Surgical-only treatment of pancreatic and extra-pancreatic metastases from renal cell carcinoma - quality of life and survival analysis.

BACKGROUND: Treatment of pancreatic metastases (PM) from renal cell carcinoma (RCC) is still an issue between surgeons and oncologists, in the era of target-therapy. METHODS: Data from 26 patients undergoing resection of PM and extra-PM from RCC, with R0 intention were retrospectively analysed. No one received adjuvant chemotherapy. Patients were divided into two groups; Group A comprehends 14 patients who developed synchronous (5) or methacronous (9) extra-PM. Group B comprehends 12 patients that developed PM only. RESULTS: No intraoperative mortality was recorded. Complications occurred in 14 patients (53.8%), all but 2 (7.26%) were graded I and II according to Clavien-Dindo classification. Recurrences occurred in 8 patients (30.8%), of whom, 5 (62.5%) were submitted for further resections in other sites. Three-, five- and ten-year observed overall survival were respectively 88,5% [95%CI: 0,56 - 1,33], 76,9% [95%CI: 0,47 - 1,19] and 50% [95%CI: 0,20 - 1,03]. Disease-free survival was 65,4% [95%CI: 0,38 - 1,05], at 3 years, 57,7% [95%CI 0,323 - 0,952] at 5 years and 42,9% [95%CI 0,157 - 0,933], at 10 years. QoL analysis, through WHOQOL-BREF questionnaire, assessed at last available follow up revealed a mean score of 75,9 ± 11,6 on 100 points. CONCLUSION: Despite no significant differences in survival between patients affected by Pancreatic or Extra-Pancreatic metastases, PM patients seems to show better outcome when managed surgically. mRCC patients, eligible for radical metastasectomy, tend to have long survival rates, reduced recurrence rates and good QoL. STUDY REGISTRATION: This paper was registered retrospectively in ClinicalTrials.gov with Identification number: NCT03670992.

Full Robotic Distal Pancreatectomy: Safety and Feasibility Analysis of a Multicenter Cohort of 236 Patients.

Introduction. Despite the widespread use of the robotic technology, only a few studies with small sample sizes report its application to pancreatic diseases treatment. Our aim is to present the results of a multicenter study on the safety and feasibility of robot-assisted distal pancreatectomy (RDP). Materials and Methods. All RDPs for benign, borderline, and malignant diseases performed in 5 referral centers from 2008 to 2016 were included. Perioperative outcomes were evaluated. Results. Two hundred thirty-six patients were included. Spleen preservation was performed in 114 cases (48.3%). Operative time was 277.8 ± 93.6 minutes. Progressive improvement in operative time was observed over the study period. Conversion rate was 6.3%. Morbidity occurred in 102 cases (43.2%), mainly due to grade A fistulas. Reoperation was required in 10 patients. Postoperatively, 2 patients died of sepsis due to a grade C fistula. Hospital readmission was necessary in 11 cases. A R0 resection was always achieved, with a mean number of 16.2 ± 15 harvested lymph nodes. Conclusion. To our knowledge, this is one of the largest RDP series. Safety and feasibility including the low conversion rate, the high spleen preservation rate, the adequate operative time, and the acceptable morbidity and mortality rates confirm the validity of this technique. Appropriate oncological outcomes have been also obtained.

Short-term and long-term outcomes after robot-assisted versus laparoscopic distal pancreatectomy for pancreatic neuroendocrine tumors (pNETs): a multicenter comparative study.

PURPOSE: Minimally invasive surgery has increasingly gained popularity as a treatment of choice for pancreatectomy with encouraging initial results in robotic distal pancreatectomy (RDP). However, few data are available on the comparison between RDP and laparoscopic distal pancreatectomy (LDP) for pancreatic neuroendocrine tumors (pNETs). Our aim, thus, is to compare perioperative and long-term outcomes as well as total costs of RDP and LDP for pNETs. METHODS: All RDPs and LDPs for pNETs performed in four referral centers from 2008 to 2016 were included. Perioperative outcomes, histopathological results, overall (OS) and disease-free survival (DFS), and total costs were evaluated. RESULTS: Ninety-six RDPs and 85 LDPs were included. Demographic and clinical characteristics were comparable between the two cohorts. Operative time was 36.5 min longer in the RDP group (p = 0.009) but comparable to LDP after removing the docking time (247.9 vs 233.7 min; p = 0.6). LDP related to a lower spleen preservation rate (44.7% vs 65.3%; p < 0.0001) and higher blood loss (239.7 ± 112 vs 162.5 ± 98 cc; p < 0.0001). Advantages in operative time for RDP were documented in case of the spleen preservation procedures (265 ± 41.52 vs 291 ± 23 min; p = 0.04). Conversion rate, postoperative morbidity, and pancreatic fistula rate were similar between the two groups, as well as histopathological data, OS, and DFS. Significant advantages were evidenced for LDP regarding mean total costs (9235 (± 1935) € vs 11,226 (± 2365) €; p < 0.0001). CONCLUSIONS: Both RDP and LDP are safe and efficacious for pNETs treatment. However, RDP offers advantages with a higher spleen preservation rate and lower blood loss. Costs still remain the main limitation of the robotic approach.

Laparoscopic pancreaticoduodenectomy: a systematic literature review.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is gaining momentum, but there is still uncertainty regarding its safety, reproducibility, and oncologic appropriateness. This review assesses the current status of LPD. METHODS: Our literature review was conducted in Pubmed. Articles written in English containing five or more LPD were selected. RESULTS: Twenty-five articles matched the review criteria. Out of a total of 746 LPD, 341 were reported between 1997 and 2011 and 405 (54.2 %) between 2012 and June 1, 2013. Pure laparoscopy (PL) was used in 386 patients (51.7 %), robotic assistance (RA) in 234 (31.3 %), laparoscopic assistance (LA) in 121 (16.2 %), and hand assistance in 5 (0.6 %). PL was associated with shorter operative time, reduced blood loss, and lower rate of pancreatic fistula (vs LA and RA). LA was associated with shorter operative time (vs RA), but with higher blood loss and increased incidence of pancreatic fistula (vs PL and RA). Conversion to open surgery was required in 64 LPD (9.1 %). Operative time averaged 464.3 min (338-710) and estimated blood 320.7 mL (74-642). Cumulative morbidity was 41.2 %, and pancreatic fistula was reported in 22.3 % of patients (4.5-52.3 %). Mean length of hospital stay was 13.6 days (7-23), showing geographic variability (21.9 days in Europe, 13.0 days in Asia, and 9.4 days in the US). Operative mortality was 1.9 %, including one intraoperative death. No difference was noted in conversion rate, incidence of pancreatic fistula, morbidity, and mortality when comparing results from larger (≥30 LPD) and smaller (≤29 LPD) series. Pathology demonstrated ductal adenocarcinoma in 30.6 % of the specimens, other malignant tumors in 51.7 %, and benign tumor/disease in 17.5 %. The mean number of lymph nodes examined was 14.4 (7-32), and the rate of microscopically positive tumor margin was 4.4 %. CONCLUSIONS: In selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is feasible and safe.

Laparoscopic robot-assisted versus open total pancreatectomy: a case-matched study.

BACKGROUND: The enhanced dexterity offered by robotic assistance could be excessive for distal pancreatectomy but not enough to improve the outcome of laparoscopic pancreaticoduodenectomy. Total pancreatectomy retains the challenges of uncinate process dissection and digestive reconstruction, but avoids the risk of pancreatic fistula, and could be a suitable operation to highlight the advantages of robotic assistance in pancreatic resections. METHODS: Eleven laparoscopic robot-assisted total pancreatectomies (LRATP) were compared to 11 case-matched open total pancreatectomies. All operations were performed by one surgeon during the same period of time. Robotic assistance was employed in half of the patients, based on robot availability at the time of surgery. Variables examined included age, sex, American Society of Anesthesiologists score, body mass index, estimated blood loss, need for blood transfusions, operative time, tumor type, tumor size, number of examined lymph nodes, margin status, post-operative complications, 90-day or in-hospital mortality, length of hospital stay, and readmission rate. RESULTS: No LRATP was converted to conventional laparoscopy, hand-assisted laparoscopy or open surgery despite two patients (18.1 %) required vein resection and reconstruction. LRATP was associated with longer mean operative time (600 vs. 469 min; p = 0.014) but decreased mean blood loss (220 vs. 705; p = 0.004) than open surgery. Post-operative complications occurred in similar percentages after LRATP and open surgery. Complications occurring in most patients (5/7) after LRATP were of mild severity (Clavien-Dindo grade I and II). One patient required repeat laparoscopic surgery after LRATP, to drain a fluid collection not amenable to percutaneous catheter drainage. One further patient from the open group required repeat surgery because of bleeding. No patient had margin positive resection, and the mean number of examined lymph nodes was 45 after LRATP and 36 after open surgery. CONCLUSIONS: LRATP is feasible in selected patients, but further experience is needed to draw final conclusions.

Transplantation of the pancreas.

Pancreas transplantation consistently induces insulin-independence in beta-cell-penic diabetic patients, but at the cost of major surgery and life-long immunosuppression. One year after grafting, patient survival rate now exceeds 95 % across recipient categories, while insulin independence is maintained in some 85 % of simultaneous pancreas and kidney recipients and in nearly 80 % of solitary pancreas transplant recipients. The half-life of the pancreas graft currently averages 16.7 years, being the longest among extrarenal grafts, and substantially matching the one of renal grafts from deceased donors. The difference between expected (100 %) and actual insulin-independence rate is mostly explained by technical failure in the postoperative phase, and rejection in the long-term period. Death with a functioning graft remains a further major issue, especially in uremic patients who have undergone prolonged periods of dialysis. Refinements in graft preservation, surgical techniques, immunosuppression, and prophylactic treatments are expected to further improve the results of pancreas transplantation.

Central pancreatectomy with inframesocolic pancreatojejunostomy.

PURPOSE: Pancreatic fistula (PF) occurs frequently after central pancreatectomy (CP), but it is not clear from which pancreatic stump it arises and, consequently, which interventions can reduce its incidence and severity. The information could be obtained if the two pancreatic remnants were segregated into different body compartments. METHODS: In eight consecutive patients, the cut end of the distal pancreatic stump after CP was brought in the inframesocolic compartment through a small defect created in the transverse mesocolon. Pancreatojejunostomy was hence constructed in the intraperitoneal compartment, being divided by the retroperitoneal right-sided pancreatic stump by the transverse mesocolon itself. Five patients were operated on open, and three by robot-assisted laparoscopy. PF was defined according to the criteria proposed by the International Study Group on Pancreatic Fistula. RESULTS: PF fistula developed in five out eight patients (three grade A and two grade B). Amylase concentration in the fluid obtained from surgical drains showed that the two pancreatic remnants were actually segregated into different body compartments and that four out of five PF originated from the right remnant. Mean hospital stay was 12.5 days. No patient was readmitted, developed peripancreatic fluid collections, required interventional radiology procedures, or underwent repeat surgery. CONCLUSIONS: In CP, interposing an anatomic barrier, such as the transverse mesocolon, between the two pancreatic remnants is a simple maneuver that, if on one hand, adds little to the complexity of the operation, on the other, provides insights into the origin of PF after CP.

Incidence, diagnosis, and treatment of chylous leakage after laparoscopic live donor nephrectomy.

BACKGROUND: Chylous leakage (CL) is a rare complication of laparoscopic live donor nephrectomy (LLDN). It may lead to malnutrition and immunological deficits because of protein and lymphocyte depletion. METHODS: Data from 208 consecutive LLDN performed at two institutions, between April 2000 and September 2010, were reviewed to identify the anatomical basis behind CL along with its diagnostic and therapeutic options. RESULTS: CL developed in eight donors (3.8%), as determined by high-volume drainage (range 540-800 mL/24 hr) of triglyceride-rich fluid. All donors were managed conservatively. Seven were put on total parenteral nutrition plus octreotide. One received low-fat diet, medium-chain triglyceride supplementation, and octreotide. Chylous fistulas resolved in 5 to 16 days (mean time 12.3 days). Drains were removed before hospital discharge, and no donor was readmitted and/or needed outpatient care. CONCLUSIONS: CL is a potentially insidious and perhaps misdiagnosed complication after LLDN. It occurs in nearly 4% of LLDN and it seems to be uniquely associated to left-sided kidney recovery because of distinctive lymphatics distribution around the periaortic area of dissection. Conservative therapy is effective in most donors and should be initially attempted. Surgical ligatures or fibrin sealants may be indicated in case of refractory CL before the arising of malnutrition and/or relevant immunodeficiency.

High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.

BACKGROUND: Only a subset of radically resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from chemotherapy, and identification of prognostic factors is warranted. Recently miRNAs emerged as diagnostic biomarkers and innovative therapeutic targets, while high-throughput arrays are opening new opportunities to evaluate whether they can predict clinical outcome. The present study evaluated whether comprehensive miRNA expression profiling correlated with overall survival (OS) in resected PDAC patients. METHODOLOGY/PRINCIPAL FINDINGS: High-resolution miRNA profiles were obtained with the Toray's 3D-Gene™-miRNA-chip, detecting more than 1200 human miRNAs. RNA was successfully isolated from paraffin-embedded primary tumors of 19 out of 26 stage-pT3N1 homogeneously treated patients (adjuvant gemcitabine 1000 mg/m(2)/day, days-1/8/15, every 28 days), carefully selected according to their outcome (OS<12 (N = 13) vs. OS>30 months (N = 6), i.e. short/long-OS). Highly stringent statistics included t-test, distance matrix with Spearman-ranked correlation, and iterative approaches. Unsupervised hierarchical analysis revealed that PDACs clustered according to their short/long-OS classification, while the feature selection algorithm RELIEF identified the top 4 discriminating miRNAs between the two groups. These miRNAs target more than 1500 transcripts, including 169 targeted by two or more. MiR-211 emerged as the best discriminating miRNA, with significantly higher expression in long- vs. short-OS patients. The expression of this miRNA was subsequently assessed by quantitative-PCR in an independent cohort of laser-microdissected PDACs from 60 resected patients treated with the same gemcitabine regimen. Patients with low miR-211 expression according to median value had a significantly shorter median OS (14.8, 95%CI = 13.1-16.5, vs. 25.7 months, 95%CI = 16.2-35.1, log-rank-P = 0.004). Multivariate analysis demonstrated that low miR-211 expression was an independent factor of poor prognosis (hazard ratio 2.3, P = 0.03) after adjusting for all the factors influencing outcome. CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.

Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients.

BACKGROUND: Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. METHODS: We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. RESULTS: Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. CONCLUSIONS: PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.

Current perspectives on laparoscopic robot-assisted pancreas and pancreas-kidney transplantation.

Pancreas transplant recipients continue to suffer high surgical morbidity. Current robotic technology provides a unique opportunity to test whether laparoscopy can improve the post-operative course of pancreas transplantation (PT). Current knowledge on robotic pancreas and renal transplantation was reviewed to determine feasibility and safety of robotic PT. Information available from literature was included in this review, together with personal experience including three PT, and two renal allotransplants. As of April 2011, the relevant literature provides two case reports on robotic renal transplantation. The author's experience consists of one further renal allotransplantation, two solitary PT, and one simultaneous pancreas-kidney transplantation. Information obtained at international conferences include several other renal allotransplants, but no additional PT. Preliminary data show that PT is feasible laparoscopically under robotic assistance, but raises concerns regarding the effects of increased warm ischemia time on graft viability. Indeed, during construction of vascular anastomoses, graft temperature progressively increases, since maintenance of a stable graft temperature is difficult to achieve laparoscopically. There is no proof that progressive graft warming produces actual damage to transplanted organs, unless exceedingly long. However, this important question is likely to elicit a vibrant discussion in the transplant community.

Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients.

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.