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.

Simultaneous pancreas-kidney transplantation: which graft warns the most?

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is still characterized by high rates of postoperative complications. This study aims to offer an in-depth characterization of early, medium-term, and late complications following SPK to derive insights for postoperative management and follow-up. METHODS: Consecutive SPK transplantations were analysed. Pancreatic graft (P-graft)- and kidney graft (K-graft)-related complications were analysed separately. The global postoperative course was assessed in three timeframes (early, medium-term, and late) using the comprehensive complication index (CCI). Predictors of complications and early graft loss were explored. RESULTS: Complications occurred in 61.2% of patients, and the 90-day mortality was 3.9%. The overall burden of complications was significantly high during admission (CCI 22.4 ± 21.1) and decreased gradually afterwards. P-graft-related complications burdened the most in the early postoperative course (CCI 11.6 ± 13.8); postoperative ileus and perigraft fluid collection were the most frequent complications, and pseudoaneurysms, haemorrhages, and bowel leaks were the major concerns. K-related complications were milder but represented the largest proportion of the CCI in the late postoperative timeframe (CCI 7.6 ± 13.6). No predictors of P-graft- or K-graft-related complications were found. CONCLUSION: Pancreas graft-related complications represent the largest part of the clinical burden in the early postoperative timeframe but are negligible after 3 months. Kidney grafts have a relevant impact in the long term. The multidisciplinary approach to SPK recipients should be driven based on all graft-specific complications and tailored on a time-dependent basis.

Two stage hepatectomy (TSH) versus ALPPS for initially unresectable colorectal liver metastases: A systematic review and meta-analysis.

BACKGROUND: Although numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM). METHODS: Main electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded. RESULTS: A total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04-2.06, I2 = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64-3.62, I2 = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09-1.61, I2 = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13-2.30, I2 = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68-1.27, I2 = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47-2.49, I2 = 54%), respectively. CONCLUSION: ALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results.

Pancreatic cancer, radiomics and artificial intelligence.

Patients with pancreatic ductal adenocarcinoma (PDAC) are generally classified into four categories based on contrast-enhanced CT at diagnosis: resectable, borderline resectable, unresectable, and metastatic disease. In the initial grading and staging of PDAC, structured radiological templates are useful but limited, as there is a need to define the aggressiveness and microscopic disease stage of these tumours to ensure adequate treatment allocation. Quantitative imaging analysis allows radiomics and dynamic imaging features to provide information of clinical outcomes, and to construct clinical models based on radiomics signatures or imaging phenotypes. These quantitative features may be used as prognostic and predictive biomarkers in clinical decision-making, enabling personalised management of advanced PDAC. Deep learning and convolutional neural networks also provide high level bioinformatics tools that can help define features associated with a given aspect of PDAC biology and aggressiveness, paving the way to define outcomes based on these features. Thus, the prediction of tumour phenotype, treatment response and patient prognosis may be feasible by using such comprehensive and integrated radiomics models. Despite these promising results, quantitative imaging is not ready for clinical implementation in PDAC. Limitations include the instability of metrics and lack of external validation. Large properly annotated datasets, including relevant semantic features (demographics, blood markers, genomics), image harmonisation, robust radiomics analysis, clinically significant tasks as outputs, comparisons with gold-standards (such as TNM or pretreatment classifications) and fully independent validation cohorts, will be required for the development of trustworthy radiomics and artificial intelligence solutions to predict PDAC aggressiveness in a clinical setting.

The Impact of Sleeve Gastrectomy on Gastroesophageal Reflux Disease in Patients with Morbid Obesity.

INTRODUCTION: The impact of laparoscopic sleeve gastrectomy (LSG) on gastroesophageal reflux disease (GERD) has not been widely quantified, and the data in the literature remain controversial. MATERIALS AND METHODS: Candidates for LSG underwent barium swallow, esophageal manometry, ambulatory 24-h esophageal pH monitoring (APM), and gastric emptying scintigraphy before and after surgery (1 and 18 months). Symptoms were evaluated using a gastroesophageal reflux disease questionnaire (GERDq). Esophagogastroduodenoscopy was performed preoperatively in all patients and at 18 months postoperatively in patients who had suffered from preoperative esophagitis. RESULTS: Fifty-two patients were included in the study (64.4% women and 34.6% men) with a median age of 46 years (25-63 years) and BMI of 45.0 ± 5.6 kg/m2. The follow-up rates at 1 and 18 months were 82.7% and 80.8%. At 18 months, the percentage of weight loss (%TWL) was 33.6 ± 10.4% and the percentage of excess BMI loss (%EBMIL) was 77.6 ± 25%. Postoperatively, a significant increase in accelerated gastric emptying and impaired esophageal body motility occurred at 1 and 18 months. A significant worsening of all the values obtained at both 1 and 18 months postoperatively becomes evident when comparing the results of the APM. After surgery, 76.4% of patients had developed "de novo" GERD at 1 month and 41% at 18 months. No improvement was found in patients with symptomatic GERD. CONCLUSION: Based on the results of this study, LSG led to a considerable rate of postoperative "de novo" GERD. In addition, no improvement was found in patients with symptomatic GERD.

From conventional two-stage hepatectomy to ALPPS: Fifteen years of experience in a hepatobiliary surgery unit.

BACKGROUND: Hepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal. Conventional two-stage hepatectomy (TSH) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique are possible solutions to this problem. Colorectal liver metastases (CRLM) is the most frequent indication, and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients. METHODS: A single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020. ALPPS was performed from January 2012 onwards as the technique of choice. Long-term overall survival (OS) and disease-free survival (DFS) were evaluated as primary outcome in CRLM patients. Postoperative morbidity, mortality and liver growth in all patients were also evaluated. RESULTS: A total of 38 staged hepatectomies were performed: 17 TSH and 21 ALPPS. Complete resection rate was 76.5% (n = 13) in the TSH group and 85.7% (n = 18) in the ALPPS group (P = 0.426). Overall major morbidity (Clavien-Dindo ≥ 3a) (stage 1 + stage 2) was 41.2% (n = 7) in TSH and 33.3% (n = 7) in ALPPS patients (P = 0.389), and perioperative 90-day mortalities were 11.8% (n = 2) vs. 19.0% (n = 4) in each group, respectively (P = 0.654). Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH (n = 15) were 80% and 33%, and for ALPPS (n = 17) 76% and 35%, respectively. DFS rates at 1 and 5 years were 36% and 27% in the TSH group vs. 33% and 27% in the ALPPS group, respectively. CONCLUSIONS: ALPPS is an effective alternative to TSH in bilateral affecting liver tumors, allowing higher resection rate, but patients must be carefully selected. In CRLM patients similar long-term OS and DFS can be achieved with both techniques.

Extended distal pancreatectomy with thoracic wall resection after neoadjuvant FOLFIRINOX: Is there a limit of resection for pancreatic cancer after downstaging?

Indications and outcomes of extended pancreatectomies have been recently appraised by the International Study Group for Pancreatic Surgery. However, no definitive conclusions have been drawn, particularly in the setting of neoadjuvant treatments. We present here a case of 53-year-old man diagnosed with a bulky adenocarcinoma of the tail of the pancreas and infiltrating the adjacent organs and the thoracic wall. The patient was sent to neoadjuvant chemotherapy and he underwent 12 cycles of FOLFIRINOX. Since a significant radiological response was observed after chemotherapy, the patient was scheduled for extended distal pancreatectomy with en bloc resection of the thoracic wall, in order to achieve a radical resection. The surgery is herein described with all technical details. The patient was discharged after an uneventful early post-operative course and subsequently readmitted for a late grade B post-operative pancreatic fistula, which was ultimately treated successfully. Pathology showed complete response. When performed in centers with ample experience in pancreatic surgery, extended pancreatic resections represent a viable curative option with acceptable surgical outcomes. In this setting, challenging tailored resections should be considered to achieve negative margins, particularly following maximized effective downstaging strategies.

Evaluation of patient safety and satisfaction in a program of ambulatory laparoscopic cholecystectomy program with expanded criteria. / Evaluación de la seguridad y satisfacción de los pacientes en un programa de colecistectomía laparoscópica ambulatoria con criterios expandidos.

INTRODUCTION: The good results obtained with the implementation of ambulatory laparoscopic cholecystectomy programs have led to the expansion of the initial inclusion criteria. The main objective was to evaluate the results and the degree of satisfaction of the patients included in a program of laparoscopic cholecystectomy without admission, with expanded criteria. METHODS: Observational study of a cohort of 260 patients undergoing ambulatory laparoscopic cholecystectomy between April 2013 and March 2016 in a third level hospital. We classified the patients into 2groups based on compliance with the initial inclusion criteria of the outpatient program. Group I (restrictive criteria) includes 164 patients, while in group ii (expanded criteria) we counted 96 patients. We compared the surgical time, the rate of failures in ambulatory surgery, rate of conversion, reinterventions and mortality and the satisfaction index. RESULTS: The overall success rate of ambulatory laparoscopic cholecystectomy was 92.8%. The most frequent cause of unexpected income was for medical reasons. There was no statistically significant difference between the 2groups for total surgery time, the rate of conversion to open surgery and the number of major postoperative complications Do not demostrate differences in surgical time, nor in the number of perioperative complications (major complications 1,2%), or the number of failures in ambulatory surgery, nor the number of readmissions between both groups. There was no death. 88.5% of patients completed the survey, finding no differences between both groups in the patient satisfaction index. The overall score of the process was significantly better in group ii(P=.023). CONCLUSIONS: Ambulatory laparoscopic cholecystectomy is a safe procedure with a good acceptance by patients with expanded criteria who were included in the surgery without admission program.

Management of pancreatic gastrinoma associated with Von Hippel-Lindau disease: a case report.

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group and constitute 1.3% of all pancreatic tumors. Approximately 10% of these occur in the context of hereditary syndromes, such as VHL disease. CASE REPORT: We report a case of a female patient of 37 years diagnosed VHL and intervened on several occasions by cerebral hemangioblastoma and renal carcinomas. During its follow-up she was diagnosed 2 gastrinomas functioning under 2 cm were enucleated. Later developed new PNET and underwent a total duodenopancreatectomy without pyloric preservation. DISCUSSION: The management of PNET in VHL is difficult due to the association of multiple tumors in different organs and the morbidity and mortality associated with the surgery of the pancreas. Management must be individualized for each patient, based on the ability to produce hormones and present symptoms, the size and location, and in the context of other tumors that usually present in these patients.

Efficacy of hydrodynamic interleukin 10 gene transfer in human liver segments with interest in transplantation.

Different diseases lead, during their advanced stages, to chronic or acute liver failure, whose unique treatment consists in organ transplantation. The success of intervention is limited by host immune response and graft rejection. The use of immunosuppressant drugs generally improve organ transplantation, but they cannot completely solve the problem. Also, their management is delicate, especially during the early stages of treatment. Thus, new tools to set an efficient modulation of immune response are required. The local expression of interleukin (IL) 10 protein in transplanted livers mediated by hydrodynamic gene transfer could improve the organ acceptance by the host because it presents the natural ability to modulate the immune response at different levels. In the organ transplantation scenario, IL10 has already demonstrated positive effects on graft tolerance. Hydrodynamic gene transfer has been proven to be safe and therapeutically efficient in animal models and could be easily moved to the clinic. In the present work, we evaluated efficacy of human IL10 gene transfer in human liver segments and the tissue natural barriers for gene entry into the cell, employing gold nanoparticles. In conclusion, the present work shows for the first time that hydrodynamic IL10 gene transfer to human liver segments ex vivo efficiently delivers a human gene into the cells. Indexes of tissue protein expression achieved could mediate local pharmacological effects with interest in controlling the immune response triggered after liver transplantation. On the other hand, the ultrastructural study suggests that the solubilized plasmid could access the hepatocyte in a passive manner mediated by the hydric flow and that an active mechanism of transportation could facilitate its entry into the nucleus. Liver Transplantation 23:50-62 2017 AASLD.

Monosegment ALPPS: A new variant of the techniques for rapid hepatic regeneration. Critical review of the initial results of our series.

Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a novel surgical technique that provides fast and effective growth of liver remnant volume, allowing surgical resection of hepatic lesions initially considered unresectable. Short and long-term results and the convenience of carrying out this technique are issues that still remain under debate while waiting for the final outcomes of the multicenter registries with larger number of cases. The aim of this paper is to describe, from a critical point of view, the outcomes of the cases performed at our center (n=8). On the other hand, it is possible to leave only one hepatic segment as a liver remnant and we illustrate this new surgical procedure (ALPPS monosegment) performed in one patient.

Metastasis of the gallbladder in clear cell renal carcinoma.

Metastasis of the gallbladder due to renal cell tumors is rare. We present a case of gallbladder and metachronous left adrenal metastasis at six months follow-up, which demonstrates the importance of radiological tests and histology when making a definitive diagnosis. Clinical findings are not specific enough to arrive at a final diagnosis. However, immunohistochemistry is necessary to differentiate between primary and secondary metastatic tumors. Cholecystectomy should be performed to obtain a definitive diagnosis and to improve survival in cases of single lesions in the gallbladder.

[Donors yesterday and today: have the characteristics of liver donors changed over the last 15 years?]. / Donantes de ayer y de hoy: han cambiado las características de los donantes de hígado durante los últimos 15 años?

INTRODUCTION: The social, medical and demographic changes of our population and the increase in the number of patients on waiting lists have led to some changes in the selection criteria of organ donors. MATERIAL AND METHOD: A retrospective, descriptive and comparative study of the liver cadaveric donors features accepted in the Liver Transplant Unit in La Fe University Hospital of Valencia (Spain) in 2 different periods. We distributed the cases into 2 groups, including in group A the first 200 first donors (from January 1991 to June 1995) and in group B the last 200 donors (from February 2004 to December 2005). RESULTS: The number of donors increased from 18 during 1991 to 106 in 2006. In group A the mean age was 32.4 years, compared to 52.3 years in group B. In group A, the main cause of death was craneoencephalic traumatism and in group B cerebrovascular accidents. The mean time in the intensive care unit was longer in the second group with 67.2 hours. In group B, considerable atherosclerosis was reported in 17% of cadaveric donors and macroscopic liver steatosis in 29.5%, compared to 5 and 12%, respectively, in group A. CONCLUSIONS: Nowadays, cadaveric liver donors are older, suffer more chronic diseases, die due to cerbrovascular diseases, remain longer in intensive care units and the livers are macroscopically worse compared to donors accepted 15 years ago.