Carlo Lombardo

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study

BackgroundWestern multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE).MethodsRetrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C).ResultsWe included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18xa0months (CI 10–37). We observed no impact of PHAE on ischemic complications.ConclusionsDP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes.

Update on pancreatic transplantation on the management of diabetes

Pancreas transplantation is the only therapy that can restore insulin independence in beta-cell penic diabetic recipients. Because of the need for life-long immunosuppression and the intial surgical risk associated with the transplant procedure, Pancreas transplantation is a therapeutic option only in selected diabetic patients. Based on renal function, three main populations of diabetic recipients of a pancreas transplant can be identified: uremic patients, posturemic patients (following successful kidney transplantation), and non-uremic patients. Uremic patients are best treated by simultaneous kidney-pancreas transplantation with grafts obtained from the same deceased donor. Posturemic patients can receive a pancreas after kidney transplantation, if the previous renal graft has a good functional reserve. Non-uremic patients can receive a pancreas alone transplant if their diabetes is poorly controlled, despite optimal insulin therapy, suffer from unawareness hypoglycemia events and/or develop progressive chronic complications of diabetes. The results of pancreas transplantation have improved over the years and are currently not inferior to those of renal transplantation in non-diabetic recipients. A functioning pancreatic graft can prolong the life of diabetic recipients, improves their quality of life, and can halt, or reverse, the progression of chronic complications of diabetes. Unfortunately, because of ageing of donor population and lack of timely referral of potential recipients, the annual volume of pancreas transplants is declining. Considering that the results of pancreas transplantation depend on center volume, and that adequate center volume is required also for training of newer generations of transplant physcians and surgeons, centralization of pancreas transplantation activity should be considered.

Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five‐year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1‐PRSS2‐rs10273639 and an increased risk of developing PDAC (ORhomozygousu2009=u20091.19, 95% CI 1.02–1.38, pu2009=u20090.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1‐PRSS2‐rs10273639 (ORheterozygousu2009=u20090.51, 95% CI 0.39–0.67, pu2009=u20091.10 × 10−6) and MORC4‐rs 12837024 (ORhomozygousu2009=u20092.07 (1.55–2.77, ptrendu2009=u20090.7 × 10−11). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.

Robotic Pancreas Transplantation

Abstract Beta-cell replacement, by means of either pancreas or islet transplantation, offers unquestionable benefits to selected diabetic patients who face poor metabolic control and/or develop severe secondary complications of diabetes. Efficacy favors pancreas transplantation (PTx), while less invasiveness favors islet transplantation so that, at least in theory, minimally invasive PTx could be the ideal modality for beta-cell replacement. However, the intrinsic limitations of classical laparoscopic techniques have not permitted the development of this procedure. The da Vinci system is a computer-assisted electromechanical device that enhances surgical dexterity in minimally invasive procedures. The availability of this tremendous technology provides the unique opportunity to verify if the concept of minimally invasive PTx can be translated into facts and is eventually associated with the hoped clinical benefits. This chapter presents the technique for robotic PTx, as developed at the University of Pisa, and provides a comprehensive review of current knowledge on this revolutionary procedure.

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

BackgroundNo study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC).MethodsThis is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤u20091xa0mm). 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).ResultsFactors 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%) (pu2009=u20090.38). 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.ConclusionsRPD 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/OBJECTIVESnManagement of patients with pregnancy-associated cyst pancreatic cystic tumors (PA-PCT) is complicated by lack of large series.nnnMETHODSnA 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.nnnRESULTSnThe literature review demonstrated a total of 35u202fPA-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: 11.2u202f±u202f4.5u202fcm), 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 13.5u202f±u202f4.9u202fcm, 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: 40.5u202f±u202f0.7 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.nnnCONCLUSIONSnPA-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/OBJECTIVESnDespite 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.nnnMETHODSnA 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.nnnRESULTSnOverall, 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%), 18u202fF-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.nnnCONCLUSIONSnManagement 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.

Feasibility of Percutaneous Intrahepatic Split by Microwave Ablation (PISA) After Portal Vein Embolization for Hypertrophy of Future Liver Remnant: The Radiological Stage-1 ALPPS

PurposeTo assess the feasibility of radiological stage-1 ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, by combining portal vein embolization (PVE) with percutaneous intrahepatic split by ablation (PISA).Materials and MethodsThree patients (mean age 65.0xa0±xa07.3xa0years) underwent PVE and PISA. PISA was performed 21xa0days after PVE by microwave ablation to create a continuous intrahepatic cutting plane. Abdominal CT examinations were performed before and after PVE and PISA. The future liver remnant (FLR) volume was calculated by semiautomatic segmentation, and increase was reported as a percentage of the pre-procedural volume. The FLR/body weight (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered sufficient for guaranteeing adequate liver function after surgery. The liver function before and after PISA was also evaluated by 99mTc-mebrofenin hepatobiliary scintigraphy. Patients’ laboratory tests, performance status, ability to walk were assessed before and after PVE and PISA procedures.ResultsNo procedure-related complications were recorded. The FLR volume increase in each patient was 42.0, 33.1 and 30.4% within 21xa0days of PVE and 109.3, 68.1 and 71.7% within 10xa0days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13, 0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was not performed because of the absolute rejection of blood transfusion due to the patient’s religious convictions.ConclusionRadiological stage-1 ALPPS is a feasible, minimally invasive option to be further investigated to become an effective alternative to surgical stage-1 ALPPS.

Duodenal graft complications requiring duodenectomy after pancreas and pancreas–kidney transplantation

Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow‐up period of 126 months (range 23‐198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin‐independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n = 10, 71.5%) and refractory duodenal graft bleeding (n = 4, 28.5%). In patients with duodenal graft bleeding, a total duodenectomy was performed. In patients with duodenal graft perforation, preservation of a duodenal segment was possible in five patients but completion duodenectomy was necessary in one patient. After total duodenectomy, immediate enteric duct drainage was feasible in seven patients. In two patients, a pancreaticocutaneous fistula was created that was subsequently converted to enteric drainage in one patient. In the other patient, enteric fistulization occurred as a consequence of silent pressure perforation of the draining catheter on the ascending colon. After a mean follow‐up period of 52 months (21‐125), all patients were alive, well, and insulin‐independent. An aggressive and timely surgical approach may permit graft rescue in patients with severe duodenal graft complications occurring after pancreas transplantation. Generalization of these results remains to be established.

Robot Assisted Partial Pancreatectomy and Duodenopancreatectomy

Laparoscopy has revolutionized surgery, by showing that many abdominal operations can be performed safely and effectively despite minimally invasive access. Patients’ demand for minimally invasive surgery, on one hand, and surgeons’ motivation to pursue innovation and accept challenge, on the other, did the rest making laparoscopy an essential component of modern surgery. Laparoscopy, however, has intrinsic limitations, that are not completely overcome by expertise. These limitations have made the outcome of laparoscopy highly operator dependent [2], and have restricted the range of complex operations that can be safely performed using this technique [3].