nodules. Abdominal paracentesis was performed.

The ascitic fluid cytology demonstrated multiple three-dimensional, often papillary-like, groups of neoplastic cells, often scalloped. There was variation in cell size and high nuclear/cytoplasmic ratios, nuclear membrane irregularities and macronucleoli. The cells were positive to WT1, calretinin and CK7 and negative to CDX2, TTF1 and CK20. The diagnosis was peritoneal mesothelioma and was confirmed by the biopsy.

The peritoneal mesothelioma is a rare aggressive neoplasm. It is often hard to be diagnosed. The clinical manifestations (weight loss, malaise, ascites) are usually non specific. It may also mimic radiologically carcinomatosis and has to be differentiated from malignant lymphoma, stromal tumors and tuberculosis. The therapy is most often a combination of cytoreductive surgery and intraoperative hyperthermic chemotherapy. Immunotherapy brings new perspectives (anti-CTLA4 monoclonal antibody and PD-L1 blockade). The 5-year survival rate is 40–60% after therapy.

Primary malignant melanoma of the breast (PMMB) is a rare, non-cutaneous malignancy of the breast parenchyma, which accounts for less than 0,5% of the breast tumors.

The aim of this survey is to meticulously review the literature of PMMB and report its epidemiologic and clinicopathologic data.

Two independent reviewers searched for clinical cases published on PubMed concerning primary melanoma of the breast. Fifteen cases were found, all of which were studied according to their epidemiological, clinical and histological findings.

Regarding these 15 cases, the patients’ age varied between 26 to 83 years old and the range of the tumor's size was between 1 to 11 cm. Most of the patients were asymptomatic or they presented with a palpable mass, without any involvement of the skin. The most convincing histological evidence for primary non-cutaneous melanoma is the presence of clustered melanocytes at the mucosal-submucosal junction adjacent to the tumor mass, 43% of which were amelanotic¹. Diagnostic approach for PMMB is substantiated by fine needle aspiration (FNA) cytology along with immunohistochemistry. The therapeutic approach consists of surgical resection of the tumor along with lymph node dissection in case of nodal involvement. Adjuvant therapy with compounds targeting BRAF and CTL-4 is highly recommended.²

The clinical appearance of primary malignant melanoma of the breast is similar to other mammary malignancies such as metastatic melanoma, metaplastic carcinoma and adenocarcinoma of the breast, therefore they should be part of the differential diagnosis. Due to its rarity, our knowledge concerning PMMB is inadequate. Thus, further research is required in order to ameliorate the therapeutic approach and report prognostic data.

Early cancer diagnosis allows in time medical intervention, significantly improving patient's survival and quality of life. Biomarkers assist in the diagnosis and follow up of tumor development. Basic research has brought in light hundreds of potential cancer biomarkers, more and more of which are introduced in the everyday clinical practice. The primary tumor site is most of the time minute and hard to retrieve material, on which many different analyses have to be performed in order to guide therapeutic decisions.

Application of a comprehensive genetic tumor analysis for known and emerging cancer biomarkers in single test.

In 20–40 ng of DNA/RNA from primary and metastatic lesions of solid tumors, we performed Trusight Oncology 500 assay on Illumina NextSeq 500 platform, according to the manufactures’ directions. The NGS data were analyzed using the validated PierianDx platform and the results were correlated with the patient's clinical phenotype.

From a total of 25 clinical samples analyzed, 11 were examined only on DNA level for SNVs, In/Dels, CNVs, splice variants, MSI and TMB and the other 14 for the above DNA level variants as well as on RNA level for gene fusions. A total of 130 pathogenic/likely pathogenic variants in known genetic biomarkers were detected that are related with clinically useful information, as well as 175 variations in genes that are not related at the moment with any known pharmacologically useful biologic pathway.

The application of the most comprehensive analysis of the genetic tumor profile using Illumina's Trusight Oncology 500 on primary and metastatic lesions from different cancer types, offers a holistic approach for the identification of known and novel genetic alterations. It comprises the most rational management of the precious and usually limited tumor biopsy material, offering all possible information for existing and emerging diagnostic, prognostic and predictive biomarkers that will allow the clinician to optimally care for cancer patients.

Definitive Radiation Therapy for T1-T2N0 glottic cancer may affects quality of life of patients due to late toxicity as dysphagia and quality of voice disorders.

To evaluate on retrospectively collected data, the impact of definitive radiotherapy to patients with T1-T2N0 glottic cancer to long term toxicity, as dysphagia and quality of voice disorders, using Voice-Handicap Index (VHI) and also determine correlation with smoking.

Between 2011 and 2018, thirty two patients with T1-T2N0 glottic cancer treated with radical radiotherapy were retrospectively reviewed. All patients were treated with 3D-conformal RT and received 70Gy with 2Gy per/fraction. The parameters measured were smoking history, T-stage and also anterior commissure (AC) involvement. We determined quality of voice according to questionnaires of Voice Handicap Index 10(VHI). Median follow-up was of 26 months(range 8–84 months).

All patients witnessed significant voice improvement following treatment. The incidence of dysphagia grade ≥2 to six and twelve months, was 12.5 % and 8%respectively and patients who suffered had not ceased smoking. Voice quality and communicative ability were satisfying to all patients but slightly worse to patients who continued smoking. Patients who continued smoking had inferior results to VHI than those who had ceased smoking. Also AC involvement and larger RT volumes resulted in poorer voice quality. Patients withT2 tumors experienced worse voice quality before treatment, but voice quality did not remain inferior after RT.

There is a substantial improvement of voice quality after RT. Continuation of smoking has a negative impact on late toxicity and voice quality after RT. Different factors may have specific effects on pre-treatment and post-treatment voice. Advanced RT techniques, better knowledge of tumor biology and function of critical organs involved in speech and swallowing, are necessary to reduce late toxicity and optimize voice quality after RT for early glottic cancer.

With the exception of PD-L1 (programmed death-ligand 1) expression and TMB (Tumour Mutational Burden) marker, which have been introduced in clinical practice, no other clinically useful predictive biomarker for immune checkpoint inhibitors (ICIs) has been established so far.

The aim of the present study was the development of a new, non-invasive and clinically useful biomarker for patients with advanced/metastatic NSCLC treated with ICIs.

The present study recruited retrospectively and prospectively 112 patients with advanced (stage III and IV) and histologically confirmed NSCLC (adenocarcinoma or squamous cell carcinoma), treated with immunotherapy agents (nivolumab or pembrolizumab) in the Division of Oncology of the University Hospital of Patras. Clinicopathological data, molecular characteristics and response data were collected. Based on clinical parameters, we developed the PIOS (Patras Immunotherapy Score) biomarker in relation to best response (BOR) to ICIs.

Four out of all studied factors that were evaluated -Performance Status (PS), Body Mass Index (BMI), age and lines of treatment (LOT)- were incorporated in the model we developed (PS *BMI/LOT*age). This biomarker was associated with BOR, with patients having good response [stable disease (SD), partial response (PR) or complete response (CR)] presenting higher levels of PIOS score compared to patients with disease progression (PD) (p<0.001). The association remained statistically significant when the 4-tier evaluation (PD, SD, PR and CR) for best response was used (p<0.001). The predictive value of PIOS was also validated using binary logistic regression analysis (p<0.001). Moreover, PIOS was positively associated with duration of best response (p=0.019).

The present study suggests that the PIOS model, which incorporates 4 basic clinical parameters, may allow the selection of NSCLC patients with increased possibility to have clinical benefit from treatment with ICIs.

Clear sell sarcoma is a very rare type of sarcoma. The diagnosis of this subtype of sarcoma is very challenging.

Male 45 years old. He presented with a non typical skin lesion in the area of left heel in Sep 2019. Initially some focal treatment maybe with ablation or a kind of laser took place by a dermatologist without any improvement. Afterwards, in Oct 2019 a biopsy from that lesion took place and the pathology examination revealed a neoplasm without necrosis, number of mitoses around 3–4 and Ki-67 around 10%. The more possible diagnosis was clear cell sarcoma or malignant melanoma. Further molecular diagnosis in Nov 2019 confirms the diagnosis of clear cell sarcoma with the presence of EWSR1 in approximately 50% of tumors cells (typical 49% and not typical 29%). Moreover, BRAF mutation analysis was negative. Therefore, a proper surgical approach by our plastic surgeons took place in Dec 2019. In particular excision of left calcaneum with sentinel lymph node took place. Pathology examination revealed a neoplasm of 1.3cm max diameter with clear cell sarcoma characteristics. Regarding surgical margins tumor the nearest was 2.2mm. There were multiple small metastatic lesions-infiltrations in the sentinel lymph node the largest one was >2.5mm (without any exocapsic infiltrations). Moreover, in sentinel lymph node some neoplasmatic emboli in veins were found (vascular invasion). Regarding TNM stage it was evaluated as pT1N1Mx by the pathology report. Further and extensive work up with clinical and radiological examinations took place (CT scans, MRIs, Bone-scan and PET-Scan) and was negative for any distant metastases. Additional, due to the close surgical margins a second surgical excision in left heel took place but fortunately the histology examination of new tissue biopsies was negative for any remaining neoplasm or any tumor infiltration. In summary, this gentleman was diagnosed with a Clear Cell Sarcoma of left calcaneum EWSR1 positive that was resected. It is stage IV (T1N1M0) probably G3, without necrosis, number of mitoses around 3–4 and Ki-67 10%, with some vascular invasion and questionable surgical margins in some areas of surgical excision (second surgical excision took place that was negative for any remaining tumor).

Clear Cell Sarcoma is a very uncommon type of sarcomas that should be differentiated from melanoma. The diagnosis sometimes is very difficult and challenging. Molecular diagnosis is recommended.

Mesothelioma is an extremely rare malignant neoplasm, with frequency 1 case/1.000.000/year. It concerns mostly adults aged over 60 years, most often men, although it has been reported also in children. The main risk factor is the exposure to asbestos and the frequency of occurrence in people that have been exposed to asbestos is 300 times higher. It is one of the most malignant neoplasms in humans, with very aggressive biological course and without effective treatment. Most of the patients die in a few months after the moment of diagnosis (mortality 100%). Clinically, it presents with cough, dyspnea, loss of weight, thoracic pain, and malaise.

The presentation of a rare case of mesothelioma with an emphasis on the differential diagnosis.

A male patient, 76 years old, came with progressively increasing dyspnea and cough for the last weeks. Imaging revealed nodular thickening of pleura and pleural effusion in the right side. Thoracentesis was performed and we received a specimen from the pleural effusion for cytological examination.

The cytological examination of the smears revealed a population of neoplastic cells consisting of single cells or variously sized three-dimensional aggregations of cells, with sizeable, polymorphous nuclei, nuclear overlapping, and prominent nucleoli. Immunocytochemically, positivity for Calretinin and CK5/6 was revealed, with negativity for TTF-1 and MOC1. These findings were compatible with pleural mesothelioma. Patient underwent chemotherapy and died after few months.

Mesothelioma is a rare aggressive neoplasm with poor prognosis. The prompt diagnosis is crucial. The reactive mesothelial cells are not easily distinguished from the cells of epithelioid mesothelioma, whereas fibrous pleuritis imitates desmoplastic mesothelioma. Mesothelioma is difficult to be distinguished from adenocarcinoma and it should be also distinguished from squamous cell carcinoma. Vascular tumors of the lung may expand in the pleura and imitate mesothelioma. Immunocytochemistry is a useful tool and assists in resolving these diagnostic dilemmas.

Klawiter A, Damaszke T. Pleural mesothelioma - case report. Pol J Radiol. 2010;75(4):61–63.

The aim of our study is to evaluated the esophagus acute toxicity in patients with inoperable non small lung cancer after chemotherapy and radiotherapy.

From January 2012 to Dicembre 2018,187 patients with locally advanced non small lung cancer received in our department radiotherapy and chemo-therapy. The median age was 62 years. From these patients 119 had received sequential chemo-radiation therapy, initially three cycle of chemotherapy (cisplatin/gemcitabine)and then radiotherapy and 68 patients received concurrent chemo-radiotherapy (cis-platin). The total dose of radiotherapy was 60Gy(3-D CONFORMAL RT). The early esophagus toxicity has been evaluated according the RTOG/EORTC criteria

The grade I toxicity (Mild dysphagia or odynophagia / may require topical anesthetic or non-narcotic analgesics / may require soft diet) was ranged in the same level in the concurrent chemo-radiotherapy and the sequential chemo-radiotherapy (41%% versus 44%). The grade II toxicity (Moderate dysphagia or odynophagia / may require narcotic analgesics / may require puree or liquid diet) was 27% for the sequential and 29% to the concurrent. But the grade III toxicity (Severe dysphagia or odynophagia with dehydration or weight loss > 15% from pretreatment baseline requiring NG feeding tube, IV fluids, or hyperalimentation) was 2% for the sequential chemoradiotherapy and 18% for the concurrent chemo-radiotherapy. Only one patient had grade IV toxicity(Complete obstruction, ulceration, perforation, fistula). The concurrent chemo-radiation is the most important factor for the early esophagus toxicity, but there is another dosimetrical factor that increase the toxicity, the volume of esophagus that received 35 Gy. Our results seems that the esophagus toxicity was bigger when the irradiated volume of esophagus was bigger (V50<32 Gy).

The grade of the early esophagus toxicity in patients with locally advanced non small cell shows that it is significantly burdened, from the concurrent chemo-radiotherapy and the total volume of the irradiated esophagus.

Sex-cord tumors – tumors of the ovarian stroma - come from the developing gonad and respectively from the primitive sex cords or the specialized ovarian substrate. They concern 8% of all the primary ovarian neoplasms. Fibromas are rare, compact, benign tumors of ovarian stroma, which represent 1% – 4% of all benign ovarian tumors. They are usually unilateral, 1 to 10 centimeters in diameter and they appear in women aged from 20 to 80 years.

The presentation of interesting case of fibroma, which was diagnosed cytologically, in 58-year old patient.

A female patient 58 years old came with persistent abdominal pain for the last weeks. Her history was free. Imaging revealed a compact lesion in the left uterine appendage, with some cystic features, the biggest of them 14 cm in diameter. Patient underwent total hysterectomyand bilateral salpingo-oophorectomy. For cytological examination, we received liquid from the cystic part of the lesion.

The cytological examination of the smears revealed aggregations of medium-sized cells, with ovular or circular nuclei, nucleoli, thin chromatin, with partial nuclear overalapping and a little of cytoplasm. Sparse spindle-shaped cells with regular nuclei were also observed. The immunocytochemical assessment showed positivity for Vimentin and Calretinin. These findings were compatible with ovarian fibroma and the diagnosis was confirmed furtherly with the histological diagnosis.

Ovarian fibromas are rare, benign neoplasms which are treated surgically. Prognosis is excellent, and the recurrences concern more the cellular fibromas. They have a remarkably interesting differential diagnosis and they should be distinguished from leiomyomata and mainly from other malignant neoplasms of the ovary, which they imitate clinically and radiologically. The cytological examination in combination with immunocytochemistry is a precise and reliable diagnostic method. The histological examination confirms the diagnosis.

Bandyopadhyay A, Chakraborty J, Chowdhury AR, Bhattacharya A, Bhattachrya P, Chowdhury M. Fine needle aspiration cytology of ovarian tumors with histological correlation. J Cytol. 2012;29(1):35–40. doi:10.4103/0970-9371.93218

Anaplastic thyroid carcinoma (ATC), though rare, is the most aggressive form of thyroid cancer. It originates from the follicular cells and it seems that the most “sarcomatoid” thyroid tumors are anaplastic carcinomas. It comprises only the 2–5% of the malignant thyroid tumors but is responsible for more than 50% of deaths due to thyroid cancer. It is usually a rapidly growing neck mass that infiltrates the surrounding tissues. It is more common in women (f:m 2:1) and in older ages. There are three histologic patterns, singly or in combination: giant cell, sarcomatoid and epithelial.

The presentation of a rare case of anaplastic thyroid carcinoma in a male patient.

A 89-year-old male presented with dyspnea and voice hoarseness since a month. Clinical examination demonstrated a large, firm, ill defined neck mass. Ultrasound revealed diffuse enlargement of the right lobe which was almost totally replaced by an hypoechoic mass of about 6cm. FNA was performed.

The smears were cellular comprising of pleomorphic cells arranged in clusters, diffusely or singly scattered. The cells were large, with round to oval nuclei, coarse chromatin, prominent nucleoli and moderate to abundant cytoplasm. Few bizarre cells were observed. The background was inflammatory and focally necrotic. The diagnosis was anaplastic thyroid carcinoma.

The anaplastic thyroid carcinoma is a rare but very aggressive tumor. The patients usually have distant metastases at the time of diagnosis (30–40% lung, brain, bones). Treatment of anaplastic thyroid carcinoma (ATC) is mostly palliative. Surgical resection with adjuvant radiation therapy and chemotherapy may prolong survival somewhat and improve quality of life. The median survival is about 6 months. FNAC is important for the right diagnosis.

Testicular cancer is the most common malignancy among men aged 18 to 39. The main symptom leading to diagnosis is testicular pain, followed by lower back pain and dyspnea. Ten-year survival is as high as 95%, even in case of advanced disease, due to high response rates to chemotherapy (BEP, VeIP, TIP). Since the 1980's, no new drugs have been introduced for the management of the disease. However, we now have data supporting the administration of fewer cycles of chemotherapy in patients with stage I disease.

Data was collected retrospectively from 125 patients diagnosed with testicular cancer from 2010 to 2019 and treated in our clinic. The age at diagnosis ranged from 18 to 63 years. 59 of the patients (47%) had cancer of the right testicle, 66 (53%) of the left testicle, and 5 of both testicles. 46 (36%) were seminomas, 76 (58%) were non-seminomas, and for 6% no data was recorded.

Most patients were diagnosed at stage I (64 patients), with fewer at stage II (48) and III (17). Patients with stage I non-seminomas received BEP for 2 cycles (32), EP for 2–3 cycles (2), or BEP for 1 cycle (1). Patients with stage I seminomas received no chemotherapy (14), carboplatin for 2 cycles (10), carboplatin for 1 cycle (1), or radiotherapy (1). Some patients with stage III disease received chemotherapy prior to surgery based on tumor marker levels; in 5 of them no evidence of disease was found when the surgery was performed. To date, recurrence of the disease was seen in only 8 out of all the patients. All of them received treatment, including surgery in some cases, and only two died because of the disease.

The data collected over the past decade from patients in our clinic in Northern Greece confirm the effective management of testicular cancer and the high survival rates.

The 5-year survival rate for patients diagnosed with lung cancer is below 20% even nowadays. The prognostic role of platelet value hasn’t been fully clarified in this group of patients.

The purpose of this study was to investigate the connection between platelet count and the response to 1st line therapy, as well as the prognosis, for advanced non-small cell lung cancer (NSCLC).

40 previously untreated patients with stage IV NSCLC were divided into two equal groups according to their platelet status. Thrombocytosis was defined as platelet counts ≥ 450.000/mm³. We collected clinical parameters and the value of platelets at three different time points: before chemotherapy, at the evaluation of the disease and after progression. The results were correlated with Progression-Free Survival (PFS) and Overall Survival (OS) using univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier analysis.

Patients with normal platelets had a median PFS of 7,8 months, while median PFS was 8,3 months for the group of patients with thrombocytosis. This difference was not statistically significant. Median OS for the two groups was 18,7 and 18,5 months respectively, but there was no statistically significant difference, either. Multivariate survival analyses demonstrated that bone or adrenal metastases were independently associated with disease progression. Finally, adrenal metastases were the only independent prognostic variable.

The present study showed that platelet count cannot be used as a predictive and prognostic marker for our patients. However, further larger studies are needed to evaluate the precise prognostic significance of this parameter for the treatment of NSCLC.

Prostatic ductal adenocarcinoma (PDA), even though it is the second most common histological subtype, accounts for only 0.4%–0.8% of prostate carcinomas. It usually has a more aggressive biological behavior associated with low resectability and a greater tendency for visceral metastases. Hormonal therapy seems to be effective, and there are literature reports describing a shorter duration of response to docetaxel, as well as data concerning three patients with metastatic PDA who received gemcitabine / cisplatin with good response to this treatment.

The description of a patient case with prostatic ductal adenocarcinoma and long-term survival as well as the review of bibliographic data concerning the therapeutic approach for these patients.

A 60-year-old patient with PDA, Gleason score 8 (4 + 4), microsatellite stable, BRCA wt, with lung and bone metastases since 7 years, initially was offered androgen deprivation therapy, but due to rapid disease progression he was treated with docetaxel, with a subsequent drop in PSA level and imaging stabilization lasting more than one year. Further hormonal manipulations were performed with bicalutamide and enzalutamide without a good response. He then received consecutively 10 cycles of cabazitaxel, 6 cycles of docetaxel and 8 cycles of paclitaxel / carboplatin, showing good tolerability, clinical and imaging improvement. Afterwards, due to gradual imaging progression of the disease and lack of treatment options, he was offered mitoxantrone and again docetaxel and cabazitaxel. After neuroendocrine differentiation of the disease was ruled out, treatment with gemcitabine / cisplatin was finally started, based on 3 case reports describing its effectiveness in PDA. The patient received a total of 7 cycles, showing a continuous response and reduction of tumor burden by 60%. Since the last 3 months he has been taking a treatment break and remains in good condition, having only mild peripheral neuropathy.

The metastatic PDA seems to respond to chemotherapy based on taxanes as well as to the combination of gemcitabine / cisplatin, with potentially long-term survival.

Hepatoid carcinoma is an exceedingly rare type of malignant tumor, which histologically is similar to hepatocellular carcinoma. It is defined as an adenocarcinoma with typical glandular or papillary formations and features of hepatoid differentiation and expression of alpha-FetoProtein (AFP). The tumor cells show a centrally located nucleus and abundant eosinophilic cytoplasm, similar to the cells of hepatocellular carcinoma. It is localized more usually in the stomach (63%), following the ovary (10%0, the gallbladder, pancreas, and endometrium. The development in the lung is extremely rare, with 22 reported cases in international bibliography. The majority of the patients were males, smokers and the disease was diagnosed in an advanced stage.

Presentation of a rare case of hepatoid adenocarcinoma of the lung in a female patient.

A female patient 50 years old came to our hospital reporting non-productive cough. Radiology revealed atelectasia of the right lower lobe, small pleural effusion ipsilaterally and enlarged lymph nodes were revealed, of antecarinal and subcarinal region. EBUS-TBNA was performed (endobronchial ultrasound guided transbronchial needle aspiration) and a sample was collected for cytological examination.

The cytological examination of the smears of the transbronchial needle aspiration from a mediastinal lymph node (RLN4) revealed aggregations of tumor cells with sizeable nuclei with polymorphism, coarse chromatin, frequent nucleoli, and abundant cytoplasm. Immunocytochemically, positivity of tumor cells was observed for TTF-1 (cytoplasmic), CK7 and AFP and negativity for CK5/6, CK20, p63 and CDX2. The above findings in correlation with the clinical data (no findings in the gastrointestinal tube / liver) were compatible with metastatic infiltration of lymph node by hepatoid lung carcinoma.

Hepatoid lung adenocarcinoma is an extremely rare neoplasm with aggressive biological course and frequent liver metastases. In the differential diagnosis metastatic hepatocellular carcinoma is firstly included and its distinction could be difficult, especially in patients with sites in the lungs and the liver. Also, metastasis from stomach should be excluded. The combination of clinical, radiological, and cytological – histological findings and obviously the immunocytochemistry-immunohistochemistry lead to the correct diagnosis.

Motooka Y, Yoshimoto K, Semba T, et al. Pulmonary hepatoid adenocarcinoma: report of a case. Surg Case Rep. 2016;2(1):1. doi:10.1186/s40792-016-0129-6

The colorectal cancer is the third most frequent cancer at men and the second at women. The oxaliplatin is used in the adjuvant therapy and also in the metastatic disease at the chemotherapeutic combinations FOLFOX and XELOX. The incidence of the acute peripheral neuropathy caused by oxaliplatin is between 4% and 98%. Also the incidence of chronic neuropathy is about 70%.

This research attempted to lighten the relation between the oxaliplatin induced peripheral neuropathy and the mutation status of ras gene, the blood's serum levels of the magnesium, the calcium, the sodium, the potassium, the haemoglobin, the albumin, the transaminases, the uric acid and the LDH. Also evaluated the relation of the neurotoxicity of the oxaliplatin and the GFR, the ejection fraction, the age, the sex, the stage of cancer and the cumulative dose of oxaliplatin of the patients.

This retrospective research included 39 patients, who treated with FOLFOX in the First Department of Clinical Oncology of Theageneio Anticancer Hospital. The evaluation of neurotoxicity based on NCI-CTCAE criteria. The univariate statistical analysis of the quantitative variates was conducted using the t-tests or the Mann–Whitney U test. For the clinical categorical variates was used the ×2 test. The multivariate analysis followed using logistic regression model.

From the univariate analysis was concluded statistically significant correlation of the oxaliplatin's neurotoxicity with the uric acid of the blood serum (p:0.042), especially when the uric acid is more than 5.3 mg/dl (p:0.037), the serum albumin less than 4.3 gr/dl (p:0.034), the total number of the cycles of the chemotherapy (p: 0,022) and the ejection fraction (p: 0.003), especially when the EF is lower than 60% (p:0.012). At the multivariate analysis the statistical significance was reserved for the uric acid (OR 8.80) and the ejection fraction (OR 0.095).

The oxaliplatin's induced neuropathy is associated with the pre-chemotherapy increased levels of the blood serum's uric acid and with the decreased ejection fraction.

Immunotherapy has emerged as the core of oncology treatment. Nonetheless, only a subset of patients derives clinical benefit, emphasizing the need to use predictive biomarkers; many of these biomarkers (i.e. PDL1, MSI, TMB) rely on tissue, limiting their use in daily practice. Measurements of routine blood markers such as CRP or neutrophil to lymphocyte ratio have spurred interest for their potential prognostic value and ease of use.

The purpose of this study was to identify useful biomarkers from our daily clinical practice. From 2016 to 2019, a total of 146 patients with various types of neoplasms, who have received immunotherapy, were identified from the archives of the University Hospital of Ioannina (PGNI). We retrospectively recorded age, sex, pathological diagnosis, stage, line/type of immunotherapy, autoimmune diseases, allergies or infections at baseline, survival data (OS & PFS), response, LDH, calcium, albumin levels and complete blood count to identify prognostic or predictive factors.

In the present study we present our experience from the use of immunotherapy in the Oncology Department of the University hospital of Ioannina and we examine the prognostic and predictive utility of simple clinical and laboratory parameters.

Biomarkers with strong predictive and prognostic value, in addition to guiding clinical trial design, will be critical to individualize immunotherapy in clinical practice.

Extramedullary hematopoiesis is a common occurrence in patients with severe beta-thalassemia. Most often it affects organs such as the liver, spleen and lymph nodes. It is rarely met in the vertebral column. It is observed primarily in the thoracic spine and then in the lumbar spine. A not-so-common consequence of this is compression of the spinal cord due to hematopoiesis foci and subsequent neurological symptoms.

Presentation of the clinical, laboratory and imaging findings and treatment of spinal cord compression due to extramedullary hematopoietic foci in a patient with beta-thalassemia.

We reviewed the recent literature on this clinical entity in the PubMed / MEDLINE database until 12/2019.

A 53-year-old man presents with progressively worsening gait and instability. The patient has a history of beta-thalassemia, for which he receives blood transfusions every 15 days, while since 1988, foci of extramedullary hematopoiesis have been found in the region of thoracic spine and for which he underwent transfusions from 1994 to 1996 and radiotherapy sessions in 1996 due to their increase and instability of gait and spinal cord pressure. Since then, the patient has remained stable without the need for new sessions. Recurrent symptoms have been reported in the last year (gait instability, sphincter dysfunction and difficulty in climbing up stairs). In a new imaging test with MRI of the thoracic and lumbar spine, an increase in the size and number of foci was shown. It was initially treated with transfusions, corticosteroids and analgesics. Due to the worsening of the pain, he finally underwent new sessions of radiotherapy in the area (L5-S1).

The treatment of this rare clinical entity can be achieved through transfusions, surgery, radiotherapy or a combination of all of the above. There is no agreement on the total dose of radiation therapy and the doses range from 20–30 Gy, with a daily dose of 2–3 Gy.

Intraductal papillary neoplasm of the liver and the bile ducts is a rare neoplasm, representing 10 – 15% of the bile duct tumors. It is characterized as a macroscopically visible, pre-cancerous lesion, with papillary or villous architectural pattern of dysplastic epithelium inside the intrahepatic or extrahepatic bile ducts and mucin production. The mean age of occurring is 50–70 years. Histologically, it is characterized by papillary structures, with thin fibrovascular cores, which are covered by intestinal, pancreatobiliary, gastric or oncocytic type of epithelium. According to WHO classification it is classified in papillary neoplasms with low- or high-grade dysplasia, with coexisting infiltrative component.

The presentation of a rare case of intraductal papillary neoplasm of intrahepatic biliary ducts.

A female patient, 81 years old came with pain in the lower right abdomen. By the laboratory examinations, increased CA 19-9 was observed. Ultrasound imaging revealed a focal, oval-shaped, relatively hyperechoic lesion with halo, in the right lobe of the liver, which was aspirated.

The cytological examination of the smears of the aspiration sample revealed the presence of complex three-dimensional papillary formations, with frequently visible thin fibrovascular cores. The epithelial cells showed severe dysplasia, with dark-colored or frequently clear nuclei, thickening of the nuclear membrane, visible nucleoli and mucinous vacuolation of the cytoplasm. The above presented findings in correlation with the radiological findings were suggestive for intraductal papillary neoplasm of the intrahepatic bile ducts, with moderate to severe dysplasia. The diagnosis was confirmed by the histological examination of liver biopsy. Patient died because of bad general condition before the performance of the surgical procedure.

IPNB is a rare entity, especially in Western countries, which increases the risk of development of cholangiocarcinoma and it is included in “precursor lesions”. The sequence of carcinogenesis includes a lot of mutations concerning common pathways of oncogenesis (KRAS, loss of p16 and mutation of TP53). It is treated with surgical excision and histological examination of the specimen, in order to exclude the infiltrative cholangiocarcinoma, which frequently coexists and worsens prognosis.

Intraductal papillary neoplasm of the bile ducts: A case report and literature review Yaohong Tan, Clara Milikowski, Yanelba Toribio, Adam Singer, Claudia P Rojas, Monica T Garcia-Buitrago World J Gastroenterol. 2015 Nov 21; 21(43): 12498–12504. Published online 2015 Nov 21. doi: 10.3748/wjg.v21.i43.12498

Immunotherapy with checkpoint inhibitors has changed the treatment of many cancers, but often present adverse events (AE) that affect many organs. Among these, endocrine AE is common. CTLA-4 inhibitor ipilimumab alone or in combination with PD-1 inhibitors can cause pituitary insufficiency with impaired pituitary hormone secretion at 3.2% and 6.4%, respectively. While PD-1 and PDL-1 inhibitors rarely cause hypophysitis up to 1%.

To highlight the prevalence of hypophysitis as an AE of immunotherapy and its clinical significance.

Retrospective study of patients who received immunotherapy from March 2018 to January 2020 at the Second Department of Medical Oncology, St Savvas Anticancer Hospital. Epidemiological, clinical and laboratory were analyzed.

55 patients were studied (33 men, mean age 66.5 years, range 37–85). 40% had lung cancer, 29.1% melanoma, and 12.7% urethral cancer. 83% had metastatic disease. Of the 55 patients, 28 (50.9%) received immunotherapy with pembrolizumab, 21 (38.2%) with nivolumab, 4 (7.3%) with durvalumab and 2 (3.6%) with a combination of ipilimumab and nivolumab. The median treatment time was 7.23 months (range 1–28). A total of 5 patients out of 55 who received immunotherapy (9%) presented with hypophysitis based on laboratory tests: 2/28 (7.1%) with pembrolizumab, 1/2 (50%) with a combination of ipilimumab and nivolumab, and 2/21 (9.5%) with nivolumab. No patients presented clinical manifestations. All of them, were treated with hydrocortisone or prednisolone and continued to receive treatment with close endocrinologic monitoring. Statistical analysis of epidemiological, clinical and laboratory data demonstrate no predictive factors for the development of hypophysitis.

In our study, the prevalence of hypophysitis is 9%. None of the patients had clinical symptoms and all of them continued to receive immunotherapy with close endocrinologic monitoring and appropriate hormone replacement therapy.

NeuroEndocrine Neoplasms (NENs) have been characterized as rare neoplasms. NETs are epithelial neoplasms with prominent neuroendocrine differentiation and can develop in any tissue. The histological, molecular and imaging features of NETs are in general indicative of the primary origin, yet in some cases the detection of primary side can be very challenging.

42-year-old male with a past medical history of Multiple Endocrine Neoplasia type 1 (MEN 1) presented with an anterior mesothorasic mass and a second one in the inferior cervical region. The lesions were identified during the work-up which followed a pancreatic surgery. Particularly, patient was diagnosed with primary hyperparathyroidism and nephrolithiasis 20 years ago and underwent sequential excision of three parathyroid glands. Due to family history of primary hyperparathyroidism further and extensive work-up took place, which revealed the presence of MEN 1 syndrome. Molecular diagnoses detected the presence of the likely pathogenic p. A541T mutation and radiological examinations depicted two large pancreatic masses. Therefore, a segmental pancreatecomy, splenectomy and a cholecystectomy (due to chololithiasis) took place. The pathology examination revealed infiltration of well differentiated NET, grade2 (NETG2WHO,2MF/10HPF, Ki-67=5%), chromogranin, synaptophysin, PGP9.5 and CD56 positive. Postoperatively pancreatic pseudocysts occurred, which were treated with proper surgical approach (trans-gastric drainage). As a result of pancreatectomy, a mild diabetes mellitus was detected and treated with metformin. Additionally, MRI scan of pituitary gland revealed a small adenoma 2mm, stable in size without secretion of hormones. Patient underwent a thoracoscopic biopsy of the mesothorasic mass and a fine-needle aspiration biopsy of the cervical mass. The pathology examination revealed neuroendocrine tumor, grade2 (NETG2WHO,0MF/10HPF, Ki-67=25%), chromogranin, synaptophysin positive, as well as positive in CD56 and Bcl2, and partially positive in pankeratin AE1/3.

MEN syndromes are rare. Most of the time, acquiring a proper medical history (individual and family) may reveal the presence of MEN. Molecular diagnosis is essential and medical treatment in specialized centers is recommended.

Hormone receptor-positive advanced breast cancer comprises the majority of breast cancer (BC) cases and is preferably treated with endocrine therapies except in cases of visceral crisis. The addition of CDK4/6 inhibitors to standard endocrine treatment in the metastatic setting is currently the golden standard. In Greece, the CDK4/6 inhibitors Palbociclib and Ribociclib are used, but there is limited experience with the Abemaciclib.

In this abstract, we aim to present real-world data from the use of abemaciclib with either an aromatase inhibitor or fulvestrant for patients with metastatic BC treated in a tertiary cancer centre in the UK.

We collected retrospectively individual patient's data for 19 women (aged 41–90) from electronic medical records. Patients were treated between April 2019 and February 2020 (follow up time was ten months). 3/19 were premenopausal and received goserelin 4-weekly concurrently. 7/19 patients had abemaciclib with AI as first-line treatment, 6/19 as second-line and 6/19 as third line with fulvestrant. Patients characteristics: 12/19 had visceral metastases (liver, lung), one of them had brain mets, and one patient had meningeal disease, whereas 6/19 had bone-only disease. 5/19 patients had primary endocrine resistance (relapsed while on the first 2 years of adjuvant ET or PD within 6 months of first-line for advanced BC), and 4/19 had Gr.3 disease. 5/19 patients had been previously treated with chemotherapy in the metastatic setting.

16/19 patients had disease control (PR or SD) and 12/19 are still on the treatment. Maximum duration time is ten months. Fatigue gr I, II (12/19) and diarrhoea gr I, II, III (10/19) were the most frequent adverse events. Other AEs were hepatotoxicity gr II (1/19), mucositis gr II (1/19) and neutropenic fever that required hospitalization (2/19). 2/19 patients discontinued treatment due to toxicity (neutropenia and acute kidney injury), 9/19 reduced dose to 100mg × 2 and 2/19 reduced to 50mg × 2. 6/19 patients tolerated reasonably well the initial dose. Diarrhoea was controlled with dose modifications. Although fatigue was a cumulative side effect that occurred later than diarrhoea, it was not resolved with dose reduction.

The abemaciclib in daily clinical practise has been proven effective in high-risk patients with high-grade tumours, visceral disease and endocrine resistance while the toxicity was manageable. The effectiveness and toxicity profile were in accordance with the results from MONARCH – 2 and −3 clinical trials. Despite the small numbers, this patient cohort represents a real-life population suggesting that the Abemaciclib is a safe and effective treatment option for patients with advanced HR+/Her2− BC.

BC: breast cancer, AE: adverse event, AI: aromatase inhibitor, ET: endocrine treatment

Goetz MP et all, MONARCH-3 Abemaciclib As Initial Therapy for Advanced Breast Cancer, JCO, Nov 2017,

The adenocarcinoma of the pancreas is the 4^th cause of overall deaths due to cancer. The overall survival declines in association with the TNM tumor's staging, something that happens at the recurrence after a definite surgery, as well. There are no many published references about the management of cases like that. Herein, we describe a case of constantly recurrent, locally, adenocarcinoma of the pancreas that has overcome the expected five year overall survival.

The aim of this reference is to highlight the importance of surgical excision at the local recurrences.

A 55 years old man, without any medical record, after a medical investigation due to dyspepsia and abdominal pain, found to suffer from an adenocarcinoma of pancreas. At the computed tomography revealed a mass of the body to tail of pancreas, that it was characterized as inoperable. The patient started with ‘neoadjuvant’ chemotherapy (FOLFOXIRI regimen) with the aim to make the tumor operable. After the completion of the systemic treatment the patient underwent a peripheral pancreatectomy with splenectomy. He received adjuvant systemic chemotherapy with Gemcitabine/Abraxane. Twelve months post-surgery, the tumor relapsed and the patient received radiotherapy and chemotherapy with capecitabine. A year after he had a second relapse locally and the patient underwent a total pancreatectomy with partial gastrectomy. After that the patient is free of disease.

As long as, there are no guidelines for this small subgroup of patients, there is not a gold standard approach for a patient with a locally recurrent adenocarcinoma of pancreas, especially if there are more than one recurrences. From the describing case, we could assume that a more aggressive treatment with the aim of the excision of the recurrent disease, could be a good way of dealing with cases like that, trying to achieve the most of overall survival.

The patients with locally recurrent adenocarcinoma of pancreas after surgery, form a unique, rare subgroup of the patients with pancreatic neoplasms. There are no trials, or evidence of the best management of these patients, so the surgical excision of the recurrence seems to be the best way of treating with the aim of prolongation of recurrence or progression free survival and overall survival.

Immunotherapy is based on the activation of our immune system, against tumor cells, and has shown impressive results in the NSCLC treatment, initially in the 2^nd line therapy, and then, in the 1st line setting. In the 1^st line setting, it was initially used as monotherapy, and lately in combination with classic chemotherapy regimens.

The aim of this retrospective analysis is to compare both the efficacy as well as the toxicity of chemotherapy and immunotherapy in the 2^nd line treatment of mNSCLC.

Fifty-nine patients, consecutively admitted in our Medical Oncology Department were enrolled in our study. 83% men, 17% women, of median ECOG 1 (0–3), median age 68 (47–86) years, stage V squamous (32%) and non-squamous (68%) histology, were treated with 1^st line chemotherapy regimens. Following disease progression, they received 2^nd line therapy, either chemotherapy or immunotherapy. We compared both the efficacy and toxicity of the two 2^nd Line therapy options. In the immunotherapy arm, patients received either Nivolumab, or Pembrolizumab.

The number of patients whose disease progressed after receiving chemotherapy in the 2^nd line, was similar to those that received immunotherapy. However, time to progression, was significantly shorter in the chemotherapy arm (p=0,015). There was significant difference in disease progression probability between the two arms in both 3 and 6 months (p<0,05). Patients with at least one adverse effect, had 2,27 times higher probability of disease progression. Median overall survival was 8 months for the chemotherapy arm in second line, compared to 14 months in the immunotherapy arm. There was no difference in survival between the two arms in the 6 months evaluation (p>0,05). However, in the 12 and 18 months evaluation, survival rates were significantly higher for patients in the immunotherapy arm (p=0,006 και p=0,001 respectively).

Patients who received immunotherapy in 2^nd line, had siginificantly higher overall survival rates, compared to those that received chemotherapy (p=0,006). There was no correlation between PD-L1 expression levels and clinical benefit. Immunotherapy showed less toxicity than chemotherapy. Data from our daily clinical practice are in line with current literature.

Accurate estimation of R0 pancreatectomy incidence is of great importance in pancreatic cancer treatment, as such excisions are correlated with higher 5-year survival rates. Despite the lack of a globally accepted definition of R0 pancreatectomy, a realistic estimation of its incidence will be attempted, via the use of the most recent diagnostic protocols.

The presentation of the histopathological findings and the accurate estimation of R0 pancreatectomy incidence in our hospital.

Forty-nine (49) histopathology reports from patients who underwent pancreatectomies performed during the last decade (2010–2019) were evaluated. Relevant literature from the MEDLINE/pubmed website were also evaluated.

After thorough examination of the available reports, an incidence of 81,6% of R0 pancreatectomies was calculated. This percentage is in compliance with global rates, which fluctuate from 20% up to 85%, owing to discrepancies in R0 pancreatectomy definition worldwide.

R0 pancreatectomy incidence, as calculated by examination of histopathological data, is in compliance with national trends. The prominence of R0 pancreatectomies is correlated with better prognosis and higher survival rates. However, the adoption of a globally accepted definition should be a high priority, so as the available research data and conclusions become more reliable.

Neuroendocrine carcinoma of the cervix is a rare aggressive form of cervical cancer, about 2% of cases. It is characterized by a high frequency of lymph node metastases and early hematogenous dissemination. Human papillomavirus (HPV) appears to be the main causative agent. The prognosis is unfavorable and there is no standard treatment based on clinical studies.

We present a clinical case with PDL-1 negative metastatic neuroendocrine cervical carcinoma heavily pretreated that received treatment with Nivolumab and experienced immediate radiographic response and clinical improvement of symptoms.

A 72-year-old women was diagnosed with metastatic neuroendocrine carcinoma of the cervix. Initially the disease extended with a lesion 20 × 17 cm to the pelvis, a mass 4 cm to the left adrenal gland, a lymph node block 4 cm to the Haler tripod and a single lesion 1.5 cm to the liver. She treated with Etoposide (100 mg/m² IV on day 1, 2 and 3) and Cisplatin (80 mg/m² IV on day 1) and a partial response was recorded. Few months after and due to vaginal bleeding she underwent urgent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Relapsed 6 months later with enlargement of the adrenal gland mass and we preferred to re-challenge her with Etoposide and Cisplatin chemotherapy and we achieved again a partial response. Subsequently due to disease progression received 3rd line treatment with Topotecan (0.75 mg/m² IV on day 1, 2 and 3) and 4th line treatment with Paclitaxel (135 mg/m² IV on day 1) and Carboplatin (AUC 4 IV on day 1). The patient is receiving hydrocortisone replacement therapy due to adrenal insufficiency as a result of adrenal masses. Finally, after approval, she received treatment with Nivolumab at a dose of 3 mg/kg IV every 2 weeks and after 6 cycles a significant decrease of all target lesions was recorded and great relief of symptoms. Molecular characterization of her tumor showed absent PD-L1 expression.

Immune checkpoint inhibitors may be active in cervical neuroendocrine carcinoma with the probability of benefit in some patients regardless of PDL-1 status.

Although immunotherapy is a promising treatment strategy on the management of patients with metastatic NSCLC, there are subsets of patients that do not respond or become resistant to treatment. Chemotherapy (Ch) and radiotherapy (RT) may increase the benefit of immunotherapy. We aimed to investigate the effect of prior chemotherapy or radiotherapy on patients with metastatic NSCLC who received immunotherapy in our Department.

We investigated the data from 68 patients with metastatic NSCLC managed in our Department in the period from 01/2016 to 06/2019 and were treated with immunotherapy. The Overall Survival (OS) and Progression Free Survival (PFS) were estimated from the date of diagnosis. The statistical analysis was performed by using the SPSS package IBM version 25.

57.1% of patients had Adenocarcinoma and 33.3% had Squamus Cell Carcinoma. 97% were smokers, while a genetic mutation was detected in 17% of patients. Patients that had received radical RT in the past had better OS as compared with patients that received palliative or no RT (HR:0.162, p=0.016 και HR:0.178, p=0.027 respectively). The number of previous chemotherapy treatment lines did not have any effect on OS in patients that received immunotherapy. However patients that received immunotherapy in the first line had better PFS as compared to patients that received immunotherapy in latter lines (HR: 0.23, P:0.045).

Prior radical RT had a positive effect on the OS of patients with metastatic NSCLC treated with immunotherapy. A possible abscopal effect may be related with this observation that needs prospective validation.

Pigmented villonodular synovitis (PVNS) is a rare, idiopathic, benign, but potentially locally aggressive, recurrent clinical entity. It is characterized by hyperplasia, deposition of pigment (hemosiderin) in the joints and formation of focal nodules and follicles. It most commonly occurs in patients between the ages of 20 and 50 years and mainly affects large joints such as the knee and hip joints.

Presentation of the clinical picture, laboratory findings and treatment of a patient with PVNS and review of the recent literature regarding this disease.

We conducted a recent literature search on the PubMed / MEDLINE website until 12/2019.

A 37-year-old man, with a free personal and family medical history, presented with a six month edema, gradually worsening pain and reduced functionality in the knee joint area. Orthopedic assessment was performed and initially treated it as a case of patellar chondropathy. The X-ray images of the area were normal. The patient then underwent an MRI scan and a biopsy (with a small anterior approach), which was used to diagnose PVNS. He underwent two procedures for the surgical resection of the lesion in a time period of two months due to residual disease. He then underwent postoperative radiotherapy (38 Gy, in 19 sessions, with a daily dose of 2 Gy), four weeks after the second surgery, due to diffuse PVNS.

Adjuvant postoperative radiotherapy can improve the percentage of local control in case of diffuse PVNS and reduce the chance of recurrence.

Fibroadenoma is the most frequent benign tumor of the female breast, which appears often in adolescents and young women, and the peak age of incidence is the 2nd – 3rd decade of life. It is a biphasic, histologically, neoplasm, consisting of an epithelial glandular portion and the specialized stroma of the terminal ductal lobular unit (T.D.L.U). It can be single or multiple and bilateral. Its size is generally smaller than 3 cm, although it may be large sized. On ultrasound imaging, it appears as a hypo- or isoechoic ovular mass with regular margins.

The presentation of a rare case of ductal carcinoma of the breast as an incidental finding during the cytological examination of a fibroadenoma.

A female patient 46 years old was referred to our laboratory for ultrasound-guided fine needle aspiration (FNA) of a compact tumor in the right breast below and in the external region of the nipple, 6 millimeters in diameter.

The cytological examination of the smears of the FNA specimen revealed a lot of cellular aggregations, with nuclear crowding and overlapping. In many sites architectural distortion was observed with loss of cellular cohesion and cellular spreading. The cells had eccentric nuclei and nucleoli, whereas they were positive for p53. Also, a lot of cellular aggregations were revealed, characteristic for fibroadenoma. These findings were compatible with ductal adenocarcinoma of the breast with coexisting fibroadenoma.

The development of carcinoma in a fibroadenoma an extremely rare incident. The frequency in retrospective studies is considered 0,002–0,0125%. Carcinomas can develop inside a benign lesion or they may coexist independently. Generally, fibroadenoma is not considered a risk factor for development of cancer, however the existence of characteristics which classify it as complex, such as sclerotic adenosis, calcifications and the papillary apocrine metaplasia, increase this risk. Also, the presence of hyperplastic lesions in the surrounding parenchyma increase more the risk. The correct cytological assessment is necessary also in lesions that do not raise clinical and imaging suspicions for malignancy.

Swetha N, Geetha Ch, Prayaga AK. Role of cytology in fibroadenoma with clinging carcinoma. J Cytol. 2013;30(1):78–80. doi:10.4103/0970-9371.107530

Cystadenolymphoma (Warthin Tumor) is a benign tumor of the salivary glands. It is the second most frequent tumor after pleiomorphic adenoma, and it concerns 10% of all tumors of the parotid gland. The majority of this tumors is found in the parotid and occasionally in the buccal cavity, larynx, and the cervical lymph nodes. It is more frequent in male smokers, aged 40 years and over. Histologically is characterized by a double layer of epithelial cells in dense lymphoid stroma with frequent lymph follicles. Malignant transformation to lymphoma, Merkel cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, squamous cell carcinoma and others is rare. The preoperative diagnosis is based mainly in Fine Needle Aspiration and the Cytological Examination.

The presentation of an interesting case of cystadenolymphoma which cytologically imitated squamous cell carcinoma.

A male patient 54 years old with painless enlargement at the right parotid region. Clinically and radiologically it was considered as possible malignancy. Patient underwent ultrasound-guided fine needle aspiration.

The cytological examination of the smears revealed sparse or small aggregations of oncocytes with granular cytoplasm, hyperchromatic nuclei, occasional nucleoli, and a lot of spindle-shaped squamous atypical cells. In the substrate, a lot of histiocytes were found and a lot of inflammatory cells, amorphous substance, and necrotic elements. These findings corresponded to cystadenolymphoma with features suggesting squamous metaplasia, however the histological examination, which was considered necessary, confirmed the cytological findings.

Cystadenolymphoma is a frequent benign tumor of the parotid with extremely good prognosis and infrequent recurrences (2%). In rare cases it could be a diagnostic trap even for the experienced cytologist. The main malignancies with which should be distinguished are mucoepidermoid carcinoma, squamous cell carcinoma, mainly in cases with extended mucinous and squamous metaplasia. The possibility of false positive results should be taken in consideration by the clinicians, especially in cases where the clinical and the other findings do not suggest malignancy.

Parwani AV, Ali SZ. Diagnostic accuracy and pitfalls in the fine-needle aspiration interpretation of Warthin's tumor. Cancer Cytopathology 2003; 99: 166–71.

Women who receive chemotherapy for treatment of the breast cancer, have a tendency to gain weight. About 50 to 90% of women had gain weight and 20% of them had gain a total weight of more than 10 kilos.

The aim of this review is to investigate the association between chemotherapy and weight gain in women receiving chemotherapy.

A literature review was conducted using the electronic databases PubMed and Google scholar. The following key words were entered: “weight gain”, “chemotherapy”, “breast cancer” and “cancer patients” and a combination thereof. Exclusion criteria of articles were the language, except English and the type of cancer that exclusively concerned women with breast cancer. About 30 articles were found on the subject and 15 of them were included. The review was conducted in the last 20 years

Factors that contribute to weight gain during chemotherapy are the intake of large amounts of food associated with stress, reduced physical activity and also the modification of basic metabolic rate. Additionally, women in premenopausal period and use of corticosteroids in chemotherapy protocols have been identified as risk factors for weight gain. Weight gain is predisposed to chronic diseases such as high blood pressure, diabetes and osteoarthritis, which negatively affect quality of life and possibly the survival of these patients.

Weight gain in women with breast cancer receiving chemotherapy is a common side effect of treatment. Healthcare professionals need to inform patients about this possibility in order to be properly prepared and follow a diet that will allow them to maintain a normal weight throughout the treatment in order to avoid the occurrence of chronic diseases.

Pancreatic adenocarcinoma is the most common type of pancreatic cancer and is a leading cause of death worldwide. It is a very aggressive type of cancer with a life expectancy of five years. Whipple surgery, which is used to treat pancreatic adenocarcinoma and is one of the most complex oncological surgeries, involves the removal of the pancreas head, lymph node clearance of the area as well as pancreato static, cholepeptic and gastronomic anastomosis. Rupture of pancreato static anastomosis with pancreatic fluid leakage is the most common postoperative complication.

The aim of the study is to describe an incident involving the rupture of pancreato static anastomosis after Whipple surgery.

This is a case study of a 63-year-old woman who underwent surgery to remove a pancreatic adenocarcinoma in a large hospital in northern Greece.

A 63-year-old female patient with pancreatic head adenocarcinoma arrived in May 2019 for surgery. The patient underwent pancreatodecadactylectomy with lymph node dissection and the development of gastronomic, pancreato static and biliary-fasting anastomosis. For the first 24 hours the patient was transferred to the clinic, while on the second postoperative day, the patient had a good postoperative course. On the tenth postoperative day, she presented with rupture of pancreatic anastomosis with pancreatic fistula formation, while on the twelfth day she presented hemodynamic instability. The rupture was treated with more adequate drainage and administration of somatostatin, while she also underwent a computed tomography scan. Nursing care consisted of evaluating the functioning of the drainage system, monitoring the patient's body temperature, replenishing oxygen in the blood and monitoring blood glucose levels regularly. In order to prevent a more serious hemodynamic complication, the nurse monitored the patient's vital signs and urination every three hours.

Rupture of pancreatic anastomosis is a life-threatening complication. When it occurs, appropriate nursing care is required to treat it adequately.

Carcinomas of unknown primary site are a heterogenous group of neoplasms with poor prognosis. Their frequency ranges from 2% to 4 % of all patients with cancer. They may present as multiple sites in the liver, as lymphadenopathy of mediastinum, retroperitoneum, head, axilla, or inguinal region, as peritoneal carcinomatosis and also as multiple nodular sites in the pulmonary parenchyma or as metastatic sites in the bones or the brain. Malignant effusions in serous cavities may be the first manifestation of a malignancy. However, cardiac tamponade resulting from malignant pericardial effusion is rarely the first presentation of an undiagnosed malignancy.

The presentation of a case of adenocarcinoma of unknown primary site which manifested with cardiac tamponade.

A male patient, 40 years old, with free personal anamnesis, came with productive cough for the last five days, retrosternal pain and fever. The clinical examination revealed tachycardia, tachypnea, and hypotension. Electrocardiogram, cardiac ultrasound, and further imaging showed a large pericardial effusion and cardiac tamponade. Also, CT scan revealed mediastinal lymphadenopathy. Patient underwent aspiration of pericardial cavity and we received the liquid for cytological examination.

The cytological examination of the smears from the aspiration specimen (pericardial fluid) revealed a lot of malignant cells in papillary aggregations with nuclear overlapping, hyperchromasia, multiple nucleoli and vacuolated cytoplasm. The immunophenotype was MOC-31 (+), CK7 (+), CK20 (+), WT-1 (−). These findings were compatible with metastatic adenocarcinoma. Despite the detailed clinical and laboratory investigations and the histological – immunohistochemical investigation of lymph nodes, the determination of the primary site was not possible.

A malignant pericardial effusion is observed sometimes during the course of diagnosed malignant neoplasms. Rarely, cardiac tamponade is the first presentation of a malignancy, however it should be included in the differential diagnosis of this critical condition. The primary site is more often found in the lung, the breast, or the lymphatic system. In our case, the primary site was not found. Patient receives chemotherapy neoplasms of unknown primary site an after a month he presents an improved clinical condition.

Isabel de la Gàndara, Enrique Espinosa, Jorge Gómez Cerezo, Jaime Feliu & Carlos Garcia Girón (1997) Pericardial Tamponade as the First Manifestation of Adenocarcinoma, Acta Oncologica, 36:4, 429–431, DOI:10.3109/02841869709001291

Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide and despite improvements in surgical techniques, chemotherapy, and radiotherapy, the incidence of local recurrence still ranges between 4%–8%, with distant recurrences predominating (1,2)

The purpose of this article is to present a clinical case of rectal cancer, with rare recurrence (small intestine) and how it was treated.

A 65-year-old patient was diagnosed with grade II rectal adenocarcinoma and received neoadjuvant chemotherapy with concurrent radiotherapy and then underwent low anterior resection and afterwards he received adjuvant chemotherapy. Immunohistochemical study revealed intestinal adenocarcinoma with CK7 (−), CD20 (+), CDX2 (+) and DPC4 (+).

Two years later, as part of the follow-up, he underwent an abdominal CT scan and a thickening of the second part of duodenum was revealed. He underwent a gastroscopy and biopsy of the suspicious site, and an intestinal adenocarcinoma with a similar immunophenotype to rectal cancer, namely CK7 (−), CD20 (+), CDX2 (+) and DPC4 (+). An integrated positron emission tomography (PET)/CT scan was performed, that showed increased metabolic activity [standardized uptake values (SUV): 10,3] only in the second part of the duodenum and a right hemicolectomy was performed.

The most common sites of metastatic rectal cancer are the liver, lungs, peritoneum, retroperitoneally, and lymph nodes (2). Small intestine tumors account for only 2% of gastrointestinal tumors and mainly involve primary tumors, such as adenocarcinomas, GIST, carcinoids, and lymphomas (3). Metastatic disease in the small intestine is rare and comes mainly from melanoma and breast or lung cancer (4).

The recurrence of rectal cancer in the small intestine is possible, but a detailed pathological and immunohistochemical study is required to differentiate primary small intestine cancer from metastatic rectal cancer and future studies are required to address what kind of surgery and chemotherapy is necessary.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016: Cancer Statistics, 2016. CA: A Cancer Journal for Clinicians. 2016;66(1):7–30.

Carcinosarcoma is an unusual type of malignant neoplasm of the pancreas which is characterized by a biphasic morphology, with coexistence of epithelial and sarcomatous components. Each of these components has distinctive morphological and immunohistochemical characteristics. They are usually arising in uterus. Their localization in pancreas is extremely rare (7% of the non-neuroendocrine malignant neoplasms), with few cases reported in international bibliography (less than 20). Their histogenesis remains still unclear and the small number of the studied cases does not allow the determination of an appropriate treatment. They are extremely aggressive neoplasms with poor prognosis (mean survival time 6 months). They mostly affect women in the 7^th decade of life.

The presentation of a rare case of pancreatic carcinosarcoma in a male patient 59 years old

A male patient 59 years old came with abdominal pain during the last month. By his medical history, an episode of acute pancreatitis was reported one year before. Ultrasound imaging revealed the presence of a cystic and partially compact lesion in the body of pancreas, approximately 6 cm in diameter. Patient underwent ultrasound-guided fine needle aspiration (EUS-FNA)

The cytological examination of the smears revealed a lot of flat and three-dimensional groups of cells with nuclear crowding / overlapping, well-sized and frequently multiform nuclei with thickened nuclear membrane and often visible nucleoli. Also, a lot of aggregations of spindle-shaped cells were observed, with severe atypia and polymorphism, focally with storiform pattern. The substrate was inflammatory, focally with presence of myxomatous substance and frequently necrotic. The above findings were compatible with undifferentiated carcinoma, of carcinosarcoma type. Patient underwent peripheral pancreatectomy and the diagnosis was confirmed histologically.

Pancreatic carcinosarcoma is an extremely aggressive neoplasm and its preoperative diagnosis is a challenge even for the experienced cytologists. Although rare, it should be included in the differential diagnosis of pancreatic tumors, especially of the tumors with cystic degeneration. EUS-FNA technique is a reliable method of diagnostic approach.

Oka K, Inoue K, Sugino S, et al. Anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration: a case report and review of the literature. J Med Case Rep. 2018;12(1):152. Published 2018 May 31. doi:10.1186/s13256-018-1615-1

Mucinous carcinoma (colloid, gelatinous) of the breast is a rare type of a well differentiated infiltrative carcinoma, representing 0,5 – 3% of breast carcinomas in its pure form. It is met more frequently in post-menopausal women (mean age 71 years). Histologically, it is characterized by the presence of nests of cells in lakes of mucin, separated by thin fibrous septae including capillary blood vessels. By definition, the mucin lakes represent 50% of the tumor. It is distinguished in the pure mucinous type (pure when the mucinous characteristics concern more than 90% of its total extent) and the mixed type, which has worse prognosis. Cellular atypia is generally low.

The presentation of a rare case of mucinous carcinoma of the breast, which was diagnosed cytologically.

A woman, 79 years old, with an incidental finding in chest CT scan concerning a lesion in the left breast, which ultrasonographically was considered suspicious for malignancy. She was referred for ultrasound-guided fine needle aspiration (FNA) of the lesion. Lymphadenopathy was not observed.

The cytological examination of the smears revealed loose aggregations of tumor cells, architectural distortion, and sometime single cells, with moderate polymorphism, eccentric nuclei, irregular chromatin network and occasionally visible nucleoli. The substrate was inflammatory, focally necrotic, with stromal cells and vessels with shapeless mucinous substance. The aforementioned cytolmorphological findings were compatible with mucinous carcinoma of the breast of pure type.

Mucinous carcinoma of the breast is an interesting type of carcinoma, on the one hand because of its rarity and on the other hand because of its favorable prognosis. Lymph node metastasis is rare (2–4%). Ten-year survival ranges between 80% and 100%. Thus, its early diagnosis and its distinction from a lot of other benign and malignant lesions is of great importance. The similarities with lesions such as mucocele and myxoid adenoma could be a diagnostic trap. FNAC is a reliable technique for pre-operative diagnosis.

Sharma S, Bansal R, Khare A, Agrawal N. Mucinous carcinoma of breast: Cytodiagnosis of a case. J Cytol. 2011;28(1):42–44. doi:10.4103/0970-9371.76952

Gastrointestinal Stromal Tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. They are rare neoplasms and they represent less than 1% of all primary neoplasms of the gastrointestinal tract. They appear more often in the 5^th – 6^th decade of life. They are characterized by the mutation of KIT proto-oncogene (75%) or PDGFR-α (10%). They can develop throughout the gastrointestinal tract, however they are localized more often in the stomach (60–70%) and small intestine (25–35%), whereas they may appear in the colon, rectum, esophagus, and appendix. Rarely they primarily develop in the intra-abdominal tissues outside the gastrointestinal tract and then they are characterized as EGISTs (5% of the cases in the omentum, mesentery and retroperitoneum).

The presentation of a rare case of EGIST, which was diagnosed preoperatively with FNAC-CT.

A male patient, 71 years old, came with abdominal pain and abdominal distention during the last weeks. Imaging (CT scan) revealed the presence of an intra-abdominal mass, approximately 16 cm in maximum diameter, which was pushing away the surrounding structures. CT-guided fine needle aspiration was performed (FNA-CT).

The cytological examination of the smears revealed single neoplastic cells or in loose aggregations, with nuclear overlapping, elongated / wavy nuclei, and fibrous cytoplasm, sometimes with cytoplasm of fibrous texture and cytoplasmic projections (snouts). The substrate was focally fibrous or moderately inflammatory, with cellular debris. The above findings in correlation with radiological findings were compatible with extragastrointestinal stromal tumor (EGIST). Resection was performed and the diagnosis was confirmed histologically by the surgical specimen.

EGISTs are rare neoplasms. They often present with non-specific symptoms and their preoperative diagnosis is sometimes difficult. They should be distinguished from leiomyomata, leiomyosarcomas, schwannomas, solitary fibrous tumors and also carcinomas, neuroendocrine tumors, and melanomas. FNAC in combination with immunocytochemistry is a valuable tool of preoperative diagnosis. Prognosis depends of grading (size of the tumor, number of mitoses), as this is determined in the surgical specimen.

Vij M, Agrawal V, Kumar A, Pandey R. Cytomorphology of gastrointestinal stromal tumors and extra-gastrointestinal stromal tumors: A comprehensive morphologic study. J Cytol. 2013;30(1):8–12. doi:10.4103/0970-9371.107505

Multiple primary cancers are usually defined as primary malignant tumors in different sites and with different histological origins in one person. The incidence of multiple primary malignancies seems to be increasing because of the increasing overall life expectancy, better cancer therapies and more sensitive modalities for detection. The reported frequency of multiple synchronous primary tumors is 1–3%. The frequency of pancreatic cancer in association with cancer of other organs is estimated to range from 1% to 20%. The presence of synchronous lung and pancreatic cancers is extremely rare. Smoking, genetic factors and chronic inflammation are supposed to be risk factors.

The presentation of an interesting case of a 60-yaer-old male with synchronous primary pancreatic adenocarcinoma and squamous carcinoma of the lung.

A 60-year-old male, who was recently diagnosed with squamous carcinoma of the lung, was referred to the Oncology Department for therapy. PET/CT revealed a mass in the tail of pancreas. ERCP was performed and samples were taken.

Cytopathology demonstrated multiple groups with disordered sheets of cells displaying a drunken honeycomb pattern, grooved nuclei and prominent nucleoli. These findings were compatible with pancreatic adenocarcinoma. The patient takes chemotherapy and shows no signs of regression.

The diagnosis of multiple primary in a patient, though rare, is of great importance and poses crucial dilemmas about the therapy. The early recognition and treatment is important as there exists a significant survival difference in patients who have synchronous primaries as opposed to those with metastatic pancreatic adenocarcinoma.