The Impact of Molecular Biology in the Seeding, Treatment Choices and Follow-Up of Colorectal Cancer Liver Metastases-A Narrative Review.

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.

Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain.

BACKGROUND: Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. METHODS: A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. RESULTS: After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

Radiofrequency-assisted transection of the pancreas versus stapler in distal pancreatectomy: study protocol for a multicentric randomised clinical trial (TRANSPAIRE).

INTRODUCTION: To date, no pancreatic stump closure technique has been shown to be superior to any other in distal pancreatectomy. Although several studies have shown a trend towards better results in transection using a radiofrequency device (radiofrequency-assisted transection (RFT)), no randomised trial for this purpose has been performed to date. Therefore, we designed a randomised clinical trial, with the hypothesis that this technique used in distal pancreatectomies is superior in reducing clinically relevant postoperative pancreatic fistula (CR-POPF) than mechanical closures. METHODS AND ANALYSIS: TRANSPAIRE is a multicentre randomised controlled trial conducted in seven Spanish pancreatic centres that includes 112 patients undergoing elective distal pancreatectomy for any indication who will be randomly assigned to RFT or classic stapler transections (control group) in a ratio of 1:1. The primary outcome is the CR-POPF percentage. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-ß), expected POPF in control group of 32%, expected POPF in RFT group of 10% and a clinically relevant difference of 22%. Secondary outcomes include postoperative results, complications, radiological evaluation of the pancreatic stump, metabolomic profile of postoperative peritoneal fluid, survival and quality of life. Follow-ups will be carried out in the external consultation at 1, 6 and 12 months postoperatively. ETHICS AND DISSEMINATION: TRANSPAIRE has been approved by the CEIM-PSMAR Ethics Committee. This project is being carried out in accordance with national and international guidelines, the basic principles of protection of human rights and dignity established in the Declaration of Helsinki (64th General Assembly, Fortaleza, Brazil, October 2013), and in accordance with regulations in studies with biological samples, Law 14/2007 on Biomedical Research will be followed. We have defined a dissemination strategy, whose main objective is the participation of stakeholders and the transfer of knowledge to support the exploitation of activities. REGISTRATION DETAILS: ClinicalTrials.gov Registry (NCT04402346).

Importance of Preventing Inadvertent Perioperative Hypothermia During Liver Transplant.

BACKGROUND: Inadvertent perioperative hypothermia (IPH) leads to a series of deleterious effects that can be especially in complex procedures such as liver transplant. The implementation of a protocol is key to ensure the patient's normothermia. METHODS: A cohort of 209 patients who underwent liver transplant in a tertiary hospital in a period between January 2016 and December 2018 was retrospectively analyzed. The patients were divided into 2 groups: group 1, patients with normothermia (core body temperature ≥ 36°C) and group 2, patients with hypothermia (core body temperature < 36°C). Mortality between both groups at 1 month, 1 year, and 3 years is compared. Postoperative morbidity is also compared. RESULTS: The incidence of IPH is 21.5%. Patients with normothermia present with statistical significance: a lower mortality at 1 year; a lower need for transfusion of platelets, plasma, fibrinogen consumption, or massive polytransfusion; and lower primary graft dysfunction, graft and surgical complications, rejection, hemodynamic complications, and metabolic and surgical reintervention. No significant differences were found in mortality at 1 month or 3 years in the need for prolonged mechanical ventilation; hospital readmission; length of stay in the intensive care unit or in hospital stay; rate of red blood cell transfusion; vascular, biliary, respiratory, or digestive complications; refractory ascites; or neurologic, kidney, hematological, endocrine, thrombotic, nutritional, or infectious issues. CONCLUSIONS: The incidence of IPH is relatively low in our patients, based on what is described in the literature, and in most cases it is mild. There is a reduction in complications fundamentally related to the consumption of blood products and the graft.

Impact of the Acute and Chronic Liver Failure-Sequential Evaluation of Organ Failure Scoring System on the Prognosis of Liver Transplant.

BACKGROUND: The use of the Model of End-Stage Liver Disease (MELD) to predict morbidity and mortality after orthotopic liver transplant (OLT) is controversial. Acute and chronic liver failure-sequential evaluation of organ failure (CLIF-SOFA) is a new score that assess the patient's global status and that have been developed exclusively for patients with end-stage liver disease. The objective is to evaluate whether the CLIF-SOFA system predicts postoperative morbidity and mortality in the short and medium term. METHODS: A cohort of 123 patients who underwent OLT in a tertiary care hospital between January 2016 and December 2017 was retrospectively analyzed. The patients were divided into 2 groups: group 1 with a CLIF-SOFA score <7 and group 2 with a score CLIF-SOFA ≥7. RESULTS: Patients with a CLIF-SOFA ≥7 present, with statistical significance, had higher mortality at 1 and 3 years; longer duration of admission to the critical care unit; longer hospital stay; need for prolonged mechanical ventilation; surgical reintervention; higher rate of transfusion of blood products; pulmonary, neurologic, hemodynamic, surgical, infectious, kidney, metabolic, thrombotic, vascular, and graft complications; and need for kidney replacement therapy. However, no statistically significant differences were found in mortality in the first month, the need for hospital readmission, retransplant, digestive, endocrine, nutritional, hematologic, or biliary complications, and the presence of ascites. CONCLUSIONS: The role of CLIF-SOFA as a prognostic factor for mortality after OLT must be taken into account. Our results should be taken with caution, and more studies are necessary.

KRAS Assessment Following ESMO Recommendations for Colorectal Liver Metastases. Is It Always Worth It?

BACKGROUND: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation. METHODS: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan-Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35-100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40-42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37-15.10; p = 0.013). CONCLUSION: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection.

Liver Transplantation: Analysis of Preservation Solutions in the Andalusian Registry.

BACKGROUND: The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. METHODS: A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. RESULTS: Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P < .005) with donors older than 47.6 and 47.5 years, respectively. CONCLUSIONS: Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours.

Clinical case report: endoluminal thermal ablation of main pancreatic duct for patients at high risk of postoperative pancreatic fistula after pancreaticoduodenectomy.

PURPOSE: Multiple attempts have been made to manage the pancreatic stump and the pancreatic duct in order to reduce the rate of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), however radiofrequency-based technologies could help to achieve this goal. Previous encouraging clinical and experimental results support the use of endoluminal thermal ablation (ETHA) of the main pancreatic duct to reduce pancreatic exocrine secretion and hence POPF. We here describe our initial clinical experience with ETHA of the main pancreatic duct in two cases at high risk of POPF. METHODS: Two cases underwent PD for malignancy with a high risk of POPF (adenocarcinoma, obese patients, surgical difficulties with heavy intraoperative blood loss, soft pancreas or walled-off pancreatitis and a tight small pancreatic main duct). In both cases, ETHA of the main pancreatic duct was conducted intraoperatively just before Blumgart-type pancreatic-jejunal anastomosis using a ClosureFast catheter (Medtronic, Mansfield, MA, USA) normally used for varicose vein treatment (therefore an off-label use). RESULTS: Although a clear radiological POPF was detected in the second case, the clinical postoperative course in both cases was uneventful. Little pancreatic fluid collected in the abdominal drainage with low levels of amylase enzyme, confirming low exocrine pancreatic function. No other procedure-related complications were detected. CONCLUSION: Endoluminal thermal ablation of the main pancreatic duct may be a feasible and safe technique to reduce the adverse effects of POPF after PD.

Replaced right hepatic artery arising from the gastroduodenal artery: a rare and challenging anatomical variant of the Whipple procedure.

Accurate assessment of the vascular anatomy is a prerequisite of any pancreatic resection, since an unnoticed arterial injury in the context of a complex resection such as Whipple procedure, can seriously jeopardize patient's safety. This article aims to describe an infrequent anatomic variant of a replaced right hepatic artery originating directly from the gastroduodenal artery and its potential implications for duodenopancreatectomy, as the gastroduodenal artery is routinely divided. We present here two different cases of this arterial abnormality identified during a Whipple procedure and its implications in each different setting. Preoperative identification of anatomical variations is essential for proficient surgical planning. Nevertheless, when detected during surgery, an meticulous dissection of the hepatoduodenal ligament is required to identify all the vascular relations in order to avoid irreversible damage.

Necrosis gástrica secundaria a incarceración inguinal / Gastric necrosis secondary to inguinal incarceration

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