The role of cold ischemia time and hypothermic perfusion in predicting early hepatocellular carcinoma recurrences after liver transplantation.

AIM: The aim of the study was to identify predictors of early tumor recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: Retrospective cohort study in 237 consecutive liver recipients with HCC between 2016 and 2021. Multivariate logistic analysis was performed to identify predictors of early HCC recurrences. The impact of hypothermic-oxygenated perfusion (HOPE) on outcome was analyzed after propensity score weighting. RESULTS: Early recurrences were observed in 15 cases. Microvascular invasion (OR 3.737, 95% CI 1.246-11.206, p = 0.019) and cold ischemia time (OR 1.155, 95% CI 1.001-1.333, p = 0.049) were independently associated with a lower risk of HCC recurrences. After balancing for relevant variables, patients in the HOPE group had lower rates of tumor recurrence (weighted OR 0.126, 95% CI 0.016-0.989, p = 0.049) and higher recurrence free survival (weighted HR 0.132, 95% CI 0.017-0.999, p = 0.050). CONCLUSION: Reducing cold ischemia time and graft perfusion with HOPE can lead to lower rates of early HCC recurrences and higher recurrence-free survival.

Renal Vessel Extension With Cryopreserved Vascular Grafts: Overcoming Surgical Pitfalls in Living Donor Kidney Transplant.

In LDKT, right kidneys and kidneys with anomalous vascularization are often deferred because of concerns on complications and vascular reconstructions. To date, only few reports have examined renal vessel extension with cryopreserved vascular grafts in LDKT. The aim of this study is to investigate the effect of renal vessel extension on short-term outcomes and ischemia times in LDKT. From 2012 to 2020, recipients of LDKT with renal vessels extension were compared with standard LDKT recipients. Subset analysis of rights grafts and grafts with anomalous vascularization, with or without renal vessel extension, was performed. Recipients of LDKT with (n = 54) and without (n = 91) vascular extension experienced similar hospital stays, surgical complications and DGF rates. For grafts with multiple vessels, renal vessel extension granted a faster implantation time (44±5 vs. 72±14 min), which resulted comparable to that of standard anatomy grafts. Right kidney grafts with vascular extension had a faster implantation time compared to right kidney grafts without vascular lengthening (43±5 vs. 58±9 min), and a comparable implantation time to left kidney grafts. Renal vessel extension with cryopreserved vascular grafts allows faster implantation time in right kidney grafts or grafts with anomalous vascularization, maintaining similar surgical and functional outcomes.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial.

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

Heterotopic segmental liver transplantation on splenic vessels after splenectomy with delayed native hepatectomy after graft regeneration: A new technique to enhance liver transplantation.

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.

Complex Liver Transplantation Using Venovenous Bypass With an Atypical Placement of the Portal Vein Cannula.

In liver transplantation (LT) medical literature, venovenous bypass (VVB) with the interposition of a venous graft attached to the inferior mesenteric vein (IMV) or to the splenic vein (SV) has not been reported previously. Here, we report the decompression of the portomesenteric compartment in 2 patients with complex cases of orthotopic LT. A femoroaxillary percutaneous VVB was installed prior to abdominal opening to decompress massive collateral veins in the abdominal wall. In the first patient, the IMV was connected to a donor vein graft with a lateroterminal anastomosis, and the distal part of the vein graft was cannulated and connected to the VVB. In the second patient, because of the excessive size of the spleen, it was necessary to perform a splenectomy to gain sufficient space in the abdomen to implant the new liver. The SV was connected to a donor vein graft with a terminoterminal anastomosis, and the distal part of the vein graft was cannulated and connected to the VVB. In both patients, the decompression of the portomesenteric compartment was crucial to reduce portal hypertension and to access the hepatic hilum, where the dissection was very complex due to previous major surgeries. In conclusion, VVB with the interposition of a venous graft attached to the IMV or to the SV during LT is a safe and simple technique, and it may be useful for patients needing VVB with no standard access to the portal compartment, particularly in the case of severe portal hypertension and re-LTs.

Preliminary experience of sequential use of normothermic and hypothermic oxygenated perfusion for donation after circulatory death kidney with warm ischemia time over the conventional criteria - a retrospective and observational study.

Donation after circulatory death (DCD) is a potential source of reducing organ demand. In Italy, DCD requires a 20-min no-touch period that prolongs warm ischemia and increases delayed graft function (DGF) risk and graft loss. We report here our preliminary experience of sequential use of normothermic regional perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion (HOPE), as an experimental technique of organ preservation, in 10 kidney transplants (KT) from five DCD Maastricht III with extensive functional warm ischemia time (fWIT) up to 325 min. During NRP, renal function tests were evaluated to accept organs which were retrieved according to standard fashion with biopsy. While waiting for pathology and cross-match results, organs were preserved with HOPE through pressure- and temperature-controlled arterial pulsatile flow. All grafts with Karpinski score ≤4 were used for conventional single KT with mean cold ischemia time of 584 ± 167 min and mean fWIT of 151 ± 132 min. At the end of HOPE, lactate levels increased significantly in all cases with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were recorded, and all patients had sCr < 1.5 mg/dl at 6-month post-KT. NRP and HOPE for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF.

Ten-Year Survival after Liver Resection for Breast Metastases: A Single-Center Experience.

BACKGROUND: The role of liver resection for metastatic breast carcinoma is still debated. METHODS: Fifty-one resected patients were reviewed. All patients received adjuvant chemotherapy after resection of the primary tumor. Clinicopathological characteristics and immunohistochemistry expression of estrogen (ER), progesterone (PR), human epidermal growth factor (HER2), or Ki67 were evaluated. RESULTS: The median number of metastases was 2; single metastases were present in 24 (47%) patients. The median tumor diameter was 4 cm. Major hepatectomies were performed in 31 (61%) patients. Postoperative mortality was null. Postoperative morbidity was 13.7%. The 1-, 5-, and 10-year survival rates were 92, 36, and 16% respectively. Eleven (21.6%) patients survived longer than 5 years and 8.9% are alive without recurrence 10 years after surgery. At the univariate analysis, tumor diameter, lymph node status, PR receptor status, and triple positive receptors (ER+/PR+/Her2+) were significantly related to survival. At the multivariate analysis, tumor diameter, PR receptor, and triple negative status were significantly related to the long-term outcome. CONCLUSION: Liver resection seems to be a safe and effective treatment for metastases from breast cancer, and encouraging long-term survival can be obtained with acceptable risk in selected patients. Tumors less than 5 cm and positive hormone receptor status are the best prognostic factors.

Actual Risk of Using Very Aged Donors for Unselected Liver Transplant Candidates: A European Single-center Experience in the MELD Era.

OBJECTIVE: To evaluate the whole experience of liver transplantation (LT) with donors ≥70 years in a single center not applying specific donor/recipient matching criteria. BACKGROUND: LT with very old donors has historically been associated with poorer outcomes. With the increasing average donor age and the advent of Model for End-stage Liver Diseases (MELD) score-based allocation criteria, an optimal donor/recipient matching is often unsuitable. METHODS: Outcomes of all types of LTs were compared according to 4 study groups: patients transplanted between 1998 and 2003 with donors <70 (group 1, n = 396) or ≥70 years (group 2, n = 88); patients transplanted between 2004 and 2010 with donors <70 (group 3, n = 409), or ≥70 years (group 4, n = 190). From 2003, graft histology was routinely available before cross-clamping, and MELD-driven allocation was adopted. RESULTS: Groups 1 and 2 were similar for main donor and recipient variables, and surgical details. Group 4 had shorter donor ICU stay, lower rate of moderate-to-severe graft macrosteatosis (2.3% vs 8%), and higher recipient MELD score (22 vs 19) versus group 3. After 2003, median donor age, recipient age, and MELD score significantly increased, whereas moderate-to-severe macrosteatosis and ischemia time decreased. Five-year graft survival was 63.6% in group 1 versus 59.1% in group 2 (P = 0.252) and 70.9% in group 3 versus 67.6% in group 4 (P = 0.129). Transplants performed between 1998 and 2003, recipient HCV infection, balance of risk score >18, and pre-LT renal replacement treatments were independently associated with worse graft survival. CONCLUSIONS: Even without specific donor/recipient matching criteria, the outcomes of LT with donors ≥70 and <70 years are comparable with appropriate donor management.

Combined liver-dual kidney transplant: Role in expanded donors.

Kidney injury is a common clinical feature among liver transplantation (LT) candidates that heavily affects prognosis and complicates the surgical decision-making process. Up to 20% of patients undergoing LT demonstrate some degree of renal impairment, and 2% will benefit from a combined liver-kidney transplantation (LKT). We present a case-control study of all patients who underwent LKT and combined liver-dual kidney transplantation (LDKT) from November 2013 to March 2016. For the selection of LDKT candidates, a histological-based algorithm was applied: when evaluating extended criteria donors (ECDs), with any Remuzzi score between 4 and 7, we would consider performing a LDKT instead of a simple LKT. Study groups were similar for recipient variables. In the LDKT group, donor age, donor risk index, and donor body mass index were found to be significantly higher. Biopsies obtained from all pairs of kidney grafts in the LDKT group demonstrated the following Remuzzi scores: 4+4, 4+4, 7+1, 4+5. Despite longer operative times for the LDKT procedure, no differences were observed regarding the main investigated outcome parameters. Overall survival was 100% (LDKT) and 91% (LKT, P > 0.99). This is a preliminary experience which might indicate that LDKT is a safe, feasible, and resource-effective technique. The evaluation of a larger cohort, as well as the experience from other centers, would be needed to clearly identify its role in the ECD era. Liver Transplantation 23:28-34 2017 AASLD.

Liver and Vena Cava En Bloc Resection for an Invasive Leiomyosarcoma Causing Budd-Chiari Syndrome, Under Veno-Venous Bypass and Liver Hypothermic Perfusion : Liver Hypothermic Perfusion and Veno-Venous Bypass for Inferior Vena Cava Leiomyosarcoma.

BACKGROUND: Leiomyosarcoma of vascular origin is a rare tumor, occurring mainly in the inferior vena cava (IVC). When involving the hepatic vein confluence, it often causes Budd-Chiari syndrome, and IVC removal with a complex hepatectomy is required (Mingoli in J Am Coll Surg 211:145-146, 2010; Griffin in J Surg Oncol 34:53-60, 1987; Heaney in Ann Surg 163:237-241, 1966; Fortner in Ann Surg 180:644-652, 1974). METHODS: A 57-year-old male, without previous oncological history, presented with Budd-Chiari syndrome due to a leiomyosarcoma extending to the supra-diaphragmatic IVC and involving the right and middle hepatic veins. The patient did not receive neoadjuvant treatment. RESULTS: A femoral to superior vena cava veno-venous bypass was inserted, and both a median sternotomy and phreno-laparotomy with right subcostal extension were performed. A hemi-portocaval shunt was created between the right portal branch and the IVC, while a catheter was connected to the left portal branch for cold perfusion. Under extracorporeal circulation, the IVC was sectioned after infrahepatic and supra-diaphragmatic cross-clamping. The left liver was flushed with Celsior solution and packed with ice. A right trisectionectomy extended to the caudate lobe with en bloc vena cava removal was performed. The IVC was replaced by a cryopreserved aortic homograft, to which the stump of the left hepatic vein was anastomosed. Bypass duration, warm and cold liver ischemia, and operation time were 280 min, 8 min, 112 min, and 11 h, respectively. Duct-to-duct biliary anastomosis tutored by a T-tube was performed, and the patient was discharged on postoperative day 29, without major complications. After 16 months free of disease, the patient developed bilateral lung metastases. After 4 years the patient is still alive and receiving systemic chemotherapy. CONCLUSIONS: Leiomyosarcoma of the IVC involving the hepatic veins can be treated with extended hepatectomy and removal of the IVC through extracorporeal circulation.

Risk Avoidance and Liver Transplantation: A Single-center Experience in a National Network.

OBJECTIVES: To evaluate the risk avoidance policy at liver transplant centers. BACKGROUND: Transplant center improvements have extended the indications for the sickest patients and the use of extended criteria donors (ECD). This may result in lower survival, perhaps paradoxically discouraging transplant centers from these procedures. We evaluated the outcome of recipients or donors refused by other transplant centers and transplanted by our transplant unit without risk avoidance policy. METHODS: Between 2007 and 2015, 616 patients underwent liver transplantation at our Unit; 142 patients (23%) had been rejected by other Italian centers, because of recipient selection (70 patients, 11%) or because of donor selection (78 patients, 12%), group A. Recipient and donor features were analyzed and compared with 474 patients transplanted in the same period, group B. RESULTS: Recipients were mainly rejected for comorbidity (19%), portal vein thrombosis (16%), previous surgery (9%), obesity (9%), and hepatocellular carcinoma (6%). Donors were rejected for HBcAb+ (33%), HCV+ (18%), liver biopsy (9%), HBsAg+ (6%), neoplastic (6%), or infective risk (5%).Most recipient and donor features were comparable between groups A and B.The 1- and 3-year overall graft and patient survival rates were similar in groups A and B and were comparable with national data. CONCLUSIONS: Recipients and donor grafts were rejected for reasons not accepted by scientific literature. They did not differ from control group patients and their postoperative outcome was comparable. These results highlight the discrepancy among transplant centers and the relevance of risk avoidance in LT policy.

A comprehensive analysis on expected years of life lost due to pancreatic cancer.

BACKGROUND: Pancreatic cancer represents a fatal malignancy leading to premature death and loss of life expectancy. The aim of the present study was to assess how many years of life are lost due to this cancer, in relationship with surgery and ageing. METHODS: Data from 716 consecutive patients discharged from a tertiary referral hospital (2002-2012) with a diagnosis of pancreatic cancer and with complete clinical and follow-up data were used to estimate the number of years of life-lost (YLL) through a semi-parametric extrapolation having an age-, sex- and year-of-onset- matched population derived from national life tables as reference. RESULTS: The mean entire lifespan estimated for the 716 patients was 1.4 years (95% C.I.:0.8-1.9) resulting in a number of YLL after diagnosis of 12 years (95% C.I.:11.5-12.6) per person. Surgical patients (147 cases; 20.5%) were younger and experienced higher post-diagnostic lifespan (3.5 years) than non-surgical older individuals (0.8 years; p < 0.001). These figures were reflected on the number of expected YLL (EYLL) that remained substantially unaffected by surgery (p = 0.821). Patients aged ≤68 years experienced the highest number of EYLL (20.8 years); whereas elderly patients had a loss of life that corresponded to only 6% of the entire life they had already lived. CONCLUSIONS: In a typical pancreatic cancer cohort, surgery was not able to modify population-based statistics because of a different age at tumor onset which nullifies any benefit from a "lifespan from birth" perspective. Pancreatic cancer in younger individuals must be ranked within the very first causes of EYLL due to malignancy.

Pancreas-preserving segmental duodenectomy for gastrointestinal stromal tumor of the duodenum and splenectomy for splenic angiosarcoma.

BACKGROUND: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. METHODS: We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. (111)In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. RESULTS: At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. CONCLUSIONS: We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.

The Relationship between Timing of Pretransplant Kidney Biopsy, Graft Loss, and Survival in Kidney Transplantation: An Italian Cohort Study.

INTRODUCTION: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. METHODS: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. RESULTS: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12-0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14-0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. DISCUSSION/CONCLUSION: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

Portal vein thrombosis and liver transplantation: evolution during 10 years of experience at the University of Bologna.

OBJECTIVE: To evaluate the evolution of liver transplantation (LT) in cases with partial and total portal vein thrombosis (PVT). BACKGROUND: Portal vein thrombosis and in particular total PVT are still surgically demanding conditions, which can exclude patients from LT or increase the postoperative complications after LT. METHODS: We reviewed our 10-year experience (first era 1998­2002 and second era 2003­2008), comparing the outcome of patients with PVT to a group without PVT. RESULTS: Among 889 LTs, we intraoperatively diagnosed 91 PVTs (10.2%):51 partial PVTs (56%) and 40 total PVTs (44%). The rate of complete PVTs increased from the first to the second era (2.2% vs. 6.7%, P < 0.005). Partial PVTs were mainly treated with thrombectomy while complete PVTs were managed with thrombectomy in 26 cases (63%), jumping graft in 6 (15%), portocaval hemitransposition in 6 (15%), and anastomosis to varix in 3 (7%). Among cases of PVT and no-PVT, the postoperative mortality was comparable (6.6% vs. 5.8%), as were the 1- and 5-year patient survival rates (85% and 68% PVT vs. 86% and 73% non-PVT). The postoperative outcome was similar in the PVT group between patients with partial and complete PVT, but in this last group, patient survival differed significantly between the 1st and 2nd era (57% vs. 89% at 1 year, P < 0.05). CONCLUSIONS: Liver transplantation offers good survival in patients with partial PVT but also in selected cases with total PVT, where surgical innovation has improved the results.

Improved diagnostic imaging and interventional therapies prolong survival after resection for hepatocellular carcinoma in cirrhosis: the university of bologna experience over 10 years.

BACKGROUND: With substantial improvements in perioperative care and surgical technique, both mortality and morbidity after liver resection have progressively decreased; however, long-term prognosis is greatly affected by tumor recurrence, which represents the most frequent cause of death. The aim of this study is to analyze the outcome after hepatic resection in the present clinical scenario, where great improvements in diagnostic techniques, surveillance schedules, in other active treatments will potentially have a positive impact on survival. METHODS: Data from 300 consecutive hepatic resections performed on cirrhotic patients in a tertiary-care referral hospital from 1997 and 2008 were reviewed, and survival was calculated for the two periods considered. The first group of patients underwent hepatectomy between 1997 and 2002 (n = 126) and the second group of patients between 2003 and 2008 (n = 174). RESULTS: In the more recent period, tumor selection criteria for resectability included more patients with multinodular tumors so that solitary tumors decreased from 89.7 to 78.7% (P = 0.019); however, the tumor, node, metastasis (TNM) system stage remained unaffected. The 5-year recurrence rate remained similar (67.4 vs. 65.8%; P = 0.836). Despite these features, the 5-year patient survival increased from 52.6 to 65.8% (P = 0.023). This end result was related to a larger proportion of patients with tumor recurrence undergoing repeat resection or salvage transplantation that increased from 22.2 to 36.9% (P = 0.039). CONCLUSIONS: The increased survival is most likely the result of more stringent follow-up as well as increased accuracy in detecting recurrence at earlier stages, and consequently of more chances for potential cure when treating recurrent tumor.

Comparison between observed survival after resection of transplantable hepatocellular carcinoma and predicted survival after listing through a Markov model simulation.

There is still some debate on whether hepatic resection or liver transplantation should be the initial treatment for hepatocellular carcinoma (HCC) in compensated cirrhosis. Clinical data and observed survivals of 150 transplantable patients (within Milan criteria) resected for HCC were reviewed and their predicted survival after listing for liver transplantation was calculated using a Markov model simulation. Differences between observed and predicted survival estimates were explored by standardized differences (d). The mean observed survival within 5 years after surgery was 45.35 months, and the predicted survival after listing was 49.18 months (d = 0.265). The largest gain in life-expectancy with liver transplantation would be obtained in patients with Model for End-stage Liver Disease (MELD) score >9 (d = 0.403); conversely, observed and predicted survivals were similar in HCV+ patients (d = -0.002) and in patients with MELD ≤9 (d = -0.057). For T1 tumors, the observed mean estimate of survival after hepatic resection was higher than that predicted by the simulation (d = -0.606). In conclusion, in HCV patients and in those with very well compensated cirrhosis, hepatic resection could lead to results similar to those of transplantation strategy for HCC within Milan criteria; HCC T1 patients are probably best served by resection as first-line therapy rather than listing for transplantation.

Risk factors of pancreatic fistula after pancreaticoduodenectomy: a collective review.

Postoperative pancreatic fistula (POPF) is the most frequent complication after pancreaticoduodenectomy, results in increased morbidity and mortality, and adversely affects length of stay and costs. Reported rates of postoperative pancreatic fistula vary from 0 per cent up to more than 30 per cent. Plenty of randomized trails and meta-analysis were published to analyze the ideal procedure, technique of anastomosis, and perioperative management of patients undergoing pancreaticoduodenectomy; however, results are often discordant and clear evidence on the ideal management and surgical technique to reduce POPF rate is not yet provided. This collective review examined the current evidence about risk factors contributing to postoperative pancreatic fistula and delineates methods of diagnosis and treatment of this universally dreaded complication.