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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. 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. 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. LRATP is feasible in selected patients, but further experience is needed to draw final conclusions.

Laparoscopic resection of liver tumors located in the posterosuperior segments is a challenging operation that could be facilitated by robotic assistance. Laparoscopic resection of 12 tumors located in posterosuperior segments (IVa: 1; VII: 5; VIII: 6) was carried out under robotic assistance. All patients had a single tumor nodule. Data were collected prospectively and analyzed retrospectively. Surgery required a mean of 260.4 min (115–430) and was completed laparoscopically in all but one patient, who required conversion to mini-laparotomy because of intolerance of pneumoperitoneum (8.3 %). Mean estimated blood loss was 252.7 ml (50–600), making transfusion necessary in 3 patients (25.0 %). Post-operative complications occurred in 4 patients (33.3 %), being of Clavien–Dindo grade II in 3 patients (25.0 %) and Clavien–Dindo grade IV in 1 patient (8.3 %). Reoperation was required in 1 patient, who subsequently had a long hospital stay, because of decompensated cirrhosis. Median length of hospital stay was 8.5 days (7–96). No patient was readmitted. Pathology showed hepatocellular carcinoma in 7 patients (58.3 %), liver metastasis in 2 patients (16.6 %), and hepatic adenoma, focal nodular hyperplasia, and hemangioma in one patient each (8.3 %). All patients had a margin negative resection. After a mean follow-up period of 21.4 months (±24.4), no patient with malignant histology developed recurrence. Our initial experience confirms that laparoscopic robot-assisted resection of tumors located in the posterosuperior segments is feasible. Further experience is needed before final conclusions can be drawn and meaningful comparison with other surgical techniques becomes possible.

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. Our literature review was conducted in Pubmed. Articles written in English containing five or more LPD were selected. 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 %. In selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is feasible and safe.

Background Laparoscopic pancreaticoduodenectomy is feasible, but requires adaptations to established surgical techniques. The improved dexterity offered by robotic assistance provides the opportunity to see whether laparoscopic pancreaticoduodenectomy can be performed safely when faithfully reproducing the open operation. Methods Patients were selected for robotic pancreaticoduodenectomy when generally suitable for laparoscopy. Obese patients were excluded, and those with pancreatic cancer were highly selected. A prospectively designed database was used for data collection and analysis. Results Of 238 patients undergoing pancreaticoduodenectomy, 34 (14·3 per cent) were operated on robotically. No procedure was converted to conventional laparoscopy or open surgery, despite three patients requiring segmental resection of the superior mesenteric/portal vein and reconstruction. The mean duration of operation was 597 (range 420–960) min. The mean number of lymph nodes retrieved and analysed from patients with neoplasia was 32 (range 15–76). Four patients required blood transfusions and five developed postoperative complications exceeding Clavien–Dindo grade II. There were four grade B pancreatic fistulas. One patient died on postoperative day 40. Excess mean operative cost compared with open resection was €6193. Conclusion Selected patients can safely undergo robotic pancreaticoduodenectomy. The main downsides are high costs and prolonged operating times compared with open resection.

Background Originally introduced for cutaneous T-cell lymphomas and autoimmune diseases, extracorporeal photopheresis (ECP) has been proven effective to reverse allograft rejection. The aim of the present work was to show the results of a single-center experience with ECP for the treatment of biopsy-proven rejection in selected liver transplant (LT) recipients. Patients and methods A retrospective review of five LT patients (M:F = 4:1; median age 51 years) undergoing ECP for biopsy-proven allograft rejection between January 1996 and December 2003. In this period 476 LT were performed on 441 patients. Results The indications for LT were three cases of HCV-related cirrhosis, complicated by hepatocellular carcinoma in two; one HBV-HDV-alcoholic cirrhosis; and one fulminant HBV hepatitis. All patients received calcineurin-inhibitor (CNI)-based immunosuppression with induction using anti-IL2R monoclonal antibodies. Indications for ECP were: ductopenic rejection in one patient with HCV recurrence; steroid-resistant acute rejection in two; acute rejection in a major ABO-mismatched liver graft; and one acute rejection in a patient with a proven allergy to steroids. The median interval from LT to inception of ECP was 43 days. The median number of ECP sessions per patient was 20. During the course of ECP, two patients tested positive for CMV antigenemia, associated in one case with bacterial pneumonia. All patients tolerated ECP and there were no procedure-related complications. At a median follow-up of 7.9 months after start of ECP, neither rejection relapses nor HCV/HBV recurrences have been observed. Three patients are off ECP with complete reversal and low-dose immunosuppression. Two patients are still receiving ECP with full-dose immunosuppression: one has achieved normal liver function but ECP is indicated due to a major ABO-incompatible liver graft, while the other patient's liver functions have not yet returned to baseline values.

Context Isolated involvement of an arterial segment in pancreatic tumors occurs infrequently and does not necessarily mean tumor unresctability being possibly caused by tumor location rather than by excessive growth. Objective We report on the outcome of a highly selected group of patients undergoing pancreatectomy plus resection of an isolated arterial segment at a single Institution. Methods From January 1993 to May 2011 resection of an isolated arterial segment was performed during 26 pancreatectomies. There were 12 males (46.2%) and 14 females (53.8%) with a mean age of 63.6 years. One patient was operated by robotic surgery. Two patients underwent total pancreatectomy (7.7%), 5 pancreaticoduodenectomy (19.2%) and 19 distal splenopancreatectomy (73.1%). Resected arterial segments were celiac trunk (CT) (n=14), hepatic artery (HA) (n=8), CT and HA (n=4). In 6 patients the hepatic arterial flow was re-established by end-to-end anastomosis (n=1), transposition of the left gastric artery (n=1) and interposition of a saphenous vein jump-graft (n=4). Multivisceral resection was required in 9 patients. Results Final pathology disclosed ductal adenocarcinoma (DA) in 18 patients (69.2%), other pancreatic tumor types or periampullary carcinoma in 5 (19.2%) patients and metastatic tumor in 3 patients (11.5%). Fifteen DA patients were node positive (83.3%). Post-operative morbidity and mortality were 55.5% and 3.8%, respectively. After a mean follow up period of 111 months (range 5-225 months), actual survival rate was 64% at 1 year and 20% at 3 years. Equivalent figures for DA were 30% and 15%, respectively. These data favorably compare with an historical cohort of patients with locally advanced DA undergoing palliation without resection. No patient developed local recurrence, despite none received pre- or post-operative radiation. Conclusions In patients affected by DA the resection remains key for cure and possibly provides the best palliative treatment. Highly selected patients with isolated involvement of CT and/or HA may undergo pancreatectomy with results similar to patients without vascular involvement and superior to those offered by palliation or medical therapy alone. The lack of local recurrence seems to be a relevant treatment endpoint., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

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.

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.

We retrospectively evaluated the outcome of the surgical treatment of patients with renal cell carcinoma (RCC) and extensive inferior vena cava (IVC) involvement. Our aim was to investigate if a particular surgical technique could reduce morbidity and complications associated with this condition.From 1996 to 2007, 22 patients with RCC and extensive IVC involvement underwent radical surgical treatment with the intention to avoid, whenever possible, sternotomy and cardiopulmonary bypass. The level of the tumor thrombus was I (2 cm above the renal vein) in 2 patients, II (below the intrahepatic vena cava) in 9 patients, III (intrahepatic vena cava below the diaphragm) in 7 patients, and IV (atrial) in 4 patients. Extracorporeal vascular bypass was used for 4 patients with level IV and for 2 patients with level III tumor thrombi, with hypothermic circulatory arrest in 2 patients. Extensive liver mobilization techniques were adopted in 16 patients. Overall and cancer-specific survival (CSS) were analyzed based on tumor extent (N0M0, N+M+), pathologic stage (pT3b, pT3c, pT4), thrombus level, and caval wall infiltration.Two patients died within 1 month of surgery and the remaining 20 patients have a mean follow-up of 32.2 months (range 6-90): 8 are alive (overall survival 40%), but 2 with disease (CSS 30%). A total of 10 severe complications developed in 8 patients (36%). Both overall and CSS were significantly associated with tumor stage (Log-rank P = 0.0237 and 0.0465), presence of nodal or systemic metastases (Log-rank P = 0.0835 and 0.0669; Wilcoxon's test P = 0.0407 and 0.0411), and caval wall infiltration (Log-rank P = 0.0200 and 0.0418).Despite the low overall survival, related to the high percentage of nodal and systemic metastases, aggressive surgical management with resection of synchronous metastatic disease for symptom palliation and cytoreduction, followed by immunotherapy is justified in this setting. A transabdominal approach to RCC and IVC involvement, even in patients with level III thrombus, can provide the surgeon with an exposure similar to thoracoabdominal incisions without the complications associated with thoracotomy.

Aims: This year, we plan to address the direction of future studies based on the results of the critical reviews. Materials & methods: Clinical questions (CGs) of interest were proposed by the panel. The recommendations for the CQs in representative seven guidelines were compared. The presence or absence of evidence on which these recommendations were based was evaluated. Results: Among 37 CQs, there were only five CQs where agreement based on sufficient evidence was achieved: the use of CT and MRI for diagnosis, the definition of resectable pancreatic cancer, first line chemotherapy for metastatic disease, the role of celiac neurolysis and the reporting of lymph node metastases. There was agreement in other four CQs despite the lack of sufficient evidence: optimal combination of imaging studies for staging, the role of EUS and FNA, the use of radiotherapy to imrpove quality of life and the role of pre-operative biliary drainage. In 25 CQs, there was disagreement. Conclusion: The lack of sufficient evidence is one of the resons for the disagreement among the existing guidelines. In order to create strong evidence, especially in areas where there is disagreement among the guidelines, and to create a global evidence-based consensus in future studies.

s / Pancreatology 546 staining; six fields for each patient) in surgical specimens. We evaluated the PI by Ki-67 staining for grading in 7/21 tumors (expressed by number of positive nuclei/total nuclei). Results: Pathological analysis demonstrated 5 ADN, 5 BRD and 12 WDC. All ADN were associated with pattern A, showing high MVD (463 vessels/mm2); 3/4 lesions showing pattern B1 were BRD, with middle level of MVD (373 vessels/mm2) while 3/4 lesions with pattern B2 were WDC, demonstrating low level of MVD (vessels/mm2, p 0.05). Discussion: In our opinion the MDCT post-contrastographic pattern and the MVD of PNET can suggest their biological behavior. The CA system can help the pathologist to have a rapid evaluation of Ki-67 for grading in PNET.

332 Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth highest cause of death in the western world. The adjuvant chemotherapy can increase the overall survivor (OS) of PDAC patients. The Gemcitabine (GEM) and alkaloids mixture (ALK-014) combination shows the increase two time the OS non resectable in PDAC patients with respect to gemcitabine treatment alone. Indeed the Alkaoids compound modulated the Matrix MetalloProteinase 9 (MMP9) in PDAC cell clines. AIM: Our goal was to investigate the MMP 9 protein modulation in primary cell cultures (PCCs) of PDAC by Gem and ALK-014 combination treatment. Methods: Two PCCs (LPc006 and LPc028) were seeded in 4 multi-well chamber slids (8,000 each/well) for cytotoxicity study by Gem [10 Nm], ALk-014 [1µm]and their combination. After 48 h of treatment the cells were stained Immunocytochemistry (IHC) using polyclonal antibody for MMP9. We used no-treated cells to evaluate basic level of MMP9 protein. No–stained cells were used as negative control. All experiments were done in triplicates. We evaluated protein expression and cellular morphology by computer for imaging analysis (D-Sight, Menarini, Italy). The expression differences was evaluated by ANOVA and t-test analyses. Results: We found a significant reduction of MMP9 expression in both cell lines treated with Gem/ALK-014 combination with respect to their controls ( p

R. Gradiz , A.M. Abrantes , A.C. Mamede , M.F. Botelho , A. Mota-Pinto . General Pathology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal 2 Biophysics' Unit, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal 3 CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilha, Portugal 4 CIMAGO – Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal among solid tumors. Only a subset of patients benefit from chemotherapy, and identification of novel prognostic factors is warranted. Recently, miRNAs emerged as a pivotal class of regulators for multiple genes involved in cancer, including PDAC (Giovannetti et al, Cancer Res 2010), and miRNA expression pattern classified tumors better than mRNA data (Lu et al, Nature 2005), suggesting their use for diagnostic purposes. However, high-throughput arrays detecting more than 1000 miRNAs are opening new opportunities to evaluate whether their profiles can also predict clinical outcome. Therefore, the present study evaluated whether comprehensive miRNA expression profiling by microarray technology can predict overall survival (OS) in resected PDAC patients. High-resolution miRNA profiles were obtained with the Toray's 3D-GeneTM miRNA chip, detecting 1200 types of human miRNA. RNA was isolated from formaldehyde fixed paraffin embedded primary tumors of 26 stage-pT3N1Mx homogeneously treated patients (gemcitabine 1000 mg/m2/day on days 1/8/15, every 28 days), selected according to their outcome (OS 30 months). Microarray slides of the 19 samples that passed RNA quality check were scanned using 3D-GeneTM Scanner 3000 with appropriate photomultiplier settings for red channel. Each microarray was scanned three times, and then merged into one dataset analyzed. Highly stringent statistics included t-test, Spearman ranked correlation to generate a distance matrix, and iterative approaches. Unsupervised hierarchical analysis revealed that the PDAC specimens clustered according to their long/short OS classification, while the feature selection algorithm RELIEF identified the top 10 discriminating miRNAs between the two groups. MiR211 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 RT-PCR in an independent cohort of laser microdissected tumors from 60 resected stage-pT3N1Mx PDAC patients treated with the same gemcitabine regimen. Patients with low miR211 expression, according to median value (12.8 a.u. calculated as ΔCt vs. RNU6), 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 miR211 expression was an independent factor of poor prognosis for OS (hazard ratio 2.3, P=0.03) after adjusting for all the factors influencing clinical outcome. In conclusion, through comprehensive microarray analysis and PCR validation we identified miR211 as prognostic factor in resected PDAC. This miRNA was already associated with melanoma invasiveness, but our results prompt further prospective studies as well as research on miR211 biological role in PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 186. doi:1538-7445.AM2012-186

A Kaposi's sarcoma case with involvement of the gastrointestinal tract resulting in an unusual clinical syndrome characterized by diarrhea and protein-losing enteropathy is described. A careful examination of the literature reveals only one account of this rare pathologic condition.

4062 Background: FOLFIRINOX has shown high activity in metastatic pancreatic cancer (PC) patients and could be an interesting regimen also for patients with inoperable locally advanced disease. Our group had developed a similar schedule in metastatic colorectal cancer named FOLFOXIRI with good tolerance and activity. Therefore, we have decided to perform a phase II trial to prospectively evaluate the activity of modified FOLFOXIRI in borderline resectable or unresectable PC. Methods: Modified FOLFOXIRI consisted of a lower dose of irinotecan (150 mg/sqm) and of infusional 5-fluorouracil (2800 mg/sqm as a 48-hour continuous infusion on days 1 to 3) with no bolus 5-fluorouracil. Folinic acid and oxaliplatin (85 mg/sqm) remained unchanged. The study enrolled patients with diagnosis of pancreatic adenocarcinoma, stage III borderline resectable or unresectable disease (cT4,cN0-1,cM0), ECOG PS 0-1, age 18-75. The primary end-point of the study was the percent of patients who undergo radical surgical resection after chemotherapy. Results: Thirty-two patients have been enrolled; M/F=12/20; PS 0/1=16/16. Median age was 60 years (range 44-75). Median number of FOLFOXIRI cycles was 6 (range 2-14). Grade 3-4 toxicities was experienced by 20 patients during chemotherapy. Twelve partial responses (37%) and 14 stable diseases (45%) have been observed; 2 patients had progressive diseases (6%). The remaining 4 patients (12%) have not been yet evaluated because are still in the first months of treatment. A local treatment was received after chemotherapy by 18 patients until now: 13 (41%) received radical surgical resection and 5 received concomitant chemo-radiotherapy. Three explorative laparotomy showed occult metastases. In other 7 cases surgery is planned while 2 patients refused surgery. Median progression-free survival is 14.0 months and median overall survival is 24.2 months with a two-year survival rate of 54%. Conclusions: Chemotherapy with FOLFOXIRI seems active in locally advanced PC and may allow to obtain a downstaging of disease leading to achieve a curative surgical resection in some cases. Longer follow up is needed to better evaluate long-term outcome of this strategy.