Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses.

Background: Pancreatic patient-derived organoids (PDOs) are a well-established model for studying pancreatic ductal adenocarcinoma (PDAC) carcinogenesis and are potential predictors of clinical responses to chemotherapy. Oncolytic virotherapy is envisioned as a novel treatment modality for pancreatic cancer, and candidate viruses are being tested in clinical trials. Here, we explore the feasibility of using PDOs as a screening platform for the oncolytic adenovirus (OA) response. Methods: Organoids were established from healthy pancreas and PDAC tissues and assessed for infectivity, oncoselectivity, and patient-dependent sensitivity to OA. Antitumour effects were studied in vivo in organoid xenografts. Further evaluation of oncolytic responses was conducted in organoids derived from orthotopic models or metastastic tissues.Findings: Oncolytic adenoviruses display good selectivity, with replication only in organoids derived from PDAC tumours. Furthermore, responses of PDOs to a set of OAs reveal individual differences in cytotoxicity as well as in synergism with standard chemotherapy. Adenoviral cytotoxicity in PDOs is predictive of antitumour efficacy in a subcutaneous xenograft setting. Organoids from orthotopic tumours and metastases in nude mice mirror the viral preference of PDOs, indicating that PDO sensitivity to OAs could be informative about responses in both primary tumours and metastatic foci. Interpretation: Our data imply that pancreatic PDOs can serve as predictive tools for screening for sensitivity to OA

Las complicaciones biliares en el trasplante hepático de donante vivo no afectan a los resultados a largo plazo

El transplantament hepàtic de donant viu comporta un alt índex de complicacions biliars. El nostre objectiu és avaluar-les, així com els resultats a llarg termini. Es van analitzar 70 casos retrospectivament. 39 de 70 pacients van presentar algun tipus de complicació biliar. Entre ells, 29 van presentar una fuga, 10 una estenosi i 14 ambdues. La probabilitat de presentar una estenosi fou major en els pacients amb fuga biliar prèvia (58% vs. 29,5% als 5 anys p=0,05). Un 70,8% es solucionaren mitjançant radiología intervencionista. No hi van haver diferències de supervivencia amb o sense complicacions de la via biliar.El trasplante hepático de donante vivo conlleva un alto índice de complicaciones biliares. Nuestro objetivo es evaluarlas, así como los resultados a largo plazo. Se analizaron 70 casos retrospectivamente. 39 de 70 pacientes presentaron algún tipo de complicación biliar. De ellos, 29 presentaron una fuga, 10 una estenosis y 14 ambas. La probabilidad de presentar estenosis fue mayor en los pacientes con fuga biliar previa (58% vs. 29,5% a 5 años p=0,05). Un 70,8% se solucionaron mediante radiología intervencionista. No hubo diferencias de supervivencia con o sin complicaciones de la vía biliar

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

Background: 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

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

Background: 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. (C) 2021 The Authors. Published by Elsevier Ltd

Machine Learning-Based Analysis in the Management of Iatrogenic Bile Duct Injury During Cholecystectomy: a Nationwide Multicenter Study

Background Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. Methods This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. Results We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. Discussion Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients

Primary non-functioning neuroendocrine tumor of the extrahepatic bile duct

In contrast to the primary biliary carcinoma or cholangiocarcinoma, other tumors derived from the bile duct are difficult to diagnose preoperatively, mainly because of its low incidence and difficult diagnostic process. However, since cholangiocarcinomas account for about 80% of all primary biliary tumors, it is important to think about other options despite their low frequency when a patient presents with abnormal characteristics. We present a case of a primary neuroendocrine tumor of the bile duct, and a review of the literature on this rare disease

Results obtained with the laparoscopic approach to the bile duct for the treatment of choledocholithiasis in 101 cases

Background: The optimal treatment for choledocholithiasis (CLT) is currently the subject of debate, as there is no clear evidence that a two-step (endoscopic plus surgical) approach is superior to a one-step surgical procedure. Materials and methods: We analyzed the results obtained from 101 consecutive patients diagnosed with CLT using magnetic resonance cholangiopancreatography (MRCP) or computed tomography (CT) scan undergoing cholecystectomy and laparoscopic exploration of the bile duct, carried out at our center between 2006 and 2019. In this analysis, special emphasis was made on the permanent resolution of the CLT and the associated complications. Results: The mean surgical time was 142 ± 36.7 minutes. In patients with a CLT diagnostic test more than 7 days previously, the presence of CLT was checked using intraoperative cholangiography (IOC), which was negative in 25% of patients, while in the rest, a primary exploration was performed using a choledochoscope via choledochotomy in 82.2% of patients and via the transcystic approach in two cases. A T-tube drain was inserted in 18.9% of patients. The conversion rate was 0.9%, due to a technical difficulty in removing the CLT in one patient. The laparoscopic approach treated the CLT permanently in 97/101 cases (96%), while four patients (3.9%) required postoperative endoscopic retrograde cholangiopancreatography (ERCP) due to residual cholelithiasis. A total of 15.8% of patients experienced a postoperative biliary fistula, which was resolved using conservative management in 86.7% of them, while two patients required surgical treatment and insertion of a percutaneous drain, respectively. The average postoperative stay duration was 6.5 ± 7.3 days. None of the patients showed signs of biliary stricture in the long-term postoperative follow-up. Conclusion: In our experience, the laparoscopic approach for one-step elective treatment of CLT is a safe option, with a very small number of complications and satisfactory short-and long-term results. Furthermore, despite preoperative identification of CLT, it helped to avoid unnecessary exploration of the bile duct in 25% of patients

Recommendations on intervention for hepatobiliary oncological surgery during the COVID-19 pandemic

La pandemia por SARS-CoV-2 (COVID-19) obliga a una reflexión en el ámbito de la cirugía oncológica, tanto sobre el riesgo de infección, de consecuencias clínicas muy relevantes, como sobre la necesidad de generar planes para minimizar el impacto sobre las posibles restricciones de los recursos sanitarios. La AEC hace una propuesta de manejo de pacientes con neoplasias hepatobiliopancreáticas (HBP) en los distintos escenarios de pandemia, con el objetivo de ofrecer el máximo beneficio a los pacientes y minimizar el riesgo de infección por COVID-19, optimizando a su vez los recursos disponibles en cada momento. Para ello es preciso la coordinación de los diferentes tratamientos entre los servicios implicados: oncología médica, oncología radioterápica, cirugía, anestesia, radiología, endoscopia y cuidados intensivos. El objetivo es ofrecer tratamientos eficaces, adaptándonos a los recursos disponibles, sin comprometer la seguridad de los pacientes y los profesionales.The SARS-CoV-2 (COVID-19) pandemic requires an analysis in the field of oncological surgery, both on the risk of infection, with very relevant clinical consequences, and on the need to generate plans to minimize the impact on possible restrictions on health resources. The AEC is making a proposal for the management of patients with hepatopancreatobiliary (HPB) malignancies in the different pandemic scenarios in order to offer the maximum benefit to patients, minimising the risks of COVID-19 infection, and optimising the healthcare resources available at any time. This requires the coordination of the different treatment options between the departments involved in the management of these patients: medical oncology, radiotherapy oncology, surgery, anaesthesia, radiology, endoscopy department and intensive care. The goal is offer effective treatments, adapted to the available resources, without compromising patients and healthcare professionals safety

Las complicaciones biliares en el trasplante hepático de donante vivo no afectan a los resultados a largo plazo

El transplantament hepàtic de donant viu comporta un alt índex de complicacions biliars. El nostre objectiu és avaluar-les, així com els resultats a llarg termini. Es van analitzar 70 casos retrospectivament. 39 de 70 pacients van presentar algun tipus de complicació biliar. Entre ells, 29 van presentar una fuga, 10 una estenosi i 14 ambdues. La probabilitat de presentar una estenosi fou major en els pacients amb fuga biliar prèvia (58% vs. 29,5% als 5 anys p=0,05). Un 70,8% es solucionaren mitjançant radiología intervencionista. No hi van haver diferències de supervivencia amb o sense complicacions de la via biliar.El trasplante hepático de donante vivo conlleva un alto índice de complicaciones biliares. Nuestro objetivo es evaluarlas, así como los resultados a largo plazo. Se analizaron 70 casos retrospectivamente. 39 de 70 pacientes presentaron algún tipo de complicación biliar. De ellos, 29 presentaron una fuga, 10 una estenosis y 14 ambas. La probabilidad de presentar estenosis fue mayor en los pacientes con fuga biliar previa (58% vs. 29,5% a 5 años p=0,05). Un 70,8% se solucionaron mediante radiología intervencionista. No hubo diferencias de supervivencia con o sin complicaciones de la vía biliar