Francesco De Marchi

Outcome Predictors in Morbidly Obese Recipients of an Adjustable Gastric Band

Background: The authors investigated the outcome predictors in obese patients who underwent laparoscopic adjustable banding with the Lap-Band®. Methods:The 3-year excess weight loss (EWL) and rate of band-related complications (pouch dilatation and port leackage) were analyzed in 260 morbidly obese patients, according to several possible predictive characteristics. Success rate (EWL >50%), failure rate (EWL < 20%) and weight regain rate (regain of >10%EWL between 1 and 3 yrs) were considered. Results: The Lap-Band® produced a 43.0±22.3% EWL, corresponding to a BMI reduction from 46.6±7.0 to 36.8±6.6 kg/m2. Success rate was 35.7%, failure rate was 14.1% and weight regain rate was 20.7%. Pouch dilatation occurred in 32 patients (12.3%), band erosion in 2 (0.8%), port leakage in 74 (28.5%), and port twisting in 2 (0.8%). Major band-related surgery was requested in 11 patients (4.2%) and minor port-related surgery in 62 patients (23.9%). Significant success predictors were found to be age <40 years and BMI <50 kg/m2. Significant failure predictors were found to be male sex and non-sweet eating behavior. Significant weight regain predictors were found to be BMI <50 kg/m2 and the occurrence of a port leakage. Port leakage was significantly more frequent in women and in patients with BMI <50 kg/m2. The prevalence of pouch dilatation was threefold higher in women than in men. Conclusions: Lap-Band® was associated with a good outcome and with a low rate of severe complications. The outcome was more influenced by physiological and technical reasons than by psychological or behavioural factors.

Weight loss and postoperative complications in morbidly obese patients with binge eating disorder treated by laparoscopic adjustable gastric banding.

Background: The authors investigated the outcome of morbidly obese patients with binge eating disorder (BED) treated surgically with laparoscopic adjustable gastric banding. Methods: The 5-year outcomes of 130 patients with BED and 249 patients without BED are described. The diagnosis of BED was made preoperatively and all patients with BED were supported with psychological therapy. Results: Patients with and without BED had similar BMI levels before surgery. More patients with than without BED had depressive symptoms and associated minor disturbances of eating behavior (night eating and grazing). Percent excess weight loss (%EWL) in the first 5 years after surgery was similar in patients with and without BED. The percentage of BED patients showing %EWL >50% at the 5-year evaluation was 23.1, and 25.7% in non-BED patients. The percentage of patients showing weight regain in the last 4 years of follow-up was similar in binge eaters (20.8%) and in non-binge eaters (22.5%). The 5-year frequency of gastric pouch and esophageal dilatation was significantly higher in binge eaters than in non-binge eaters (25.4 vs 17.7 %, P<0.05 and 10.0 vs 4.8%, P<0.05, respectively). Binge eaters underwent a higher number of postoperative band adjustments than non-binge eaters (3.0±2.1 vs 2.6±1.9, P<0.05) and the maximum band fill after surgery was higher in the BED patients than in non-BED patients (3.2±1.2 vs 2.8±1.3 ml, P<0.01). Conclusion: Morbidly obese patients with BED supported by adequate psychological treatment can have good outcomes after gastric banding.

Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial.

BACKGROUND: Transanal local excision has been suggested as an attractive approach for patients with rectal cancer who show a major clinical response after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the impact of transanal local excision on the local recurrence of rectal cancer in patients who had a major clinical response after preoperative chemoradiotherapy. DESIGN: Sequential 2-stage phase II study for early efficacy. SETTING: Multicenter study. PATIENTS: Patients with clinical T3 or low-lying T2 rectal adenocarcinoma that showed a major clinical response after a preoperative chemoradiotherapy. Eligible patients underwent a full-thickness transanal local excision. According to their histopathology, the patients staged as ypT0-1 were observed, while the remaining patients were recommended to undergo a subsequent total mesorectal excision. MAIN OUTCOME MEASURES: A local recurrence rate of ⩽5% was set as a successful rate for stopping the trial early after the first stage. RESULTS: The study group included 63 patients. Before chemoradiotherapy, patients were staged as clinical T3 (n = 42) and T2 (n = 21). After the local excision, 43 patients fulfilled the criteria to be observed with no further treatment. Nine of the remaining 20 patients for whom a subsequent total mesorectal excision was recommended refused surgery. Two of these patients who refused surgery had intraluminal local recurrence; both had a ypT2 tumor and underwent salvage surgery. The estimated cumulative 3-year overall survival, disease-free survival and local disease-free survival were 91.5% (95% CI: 75.9–97.2), 91.0% (95% CI: 77.0–96.6) and 96.9% (95% CI: 80.3–99.5), respectively. LIMITATIONS: The time of follow-up is still short and the sample size is limited. CONCLUSIONS: Our data suggest that local excision is a good option for patients with a major clinical response after chemoradiotherapy. A longer period of follow-up is required to confirm these findings.

Bariatric Analysis and Reporting Outcome System (BAROS) Applied to Laparoscopic Gastric Banding Patients

Background: The definition of success and failure of a bariatric procedure should include weight loss as well as improvement in comorbidity and quality of life assessment. The Bariatric Analysis and Reporting Outcome System (BAROS), introduced by Oria and Moorhead in 1997, seems to provide a standard for comparison in the surgical treatment of morbid obesity. Methods: 180 morbidly obese and super-obese patients, who underwent laparoscopic gastric banding (lap-band) at our institutions and had a follow-up > 18 months (19-55 months) were evaluated with BAROS. Results: The patients were divided into four outcome groups (failure, fair, good, and excellent) based on a scoring table that adds or subtracts points while evaluating three main areas: percentage of excess weight loss, changes in medical conditions, and assessment of quality of life. Points were deducted for complications and reoperative surgery. Conclusions: The BAROS outcome system has proved to be a useful instrument in evaluating midterm results in our series of lap-band patients.

Variation in Lipid Levels in Morbidly Obese Patients Operated with the LAP-BAND® Adjustable Gastric Banding System: Effects of Different Levels of Weight Loss

Background: A moderate weight loss is known to improve the lipid levels in simple obesity.The extent of weight loss needed to achieve a clinically meaningful effect on lipid abnormalities in morbid obesity is little understood.We analyzed the effects of different levels of body weight loss on the lipid levels of morbidly obese patients operated with the LAPBAND® System. Methods: 225 morbidly obese patients (172 F and 53 M) in which a complete lipid profile has been collected both before and 12-18 months after surgery were studied. The changes of the lipid profile were analyzed according to different levels of percent weight loss (%WL: <10%, 10-20%, 20-30%, >30%). Results: Mean weight loss was 30.7±15.2 kg, corresponding to a 23.1±9.7% reduction of body weight. A large variability in the weight loss was observed. A significant difference in the change of the lipid parameters between the group with <10%WL and the group with 10-20%WL was observed for total-cholesterol (+10.0±17.2% vs-0.7±14.7%; p<0.05), for the LDL (+18.7±26.3% vs +3.1±22.9%; p<0.05), and for the triglycerides (+7.7±26.3% vs -21.9±25.4%; p<0.05). No further significant differences were found between the two groups with greater weight loss (20-30%WL and >30%WL) and the group with 10-20%WL, the only exception being the percent change in triglycerides levels, i.e. higher in the group with %WL >30 (-33.6±31.5% vs -21.9±25.4%; p<0.05). Conclusion: A moderate weight loss of 10-20% of initial body weight produced the maximal effects on the lipid levels in morbid obesity.

Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker

The identification of prognostic determinants of colorectal cancer (CRC), including prediction of occult metastasis, is of urgent consideration, based on the tremendous differences in outcome and survival between patients who present with metastasis or develop metastasis versus those patients with organ-confined or nonrecurrent disease. Currently, a great deal of attention has been focused on using gene expression profiles of tumor specimens as a launch point for prognostic biomarker discovery. In our study, we chose to focus on functional protein-based pathway biomarkers as a new information archive because it is these proteins that form the functional signaling networks that control cell growth, motility, apoptosis, survival, and differentiation. We used reverse-phase protein microarray analysis of laser capture microdissected CRC tumor specimens to profile broad cell signaling pathways from patients who presented with liver metastasis versus patients who remained recurrence free after follow-up. Our results indicate that members of the EGFR and COX2 signaling pathways appear differentially activated in the primary tumors of patients with synchronous metastatic disease. If validated in larger study sets, this pathway defect might be useful as a prognostic clinical tool as well as a guide to potential therapeutic intervention strategies that target occult disease and/or preventative measure.

Protein pathway biomarker analysis of human cancer reveals requirement for upfront cellular-enrichment processing.

Tissues are complex structures composed of different cell types, each of which present specific functions and characteristics. To better understand and measure the effect of tumor cell enrichment on protein pathway profiling and drug target activation measurements, the signaling activation portraits of laser capture microdissected (LCM) cancer epithelium and tumor stroma were compared with patient-matched whole-tissue specimens from 53 primary colorectal cancer samples. Microdissected material and whole-tissue lysate from contiguous cryostat sections were subjected to reverse-phase protein microarray analysis to determine the level of phopshorylation and expression of 75 different proteins known to be involved in cancer progression. The results revealed distinct differences in the protein activation portraits of cancer epithelium and stroma. Moreover, we found that the signaling activation profiles of the undissected whole-tissue specimens are profoundly different from the matched LCM material. Attempts to rescale the undissected pathway information based on percent endogenous tumor epithelium content were unsuccessful in recapitulating the LCM tumor epithelial signatures. Analysis of epidermal growth factor receptor phosphorylation and COX2 expression in these same sample sets revealed wholesale differences in the rank ordering of patient determination when LCM was compared with undissected samples. On the basis of these data, we conclude that accurate protein pathway activation status, which is under evaluation as a basis for patient selection and stratification for personalized therapy, must include upfront cellular-enrichment techniques such as LCM to generate accurate drug target activation status.

Postoperative Management of Laparoscopic Gastric Banding

Background:The authors investigated the postoperative management of morbidly obese patients treated by laparoscopic adjustable gastric banding (LAGB) with the Lap-Band® System. Methods: The 3-year postoperative band management is presented in 379 morbidly obese patients, divided according to intra-operative band filling and quartiles of maximum postoperative band filling. Results: LAGB resulted in a 40.8±24.5 percent excess weight loss (%EWL). Stoma stenosis occurred in 87 patients (23.0%), pouch dilatation in 52 (13.7%) and esophageal dilatation in 22 (5.8%). Most bandrelated complications were controlled by simple band deflation. The mean number of postoperative band adjustments was 2.3±1.7, and mean maximum band filling after surgery was 2.8±1.2 ml. Weight loss at 3 years was identical in 205 patients who had the band completely unfilled at surgery and in 174 patients who had the band filled with 1 to 3 ml of sterile saline.The rate of band-related complications was significantly lower in the first group. No differences in %EWL were observed between quartiles of maximum band filling after surgery.The rate of band-related complications increased with increasing levels of postoperative maximum band filling. In patients with the band filled with <3.0 ml of sterile saline at 6 months, the inflation of further saline produced a dose-related increase in the rate of weight loss. In patients with the band filled with ≥ 3.0 ml of sterile saline at 6 months, the inflation of further saline was associated with a reduced %EWL. Conclusion: Postoperative adjustability of the LapBand® was useful in the treatment of band-related complications and was able to significantly influence the rate of weight loss. On the other hand, aggressive postoperative band filling was associated with an increased rate of complications.

The Influence of a New Timing Strategy of Band Adjustment on the Vomiting Frequency and the Food Consumption of Obese Women Operated with Laparoscopic Adjustable Silicone Gastric Banding (LAP-BAND)

Objective: To evaluate the effects of a new timing strategy of band adjustment on the short-term outcome of obese women operated with adjustable silicone gastric banding. Subjects: The outcome of 30 women without binge-eating disorder operated with laparoscopic adjustable silicone gastric banding with a wider intraoperatory band calibration (LAP-BAND) was compared to that of 30 body mass index-matched women without binge-eating disorder previously operated with adjustable silicone gastric banding (ASGB) applied by laparotomy with the usual intraoperatory band calibration. The patients were evaluated 3, 6 and 12 months after surgery. Measurements: (1) weight loss; (2) total daily energy intake; (3) percent as liquid, soft or solid food; (4) vomiting frequency; (5) rate of postoperative percutaneous band adjustments; (6) rate of band-related complications. Results: Both the weight loss and the daily energy intake did not differ between patients with LAP-BAND and patients with ASGB. After surgery, the patients with LAP-BAND ate more solid food and less liquid food than the patients with ASGB. Vomiting frequency was higher in patients with ASGB than in patients with LAP-BAND. The total number of percutaneous band adjustments was higher in women with LAP-BAND than in women with ASGB. Band inflation because of weight stabilization was performed in six (20.0%) women with ASGB and in 19 (63.3%) women with LAP-BAND. Neostoma stenosis occurred in one women with ASGB, but in none of the women with LAP-BAND. One patient with LAP-BAND presented band slippage. Conclusions: The wider intraoperatory band calibration performed in patients with LAP-BAND did not reduce the short-term efficacy of adjustable silicone gastric banding. This new timing strategy of band adjustment required more postoperative percutaneous band inflations, but it improved the eating pattern of the patients (low vomiting frequency and high intake of solid food).

Protein pathway activation mapping of colorectal metastatic progression reveals metastasis-specific network alterations.

The mechanism by which tissue microecology influences invasion and metastasis is largely unknown. Recent studies have indicated differences in the molecular architecture of the metastatic lesion compared to the primary tumor, however, systemic analysis of the alterations within the activated protein signaling network has not been described. Using laser capture microdissection, protein microarray technology, and a unique specimen collection of 34 matched primary colorectal cancers (CRC) and synchronous hepatic metastasis, the quantitative measurement of the total and activated/phosphorylated levels of 86 key signaling proteins was performed. Activation of the EGFR–PDGFR-cKIT network, in addition to PI3K/AKT pathway, was found uniquely activated in the hepatic metastatic lesions compared to the matched primary tumors. If validated in larger study sets, these findings may have potential clinical relevance since many of these activated signaling proteins are current targets for molecularly targeted therapeutics. Thus, these findings could lead to liver metastasis specific molecular therapies for CRC.