First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Additional modifications to the Blumgart pancreaticojejunostomy: Results of a propensity score-matched analysis versus Cattel-Warren pancreaticojejunostomy.

BACKGROUND: Postoperative pancreatic fistula continues to occur frequently after pancreatoduodenectomy. METHODS: We have described a modification of the Blumgart pancreaticojejunostomy. The modification of the Blumgart pancreaticojejunostomy was compared to the Cattel-Warren pancreaticojejunostomy in cohorts of patients matched by propensity scores based on factors predictive of clinically relevant postoperative pancreatic fistula, which was the primary endpoint of this study. Based on a noninferiority study design, 95 open pancreatoduodenectomies per group were needed. Feasibility of the modification of the Blumgart pancreaticojejunostomy in robotic pancreatoduodenectomy was also shown. All pancreaticojejunostomies were performed by a single surgeon. RESULTS: Between October 2011 and May 2019, there were 415 pancreatoduodenectomies with either a Cattel-Warren pancreaticojejunostomy (n = 225) or a modification of the Blumgart pancreaticojejunostomy (n = 190). There was 1 grade C postoperative pancreatic fistula in 190 consecutive modification of the Blumgart pancreaticojejunostomies (0.5%). Logistic regression analysis showed that the rate of clinically relevant postoperative pancreatic fistula was not affected by consecutive case number. After exclusion of robotic pancreatoduodenectomies (the Cattel-Warren pancreaticojejunostomy: 82; modification of the Blumgart pancreaticojejunostomy: 66), 267 open pancreatoduodenectomies were left, among which the matching process identified 109 pairs. The modification of the Blumgart pancreaticojejunostomy was shown to be noninferior to the Cattel-Warren pancreaticojejunostomy with respect to clinically relevant postoperative pancreatic fistula (11.9% vs 22.9%; odds ratio: 0.46 [0.21-0.93]; P = .03), grade B postoperative pancreatic fistula (11.9% vs 18.3%; P = .18), and grade C postoperative pancreatic fistula (0 vs 4.6%; P = .05) as well as to all secondary study endpoints. The modification of the Blumgart pancreaticojejunostomy was feasible in 66 robotic pancreatoduodenectomies. In this subgroup with 1 conversion to open surgery (1.5%), a clinically relevant postoperative pancreatic fistula occurred after 9 procedures (13.6%) with no case of grade C postoperative pancreatic fistula and a 90-day mortality of 3%. CONCLUSION: The modification of the Blumgart pancreaticojejunostomy described herein is noninferior to the Cattel-Warren pancreaticojejunostomy in open pancreatoduodenectomy. This technique is also feasible in robotic pancreatoduodenectomy.

Induction and Immunosuppressive Management of Pancreas Transplant Recipients.

BACKGROUND: Despite improved overall outcomes, rejection continues to occur frequently after pancreas transplantation. OBJECTIVE: To review the literature and to provide a state-of-the-art assessment of current practice and developments of immunosuppressive regimens in pancreas transplantation. METHODS: The literature was reviewed and relevant articles were retrieved and analyzed. RESULTS: Induction therapy is used in approximately 90% of the transplants, with T-cell depleting antibodies being the prevalent therapy (>90%). Despite the initial enthusiasm on steroid-free regimens, maintenance protocols continue to be mostly based on a combination of steroids, tacrolimus, and mycophenolate mofetil. Tacrolimus is used in the majority of recipients. Sirolimus is rarely used at the time of transplant and is introduced later on in approximately 10% of the recipients, mostly in the context of a switching strategy to address the side effects of calcineurin inhibitors. The overall quality of published studies was quite low, because of the retrospective design, the heterogeneity of study groups with respect to PTx categories, the inclusion of mixed recipient categories with respect to immunologic risk profile, and the use of non-standardized concurrent immunosuppressive therapies. In addition, most reported studies were clearly underpowered, and treatment outcomes were not standardized. CONCLUSION: Since approximately two decades, immunosuppression in pancreas transplantation mostly consists of induction with depleting antibodies and maintenance therapy using a combination of steroids, tacrolimus, and mycophenolate mofetil. While true novelty would be very much needed, this review confirms the wide use and the clinical efficacy of this regimen.

Robot-Assisted Radical Antegrade Modular Pancreatosplenectomy Including Resection and Reconstruction of the Spleno-Mesenteric Junction.

This article shows the technique of robot-assisted radical antegrade modular pancreatosplenectomy, including resection and reconstruction of the spleno-mesenteric junction, for cancer of the body-tail of the pancreas. The patient is placed supine with the legs parted and a pneumoperitoneum is established and maintained at 10 mmHg. To use the surgical system, four 8 mm ports and one 12 mm port are required. The optic port is placed at the umbilicus. The other ports are placed, on either side, along the pararectal line and the anterior axillary line at the level of the umbilical line. The assistant port (12 mm) is placed along the right pararectal line. Dissection begins by detaching the gastrocolic ligament, thus opening the lesser sac, and by a wide mobilization of the splenic flexure of the colon. The superior mesenteric vein is identified along the inferior border of the pancreas. Lymph node number 8a is removed to permit clear visualization of the common hepatic artery. A tunnel is then created behind the neck of the pancreas. To permit safe resection and reconstruction of the spleno-mesenteric junction, further preemptive dissection is required before dividing the pancreatic neck to bring in clear view all relevant vascular pedicles. Next, the splenic artery is ligated and divided, and the pancreatic neck is divided, with selective ligature of the pancreatic duct. After vein resection and reconstruction, dissection proceeds to complete the clearance of peripancreatic arteries that are peeled off from all lympho-neural tissues. Both celiac ganglia are removed en-bloc with the specimen. The Gerota fascia covering the upper pole of the left kidney is also removed en-bloc with the specimen. Division of short gastric vessels and splenectomy complete the procedure. A drain is left near the pancreatic stump. The round ligament of the liver is mobilized to protect the vessels.

A propensity score-matched analysis of robotic versus open pancreatoduodenectomy for pancreatic cancer based on margin status.

BACKGROUND: No study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC). METHODS: This is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤ 1 mm). Only patients operated on after completion of the learning curve in both procedures and for whom circumferential margins were assessed according to the Leeds pathology protocol were included. The primary study endpoint was the rate of R1 resection. Secondary study endpoints were as follows: number of examined lymph nodes (N), rate of perioperative transfusions, percentage of patients receiving adjuvant therapies, occurrence of local recurrence, overall survival, disease-free survival, and sample size calculation for randomized controlled trials (RCT). RESULTS: Factors associated with R1 resection were tumor diameter, number of positive N, N ratio, logarithm odds of positive N, and duodenal infiltration. The matching process identified 20 RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no difference in the rate of R1 at each margin as well as in the proportion of patients with multiple R1 margins. RPD and OPD were also equivalent with respect to all secondary study endpoints, with a trend towards lower rate of blood transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT comparing RPD and OPD having the rate of R1 resection as the primary study endpoint requires 3355 pairs. CONCLUSIONS: RPD and OPD achieved the same rate of R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to all secondary study endpoints. Because of the high number of patients required to run a RCT, further assessment of RPD for PC would require the implementation of an international registry.

Management of pregnancy-associated pancreatic cystic tumors: Review of the literature and results of a Pancreas Club Inc. Survey.

BACKGROUND/OBJECTIVES: Management of patients with pregnancy-associated cyst pancreatic cystic tumors (PA-PCT) is complicated by lack of large series. METHODS: A systematic literature review was conducted to extrapolate data on management of PA-PCT, and make a questionnaire on pending issues to be administered to the members of the Pancreas Club Inc. RESULTS: The literature review demonstrated a total of 35 PA-PCT in 34 women, described exclusively in the form of case reports, and permitted the identification of eleven key questions to be addressed in the survey. The combined analysis of literature review and survery responses provided several information. First, PA-PCT are predominantly located in the body-tail of the pancreas, cause non-specific symptoms, are of large size (mean size: 11.2 ±â€¯4.5 cm), and are nearly always malignant or premalignant, making timing of surgery, and not indication for surgery, the main issue in the management of these tumors. Second, there is a risk of PA-PCT rupture during pregnancy. Ruptured PA-PCT had a mean size 13.5 ±â€¯4.9 cm, but no prognostic factor could be identified. Survey opinions suggested that this occurrence is quite rare, even for large tumors. Third, most pregnancies were conducted to term (mean gestational age: 40.5 ±â€¯0.7 weeks), with a vaginal delivery. Fourth, all procedures were carried out through an open approach and the spleen was rarely preserved. Survey indicated instead that laparoscopy could play a role, and that the spleen should be preserved when feasible. CONCLUSIONS: PA-PCT require individualized treatment. The definition of a management algorithm requires the implementation of an International Registry.

Incidence and reasons of pancreatic resection in patients with asymptomatic serous cystadenoma.

BACKGROUND/OBJECTIVES: Despite diagnostic refinements, pancreatic resection (PR) is eventually performed in some patients with asymptomatic serous cystadenoma (A-SCA). The aim of this study was to define incidence and reasons of PR in A-SCA. METHODS: A retrospective analysis of a prospectively maintained database was performed for all the patients referred for pancreatic cystic lesions (PCL) between January 2005 and March 2016. RESULTS: Overall, there were 1488 patients with PCL, including 1271 (85.4%) with incidental PCL (I-PCL). During the study period referral of I-PCL increased 8.5-fold. Surgery was immediately advised in 94 I-PCL (7.3%) and became necessary later on in 11 additional patients (0.9%), because of the development of symptoms. Overall, PR was performed in 105/1271 patients presenting with I-PCL (8.2%), including 27 with A-SCA (2.1%). All patients with A-SCA underwent ultrasonography and contrast-enhanced computed tomography. Magnetic resonance imaging was performed in 21 patients (77.8%), 18 F-FDG positron emission tomography in 8 (29.6%), endoscopic ultrasonography (EUS) in 2 (7.4%), and EUS-guided fine needle aspiration (EUS-FNA) in 1 (3.7%). These studies demonstrated a combination of atypical features such as solid tumor (3; 11.1%), oligo-/macrocystic tumor (24; 88.8%), mural nodules (14; 51.8%), enhancing cyst walls (17; 62.9%), dilation of the main pancreatic duct (3; 11.1%), and upstream pancreatic atrophy (1; 3.7%). Additionally, 14/27 patients (51.8%) were females with oligo-/macrocystic tumors located in the body-tail of the pancreas. CONCLUSIONS: Management of patients with A-SCA entails a small risk of PR especially when these tumors demonstrate atypical radiologic features associated with confounding anatomic and demographic characteristics.

Robotic versus open pancreatoduodenectomy: a propensity score-matched analysis based on factors predictive of postoperative pancreatic fistula.

BACKGROUND: Improvement in morbidity of pancreatoduodenectomy (PD) largely depends on the reduction in the incidence of clinically relevant (CR) postoperative pancreatic fistula (POPF). METHODS: After internal validation of the clinical risk score (CRS) of POPF, and identification of other predictive factors for POPF, robotic (RPD), and open (OPD) PDs were stratified into risk categories and matched by propensity scores. The primary endpoint of this study was incidence of CR-POPF. Secondary endpoints were 90-day morbidity and mortality, and sample size calculation for randomized controlled trials (RCT). RESULTS: No patient undergoing RPD was classified at negligible risk for POPF, and no CR-POPF occurred in 7 RPD at low risk. The matching process identified 48 and 11 pairs at intermediate and high risk for POPF, respectively. In the intermediate-risk group, RPD was associated with higher rates of CR-POPF (31.3% vs 12.5%) (p = 0.0026), with equivalent incidence of grade C POPF. In the high-risk group, CR-POPF occurred frequently, but in similar percentages, after either procedures. Starting from an unadjusted point estimate of the effect size of 1.71 (0.91-3.21), the pair-matched odds ratio for CR-POPF after RPD was 2.80 (1.01-7.78) for the intermediate-risk group, and 0.20 (0.01-4.17) for the high-risk group. Overall morbidity and mortality were equivalent in matched study groups. Sample size calculation for a non-inferiority RCT demonstrated that a total of 31,669 PDs would be required to randomize 682 patients at intermediate risk and 1852 patients at high risk. CONCLUSIONS: In patients at intermediate risk, RPD is associated with higher rates of CR-POPF. Incidence of grade C POPF is similar in RPD and OPD, making overall morbidity and mortality also equivalent. A RCT, with risk stratification for POPF, would require an enormous number of patients. Implementation of an international registry could be the next step in the assessment of RPD.

Robotic-Assisted Pancreatic Resections.

BACKGROUND: Robotic assistance enhances surgical dexterity and could facilitate wider adoption of laparoscopy for pancreatic resections (PR). METHODS: Data were prospectively entered into a database and analyzed retrospectively to assess feasibility and safety of robotic-assisted PR (RAPR). Additionally, robotic-assisted pancreaticoduodenectomy (RAPD) was compared to a contemporary group of open pancreaticoduodenectomies (OPD). RESULTS: Between October 2008 and October 2014, 200 consecutive patients underwent RAPR. Three procedures were converted to open surgery (1.5 %), despite 14 patients required associated vascular procedures. RAPD was performed in 83 patients (41.5 %), distal pancreatectomy in 83 (41.5 %), total pancreatectomy in 17 (8.5 %), tumor enucleation in 12 (6 %), and central pancreatectomy in 5 (2.5 %). Thirty-day and 90-day mortality rates were 0.5 and 1 %, respectively. Both deaths occurred after RAPD with vein resection. Complications occurred in 63.0 % of the patients (≥Clavien-Dindo grade IIIb in 4 %). Median comprehensive complication index was 20.9 (0-26.2). Incidence of grade B/C pancreatic fistula was 28.0 %. Reoperation was required in 14 patients (7.0 %). The risk of reoperation decreased after post-operative day 20 (OR 0.072) (p = 0.0015). When compared to OPD, RAPD was associated with longer mean operative time (527.2 ± 166.1 vs. 425.3 ± 92.7; <0.0001) but had an equivalent safety profile. The median number of examined lymph nodes (37; 28.8-45.3 vs. 36; 28-52.8) and the rate of margin positivity in patients diagnosed with pancreatic cancer were also similar (12.5 vs. 45.5 %). CONCLUSIONS: RAPR, including RAPD, are safely feasible in selected patients. The results of RAPD in pancreatic cancer are encouraging but deserve further investigation.