Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Gallbladder cancer mimicking perihilar cholangiocarcinoma-considerable rate of postoperative reclassification with implications for prognosis.

BACKGROUND: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3-15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA. METHODS: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009-May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15-25 months) for patients with pCCA and 17 months (95% CI 11-23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3-17 months) compared 17 months (95% CI 15-19 months) for patients with pCCA (p = 0.010). CONCLUSIONS: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies.

Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study).

BACKGROUND/PURPOSE: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. METHODS: A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. RESULTS: A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P =0.03) was an independent prognostic factor of poor overall survival. CONCLUSIONS: Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Surgical Outcomes and Trends for Chronic Pancreatitis: An Observational Cohort Study from a High-Volume Centre.

Surgery for chronic pancreatitis (CP) is considered as a last resort treatment. The present study aims to determine the short- and medium-term outcomes of surgical treatment for CP with a comparison between duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD). The trends in surgical procedures were also examined. This was a retrospective cohort study of patients who underwent surgery for CP between 2000 and 2019 at the Karolinska University Hospital. One hundred and sixty-two patients were included. Surgery performed included drainage procedures (n = 2), DPPHR (n = 35), resections (n = 114, of these PD in n = 65) and other procedures (n = 11). Morbidity occurred in 17%, and the 90-day mortality was 1%. Complete or partial pain relief was achieved in 65% of patients. No significant difference in morbidity was observed between the DPPHR and PD groups: 17% vs. 20% (p = 0.728). Pain relief did not differ between the groups (62% for DPPHR vs. 73% for PD, p = 0.142). The frequency of performed DPPHR decreased, whereas the rate of PD remained unaltered. Surgical treatment for CP is safe and effective. DPPHR and PD are comparable regarding post-operative morbidity and are equally effective in achieving pain relief. Trends over time revealed PD as more commonly performed compared to DPPHR.

Redefining resection margins and dissection planes in perihilar cholangiocarcinoma-radical resection is a rare event.

Radical tumor resection (pR0) is prognostic for disease-free and overall survival after resection of perihilar cholangiocarcinoma (pCCA). However, no universal agreement exists on the definition of radical resection and histopathological reporting. The aim of this study was to provide a standardized protocol for histopathological assessment and reporting of the surgical specimen obtained after resection for pCCA. All consecutive patients operated for pCCA with curative intent at the Karolinska University Hospital, Stockholm, Sweden between 2012 and 2021 were included. A standardized protocol for histopathological assessment and reporting of the surgical specimen after liver resection for pCCA is presented. A detailed mapping of the transection margins and dissection planes was performed. The results of applying different existing pR0 definitions were compared. Sixty-eight patients with pCCA were included. Five transection margins and two dissection planes were defined. By defining pR0 as cancer-free margins and planes tolerating distances <1mm, the pR0 rate was 66%. However, when pR0 was set as >1mm from invasive cancer to all resection margins and dissection planes, the pR0 rate fell to 16%. This study supports the use of thorough and standardized pathological handling, assessment and reporting of resection margins and dissection planes of surgical specimens of pCCA.

Intrahepatic Microdialysis for Monitoring of Metabolic Markers to Detect Rejection Early After Liver Transplantation.

OBJECTIVES: The clinical and biochemical manifestations of acute rejection after liver transplantation are nonspecific, and a liver biopsy is often needed to verify the diagnosis. This may delay treatment. The aim of this study was to evaluate whether monitoring of intrahepatic glucose, lactate, pyruvate, and glycerol by microdialysis can be used to predict rejection early after liver transplantation. METHODS: Seventy-one patients undergoing liver transplantation were included in the study. The patients were monitored using microdialysis for up to 6 days postoperatively. Patients who developed acute rejection within 1 month were identified according to standard protocol. Area under the curve (AUC) was calculated for 12-hour intervals for glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio. Patients with and without rejection were compared with respect to these parameters, as well as standard liver blood investigations and time-zero biopsies. RESULTS: The lactate/pyruvate ratio was higher at 0 to 12 hours in the group with rejection as compared to the group without rejection. Glucose was lower in the group with rejection at 24 to 48 hours. Also, the intrahepatic lactate levels at 48 to 72 hours and pyruvate levels at 60 to 72 hours after liver transplantation, were higher in the rejection group. The lactate/pyruvate ratio at 0 to 12 hours and lactate at 60 to 72 hours were two independent risk factors for rejection within the first month after liver transplantation. No significant differences in glycerol levels could be detected between the two patient groups. CONCLUSIONS: Microdialysis monitoring following liver transplantation may be useful in the detection of the metabolic events that precede rejection. The metabolic patterns detected by microdialysis early after transplantation indicate a possible relation between primary ischemia-reperfusion injury and the development of rejection. Identifying these patterns may help to identify patients at risk for the development of acute rejection and may help select those who may benefit from higher dose of immunosuppression early after liver transplantation.

Hepatopancreatoduodenectomy -a controversial treatment for bile duct and gallbladder cancer from a European perspective.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

Evaluation of Intrahepatic Lactate/Pyruvate Ratio As a Marker for Ischemic Complications Early After Liver Transplantation-A Clinical Study.

BACKGROUND: Lactate/pyruvate ratio has been introduced as a sensitive marker for ischemia in the transplanted liver. In the present study, we aimed to evaluate lactate/pyruvate ratio measured in the liver by microdialysis as a marker for ischemic complications early after liver transplantation. METHODS: Forty-five patients undergoing liver transplantation were included in the study. A microdialysis catheter was placed in the liver graft directly following liver transplantation and the metabolites lactate and pyruvate measured for up to 6 days and the lactate/pyruvate ratio calculated. The association between increased intrahepatic lactate/pyruvate ratio and ischemic complications was studied. RESULTS: One of 45 patients developed hepatic arterial thrombosis. Forty-four events with increased lactate/pyruvate ratio were identified in 24 patients. In none of the 24 patients that had a raised lactate/pyruvate ratio could we detect occurrence of any ischemic complication. In the patient that did have hepatic arterial thrombosis, the lactate/pyruvate ratio did not show a significant prolonged rise. CONCLUSIONS: An increase in the intrahepatic lactate/pyruvate ratio is not necessarily indicative of ischemic complications and is thus not a reliable marker for monitoring of clinically significant ischemia in the liver early after transplantation.

Membrane cut-off does not influence results regarding the measurement of small molecules - a comparative study between 20- and 100-kDa catheters in hepatic microdialysis.

BACKGROUND: Microdialysis is a method used to monitor hepatic tissue metabolism. Membranes with a molecular cut-off of 20 kilodalton (kDa) are currently used to measure the small metabolites glucose, glycerol, lactate and pyruvate. Using membranes with higher cut-off such as 100 kDa allows the possibility of measuring larger molecules but may affect results regarding small molecules. The aim was to compare microdialysis catheters with a cut-off of 20 and 100 kDa in the measurement of small molecules in a pig liver model. METHODS: Four microdialysis catheters were inserted into the liver of each pig used in the experiment (n = 6). Two catheters with cut-off of 20 kDa were perfused with Ringer acetate, and two catheters with cut-off of 100 kDa: one perfused with Ringer acetate and one with hydroxyethyl starch (Voluven) at a flow rate of 0·3 µl min(-1). Dialysate samples were collected at 40-min intervals and analysed for glucose, glycerol, lactate and pyruvate. RESULTS: Compared to the other catheters, the 100-kDa catheters perfused with Ringer acetate tended to measure higher dialysate concentrations of the small molecules, the difference reaching statistical significance in the case of pyruvate. Concentrations measured by the 100-kDa catheters perfused with Voluven were, however, comparable to the 20-kDa catheters. CONCLUSIONS: Microdialysis catheters with membrane cut-off of 20 and 100 kDa can be used equally in hepatic microdialysis for the monitoring of glucose, glycerol, lactate and pyruvate, and lactate/pyruvate ratio if a high osmotic solution (Voluven) is used to perfuse the 100-kDa catheters.

The clinicopathological spectrum and management of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B).

BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a rare but increasingly diagnosed clinical entity. Typical cholangioscopic findings usually include intraductal protruding papillary tumors that secrete mucus. METHODS: Clinical, radiological and histopathological data of seven consecutive patients who were found to have IPMN-B were analyzed. RESULTS: Six of the seven patients presented with obstructive jaundice/cholangitis as the presenting complaint. ERCP and other imaging were equivocal in five of these patients and peroral cholangioscopy (POCS, single-operator cholangioscopy system) was performed. This revealed mucin-producing intraductal tumors with numerous frond-like papillary projections; a macroscopic appearance consistent with IPMN-B. Preoperative biopsy revealed adenoma, with low-grade dysplasia in two patients and high-grade dysplasia in three. Three patients underwent Whipple resection; one underwent total pancreatectomy with left hepatectomy, one patient a pancreas preserving duodenectomy with common bile duct reimplantation and one patient an extended right hepatectomy. These patients were found to have IPMN-B with adenomatous changes with varying grades of dysplasia and even cholangiocarcinoma on final histopathology. One patient first underwent endoscopic papillectomy and on follow-up was found to have cholangiocarcinoma with metastases to the liver. CONCLUSION: POCS can be a key diagnostic investigation in the evaluation of patients with papillary tumors of the bile duct. IPMN-B has a heterogenous pathology and varying grades of dysplasia and even carcinoma may exist in the same patient. Surgical management should be radical and based on tumor extent.

Borderline resectable pancreatic tumors: is there a need for further refinement of this stage?

BACKGROUND: The ideal treatment of patients with "borderline resectable pancreatic tumors (BRTs)" needs to be established. Current protocols advise neoadjuvant chemo(radio)therapy, although some patients may appear to have BRT on preoperative imaging and a complete resection may be achieved without the need for vascular resection. The aim of the present study was to identify specific findings on preoperative imaging that could help predict in which patients with BRT a complete resection, with or without vascular resection (VR), could be achieved. METHODS: Twelve patients with BRTs were identified. Tumor location, maximum degree of circumferential contact (CC), length of contact of the tumor with major vessels (LC), and luminal narrowing of vessels at the point of contact with the tumor (venous deformity, VD) were graded on preoperatively acquired multidetector computed tomography (MDCT) images and then compared with the intraoperative findings and need for VR. RESULTS: A complete resection (R0) was achieved in 10 patients with 2 having microscopic positive margins (R1) on histopathology at the uncinate margin. Four of the 10 patients required VR (40%). In 3 of the 4 patients whose tumors required VRs, CC was ≥grade III and VD was grade 2. LC did not influence the need for VR. CONCLUSIONS: It is possible to achieve a complete resection at the first instance in patients found to have BRTs on preoperative imaging. Preoperative MDCT-based grading systems and our proposed criteria may help identify such patients, thus avoiding any delay in curative resections in such patients.

Continuous assessment of intrahepatic metabolism by microdialysis during and after portal triad clamping.

BACKGROUND: Ischemia-reperfusion injury is a major concern with portal triad clamping (PTC) in liver surgery. Microdialysis allows continuous intraoperative monitoring of tissue metabolism in the liver. Our aim was to evaluate the feasibility of microdialysis as a tool to assess the intrahepatic metabolic effects of PTC in patients undergoing liver resection. METHODS: Eleven patients who underwent liver resection were subjected to intrahepatic microdialysis. Dialysis fluid samples were collected before, during, and after a 20-min period of PTC. Glucose, lactate, pyruvate (markers of ischemia), and glycerol (marker of cell membrane damage) were analyzed and the lactate/pyruvate ratio was calculated. RESULTS: During PTC, intrahepatic glucose, lactate, and glycerol increased from 9.1±2.2 to 14.5±2.4 mM, from 2.2±0.3 to 5.8±0.5 mM, and from 63±14 to 142±28 µM, respectively. Pyruvate was unchanged, resulting in an increased lactate/pyruvate ratio (from 39±10 to 104±32). During initial reperfusion, glucose further increased to 16.4±2.9 mM. Pyruvate increased after reperfusion (from 93±18 to 138±23 µM), while lactate was stable, resulting in a normalized lactate/pyruvate ratio. Glycerol continued to increase during initial reperfusion. CONCLUSIONS: PTC was associated with considerable intrahepatic metabolic alterations with anaerobic metabolism, increased glycogenolysis, and cellular membrane damage resulting in increased levels of glucose, lactate, glycerol, and lactate/pyruvate ratio. Microdialysis is easy to use and allows continuous monitoring of intrahepatic metabolism during liver surgery.

Mechanisms for skeletal muscle insulin resistance in patients with pancreatic ductal adenocarcinoma.

OBJECTIVE: Weight loss, glucose intolerance, and insulin resistance are seen in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral insulin resistance is decreased after tumor resection in patients with PDAC, which is consistent with the hypothesis that factors from the tumor may induce skeletal muscle insulin resistance. Our aim was to investigate the possible mechanisms for their skeletal muscle insulin resistance. Accordingly, the action of insulin on glucose metabolism and content of energy metabolites in muscle of patients with PDAC were investigated. To explore whether PDAC cells could influence muscle glucose uptake, myotubes were exposed to media conditioned by PDAC cells. METHODS: Muscle biopsies from patients with PDAC (n=13), cancer of other sites (n=8), chronic pancreatitis (n=8), and controls with benign diseases (n=8) were assessed for glycogen, adenosine triphosphate, and phosphocreatine content. Basal and insulin-stimulated glucose transport and incorporation into glycogen were also assessed. Myotubes were treated with media conditioned by PDAC (MiaPaca 2) cells and glucose transport was monitored. RESULTS: Insulin-stimulated glucose transport, muscle glycogen, and adenosine triphosphate content were decreased in patients with PDAC compared with controls, and insulin stimulation did not significantly increase glucose incorporation into glycogen in vitro in patients with PDAC. Adenosine triphosphate content correlated with glycogen content but not with glucose transport in skeletal muscle. Media conditioned with human PDAC cells did not affect basal or insulin-stimulated glucose transport in L6 myotubes. CONCLUSION: In patients with PDAC, muscle insulin resistance is an early and specific finding unrelated to weight loss, plasma free fatty acid levels, and energy status of the cell. PDAC cell-derived factors did not directly induce insulin resistance in myotubes, suggesting a lack of direct tumor-related effects.

The vascular stapler in uncinate process division during pancreaticoduodenectomy: technical considerations and results.

BACKGROUND: Few studies describing the use of stapling devices for uncinate process division during pancreaticoduodenectomy (PD) have data regarding outcomes. Our aim is to discuss our technique and the peri-operative outcomes with the use of the linear vascular stapler for division of the uncinate process during PD. MATERIALS AND METHODS: 19 consecutive patients who underwent stapler division of the uncinate process ('stapler' group) were compared to 20 consecutive patients operated without stapler ('no-stapler' group). RESULTS: The overall surgical morbidity in the no-stapler group was 25% (5/20) and 31.6% (6/19) in the stapler group (p = 0.731). The mean blood loss in the no-stapler group was 1,077.5 +/- 594 ml compared to 778 +/- 302 ml in the stapler group (p = 0.113). The mean operative duration was 498 +/- 105 min in the no-stapler group and 490 +/- 60 min in the stapler group (p = 0.773). The average number of lymph nodes retrieved was 6.1 +/- 3 in the no-stapler group versus 5.9 +/- 4 in the stapler group (p = 0.627). Neither group had positive resection margins. CONCLUSION: Stapler division of the uncinate process for selected periampullary tumours compares well with the conventional method, has comparable peri-operative outcomes without compromising oncological radicality and has the potential to simplify uncinate resection.

Bile duct stricture due to caused by portal biliopathy: Treatment with one-stage portal-systemic shunt and biliary bypass.

Portal biliopathy is a rare complication of extrahepatic portal vein obstruction. Jaundice occurs in symptomatic patients with fibrotic strictures. Short-term improvement in such patients can be achieved with endoscopic retrograde cholangio-pancreatography with balloon dilatation and stent placement. Surgery in these patients is traditionally two staged. We report the results of a one-stage procedure combining non-selective portal-systemic shunt surgery with biliary bypass, performed successfully on a 24-year-old man with a tight biliary stricture resulting from portal biliopathy. At 18-month follow up, the patient shows he is doing well, with normal liver function tests.

Surgery for gastric cancer: an evidence-based perspective.

Despite a decreasing incidence, stomach cancer is the second leading cause of cancer mortality worldwide. Surgical resection offers the only chance for cure in this aggressive cancer. The surgical management of gastric cancer has witnessed numerous debates in the past decades. These include the extent of lymphadenectomy, extent of surgery, role of laparoscopic gastrectomy, and the impact of high volume of centers, on the outcome of surgery. This review attempts to address these controversies with an evidence-based perspective. A literature search in MEDLINE (www.pubmed.org) has been performed with the relevant key words and corresponding MeSH terms. The search has been limited to English publications on human subjects. A manual search of the bibliographies has also been carried out, to identify the relevant publications for possible inclusion.

Pancreatic fistula after pancreatectomy: evolving definitions, preventive strategies and modern management.

Pancreatic resection is the treatment of choice for pancreatic malignancy and certain benign pancreatic disorders. However, pancreatic resection is technically a demanding procedure and whereas mortality after a pancreaticoduodenectomy is currently < 3%-5% in experienced high-volume centers, post-operative morbidity is considerable, about 30%-50%. At present, the single most significant cause of morbidity and mortality after pancreatectomy is the development of pancreatic leakage and fistula (PF). The occurrence of a PF increases the length of hospital stay and the cost of treatment, requires additional investigations and procedures, and can result in life-threatening complications. There is no universally accepted definition of PF that would allow standardized reporting and proper comparison of outcomes between different centers. However, early recognition of a PF and prompt institution of appropriate treatment is critical to the prevention of potentially devastating consequences. The present article, reviews the evolution of post resection pancreatic fistula as a concept, and discusses evolving definitions, the current preventive strategies and the management of this problem.

The gray zone between postpancreaticoduodenectomy collections and pancreatic fistula.

OBJECTIVES: Despite the International Study Group for Pancreatic Fistulae (ISGPF) definition, there exist reports of postoperative collections of uncertain etiology. There is a recent report questioning the ISGPF criteria's ability to accurately predict pancreatic anastomotic failure and outlining new criteria. We decided to validate both proposed criteria based on our experience. METHODS: Between January 2003 and November 2007, we retrospectively analyzed patients with postpancreaticoduodenectomy collections at the Tata Memorial Hospital. RESULTS: Of 149 patients evaluated, 17 (11.4%) had intra-abdominal collections, 9 had early collections (with abdominal drains in situ, ie,< or =7 days postoperative), whereas 8 had delayed collections (after removal of drains, ie, >7 days postoperative). Early collections were attributed to pancreatic anastomotic leaks (n = 5; confirmed by ISGPF guidelines), biliary leaks (n = 3), or chyle leaks (n = 1). In patients with "delayed" collections of unclear etiology (normal drain amylase levels on days 3 and 7), 5 had normal amylase levels in the aspirated/pigtailed collections, whereas 3 had drain amylase content more than 3 times the normal, indicating postoperative pancreatic fistulae. CONCLUSION: Assessment of amylase levels in delayed collections (despite initial amylase levels being normal) may aid in uncovering previously undrained, or newly formed, pancreatic anastomotic leaks. This will likely reduce reported rates of uncertain postoperative collections while providing more precise (perhaps higher) rates of postoperative pancreatic fistulae.