Radiol Oncol 2018; 52(1): 54-64. doi: 10.1515/raon-2017-0036 54 research article Impact factors for perioperative morbidity and mortality and repercussion of perioperative morbidity and long-term survival in pancreatic head resection Stojan Potrc1, Arpad Ivanecz1, Vid Pivec, Urska Marolt1, Sasa Rudolf2, Bojan Iljevec1, Tomaz Jagric1 1 Department of Abdominal Surgery, Surgical Clinic, University Medical Centre Maribor, Maribor, Slovenia 2 Department of Radiology, University Medical Centre Maribor, Maribor, Slovenia Radiol Oncol 2018; 52(1): 54-64. Received 11 June 2017 Accepted 9 August 2017 Correspondence to: Assoc. Prof. Stojan Potrč, M.D., Ph.D., Department of Abdominal Surgery, Surgical Clinic, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia. Phone: +386 2 321 1301; Fax: +386 2 321 1257; E mail: potrc13@gmail.com Disclosure: No potential conflicts of interest were disclosed. Background. The focus of the present study was to reveal any impact factors for perioperative morbidity and mortal- ity as well as repercussion of perioperative morbidity on long-term survival in pancreatic head resection. Patients and methods. In a retrospective study, clinic-pathological factors of 240 patients after pancreatic head (PD) or total resection were analyzed for correlations with morbidity, 30- and 90-day mortality, and long-term survival. According to Clavien-Dindo classification, all complications with grade II and more were defined as overall compli- cations (OAC). OAC, all surgical (ASC), general (AGC) and some specific types of complications like leaks from the pancreatoenteric anastomosis (PEA) or pancreatic fistula (PF, type A, B and C), leaks from other anastomoses (OL), bleeding (BC) and abscesses (AA) were studied for correlation with clinic-pathological factors. Results. In the 9-year period, altogether 240 patients had pancreatic resection. The incidence of OAC was 37.1%, ASC 29.2% and AGC 15.8%. ASC presented themselves as PL, OL, BC and AA in 19% (of 208 PD), 5.8%, 5.8%, and 2.5% respectively. Age, ASA score, amylase on drains, and pancreatic fistulas B and C correlated significantly with differ- ent types of complications. Overall 30- and 90-day mortalities were 5 and 7.9% and decreased to 3.5 and 5% in P2. Conclusions. High amylase on drains and higher mean age were independent indicators of morbidity, whereas PL and BC revealed as independent predictor for 30-day mortality, and physical status, OAC and PF C for 90-day mortality. Key words: pancreatic resections; complications; impact factors Introduction Resection of the head of pancreas remains a sig- nificant challenge for many pancreaticobiliary surgeon. Recently, better perioperative care, surgi- cal technique, and better patient’s selection have undoubtedly led to better survival and have re- duced 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 proce- dures are well described.1,2 These are usually of higher grade than in comparable abdominal sur- gical procedures. Even more, they are usually as- sociated 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 pa- tients would decrease the morbidity and mortal- Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection 55 ity.8–13 Since perioperative morbidity and mortality are important predictors for long-term survival of patients after PD’s 14,15, we performed a retrospec- tive study to determine factors associated with perioperative and specific surgical complications, general complications, and perioperative mortal- ity. 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 de- termined to have a negative impact on the postop- erative course.1,4,13,16,17 The drawbacks of some of these studies, however, are the small number of in- cluded patients, the inclusion of low-volume cent- ers, and the short-term postoperative follow-up of the patients. In our study, we therefore evaluated which clinic-pathological factors significantly in- fluence morbidity, mortality, and long-term results in a tertiary reference institution for pancreatic diseases, where about 50 pancreatic resections are performed annually. Preoperative workup, surgi- cal procedures, and postoperative care are highly standardized. All these factors enabled us to per- form a detailed study of factors influencing the perioperative course after pancreatic surgery. Patients and methods 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 ana- lyzed. Clinical and pathological data were pro- spectively stored in a computerized database. Data for the follow-up were obtained by our own outpa- tient 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 accord- ing 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. Preoperative workup Patients’ preoperative physical status was ex- pressed by the American Society of Anesthesiology score (ASA).18 Three ASA 4 patients from this pe- riod were not included in the study. Prior to the surgery, all patients were submitted to computer tomography (CT). Additional abdominal magnetic resonance imaging (MR) or endo-ultrasonography (EUS) with or without biopsy were done only in selected patients. Beside usual standard laboratory blood tests, tumor markers CEA and Ca 19-9 were also evaluated. Preoperative endoscopic biliary drainage (EBD) was done in patients with bilirubin value > 200 mmol/l or in subicteric patients when further preoperative workup was necessary. Preoperative preparation Intravenous antibiotic (1.5 g cefuroxime and 0.5 g metronidazole or 0.35 g gentamycin and 0.6 g clindamycin) and subcutaneous antithrombotic (4000 IE enoxaparin or 3800 nadroparin or 5000 IE dalteparine) prophylaxis were successively used in all patients 1 hour and 12 hours prior to operation. Urine catheter and nasogastric tube were usually inserted after induction of anesthesia. Surgical technique The usual operative approach was median or bi- lateral subcostal laparotomy. After confirming re- spectability (no distant dissemination, no tumor infiltration of the coeliac trunk, hepatic artery or superior mesenteric artery), the strategy was to perform a curable resection (R0) in malignant and premalignant lesions, and/or to relieve symptoms as in chronic pancreatitis. Usually pylorus-pre- serving PD, Whipple resection or TP (in patients with very soft texture of the pancreas unsuitable for anastomosis) were performed. In malignant disease, lymphadenectomy was done in hepa- toduodenal ligament, around common hepatic artery, superior mesenteric artery (usually 180 to 2700), and occasionally between vena cava and aorta. Resection borders on the bile duct and pan- creas were checked for neoplastic infiltration by frozen section examination. If infiltration of the superior mesenteric or portal vein was suspected, “En-block” resection of the infiltrated vein was done to assure the curability of resection. Vascular reconstruction was done by direct continuous 6.0 monofilament non-absorbable suture; however, if more extended distance had to be bridged, vascu- lar prosthesis was used. Anastomosis to pancre- atic stump was exclusively performed by duct to mucosa end to side pancreaticoenteric anastomo- sis (PEA) using 5.0 monofilament non-absorbable Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection56 sutures in two layers followed by single-layer bilioenteric anastomosis (BEA) with interrupted 5.0 absorbable polyfilament sutures. In selected patients (mostly with thin duct and/or soft tex- ture of the pancreas), trans-anastomotic lost stent was used. The continuity of the gastrointestinal tract was further established by omega gastroen- teric anastomosis (GEA) done with 3.0 absorbable monofilament sutures. In all patients, single-layer continuous entericenteric anastomosis (EEA) be- tween afferent and efferent loop was done with 4.0 polyfilament absorbable suture. Two drains were placed in the right subhepatic region (one in space of resected head of the pancreas and one above bilioenteric anastomosis) and one in the Douglas region. Postoperative care Almost all patients were admitted in the high de- pendency unit except if admission to the inten- sive care unit was indicated. Patients started to receive fluid food on the first day. Gastric tube was removed after appearance of bowel move- ments or the first stools. Amylase was checked in the drained fluid on day 3 and thereafter when any clinical suspicion for anastomotic leaks was pre- sent. In selected patients (soft pancreas remnant) however, parenteral somatostatin (6 mg/24 h) was administrated for 6 to 10 days in the presence of clinical relevant amylase leak until the cessation of secretion on abdominal drains. Definitions and statistical analyses All complications (OAC) according to Clavien– Dindo classification grade II or more were consid- ered as postoperative morbidity.19 All surgical (ASC), all general (AGC), and all surgical and general complications (SGC) were an- alyzed. In addition, special group of complications like leak from PEA (PL), leaks not from PEA (OL), abdominal abscess (AA) and abdominal or intesti- nal bleeding (BC) were identified. Any postoperative mortality within 30 and 90 days was considered a probable consequence of TABLE 1. Indications for pancreatic resection Indication for pancreatic resection P1(n/ %) P2 (n/ %) All (n/ %) p Pancreatic adeno carcinoma 64 71 135 66.7% 50.0% 56.7% Neuroendocrine tumor of the pancreas 2 7 9 2.1% 4.9% 3.8% Main duct intraductal papillary mucinous neoplasm 0 3 3 0.0% 1.4% 0.8% Franz’s tumor 1 0 1 1.0% 0.0% 0.4% Non-Hodgkin lymphoma of the pancreas 1 1 2 1.0% 0.7% 0.8% Adenocarcinoma of the distal bile duct 13 30 43 13.5% 20.8% 17.9% Adenocarcinoma of the papilla Vateri 12 18 30 12.5% 12.5% 12.5% Duodenal adenocarcinoma 2 6 8 2.1% 4.2% 3.3% Gastric cancer 0 2 2 0.0% 1.4% 0.8% Chronic pancreatitis 1 6 7 1.0% 4.2% 2.9% P1 (period 1) = from January 1, 2008 to December 31, 2012 (96 pts); P2 (period 2): from January 1, 2013 to March 31, 2017 Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection 57 surgery and was declared as postoperative mortal- ity (30- and 90-day mortality). Receiver operating curve analysis for morbidity and mortality determined the threshold values of amylase secretion on abdominal drains. An area under curve (AUC) of > 0.75 was used to determine the value of significance. The ROC analysis was used to determine sensitivity and specificity of the determined amylase cut-off, which revealed to be more than 7 ukat/l. Sensitivity and specificity for prediction of pancreatic fistula type B or C (PF B or C) at cut-off 7 ng/ml were 100% and 85.4% re- TABLE 2. Observed clinicopathological features in 240 operated patients P1 (n/%) P2 (n/%) All (n/%) p Gender (n = 240) male 51 80 131 0.4 53.1% 55.6% 54.6% female 45 64 109 46.9% 44.4% 45.4% Age (n = 240) Mean (years) 66.1 ± 9.9 65.98 ± 10.1 66.4 0.91 ASA (n = 240) 1 17 43 17 0.103 17.7% 29.9% 17.7% 2 53 68 53 55.2% 47.2% 55.2% 3 26 33 26 27.1% 22.9% 27.1% Preoperative histology (n = 240) 4 32 36 0.0001 4.2% 22.2% 15.0% Hospital stay (n = 222) Mean (days) 21.2 ± 14.5 19 ± 11.6 19.8 0.138 Preoperative total bilirubin (n = 240) Mean (mmol/l) (mmol/l) 67.6 ± 71.5 79.0 ± 85.5 74.7 0.028 Preoperative endoscopic biliary drainage (EBD) (n = 240) 34 51 85 0.554 35.4% 35.4% 35.4% P1 (n/%) P2 (n/%) All (n/%) p Type of pancreatic resection (n = 240) PD 92 115 207 0.0001 95.8% 79.9% 86.3% TP 4 29 33 4.2% 20.8% 14.2% Resection of VMS/VP (n=240) 12 28 40 0.17 12.5% 19.4% 16.7% Type of vascular reconstruction (n=240) Direct suture 10 14 24 0.043 10.4% 9.7% 10.0% Vascular graft 2 14 16 2.1% 9.7% 6.7% Overall complications (OAC) (n=240) 34 55 89 0.383 35.4% 38.2% 37.1% 30-day mortality (n=240) 7 5 12 0.152 7.3% 3.5% 5.0% 90-day mortality (n=240) 11 8 19 0.080 11.5% 5.6% 7.9% ASA = American Society of Anesthesiologist Physical Status; VMS = mesenteric superior vein; VP = portal vein; P1 (period 1) = from January 1, 2008 to December 31, 2012 (96 pts); P2 (period 2): from January 1, 2013 to March 31, 2017 Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection58 spectively. Consequently, any secretion of amylase rich fluid on drains more than 7 ukat/l was defined as elevated. Patients with high amylase on drains from PEA were declared to have (PF) and retro- grade classified in three types of PF (A, B, C) re- specting clinical picture, therapeutic consequences, and ISGPF PF recommendations.20 Two chronologically successive groups of pa- tients (period 1 (P1): from January 1, 2008 to December 31, 2012 (96 pts); and period 2 (P2): from January 1, 2013 to March 31, 2017 (144 pts)) were compared for perioperative morbidity, and 30- and 90-day mortality. Continuous data are expressed as mean ± stand- ard deviation and categorical variables are given as percentages. Continuous variables were compared with Student’s t-tests for parametric data and Mann-Whitney U tests for nonparametric data. Chi-square tests were used for comparisons of dis- crete variables. All of the predictors that were significant on univariate analysis were included in the multivari- ate analysis. In the multivariate analysis, a binary logistic model was used. Survival analysis was per- formed with the Kaplan-Meier method. The dif- ferences between groups were compared with the log-rank test. P values < 0.05 were defined as the limit of significance. For statistical analysis, SPSS version 22 for Windows 7 (IBM Analytics, Armonk, NY) was used. The aim of our study was to evaluate the inci- dence of morbidity and mortality, and to reveal any correlations with clinicopathological factors. In addition to morbidity and mortality, the impact of morbidity and mortality on survival was stud- ied. The second aim was to reveal any differences between two chronologically successive groups (P1 and P2). Results 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. 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. 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 pa- tients 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 dis- TABLE 3. Surgical complications in 240 operated patients Type of all surgical complications (n = 240) n % % 90-day mortality No surgical complications 169 70.4 3 PF B or C 28 11.7 25 PF B or C and bleeding 8 3.3 62.5 Bleeding in the intestines 2 0.8 0 Intraabdominal bleeding – no PF 4 1.7 25 Bile leak 10 4.2 0 Leak from GEA 5 2.1 20 Dehiscence of laparotomy 3 1.3 0 Intraabdominal abscess 6 2.5 0 Ileus 1 0.4 0 Thrombosis of vascular graft 2 0.8 0 Volvulus coeci 1 0.4 0 Stenosis of coeliac trunk 1 0.4 0 Total 240 100.0 7.9% GEA = gastroenteroanastomosis; PF B and C = pancreatic fistula type B and C TABLE 4. General complications in 240 operated patients Type of all general complications (n = 240) n % % 90-day mortality No general complications 202 84.2 5.0 Pneumonia 8 3.3 25 Cardiorespiratory decompensation 3 1.3 100 Heart failure 9 3.8 11.1 Pulmonary embolism 4 1.7 25 Different infections 10 4.2 10 Renal failure 1 .4 100 Brain stroke 1 .4 0 Miscellaneous 2 .8 0 Total 240 100.0 7.9 Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection 59 charged secretion on drains in ordinal fashion; it was rather the consequence of clinical factors and therapeutic measures. One of the common consequences of compli- cations 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%. Correlation of clinicopathological factors and perioperative morbidity Age and physical status Patients with OAC and AGC were older, and their physical status according to ASA was worse. Physical status was worse also in a group of patients with PL (29.5% vs. 16.1%; p = 0.042). Regarding this, no correlations were found in other subsets of complications (AA, BC, and OL) (Table 5). Preoperative bilirubin value and EBD. At our dis- posal were only bilirubin values from the period within a week before the PD, and the majority of patients was transferred to our institution with already placed EBD more than 1 week before the operation. This prevented us to make any conclu- sive analysis on this issue. Generally, patients with preoperative placed EBD had lower mean preop- erative bilirubin values than those without EBD (57.4 ± 66 vs. 83.8 ± 86mmol/l; p = 0.005). Increased mean bilirubin level was noted in BC (134.7 ± 104 vs. 70.7 ± 71.6 mmol/l; p = 0,005). EBD was in 37.6% of our patients associated with the occurrence of ASC and in 30% with PL (ASC: 37.6% vs. 24.5%, p = 0,024, PL: 30% vs. 12.5%, p = 0,004), but there have been no correlations of EBD with other settings of complications (Table 5). TABLE 5. Correlation of clinicopathological factors and perioperative morbidity and mortality in 240 operated patients N OAC P ASC P BC P OL P AA P PL P AGC P Age (years) 240 No compl.Compl. 64.6 ± 10 68.4 ± 9.1 0.005 65.3 ± 10.3 67.9 ± 9.1 0.051 66.2 ± 10 63.5 ± 12 0.452 66 ± 10 67.1 ± 8 0.665 65 73 0 056 65.7 ± 10 67.3 ± 8 0.256 65.4 ± 10 70.1 ± 9 0.007 Age (<70 and >69) 240 <70 >69 28.6% 43.7F% 0.011 23.8% 33.3% 0.071 8.6% 3.7% 0.094 4.8% 6.7% 0.369 0% 100% 0.030 16.3% 21.4% 0.234 8.6% 18.5% 0.021 ASA 1.2 vs. 3 240 ASA 1+2ASA 3 32% 52.5% 0.004 23.8% 33.3% 0.042 5.5% 6.8% 0.465 5.5% 6.8% 0.465 0.457 16.1% 29.5% 0.042 10.5% 25.4% 0.006 Total bilirubin (mmol/l) 240 No compl. Compl. 70.1 ± 74 82.9 ± 89 0.271 68.3 ± 73.6 89.5 ± 93.1 0.062 71 ± 77 134 ± 104 0.005 74.4 ± 78 75.5 ± 108 0.969 0.231 68.1 ± 70 91.4 ± 99 0.195 79 ± 82 47.4 ± 61 0.033 EBD (no/yes) 240 No EBD EBD 33.5% 43.5% 0.082 24.5% 37.6% 0.024 5.8% 5.9% 0.594 7.1% 3.5% 0.203 0.640 12.8% 30% 0.004 11.6% 18.8% 0.092 PD/TP 240 PDTP 37.2% 36.4% 0.545 29.5% 27.3% 0.488 6.3% 3% 0.400 5.8% 6.1% 0.600 1% 12.1% 0.004 - - 13% 21.2% 0.126 Vasc. resect. (yes/no) 240 No vasc. Vasc. resect. 39.5% 27.5% 0.115 30.0% 25.0% 0.334 4.5% 12.5% 0.063 6% 5% 0.578 0.738 21.1% 7.7% 0.083 16.5% 2.5% 0.011 Size of tumor (mm) 201 No compl. Compl. 32.3 ± 19 24.6 ± 12 0.001 31.7 ± 18.8 23.7 ± 10.1 0.002 29.5 ± 17 25 ± 10 0.187 29.4 ± 17 25.1 ± 13 0.320 0.069 30.3 ± 18 22.5 ± 9 0.001 29.7 ± 17 25.7 ± 15 0.211 Type of tumor PAC/NPC 216 PAC NPC 34.1% 46.9% 0.042 26.7% 37.0% 0.074 6.7% 4.9% 0.421 5.9% 7.4% 0.435 0.403 16.2% 25.7% 0.092 69.8 ± 183 83.5 ± 127 0.094 Amylase level (ukat/l) 187 No compl. Compl. 21.3 ± 62.1 150.6 ± 252 0.0001 24.0 ± 73 179.9 ± 270 0.0001 68.6 ± 175 128.1 ± 199 0.333 72.3 ± 180 62.5 ± 100 -0.773 72.5 ± 177 1.1 ± 1 0.0001 22.2 ± 70 260 ± 310 0.0001 69.8 ± 183 83.5 ± 127 0.640 Amylase (>7 ukat/l) 187 < 7 > 7 20.2% 69.8% 0.0001 11.4% 61.6% 0.0001 3.5% 12.7% 0.022 1.7% 60.3% 0.0001 0.529 19.1% 100% 0.0001 35.6% 57.7% 0.033 PF C (yes/no) 187 No PF C PF C 33.1% 100% 0.0001 23.7% 100% 0.0001 3% 38.9% 0.0001 0.318 0.818 10.7% 100% 0.0001 - 0.464 PF B (yes/no) 187 No PF B PF B 33.1% 100% 0.0001 23.7% 100% 0.0001 6.5% 5.6% 0.676 0.318 0.818 10.7% 100% 0.0001 - 0.221 PF A (yes/no) 187 No PF A PF A 42.5% 22.2% 0.035 36.3% 0 0.0001 0.148 0.171 0.734 24% 100% 0.0001 - 0.141 PF B or C 187 No PF B+CPF B+C 25.2%. 100% 0.0001 14.6% 100% 0.0001 2.6% 22.2 0.0001 0.088 0.655 Period of the study 240 P1P2 35.4% 38.2% 0.383 25.0% 31.9% 0.155 2.1% 8.3% 0.036 5.2% 6.3% 0.485 0.230 16.9% 21.2% 0.292 17.7 11.8 0.137 Hospital stay (days) 240 14.2 ± 4 31.4 ± 16 0.0001 15.2 ± 6 32.9 ± 17 0.0001 19.3 ± 13 31.9 ± 8 0.003 18.1 ± 9 44.9 ± 29 0.0001 19.6 ± 13 29 ± 10 0.075 17.8 ± 12 30.7 ± 9 0.0001 18.4 ± 12 30.9 ± 10 0.0001 AA = intraabdominal abscess; ASC = all surgical complications; AGC = all general complications; BC = bleeding complications; comp. = complications, EBD = external biliary drainage; No compl. = no complications; NPC = non-pancreatic carcinoma; OAC = overall complications; OL = other anastomotic leak; PAC = pancreatic adenocarcinoma; PD = pancreaticoduodenectomy; PL = pancreatic leak anastomosis; PF C/ B/ A = pancreatic fistula type C/ B/ A; TP = total pancreatectomy; Vasc. resect. = vascular resection; No vasc. = no vascular resection Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection60 Type of resection and vascular resections PD and TP were comparable regarding all clinico- pathological factors except of AA which was more likely after TP (1% vs. 12.1%; p = 0.004). Resections of VMS/VP correlated only with AGC revealing even less complications if vascular resection has been done (2.5% vs. 16.5%; p = 0.011). This correla- tion was difficult to explain since patients with vas- cular resection were comparable regarding the age and physical status (mean age: 65.2 vs. 66.1 years; p = 0.556; ASA 3 vs. ASA 1 and 2: 22.2% vs. 25%; p = 0.456) (Table 5). Type and size of the tumor Data of tumor dimensions were available for 201 patients. There was a high correlation between tumor size and tumor type revealing NPCs to be smaller and PACs to be larger. In groups of OAC, ASC and PL, smaller size of tumor significantly predicted the onset of complications. Calculation revealed that patients with NPC were more prone for onset of OAC than those with PAC (Table 5). Amylase on drains Complications after PD were associated with am- ylase rates more than 7 ukat/l. The mean amylase value was increased only in OAC and ASC (OAC: 150.6 ± 252 vs. 21 ± 62; p < 0.0001, ASC: 179.9 ± 270 vs. 24 ± 73; p < 0.0001). Since PF A has never been noticed, it did not have any negative impact on any type of complications. There is an inverse correlation of mean amylase level and AA (1.1 ± vs. 72.5 ± 177 ukat/l; p < 0.0001) proving that ab- scesses did not originate from pancreatic leak. Smaller size of the tumor proved to be a predictor for the occurrence of PL (30.3 ± 18 vs. 22.5 ± 9; p = 0.001). Amylase rates more than 7 ukat/l and PF B were more often noted in NPCs (amylase < 7 ukat/l: 48.4% vs. 25.3%; p = 0.002, PF B: 17.2% vs. 6.3%; p = 0.029), but there was no correlation at the whole between PF C and type of tumor (Table 5). Correlation of clinicopathological factors and perioperative mortality Patients who suffered complications in terms of OAC, ASC, AGC, BC, PL and PF C were at a signif- icant higher risk for postoperative mortality (OAC 30-day: 13.5% vs. 0%; p < 0.0001, OAC 90-day: 20% vs. 0.7%; p < 0.0001, ASC 30-day: 14.3% vs. 1.2%; p < 0.0001, ASC 90-day: 20% vs. 2.9%; p < 0.0001, AGC 30-day: 14.1% vs. 4.3%; p < 0.0001, AGC 90- day: 20% vs. 2.9%; p < 0.0001, BC 30-day: 35.7% Vs. 3.1%; p < 0.0001, BC 90-day: 34.3% vs. 7.2%; p < 0.0001, PL 30-day: 22.2% vs. 2%; p < 0.0001, PL 90- day: 33.3% vs. 3.2%; p < 0.0001, PF C 30-day: 33.3% vs. 2.9%; p < 0.0001, PF C 90-day: 50% vs. 4.7%; p < 0.0001). On the other hand, OL and AA did not impact the 30- and 90-day mortality. Age did not correlate to 30- or 90-day mortality; however, ASA physical status did (30-day: 11.9% vs. 2.8%; p = 0.011, 90-day: 18.6% vs. 4.4%; p = 0,001). Patients with amylase rich secretion more than 7 ukat/l were also at a higher risk to die within 30 or 90 days after operation (amylase > 7ukat/l 30- day: 14.3% vs. 1.7%; p = 0.002, amylase > 7ukat/l 90-day: 20.6% vs. 3.4%; p < 0.0001). However, mean value of amylase on drains was significantly higher in patients that died within 90 days compared to those who died in 30 days (90-day: 172 ± 231 vs. 59.1 ± 170ukat/l; p = 0.013). Tumor type or size of the tumor, mean preoperative total bilirubin, EBD, and PF A and B did not correlate with 30- and 90- day mortality. Multivariate analysis Predictors found to be significant for 30- and 90- day morbidity and mortality in the univariate analysis were included in the multivariate logistic regression analysis. For OAC, higher mean age and drained amyl- ase more than 7 ukat/l (age: CI 95%: 1.019-1.103; p = 0.004, amylase > 7ukat/l: 95% CI: 0.045-0.204; p < 0.0001) were predictive. For ASC, higher mean amylases and drained amylase more than 7 ukat/l (mean amylase: 95% CI: 1.000-1.007; p = 0.047, 95%, amylase > 7 ukat/l: CI: 0.070 – 0.427; p < 0.0001) were specific. Moreover, for AGC, physical status, mean age and mean level of total bilirubin pre- operatively (ASA: 95% CI: 1.007 -1.121; p = 0.028, mean age: 95% CI: 1.042-6.715; p < 0.041, mean total bilirubin: 95% CI: 0.981-0.999; p < 0.027) revealed as independent predictors. For 30-day mortality, PL and BC revealed as in- dependent predictors (PL: 95% CI: 0.026-0,522; p = 0.005, BC: 95% CI: 0.024-0 537; p = 0.006). In case of 90-day mortality, physical status, OAC and PF C (ASA: 95% CI: 1.404 -16.514; p = 0.012, OAC: 95% CI: 1.622-117.599; p = 0.016, PF C: 2.030-28.244, p = 0.003) were noticed as predictive factors. Survival analyses Patients who had OAC, ASC, AA, OL or AGC have had comparable expectation for long-term survival to those without complications (OAC: 866 ± 139 Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection 61 vs. 760 ± 174 days, Log Rank: p = 0.242; ASC: 866 ± 134 vs. 901 ± 216 days, Log Rank: p = 0.234; AA: Log rank: p = 0,048, OL: 836 ± 123 vs. 1159 ± 673 days; Log rank: p = 0.760, AGC: 866 ± 135 vs. 760 ± 197 days, Log Rank: p = 0.431). Complications like PL in PD and BC in all resected patients seriously compromised the expected long-term survival (PL: 938 ± 67 vs. 499 ± 146 days; Log Rank: p = 0.010, BC: 901 ± 128 vs. 409 ± 457 days; Log Rank: p = 0.046). On the other hand, in patients who survived complications, the long-term survival was not im- pacted by any type of complications (Figures 1,2). Differences between two chronologically successive groups Two chronologically successive groups of patients were comparable on most clinicopathological fac- tors except for preoperative gained histology, preoperative total bilirubin, and type of resection (Table 2). The indications for TP were: postop- erative bleeding from the pseudo-aneurism of the proximal part of the common hepatic artery com- bined with leak of the PEA (1 patient); PAC and main duct IPMN (9 patients); diffuse main duct IPMN (1 patient); very soft pancreas (10 patients); positive resection margins (5 patients); tumor ex- tending to the body of the pancreas (5 patients); and formerly removed left pancreas (2 patients) (Table 1). Five out of 10 patients with extremely soft pancreas had also vascular reconstructions with prosthetic interposition, and three already had insulin dependent diabetes. The overall (P1 and P2) 30- and 90-day mortality in our cohort were 5 and 7.9% respectively. In P2, the rates for 30- and 90-day mortality became lower, 3.5% and 5% respectively, but the statistical difference be- tween P1 and P2 reveals only borderline statistical value (p = 0.08) (Table 2). Discussion Pancreatic resections present the only curative option for patients with malignant and prema- lignant diseases, and for relief of symptoms in selected group of patients with chronic pancreati- tis. However, due to high morbidity and mortal- ity, 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 gradu- ally 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 pa- tients 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 dur- ing 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 sig- nificantly differs concerning the hospital volume. One of the consequences of postoperative morbid- ity 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 pre- dictor 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 independ- ent 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 select- ing the patients for PD or TP. There is an ongoing debate on whether jaun- diced 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 pro- foundly 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 regard- ing the perioperative morbidity and mortality between PDs and TPs except for abdominal ab- scesses, 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 Radiol Oncol 2018; 52(1): 54-64. Potrc S et al. / Impact factors for perioperative morbidity and mortality in pancreatic head resection62 tolerate this kind of complications at all.41–43 In pa- tients 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 for- merly regarded as a relative contraindication for the PD. However, nowadays it presents a stand- ard 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 mor- bidity and mortality.47–52 The proportion of chronic pancreatitis in PACs and NPCs included in the reports can differ sig- nificantly, and if cases with predominantly hard pancreas remnant predominate, as in patients with chronic pancreatitis, the overall risk for postopera- tive 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 tu- mor affects the onset of OAC, ASC and PL; howev- er, 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 be- tween PF A, B and C. There is consensus among all reports that PF negatively affected the postopera- tive 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 am- ylases on drains were low proving that abscesses did not originate from pancreatic leak. PF A was not associated with any serious morbidity in post- operative course of our patients. Patients with OAC, ASC, AGC, BC, PL, PF C and high mean am- ylase 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 re- garding almost all clinicopathological factors ex- cept 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 compa- rable regarding age, physical status, tumor mark- ers, 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 respon- sible, even the inform consent must be done pre- operatively 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 correla- tion. Most subtypes of complications did not com- promise 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 sig- nificantly compromised. On the other hand, in pa- tients 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 mor- tality. Even though the decrease in 30- and 90-day mortality (3.5% and 5%) tightly missed the signifi- cance in our cohort of patients, the trends of better surgery in pancreatic resections in our institution seemed to be encouraging. 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