Mechanisms linking bariatric surgery to adipose tissue, glucose metabolism, fatty liver disease and gut microbiota.

PURPOSE: In the last 20 years, bariatric surgery has achieved an important role in translational and clinical research because of obesity comorbidities. Initially, a tool to lose weight, bariatric surgery now has been shown to be involved in several metabolic pathways. METHODS: We conducted a narrative review discussing the underlying mechanisms that could explain the impact of bariatric surgery and the relationship between obesity and adipose tissue, T2D, gut microbiota, and NAFLD. RESULTS: Bariatric surgery has an impact in the relation between obesity and type 2 diabetes, but in addition  it induces the white-to-brown adipocyte trans-differentiation, by enhancing thermogenesis. Another issue is the connection of bariatric surgery with the gut microbiota and its role in the complex mechanism underlying weight gain. CONCLUSION: Bariatric surgery modifies gut microbiota, and these modifications influence lipid metabolism, leading to improvement of non-alcoholic fatty liver disease.

Effectiveness of near-infrared fluorescent cholangiography in the identification of cystic duct-common hepatic duct anatomy in comparison to magnetic resonance cholangio-pancreatography: a preliminary study.

INTRODUCTION: Bile duct injury represents the most serious complication of LC, with an incidence of 0.3-0.7% resulting in a significant impact on quality-of-life, overall survival, and frequent medico-legal litigations. Near-infrared fluorescent cholangiography (NIRF-C) represents a novel intra-operative imaging technique that allows a real-time enhanced visualization of the extrahepatic biliary tree by fluorescence. The role of routine use of pre-operative magnetic resonance cholangio-pancreatography (MRCP) to better clarify the biliary anatomy before laparoscopic cholecystectomy is still a matter of debate. The primary aim of this study was to evaluate the effectiveness of NIRF-C in the detection of cystic duct-common hepatic duct anatomy intra-operatively in comparison with pre-operative MRCP. METHODS: Data from 26 consecutive patients with symptomatic cholelithiasis or chronic cholecystitis, who underwent elective laparoscopic cholecystectomy with intra-operative fluorescent cholangiography and pre-operative MRCP examination between January 2018 and May 2018, were analyzed. Three selected features of the cystic duct-common hepatic duct anatomy were identified and analyzed by the two different imaging methods: insertion of cystic duct, cystic duct-common hepatic duct junction, and cystic duct course. RESULTS: Fluorescent cholangiography was performed successfully in all twenty-six patients undergoing elective laparoscopic cholecystectomy. The visualization of cystic duct was reported in 23 out of 26 cases, showing an overall diagnostic accuracy of 86.9%. The level of insertion, course, and wall implantation of cystic duct were achieved by NIRF-C with diagnostic accuracy values of 65.2%, 78.3%, and 91.3%, respectively in comparison with MRCP data. No bile duct injuries were reported. CONCLUSION: Fluorescent cholangiography can be considered a useful imaging diagnostic tool comparable to MRCP for detailed intra-operative visualization of the cystic duct-common hepatic duct anatomy during elective laparoscopic cholecystectomies.

Involvement of the Nrf2/HO-1/CO axis and therapeutic intervention with the CO-releasing molecule CORM-A1, in a murine model of autoimmune hepatitis.

Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2, and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM-A1 determines an improvement in several sero-immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM-A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans.

Near-infrared fluorescent cholangiography - real-time visualization of the biliary tree during elective laparoscopic cholecystectomy.

BACKGROUND: The purpose was to evaluate the efficacy of near-infrared fluorescent cholangiography (FC) in real-time visualization of the biliary tree during elective laparoscopic cholecystectomy. METHODS: Fifty consecutive elective laparoscopic cholecystectomies were performed with fluorescent cholangiography. FC was performed at three time points: following exposure of Calot's triangle, prior to any dissection; and after partial and complete dissection of Calot's triangle. RESULTS: The cystic duct (CD) was identified successfully by FC in 43 of 50 patients (86%) and in 45 of 50 patients (90%) before and after Calot's dissection respectively (p > 0.05). The common hepatic duct (CHD) and the common bile duct (CBD) were identified successfully in 12 of 50 patients (24%) and in 33 of 50 patients (66%) before Calot's dissection respectively and in 26 of 50 patients (52%) and in 47 of 50 patients (94%) after complete Calot's dissection (p = 0.007 and p = 0.001, respectively). Significant differences were observed for CBD visualization rate, in relation to BMI after Calot's dissection (p < 0.05) and history of cholecystitis, before Calot's dissection (p = 0.017). No bile duct injuries were reported. CONCLUSION: Fluorescent cholangiography can be considered as a useful tool for intra-operative visualization of the biliary tree during laparoscopic cholecystectomies.

Comparative analysis of the incidence of surgical site infections in patients with liver resection for colorectal hepatic metastases after neoadjuvant chemotherapy.

BACKGROUND: The aim of this study was to identify the incidence of surgical site infections (SSIs) and postoperative complications, as defined by the Clavien-Dindo classification, after hepatic resection for metastatic colorectal cancer in patients with and without associated neoadjuvant chemotherapy. METHODS: A total of 181 patients were studied retrospectively. Patients were divided into two groups: the first group comprised patients with associated neoadjuvant chemotherapeutic treatment for liver metastases with a latency time <8 wk and the second group comprised patients without associated neoadjuvant chemotherapy. RESULTS: Variables of duration of liver surgery, length of total hospital stay, and length of postoperative hospital stay seem to be correlated with SSIs and postoperative complications, P < 0.005 and P < 0.0001, respectively. Duration of surgery is a risk factor for SSIs, with an odds ratio of 1.15, and for complications according to the Clavien-Dindo classification, with an odds ratio of 1.35. CONCLUSIONS: Neoadjuvant chemotherapy was not a significant risk factor for SSIs, whereas the total length of hospital stay, length of postoperative hospital stay, and duration of surgery were independent predictors of SSIs and complications according to the Clavien-Dindo classification.

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.

Redox State Modulatory Activity and Cytotoxicity of Olea europaea L. (Oleaceae) Leaves Extract Enriched in Polyphenols Using Macroporous Resin.

The food products derived from Olea europaea are a fundamental part of the Mediterranean diet, and their health-promoting effects are well known. In this study, we analyzed the phytochemical characteristics, the redox state modulatory activity, and the cytotoxic effect of an olive leaf aqueous extract enriched by macroporous resin on different tumor and normal cell lines (LNCaP, PC3, HFF-1). HPLC-DAD analysis, the Folin-Ciocalteu and aluminum chloride methods confirmed the qualitatively and quantitatively high content of phenolic compounds (130.02 ± 2.3 mg GAE/g extract), and a DPPH assay (IC50 = 100.00 ± 1.8 µg/mL), the related antioxidant activity. The biological investigation showed a significant cytotoxic effect, highlighted by an MTT test and the evident cellular morphological changes, on two prostate cancer cell lines. Remarkably, the extract was practically non-toxic on HFF-1 at the concentrations (100, 150, 300 µg/mL) and exposure times tested. Hence, the results are selective for tumor cells. The underlying cytotoxicity was associated with the decrease in ROS production (55% PC3, 42% LNCaP) and the increase in RSH levels (>50% PC3) and an LDH release assay (50% PC3, 40% LNCaP, established necrosis as the main cell death mechanism.

Is BCLC algorithm useful in clinical practice? Study on 164 HCC patients.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification has been recently validated as the best system for treatment guidance for hepatocellular carcinoma (HCC). The aim of this retrospective study is to evaluate the usefulness of BCLC in the treatment of HCC comparing our treatment decision and the BCLC algorithm indications. METHODOLOGY: In 102 patients affected by HCC observed from 1991 to 2002 a retrospective analysis was performed. The choice of treatment was compared with the treatment schedule proposed by BCLC. Whereas the second group of 62 patients observed from 2008 to 2010 was analysed both retrospectively in comparison with the BCLC classification. RESULTS: We found a disagreement in between our decision making and the choices suggested by BCLC. We only found a statistical significance for age and performance status test. In surgical patients the median age and the PST class were lower with a statistically significant p value (0.04 and 0.03, respectively). CONCLUSIONS: The BCLC system would not have changed our decision either in the past, or in present days, especially in surgical indications. Even if the decision making is affected by BCLC, actually that process still needs the support of the experience of each clinical centre involved.

Ileocolonic anastomosis: preferred techniques in 999 patients. A multicentric study.

PURPOSE: There is no standard anastomosis technique for performing reconstruction after right hemicolectomy, and, in the literature, studies on ileocolonic anastomosis are rare. The aim of this retrospective work was to analyze the type of anastomosis techniques used and the related results in a multicentric enquiry. METHODS: A questionnaire was sent to the departments of surgery covering a 1.8 million inhabitant area to collect data concerning the anastomosis techniques used and the results related to complications. RESULTS: Data for 999 patients from 14 departments of surgery were collected. 95.8% of the patients were affected by cancer and 4.2% were affected by inflammatory bowel disease (IBD). The positioning of the anastomosing bowel was side-to-side in 60.5% of the patients, end-to-side (E-S) in 38.1% of the patients and end-to-end in 1.3% of the patients. 46.4% of the anastomoses were handsewn and 53.6% were stapled. The complication rate in the cancer group was 5.1% for handsewn techniques and 4.7% for stapled techniques. The rate of anastomotic leakage was higher in the handsewn group than that in the stapled group (P < 0.05). The data for the IBD group were not statistically relevant. CONCLUSIONS: This wide multicentric retrospective analysis showed that there remains variability in ileocolonic anastomosis techniques. Stapled anastomoses are associated with a lower incidence of leakage. In stapled anastomoses, the E-S configuration is also related to a lower incidence of leakage.

Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database.

There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention. The purpose of this bibliometric analysis is to assess recent publishing trends concerning the role of the gut microbiome in the progression of NAFLD, NASH and cirrhosis and its connection with biotics. The free access version of the Dimensions scientific research database was used to find publications in this field from 2002 to 2022. VOSviewer and Dimensions' integrated tools were used to analyze current research trends. Research into the following topics is expected to emerge in this field: (1) evaluation of risk factors which are correlated with the progression of NAFLD, such as obesity and metabolic syndrome; (2) pathogenic mechanisms, such as liver inflammation through toll-like receptors activation, or alteration of short-chain fatty acids metabolisms, which contribute to NAFLD development and its progression in more severe forms, such as cirrhosis; (3) therapy for cirrhosis through dysbiosis reduction, and research on hepatic encephalopathy a common consequence of cirrhosis; (4) evaluation of diversity, and composition of gut microbiome under NAFLD, and as it varies under NASH and cirrhosis by rRNA gene sequencing, a tool which can also be used for the development of new probiotics and explore into the impact of biotics on the gut microbiome; (5) treatments to reduce dysbiosis with new probiotics, such as Akkermansia, or with fecal microbiome transplantation.

Bile duct injury during laparoscopic cholecystectomy without intraoperative cholangiography: a retrospective study on 1,100 selected patients.

BACKGROUND: Whether to routinely or selectively use intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) has been a controversial issue for many years. Many authors maintain that IOC decreases the rate of biliary complications such as bile duct injuries, biliary leak, and missed common bile duct (CBD) stones. However, in contrast to these claims, many centers have opted to perform LC without IOC. In this retrospective study, the results of a series of 1,100 LCs, all of which involved major biliary complications and which were performed without the use of IOC, were reviewed. METHODS: Data from 1,100 selected patients (728 females and 372 males) undergoing LC without the use of IOC from January 2003 to November 2011 were analyzed. One hundred and seventy LCs were performed by young surgeons during the learning curve, and 930 by surgeons with over 10 years of experience. Two techniques were used to create pneumoperitoneum: the Veress technique in 319 cases (29%) and the Hasson technique in the remaining 781 cases (71%). Patients with a suspicion of CBD stones were excluded from the study. RESULTS: Two CBD injuries (0.18%) and three biliary leaks (0.27%) were detected among this group. Thirty-three patients (3%) needed conversion to open cholecystectomy. Missed CBD stones were reported in 4 cases (0.36%). There was no postoperative mortality. CONCLUSION: LC can be performed safely without the use of IOC and with acceptable low rates of biliary complications. An accurate preoperative evaluation of clinical risk factors, precise operative procedures, and conversion to an open approach in doubtful cases are important measures which must be taken to prevent CBD injury.

Does transient elastography (FibroScan®) have a role in decision making in hepatocellular carcinoma?

OBJECTIVES: Portal hypertension has been reported as a negative prognostic factor and a relative contraindication for liver resection. This study considers a possible role of fibrosis evaluation by transient elastography (FibroScan(®)) and its correlation with portal hypertension in patients with cirrhosis, and discusses the use of this technique in planning therapeutic options in patients with hepatocellular carcinoma (HCC). METHODS: A total of 77 patients with cirrhosis, 42 (54.5%) of whom had HCC, were enrolled in this study during 2009-2011. The group included 46 (59.7%) men. The mean age of the sample was 65.2 years. The principle aetiology of disease was hepatitis C virus (HCV)-related cirrhosis (66.2%). Liver function was assessed according to Child-Pugh classification. In all patients liver stiffness (LS) was measured using FibroScan(®). The presence of portal hypertension was indirectly defined as: (i) oesophageal varices detectable on endoscopy; (ii) splenomegaly (increased diameter of the spleen to ≥ 12 cm), or (iii) a platelet count of <100,000 platelets/mm(3). RESULTS: Median LS in all patients was 27.9 kPa. Portal hypertension was recorded as present in 37 patients (48.1%) and absent in 40 patients (51.9%). Median LS values in HCC patients with and without portal hypertension were 29.1 kPa and 19.6 kPa, respectively (r = 0.26, P < 0.04). Liver stiffness was used to implement the Barcelona Clinic Liver Cancer algorithm in decisions about treatment. CONCLUSIONS: The evaluation of liver fibrosis by transient elastography may be useful in the follow-up of patients with cirrhosis and a direct correlation with portal hypertension may aid in the evaluation of surgical risk in patients with HCC and in the choice of alternative therapies.

Comparison of clinical and pathological findings of patients undergoing elective colectomy for uncomplicated diverticulitis.

Diverticular disease affects ∼5-10% people worldwide, yet the indications for elective colectomy in uncomplicated diverticulitis are unclear. As there is no strong scientific evidence regarding histology in diverticular disease, the primary outcome of the study was to analyze the degree of inflammation of colonic wall in patients that underwent elective colectomy for uncomplicated diverticulitis and to retrospectively assess the correlation between patient clinical history and pathological features of surgical specimens in order to find some predictive factors that may be strictly correlated with histology. An observational retrospective study was conducted. Patients undergoing elective colectomy for uncomplicated diverticulitis between January 2014 and January 2016 in an academic medical center were collected. The majority of patients (46.2%) had previously encountered one episode of acute diverticulitis prior to colectomy, while 21.5% and 10.8% had experienced two and three or more prior episodes respectively. Most patients had recurrent or chronic abdominal pain in the left iliac fossa (66.2%) for diverticular disease and a large proportion also experienced constipation (40.0%). Diverticulitis was identified pathologically as being "mild" in 44.6% patients and "severe" in 55.4% patients. The mean age was significantly lower in patients with severe diverticulitis (56.7 years) than in patients with mild diverticulitis (67.0 years). 71.9% of males had severe diverticulitis compared to 39.4% of females. Males have a 3.9 times higher risk of histological severe diverticulitis than females (OR = 3.932; 1.390-11.122; p = 0.008). Multivariate logistic regression analysis confirmed that age and gender were independent factors associated with histological diagnosis. Single-institution data and retrospective design were main limitations of this study. Age and gender are independent factors associated with severity inflammation index derived at histological analysis and they could be translated to clinical practice to better categorize patients with uncomplicated diverticulitis at the bedside.

Biliary stent migration into the abdominal wall: a case report.

Biliary stent migration occurs in about 5% of patients. The most common complications secondary to stent migration are pancreatitis, small bowel perforation and peritonitis. We report the case of a patient presenting with an abdominal wall abscess secondary to migration of a biliary stent. Direct abdominal radiography, abdominal ultrasound and CT scan have proved very useful in the diagnosis, providing the correct localisation of the stent in the left rectus muscle of the abdominal wall that led to a surgical approach under local anaesthesia for the removal, and abscess formation surrounding the stent. The patient was discharged on the day after surgery. After reviewing the literature concerning this rare complication, the Authors conclude that closer monitoring of patients with biliary prostheses is needed to prevent the migration and the consequent serious complications.

Iatrogenic bile duct injury: impact and management challenges.

Iatrogenic bile duct injuries (BDIs) after laparoscopic cholecystectomy, being one of the most common performed surgical procedures, remain a substantial problem in gastrointestinal surgery with a significant impact on patient's quality of life. The primary aim of this review was to discuss the classification of BDIs, the proposed methods to prevent biliary lesions, the associated risk factors, and the management challenges depending on the timing of recognition of the injury, its extension, the patient's clinical condition, and the availability of experienced hepatobiliary surgeons. Early recognition of BDI is of paramount importance and limiting the diagnosis delay is crucial for an optimal postoperative outcome. The therapeutic management depends on the type and gravity of the biliary lesion, and includes endoscopic, radiologic, and surgical approaches.

A rare case of Krukenberg tumor by gallbladder cancer.

INTRODUCTION: Gallbladder cancer commonly spreads by direct extension to the liver and adjacent organs of the gastrointestinal tract. Ovarian metastases by biliary origin, though known, are a very uncommon finding. PRESENTATION OF CASE: We report a rare metastatic localization by gallbladder cancer, Krukenberg tumor mimicking a primitive ovarian cancer. A comprehensive critical review was performed and suggested strategies were analyzed. DISCUSSION: The prognosis of ovarian metastastes by biliary origin is very poor with an overall survival estimated at around 6 months. The variable clinical presentation, radiology and serum markers make the appropriate histological diagnosis mandatory. CONCLUSION: The presence of Krukenberg tumor should be considered in the work-up of gallbladder cancer.

Lymph node ratio and liver metachronous metastases in colorectal cancer.

AIM: The authors seek to assess whether the lymph node ratio (the ratio of positive nodes divided by the total number of retrieved nodes) could predict the risk of metachronous liver metastases. MATERIAL AND METHODS: A homogeneous group of 280 patients, followed-up for at least 5 years, was evaluated. In order to highlight the groups with the highest risk of metachronous liver metastases, patients were divided into four quartiles groups in relation to the LNR. RESULTS: The number of lymph nodes sampled in group "stage I" was significantly lower. Even if statistical significance between the global LNR and the development of liver metastases has not been reached, the subdivision into quartiles has made it possible to highlight that in the more advanced ratio groups, a higher incidence of metachronous liver metastases (p <0.028) was registered and was a different distribution of patients with or without liver metastasis in function of quartiles (P =0.01). DISCUSSION: The LNR has enabled us to prognosticate patients who are at greater risk of developing metachronous liver metastases. The lower lymph node sampling in the patients with less advanced staging (I) and in patients with nodenegative cancer (I+II) who developed liver metastases, leads us to believe that some patients have been understaged. CONCLUSION: We believe that the LNR, especially in cases of adequate lymph node sampling, is a useful gauge to better sub-stratify "node-positive" patients. KEY WORDS: Colorectal cancer, Liver metastases, Lymph node ratio.