Faculty Bibliography

Laparoscopic adjustable gastric banding is the most commonly performed operation for morbid obesity in Europe and Australia and has been shown to result in significant long-term weight loss. The US Food and Drug Administration (FDA)-monitored clinical trial results with the LAP-BAND system (INAMED Health, Santa Barbara, CA) did not reproduce the results of studies performed elsewhere in the world. This article reviews data from the first and second FDA clinical trials as well as data from continuing US clinical experience. Four American surgeons at 4 centers have performed more than 500 LAP-BAND procedures not included in the first 2 FDA clinical trials. Of these patients, 115 have been followed for at least 9 months, and 43 have been followed for at least 12 months. A retrospective analysis of prospective data gathered from these patients is presented. The percent excess weight loss was 35.6% at 9 months and 41.6% at 12 months. The average body mass index decreased from 47.5 to 38.8 in 9 months and from 47.5 to 37.3 in 12 months. There were no deaths related to the insertion of the device. Of 15 complications requiring operative management (13%) in 12 patients, there were 8 port displacements or tubing breaks (7%), 2 elective explantations (2%), 2 cases of gastric prolapse (2%), 1 gastric pouch dilatation (<1%), 1 port abscess (<1%), and 1 hemorrhage (<1%). Clinical experience with the LAP-BAND system in the United States shows the device to be a safe and effective treatment for morbid obesity, with results comparable to the international data. The combination of proper surgical technique and close patient follow-up with frequent band adjustments, performed in a comprehensive bariatric program setting, may make the LAP-BAND system a powerful surgical tool in the treatment of morbid obesity

Although the laparoscopic technique is an accepted method for elective splenectomy, it is controversial in the setting of trauma. A few reports have described laparoscopic splenorrhaphy for trauma, but none have performed laparoscopic splenectomy for splenic rupture. When the spleen is injured, vascular control and poor visibility due to bleeding present obstacles to laparoscopy. The development of the hand-assist device has helped surgeons make the transition from laparotomy to laparoscopy because of the advantages it provides, such as tactile sensation and immediate vascular control. We utilized these benefits of the hand-assist device to convert a laparoscopic operation to a hand-assisted laparoscopic operation and were thus able to avoid a laparotomy. We report a case in which the hand-assist device was used as an alternative to conversion during a laparoscopic splenectomy for ruptured spleen

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is an operation which provides one of the greatest maintained weight losses of any bariatric procedure. We looked at the safety and efficacy of laparoscopic BPD-DS for morbid obesity. METHODS: A 150-200 ml sleeve gastrectomy was created and anastomosed to the distal 250 cm of divided ileum. The median length of the common channel was 100 cm. All patients were prospectively followed up to 12 months. RESULTS: 40 consecutive patients underwent laparoscopic BPD-DS as a primary procedure for morbid obesity. Median patient body mass index (BMI) was 60 kg/m2 (range 42-85 kg/m2). Mean age was 43 +/- 1 years (+/- SEM), with 12 males and 28 females. One patient was converted to open laparotomy (2.5%). Median operative time was 210 +/- 9 minutes (range 110-360 minutes) with a significant correlation between BMI and operative time (p = 0.04). Median length of stay was 4 days (range 3-210 days). There was one 30-day mortality (2.5%). Major morbidities occurred in 6 patients (15%), including 1 anastomotic leak (2.5%), 1 venous thrombosis (2.5%), 4 staple-line hemorrhages (10%) and 1 subphrenic abscess (2.5%). Median follow-up at 6 months (range 1-12 months) resulted in 46% +/- 2% excess weight loss (EWL) and at 9 months 58% +/- 3% EWL. CONCLUSION: Laparoscopic BPD-DS is a complex, yet feasible, procedure resulting in effective weight loss with an acceptable morbidity. A BMI >65 was associated with increased morbidity and mortality. A long-term study is needed to confirm efficacy and proper patient selection

Angiogenesis has been correlated with increased invasion and metastases in a variety of human neoplasms. Inadequate inhibition of the growth of tumor microvessels by anticancer agents may result in treatment failure, rated clinically as progressive or stable disease. We have investigated the antiangiogenic properties of three camptothecin analogues, 9-amino-20(S)-camptothecin, topotecan, and camptosar (CPT-11), currently under investigation in clinical settings. Angiogenesis was induced by basic fibroblast growth factor in the cornea of inbred Swiss-Webster mice, with the aim of exploring the suppression of neovascularization by the analogues injected into the mice daily over a period of 6 days. The dose range chosen is known to inhibit, in the mouse model, the growth of various human tumor xenografts or murine tumors. The statistical analysis evaluated the association between the area of neoangiogenesis and the dose of the drugs tested and correlated the effects with observed drug toxicity. It was established that, as the drug doses increased, the area of neovascularization decreased, appearing to approximate a negative exponential curve. 9-Amino-20(S)-camptothecin at 6.89 and 8.26 micromol/kg (2.5 and 3.0 mg/kg) and topotecan at 8.31 micromol/kg (3.5 mg/kg), both drugs being delivered over a 6-day period, had statistically significant reduction (47.2-72.5%) of neoangiogenesis and acceptable toxicity. At higher doses of the two analogues, toxic body-weight losses and deaths were observed. CPT-11 showed statistically significant reduction of neoangiogenesis at a dose of 359 micromol/kg (210 mg/kg) delivered over a 6-day course. Unlike camptothecin analogues, the nontoxic dose of vincristine did not induce a statistically significant inhibition of angiogenesis, and there was no dose-dependent escalation of antiangiogenic effects. The results indicate that camptothecins are most likely cytotoxic against two tumor compartments: in addition to tumor cells of epithelial origin, the drugs act against endothelial cells and prevent the growth of the tumor microvessels. We have hypothesized that treatment failure in some patients is due to incomplete or inadequate inhibition of the microvessel growth by camptothecins. Presumably, an intensive inhibition of the remaining tumor microvasculature in such patients could be achieved by combining a camptothecin with another antiangiogenic anticancer agent or with a highly selective angiogenic inhibitor exerting minimal dose-limiting toxicity. Such treatment by a camptothecin plus a less toxic inhibitor of angiogenesis can improve antitumor efficacy. To validate this concept, preclinical studies followed by clinical trials are planned

BACKGROUND: The activation of the zymogen plasminogen to the serine protease plasmin by urokinase-type (uPA) and tissue-type (tPA) plasminogen activators (PA) is an important event in a variety of physiologic and pathophysiologic processes in mammals. Enhanced PA activity occurs during angiogenesis and has been correlated in vitro and in vivo with increased tumor aggressiveness and is an indicator of poor prognosis in a variety of tumors in humans. Preliminary studies suggest that the antiulcer drug irsogladine maleate (IM) diminishes PA activity in vitro and may inhibit angiogenesis in vivo. To define the precise mechanism of angiogenesis inhibition by IM in vivo, we tested the ability of IM to blunt angiogenesis in a mouse cornea neovascularization model performed in wild-type and PA-knockout mice. METHODS: Three days prior to pellet implantation, groups of C57Bl/6 wild-type, uPA-deficient (upA-/-), and tPA-deficient (tPA-/-) mice received IM (300 mg/kg), IM (500 mg/kg), or vehicle (0.5% carboxymethylcellulose) via oral gavage. After 3 days of treatment, hydron polymer-coated pellets of sucrose aluminum sulfate containing 100 ng of basic fibroblast growth factor (bFGF) were inserted into surgically created pockets in the cornea of each mouse. On postoperative day 6, the neovascularization of each cornea was evaluated by a blinded observer using slit lamp microscopy and photographed. Angiogenesis was quantified by calculating vascular area (mm2) +/- SEM using a modified formula for a half ellipse that incorporates calibrated vessel measurements [Vessel length (mm) x Clock hours x pi x 0.2]. RESULTS: IM treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3% (P < 0.02, P < 0.001), in tPA-deficient mice by 42.6 and 46% (P < 0.001, P < 0.001), and in uPA-deficient mice by 27.2 and 46% (P < 0.05, p < 0.001), respectively. No quantitative differences in neovascularization were observed in either treatment group between transgenic mouse strains. No toxicity was noted in any group. CONCLUSION: IM inhibits bFGF-induced angiogenesis in wild-type, tPA-knockout, and uPA-knockout mice. The observation that IM significantly diminishes angiogenesis in both PA-deficient mice and wild-type mice suggests that the mechanism of action of IM may be independent of plasminogen activation.

FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2-induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22-24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF