Search

Endoplasmic reticulum (ER) is a central organelle in eukaryotic cells that regulates protein synthesis and maturation. Perturbation of ER functions leads to ER stress, which has been previously associated with a broad variety of diseases. ER stress is generally regarded as compensatory, but prolonged ER stress has been involved in apoptosis induced by several cytotoxic agents. Choline kinase α (ChoKα), the first enzyme in the Kennedy pathway, is responsible for the generation of phosphorylcholine (PCho) that ultimately renders phosphatidylcholine. ChoKα overexpression and high PCho levels have been detected in several cancer types. Inhibition of ChoKα has demonstrated antiproliferative and antitumor properties; however, the mechanisms underlying these activities remain poorly understood. Here, we demonstrate that ChoKα inhibitors (ChoKIs), MN58b and RSM932A, induce cell death in cancer cells (T47D, MCF7, MDA-MB231, SW620 and H460), through the prolonged activation of ER stress response. Evidence of ChoKIs-induced ER stress includes enhanced production of glucose-regulated protein, 78 kDa (GRP78), protein disulfide isomerase, IRE1α, CHOP, CCAAT/enhancer-binding protein beta (C/EBPβ) and TRB3. Although partial reduction of ChoKα levels by small interfering RNA was not sufficient to increase the production of ER stress proteins, silencing of ChoKα levels also show a decrease in CHOP overproduction induced by ChoKIs, which suggests that ER stress induction is due to a change in ChoKα protein folding after binding to ChoKIs. Silencing of CHOP expression leads to a reduction in C/EBPβ, ATF3 and GRP78 protein levels and abrogates apoptosis in tumor cells after treatment with ChoKIs, suggesting that CHOP maintains ER stress responses and triggers the pro-apoptotic signal. Consistent with the differential effect of ChoKIs in cancer and primary cells previously described, ChoKIs only promoted a transient and moderated ER stress response in the non-tumorogenic cells MCF10A. In conclusion, pharmacological inhibition of ChoKα induces cancer cell death through a mechanism that involves the activation of exaggerated and persistent ER stress supported by CHOP overproduction.

Introduction and Aims: Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making., Materials and Methods: Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed., Results: Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ± 37.2 and 27.4 ± 28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality., Conclusions: There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making., (Copyright © 2023 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.)

(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.

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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Liver transplantation (LT) is a curative treatment for early-stage hepatocellular carcinoma (HCC) unsuitable for surgical resection. However, tumor recurrence (TR) rates range from 8% to 20% despite strict selection criteria. The validation of new prognostic tools, such as pre-MORAL or RETREAT risks, is necessary to improve recurrence prediction. A retrospective study was conducted at Marqués de Valdecilla University Hospital in Cantabria, Spain, between 2010 and 2019 to determine the rate of TR in LT patients and identify associated factors. Patients with liver-kidney transplantation, re-transplantation, HIV infection, survival less than 90 days, or incidental HCC were excluded. Data on demographic, liver disease-related, LT, and tumor-related variables, as well as follow-up records, including TR and death, were collected. TR was analyzed using the Log-Rank test, and a multivariate Cox regression analysis was performed. The study was approved by the IRB of Cantabria. TR occurred in 13.6% of LT patients (95% CI = 7.3-23.9), primarily as extrahepatic recurrence (67%) within the first 5 years (75%). Increased TR was significantly associated with higher Body Mass Index (BMI) (HR = 1.3 [95% CI = 1.1-1.5]), vascular micro-invasion (HR = 8.8 [1.6-48.0]), and medium (HR = 20.4 [3.0-140.4]) and high pre-MORAL risk (HR = 30.2 [1.6-568.6]). TR also showed a significant correlation with increased mortality. Conclusions: LT for HCC results in a 13.6% rate of tumor recurrence. Factors such as BMI, vascular micro-invasion, and medium/high pre-MORAL risk are strongly associated with TR following LT.

The atlantoaxial joint C2 (axis) with the anterior arch of C1 (atlas) allows 50% of cervical lateral rotation. It is responsible for precise and important movements that allow us to perform precise actions, both in normal and working life. Due to low incidence in adults, this condition often goes undiagnosed, or the diagnosis is delayed and the outcome is worse. An early diagnosis and treatment are essential to ensure satisfactory neurological and functional outcomes. The aim of this review is to analyze C1-C2 rotatory subluxation in adults, given its rarity. The time between injury and reduction is key, as it is directly related to prognosis and the severity of the treatment options. Due to low incidence in adults, this condition often goes undiagnosed, or the diagnosis is delayed as a lot of cases are not related to a clear trauma, with a poor prognosis just because of the late diagnosis and the outcome is worse. The correct approach and treatment of atlantoaxial dislocation requires a careful study of the radiological findings to decide the direction and plane of the dislocation, and the search for associated skeletal anomalies.

Different reports have shown the clinical and serologic response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in preventing coronavirus disease 2019 (COVID-19) in the general population, but few studies have examined these responses in transplant recipients. We assessed the vaccine immunogenicity of two doses (100 μg) of the mRNA-1273 vaccine (Moderna) administered with a 28-day interval in liver transplant recipients (LTRs) at follow-up at the Marques de Valdecilla University Hospital. LTRs without a history of COVID-19 infection were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies directed against the spike protein (S) a median of 43 days after receiving the second Moderna vaccine dose. Clinical data, including immunosuppressive regimen and routine laboratory data, were obtained from the medical record of each patient up to 3 months before the date of the first vaccination. Factors associated with serologic response were evaluated through logistic regression. In total, 129 LTRs who had anti-S results were included. Most patients were men (n = 99; 76.7%) with a median age of 63 years (interquartile range, 56-68). Alcohol (43.4%) and chronic hepatitis C (18.6%) were the most frequent causes of liver transplantation. A positive anti-S IgG response was observed in 113 LTRs (87.6%; 95% confidence interval [CI], 80.8-92.2). A strong inverse relationship between mycophenolate mofetil use and serologic response was found (odds ratio, 0.07; 95% CI, 0.02-0.26; p = 0.001). Conclusion: Most LTRs develop an immunological response to the Moderna SARS-CoV-2 mRNA-based vaccine. An immunosuppressive regimen that includes mycophenolate predicts a weak serologic response., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., Competing Interests: Declaration of competing interest All authors state that they have no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Balance of Risk (BAR) score is a simple test that combines donor and recipient variables to predict liver transplant success. It has been validated in different publications, with cut-off points of between 15 and 18 points proposed depending on the region. The aim of this study is to test the validity of the BAR score and to find the optimal cut-off point for our population., Materials and Methods: A retrospective cohort of 164 liver transplant patients was selected between January 2012 and July 2019. All were older than 18 years and were treated in a Spanish tertiary-level hospital., Results: The receiver operating characteristic curve between BAR and 5-year survival yields a result of 0.622 (P = .046), placing the cut-off point at ≥7 (sensitivity 61.5%, specificity 61.6%). Patients with a BAR score <7 and a BAR score ≥7 have an estimated 5-year survival of 53.91 vs 47.51 months, respectively (log rank = .032). The only 2 variables associated with increased survival were a BAR score of <7 (hazard ratio = 2.566; P < .001) and a body mass index <30 (hazard ratio = 6.667; P < .001)., Conclusions: A low BAR score correlates well with liver transplant survival at 5 years. The BAR is a simple tool that should be used for donor-recipient matching. Due to the characteristics, resources, and population in our environment, a BAR score of 7 would be the optimum cut-off point for a liver transplant., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction and Objectives: To analyze the evolution of kidney function after radical nephrectomy and to evaluate risk factors for adverse cardiovascular events during a long follow-up., Material and Methods: Retrospective study of patients submitted to radical nephrectomy due to renal cancer from January of 1996 to January of 2016. We evaluated their renal function after nephrectomy and during follow-up. We analyzed the possible predictive factors for adverse cardiovascular events with univariate and multivariate logistic regression analyses., Results: There was an acute drop in glomerular filtration rate (GFR) after nephrectomy (21.2ml/min), which stabilized during follow-up in most cases. We evaluated the possible predictive factors for adverse cardiovascular events with logistic regression analyses, which presented previous cardiovascular disease (0,270, 95% CI 0,123-0,594, P<.001), diabetes (0,364, 95% CI 0,162-0,818 P=.015) and de novo hypertension (0,239, 95% CI 0,098-0,581, P=.002) as independently associated with the occurrence of adverse cardiovascular events., Conclusion: There was a deleterious effect in renal function after nephrectomy which remained stable during subsequent years in most patients. Approximately half of our patients had a GFR lower than 60mL/min after nephrectomy. Previous cardiovascular disease, diabetes and de novo hypertension were shown as risk factors for adverse cardiovascular events., (Copyright © 2020 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Surgical training based on simulation seeks the acquisition of skills in novice participants and ongoing sill development in experts. The aim of this study is to assess the evolution of students in an intensive laparoscopic anastomosis course and to analyse their results depending on their level and previous experience., Methods: The students of all the anastomosis courses conducted during 30 months in the Valdecilla virtual hospital (Santander) were analysed. Manual side-to-side intestinal anastomoses with porcine 'ex vivo' viscera were performed in a laparoscopic endotrainer. The technical and quality differences between the first and the last anastomoses were analyzed and the progression between residents and specialists was compared., Results: We analyzed 45 participants, 22 of them residents and 23 specialists. A statistically significant improvement of 80.5% was observed in all procedural parameters (94.8% residents vs. 67.3% specialists). The time was reduced by 48.1% in the residents and 43.2% in the specialists (p<.001). In terms of quality, significant improvements were obtained in the group of residents: an increase of 90% in adequate tension, and a reduction of 75% of everted edges and 60% of leaks. In addition, they obtained results comparable to the specialists (27.3% leak in the last anastomosis vs. 34.8% by the specialists, p=.59), which presented improvement without statistical significance., Conclusions: The group of residents presented a major and significant improvement in procedural skills and in the quality of the technique, reaching the level of the specialists after completion of the course., (Copyright © 2019 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: There are no quantified data on the real activity carried out by residents during the 5 years of training in the specialty of general and digestive surgery (GGS) in Spain. There are also limited data on programs in other surgical specialities, and in other countries. The aim of the study is to estimate the mean overall surgical activity by specific skill areas and by the level of complexity of the Spanish program in the specialty of GGS., Patients and Method: A prospective, observational, multicentre study was performed on the activity of GGS residents in Spain using the Resident Computerised Logbook of the Spanish Surgeons Association (LIR-AEC). Each of the residents registered their own activity supervised by their tutor. The sample period was 6 months. The medians of the annual activity and the period of residency were calculated from the results., Results: Surgical activity: during the residency, it was estimated that that they attended 1,325 operations, 654 (49%) as lead surgeon. Health care activity: the mean number of times on-call was 5.2±1.8 per month. Activity in outpatient clinics was 548 first visits, and almost double for second visits. Scientific activity: the total number of courses and conferences attended was 34. The estimated mean number of presentations at conferences was 14, with 3 publications., Conclusions: LIR-AEC is a suitable tool to verify activity in the Spanish GGS Program. These results may be useful for comparing with training programs in other countries and in other surgical specialties., (Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.)

Introduction: The rapid development of laparoscopic surgery makes resident training programmes necessary., Objective: To analyse the results of a structured programme of laparoscopic training in an experimental laboratory., Material and Method: From 2003 until 2007, we trained 11 general surgery residents for 20 h every 3 months, for three years. The practice consisted of suture and anastomosis in Endo-Trainer with animal organs, as well as laparoscopic techniques in live animals. In the Endo-Trainer practice we evaluated the time and quality of anastomosis performance. In laparoscopic techniques (cholecystectomy and anti-reflux surgery) a task table was evaluated, from 0 (no errors) to 100 (severe lesion)., Results: In total, 314 anastomosis were performed by the 11 residents, with a median of 28.5 per resident (24-42). The mean time for the first gastro-jejunal anastomosis was 135 min (100-140) and 65 min (57.5-105) for the first jejunal-jejunal anastomosis. Maximum learning was achieved after 45 training hours. There were no appreciable differences between both types of anastomosis. There was inadequate anastomosis quality due to leakage in 17.1% during the learning period and 13.7% during the consolidation period. In the animal, 172 procedures were performed. In cholecystectomy and anti-reflux surgery the mean scores were 2.4 and 5.6 points, respectively. In the remaining procedures, subjectively evaluated by the monitors, the quality was adequate in 65%, deficient in 22% and highly deficient in 13%., Conclusions: This structured programme of laparoscopic skills based on intestinal anastomosis allows for quicker resident training.

Aims: Mutations of the E-cadherin gene (CDH1) result in dominantly inherited hereditary diffuse gastric cancer (HDGC). We report a study in the first family diagnosed with HDGC in Spain, examining the presence of mutations in the CDH1 gene., Methods: The presence of mutations was studied by direct sequencing of all CDH1 exons. Immunohistochemical analysis with specific antibodies was used to detect the expression of E-cadherin in normal and tumour tissue., Results: A novel 1610delC mutation in exon 11 has been found in a Spanish family diagnosed with HDGC. This mutation generates a premature stop codon at position 1667 giving rise to a truncated protein that lacks the transmembrane and beta-catenin-binding domains. The presence of a 1610delC germline mutation was confirmed in three family members diagnosed with diffuse gastric cancer, and also in six asymptomatic members. Of note, the diffuse gastric cancer coexisted with a gastric lymphoma in the proband. Furthermore, immunohistochemical analyses of tumour tissue showed the complete absence of E-cadherin in the proband, revealing a second genetic hit at the CDH1 locus., Conclusions: We have identified a HDGC family in Spain that carries a novel germline truncating mutation in the CDH1 gene.

Background: Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist., Methods: We report a morbidity obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD., Results: Because of irreversible liver failure the decision to perform a liver transplantation was made. The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patient's recovery were uneventful., Conclusion: Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.