Laparoscopic intraoperative pancreatoscopy for main duct intraductal papillary mucinous neoplasms assessment.

Video 1Intraoperative pancreatoscopy during laparoscopic pancreatic resection for main pancreatic duct intraductal papillary mucinous neoplasms.

The Theory and Practice of Pancreatic Surgery in France.

OBJECTIVE: Measure the caseload of pancreatectomies that influences their short-term outcome, at a national level, and assess the applicability of a centralization policy. BACKGROUND: There is agreement that pancreatectomies should be centralized. However, previous studies have failed to accurately define a "high-volume" center. METHODS: French healthcare databases were screened to identify all adult patients who had elective pancreatectomies between 2007 and 2012. The patients' age, comorbidities, indication, and extent of surgery, and also the hospital administrative-type and location were retrieved. The annual-caseload of pancreatectomy was calculated for each hospital facility. The primary endpoint was 90-day mortality. Spline modeling was used to identify the different annual-caseload that influenced mortality. Logistic regressions were performed to assess if their influence was independent of confounders, and the accuracy of the model calculated. RESULTS: Overall, 22,366 patients underwent a pancreatectomy and the mortality was 8.1%. Two cut-offs were identified (25 and 65 per year): compared with centers performing >65 resections per year, the adjusted OR of mortality was 1.865 (1.529-2.276) in centers performing ≤25 resections per year and 1.234 (1.031-1.478) in those performing 26 to 65 resections per year. The average number of facilities performing ≤25, 26 to 65, and >65 pancreatectomies per year was 456, 20, and 9, respectively. The percentage of patients operated in these facilities was 56.6%, 19.9%, and 23.3%, respectively.For pancreaticoduodenectomies (12,670 patients; mortality 9.2%), there were 2 cut-offs (16 and 40 pancreaticoduodenectomies per year), and both were independent predictors of mortality (adjusted OR of 1.979 and 1.333). For distal pancreatectomies (7085 patients; 6.2% mortality), there were 2 cut-offs (13 and 25 distal pancreatectomies per year), but neither was an independent predictor of outcome (area under the receiver-operating characteristic curve of the model = 0.778). CONCLUSIONS: Centralization of pancreatic surgery is theoretically justified, but currently unrealizable. As the incidence of pancreatic cancer increases, there is an urgent need to improve the training of surgeons and develop both intermediate and high-volume centers.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.

Laparoscopic left lateral resection is the gold standard for benign liver lesions: a case-control study.

INTRODUCTION: A left lateral section is the first choice for a laparoscopic anatomic liver resection. The objective of this case-control study was to assess the surgical outcome after a laparoscopic left lateral resection for benign liver lesions compared with the open approach. METHODS: From January 2004 to April 2011, 31 laparoscopic left lateral resections were matched with 31 open left lateral resections by selection based on pathology of the lesion, size of the lesion, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), age and gender of the patient. RESULTS: Duration of the operation (laparoscopic: 182 ± 71 versus open: 244 ± 105 min; P = 0.04), blood loss (223 ± 281 versus 455 ± 593 ml; P = 0.03), duration of hospital stay (4.1 ± 1.7 versus 8.1 ± 4.4 days; P < 0.001) and total cost of hospitalization (7475 ± 2679 versus 11504 ± 7776 Euros; P < 0.001) were significantly lower in the laparoscopic group. CONCLUSIONS: This matched case-control study demonstrated procedural safety, excellent post-operative outcomes and economic benefits for a laparoscopic liver resection. A laparoscopic left lateral liver sectionectomy is recommended as a gold standard for benign liver lesions.

Impact of total pancreatectomy: short- and long-term assessment.

BACKGROUND: The aim was to assess the outcome of a total pancreatectomy (TP). METHODS: From 1993 to 2010, 56 patients underwent an elective TP for intraductal papillary mucinous neoplasia (n = 42), endocrine tumours (n = 6), adenocarcinoma (n = 5), metastases (n = 2) and chronic pancreatitis (n = 1). Morbidity and survival were analysed. Long-term survivors were assessed prospectively using quality-of-life (QoL) questionnaires. RESULTS: Five patients developed gastric venous congestion intra-operatively. Post-operative morbidity and mortality rates were 45% and 3.6%, respectively. An anastomotic ulcer occurred in seven patients, but none after proton pump inhibitor therapy. There were five inappropriate TPs according to definitive pathological examination. Overall 3- and 5-year survival rates were 62% and 55% respectively; five deaths were related to TP (two postoperative deaths, one hypoglycaemia, one ketoacidosis and one anastomotic ulcer). Prospective evaluation of 25 patients found that 14 had been readmitted for diabetes and that all had hypoglycaemia within the past month. The glycated haemoglobin (HbA1c) was 7.8% (6.3-10.3). Fifteen patients experienced weight loss. The QLQ-C30 questionnaire showed a decrease in QoL predominantly because of fatigue and diarrhoea, and the QLQ-PAN26 showed an impact on bowel habit, flatulence and eating-related items. DISCUSSION: Morbidity and mortality rates of TP are acceptable, although diabetes- and TP-related mortality still occurs. Endocrine and exocrine insufficiency impacts on the long-term quality of life.

Proteomic assessment of markers for malignancy in the mucus of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. METHODS: Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. RESULTS: Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. CONCLUSIONS: Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. ABBREVIATIONS: IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography.

Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree. Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning (FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive, in order to avoid an excessive pancreatic resection. Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease. FS accuracy averages 95%. Eroded epithelium on the main duct, severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results. FS results change the planned extent of resection in up to 30% of cases. The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatectomy if FS reveals: (1) at least IPMN adenoma on the main duct; or (2) at least borderline IPMN on branch ducts; or (3) invasive carcinoma. However, the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age, general condition and expected prognosis after resection. The main limitation of using FS is the existence of discontinuous ("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

Ischemic complications after pancreaticoduodenectomy: incidence, prevention, and management.

OBJECTIVE: To assess prevalence, prevention, and management strategy of visceral ischemic complications after pancreaticoduodenectomy (PD). BACKGROUND: Ischemic complications after PD resulting from preexisting celiac axis (CA), superior mesenteric artery (SMA), stenosis, or intraoperative arterial trauma appear as an underestimated cause of death. Their prevention and adequate management are challenging. METHODS: From 1995 to 2006, 545 PD were performed in our institution. All patients were evaluated by thin section multidetector computed tomography (CT) with arterial reconstruction to detect and class SMA or CA stenosis. Hemodynamical significance of stenosis was assessed preoperatively by arteriography for atherosclerotic stenosis and intraoperatively by gastroduodenal artery clamping test for CA compression by median arcuate ligament. Significant atherosclerotic stenosis was stented or bypassed, whereas CA compression was treated by median arcuate ligament division during PD. Multidetector-CT accuracy to detect arterial stenosis, results of revascularization procedures, and both prevalence and prognosis of ischemic complications after PD were analyzed. RESULTS: Among 62 (11%) stenoses detected by multidetector-CT, 27 (5%) were hemodynamically significant, including 23 CA compressions by median arcuate ligament, 2 CA, and 2 SMA atherosclerotic stenoses, respectively. All atherosclerotic stenoses were successfully treated by preoperative stenting (n = 3) or bypass (n = 1). Among the 23 cases who underwent median arcuate ligament division, 3 (13%) failed due to 1 CA injury and 2 misdiagnosed intrinsic CA stenoses. Overall, 6 patients developed ischemic complications, due to intraoperative hepatic artery injury (n = 4), unrecognized SMA atherosclerotic stenosis (n = 1), or CA fibromuscular dysplasia (n = 1). Five (83%) of them died, representing 36% of the 14 deaths of the whole series (overall mortality = 2.6%). Overall, CT detected significant arterial stenosis with a 96% sensitivity and determined etiology of CA stenosis with a 92% accuracy. CONCLUSIONS: Ischemic complications are an underestimated cause of death after PD and are due to preexisting stenoses of CA and SMA, or intraoperative hepatic artery injury. Preexisting arterial stenoses are detected by routine multidetector CT. Preoperative endovascular stenting for intrinsic stenosis, division of median arcuate ligament for extrinsic compression, and meticulous dissection of the hepatic artery can contribute to minimize ischemic complications.