Lattuada E

HFE Genotype, Parenchymal Iron Accumulation, and Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

BACKGROUND & AIMS Mutations in the hemochromatosis gene (HFE) (C282Y and H63D) lead to parenchymal iron accumulation, hemochromatosis, and liver damage. We investigated whether these factors also contribute to the progression of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS We studied clinical, histologic (liver biopsy samples for hepatocellular iron accumulation), serologic (iron and enzyme levels), and genetic (HFE genotype) data from 587 patients from Italy with NAFLD and 184 control subjects. RESULTS Iron accumulation predominantly in hepatocyes was associated with a 1.7-fold higher risk of a fibrosis stage greater than 1 (95% confidence interval [CI]: 1.2-2.3), compared with the absence of siderosis (after adjustment for age, body mass index, glucose tolerance status, and alanine aminotransferase level). Nonparenchymal/mixed siderosis was not associated with moderate/severe fibrosis (odds ratio, 0.72; 95% CI: 0.50-1.01). Hepatocellular siderosis was more prevalent in patients with HFE mutations than in those without; approximately one third of patients with HFE mutations had parenchymal iron accumulation (range, 29.8%-35.7%, depending on HFE genotype). Predominantly hepatocellular iron accumulation occurred in 52.7% of cases of patients with HFE mutations. There was no significant association between either the presence of HFE mutations or specific HFE genotypes and the severity of liver fibrosis. CONCLUSIONS Iron deposition predominantly in hepatocyes is associated with more severe liver damage in patients with NAFLD. However, HFE mutations cannot be used to identify patients with hepatocellular iron accumulation.

Effects of the Beach Chair Position, Positive End-expiratory Pressure, and Pneumoperitoneum on Respiratory Function in Morbidly Obese Patients during Anesthesia and Paralysis

Background:The authors studied the effects of the beach chair (BC) position, 10 cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on respiratory function in morbidly obese patients undergoing laparoscopic gastric banding. Methods:The authors studied 20 patients (body mass index 42 ± 5 kg/m2) during the supine and BC positions, before and after pneumoperitoneum was instituted (13.6 ± 1.2 mmHg). PEEP was applied during each combination of position and pneumoperitoneum. The authors measured elastance (E,rs) of the respiratory system, end-expiratory lung volume (helium technique), and arterial oxygen tension. Pressure–volume curves were also taken (occlusion technique). Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5 ± 1 ml/kg ideal body weight) and respiratory rate (11 ± 1 breaths/min) were kept constant throughout. Results:In the supine position, respiratory function was abnormal: E,rs was 21.71 ± 5.26 cm H2O/l, and end-expiratory lung volume was 0.46 ± 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End-expiratory lung volume almost doubled (0.83 ± 0.3 and 0.85 ± 0.3 l, BC and PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no evidence of lung recruitment (0.04 ± 0.1 l in the supine and 0.07 ± 0.2 in the BC position). PEEP was associated with higher airway pressures than the BC position (22.1 ± 2.01 vs. 13.8 ± 1.8 cm H2O; P < 0.01). Pneumoperitoneum further worsened E,rs (31.59 ± 6.73; P < 0.01) and end-expiratory lung volume (0.35 ± 0.1 l; P < 0.01). Changes of lung volume correlated with changes of oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during pneumoperitoneum, only the combination of the BC position and PEEP improved oxygenation. Conclusions:The BC position and PEEP counteracted the major derangements of respiratory function produced by anesthesia and paralysis. During pneumoperitoneum, only the combination of the two maneuvers improved oxygenation.

Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease

Background/aims The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. Patients and methods 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. Results The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage >1 and >2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis >1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. Conclusions The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.

Adjustable Gastric Banding: 5-Year Experience

Background: From 1993 to 1999, 172 patients underwent adjustable silicone gastric banding (ASGB) or laparoscopic adjustable silicone gastric banding (LASGB). In 109 patients the adjustable band was placed via laparoscopy; in the other patients it was placed via laparotomy (prelaparoscopic era, conversions from other bariatric operations, conversions for laparoscopic failure). The conversion rate from laparoscopy to laparotomy was 9.3%, occurring in the early part of our experience. Methods: Mean age was 37.9 years, weight 135 ± 14.8 kg (82-218) and BMI 46.3 ± 5.4 (35.1-69.5). All patients had multiple band adjustments, temporary antisecretive, electrolyte and vitamin therapy, and follow-up per routine. Results: Weight loss at 3 years was 30.2%; mean percent loss of excess weight was 62.5%.There was no mortality.The most important technical complications were: gastric pouch dilatation that required band replacement or removal (5.8 %); mild gastric pouch dilatation reversible with adequate dietary and pharmacological treatment (4.6%); intraoperative gastric perforation (2.3%); band migration (0.6%).The band was removed in 2.3%, with conversion to another bariatric procedure in 1.1%. Conclusions: Results have been satisfactory thus far.

Preoperative laparoscopy in management of patients with carcinoma of the esophagus and of the esophagogastric junction

Adequate preoperative staging of patients with esophageal and cardia carcinoma offers the potential for a rational choice of the therapy. The aim of this study was to assess the diagnostic value of laparoscopy compared to ultrasonography (US) and computed tomography (CT) in detecting intra‐abdominal metastatic spread.

An Unusual Complication of Gastric Banding: Recurrent Small Bowel Obstruction Caused by the Connecting Tube

Laparoscopic adjustable gastric banding (LAGB) is a widely performed surgical procedure for morbid obesity. The application of this mini-invasive approach has given the benefits of shorter hospital stay, less postoperative pain and quicker functional recovery. LAGB complications are related either to the access-port, such as port-site infection or tubing disconnection, or to the band, such as band slippage, pouch dilatation, or intragastric migration. We report a case of recurrent small bowel obstruction caused by the connecting tube around a jejunal loop, in a woman who had under-gone LAGB 3 years before. The diagnosis was difficult to establish because the clinical history and examination were non-specific. A 3-dimensional CT scan was needed to explain the cause of the recurrent abdominal pain, and the small bowel loop was freed from the connecting tube at laparoscopy.

Prevention of Pouch Dilatation after Laparoscopic Adjustable Gastric Banding

Background: The major long-term complication of laparoscopic adjustable gastric banding (LAGB) is dilatation of the gastric pouch, that is reported with a frequency ranging from 1 to 25%, and often requires removal of the band. In addition to the usual recommendations of bariatric surgery centers and dietetic advice to prevent this complication, over the last 4 years we introduced a technical modification of the procedure. Methods: From Nov 1993 to Dec 2004, 684 morbidly obese patients underwent adjustable gastric banding, 83 patients by open surgery and 601 patients by laparoscopy. The first 323 patients (group A) were operated by the perigastric approach, and 57 patients (group B) were operated by the pars flaccida approach. Since Dec 2000, 304 patients (group C) were operated with a modified pars flaccida technique, which consisted in suturing the gastric lesser curvature below the band with one or two stitches to the right phrenic crus to secure the band in place. Results: In group A, the most important late complication was irreversible dilatation of the gastric pouch, which occurred in 35 patients (10.8%), and required removal of the band in 30 cases and replacement in 5. In group B, there were 3 pouch dilatations (5.2%). In group C, only 4 dilatations occurred (1.31%), which required 3 band removals and 1 band replacement. Conclusion: Dilatation of the gastric pouch appears to be dramatically reduced by our minor technical modification of band placement.

Histologic Study of Tissue Reaction to the Gastric Band: Does it Contribute to the Problem of Band Erosion?

Background: One of the major complications of gastric banding is intragastric migration of the band. The frequency ranges from 0.5% to 3.8%, and removal of the band is always required. We undertook a prospective study with the aim to determine the reasons for this significant complication in bariatric surgery. Methods: 480 morbidly obese patients underwent adjustable gastric banding in our Surgical Department, from February 1998 to October 2005. 31 of them were reoperated for different surgical problems, at an average time of 39 months after the bariatric procedure. During the reoperation, some fragments of fibro-adipose tissue in close contact with the band were removed. They were examined, focusing on the following parameters: acute and chronic inflammation, fibrosclerosis, and foreign body granulomatous reaction. Results: Histological assessment showed the presence of acute and chronic inflammation, generally of mild and medium grade; fibrosclerosis was present mostly in a severe form, indicating a biological periprosthesic wall that separates and protects the gastric wall from the band; no cases of foreign body reaction were observed, nor were silicone inclusions found inside the inflammatory cells. Conclusion: The histologic changes of periprosthesic tissue do not appear to account for endoluminal migration of the gastric band. Thus, band erosion could have a closer correlation with other causes, such as infection of the band or intraoperative surgical damage, possibly due to direct mechanical action or to the thermal effect of the electric scalpel.

Ultrasonographic evaluation of the cervical lymph nodes in preoperative staging of esophageal neoplasms

Abstract.Background: The detection of cervical lymph node metastases plays an important role in staging of patients affected by esophageal cancer to perform the best therapeutic approach. Methods: We report our experience concerning the ultrasound evaluation of the cervical area in 174 patients with esophageal cancer. Ultrasonographic evaluation of the neck can be done with a 7.5- or 10 MHz transducer in all cases, with selective scanning of the lymph node chains of the internal jugular veins and supraclavicular regions. The short-to-long axis ratio (S/L) was a useful way to detect lymph node metastasis. Histopathologic diagnoses were obtained by sonographically guided fine-needle aspiration biopsy. Results: At ultrasound examination, we found 18 (10.3%) patients with metastatic cervical nodes. Of these, 17 (94.4%) had metastatic cervical lymph nodes confirmed by cytology from fine-needle biopsy. Lymph node exceeding 5 mm in long axis and with an S/L over 0.5 showed a higher incidence of metastasis than those with an S/L under 0.5. Our experience shows a high incidence of lymph node metastases in patients with esophageal cancer localized to the thoracic supracarinal tract and in patients with cervical and lower esophageal cancer. Conclusion: In the ultrasound evaluation of nodes, the most useful parameters are size of nodes, heterogeneity of internal echoes, morphology of the margins, and the deformation caused by compressive instrumental manipulation. These criteria, indicated by the Japanese Society for Esophageal Diseases, yield a high sensitivity and diagnostic specificity when the ultrasonographic studies are performed.

Treatment of band erosion: feasibility and safety of endoscopic band removal

BackgroundBand erosion is reported with a highly variable incidence (0.3–14%) after laparoscopic adjustable gastric banding. Removal of the band is mandatory because the patient regains weight and may become symptomatic, but no consensus exists about the best method, surgical or endoscopic, for this purpose. This study aimed to evaluate the feasibility and effectiveness of endoscopic management of band erosion.MethodsIn this study, 23 patients were treated for band erosion after gastric banding: 8 from the authors’ series of 951 patients (incidence, 0.84%) and 15 referred to the authors’ surgical department from other hospitals. The endoscopic method of band removal was used in 20 cases. Because of complications associated with erosion, three patients were submitted instead to laparoscopic removal.ResultsEndoscopic removal of the band was successful for 16 of 20 patients. Four cases required conversion of the procedure to surgery: in one case due to complications with the endoscopic cutting wire and in the three remaining cases due to dense perigastric adhesions blocking the band. The follow-up evaluation of the patients who had the endoscopic removal was uneventful, with quick discharge at resumption of oral feeding. The patients who underwent laparoscopic removal had a longer hospital stay, and one patient had a leak from the anterior gastrotomy.ConclusionsDespite a few complications, endoscopic removal seems to be the procedure of choice for the treatment of band erosion. It allows quick resumption of oral feeding and rapid discharge of patients and appears to be safer and more effective than laparoscopic removal. Conversion to surgery is unlikely but possible. Therefore, the authors always recommend that the procedure be performed in the operating room.