Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux

Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels

BACKGROUND: Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management. METHODS: Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m(2) ) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed. RESULTS: Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level. CONCLUSION: Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevance Insulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat. Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated. This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism

COVID-19 infection is a significant risk factor for death in patients presenting with acute cholecystitis: a secondary analysis of the ChoCO-W cohort study

Background: During the coronavirus disease (COVID-19) pandemic, there has been a surge in cases of acute cholecystitis. The ChoCO-W global prospective study reported a higher incidence of gangrenous cholecystitis and adverse outcomes in COVID-19 patients. Through this secondary analysis of the ChoCO-W study data, we aim to identify significant risk factors for mortality in patients with acute cholecystitis during the COVID-19 pandemic, emphasizing the role of COVID-19 infection in patient outcomes and treatment efficacy.” Methods: The ChoCO-W global prospective study reported data from 2546 patients collected at 218 centers from 42 countries admitted with acute cholecystitis during the COVID-19 pandemic, from October 1, 2020, to October 31, 2021. Sixty-four of them died. Nonparametric statistical univariate analysis was performed to compare patients who died and patients who survived. Significant factors were then entered into a logistic regression model to define factors predicting mortality. Results: The significant independent factors that predicted death in the logistic regression model with were COVID-19 infection (p < 0.001), postoperative complications (p < 0.001), and type (open/laparoscopic) of surgical intervention (p = 0.003). The odds of death increased 5 times with the COVID-19 infection, 6 times in the presence of complications, and it was reduced by 86% with adequate source control. Survivors predominantly underwent urgent laparoscopic cholecystectomy (52.3% vs. 23.4%). Conclusions: COVID-19 was an independent risk factor for death in patients with acute cholecystitis. Early laparoscopic cholecystectomy has emerged as the cornerstone of treatment for hemodynamically stable patients

The Unexpected Evolution of an Expected Complication: Hemophagocytic Lymphohistiocytosis

Severe obesity is associated with consistent morbidity and mortality. Bariatric surgery is presently the most effective treatment for this condition, and laparoscopic Rouxen-Y gastric bypass (RYGB) is the most common surgical procedure performed. RYGB carries a mortality risk of 0.5\u20131.9%. One fearedearly surgical complications is postoperative leak,occurringin2.1\u20135.2% of patients and having a mortality rate up to 50%. Hemophagocytic lymphohistiocytosis (HLH) is a rare disease, characterized by an uncontrolled inflammatory response that leads to systemic compromise and in the end to death by multi-organ failure, bleeding, sepsis, or disseminated intravascular coagulation (DIC). We report the first case of HLH associated with complicated bariatric surgery, investigating possible reasons for this associatio

Effect of Gastric Bypass Versus Diet on Cardiovascular Risk Factors

Objective: To assess the effect of Roux-en-Y gastric bypass (RYGB) on high-density lipoprotein cholesterol (HDL-C) concentration and its apolipoprotein A4 (ApoA4) content at 1 year after bariatric surgery in comparison with a hypocaloric diet. Secondary aim was to measure total cholesterol and triglycerides levels and insulin sensitivity after interventions.Background: Very few prospective uncontrolled studies have investigated the effects of RYGB on cardiovascular risk factors. No controlled studies had as primary goal the changes in HDL-C after gastric bypass.Methods: Forty subjects with a body mass index more than 40 or 35 kg/m2 or more in the presence of diabetes were enrolled. Twenty of them underwent RYGB, whereas 20 received lifestyle modification suggestions and medical therapy for obesity complications (diabetes, hypertension, and hyperlipidemia).Results: A significant (P < 0.0001) increase in HDL-C concentrations was observed only in the surgical arm (from 41.95 ± 7.24 to 56.55 ± 9.01 mg/dL). Mean systolic and diastolic blood pressures were significantly reduced (P < 0.0001) in both groups with no between-group differences, probably in relation to the optimization of the antihypertensive treatment. Plasma concentration of ApoA4, a major HDL-C protein fraction, significantly increased 1 year after RYGB (from 496.61 ± 400.41 to 987.88 ± 637.41μg/L, P < 0.01). Circulating triglycerides concentration significantly decreased after surgery, whereas both peripheral and hepatic insulin resistance increased significantly.Conclusions: Our study shows that HDL-C and ApoA4 significantly increase after gastric bypass and that this increase is associated with a net improvement in hepatic insulin sensitivity. Furthermore, we speculate that ApoA4, which induces satiety in animals, can eventually play a role on the appetite reduction after RYGB because there is a strict and inverse relationship between weight and ApoA4 changes. (NCT01707771

Polypoid Gallbladder Lesion in the Context of Renal Cell Carcinoma

Introduction . The only curative therapeutic approach for renal cell carcinoma (RCC) is surgery. Laparoscopic surgery for RCC has become an established surgical procedure with equivalent cancer-free survival rate, following the same surgical oncological principles as open surgery. Metastatic RCC of the gallbladder is a rare phenomenon. Hence, there are few reports regarding their management. Case Presentation . We report 2 cases of gallbladder metastasis from clear cell RCC treated by laparoscopic cholecystectomy. The first case was that of a 44-year-old male patient who underwent palliative cholecystectomy, the second case was that of an 83-year-old female patient who is doing well 55 months after surgery without evidence of disease recurrence. Conclusion . The outcome allows us to demonstrate the interest of surgical resection of RCC metastases in the gallbladder by laparoscopic cholecystectomy, respecting surgical oncological principles. Laparoscopic resection of an uncommon gallbladder metastasis can provide long-term favorable outcome

Transhepatic metallic stenting for hepaticojejunostomy stricture following laparoscopic cholecystectomy biliary injury: A case of successful 20 years follow-up

Laparoscopic cholecystectomy is still associated with a considerable rate of biliary injuries and related strictures. Advances in interventional endoscopy and percutaneous techniques have made stenting a preferred treatment modality for the management of these strictures. We report successful 20 years of follow-up of a case of trans-hepatic metallic stenting (2 Gianturco(®) prostheses, 5 cm long, 2 cm in diameter) done for stenosed hepatico-jejunostomy anastomosis after laparoscopic CBD injury. Percutaneous transhepatic stenting and long-term placement of metallic stents need to be re-evaluated as a minimally invasive definitive treatment option for benign biliary strictures in patients with altered anatomy such as hepatico-jejunostomy or in whom re-operation involves high risk

Vacuum Assisted Closure (VAC) therapyTM as a swiss knife multi-tool for enteric fistula closure: tips and tricks: a pilot study.

OBJECTIVE: Enterocutaneous fistulas (ECFs) are an uncommon surgical problem, but they are characterized by a difficult management. Vacuum-assisted closure (VAC) therapy is a method utilized for chronic and traumatic wound healing. At first, VAC therapy had been contraindicated in the treatment of intestinal fistulas, but as time went by, VAC therapy revealed itself to be a "Swiss knife multi-tool". This paper presents some clinical cases of enterocutaneous (ECF) and enteroatmospheric fistulas (EAF) treated with VAC therapy™. MATERIALS AND METHODS: The history of 8 patients treated for complex fistulas was revised. Four of them presented with enterocutaneous and four with enteroatmospheric fistulas. All were treated with VAC therapy with variations elaborated to help in accelerated closure of intestinal wall lesions. RESULTS: Four out of four ECFs closed spontaneously. In the EAF group, in three cases the fistula turned slowly into an entero-cutaneous fistula, and in one out of four it closed spontaneously. The mean length of VAC therapy™ was 35.5 days and that of spontaneous closure was 36.4 days. CONCLUSIONS: The results of our study encourage the use of VAC therapy™ for the treatment of enterocutaneous fistulas. VAC therapy™ use has a double therapeutic value: (1) it promotes the healing of the skin and allows also the management of EAFs; (2) in selected cases, those in which it is possible to create a deep fistula tract ("well") it is possible to assist to a complete healing with closure of the ECFs