Paolo Gentileschi

The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism

Objective:To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. Significant Background Data:The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes. Methods:Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m2 (40–53 kg/m2) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulin-like growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY). Results:Changes in mean BMI were rather minimal (43.2 kg/m2; P = not significant), but there was a significant decrease in blood glucose (P = 0.005), insulin (P = 0.02), IGF-1 (P < 0.05), leptin (P = 0.001), and an increase in ACTH levels (P = 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P < 0.01), whereas no changes in GIP levels were found in nondiabetics. Conclusions:Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB.

Evidence-Based Appraisal of Antireflux Fundoplication

Objective:To highlight the current available evidence in antireflux surgery through a systematic review of randomized controlled trials (RCTs). Summary Background Data:Laparoscopic fundoplication is currently suggested as the gold standard for the surgical treatment of gastroesophageal reflux disease, but many controversies are still open concerning the influence of some technical details on its results. Methods:Papers related to RCTs identified via a systematic literature search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes were abstracted and summarized across studies. Defined outcomes were examined for 41 papers published from 1974 to 2002 related to 25 RCTs. A meta-analysis was performed pooling the results as odds ratios (OR), rate differences (RD), and number needed to treat (NNT). Data given as mean and/or median values were pooled as a mean ± SD (SD). Results:No perioperative deaths were found in any of the RCTs. Immediate results showed a significantly lower operative morbidity rate (10.3% versus 26.7%, OR 0.33, RD −12%, NNT 8), shorter postoperative stay (3.1 versus 5.2 days, P = 0.03), and shorter sick leave (20.1 versus 35.8 days, P = 0.03) for laparoscopic versus open fundoplication. No significant differences were found regarding the incidence of recurrence, dysphagia, bloating, and reoperation for failure at midterm follow-up. No significant differences in operative morbidity (13.1% versus 9.4%) and in operative time (90.2 versus 84.2 minutes) were found in partial versus total fundoplication. A significantly lower incidence of reoperation for failure (1.6% versus 9.6%, OR 0.21, RD −7%, NNT 14) was found after partial fundoplication, with no significant differences regarding the incidence of recurrence and/or dysphagia. Routine division of short gastric vessels during total fundoplication showed no significant advantages regarding the incidence of postoperative dysphagia and recurrence when compared with no division. The use of ultrasonic scalpel compared with clips or bipolar cautery for the division of short gastric vessels showed no significant effect on operative time, postoperative complications, and costs. Conclusions:Laparoscopic antireflux surgery is at least as safe and as effective as its open counterpart, with reduced morbidity, shortened postoperative stay, and sick leave. Partial fundoplication significantly reduces the risk of reoperations for failure over total fundoplication. Routine versus no division of short gastric vessels showed no significant advantages. A word of caution is needed when implementing these results derived from RCTs performed in specialized centers into everyday clinical practice, where experience and skills may be suboptimal.

Laparoscopic Reoperative Bariatric Surgery: Experience from 27 Consecutive Patients

Background: 10 to 25% of patients undergoing bariatric surgery will require a revision, either for unsatisfactory weight loss or for complications. Reoperation is associated with a higher morbidity and has traditionally been done in open fashion.The purpose of this study was to determine the safety and efficacy of reoperative surgery using a laparoscopic approach. Methods: A retrospective review of medical records over a 22-month period was conducted. 27 consecutive obesity surgery patients, who had undergone a laparoscopic revision, were identified. 26 of the 27 patients were women. The average age was 40.3 years (range 20 to 58 years) and average original preoperative body mass index (BMI) was 51.6 kg/m2 (range 42 to 66.5).The 27 primary bariatric operations consisted of vertical banded gastroplasty (12), gastric band placement (9) and gastric bypass (6). 17 of them were open procedures. After the primary surgery, the lowest average BMI was 37.6 kg/m2 (range 21 to 52), which increased to 42.7 kg/m2 (range 29 to 56) before reoperation. 24 of the 27 reoperations were indicated for insufficient weight loss. On average, revision was undertaken 52 months after the primary procedure (range 12 to 240 months). Results: 24 of the 27 laparoscopic reoperations were conversions to a gastric bypass. A second reoperation was indicated for insufficient weight loss on four occasions. In one case, conversion to open surgery was required. The average operative time was 232 ± 18.5 minutes (range 120 to 480) and length of hospital stay was 3.7 days (range 1 to 9). 22% percent of patients (6) experienced complications, including pneumothorax, gastric remnant dilation, gastrojejunostomy stenosis, port-site hernia and protein malnutrition. There was no mortality in the study.The average BMI was 35.9 kg/m2 (range 27 to 45.5) 8 months after surgery (range 1 to 22 months). Compared with a preoperative BMI of 42.7 kg/m2, the weight loss was statistically significant (p<0.001). Conclusion: Our results compare favorably with those reported for open reoperative bariatric surgery. A laparoscopic approach may be considered a feasible and safe alternative to an open operation.

Major and minor injuries during the creation of pneumoperitoneum

Background: Lap Group Roma was established in 1999 to promote and control the development of laparoscopic surgery in the area of Rome and its province. Complications during the creation of pneumoperitoneum were given a high priority of investigation, and a retrospective enquiry was immediately carried out. Methods: A questionnaire about all laparoscopic surgical practice performed from January 1994 to December 1998 was sent to the supervisors of 28 centers of general surgery in the area of Rome and its province participating to the Lap Group Roma, requesting demographics, type of procedure for the creation of pneumoperitoneum, type and timing of operation, and major vascular, visceral, and minor vascular injuries related to the creation of pneumoperitoneum. Results: The questionnaire was returned by 57% of the centers, for a total of 12,919 laparoscopic procedures. The type of procedure used to create the pneumoperitoneum involved a standard closed approach (Veress needle + first trocar) in 82% of the cases, an open (Hasson) approach in 9% of the cases, and the use of an optical trocar in 9% of the cases. There were seven major vascular injuries (0.05%), eight visceral lesions (0.06%), and nine minor vascular lesions (0.07%), for an overall morbility of 0.18%. There was no death related to these complications. The rate of complications differed significantly (p < 0.0001) depending on the type of approach used. It was 0.27% with the optical trocar (3 of 1,009 cases), 0.18% with the closed approach (20 of 10,664 cases), and 0.09% with the open approach (1 of 1,135 cases). Conclusions: There is no foolproof technique for the creation of pneumoperitoneum, and this inquiry confirms the need of a constant search for prevention and early treatment of complications encountered during this obligatory phase of any laparoscopic approach. A well-conducted and prolonged prospective audit of clinical practice could help in identifying the risk factors that can make an alternative approach (open or video controlled) preferable to the widely used closed approach.

Evidence based medicine: open and laparoscopic bariatric surgery

BackgroundThe aim of this study was to perform an evidence-based analysis of the literature on open and laparoscopic surgery for morbid obesity.MethodsHuman studies on surgery for morbid obesity were conducted. Multiple publications of the same studies, abstracts, and case reports were reviewed. Current Content, MEDLINE, EMBASE, and Cochrane Library database were investigated.ResultsOpen Roux-en-Y gastric by pass (RYGB) for morbidly obese patients and long-limb RYGB for superobese patients are highly effective procedures. Randomized controlled trials comparing malabsorptive procedures with other bariatric operations are needed. The long-term efficacy of adjustable silicone gastric banding (ASGB) still is undetermined because of poor evidence. Laparoscopic RYGB is as safe as its open counterpart, although its long-term results are lacking. Laparoscopic ASGB is less invasive than open ASGB, although its efficacy cannot be determined because of poor evidence. Laparoscopic vertical banded gastroplasty (VBG) is becoming unpopular since the decreasing trend of open VBG. Laparoscopic biliopancreatic diversion with duodenal switch is feasible, but needs further studies.ConclusionsRandomized controlled trials comparing the various laparoscopic operations are strongly needed.

Virtual Gastroduodenoscopy: A New Look at the Bypassed Stomach and Duodenum After Laparoscopic Roux-en-Y Gastric Bypass for Morbid Obesity

Background: After open or laparoscopic Roux-en-Y gastric bypass (RYGBP) for morbid obesity, the bypassed stomach and duodenum are not readily available for radiological and endoscopic evaluation. Furthermore, little is known about the long-term physiologic and histologic changes that occur in the bypassed GI segments following these procedures. Many alternative radiological and endoscopic techniques have been described to access the distal gastric pouch and the duodenum after RYGBP. Apart from percutaneous gastrografin® studies, all these techniques require the insertion of a gastrostomy tube in the distal stomach. Methods: a new diagnostic method to access the bypassed segments by virtual CT gastroscopy (VG) was used in 5 morbidly obese patients who underwent laparoscopic RYGBP (LRYGBP). Results: All patients tolerated the procedure well, which appears safe and suitable for an outpatient setting.The virtual images offered an excellent intraluminal view of the stomach and duodenum. Conclusions: VG holds promise as the method of choice in the follow-up of LRYGB patients, having the potential to detect inflammatory changes and cancer in the excluded segments early.

Overexpression of Tissue Inhibitor of Metalloproteinase 3 in Macrophages Reduces Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice

Objective— Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of proteases and receptors. TIMP3 is downregulated in metabolic and inflammatory disorders, such as type 2 diabetes mellitus and atherosclerosis, particularly in regions enriched with monocyte/macrophage cells. To investigate the role of TIMP3 in atherosclerosis, we generated a new mouse model in which Timp3 was overexpressed in the atherosclerotic plaque via a macrophage-specific promoter (MacT3). We elucidated any potential antiatherosclerotic effects of TIMP3, including regulation of monocyte/macrophage recruitment within atherosclerotic plaques, in MacT3 mice crossbred with low-density lipoprotein receptor knockout (LDLR−/−) mice. Methods and Results— MacT3/LDLR−/− mice had an improvement of atherosclerosis and metabolic parameters compared with LDLR−/−. En face aorta and aortic root examination of MacT3/LDLR−/− mice revealed smaller atherosclerotic plaques with features of stability, such as increased collagen content and decreased necrotic core formation. Atherosclerotic plaques in MacT3/LDLR−/− mice contained fewer T cells and macrophages. Furthermore, TIMP3 overexpression in macrophages resulted in reduced oxidative stress signals, as evidenced by lower lipid peroxidation, protein carbonylation, and nitration in atheromas. Conclusion— Our study confirmed that macrophage-specific overexpression of TIMP3 decreases the inflammatory content and the amplitude of atherosclerotic plaques in mice.

Clinical Evaluation of Fibrin Glue in the Prevention of Anastomotic Leak and Internal Hernia after Laparoscopic Gastric Bypass: Preliminary Results of a Prospective, Randomized Multicenter Trial

Background: Gastro-jejunal anastomotic leak and internal hernia can be life-threatening complications of laparoscopic Roux-en-Y gastric bypass (LRYGBP), ranging from 0.1-4.3% and from 0.8-4.5% respectively. The safety and efficacy of a fibrin glue (Tissucol®) was assessed when placed around the anastomoses and over the mesenteric openings for prevention of anastomotic leaks and internal hernias after LRYGBP. Methods: A prospective, randomized, multicenter, clinical trial commenced in January 2004. Patients with BMI 40-59 kg/m2, aged 21-60 years, undergoing LRYGBP, were randomized into: 1) study group (fibrin glue applied on the gastro-jejunal and jejuno-jejunal anastomoses and the mesenteric openings); 2) control group (no fibrin glue, but suture of the mesenteric openings). 322 patients, 161 for each arm, will be enrolled for an estimated period of 24 months. Sex, age, operative time, time to postoperative oral diet and hospital stay, early and late complications rates are evaluated. An interim evaluation was conducted after 15 months. Results: To April 2005, 204 patients were randomized: 111 in the control group (mean age 39.0±11.6 years, BMI 46.4±8.2) and 93 in the fibrin glue group (mean age 42.9±11.7 years, BMI 46.9±6.4). There was no mortality or conversion in both groups; no differences in operative time and postoperative hospital stay were recorded. Time to postoperative oral diet was shorter for the fibrin glue group (P=0.0044). Neither leaks nor internal hernias have occurred in the fibrin glue group. The incidence of leaks (2 cases, 1.8%) and the overall reoperation rate were higher in the control group (P=0.0165). Conclusion: The preliminary results suggest that Tissucol® application has no adverse effects, is not time-consuming, and may be effective in preventing leaks and internal hernias in morbidly obese patients undergoing LRYGBP.

Antibiotic prophylaxis in elective laparoscopic cholecystectomy: lack of need or lack of evidence?

Background: The need to administer antibiotic prophylaxis (ABP) during laparoscopic cholecystectomy (LC) is still a matter of significant controversy. The purpose of this study was to resolve this issue by performing a meta-analysis of the available randomized controlled trials (RCT) on this topic. Methods: Papers identified via a systematic literature search were evaluated according to standard criteria. Data regarding the patient sample, study methods, and outcomes were abstracted and summarized across studies. The outcome measures were the rates of all perioperative infections, the rates of surgical site infections, and the rates of infections at other sites. Results were examined for 974 patients randomized to ABP or placebo prior to LC in six RCT published from 1997 to 2001. Results: The cumulative rates of all infections were 2.8% in the ABP group and 4.4% in the placebo group. The pooled odds ratio (OR) (95% confidence interval [CI]) was 0.69 (0.34–1.43; p = 0.32). The cumulative rates of surgical site infections were 2.1% in the ABP group and 2.9% in the placebo group. The pooled OR (95% CI) was 0.82 (0.36–1.86; p = 0.63). The cumulative rates of infections at other sites were 0.7% in the ABP group and 1.5% in the placebo group. Pooled OR (95% CI) was 0.82 (0.18–1.90; p = 0.37). No significant heterogeneity was found in any data pooling. Conclusions: Based on the available evidence, there appears to be no need to administer routine ABP to low-risk patients during LC. However, the number of patients enrolled to date into RCT is insufficient to avoid a type II error. A large and well-designed trial is urgently needed to find a conclusive answer to this question.

TIMP3 Overexpression in Macrophages Protects From Insulin Resistance, Adipose Inflammation, and Nonalcoholic Fatty Liver Disease in Mice

The tissue inhibitor of metalloproteinase (TIMP)3, a stromal protein that restrains the activity of proteases and receptors, is reduced in inflammatory metabolic disorders such as type 2 diabetes mellitus (T2DM) and atherosclerosis. We overexpressed Timp3 in mouse macrophages (MacT3) to analyze its potential antidiabetic and antiatherosclerotic effects. Transgenic mice with myeloid cells targeting overexpression of TIMP3 were generated and fed a high-fat diet for 20 weeks. Physical and metabolic phenotypes were determined. Inflammatory markers, lipid accumulation, and insulin sensitivity were measured in white adipose tissue (WAT), liver, and skeletal muscle. In a model of insulin resistance, MacT3 mice were more glucose tolerant and insulin sensitive than wild-type mice in both in vitro and in vivo tests. Molecular and biochemical analyses revealed that increased expression of TIMP3 restrained metabolic inflammation and stress-related pathways, including Jun NH2-terminal kinase and p38 kinase activation, in WAT and liver. TIMP3 overexpression in macrophages resulted in reduced activation of oxidative stress signals related to lipid peroxidation, protein carbonylation, and nitration in WAT and liver. Our data show that macrophage-specific overexpression of TIMP3 protects from metabolic inflammation and related metabolic disorders such as insulin resistance, glucose intolerance, and nonalcoholic steatohepatitis.