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Background Organ transplant recipients are at increased risk of nonmelanotic skin cancers (NMSC). Scarce data exist regarding secondary malignancies developing post–simultaneous pancreas-kidney (SPK) transplantations. Our aim was to assess long-term risk of skin cancers among kidney alone (KA) and SPK transplantation recipients. Methods In this study, 521 patients who underwent KA or SPK transplantation at our medical center were observed up by dedicated nephrologists and dermatologists. SPK transplantation recipients were matched with a control group of KA transplantation recipients based on demographic and clinical data. A multivariate analysis was performed to find independent cancer risk factors. Results Patients who developed skin cancer were generally older, had a fair skin type, and had a higher incidence of NMSC before transplantation. Older age and fair skin type were independent risk factors on multivariate analysis. SPK transplantation in itself was not an independent risk factor. Cancer recurrence was associated with older age and male sex. Darker skin type and lowered immunosuppressive burden were protective. Conclusion In contrast to previous studies, the use of antithymocytic agents or SPK transplantation were not independently associated with increased skin cancer risk in this multivariate analysis. These findings emphasize the complex interplay between posttransplantation NMSC and various clinical and epidemiologic risk parameters.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a developing therapeutic approach for premalignant pancreatic-cystic neoplasms (PCNs) and small pancreatic neuroendocrine tumors (PNETs). The safety and efficacy of pancreatic EUS-RFA were previously reported in small series. Herein we report our initial experience with RFA of PCNs and small PNETs.This is a prospective single-center study including 12 patients with a median follow-up of 7 months, with either PCN or PNETamp;lt;2 cm. Eligible PCNs were either intraductal papillary mucinous neoplasms (IPMN) with worrisome features or mucinous cystic neoplasms (MCN) that were not eligible or refused surgery. Ablation was performed using a 19-gauge dedicated needle.Twelve patients were treated, five had PCNs (four IPMNs, one MCN; median size of 36 mm, range 12-60) and seven had PNETs (median size 8.9 mm, range 6-18). Among patients with PCNs, the complete radiologic response was achieved in 3/5 (60%), partial response in 1/5 (20%) and failure in 1/5 (20%). Among six patients with nonfunctioning PNETs, the complete radiologic response was achieved in 4/6 (66.7%), partial radiologic response in 0/6 (0%) and failure in 2/6 (33.3%). Following a median follow-up of 7 months. One patient with insulinoma showed complete resolution of hypoglycemia-related symptoms. Three postprocedural adverse events occurred, including one case (1/12, 8.3%) of mild acute pancreatitis and two cases (2/12, 16.7%) of abdominal pain.EUS-guided RFA for premalignant PCNs and PNETs is feasible and well-tolerated. Efficacy would be further evaluated with continued follow-up of patients.

Background Mammalian target of rapamycin (mTOR) inhibitors following liver transplantation (LT) are used to minimize calcineurin inhibitor (CNI)-related nephrotoxicity. Data about metabolic effects of mTOR inhibitors are still limited. Aim This study aims to determine the renal and metabolic effects of different mTOR inhibitor–based protocols in real-life LT patients. Methods This is a retrospective cohort study of patients treated with mTOR inhibitors after LT. Demographics, treatment protocols, glomerular filtration rate (GFR), and metabolic parameters were collected over a period of 4 years. Initiation of blood pressure (BP), diabetes mellitus, and lipid medications was also noted. Results Fifty-two LT recipients received mTOR inhibitors. GFR improved significantly (by 1.96 mL/min/year), with greater improvement in patients with baseline renal dysfunction (+13.3 mL/min vs +4.5 mL/min at 3 years). Conversion to an mTOR inhibitor during the first post-transplant year resulted in a more durable improvement in GFR (for 4 years vs only 1 year for later conversion).No significant weight gain or new-onset diabetes mellitus was observed. However, there was some increase in total cholesterol (+7 mg/dL) and blood pressure (+2 mm Hg during the third year and +8 mm Hg in the fourth years), followed by initiation of lipid-lowering and BP medications in 25% and 13% of patients, respectively. Conclusions Treatment with an mTOR inhibitor following LT resulted in improved kidney functions without significant negative metabolic effects such as weight gain or new-onset diabetes mellitus. This makes mTOR inhibitors a valuable immunosuppressive option in the face of the growing incidence of nonalcoholic steatohepatitis as a leading cause for LT.

Endoscopic retrograde cholangiopancreatography (ERCP) is the first line treatment for choledocholithiasis. In many occasions, several attempts of ERCP are performed until failure is declared and surgical treatment is applied, in many times following procedure-related complications. We present the results of surgical management of patients with choledocholithiasis following repeated failures of ERCP due to impaction of multiple large stones.Patients that underwent surgical treatment for choledocholithiasis following repeated ERCP attempts between January 2006 and December 2018 were retrospectively assessed. Post-ERCP complications were evaluated and the surgical approach, technique, and outcomes were assessed.One hundred and two patients were operated on for choledocholithiasis following repeated failed ERCP. All the patients had at least 2 failed attempts (mean = 3.2 ± 1.7), and 25 (23.5%) suffered major ERCP-related complications. Following choledochotomy and stone extraction, bilioenteric anastomosis was done in the vast majority of patients (90.2%), most commonly choledochoduodenostomy (62%). Thirty-eight (37%) patients had minimally invasive procedure (laparoscopic n = 26, robotic assisted n = 12). Major post-operative complications (Clavien-Dindo ≥ 3) occurred in 24 patients (23.5%). Nine patients (8.8%) were re-operated and 10 (9.8%) were readmitted within 30 days from surgery. Three patients died within 30 days from surgery. Older patients had significantly more ERCP attempts and suffered higher post-operative mortality. During a median follow-up of 70 months, the only biliary complication was an anastomotic stricture in one patient.Surgery for CBDS after failure of ERCP is safe and provides a highly effective long-term solution.

Background Reoperation following PD is a surrogate marker for a complex post-operative course and may lead to devastating consequences. We evaluate the indications for early reoperation following PD and analyze its effect on short- and long-term outcome. Methods Four hundred and thirty-three patients that underwent PD between August 2006 and June 2016 were retrospectively analyzed. Results Forty-eight patients (11%; ROp group) underwent 60 reoperations within 60 days from PD. Forty-two patients underwent 1 reoperation, and 6 had up to 6 reoperations. The average time to first reoperation was 10.1 ± 13.4 days. The most common indications were anastomotic leaks (22 operations in 18 patients; 37.5% of ROp), followed by post-pancreatectomy hemorrhage (PPH) (14 reoperations in 12 patients; 25%), and wound complications in 10 (20.8%). Patients with cholangiocarcinoma had the highest reoperation rate (25%) followed by ductal adenocarcinoma (12.3%). Reoperation was associated with increased length of hospital stay and a high post-operative mortality of 18.7%, compared to 2.6% for the non-reoperated group. For those who survived the post-operative period, the overall and disease-free survival were not affected by reoperation. Conclusions Early reoperations following PD carries a dramatically increased mortality rate, but has no impact on long-term survival.

Background Only few studies of living kidney donors have included controls that were similarly healthy, including excellent kidney function. Methods In this study, we aimed to estimate long term metabolic and renal outcome in a cohort of 211 living donors compared to two control groups: paired-matched controls, and another control group of 2534 healthy individuals with excellent kidney function. Results Donors presented with higher estimated Glomerular Filtration Rate (eGFR): (97.6 ± 15.2 vs 96.1 ± 12.2 vs 94.5 ± 12.4 ml/min/1.73m2) and lower urine albumin to creatinine ratio (UACR) (4.3 ± 5.9 vs 5.9 ± 6.1 vs 6.1 ± 6.9 mg/g) for donors, matched controls and healthy controls, respectively (p

Background and aims Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. Methods LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. Results Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p, Graphical abstract

Abdominal tumors invading the inferior vena cava (IVC) present significant challenges to surgeons and oncologists.To describe a surgical approach and patient outcomes.The authors conducted a retrospective analysis of surgically resected tumors with IVC involvement by direct tumor encasement or intravascular tumor growth. Patients were classified according to level of IVC involvement, presence of intravascular tumor thrombus, and presence of hepatic parenchymal involvement.Study patients presented with leiomyosarcomas (n=5), renal cell carcinoma (n=7), hepatocellular carcinoma (n=1), cholangiocarcinoma (n=2), Wilms tumor (n=1), neuroblastoma (n=1), endometrial leiomyomatosis (n=1), adrenocortical carcinoma (n=1), and paraganglioma (n=1). The surgeries were conducted between 2010 and 2019. Extension of tumor thrombus above the hepatic veins required a venovenous bypass (n=3) or a full cardiac bypass (n=1). Hepatic parenchymal involvement required total hepatic vascular isolation with in situ hepatic perfusion and cooling (n=3). Circular resection of IVC was performed in five cases. Six patients had early postoperative complications, and the 90-day mortality rate was 10%. Twelve patients were alive, and six were disease-free after a mean follow-up of 1.6 years.Surgical resection of abdominal tumors with IVC involvement can be performed in selected patients with acceptable morbidity and mortality. Careful patient selection, and multidisciplinary involvement in preoperative planning are key for optimal outcome.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The aim of this study was to characterize patients diagnosed with ACC at a single center between 2014-2019. METHODS: We retrospectively reviewed data regarding demographics, tumor characteristics and functionality, treatment and survival. RESULTS: The study cohort included 27 subjects (56% females), followed for 27±10.6 months. The mean age at diagnosis was 49.4±9 years. Co-morbidities at presentation included hypertension (63%), diabetes mellitus (22%) and dyslipidemia (26%). 74.1% of tumors were functioning – of which 85% were cortisol-secreting and 15% androgen-secreting. Aldosterone was secreted additionally in 15%. ENSAT stage at diagnosis was stage 1 in 15%, stage 2 in 35%, stage 3 in 12% and stage 4 in 38%. Eighty-nine % of patients underwent surgery. Treatment with mitotane was initiated in 82% of patients, reaching a mean maximal dose of 3.3 ±0.4 grams/day. Chemotherapy and/or radiation were given in 37% and 22%, respectively. Several patients (14.8%) had a second primary cancer, diagnosed before ACC in 75%. Progression was observed in 48% of patients, with a progression-free survival of 8.3±6.6 months. Thirty-five % of patients died during follow up, time to death was 12.8±0.4 months. Twenty two % of patients survived over 30 months after diagnosis. KI67 above 20% or stage above 2 negatively affected survival. CONCLUSIONS: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients achieving survival of over 30 months after diagnosis. Further characterization of this population may improve our understanding of the biology and treatment of this rare disease.

Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.

Inflammatory bowel diseases (IBD) is a systemic disorder with possible renal involvement, yet data regarding the outcome of kidney transplantation (KT) in those patients, and IBD course post KT, are scarce. In this retrospective analysis, we studied the outcome of 12 IBD kidney recipients (seven Crohn's disease, five ulcerative colitis; primary kidney disease was IgA nephropathy in five, polycystic disease in four), compared to two control groups: matched controls and a cohort of recipients with similar kidney disease. During a follow-up period of 60.1 (11.0-76.6) months (median, interquartile range), estimated 5-year survival was 80.8 vs. 96.8%, with and without IBD, respectively (P = 0.001). Risk of death with a functioning graft was higher with IBD (HR = 1.441, P = 0.048), and with increased age (HR = 1.109, P = 0.05). Late rehospitalization rate was higher in IBD [incidence rate ratio = 1.168, P = 0.030], as well as rate of hospitalization related to infection [1.42, P = 0.037]. All patients that were in remission before KT, remission was maintained. Patients that were transplanted with mild or moderate disease remained stable or improved with Infliximab or Adalimumab treatment. In conclusion, IBD is associated with an increased risk of mortality, hospitalization because of infection and late rehospitalization after KT. Clinical course of IBD is stable after KT.

Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2(+) lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

Management of asymptomatic, nonfunctioning small pancreatic neuroendocrine tumors (PNETs) is controversial because of their overall good prognosis, and the morbidity and mortality associated with pancreatic surgery. Our aim was to compare the outcomes of resection with expectant management of patients with small asymptomatic PNETs. Retrospective review of patients with nonfunctioning asymptomatic PNETs

BACKGROUND AND OBJECTIVES The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection. METHODS Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed. RESULTS In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.

Background The influence of postoperative complications, specifically, pancreatic fistula (PF), on long-term oncologic outcome in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear. Methods Prospectively collected data of patients who underwent pancreaticoduodenectomy (PD) for PDAC between 2008 and 2016 were retrospectively reviewed and analyzed. Deaths within 90 days were excluded. Median follow-up time was 22 months for the entire cohort (range 2–102 months). PF was graded as biochemical leak, grade B, or grade C according to the criteria of the International Study Group on Pancreatic Fistula. Postoperative complications were graded according to the Clavien-Dindo classification (CDC). Data on clinical and pathological characteristics as well as on recurrence and survival were collected. Results Twenty-nine of the 148 identified patients (19%) developed PF, of whom 17 (11.4%) had a PF grade B or C. 29 patients developed a postoperative complication CDC grade 3 or 4. The respective 3-year disease-free survival was 15.5% and 19.2% (P = 0.725), and the 5-year overall survival was 20% and 16% (P = 0.914) in patients with and without PF. On multivariate analysis, the use of adjuvant chemotherapy, lymph node involvement, surgical margin involvement, and tumor grade were associated with patient survival. PF and postoperative complications CDC grade 3 or 4 were not associated with decreased long-term survival, disease-free survival or local recurrence rate. Conclusions While acknowledging the limited sample size, no association was seen between PF or postoperative complications and overall or disease-free survival in patients undergoing PD for PDAC.

Although laparoscopic distal pancreatectomy (LDP) is gradually recognized as a safe and effective alternative to open distal pancreatectomy (ODP), it is not yet widely accepted.We describe our experience, with emphasis on the learning curve of LDP.Patients who underwent distal pancreatectomy (DP) between January 2011 and August 2014 were included. Operative and postoperative parameters, as well as pathology reports were evaluated.Thirty-nine and 41 patients underwent LDP and ODP, respectively. The mean age and gender distribution were comparable between groups. In six patients (15.4%), a conversion to open surgery was indicated. Operating time and intraoperative blood transfusion rates were comparable between groups. One patient of the LDP group died postoperatively. Postoperative complications were comparable with similar Dindo-Clavien (DC) score. Length of stay (LOS) was shorter following LDP (8.15 ± 4.68 versus 11.3 ± 6.3 days, P = .014). Patients selected to have LDP had larger lesions compared to those who underwent ODP (4.59 ± 4.23 versus 3 ± 2.52 cm, respectively, P = .048). R0 resection rates between the groups were comparable (92.3% in LDP versus 97.5% in ODP) as well as lymph node (LN) harvest (6.4 ± 6.4 LN in LDP versus 7.6 ± 6.6 LN in ODP). Following the 17th patient, LDP operative time decreased by more than 35 minutes, no conversions were done, no blood transfusion was needed, and the LOS was shortened by over 2 days.Short learning curve, shorter LOS, and satisfactory short-term oncological outcome place LDP as an attractive alternative for selected patients requiring DP.

Background and Objectives Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations. Methods Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 ± 4 and 56.5 ± 9 years). Patient and tumor characteristics, perioperative, and long-term outcomes were compared. Results Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 ± 109 versus 261 ± 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P

Background Liver transplantation (LT) and liver resection (LR) are curative treatment options for patients with hepatocellular carcinoma within the Milan criteria. Severe organ shortage dictates the preference for LR. Our aim was to provide an intention-to-treat retrospective comparison of survival between patients who were placed on waiting lists for LT and those who underwent LR. Methods The medical records of patients with hepatocellular carcinoma within the Milan criteria treated by LR or listed for LT between 2007 and 2016 were reviewed. We performed intention-to-treat analyses of overall survival and recurrence. Results There were 54 patients on the waiting list for LT, and 30 of them underwent LR. Thirteen of the 54 patients (24%) were not transplanted because of disease-related mortality or tumor progression. The median waiting time to transplantation was 304 days. The 90-day mortality was higher in transplanted patients (9.8% vs 3.3%, P = .003). Intention-to-treat survival was similar for the LT and LR groups (5-year survival, 47.8% vs 55%, respectively, P = .185). There was a trend toward improved 5-year disease-free survival for listed patients (56.2% vs 26.3% for patients undergoing LR, P = .15). Conclusion Intention-to-treat survival is similar in patients undergoing LR and those on waiting lists for LT. There is a 24% risk to drop from the transplant list. The higher perioperative mortality among patients undergoing LT is balanced by a higher tumor recurrence rate after LR

Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC), representing an advanced disease stage and independently predicting patient survival. Current nodal staging is inadequate preoperatively and even less so postoperatively, and molecular biomarkers are needed to improve prognostication and selection of therapy. Recent data have suggested important roles of miRNAs in PDAC tumorigenesis and progression. The aim of the present study was to identify miRNA expression signature for nodal spread in PDAC patients. Using PDAC human tissue specimens, we identified 39 miRNAs which were differently expressed in LN positive compared to LN negative PDAC samples. Of them, six miRNAs have been reported to play a role in cancer invasion and metastasis. A high versus low six- miRNA signature score was predictive of LN metastasis in the PDAC validation cohort. We demonstrated a similar expression pattern of four out of the six miRNAs in the plasma of PDAC patients. The results of our in-vitro studies revealed that miR-141 and miR-720 are involved in the process of epithelial to mesenchymal-transition in PDAC. These miRNAs significantly inhibited in vitro proliferation, migration and invasion of PDAC cells as evidence by gain- and loss- of function studies, specifically, via ZEB-1 and TWIST1 transcription factors, as well as through the activation of the MAP4K4/JNK signaling pathway.

Objective To assess clinical and pathologic efficacy of neoadjuvant FOLFIRINOX for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). Methods Patients receiving neoadjuvant FOLFIRINOX for LAPC and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017. Results Thirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, p = 0.016), and pancreatic fistula rate (0 versus 14.8%, p = 0.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, p = 0.001), lymph node involvement (22% vs 54.3%, p = 0.01), and surgical margin involvement (0 vs 17.4%, p = 0.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (p = 0.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months. Conclusions Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.

Background The utilization of extended criteria liver allografts (ECD) shortens time to transplantation. Objective To characterize the effect of liver allograft fibrosis on graft and patient survival after liver transplantation (LT), with particular attention to fibrosis progression. Methods Retrospective database search of donor and recipient liver allograft histology of liver transplants performed between 2007 and 2011. Donor and patient characteristics were analyzed. Results One hundred and one patients underwent LT with donor liver allografts with early-stage fibrosis (stage 1 fibrosis and stage 2 fibrosis). The level of liver fibrosis did not progress in 40% of the patients tested, and there was a regression of fibrosis in 30%. At a median follow-up of 71 months, of 101 patients transplanted with fibrotic livers, 63 patients (63%) were alive with functioning initial grafts, six patients (6%) were retransplanted, and 35 patients expired. The graft survival rates were 82% and 69% at 1 and 5 years, respectively. Graft survival differences were not found to be statistically significant between the degrees of liver allograft fibrosis: 5-year graft survival (73% for stage 1 fibrosis and 62% for stage 2 fibrosis, P = .24). The entire fibrosis group was further compared with a control group of 208 consecutive primary liver transplant patients with allografts having no fibrosis. The 5-year graft survival was not significantly different between the groups (69% for the fibrosis group vs 75% for the nonfibrosis group, P = .19). Survival was also not statistically different between the groups (5-year survival of 73% for the fibrosis group vs 79% for the nonfibrosis group, P = .2). In patients with HCV, graft survival differences were not found to be statistically significant with the use of early-stage fibrotic livers: 5-year graft survival of 60% for fibrosis group vs 70% for the nonfibrosis group, P = .22). Conclusion This study demonstrates that allografts with early-stage fibrosis achieve acceptable long-term survival after liver transplantation. Given these preliminary results, the use of organs with early-stage fibrosis warrants further studies at a larger scale to validate these results.

Our aim was to evaluate the association between visceral fat content with soft tissue sarcoma (STS) local recurrence and survival. One hundred and one computed tomography imaging studies of primary STS patients who had complete macroscopic resection at our institution between 2002 and 2012 were reviewed, and retroperitoneal and circumferential fat contents were measured. Correlations between imaging findings and clinical data were analyzed. Fifty-seven STS tumors (56.4 %) were retroperitoneal; of them, 65 % were high grade, median size was 15 cm (range 3–49), and the most common histological subtype was high grade liposarcoma (31.6 %). Median follow-up length for the entire cohort was 64 months (range 6–95). High visceral fat (VF) content ≥15 versus

Patients with liver disease and portal hypertension are at increased risk of complications from surgery. Recent advances have allowed better optimization of patients with cirrhosis before surgery and a reduction in postoperative complications. Despite this progress, the estimation of surgical risk in a patient with cirrhosis is challenging. The MELD score has shown promise in predicting postoperative mortality compared with the Child-Turcotte-Pugh score. This article addresses current concepts in the perioperative evaluation of patients with liver disease and portal tension, including a preoperative liver assessment (POLA) checklist that may be useful towards mitigating perioperative complications.

Objectives: To evaluate long-term morbidity, mortality, and quality of life (QoL) after pancreaticoduodenectomy (PD) in elderly adults. Design: Retrospective cohort study. Setting: Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. Participants: One hundred and sixty-eight individuals aged 70 and older who underwent PD between 1995 and 2010. Measurements: A prospective pancreatic surgery database was analyzed for postoperative morbidity; mortality; intensive care unit (ICU), hospital, and rehabilitation facility stay; and readmissions after surgery. QoL was assessed using a validated questionnaire completed 3, 6, and 12 months after surgery. Results: Seventy-two percent of the participants had an American Society of Anesthesiologists score of 3 or greater. There was no intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9% and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was 22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation facility. The first-year readmission rate was 31%. One- and 2-year overall survival rates were 58% and 36%, respectively. Global QoL scores 3 and 12 months after surgery were 68% and 73%, respectively. Scores were lower yet comparable with those of matched individuals undergoing laparoscopic cholecystectomy. Conclusion: Most elderly adults with pancreatic cancer survive longer than 1 year after PD; 36% survive longer than 2 years. These individuals are likely to have acceptable long-term morbidity and overall good QoL, corresponding with their age.

Background Living donor liver transplantation is a viable option to increase access to transplantation and techniques to limit the operative incision is one way to increase donation by decreasing donor morbidity. We describe our experience with a limited upper midline incision (UMI) for living donor right hepatectomy. Study design Prospective data were collected on 58 consecutive living liver donors who underwent right hepatectomy via a UMI. Results Donor median age was 32 years, with median body mass index of 24.6. The mean incision length was 11.7 cm. Ten liver grafts included middle hepatic vein. The mean graft volume by preoperative imaging was 940 cc. The mean operative time was 407 minutes; cellsaver was utilized in 35 patients with median of 1 unit. Mean peak aspartate transaminase (AST) and alanine transaminase (ALT) were 492 and 469, and peak bilirubin and international normalized ratio (INR) were 3.3 and 1.8. The average length of stay was 6 days. There were 10 Clavien grade I and 11 Clavien grade II complications. Three patients developed an incisional hernia requiring surgical repair. Conclusion Living liver donor hepatectomy can be safely performed through a UMI. This approach consolidates the steps of liver mobilization, hilar dissection, and parenchymal transection in a single-exposure technique, with incision comparable to the laparoscopic-assisted modality.

Previous data demonstrated that high retroperitoneal visceral fat content increases retroperitoneal soft-tissue sarcoma (RSTS) local recurrence and patients' mortality. Most RSTS tumors initiate and recur within visceral fat. The objective of the current study was to evaluate potential paracrine effects of visceral fat on RSTS. A xenograft model was used to evaluate in vivo effects of human visceral fat on STS growth. Tissue explants were prepared from visceral fat, and their conditioned medium (CM) was utilized for various in vitro experiments designed to evaluate growth, survival, migration, and invasion of STS and endothelial cells. Visceral fat–secreted protumorigenic factors were identified by mass spectrometry. The in vivo experiments demonstrated a significant increase in STS tumor growth rate when SK-LMS-1 leiomyosarcoma cells were colocalized with human visceral fat compared with subcutaneous injection of cancer cells only. The in vitro model demonstrated that visceral fat CM increased STS cellular growth and reduced doxorubicin-induced apoptosis. Visceral fat also enhanced STS cellular migration and invasion. In addition, visceral fat CM significantly increased endothelial cell tube formation, suggesting its role as a proangiogenic factor in the STS tumor microenvironment (TME). Using a robust proteomic approach, liquid chromatography and tandem mass spectrometry resolved various molecules within the visceral fat CM, of which a subset was associated with protumorigenic biologic processes. These results suggest that visceral fat directly interacts with STS cells by secreting specific adipokines into the TME, thus augmenting STS tumor cell proliferation and invasiveness. Fat-induced STS molecular deregulations should be studied to identify new potential prognostic and therapeutic targets. Implications: Visceral fat induces protumorigenic effects, in STS, through various secreted factors that should be investigated to improve our understanding of adipose–cancer cell interactions. Mol Cancer Res; 14(12); 1254–65. ©2016 AACR.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgery is the mainstay of HCC treatment.

Background High rates of extrapancreatic malignancies (EPM) have been observed in patients with intraductal papillary mucinous neoplasm (IPMN). IPMN in patients with familial pancreatic cancer have also been reported. Our purpose was to evaluate the association of IPMN with EPM, malignancies in family members, and germline BRCA1 and BRCA2 mutations. Methods Using retrospective analysis on prospectively collected data from 82 patients with IPMN and direct contact for familial cancer history, data were compared with those of 150 patients with pancreatic ductal adenocarcinoma (PDAC). The common germline mutations in the BRCA1 and BRCA2 genes were evaluated on available IPMN patients. Results EPM rates were greater in IPMN than PDAC patients (P = .002). Malignancies in first-degree relatives, specifically pancreatic cancer, were more common among IPMN than PDAC patients (P = .028). IPMN patients with EPM had high rates of relatives with colorectal cancer (31%). Two of the 51 genetically tested patients (4%) were BRCA2 mutation carriers, and both had first-degree relatives with pancreatic cancer. One patient fulfilled the Amsterdam criteria for hereditary nonpolyposis colon cancer; however, the neoplasm was microsatellite stable. Conclusion Our results demonstrated high rates of EPM among IPMN patients. There was an increased rate of cancer in families of IPMN patients, specifically pancreatic cancer. A high rate of colorectal cancer in families of IPMN patients who have EPM was also observed. These findings suggest a genetic component in the pathogenesis of IPMN. Possible genetic changes include BRCA2 mutations, which are found in 25% of IPMN patients with a family history of pancreatic cancer.

Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations.Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 ± 4 and 56.5 ± 9 years). Patient and tumor characteristics, perioperative, and long-term outcomes were compared.Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 ± 109 versus 261 ± 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P 0.0001). One elderly patient died following surgery (1.8%). Length of hospital stay was similar between groups. No difference in 3-year survival was demonstrated.Although associated with a small increase in postoperative morbidity and mortality, liver resection may be performed safely and effectively in carefully selected elderly patients. J. Surg. Oncol. 2016;113:485-488. © 2016 Wiley Periodicals, Inc.

Background Pulmonary embolism (PE) is an uncommon, life-threatening complication after living donor nephrectomy (LDN), and is considered among the most common causes for donor mortality. Most cases of postoperative PEs are thought to originate in deep venous thrombosis (DVT) of the lower extremities. Case Report A 56-year-old, healthy woman underwent laparoscopic left LDN. Her postoperative course was complicated by PE, presenting at postoperative day 7. Doppler ultrasonography of her lower extremities did not demonstrate DVT. Both transthoracic echocardiogram and contrast-enhanced computed tomography demonstrated a floating thrombus within the inferior vena cava (IVC) originating from a thrombus in the left renal vein stump. Symptoms resolved with systemic anticoagulation. Repeat transesophageal echocardiography demonstrated resolution of the IVC thrombus. Conclusions Thrombus originating in left renal vein stump should be considered in patients who develop PE after LDN, especially when lower extremity DVT is not demonstrated.

The benefits of adding chemotherapy to surgery in patients with hepatic colorectal metastases at moderate and high risk for recurrence and the optimal sequence of administration are undetermined.We followed the overall-survival and event-free survival rates after operation in patients with resectable colorectal metastases confined to the liver. The adjuvant patients first underwent surgery and then treatment, whereas the neoadjuvant patients underwent treatment, surgery, and re-treatment. Assignment was by oncologist and patient preferences. Chemotherapy was oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) based.Fifty-six of 105 patients who underwent liver resections for colorectal metastases (2002-2005) are included. The two groups were comparable for demographics, characteristics of disease (including recurrence risk), treatment protocols, and follow-up. The respective 1-, 2-, and 3-year overall survival rates were 91%, 91%, and 84%, and the event-free survival rates were 63%, 49%, and 49% for the 19 adjuvant patients, and 95%, 91%, and 70%, and 94%, 50%, and 50% for the 37 neoadjuvant patients.The midterm overall survival and disease-free survival rates in this group of patients with resectable colorectal metastases to the liver, who were treated with combination of resection and chemotherapy, were similar, regardless of the sequence of treatment.

Background Prognosis of patients following resection of CRC metastases to the liver has traditionally been predicted by clinical risk factors. In the era of neoadjuvant chemotherapy, determination of new prognostic indicators of outcome are necessary. Methods This retrospective study includes patients with CRC liver metastases, who received oxaliplatin or irinotecan based neoadjuvant chemotherapy and underwent R0 resection. Patients were followed by CT and PET-CT, before, during and after chemotherapy and surgery. The predictive value of the Memorial Sloan-Kettering Cancer Center Clinical Score (MSKCC-CS) and degree of response to chemotherapy (measured by CT and PET-CT), were analyzed by univariate and multivariate COX regression. Results Included are 54 patients. Overall 1-, 2-, 3-year survival rates 88%, 70%, and 39%. Response to chemotherapy on CT was a significant predictor of survival on univariate (P = 0.03) and multivariate analysis (P = 0.03), whereas MSKCC-CS and response to chemotherapy on PET-CT were not. Multivariate analysis demonstrated response to chemotherapy as a predictor of time to recurrence on CT (P = 0.02) and PET-CT (P = 0.03), while the MSKCC-CS (P = 0.64) was not. Conclusions In this cohort of patients treated by neoadjuvant chemotherapy, the outcome was not predicted by the traditional clinical scoring system, but rather by response to chemotherapy as evaluated by CT and PET-CT. J. Surg. Oncol. 2009;99: 93–98. © 2008 Wiley-Liss, Inc.

Background Recent data confirmed the importance of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the selection of patients with colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before hepatic resection in selected cases may improve outcome. The influence of chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases is not known. Methods Patients were assigned to either neoadjuvant treatment or immediate hepatic resection according to resectability, risk of recurrence, extrahepatic disease, and patient preference. Two-thirds of them underwent FDG-PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and FDG-PET/CT. Those without extensive extrahepatic disease underwent open exploration and resection of all the metastases according to original imaging findings. Operative and pathological findings were compared to imaging results. Results Twenty-seven patients (33 lesions) underwent immediate hepatic resection (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET: 93.3 vs 49%, P

Background Application of minimally invasive surgery for oncologic liver resection is still limited to expert centers. We describe our experience in laparoscopic liver resection (LLR) for colorectal liver metastases (CLM). Patients and methods Between February 2010 and February 2015, 174 patients underwent resection of CLM. LLR was chosen according to surgeon's preferences. Data was retrieved from the institutes' electronic charts and retrospectively analyzed. Results LLR was performed in 42 patients (24.5%) and OLR in 132. Increased number of metastases were found in OLR (2.82 ± 2.81 versus 1.78 ± 1.16, P = 0.02), with no difference in maximal lesion size (33.1 ± 22 versus 34.9 ± 27.5 cm, P = 0.7). Altogether 55 patients underwent major hepatectomy, and 50 of the OLR group (37.8%, 37 right hepatectomy and 7 left hepatectomy) ( P = 0.02). In 5 patients (11.6%) a conversion to open surgery was indicated. Operative time was longer in LLR. Estimated blood loss was decreased in laparoscopic minor resections. One OLR patient died during the postoperative period (0.7%). Eight patients in the OLR group had major complications, versus 1 in the LLR group ( P = 0.0016). Reoperation within 30 days was performed in 4 OLR patients and none in the LLR group. Patients in the LLR group had shorter length of stay (LOS) (6.78 ± 2.75 versus 8.39 ± 5.64 days, P = 0.038). R0 resection was 88% in both groups. Conclusions In selected patients with CLM, LLR is feasible, safe and may achieve shorter LOS without inferior oncologic outcome.