Long-term outcomes after breast cancer liver metastasis surgery: A European, retrospective, snapshot study (LIBREAST STUDY).

INTRODUCTION: Breast cancer (BC) is the most common malignant tumor in women. Between 20 % and 30 % of patients develop metastases from BC, 50 % of them in the liver. The mean survival rate reported in patients with liver metastases from BC (LMBC) ranges from 3 to 29 months. The role of surgery in LMBC is not clearly defined. The objective of the present study was to determine the long-term survival and disease-free survival of patients undergoing surgery for LMBC and to identify the patients who most likely benefit from surgery. MATERIAL AND METHODS: This retrospective multicenter cohort study included all consecutive patients undergoing LMBC surgery at the participating European centers from January 1, 2010, to December 31, 2015. The ClinicalTrials.gov ID is NCT04817813. RESULTS: A hundred women (mean age 52.6 years) undergoing LMBC surgery were included. Five-year disease-free survival was 29 %, and 5-year overall survival was 60 %. Median survival after BC surgery was 12.4 years, and after LMBC surgery, 7 years. Patients with ECOG 1, ASA score I-II, metachronous LMBC, positive hormone receptors, and who had received neoadjuvant and adjuvant hormone treatment obtained the best overall and disease-free survival results. CONCLUSIONS: In cases of correct patient selection and as part of a comprehensive onco-surgical strategy, surgery for LMBC improves overall long-term survival. In our series, certain factors were linked to better disease-free and overall survival; consideration of these factors could improve the selection of the best candidates for LMBC surgery. GOV ID: NCT04817813.

Interference with mitochondrial function as part of the antifibrogenic effect of Rilpivirine: A step towards novel targets in hepatic stellate cell activation.

Activated hepatic stellate cells (aHSCs), the main perpetrators of liver fibrosis, are a promising therapeutic target in the treatment of chronic liver disease. During liver injury, HSCs transcend from a quiescent to a fibrotic phenotype, a process which involves major metabolic reprogramming with altered mitochondrial function. The antiretroviral drug Rilpivirine (RPV) has demonstrated a hepatoprotective and specifically antifibrotic effect in several animal models of chronic liver injury, as well as in vitro. Herein, we use HSCs activated with the profibrogenic cytokine TGF-ß to explore whether mitochondrial function is implicated in this effect. The mitochondrial bioenergetic profile, morphology and dynamics of TGF-ß-treated cells (48 h) were altered and these effects were prevented by co-treatment with clinically relevant concentrations of RPV. A MitoStress Test (Seahorse Analyzer) revealed that TGF-ß increased both oxygen consumption rate (basal respiration, maximal respiration and spare respiratory capacity) and extracellular acidification rate (indicative of increased glycolysis). Cells exposed to TGF-ß also displayed diminished mitochondrial membrane potential and enhanced mitochondrial fission. All of these effects were rescued with RPV. RNA sequencing analysis of cells exposed to TGF-ß revealed the presence of 338 differentially expressed genes that encode mitochondrial proteins (mito-DEGs), of which 139 and 199 were significantly up- and down-regulated (adjusted p<0.05). This alteration in 15 (10.79 %) and 31 (22.03 %) of the up-regulated and 16 (8.04 %) and 49 (24.62 %) of the down-regulated mitoDEGs was prevented with co-exposure to RPV 4µM or 8µM, respectively. In conclusion, alterations in mitochondrial function are implicated in the antifibrogenic action of RPV, pointing to potential novel antifibrotic targets.

ctDNA whole exome sequencing in pancreatic ductal adenocarcinoma unveils organ-dependent metastatic mechanisms and identifies actionable alterations in fast progressing patients.

Understanding progression mechanisms and developing new targeted therapies is imperative in pancreatic ductal adenocarcinoma (PDAC). In this study, 80 metastatic PDAC patients were prospectively recruited and divided into discovery (n=37) and validation (n=43) cohorts. Tumor and plasma samples taken at diagnosis were pair analyzed using whole exome sequencing (WES) in patients belonging to the discovery cohort alone. The variant allele frequency (VAF) of KRAS mutations was measured by ddPCR in plasma at baseline and response assessment in all patients. Plasma WES identified at least one pathogenic variant across the cohort, uncovering oncogenic mechanisms, DNA repair, microsatellite instability, and alterations in the TGFb pathway. Interestingly, actionable mutations were mostly found in plasma rather than tissue. Patients with shorter survival showed enrichment in cellular organization regulatory pathways. Through WES we could identify a specific molecular profile of patients with liver metastasis, which exhibited exclusive mutations in genes related to the adaptive immune response pathway, highlighting the importance of the immune system in liver metastasis development. Moreover, KRAS mutations in plasma (both at diagnosis and persistent at follow-up) correlated with shorter progression free survival (PFS). Patients presenting a reduction of over 84.75 % in KRAS VAF at response assessment had similar PFS to KRAS-negative patients. Overall, plasma WES reveals molecular profiles indicative of rapid progression, potentially actionable targets, and associations between adaptive immune response pathway alterations and liver tropism.

Short- and long-term outcomes after distal pancreatectomy with radiologic infiltration of splenic vessels for pancreatic ductal adenocarcinoma.

BACKGROUND: The effect of radiologic splenic vessels involvement (RSVI) on the survival of patients with pancreatic adenocarcinoma (PAC) located in the body and tail of the pancreas is controversial, and its influence on postoperative morbidity after distal pancreatectomy (DP) is unknown. This study aimed to determine the influence of RSVI on postoperative complications, overall survival (OS), and disease-free survival (DFS) in patients undergoing DP for PAC. METHODS: A multicenter retrospective study of DP was conducted at 7 hepatopancreatobiliary units between January 2008 and December 2018. Patients were classified according to the presence of RSVI. A Clavien-Dindo grade of >II was considered to represent a major complication. RESULTS: A total of 95 patients were included in the analysis. Moreover, 47 patients had vascular infiltration: 4 had arterial involvement, 10 had venous involvement, and 33 had both arterial and venous involvements. The rates of major complications were 20.8% in patients without RSVI, 40.0% in those with venous RSVI, 25.0% in those with arterial RSVI, and 30.3% in those with both arterial and venous RSVIs (P = .024). The DFS rates at 3 years were 56% in the group without RSVI, 50% in the group with arterial RSVI, and 16% in the group with both arterial and venous RSVIs (P = .003). The OS rates at 3 years were 66% in the group without RSVI, 50% in the group with arterial RSVI, and 29% in the group with both arterial and venous RSVIs (P < .0001). CONCLUSION: RSVI increased the major complication rates after DP and reduced the OS and DFS. Therefore, it may be a useful prognostic marker in patients with PAC scheduled to undergo DP and may help to select patients likely to benefit from neoadjuvant 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.

Textbook outcome in distal pancreatectomy: A multicenter study.

BACKGROUND: Textbook outcome is an interesting quality metrics tool. Information on textbook outcomes in distal pancreatectomy is very scarce. In this study we determined textbook outcome in a distal pancreatectomy multicenter database and propose a specific definition of textbook outcome-distal pancreatectomy that includes pancreatic fistula. METHODS: Retrospective multicenter observational study of distal pancreatectomy performed at 8 hepatopancreatobiliary surgery units from January 1, 2008, to December 31, 2018. The inclusion criteria were any scheduled distal pancreatectomy performed for any diagnosis and age > 18 years. Specific textbook outcome-distal pancreatectomy was defined as hospital stay P < 75, no Clavien-Dindo complications (≥ III), no hospital mortality, and no readmission recorded at 90 days, and the absence of pancreatic fistula (B/C). RESULTS: Of the 450 patients included, 262 (58.2%) obtained textbook outcomes. Prolonged stay was the parameter most frequently associated with failure to achieve textbook outcomes. The textbook outcome group presented the following results. Preoperative: lower American Society of Anesthesiologists score < III, a lower percentage of smokers, and less frequent tumor invasion of neighboring organs or vascular invasion; operative: major laparoscopic approach, and less resection of neighboring organs and less operative transfusion; postoperative: lower percentage of delayed gastric emptying and pancreatic fistula B/C, and diagnosis other an adenocarcinoma. In the multivariate study, the American Society of Anesthesiologists score > II, resection of neighboring organs, B/C pancreatic fistula, and delayed gastric emptying were associated with failure to achieve textbook outcomes. CONCLUSION: The textbook outcome rate in our 450 pancreaticoduodenectomies was 58.2%. In the multivariate analysis, the causes of failure to achieve textbook outcomes were American Society of Anesthesiologists score > II, resection of neighboring organs, pancreatic fistula B/C, and delayed gastric emptying. We believe that pancreatic fistula should be added to the specific definition of textbook outcome-distal pancreatectomy because it is the most frequent complication of this procedure.

Pancreatic mucinous cystic neoplasms located in the distal pancreas: a multicenter study.

Background: Mucinous cysts of the pancreas (MCN) are infrequent, usually unilocular tumors which occur in postmenopausal women and are located in the pancreatic body/tail. The risk of malignancy is low. The objective is to define preoperative risk factors of malignancy in pancreatic MCN and to assess the feasibility of the laparoscopic approach. Methods: Retrospective multicenter observational study of prospectively recorded data regarding distal pancreatectomies was carried out at seven hepatopancreatobiliary (HPB) Units between 01/01/08 and 31/12/18 (the ERPANDIS Project). Results: Four hundred and forty-four distal pancreatectomies were recorded including 47 MCN (10.6%). Thirty-five were non-invasive tumors (74.5%). In all, 93% of patients were female, and 60% were ASA (American Society of Anaesthesiology) II. The mean preoperative size was 46 mm. Patients with invasive tumors were older (54 vs. 63 years). Invasive tumors were larger (6 vs. 4 cm), although the difference was not significant (P=0.287). Sixty percent was operated via laparoscopic approach, which was used in 74.6% of non-invasive tumors and in 16.7% of the invasive ones. The spleen was not preserved in 93.6% of the patients. R0 resection was obtained in all patients. Two patients with invasive tumors died. Conclusions: In our surgical series of MCN, patients with malignancy were older and presented larger tumors, although the difference was not statistically significant. Laparoscopy is a safe and feasible approach for MCN. Prospective studies are now needed to define risk factors that can guide the decision whether to administer conservative treatment or to operate.

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.

¿Qué aporta la imagen tridimensional preoperatoria en la cirugía pancreática compleja? / What does preoperative three-dimensional image contribute to complex pancreatic surgery?

La posibilidad de modelización de imágenes diagnósticas en tres dimensiones (3D) en cirugía pancreática es una novedad que nos aporta múltiples ventajas. Una mejor visualización de las estructuras nos permite una planificación de la técnica quirúrgica más precisa y nos facilita la realización de la cirugía en casos complejos. Presentamos el caso de un paciente diagnosticado de un adenocarcinoma de cabeza de páncreas borderline para ilustrar las ventajas de la modelización 3D en cirugía pancreática compleja. La ayuda de la tecnología 3D nos permitió planificar de manera óptima la intervención facilitando la resección quirúrgica. El uso de esta herramienta podría traducirse en: menor tiempo operatorio, menores complicaciones intraoperatorias o un aumento de las resecciones R0. La usabilidad del programa utilizado en nuestro caso, ágil e intuitivo, fue una ventaja añadida. (AU)

The possibility of modelling diagnostic images in three dimensions (3D) in pancreatic surgery is a novelty that provides us multiple advantages. A better visualization of the structures allows us a more accurate planning of the surgical technique and makes it easier the surgery in complex cases. We present the case study of a borderline pancreatic head adenocarcinoma patient to illustrate the advantages of 3D modelling in complex pancreatic surgery. The help of 3D technology allowed us to optimally plan the intervention and facilitate surgical resection. The use of this tool could translate into: shorter operative time, fewer intraoperative complications or an increase in R0 resections. The usability of the program used in our case, agile and intuitive, was an added advantage. (AU)

What does preoperative three-dimensional image contribute to complex pancreatic surgery?

The possibility of modelling diagnostic images in three dimensions (3D) in pancreatic surgery is a novelty that provides us multiple advantages. A better visualization of the structures allows us a more accurate planning of the surgical technique and makes it easier the surgery in complex cases. We present the case study of a borderline pancreatic head adenocarcinoma patient to illustrate the advantages of 3D modelling in complex pancreatic surgery. The help of 3D technology allowed us to optimally plan the intervention and facilitate surgical resection. The use of this tool could translate into: shorter operative time, fewer intraoperative complications or an increase in R0 resections. The usability of the program used in our case, agile and intuitive, was an added advantage.

Tratamiento quirúrgico de neoplasia mucinosa papilar intraductal de la vía biliar diagnosticada mediante SpyGlass(R) / No disponible

Presentamos el caso de un varón de 76 años con antecedente de colecistitis aguda intervenido mediante colecistectomía laparoscópica. Intraoperatoriamente, se evidenció una colecistitis crónica con conducto cístico engrosado. La anatomía patológica informó de displasia de alto grado que afectaba al borde distal del cístico. Ante los hallazgos, se practicó colangiopancreatografía retrógrada endoscópica (CPRE) con SpyGlass(R) con la cual se observó, adyacente a la unión del cístico-colédoco, lesión excrecente sugestiva de malignidad. Se decidió nueva intervención quirúrgica y se realizó una resección de vía biliar extrahepática con linfadenectomía del hilio hepático y hepaticoyeyunostomía. El informe anatomopatológico definitivo informó de neoplasia mucinosa papilar intraductal pancreatobiliar con displasia de alto grado con márgenes libres

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What does preoperative three-dimensional image contribute to complex pancreatic surgery? / ¿Qué aporta la imagen tridimensional preoperatoria en la cirugía pancreática compleja?

The possibility of modelling diagnostic images in three dimensions (3D) in pancreatic surgery is a novelty that provides us multiple advantages. A better visualization of the structures allows us a more accurate planning of the surgical technique and makes it easier the surgery in complex cases. We present the case study of a borderline pancreatic head adenocarcinoma patient to illustrate the advantages of 3D modelling in complex pancreatic surgery. The help of 3D technology allowed us to optimally plan the intervention and facilitate surgical resection. The use of this tool could translate into: shorter operative time, fewer intraoperative complications or an increase in R0 resections. The usability of the program used in our case, agile and intuitive, was an added advantage.

Surgical treatment of an intraductal papillary mucinous neoplasm of the biliary tract diagnosed by SpyGlass®.

We present the case of a 76-year-old male with a history of acute cholecystitis who underwent a scheduled laparoscopic cholecystectomy. Chronic cholecystitis with a thickened cystic duct was observed intraoperatively. The anatomic pathology report found high-grade dysplasia that affected the distal edge of the cystic duct. In view of these findings, an endoscopic retrograde cholangiopancreatography (ERCP) was performed with SpyGlass® and an excrescent lesion suggestive of malignancy adjacent to the cystic-common bile duct junction was observed. A resection of the extrahepatic bile duct was performed with lymphadenectomy of the hepatic hilum and hepaticojejunostomy in a subsequent procedure. The definitive pathology report confirmed pancreaticobiliary intraductal papillary mucinous neoplasia with high-grade dysplasia and free margins.

The actual management of colorectal liver metastases.

Colorectal cancer is one of the most frequent cancers in the world and between 50% and 60% of patients will develop colorectal liver metastases (CRLM) during the disease. There have been great improvements in the management of CRLM during the last decades. The combination of modern chemotherapeutic and biological systemic treatments with aggressive surgical resection strategies is currently the base for the treatment of patients considered unresectable until few years ago. Furthermore, several new treatments for the local control of CRLM have been developed and are now part of the arsenal of multidisciplinary teams for the treatment of these complex patients. The aim of this review was to summarize and update the management of CRLM, its controversies and relevant evidence.

Distal pancreatectomy with multivisceral resection: A retrospective multicenter study - Case series.

BACKGROUND: Multivisceral resection (MVR) is sometimes necessary to achieve disease-free margins in cancer surgery. In certain patients with pancreatic tumors that invade neighboring organs these must be removed to perform an appropriate oncological surgery. In addition, there is an increasing need to perform resections of other organs like liver not directly invaded by the tumor but which require synchronous removal. The results of MVR in pancreatic surgery are controversial. MATERIAL AND METHODS: A distal pancreatectomy retrospective multicenter observational study using prospectively compiled data carried out at seven HPB Units. The period study was January 2008 to December 2018. We excluded DP with celiac trunk resection. RESULTS: 435 DP were performed. In 62 (14.25%) an extra organ was resected (82 organs). Comparison of the preoperative data of MVR and non-MVR patients showed that patients with MVR had lower BMI, higher ASA and larger tumor size. In the MVR group, the approach was mostly laparotomic and spleen preservation was performed only in 8% of the cases, Blood loss and the percentage of intraoperative transfusion were higher in MVR group. Major morbidity rates (Clavien > IIIa) and mortality (0.8vs.4.8%) were higher in the MVR group. Pancreatic fistula rates were practically the same in both groups. Mean hospital stay was twice as long in the MVR group and the readmission rate was higher in the MVR group. Histology study confirmed a much higher rate of malignant tumors in MVR group. CONCLUSIONS: In order to obtain free margins or treat pathologies in several organs we think that DP + MVR is a feasible technique in selected patients; the results obtained are not as good as those of DP without MVR but are acceptable nonetheless. CLINICALTRIALS. GOV IDENTIFIER: NCT04317352.

Late parastomal evisceration.

BACKGROUND: Parastomal evisceration is a very uncommon complication of stomas with only few cases reported in the literature. This complication can be developed in the early postoperative period due to technical aspects of stoma creation, but late parastomal evisceration appearing after 6 months from surgery is an exceptional condition. Herein, we present a rare case of a patient with late parastomal evisceration. CASE PRESENTATION: A 44-year-old man with sigmoid volvulus underwent a temporary end-terminal colostomy. The ostomy was complicated by a parastomal hernia and stoma prolapse 5 months postoperatively. He was brought into our emergency department having been found collapsed in the street. On physical examination, the patient presented signs of shock and evisceration of small bowel through the colostomy. Intraoperatively, a perforation of prolapsed colon was assessed as the point for intestinal evisceration. We discuss this case and all similar cases reported in the literature. CONCLUSION: Parastomal evisceration is a potentially life-threatening complication. Patients with parastomal hernia and stoma prolapse must be considered for surgical treatment to avoid this complication.

Tratamiento quirúrgico de un aneurisma micótico roto de la arteria hepática / Surgical treatment of ruptured mycotic hepatic artery aneurysm

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