Pancreatic metastases from renal cell carcinoma: postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Metastases; Pancreatectomy; Renal cell carcinomaMetástasis; Pancreatectomía; Carcinoma de células renalesMetàstasis; Pancreatectomia; Carcinoma de cèl·lules renalsBackground: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival

The etiology, incidence, and impact of preservation fluid contamination during liver transplantation

The role of contaminated preservation fluid in the development of infection after liver transplantation has not been fully elucidated. To assess the incidence and etiology of contaminated preservation fluid and determine its impact on the subsequent development of infection after liver transplantation, we prospectively studied 50 consecutive liver transplants, and cultured the following samples in each instance: preservation fluid (immediately before and at the end of the back-table procedure, and just before implantation), blood, and bile from the donor, and ascitic fluid from the recipient. When any culture was positive, blood cultures were obtained and targeted antimicrobial therapy was started. We found that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of liver transplantation per year), but only 28% (14/50) were contaminated by recognized pathogens. Blood and bile cultures from the donor were positive in 28% and 6% respectively, whereas ascitic fluid was positive in 22%. The most frequently isolated microorganisms were coagulase-negative staphylococci. In nine cases, the microorganisms isolated from the preservation fluid concurred with those grown from the donor blood cultures, and in one case, the isolate matched with the one obtained from bile culture. No liver transplant recipient developed an infection due to the transmission of an organism isolated from the preservation fluid. Our findings indicate that contamination of the preservation fluid is frequent in liver transplantation, and it is mainly caused by saprophytic skin flora. Transmission of infection is low, particularly among those recipients given targeted antimicrobial treatment for organisms isolated in the preservation fluid

Endoscopic closure of duodenal perforation with an over-the-scope clip during endoscopic ultrasound-guided cholangiopancreatography

Duodenal perforations are a rare complication during interventional endoscopy. Their mortality is high, and the treatment in most cases is surgical. We report a case of duodenal perforation (type I, Stapfer) (1) during an interventional endoscopic ultrasound (EUS) procedure resolved using an over-the-scope clip called OTSC

Duodenopancreatectomía cefálica de urgencia tras una ingesta masiva de cáusticos

La ingesta de sustancias cáusticas es una emergencia que sigue observándose en adultos, principalmente con intención autolítica. Se recomienda un manejo agresivo de estos pacientes, ya que en caso de presentarse hemorragia o sospecha de necrosis y perforación, sólo la cirugía precoz con resección de todas las estructuras lesionadas puede salvar sus vidas. Cuando la..

Targeting the CYP2B1/cyclophosphamide suicide system to fibroblast growth factor receptors result in a potent antitumoral response in pancreatic cancer models

The CYP2B1/cyclophosphamide (CPA) suicide gene therapy approach has been shown to be highly promising in clinical trials for the treatment of pancreatic cancer. However, delivering the therapeutic gene to a sufficient number of tumor cells able to trigger a complete response remains a challenge. Target-specific delivery of adenovirus to fibroblast growth factor receptors (FGFRs) has been obtained in a variety of tumor models and has been shown to highly increase transduction efficiency. In the present paper we have tested the therapeutic outcome of retargeting the adenoviral vector, Ad-CYP2B1, to FGFRs, using an FGF2-Fab' conjugate, in pancreatic cancer models. First, we show a heterogeneous subcellular distribution of overexpressed FGFR-1 in pancreatic cancer cells. Higher transduction efficiency was observed in five of the six cell lines studied after FGF2-AdGFPLuc infection. Interestingly, an association between FGFR-1 membrane cell expression and viral entry was found. Moreover, tumors injected with FGF2-AdGFPLuc showed enhanced and persistent transgene expression. Importantly, we demonstrate the relevant enhanced cytotoxic effect of the FGF2-Ad-CYP2B]/CPA system in four of the six cell lines studied. Moreover, retargeting Ad-CYP2B1/CPA to FGFRs resulted in a potent antitumoral effect and in an increased survival rate, in two human pancreatic xenograft models. Thus, our results indicate that redirecting adenoviruses to FGFRs highly increases the potency of the suicide system CYP2B1/CPA. Consequently, it may constitute a promising approach to the treatment of patients with pancreatic tumors, in which a high proportion of FGF receptors precisely localize to the plasma membrane

Endoscopic biliary drainage in unresectable biliary obstruction: the role of endoscopic ultrasound-guidance in a cohort study

Background and study aims: the use of endoscopic ultrasound-guided biliary drainage (EUS-BD) has increased in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) and there are some concerns. The main aim of the study was to determine the role of EUS-BD in a palliative case cohort. The secondary aim was to compare the efficacy, safety and survival of EUS-BD and ERCP procedures. Patients and methods: this was an observational study at a single tertiary institution, with a consecutive inclusion from January 2015 to December 2016. The inclusion criteria were unresectable tumors of the biliopancreatic region with an indication of BD. Statistical comparison analysis was performed between the ERCP and EUS-BD groups. The incidence between groups was compared using the Chi-square and Fisher exact tests. The log rank test was used to compare the risk of death. Results: fifty-two cases with an indication of palliative BD were included in the study. Transpapillary drainage via ERCP was possible in 44 procedures and EUS-BD was required in eight cases; 15.4% of the cohort and seven using lumen apposing metal stent (LAMS). The technical and clinical success of global endoscopic BD was 100% and 88.5% (ERCP: 84.6% and 78.9%; EUS-BD: 100% and 62.5%, respectively). Pancreatitis was the most frequent adverse event (AE) in the ERCP group (9.62%) and bleeding in the EUS-BD (25%). There were fatal AEs in ERCP (1.9%) and EUS-BD (25%) cases. Patient survival was higher with ERCP transpapillary stents compared to EUS-guided stents, which was statistically significant (p = 0.007). Conclusions: the requirement of EUS-BD in palliative biliopancreatic pathology is not marginal. EUS-BD is associated with a lower survival rate and a higher rate of fatal AE, which argues against its use as a first choice procedure

Expression and Role of MicroRNAs from the miR-200 Family in the Tumor Formation and Metastatic Propensity of Pancreatic Cancer

MicroRNAs from the miR-200 family are commonly associated with the inhibition of the metastatic potential of cancer cells, following inhibition of ZEB transcription factors expression and epithelial-to-mesenchymal transition. However, previous studies performed in pancreatic adenocarcinoma revealed a more complex picture challenging this canonical model. To gain better insights into the role of miR-200 family members in this disease, we analyzed the expression of miR-200a, miR- 200b, miR-200c, miR-141, miR-429, and miR-205, and ZEB1, ZEB2, and CDH1 in pancreatic tumors and matching normal adjacent parenchyma and patient-derived xenografts. We found that miR-200a, miR-429, and miR-205 are frequently overex- pressed in pancreatic tumors, whereas CDH1 is downregulated, and ZEB1 and ZEB2 levels remain unchanged. Furthermore, we measured a positive correlation between miR-200 family mem- bers and CDH1 expression, and a negative correlation between ZEB1 and miR-200c, miR-141, and miR-205 expression, respec- tively. Interestingly, we identified significant changes in expres- sion of epithelial-to-mesenchymal transition regulators and miR-200 members in patient-derived xenografts. Lastly, func- tional studies revealed that miR-141 and miR-429 inhibit the tumorigenic potential of pancreatic cancer cells. Taken together, this comprehensive analysis strongly suggests that miRNAs from the miR-200 family, and in particular miR-429, may act as a tu- mor suppressor gene in pancreatic cancer

Prognostic value and risk stratification of residual disease in patients with incidental gallbladder cancer

Background and aim: given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods: a prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience