Ronald H. Clements

Adhesion formation is reduced after laparoscopic surgery

AbstractBackground: Adhesion formation after abdominal operations causes significant morbidity. Methods: Adhesion formation in pigs was compared after placement of prosthetic mesh during celiotomy (group 1), laparoscopy with large incision (group 2), and laparoscopy (group 3). After peritoneum was excised, polypropylene mesh was fixed to the abdominal wall, then to the opposite abdominal wall in the preperitoneal space followed by peritoneal closure. Adhesion area, grade, and vascularity were measured. Results: More adhesions (p < 0.02) covered intraperitoneal mesh (7.57 ± 1.89 cm2) than covered reperitonealized mesh (2.16 ± 1.13 cm2), and adhesion grade was significantly greater (p < 0.02). Adhesion areas were significantly greater in groups 1 and 2 than in group 3 (p= 0.001 and 0.03, respectively). Adhesion grade was significantly greater in groups 1 and 2 than in group 3 (p= 0.02 and p= 0.04, respectively). Groups 1 and 2 had more vascular adhesions than group 3 (p < 0.01 and p= 0.02, respectively) Conclusions: A foreign body within the peritoneum stimulates more numerous and denser adhesions. Tissue trauma distant from the site of adhesions increases their formation. A major advantage of laparoscopic surgery is decreased adhesion formation.

Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women

The upper limit of normal for ALT activity has been recommended to be lowered to ≤30 U/L in men and ≤19 U/L in women. These changes have been suggested to be diagnostically useful in subjects with nonalcoholic fatty liver disease (NAFLD). Our aim was to investigate the prevalence and spectrum of NAFLD with regard to the new ALT guidelines in 233 women with class II/III obesity. We compared our prior reference range for ALT (ULN ≤ 30 U/L in women) with the new standard. Our study demonstrates that only 86 patients (36.9%) would be classified as having normal ALT levels compared with 169 patients (72.5%) by the new and old standards, respectively. In patients with normal ALT activity (new vs. old standard), the prevalence of fatty liver (FL: 39.5% vs 40.2%), portal fibrosis, and steatosis (IPF: 37.2% vs. 33.7%) and nonalcoholic steatohepatitis (NASH: 23.3% vs. 26%) were similar. In comparison, newly defined patients with elevated ALT levels (>19 U/L) demonstrated an increased prevalence of FL (36%) and IPF (11.6%) but a 23.8% decrease in the prevalence of NASH as compared with the old standard. The sensitivity and specificity for NASH were 42% and 80% (ALT > 30 U/L) compared with 74% and 42% (ALT > 19 U/L). In conclusion, a significant increase in the prevalence of FL and IPF is detected in subjects with elevated ALT levels with the application of the new standard. However, the diagnostic utility for ALT to identify NASH or IPF remains poor, and significant healthcare expenditures may be incurred if this standard is adopted. (HEPATOLOGY 2005.)

Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4‐12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2‐6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3‐19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6‐11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity. (HEPATOLOGY 2004;40:475–483.)

Changes in urinary and fecal incontinence symptoms with weight loss surgery in morbidly obese women.

OBJECTIVE: To examine changes in the prevalence and severity of urinary incontinence (UI) and fecal incontinence in morbidly obese women undergoing laparoscopic weight loss surgery. METHODS: In a prospective cohort study, 101 women (aged 20–55 years) with body mass index (BMI) of 40 or more underwent laparoscopic Roux-en-Y gastric bypass and were followed to 6 and 12 months. Presence, severity, and effect of UI were assessed using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Fecal incontinence was assessed by self-report of anal leakage. RESULTS: Mean BMI decreased from 48.9±7.2 presurgery to 35.3±6.5 at 6 months and 30.2±5.7 at 12 months postsurgery. Prevalence of UI decreased from 66.7% presurgery to 41.0% at 6 months and 37.0% at 12 months (P<.001; 95% confidence interval [CI] for change 18.6–40.0%). Reduction in prevalence of UI was significantly associated with decreases in BMI (P=.01). Among incontinent women who lost 18 or more BMI points, 71% regained urinary continence at 12 months. Medical, Epidemiological, and Social Aspects of Aging Questionnaire urge and stress scores decreased (both P<.001; 95% CI 0.5–1.85 and 2.71–5.34, respectively), as did scores on the Urogenital Distress Inventory (P<.001; 95% CI 8.31–16.21) and Incontinence Impact Questionnaire (P<.001; 95% CI 4.71–14.60), indicating reduction in severity. Prevalence of fecal incontinence (solid or liquid stool) decreased from 19.4% to 9.1% at 6 months and 8.6% at 12 months (P=.018; 95% CI 2.1–19.4%). CONCLUSION: Prevalence of UI and fecal incontinence decreased after bariatric surgery. Magnitude of weight loss was associated with reduction in UI prevalence, strengthening the inference that improvements are attributable to weight loss. LEVEL OF EVIDENCE: II

Macrophages in Vaginal but Not Intestinal Mucosa Are Monocyte-Like and Permissive to Human Immunodeficiency Virus Type 1 Infection

ABSTRACT Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis, and yet the role of lamina propria macrophages in mucosal HIV-1 infection has received little investigative attention. We report here that vaginal and intestinal macrophages display distinct phenotype and HIV-1 permissiveness profiles. Vaginal macrophages expressed the innate response receptors CD14, CD89, CD16, CD32, and CD64 and the HIV-1 receptor/coreceptors CD4, CCR5, and CXCR4, similar to monocytes. Consistent with this phenotype, green fluorescent protein-tagged R5 HIV-1 entered macrophages in explanted vaginal mucosa as early as 30 min after inoculation of virus onto the epithelium, and purified vaginal macrophages supported substantial levels of HIV-1 replication by a panel of highly macrophage-tropic R5 viruses. In sharp contrast, intestinal macrophages expressed no detectable, or very low levels of, innate response receptors and HIV-1 receptor/coreceptors and did not support HIV-1 replication, although virus occasionally entered macrophages in intestinal tissue explants. Thus, vaginal, but not intestinal, macrophages are monocyte-like and permissive to R5 HIV-1 after the virus has translocated across the epithelium. These findings suggest that genital and gut macrophages have different roles in mucosal HIV-1 pathogenesis and that vaginal macrophages play a previously underappreciated but potentially important role in mucosal HIV-1 infection in the female genital tract.

Inflammation anergy in human intestinal macrophages is due to Smad-induced IκBα expression and NF-κB inactivation

Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3–TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon β, which together mediate all TLR MyD88-dependent and -independent NF-κB signaling, did not phosphorylate NF-κB p65 or Smad-induced IκBα, and did not translocate NF-κB into the nucleus. Importantly, transforming growth factor-β released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-κB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-β-induced dysregulation of NF-κB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.

Internal Hernia After Gastric Bypass: Sensitivity and Specificity of Seven CT Signs with Surgical Correlation and Controls

OBJECTIVE The purpose of this study was to evaluate the sensitivity and specificity of seven CT signs in the diagnosis of internal hernia after laparoscopic Roux-en-Y gastric bypass. MATERIALS AND METHODS With institutional review board approval, the CT scans of 18 patients (17 women, one man) with surgically proven internal hernia after laparoscopic Roux-en-Y gastric bypass were retrieved, as were CT studies of a control group of 18 women who had undergone gastric bypass but did not have internal hernia at reoperation. The scans were reviewed by three radiologists for the presence of seven CT signs of internal hernia: swirled appearance of mesenteric fat or vessels, mushroom shape of hernia, tubular distal mesenteric fat surrounded by bowel loops, small-bowel obstruction, clustered loops of small bowel, small bowel other than duodenum posterior to the superior mesenteric artery, and right-sided location of the distal jejunal anastomosis. Sensitivity and specificity were calculated for each sign. Stepwise logistic regression was performed to ascertain an independent set of variables predictive of the presence of internal hernia. RESULTS Mesenteric swirl was the best single predictor of hernia; sensitivity was 61%, 78%, and 83%, and specificity was 94%, 89%, and 67% for the three reviewers. The combination of swirled mesentery and mushroom shape of the mesentery was better than swirled mesentery alone, sensitivity being 78%, 83%, and 83%, and specificity being 83%, 89%, and 67%, but the difference was not statistically significant. CONCLUSION Mesenteric swirl is the best indicator of internal hernia after laparoscopic Roux-en-Y gastric bypass, and even minor degrees of swirl should be considered suspicious.

Mucosal IL-8 and TGF-β recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells

The lamina propria of the gastrointestinal mucosa contains the largest population of mononuclear phagocytes in the body, yet little is known about the cellular mechanisms that regulate mononuclear cell recruitment to noninflamed and inflamed intestinal mucosa. Here, we show that intestinal macrophages do not proliferate. We also show that a substantial proportion of intestinal macrophages express chemokine receptors for interleukin (IL)‐8 and transforming growth factor‐β (TGF‐β), and a smaller proportion expresses receptors for N‐formylmethionyl‐leucyl‐phenylalanine and C5a, but, surprisingly, they do not migrate to the corresponding ligands. In contrast, autologous blood monocytes, which express the same receptors, do migrate to the ligands. Blood monocytes also migrate to conditioned medium (CM) derived from lamina propria extracellular matrix, which we show contains IL‐8 and TGF‐β that are produced by epithelial cells and lamina propria mast cells. This migration is specific to IL‐8 and TGF‐β, as preincubation of the stroma‐CM with antibodies to IL‐8 and TGF‐β significantly blocked monocyte chemotaxis to the stromal products. Together, these findings indicate that blood monocytes are the exclusive source of macrophages in the intestinal mucosa and underscore the central role of newly recruited blood monocytes in maintaining the macrophage population in noninflamed mucosa and in serving as the exclusive source of macrophages in inflamed mucosa.

Urinary and anal incontinence in morbidly obese women considering weight loss surgery.

OBJECTIVE: To estimate prevalence and correlates of urinary and anal incontinence in morbidly obese women undergoing evaluation for laparoscopic weight loss surgery. METHODS: From October 2003 to February 2005, 180 women with body mass index (BMI) of 40 or greater underwent evaluation for laparoscopic weight loss surgery. Using an established Web site, questionnaires were completed to assess symptoms of urinary incontinence, including the Medical, Epidemiological, and Social Aspects of Aging Questionnaire (MESA). Anal incontinence was assessed by asking, “Do you have any uncontrolled anal leakage?” A number of clinical and demographic variables were examined as potential risk factors for urinary incontinence and anal incontinence. RESULTS: Mean age was 39.8 years (range 16–55). Body mass index ranged from 40 to 81 (mean 49.5). Prevalence of urinary incontinence was 66.9% and anal incontinence was 32.0% (45.6% loss of gas only, 21.1% liquid stool only, 24.6% gas and liquid stool only, 8.8% solid stool). In simple logistic regression, presence of urinary incontinence was associated with age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01–1.09), number of children (OR 1.54, 95% CI 1.15–2.07), anal incontinence (OR 6.34, 95% CI 2.52–15.93), arthritis (OR 6.04, 95% CI 1.76–20.78), and sleep apnea (OR 2.30, 95% CI 1.21–4.37). Multivariable logistic regression identified 3 factors independently associated with urinary incontinence: number of children (OR 1.55, 95% CI 1.12–2.12), arthritis (OR 5.46, 95% CI 1.51–19.73), and anal incontinence (OR 6.27, 95% CI 2.42–16.26). Presence of anal incontinence was associated only with the presence of urinary incontinence (OR 6.34, 95% CI 2.52–15.93). CONCLUSION: Prevalence of urinary and anal incontinence is high in this group of morbidly obese women as compared with the general population. Studies are needed to determine the effect of weight loss on urinary and anal incontinence symptoms in the morbidly obese woman. LEVEL OF EVIDENCE: III

Gastrointestinal Symptoms are More Intense in Morbidly Obese Patients and are Improved with Laparoscopic Roux-en-Y Gastric Bypass

Background: Currently there are few reports comparing gastrointestinal (GI) symptoms in the morbidly obese versus control subjects or the effect of laparoscopic Roux-en-Y gastric bypass (LRYGBP) on such symptoms. Methods: A previously validated, 19-point GI symptom questionnaire was administered prospectively to each patient undergoing LRYGBP, and the questionnaire was re-administered 6 months postoperatively. Six symptom clusters (abdominal pain, irritable bowel [IBS], reflux, gastroesophageal reflux disease [GERD], sleep disturbances, and dysphagia) were compared in the following manner using Students t-test: 1) Control vs. Preop, 2) Control vs Postop, and 3) Preop vs Postop. Results are expressed as mean ± standard deviation, significance P=0.05. Results: 43 patients (40 female and 3 male, age 37.3 ± 8.6, BMI 47.8 ± 4.9) completed the questionnaire preoperatively, and 36 patients (34 female, 2 male, BMI 31.6 ± 5.3) completed the questionnaire 6 months postoperatively, for a response-rate of 84%. Abdominal pain, IBS, reflux, GERD and sleep disturbance symptoms were significantly worse in preop versus controls. Dysphagia was not different. Postop vs preop scores revealed abdominal pain, IBS, GERD, reflux, and sleep disturbance symptoms to be improved significantly. Dysphagia was not significantly different. Only dysphagia was worse when comparing postoperative to controls. No other symptom cluster was significantly different in controls vs postoperative. Conclusions: Morbidly obese patients experience more intense GI symptoms than control subjects, and many of these symptoms return to control levels 6 months after LRYGBP. Dysphagia is equivalent to control subjects preoperatively but increases significantly after LRYGBP. This data suggests another quality-of-life improvement (relief of GI symptoms) for morbidly obese patients. Further follow-up is needed to document the long-term reduction of GI symptoms.