Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Textbook outcome in patients with biliary duct injury during cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.

Histopathological, Clinical, And Molecular (HICAM) score for patients with colorectal liver metastases.

BACKGROUND: Histopathological and molecular features have been proposed to hold prognostic information, but few have been validated. The aim of this retrospective study was to validate the Genetic And Morphological Evaluation ('GAME') score and assess the impact of histological characteristics on the prognosis in patients with colorectal liver metastases. METHODS: Data were collected from 176 patients with metastatic colorectal cancer undergoing liver resection at Hospital de la Santa Creu i Sant Pau. Patients were classified into Genetic And Morphological Evaluation score groups and relapse-free survival and overall survival were calculated. Histopathological changes in colorectal liver metastases were documented and prognostic variables were selected to create a post-surgery score, called the Histopathological, Clinical, And Molecular ('HICAM') score. RESULTS: Regarding the Genetic And Morphological Evaluation score, the high-risk group had a median relapse-free survival of 8.8 months, compared with 20.5 months for the low-risk group (P = 0.005), and the high-risk group had a median overall survival of 37.8 months, compared with 67.0 months for the low-risk group (P = 0.005). Histological examination of 144 liver samples showed that the desertic immune phenotype was associated with worse overall survival in the multivariable analysis (P = 0.020). The Histopathological, Clinical, And Molecular score variables were age at diagnosis, tumour burden score, carcinoembryonic antigen levels greater than or equal to 20 ng/ml, primary tumour resection, TNM stage at diagnosis, molecular status, histopathological growth patterns, and immune phenotypes of the liver. The high-risk group had a median relapse-free survival of 8.4 months, compared with 20.4 months for the low-risk group (P < 0.001), and a median overall survival of 30.4 months, compared with 105.0 months for the low-risk group (P < 0.001). CONCLUSION: The Genetic And Morphological Evaluation score was validated as a preoperative prognostic tool to predict candidacy for liver resection. The Histopathological, Clinical, And Molecular score could be useful to assess adjuvant treatment after hepatic resection.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID).

BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival. METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.

Resultados obtenidos tras el tratamiento quirúrgico de los pacientes con metástasis hepáticas de sarcomas / Surgical and oncological results after surgical treatment of patients diagnosed with sarcoma liver metastases

Introducción: La presencia de metástasis hepáticas en pacientes con sarcomas se asocia a peor pronóstico, aunque en casos seleccionados la resección de dichas metástasis se ha propuesto para aumentar la supervivencia. El objetivo de este estudio es describir la evolución postoperatoria y los resultados oncológicos tras la resección hepática. Métodos: Se presenta un estudio retrospectivo unicéntrico. Se incluyen pacientes diagnosticados de metástasis hepáticas de sarcoma intervenidos quirúrgicamente entre 2003-2019. Los criterios de inclusión fueron la presencia de enfermedad resecable, la presencia de enfermedad extrahepática controlada no se consideró criterio de irresecabilidad. Resultados: Diecinueve pacientes se sometieron a resección hepática de 7 tipos distintos de estirpes sarcomatosas. La mediana de edad fue de 58 años. Las metástasis se diagnosticaron 25 meses de mediana tras el primario, 6 (32%) presentaron lesiones sincrónicas y 12 (63%) estaban afectos de enfermedad extrahepática. Se realizó hepatectomía mayor en 5 (26%) pacientes; se describieron 8 (42%) complicaciones menores. La mediana de seguimiento fue de 33 meses. El análisis de supervivencia se realizó estratificando en 2 grupos, la supervivencia fue del 100%, 85,7% y del 42,9% al año, a los 3 años y a los 5 años, en los no-GIST, y del 100% y del 40% a los 5 y 10 años en los GIST. Conclusiones: El abordaje quirúrgico de las metástasis hepáticas de sarcoma parece aumentar la supervivencia en pacientes seleccionados, asociando pocas complicaciones. En nuestra serie, la tasa de enfermedad extrahepática es elevada en comparación con series previas, no obstante la supervivencia es equiparable. Dichos resultados apoyan la resección hepática en pacientes con enfermedad extrahepática estable. (AU)

Introduction: The presence of liver metastases in sarcomatous tumors is associated with poor prognosis. However, in selected patients, surgical resection has been suggested as a tool to improve survival rates. The aim of our study is to describe postoperative and oncological outcomes after liver resection. Methods: A retrospective unicentric study was conducted including patients diagnosed with hepatic metastases from soft tissue sarcoma who underwent hepatic resection between 2003 and 2019. The inclusion criteria were the presence of resectable disease, including synchronic and metachronic lesions. The presence of extra-hepatic controlled disease was not considered unresectable. Results: Nineteen patients underwent liver resection for liver metastasis of 7 different sarcomatous subtypes. Median age was 58-yo. Liver metastases were diagnosed a median 25 months after primary tumor diagnosis. Six patients (32%) suffered of synchronic metastases and 12 (63%) were affected of extrahepatic disease. Major hepatectomy was done in 5 (26%) patients, 8 (42%) minor complications were described. Median follow-up was 33 months. Survival analysis was performed independently for, GIST tumors and non-GIST sarcomas. One, three and five-year survival rate was 100%, 85.7% and 42.9% in non-GIST sarcomas, while five and ten-year survival rate was 100% and 40% in GIST, respectively. Conclusions: Surgical approach of liver metastases of sarcomatous tumors seems to be useful in order to improve survival in selected patients, while associated to be of low complications rate. In our cohort, extrahepatic disease rate is high in comparison with series published before, nevertheless survival is comparable. These results support performing surgical resection in selected patients with stable extrahepatic disease. (AU)

Surgical and oncological results after surgical treatment of patients diagnosed with sarcoma liver metastases.

INTRODUCTION: The presence of liver metastases in sarcomatous tumors is associated with poor prognosis. However, in selected patients, surgical resection has been suggested as a tool to improve survival rates. The aim of our study is to describe postoperative and oncological outcomes after liver resection. METHODS: A retrospective unicentric study was conducted including patients diagnosed with hepatic metastases from soft tissue sarcoma who underwent hepatic resection between 2003-2019. The inclusion criteria were the presence of resectable disease, including synchronic and metachronic lesions. The presence of extra-hepatic controlled disease was not considered unresectable. RESULTS: Nineteen patients underwent liver resection for liver metastasis of 7 different sarcomatous subtypes. Median age was 58-years. Liver metastases were diagnosed a median 25 months after primary tumor diagnosis. Six patients (32%) suffered of synchronic metastases and 12 (63%) were affected of extrahepatic disease. Major hepatectomy was done in 5 (26 %) patients, 8 (42%) minor complications were described. Median follow-up was 33 months. Survival analysis was performed independently for, GIST tumors and non-GIST sarcomas. One, three and five-year survival rate was 100%, 85.7% and 42.9% in non-GIST sarcomas, while Five and ten-year survival rate was 100% and 40% in GIST, respectively. CONCLUSION: Surgical approach of liver metastases of sarcomatous tumors seems to be useful in order to improve survival in selected patients, while been associated to low complications rate. In our cohort, extrahepatic disease rate is high in comparison with series published before, nevertheless survival is comparable. These results support performing surgical resection in selected patients with stable extrahepatic disease.

Vascular injury during cholecystectomy: A multicenter critical analysis behind the drama.

BACKGROUND: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery. METHODS: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes. RESULTS: A total of 104 patients were included. Twenty-nine patients underwent vascular repair (27.9%), 13 (12.5%) liver resection, and 1 liver transplant as a first treatment. Eighty-four (80.4%) vascular and biliary injuries occurred in nonspecialized centers and 45 (53.6%) were immediately transferred. Intraoperative diagnosed injuries were rare in referred patients (18% vs 84%, P = .001). The patients managed at the hospital where the injury occurred had a higher number of reoperations (64% vs 20%, P ˂ .001). The need for vascular reconstruction was associated with higher mortality (P = .04). Two of the 4 patients transplanted died. CONCLUSION: Vascular lesions during cholecystectomy are a potentially life-threatening complication. Management of referral to specialized centers to perform multiple complex multidisciplinary procedures should be mandatory. Late vascular repair has not shown to be associated with worse results.

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.

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.

Biliary Tree Cysts and Surgical Treatment: Outcomes in a Multicentric Study.

Background: Biliary tree cysts (BTCs) represent an either localized or multifocal abnormal dilatation of the biliary tree, which entails an increased risk of acute cholangitis and cholangiocarcinoma (2.5%-16%). Its incidence in Western countries is ∼1/100.000-1/150.000, being more frequent in Asia (1/1.000). These cysts are usually classified according to Todani classification, which is based on site and morphology of cysts. Patients and Methods: This is a retrospective multicentric descriptive study of patients surgically treated for BTCs. From 2005 to 2018, 25 cases were collected between Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and Ospedale San Paolo (Savona, Italy). Clinical presentation was characterized by abdominal pain, jaundice, fever, and sometimes weight loss. Eight patients presented Todani type I, 1 patient Todani type II, 3 patients Todani III, 1 patient Todani type IV, and 12 patients Todani type V. Results: Among the 25 surgically treated patients, 12 patients underwent liver resection, 7 patients underwent resection of the extrahepatic biliary tree, 3 patients underwent BTC removal through a duodenotomy, 1 patient underwent resection of the extrahepatic biliary tree and liver resection, and 2 patients underwent pancreatoduodenectomy. Overall 30-day morbidity rate was 20%, and 90-day mortality was 0%. Pathologic examination confirmed diagnosis of cholangiocarcinoma in 5 patients (20%). After a median follow-up of 59 months, 20 patients are alive and in good conditions, whereas 50% of patients with cholangiocarcinoma died for disease progression. Conclusions: Surgical treatment for BTCs is associated with acceptable postoperative outcomes, with moderate morbidity and null mortality rates. Moreover, the risk of developing cholangiocarcinoma is still high that prompts surgical treatment once diagnosis is made.

Recomendaciones de actuación en cirugía oncológica hepatobiliopancreática durante la pandemia COVID-19 / 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. (AU)

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. (AU)

Clinical impact of preoperative tumour contact with superior mesenteric-portal vein in patients with resectable pancreatic head cancer.

INTRODUCTION: The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour ≤ 180° contact with portal vein/superior mesenteric vein (PV/SMV) as a negative prognostic feature. The aim of this study is to evaluate whether this factor is associated with higher rate of incomplete resection and poorer survival. METHODS: All patients considered for pancreatic resection between 2012 and 2017 at two Spanish referral centres were included. Patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC) according to NCCN classification were excluded. Preoperative CT scans were reviewed by dedicated radiologists to identify radiologic tumour contact with PV/SMV. RESULTS: Out of 302, 71 patients were finally included in this study. Twenty-two (31%) patients showed tumour-PV/SMV contact (group 1) and 49 (69%) did not show any contact (group 2). Patients in group 1 showed a statistically significantly higher rate of R1 and R1-direct margins compared with group 2 (95 vs 28% and 77 vs 10%) and lower median survival (24 vs 41 months, p = 0.02). Preoperative contact with PV/SMV, lymph node metastases, R1-direct margin and NO adjuvant chemotherapy were significantly associated with disease-specific survival at multivariate analysis. CONCLUSION: Preoperative radiological tumour contact with PV/SMV in patients with NCCN resectable PDAC is associated with high rate of pathologic positive margins following surgery and poorer survival.

Recommendations on intervention for hepatobiliary oncological surgery during the COVID-19 pandemic. / Recomendaciones de actuación en cirugía oncológica hepatobiliopancreática durante la pandemia COVID-19.

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.

Laparoscopic liver resection of the Spiegel lobe by a left-sided approach preserving an accessory left hepatic artery.

BACKGROUND: Caudate lobe of the liver can be divided in three portions: Spiegel lobe, paracaval portion and caudate process [1]. The anatomy of the caudate lobe and its proximity to major vascular structures makes this operation a difficult resection, especially for laparoscopic liver surgery [2]. For that reason the Iwate criteria proposed to classify this surgery at the "2nd International Consensus Conference on Laparoscopic Liver Resection" as intermediate or advanced difficulty depending on the type of resection, and the size of the tumor [3]. For tumors located in the Spiegel lobe, the left side approach is preferred [4]. METHODS: We present a 69-year-old woman with liver metastasis from previously resected sternal condrosarcoma on 30/05/2017. A unique recurrence in the caudate lobe was found on computed tomography and magnetic resonance imaging on April 2019. RESULTS: A Spiegel lobe resection with left side approach preserving an accessory left hepatic artery was performed. A resection of the artery was planned if the preservation was not possible. The operative time was 180 min and the total Pringle time was 30 min. Patient was discharged at the 4 postoperative day and there were no postoperative complications CONCLUSIONS: Laparoscopic liver resection of the caudate lobe for condrosarcoma liver metastasis is feasible and safe. Left approach seems the best option for Spiegel lobe resections even in patients with accessory left hepatic artery.

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.

Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by gemcitabine-erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD 10-03 trial).

BACKGROUND: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients. METHODS: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440. RESULTS: Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009). CONCLUSION: The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.