Impact factors for perioperative morbidity and mortality and repercussion of perioperative morbidity and long-term survival in pancreatic head resection

Resection of the head of pancreas remains a significant challenge for many pancreaticobiliary surgeon. Recently, better perioperative care, surgical technique, and better patient’s selection have undoubtedly led to better survival and have reduced the perioperative mortality. However, the high morbidity that accompanies these operations negates any positive long-term results in patients with otherwise poor prognosis that could have benefited from.

The complications associated with PD procedures are well described.1,2 These are usually of higher grade than in comparable abdominal surgical procedures. Even more, they are usually associated with significant perioperative morbidity. Many attempts have been made to lower these complications.1, 3–7 Some authors have claimed that modifications of the surgical techniques, especially the formation of the pancreatojejunostomy, could have a positive impact on the postoperative course. Others have claimed that a better selection of patients would decrease the morbidity and mortality.8–13 Since perioperative morbidity and mortality are important predictors for long-term survival of patients after PD’s14, 15, we performed a retrospective study to determine factors associated with perioperative and specific surgical complications, general complications, and perioperative mortality. The identification of such negative prognostic factors could help to prevent complications or even mortality and could therefore have an impact on log-term survival after pancreatic surgery.

Factors like postoperative pancreatic fistula, age, and poor general condition have all been determined to have a negative impact on the postoperative course.1,4,13,16,17 The drawbacks of some of these studies, however, are the small number of included patients, the inclusion of low-volume centers, and the short-term postoperative follow-up of the patients. In our study, we therefore evaluated which clinic-pathological factors significantly influence morbidity, mortality, and long-term results in a tertiary reference institution for pancreatic diseases, where about 50 pancreatic resections are performed annually. Preoperative workup, surgical procedures, and postoperative care are highly standardized. All these factors enabled us to perform a detailed study of factors influencing the perioperative course after pancreatic surgery.

For the present retrospective study, the data of patients after pancreaticoduodenectomies (PD) and total pancreatectomies (TP) performed from January 1, 2008 to March 31, 2017 at the Department of Abdominal Surgery UMC Maribor were analyzed. Clinical and pathological data were prospectively stored in a computerized database. Data for the follow-up were obtained by our own outpatient follow-up and by the National cancer register of Slovenia. Complete follow-up was obtained up to June 1, 2017. We obtained informed consent from all patients and performed all procedures according to the guidelines of the Helsinki Declaration. The analysis includes patients having had PD and TP. There are no urgent resections included. The indications for the resection were malignant and premalignant lesions of the region sited in the head of pancreas, and chronic pancreatitis in few cases.

Altogether 240 patients had pancreatic resection (male 131, female 109, mean age 66.04 years). The indications for resections and characteristics of the analyzed patients are presented in Tables 1 and 2.

Table 1

Indications for pancreatic resection

Table 2

Observed clinicopathological features in 240 operated patients

The incidence of OAC was 37.1%. ASC occurred in 29.2% whereas AGC in 14.2%. ASC presented themselves as a leak from PEA (PL), non-PEA leak (OL), bleeding complications (BC) and abdominal abscesses (AA) in 19% (of 208 PD), 5.8%, 5.8% and 2.5% respectively. In case of OL, five were from GEA. Bleeding (BC) occurred in altogether 14 of 240 patients. Two patients had early intestinal bleeding and 12 occurred after 24 hours. Other rare surgical complications occurred in altogether 4.5% (Table 3). All general complications are described in Table 4.

Table 3

Surgical complications in 240 operated patients

Table 4

General complications in 240 operated patients

Drained fluid was checked for amylase in 189 of 207 patients after PD. Elevated amylase more than 7 ukat/l on drains were found in 73 patients (38.6%). In 63 patients (33.3%), the high amylase on drains originated from PEA whereas in 10 patients amylase rich secretion evidently did not origin from PEA (6 bile leaks, 2 leaks from GEA, 1 ileus, 1 strangulation of the mobile cecum). The rate of PF A was 14.4%, PF B 9.6% and PF C 9.6%. Determination of PF in groups A, B and C did not correlate with means of amylase value in discharged secretion on drains in ordinal fashion; it was rather the consequence of clinical factors and therapeutic measures.

One of the common consequences of complications was significantly prolonged hospital stay (OAC: 30.9 ± 16 vs. 14.2 ± 4.5 days; p < 0.0001). Overall 30- and 90-day mortality were 5% and 7.9%.

Pancreatic resections present the only curative option for patients with malignant and premalignant diseases, and for relief of symptoms in selected group of patients with chronic pancreatitis. However, due to high morbidity and mortality, the treatment should not be worse than the disease.21 Despite markedly progress on the field of pancreatic resections, morbidity remains quite high for decades whereas mortality rates gradually improved.22–27 There was no exception in our study with OAC rate of 37.1%; ASC 29.2% and AGC 14.2% were AGC within the two observed periods. The 30-and 90-day mortality in our patients were 5% and 7.9% respectively. This result is well comparable to the reports of other authors. In many studies, postoperative mortality was defined traditionally as mortality within 30-days or during the initial hospitalization. This might had led to an underestimated postoperative morbidity and mortality rates. As shown by some Meta analyses, even in centers of Excellency, the 90-day mortality rate is double of the 30-day mortality rate and significantly differs concerning the hospital volume. One of the consequences of postoperative morbidity for patients who survive the complication was significantly prolonged hospitalization.5,15,26,28 In our study, it was ranging between 30 and 44 days.

It has been often documented that higher age and low physical status can significantly affect the occurrence of postoperative complications.12,13 In our study, higher mean age and higher ASA score impacted the incidence of OAC and AGC. ASA score alone impacted ASC and PL. Regarding our results, higher mean age was an independent predictor for OAC and AGC whereas ASA score was for AGC. On the other hand, specific complications like BC, AA and OL did not correlate with age or physical status. Age did not prove as an independent prognostic factor for any type of complications; however, ASA score did for 90-day mortality. Therefore, our results support the conclusion not to restrain patients from PD or TP only because of their age; however, caution is needed while selecting the patients for PD or TP.

There is an ongoing debate on whether jaundiced patients with obstructive lesion and higher bilirubin in the head of the pancreas should be drained or not,29–34 Since only relevant laboratory data from the immediate preoperative period were at our disposal for the study, we can hardly profoundly discuss this issue. Based on our own data, however, we observed higher mean total bilirubin values in patients with BC and lower for the group with AGC. The results regarding EBD match with the results from others revealing higher incidence of ASC and PL in patients with EBD.31,35–38 There was no correlation of mean total bilirubin or EBD with 30- and 90-day mortality.32,39,40

Our study confirms comparable results regarding the perioperative morbidity and mortality between PDs and TPs except for abdominal abscesses, which occurred more often in TP. This fact could speak for TP in selected cases of patients with pancreas remnant untenable for PEA, especially in elderly in less good general condition who do not tolerate this kind of complications at all.41–43 In patients with preexisting insulin dependent diabetes, this decision could even be easier. Relevant criteria for decision-making in this regard are still missing. Further analyses are needed for long-term quality of life, especially concerning insulin dependent diabetes.44–46

Resection of VMS or VP for infiltration was formerly regarded as a relative contraindication for the PD. However, nowadays it presents a standard treatment and was performed in 16.7% of our patients. In our study, neither type of pancreatic resection nor the incidence of VMS/VP resection influenced the occurrence of postoperative morbidity and mortality.47–52

The proportion of chronic pancreatitis in PACs and NPCs included in the reports can differ significantly, and if cases with predominantly hard pancreas remnant predominate, as in patients with chronic pancreatitis, the overall risk for postoperative morbidity and mortality rates could reveal at a lower rates. In our collective of patients, chronic pancreatitis and PAC contributed 2.9 and 56.7% of patients respectively, remaining more than 40% of patients with diseases where the pancreas remnant could be softer (Table 1).9, 53–55

To our results, concerning only PACs and NPCs, OACs were more likely to occur in NPCs and in tumors of smaller size. Moreover, the majority of NPCs were also smaller than PACs. The size of tumor affects the onset of OAC, ASC and PL; however, neither 30- nor 90-day mortality were impacted by type or size of the tumor.56–58

Patients with amylase more than 7 ukat/l on drains and pancreatic fistula were retrospectively classified in three types of PF (A, B, C) respecting clinical picture, therapeutic consequences, and ISGPF PF recommendations.20 Mean values of amylase in discharged secretion did not differ between PF A, B and C. There is consensus among all reports that PF negatively affected the postoperative course in patients after PD.59,60 Our experience with PF was similar. In PD, the high mean amylase on drains or amylase more than 7 ukat/l predicted the onset of complications, especially if surgical complications were involved (OAC, ASC and PL). However, exception were AA where the mean amylases on drains were low proving that abscesses did not originate from pancreatic leak. PF A was not associated with any serious morbidity in postoperative course of our patients. Patients with OAC, ASC, AGC, BC, PL, PF C and high mean amylase or amylase more than 7 ukat/l are at a higher risk to die within 30 or 90 days. Although, most studies agree about the impact of PF on morbidity and mortality, there is less consensus for how to prevent the occurrence of PF. Most effort is focused on how to perform a save anastomosis in case of soft friable pancreas texture with a thin pancreatic duct.5–7,10,61,62

Both periods (P1 and P2) were comparable regarding almost all clinicopathological factors except for type of pancreatic resection and vascular reconstructions, and the count of performed TPs. There were more TPs in P2 as in P1 (20.8% vs. 4.2%). Both types of pancreatectomies were comparable regarding age, physical status, tumor markers, mean bilirubin value, morbidity and mortality. Logically, there were no PF in TP. In addition to other indications, TP was performed in 11 patients with pancreas remnant unsuitable for anastomosis. The indications for TP must be posed very responsible, even the inform consent must be done preoperatively in this issue.24,41,43 The morbidity was stable within the whole study period, but 30- and 90-day mortality became twofold lower in P2 (3.5% and 5.7%), although without a significant correlation.

Most subtypes of complications did not compromise the long-term survival in our cohort of patients. The exceptions were PLs in PDs and BCs in PDs and TPs where the 5-year survival was significantly compromised. On the other hand, in patients who survived any of these complications the long-term survival was not impacted by any type of complications.59,60,63,64

In conclusion, the present study indicates that amylase rich secret on drains and higher mean age are independent indicator for OAC whereas. PL and BC proved as an independent predictor for 30-day mortality, and physical status, OAC and PF C for 90-day mortality. EBD, smaller size of tumor and NPC can provoke complications; however, there was no repercussion on postoperative mortality. Even though the decrease in 30- and 90-day mortality (3.5% and 5%) tightly missed the significance in our cohort of patients, the trends of better surgery in pancreatic resections in our institution seemed to be encouraging. Most subtypes of complications did not compromise the long-term survival in our cohort of patients. The exceptions were specific complications like PLs and BCs where the 5-year survival was significantly compromised. On the other hand, in patients who survived these complications, the long-term survival was not impaired by any type of complications. The worse scenario in pancreatic resection is an older patient in bad physical condition having low sized tumor or NPC, amylase reach output on drains after resection, and eventually BC.