Rats with Long-Term Cholestasis Have a Decreased Cytosolic but Maintained Mitochondrial Hepatic CoA Pool.

Previous studies showed that rats with long-term bile duct ligation have reduced coenzyme A stores per g of liver but maintained mitochondrial CoA stores. Based on these observations, we determined the CoA pool in the liver homogenate, liver mitochondria, and liver cytosol of rats with bile duct ligation for 4 weeks (BDL rats, n = 9) and sham-operated control rats (CON rats, n = 5). In addition, we tested the cytosolic and mitochondrial CoA pools by assessing the metabolism of sulfamethoxazole and benzoate in vivo and of palmitate in vitro. The hepatic total CoA content was lower in BDL than CON rats (mean ± SEM; 128 ± 5 vs. 210 ± 9 nmol/g), affecting all subfractions equally (free CoA (CoASH), short- and long-chain acyl-CoA). In BDL rats, the hepatic mitochondrial CoA pool was maintained, and the cytosolic pool was reduced (23.0 ± 0.9 vs. 84.6 ± 3.7 nmol/g liver; CoA subfractions were affected equally). The urinary excretion of hippurate after i.p. benzoate administration (measuring mitochondrial benzoate activation) was reduced in BDL rats (23.0 ± 0.9 vs. 48.6 ± 3.7% of dose/24 h), whereas the urinary elimination of N-acetylsulfamethoxazole after i.p. sulfamethoxazole administration (measuring the cytosolic acetyl-CoA pool) was maintained (36.6 ± 3.0 vs. 35.1 ± 2.5% of dose/24 h BDL vs. CON rats). Palmitate activation was impaired in the liver homogenate of BDL rats but the cytosolic CoASH concentration was not limiting. In conclusion, BDL rats have reduced hepatocellular cytosolic CoA stores, but this reduction does not limit sulfamethoxazole N-acetylation or palmitate activation. The hepatocellular mitochondrial CoA pool is maintained in BDL rats. Impaired hippurate formation in BDL rats is explained best by mitochondrial dysfunction.

Is pain control for chronic neuropathic pain after inguinal hernia repair using endoscopic retroperitoneal neurectomy effective? A meta-analysis of 142 patients from 1995 to 2022.

PURPOSE: Neuropathic pain is a complication after groin hernia surgery. Triple neurectomy of the iliohypogastric nerve, ilioinguinal nerve and genitofemoral nerve is an efficient treatment modality, with several surgical approaches. The minimally invasive endoscopic method to neurectomy was specifically investigated in this meta-analysis. Our aim is to determine the efficacy of this method in the treatment of chronic neuropathic pain posthernia repair surgery. METHODS: A systematic review was conducted using four databases to search for the keywords ("endoscopic retroperitoneal neurectomy" and "laparoscopic retroperitoneal neurectomy"). The NCBI National Library of Medicine, Cochrane Library, MEDLINE Complete and BioMed Central were last searched on 26 May 2022. Randomised control trials and retrospective or prospective papers involving endoscopic retroperitoneal neurectomy operations after inguinal hernia repair were included. All other surgeries, procedures and study designs were excluded. The internal quality of included studies was assessed using the Newcastle-Ottawa Scale. The percentage of patients who had reduction in pain ("positive treatment outcome") was used to assess the procedure's effectiveness in each analysis. RESULTS: Five comparable endoscopic retroperitoneal neurectomy studies with a total of 142 patients were analysed. Both the Wald test (Q (6) = 1.79, = .775) and the probability ratio test (Q (6) = 4.24, = .374) provide similar findings (0.000, 0.0% [0.0%; 78%]). The meta-analysis' key finding is that the intervention was up to 78% effective (95% confidence interval, 71%; 84%). CONCLUSION: Endoscopic retroperitoneal neurectomy can be an effective treatment option for postoperative neuropathic pain relief following surgical hernia repair. Although there is limited reported experience with this technique, it may provide a clinical benefit to the patient. We recommend further prospective data and long-term follow-up studies be conducted to confirm and expand on these outcomes.

Advancements of Artificial Intelligence in Liver-Associated Diseases and Surgery.

Background and Objectives: The advancement of artificial intelligence (AI) based technologies in medicine is progressing rapidly, but the majority of its real-world applications has not been implemented. The establishment of an accurate diagnosis with treatment has now transitioned into an artificial intelligence era, which has continued to provide an amplified understanding of liver cancer as a disease and helped to proceed better with the method of procurement. This article focuses on reviewing the AI in liver-associated diseases and surgical procedures, highlighting its development, use, and related counterparts. Materials and Methods: We searched for articles regarding AI in liver-related ailments and surgery, using the keywords (mentioned below) on PubMed, Google Scholar, Scopus, MEDLINE, and Cochrane Library. Choosing only the common studies suggested by these libraries, we segregated the matter based on disease. Finally, we compiled the essence of these articles under the various sub-headings. Results: After thorough review of articles, it was observed that there was a surge in the occurrence of liver-related surgeries, diagnoses, and treatments. Parallelly, advanced computer technologies governed by AI continue to prove their efficacy in the accurate screening, analysis, prediction, treatment, and recuperation of liver-related cases. Conclusions: The continual developments and high-order precision of AI is expanding its roots in all directions of applications. Despite being novel and lacking research, AI has shown its intrinsic worth for procedures in liver surgery while providing enhanced healing opportunities and personalized treatment for liver surgery patients.

A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma.

A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression over time in contrast to TT. Standardized repeated assessments of multiple immune markers in repeated biopsies will generate detailed insights in melanoma's immune evolution and adaption during therapies and might be used to support treatment decisions.

Reversible biliary occlusion in a small animal model: first description of a new technique.

BACKGROUND: Experimental models with reversible biliary occlusion resulted in a high mortality of the animals, up to 20-60% according to the literature. Our aim was to assess a safe and valid technique for reversible biliary occlusion with a low mortality. METHODS: We randomized 30 rats into two groups: with bile duct occlusion (BDO, n=18) and with sham manipulation of the extrahepatic bile duct (control, n=12). We used a removable vascular clip for temporary occlusion of the extrahepatic bile duct. The clip was removed on postoperative day (POD) 2. On POD 2, 3, and 5, we measured the hepatocellular injury and metabolic function markers in serum. Activation of mononuclear cells (HIS36) and expression of regeneration markers [cytokeratin 19, hepatic growth factor (HGF)-α, and HGF-ß] were determined by immunohistochemistry. RESULTS: The survival rate was 96.67% (1/30); one animal died. The mortality in the BDO group was 6% (1/18) and that in the control group was 0% (0/12). BDO resulted in a sharp increase of hepatocellular injury and cholestatic parameters on POD 2 with a rapid decline till POD 3. Significantly strongest activation of Kupffer cells and expression of proliferation markers were found until POD 5 after BDO. CONCLUSION: The clip technique is a safe, cheap, and valid method for reversible biliary occlusion with an extremely low mortality.

Short-term preoperative supplementation of an immunoenriched diet does not improve clinical outcome in well-nourished patients undergoing abdominal cancer surgery.

OBJECTIVE: A recent study suggested that the anti-inflammatory effect of immunonutrition starts after only two d. We therefore investigated the effect of an immunoenriched oral diet administered for three d preoperatively. METHODS: In this prospective, randomized, double-blind, placebo-controlled study, well-nourished patients (Nutrition Risk Screening 2002 <3) with gastrointestinal cancer who were scheduled for major elective abdominal cancer surgery were randomly assigned to either 750 mL of an immunoenriched formula (IEF group) or 750 mL of an isocaloric, isonitrogenous placebo diet (Con group) for 3 consecutive d preoperatively. RESULTS: A total of 108 patients (IEF group: n = 55; Con group: n = 53) were randomized. The two groups were comparable for all baseline and surgical characteristics. The overall mortality was 2.8% and not significantly different between the two groups (IEF group: 3.6% vs. Con group: 1.9%, P = 1.00). Intention-to-treat analysis showed no difference for the incidence of postoperative overall (IEF group: 29% vs. Con group: 30%; P = 1.00) and infectious (IEF group: 15% vs. Con group: 17%; P = 0.79) complications. Length of hospital stay was 12 ± 4.9 d in the IEF group and 11.6 ± 5.3 d in the Con group (P = 0.68). CONCLUSIONS: Preoperative oral supplementation with an immunoenriched diet for 3 d preoperatively did not improve postoperative outcome compared with the placebo in well-nourished patients with elective gastrointestinal cancer surgery.

Macrophage-mediated phagocytosis of apoptotic cholangiocytes contributes to reversal of experimental biliary fibrosis.

Studies have suggested the reversibility of liver fibrosis, but the mechanisms of fibrosis reversal are poorly understood. We investigated the possible functional link between apoptosis, macrophages, and matrix turnover in rat liver during reversal of fibrosis secondary to bile duct ligation (BDL). Biliary fibrosis was induced by BDL for 4 wk. After Roux-en-Y (RY)-bilio-jejunal-anastomosis, resolution of fibrosis was monitored for up to 12 wk by hepatic collagen content, matrix metalloproteinase (MMP) expression and activities, and fibrosis-related gene expression. MMP expression and activities were studied in macrophages after engulfment of apoptotic cholangiocytes in vitro. Hepatic collagen decreased to near normal at 12 wk after RY-anastomosis. During reversal, profibrogenic mRNA declined, whereas expression of several profibrolytic MMPs increased. Fibrotic septa showed fragmentation at week 4 and disappeared at week 12. Peak histological remodeling at week 4 was characterized by massive apoptosis of cytokeratin 19+ cholangiocytes, >90% in colocalization with CD68+ macrophages, and a 2- to 7.5-fold increase in matrix-degrading activities. In vitro, phagocytosis of apoptotic cholangiocytes induced matrix-degrading activities and MMP-3, -8, and -9 in rat peritoneal macrophages. We concluded that reconstruction of bile flow after BDL leads to an orchestrated fibrolytic program that results in near complete reversal of advanced fibrosis. The peak of connective tissue remodeling and fibrolytic activity is associated with massive apoptosis of cholangiocytes and their phagocytic clearance by macrophages in vivo. Macrophages upregulate MMPs and become fibrolytic effector cells upon apoptotic cholangiocyte engulfment in vitro, suggesting that phagocytosis-associated MMP induction in macrophages significantly contributes to biliary fibrosis reversal.

EuroOOPS: an international, multicentre study to implement nutritional risk screening and evaluate clinical outcome.

BACKGROUND & AIMS: The aim of the study was to implement nutritional risk screening (NRS-2002) and to assess the association between nutritional risk and clinical outcome. METHODS: NRS-2002 was implemented in 26 hospital departments (surgery, internal medicine, oncology, intensive care, gastroenterology and geriatrics) in Austria, the Czech Republic, Egypt, Germany, Hungary, Lebanon, Libya, Poland, Romania, Slovakia, Spain and Switzerland. Being a prospective cohort study, randomly selected adult patients were included at admission and followed during their hospitalisation. Data were collected on the nutritional risk screening, complications, mortality, length of stay and discharge. The correlation between risk status and clinical outcome was assessed and adjusted for confounders (age, speciality, diagnoses, comorbidity, surgery, cancer and region) by multivariate regression analysis. RESULTS: Of the 5051 study patients, 32.6% were defined as 'at-risk' by NRS-2002. 'At-risk' patients had more complications, higher mortality and longer lengths of stay than 'not at-risk' patients and these variables were significantly related to components of NRS-2002, also when adjusted for confounders. CONCLUSIONS: Components of NRS-2002 are independent predictors of poor clinical outcome.

Laparoscopic training on Thiel human cadavers: a model to teach advanced laparoscopic procedures.

BACKGROUND: Nowadays, the laparoscopic approach represents the gold standard for a wide range of various basic and advanced procedures. To reduce the learning curve in advanced laparoscopic surgery, the search for new teaching tools is of utmost importance. Our experiences with a new teaching tool to train advanced laparoscopic procedures are reported. METHODS: Hands-on training courses in colon, hernia, bariatric and vascular surgery using Thiel human cadavers (THCs) were organised by the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS). The courses were held by consultant surgeons expert in the field of minimal invasive surgery (MIS). At the end of each course, data was collected using a standardised, anonymous questionnaire using a Likert scale (1 = strongly disagree; 2 = disagree; 3 = neither agree nor disagree; 4 = agree; 5 = strongly agree). Data are presented as mean +/- standard deviation (SD), percentages (%) or total number (n), if indicated. RESULTS: From January 2005 to May 2006, six courses (colon = 2; hernia = 2; bariatric = 1; vascular = 1) were organized with a total of 33 participants (31 consultant surgeons; two senior residents). The authenticity of tissue colour, tissue consistency and operative tactility, respectively, were stated for the courses as follows: colon (mean: 4.4/4.2/4.2), hernia (mean: 4.3/4.2/4.0), bariatric (mean: 4.5/4.8/4.3) and vascular (mean: 2.8/2.8/2.6) courses. A high mean overall satisfaction with the courses (colon: 4.0; hernia: 4.2; bariatric: 5.0 and vascular surgery: 4.1) was also observed. All participants of the colon, bariatric, hernia and vascular courses will recommend the courses to other surgeons. CONCLUSION: Training on THCs might be an excellent additional model to teach advanced bariatric, hernia and colon surgery. However, an important issue that remains to be defined is which training model (THC, anesthetized animals, virtual computer training, etc.) is the most appropriate for the curriculum of the skill or procedure that is being trained.

Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study.

BACKGROUND/AIM: Perioperative administration of immunoenriched diets attenuates the perioperative inflammatory response and reduces postoperative infection complications. However, many questions still remain unresolved in this area, such as the length of diet administration, diet composition, and the mechanisms involved. We performed an open, randomized, triple-arm study comparing the effect of two perioperative feeding regimens with a postoperative one. METHODS: 46 candidates for major elective surgery for malignancy in the upper gastrointestinal tract were randomized to drink preoperatively either 1 L of an immunoenriched formula (Impact) for 5 days (IEF group) or 1 L of Impact plus (Impact enriched with glycine) for 2 days (IEF plus group). The same product as the patient received preoperatively was given to both groups for 7 days postoperatively. In the control group (CON group), patients only received Impact for 7 days postoperatively; there was no preoperative treatment. The main outcome measures were postoperative C-reactive protein (CRP) serum levels. RESULTS: In the two preoperatively supplemented groups (treatment groups), perioperative endotoxin levels, CRP (postoperative day 7), and TNF-alpha (postoperative days 1 and 3) levels were significantly lower compared to the CON group (p < .01). Furthermore, the length of postoperative IMU/ICU stay (Impact 1.9 +/- 1.3 days; Impact plus 2.2 +/- 1.1 days; control group 5.9 +/- 0.8 days) and length of hospital stay (Impact 19.7 +/- 2.3 days; Impact plus 20.1 +/- 1.3 days; control group 29.1 +/- 3.6 days) were both reduced in the treatment groups compared to the control group. Infectious complications (Impact 2/14 (14%); Impact plus 5/17 (29%); control group 10/15 (67%)) also showed a trend toward reduction in the treatment groups. CONCLUSIONS: Perioperative administration of an immunoenriched diet significantly reduces systemic perioperative inflammation and postoperative complications in patients undergoing major abdominal cancer surgery, when compared with postoperative diet administration alone. A shortened preoperative feeding regimen of 2 days with Impact enriched with glycine (Impact plus) was as effective as Impact administered for 5 days preoperatively.

Risk factors for perioperative complications in patients undergoing laparoscopic cholecystectomy: analysis of 22,953 consecutive cases from the Swiss Association of Laparoscopic and Thoracoscopic Surgery database.

BACKGROUND: Reliable risk factors for perioperative complications in patients undergoing laparoscopic cholecystectomy would be extremely useful to optimize the clinical management. This study aimed to determine risk factors that can be used for predicting perioperative complications. STUDY DESIGN: Possible risk factors for perioperative complications in patients undergoing laparoscopic cholecystectomy for acute and chronic cholecystitis were analyzed by a stepwise logistic regression model using data from the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS) database. RESULTS: A total of 22,953 patients with a mean (+/-SD) age of 54.5+/-16.1 years (range 17 to 89 years) and a male-to-female ratio of 1:2, underwent elective (85%) and emergency (15%) laparoscopic cholecystectomy. Multivariable analysis showed that male gender (odds ratio [OR]=1.16; p<0.0001), duration of intervention (OR=1.68 per 30 minutes; p<0.0001), body weight (>90 kg versus<60 kg; OR=1.34; p<0.0001), and the surgeon's own experience (>100 versus 11 to 100 interventions; OR=1.36; p<0.0002) were independently associated with an increased intraoperative local complication rate. In addition, male gender (OR=1.21; p<0.02), age (OR=1.12 per 10 years; p<0.0001), intraoperative complications (OR=2.1; p<0.0001), conversion to open surgery (OR=1.25; p<0.01), American Society of Anesthesiologists risk score (ASA score III/IV versus I/II: OR=1.28; p<0.0005), body weight (<60 kg versus>90 kg; OR=1.53; p<0.007), emergency surgery (OR=1.36; p<0.003), and duration of surgery (OR=1.28 per 30 minutes; p<0.0001) were found to be associated with a higher incidence of postoperative local complications. Higher postoperative systemic complications were encountered with conversion (OR=1.5; p<0.0002), ASA score (III/IV versus I/II: OR=1.54; p<0.0001), emergency surgery (OR=1.41; p<0.001), and a prolonged intervention time (OR=1.16 per 30 minutes; p<0.0001). CONCLUSIONS: For patients undergoing laparoscopic cholecystectomy (LC), the risk of possible perioperative complications can be estimated based on patient characteristics (gender, age, ASA score, body weight), clinical findings (acute versus chronic cholecystitis), and the surgeon's own clinical practice with LC. So in the likelihood of a case being a "difficult cholecystectomy," an experienced surgeon should be involved both in the decision-making process and during the operation. If LC lasts longer than 2 hours, the cumulative risk for perioperative complications is four times higher compared with an intervention that lasts between 30 and 60 minutes, independent of the surgeon's personal skills with LC.

Laparoscopic surgery for benign lesions of the pancreas.

BACKGROUND: Minimally invasive pancreatic surgery, although known to be feasible and safe, is still not considered a standard procedure. We report our experience with laparoscopic pancreatic surgery in a retrospective case series. MATERIALS AND METHODS: Fifteen consecutive patients (3 male, 12 female) underwent primarily laparoscopic pancreatic surgery from February 2000 to June 2005. Histologically confirmed diagnoses were: neuroendocrine pancreatic tumors (n = 11), adult nesidioblastosis (n = 1), serous cystadenoma (n = 1), and pseudocysts due to chronic pancreatitis (n = 2). RESULTS: Enucleation (n = 3) or left pancreatic resection with spleen preservation (n = 6) was performed laparoscopically in 9 patients. The mean (+/-standard deviation) operative time was 173 +/- 48 minutes (range, 120-250 minutes) and the mean postoperative hospital stay was 5.5 +/- 1.2 days (range, 5-8 days) for the laparoscopic cases. Conversion to open surgery was necessary in 6 patients because of: closeness of the lesion to the portal/mesenteric vein (n = 3), inadequate intraoperative tumor localization (n = 2), or stapler device dysfunction (n = 1). In these patients, open enucleation (n = 1), middle segment pancreatectomy (n = 2), left pancreatic resection (n = 2), and pylorus-preserving Whipple resection (n = 1) were performed. The mean operative time was 268 +/- 74 minutes (range, 150-360 minutes) with a mean postoperative hospital stay of 8 +/- 2 days (range, 6-10 days). Both operative time and hospital stay were significantly longer in patients with secondary open surgery compared to patients with successful laparoscopic operations. CONCLUSION: Laparoscopic enucleation or distal pancreatectomy with spleen preservation for benign lesions located in the body or tail of the pancreas can be performed safely, with all the potential benefits of minimally invasive surgery. Preoperative tumor localization is of utmost importance to limit pancreatic mobilization and to avoid blind pancreatic resection and conversion to open surgery.

Recurrent hypoglycaemia in HIV-positive narcotic addicts.

QUESTIONS UNDER STUDY: We describe two narcotic addict women with recurrent hypoglycaemic episodes. In both patients, hyperinsulinaemic hypoglycaemia occurring in the fasting state was documented and computed tomography of the pancreas was normal. METHODS AND RESULTS: In patient 1, selective arterial calcium stimulation with hepatic venous sampling (ASVS) revealed pronounced insulin hypersecretion predominantly in the tail and, to a lesser extent, in the corpus and the head of the pancreas. On laparoscopic exploration, tumours could not be detected be it grossly or by intraoperative ultrasound. Distal pancreatectomy was performed laparoscopically, and histological examination of the resected tissue revealed nesidioblastosis. ASVS was also performed in patient 2 revealing less marked increases in insulin secretion, ie up to 2.3-fold in response to calcium stimulation of the superior mesenteric artery, consistent with the presence of pathological beta-cells located predominantly in the head of the pancreas. Surgical exploration was not performed in this patient. CONCLUSION: HIV infection had been known in both women for around ten years and both patients were not on antiretroviral therapy. Because symptomatic nesidioblastosis in adult patients is a very rare disorder, we speculate that nesidioblastosis may develop in the context of HIV infection and/or abuse of narcotic drugs. Our observations illustrate that neurocognitive impairment in HIV positive patients is not always due to toxic compounds or a cerebral disorder but may be caused by an apparently rare pancreatic disorder, nesidioblastosis. Thus, the patients should be checked for the presence of hyperinsulinaemic hypoglycaemia.

Bleeding remains a major complication during laparoscopic surgery: analysis of the SALTS database.

BACKGROUND AND AIMS: The aim of this study was to determine the incidence of bleeding complications from various laparoscopic procedures in a nationwide prospective multicentre study in Switzerland from 1995 to 2001 following an initial learning curve. PATIENTS AND METHODS: Since 1989, the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS) has prospectively collected data from patients undergoing laparoscopic or thoracoscopic surgery at 114 surgical institutions (university, county and district hospitals, private practice). More than 130 items of data, including indication for surgery, intraoperative course, local as well as general postoperative complications, mortality and follow-up were recorded on a computerised data sheet. RESULTS: Some 43,028 procedures were assessed and analysed. Local morbidity (e.g. wound infections) occurred in 0.05% of the whole patient group, whereas 3.3% developed general postoperative complications. The overall mortality rate was 0.2%. In 1.7% of the cases, the intraoperative course was complicated by internal bleeding or haematoma of the abdominal wall. In the postoperative course, 1.5% of the patients presented with internal bleeding or bleeding of the abdominal wall. Major vascular injury occurred in 0.09%. This patient group with bleeding complications was analysed in the context of the operator's experience, instrumental lesions (Veress needle or trocar) and conversion incidence. Furthermore, a trend analysis of the complication rate from 1995 to 2001 was performed. CONCLUSION: Although the initial learning curve of laparoscopic procedures is probably finished, the rate of bleeding complications is still substantial. These results demonstrate that the collection of data in the form of multicentre studies is essential for quality control. It permits recognition and understanding of the current problems in laparoscopic surgery in order to improve the quality of daily surgical practice. The fact that the operator's experience seems to play an important role shows that improvement in learning and teaching programmes is still necessary and should be coordinated on a national basis.

Selective arterial calcium stimulation and hepatic venous sampling in the evaluation of hyperinsulinemic hypoglycemia: potential and limitations.

PURPOSE: To describe the potential and limitations of selective arterial calcium stimulation and hepatic venous sampling (ASVS) in the evaluation of patients with hyperinsulinemic hypoglycemia. MATERIALS AND METHODS: Twenty-seven consecutive adult patients with documented hyperinsulinemic hypoglycemia undergoing an ASVS test and histologically confirmed diagnosis were included. RESULTS: By histology, 24 patients were found to have an insulinoma, two had islet cell hyperplasia, and one had insulin-secreting neuroendocrine carcinoma of the liver. ASVS correctly predicted the source of excessive insulin secretion in 26 of 27 (sensitivity, 96%) patients. In two patients with an insulinoma, ASVS had to be repeated for correct diagnosis; in one patient with a glucose-sensitive insulinoma, ASVS was falsely negative. In one patient, a falsely negative ASVS test was caused by diazoxide treatment; in another patient a falsely negative ASVS test occurred because of extraordinarily high baseline insulin levels when the calcium stimulation was performed. CT and/or MR imaging correctly predicted the source of excessive insulin secretion in 59% of patients, the sensitivity of the intraoperative exploration was 88%. CONCLUSIONS: In the authors' experience, the ASVS test is superior to CT/MR imaging and even the intraoperative exploration in identifying the source of excessive insulin secretion in patients with hyperinsulinemic hypoglycemia. To prevent false negative ASVS tests, medications with an influence on insulin secretion have to be discontinued prior to ASVS and two baseline blood samples should be obtained before the calcium stimulation is performed.

Reduced hepatic glycogen stores in patients with liver cirrhosis.

BACKGROUND: Patients with alcoholic liver cirrhosis have reduced hepatic glycogen stores but the mechanisms leading to this finding are not clear. METHODS: We therefore determined the hepatic glycogen content in patients with alcoholic (n = 9) or biliary cirrhosis (n = 8), and in control patients undergoing liver surgery (n = 14). All patients were in the postabsorptive state. In addition, we performed a morphometric analysis of the livers, and measured activities and mRNA expression of several enzymes involved in glycogen metabolism. Cirrhotic and control patients were similar regarding age and body weight. RESULTS: Cirrhotic patients had a reduced glycogen content per gram liver wet weight (17 +/- 11 versus 45 +/- 17 mg/g, P < 0.05), per milliliter hepatocytes (28 +/- 16 versus 52 +/- 21 mg/ml, P < 0.05) and per liver (28 +/- 17 versus 64 +/- 22 g, P < 0.05), the reduction being observed in both patients with alcoholic or biliary cirrhosis. Liver histology confirmed these findings and revealed that the decrease in liver glycogen in cirrhotic patients was not homogeneous across cirrhotic lobules. Activities of glycogen synthase and phosphorylase (total activity and active form) were not different between cirrhotic and control patients, whereas hepatic mRNA expression was decreased in cirrhotics by approximately 50%. The activity of glucokinase was decreased in cirrhotic as compared in control patients (0.06 +/- 0.30 versus 0.42 +/- 0.21 U/ml hepatocytes, P < 0.05), the reduction being observed in both patients with alcoholic or biliary cirrhosis. CONCLUSIONS: We conclude that patients with alcoholic or biliary cirrhosis have decreased hepatic glycogen stores per volume of hepatocytes and per liver. Decreased activity of glucokinase may represent an important mechanism leading to this finding.

Impact of laparoscopic and conventional surgery on Kupffer cells, tumor-associated CD44 expression, and intrahepatic tumor spread.

BACKGROUND: The oncologic feasibility of laparoscopic surgery for the cure of colorectal cancer is under debate. The effect of laparoscopic colorectal cancer resection on hepatic tumor spread has not yet been clarified. HYPOTHESIS: Laparoscopic surgery affects cell-mediated immune response and hepatic tumor spread dependent on intraperitoneal insufflation. METHODS: Thirty WAG/Rij rats were randomized into 3 operative groups: carbon dioxide (CO( 2)) laparoscopy (n = 10), "gasless" laparoscopy (n = 10), and laparotomy (n = 10). To induce liver metastases, 50 000 CC531 colon carcinoma cells were injected into the portal vein during either laparoscopy or laparotomy. Twenty-eight days after injection, specimens were explanted, sectioned, and examined immunohistochemically for CC531 tumor cells (monoclonal antibody CC52), CD44v5, v6 (monoclonal antibody OX49), and Kupffer cells (monoclonal antibody HIS36). For quantification, a morphometric analysis system was applied. Data were analyzed using the Kruskal-Wallis, Dunn, and Holm tests. RESULTS: No statistically significant differences in hepatic tumor growth were found between CO(2) laparoscopy and laparotomy (P =.37). However, compared with CO(2) laparoscopy and laparotomy, a significant decrease in intrahepatic tumor growth was found after gasless laparoscopy (P =.02). Kupffer cells had significantly decreased after CO(2) laparoscopy and laparotomy compared with after gasless laparoscopy (P<.001 and P =.002, respectively). CD44v5, v6 expression was significantly increased after CO(2) laparoscopy and laparotomy compared with after gasless laparoscopy (P =.002 and P =.05, respectively). CONCLUSIONS: Hepatic resistance to tumor growth is best preserved by gasless laparoscopy as opposed to CO(2) laparoscopy or laparotomy. The amount of intra-abdominal pressure with circulatory changes rather than the used gas may explain this finding. On the other hand, conventional laparoscopy vs laparotomy did not preserve hepatic immune function.

Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction.

BACKGROUND/AIMS: Rats with long-term cholestasis have reduced ketosis of unknown origin. METHODS: Fatty acid metabolism was studied in starved rats with biliary obstruction for 4 weeks (bile duct ligated rats = BDL rats), and 3, 7, 14, 28 and 84 days after reversal of biliary obstruction by Roux-en-Y anastomosis (RY rats), and in sham-operated control rats. RESULTS: BDL rats had reduced beta-hydroxybutyrate concentrations in plasma (0.25 +/- 0.10 vs. 0.75 +/- 0.20 mmol/l) and liver (2.57 +/- 0.20 vs. 4.63 +/- 0.61 micromol/g) which increased after restoring bile flow. Hepatic expression and activity of carnitine palmitoyltransferase I (CPT I) or CPT II were unaffected or decreased in BDL rats, respectively, and increased after restoring bile flow. Oxidative metabolism of different substrates by isolated liver mitochondria and activation of palmitate were reduced in BDL rats and recovered 7-14 days after restoring bile flow. Ketogenesis was decreased in mitochondria from BDL rats and recovered 3 months after restoring bile flow. Both mRNA and protein expression of hydroxymethylglutaryl-coenzyme A synthase (HMG-CoA synthase), the rate-limiting enzyme of ketogenesis, was reduced in livers of BDL rats and increased after reversing biliary obstruction. CONCLUSIONS: In BDL rats, impairment of hepatic fatty acid metabolism is multifactorial. After reversing biliary obstruction, reduced activity of HMG-CoA synthase is the major factor.

Liver surgery in the era of tissue-preserving resections: early and late outcome in patients with primary and secondary hepatic tumors.

During recent decades, the understanding of the segmental-oriented liver anatomy has enabled development of resection of isolated liver segments or sectors as dictated by the localization and extent of the mass lesion. These newer surgical procedures provide the advantage of maximal preservation of functional parenchyma, therefore minimizing the occurrence of postoperative liver failure and, at the same time, expanding the indications for surgery. We analyzed the results after classical hemihepatectomies and segment-based resections in a consecutive, nonselected patient group. During the 7-year period between November 1993 and November 2000, 270 patients with primary or secondary liver tumors were treated in our hospital; 167 of these patients underwent curative resections and their relevant data were entered into a statistical database. There were 77 classical hemihepatectomies and 90 tissue-preserving resections. Total mortality and morbidity for the series was 3.6% and 29.9%, respectively. Morbidity but not mortality was significantly lower after tissue-preserving resections than after classical hemihepatectomy. Median follow-up was 36 months. Survival was comparable for the two different surgical approaches for patients with secondary liver malignancies. In contrast, patients with hepatocellular carcinomas lived significantly longer after tissue-preserving resections. Tissue-preserving liver resection is a safe technique allowing maximal preservation of functional parenchyma without compromising radicality. Therefore, tissue-preserving resection is especially useful for patients with hepatocellular carcinomas and cirrhosis.