Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity.

BACKGROUND: The surgical treatment of obesity in the high-risk, high-body-mass-index (BMI) (>60) patient remains a challenge. Major morbidity and mortality in these patients can approach 38% and 6%, respectively. In an effort to achieve more favorable outcomes, we have employed a two-stage approach to such high-risk patients. This study evaluates our initial outcomes with this technique. METHODS: In this study, patients underwent laparoscopic sleeve gastrectomy (LSG) as a first stage during the period January 2002-February 2004. After achieving significant weight loss and reduction in co-morbidities, these patients then proceeded with the second stage, laparoscopic Roux-en-Y gastric bypass (LRYGBP). RESULTS: During this time, 126 patients underwent LSG (53% female). The mean age was 49.5 +/- 0.9 years, and the mean BMI was 65.3 +/- 0.8 (range 45-91). Operative risk assessment determined that 42% were American Society of Anesthesiologists physical status score (ASA) III and 52% were ASA IV. The mean number of co-morbid conditions per patient was 9.3 +/- 0.3 with a median of 10 (range 3-17). There was one distant mortality and the incidence of major complications was 13%. Mean excess weight after LSG at 1 year was 46%. Thirty-six patients with a mean BMI of 49.1 +/- 1.3 (excess weight loss, EWL, 38%) had the second-stage LRYGBP. The mean number of co-morbidities in this group was 6.4 +/- 0.1 (reduced from 9). The ASA class of the majority of patients had been downstaged at the time of LRYGB. The mean time interval between the first and second stages was 12.6 +/- 0.8 months. The mean and median hospital stays were 3 +/- 1.7 and 2.5 (range 2-7) days, respectively. There were no deaths, and the incidence of major complications was 8%. CONCLUSION: The staging concept of LSG followed by LRYGBP is a safe and effective surgical approach for high-risk patients seeking bariatric surgery.

The impact of laparoscopic bariatric workshops on the practice patterns of surgeons.

BACKGROUND: This study was designed to evaluate the impact of a 2-day laparoscopic bariatric workshop on the practice patterns of participating surgeons. METHODS: From October 1998 to June 2002, 18 laparoscopic bariatric workshops were attended by 300 surgeons. Questionnaires were mailed to all participants. RESULTS: Responses were received from 124 surgeons (41%), among whom were 56 bariatric surgeons (open) (45%), 30 advanced laparoscopic surgeons (24%), and 38 surgeons who performed neither bariatric nor advanced laparoscopic surgery (31%). The questionnaire responses showed that 46 surgeons (37%) currently are performing laparoscopic gastric bypass (LGB), 38 (31%) are performing open gastric bypass, and 39 (32%) are not performing bariatric surgery. Since completion of the course, 46 surgeons have performed 8,893 LGBs (mean, 193 cases/surgeon). Overall, 87 of the surgeons (70%) thought that a limited preceptorship was necessary before performance of LGB, yet only 25% underwent this additional training. According to a poll, the respondents thought that, on the average, 50 cases (range, 10-150 cases) are needed for a claim of proficiency. CONCLUSION: Laparoscopic bariatric workshops are effective educational tools for surgeons wishing to adopt bariatric surgery. Open bariatric surgeons have the highest rates of adopting laparoscopic techniques and tend to participate in more adjunctive training before performing LGB. There was consensus that the learning curve is steep, and that additional training often is necessary. The authors propose a mechanism for post-residency skill acquisition for advanced laparoscopic surgery.

The impact of laparoscopy on bariatric surgery.

The rising popularity of bariatric surgery over the past several years is attributable in part to the development of laparoscopic bariatric surgery. Morbidly obese patients have associated comorbid conditions that may predispose them to postoperative morbidity. The laparoscopic approach to bariatric surgery offers a minimally invasive option that reduces the physiologic stress and provides clinical benefits, as compared with the open approach. This review summarizes the impact of laparoscopic surgery on bariatric surgery, the various risk factors that could potentially predispose morbidly obese patients to postoperative morbidity, the fundamental differences between laparoscopic and open bariatric surgery, and the physiology of reduced tissue injury associated with laparoscopic bariatric surgery.

Identification of the 72-kDa (MMP-2) and 92-kDa (MMP-9) gelatinase/type IV collagenase in preparations of laminin and Matrigel.

EDTA inhibitable type IV collagenolytic activity copurified with laminin preparations from the Engelbreth-Holm-Swarm (EHS) tumor. Several gelatinolytic and type IV collagenolytic matrix metalloproteinase (MMP) species were visualized in EHS laminin from three different sources by gelatin and type IV collagen substrate gel electrophoresis. Incubation with 4-aminophenylmercuric acetate and trypsin suggested that laminin contained both active and latent MMPs. EHS-derived reconstituted basement membrane, Matrigel, was found to possess an MMP profile identical to that of laminin. The presence of 72-kDa (MMP-2) and 92-kDa (MMP-9) gelatinases/type IV collagenases was demonstrated in laminin and Matrigel preparations by Western blot analysis. A rough quantitation of MMP-2 and MMP-9 in 30 micrograms of laminin and 100 micrograms of Matrigel was between 0.3 and 0.6 ng. The presence of these contaminants must be considered in experiments addressing the effects of EHS laminin or Matrigel on cell behavior and, in particular, stimulation of cellular proteolytic activity.

Gelatinolytic metalloproteinase secretion patterns in ocular melanoma.

Fifteen posterior uveal melanoma cell lines were analyzed qualitatively for gelatinolytic and caseinolytic proteinase activity after one to five in vitro passages. All 15 cell lines secreted a gelatinolytic metalloproteinase, with an apparent molecular weight of 72 kD, into protein-free culture media; nine of these secreted an additional gelatinolytic metalloproteinase with an apparent molecular weight of 92 kD. Neither species had the ability to degrade casein. This approach may provide insight into the mechanisms of tumor metastasis in uveal melanoma.

Effects of sulphur dioxide and nitrogen dioxide on the control of water loss by birch (Betula spp.).

The effects of SO2 and NO2 on the control of water loss by birch trees were investigated using clonal populations of both Betula pendula Roth, (silver birch) and Betula pubescens Khr. (downy birch). Plants were grown in controlled environments and were fumigated in a 2 × 2 factorial experiment with 65 nl l-1 SO2 and/or NO2 , or with equal concentrations of both SO2 and NO2 in four treatments, namely zero, 20, 40 and 60 nl l-1 . Excised leaves showed in increased rate of water loss approximately corresponding to the concentration of pollutant to which they had been previously exposed. When petroleum jelly was applied to the abaxial epidermal surface of polluted leaves the increased rate of water loss was not found, strongly implying that the damage had occurred only at this site, and not on the adaxial epidermis, which is virtually devoid of stomata. Measurements of gas exchange were made on B. pubescens exposed to the four doses of the mixture of the two gases. The rate of transpiration was approximately doubled as a result of the two higher pollution treatments, judging from measurements made later in clean air. When transpiration was measured in high and low CO2 concentrations, polluted plants had a slightly reduced and more variable response to the change in CO2 concentration. Both clones were also exposed first to the four doses of the gas mixture, and then to drought. There was a more rapid onset of water stress, accompanied by an earlier decrease in effective leaf area in the polluted plants, when compared with the unpolluted plants. The abaxial surface of frozen hydrated leaves of the Betula pubescens clone were examined at low temperature with a scanning electron microscope. Damaged epidermal cells were clearly visible on the polluted leaves and thought to be responsible for areas of wide open stomata. It is concluded that leaves of these species are less efficient in the utilization of water after a period of exposure to pollution and are less able to restrict water loss in a time of shortage.

Regulation of matrix metalloproteinases - their role in tumor invasion and metastasis.

In order for tumor cells to colonise secondary organs and tissues it is necessary for them to be able to complete all the essential steps of the metastatic cascade. We discuss here some of the important aspects of this process, highlighting those events likely to be important in the control of tumor cell invasion. The expression of matrix metalloproteinases (MMP) capable of degrading tissue matrix or basement membranes, constitutes an important feature of tumor cell escape from the primary neoplasm and entry into/ colonisation of the secondary body site. In particular, the balance between MMP and protease inhibitor expression will determine the invasive capacity of a cancer cell. The molecular control of gene expression, together with the molecules important in regulating the production of proteinases and their inhibitors is complex, and the important facets of these pathways are discussed. Cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and transforming growth factor-beta (TGF-beta), play a crucial role in modulating MMP-2 and MMP-9 expression, and these, together with other regulatory cytokines constitute an important mechanism whereby the tumor cells can increase their invasive potential through the secretion of proteases.

Dysfunctional immune-privilege in morbid obesity: implications and effect of gastric bypass surgery.

BACKGROUND: Despite the epidemiological evidence linking obesity and cancer, there has never been a causal link. We believe the chronic inflammation present in obesity may predispose the obese to cancer through Fas-receptor over-expression and L-selectin under-expression in leukocytes, and elevated Fas ligand secretion in tumors affecting the morbidly obese. METHODS: Leukocytes from 25 patients having gastric bypass surgery were compared to 15 normal controls preoperatively and at 1, 3, 6, and 12 months postoperatively using flow cytometry to measure CD3, CD4, CD8, CD56, CD62 (L-selectin), CD69, and CD95 (Fas antigen) expression on T lymphocytes, B lymphocytes, natural killer cells, and neutrophils. RESULTS: The percentage of CD95 + T cells was significantly elevated from controls (69.4% vs 56%, P = 0.005). This difference persisted through 1 month postoperatively. Furthermore, expression of CD95 per cell, was significantly greater in these patients than that of the controls (80.2 vs 62.6 gmf, P = 0.018) preoperatively, and this continued to 1 month. Polymorphonuclear cells also displayed a similar elevation in CD95 gmf expression preoperatively (54.1 vs 40.7 gmf, P = 0.023) which normalized by 3 months. Natural killer cells did not display elevated numbers of CD95 gmf preoperatively, but they did experience a significant decline by 12 months. Additionally, there was significant reduction in the number of naiveT cells [(T cells without L-selectin (CD62L)], when compared to normals preoperatively (41.8% vs 51.3%, P = 0.001). There was no statistical difference between the postoperative patients and the controls by 3 months. CD69 was not different at baseline from controls in T or B cells, but there was a significant decrease by 12 months. CONCLUSION: The reduced expression of L-selectin combined with the elevated levels of CD95 suggests that morbid obesity predisposes patients to sites of immune privilege. This could be the mechanism for increased rates of cancer and wound infections seen in obesity. Surgically-induced weight loss eliminates these risk factors.

The effect of obesity on neutrophil Fc receptors and adhesion molecules (CD16, CD11b, CD62L).

BACKGROUND: There is a large body of epidemiological data associating obesity with a wide variety of clinical disease processes, including cancer and wound infections. However, defining the specific defects of neutrophils has proved difficult and often contradictory. METHODS: 27 patients having gastric bypass surgery for obesity (BMI > 40) were compared with 10 normal controls (BMI < 26). Relative neutrophil frequencies and expression of the activation antigens CD11b (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry. RESULTS: The study control group had a mean age of 37 +/- 7.6 yrs (range 30 to 57) with no significant health problems. Their mean BMI was 23 +/- 2.5 kg/m2 (range 21-26). The mean age of the sample group was 40.36 +/- 13.7 yrs (range 18 to 60) with a mean BMI of 52 +/- 8.2 kg/m2 (range 41 to 72). These patients had a large spectrum of diseases that afflict the morbidly obese, including hypertension (14), arthritis (10), exertional dyspnea (13), venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8 smokers. The neutrophil frequency in the obese patients was comparable to the controls (control 49% vs obese 51%). Additionally, there was no apparent difference between obese and controls regarding CD11b or CD16 expression (424 vs 498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L-selectin) expression noted in the morbidly obese with respect to controls (102 vs 303 gmf, p < 0.001). An increased percentage of eosinophils when compared to controls (6.7% vs 1.73%, p < 0.001) was also observed. CONCLUSION: Discordant CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil percentages support the hypothesis that a chronic inflammatory state exists in morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool possibly affect the neutrophil's ability to activate and migrate to sites of inflammation. This may play a role in the higher incidence of infectious complications seen in morbidly obese individuals.

Effect of surgically-induced weight loss on leukocyte indicators of chronic inflammation in morbid obesity.

BACKGROUND: Recent evidence suggests that morbid obesity is a chronic inflammatory condition that may be associated with immune dysfunction. To test this hypothesis, we investigated several leukocyte cell surface markers of chronic inflammation and followed their response to surgically-induced weight loss. METHODS: 26 patients having Roux-en-Y gastric bypass (RYGBP) for morbid obesity (BMI > 40) were compared to 10 normal controls (BMI < 25). Relative monocyte and neutrophil frequencies and expression of the activation antigens CD11b (adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry preoperatively and at 1, 3, 6 and 12 months after RYGBP. Cases served as their own controls but were also compared to non-obese controls. The results were statistically analyzed using Student's t-test and ANOVA for parametric values and Mann-Whitney along with Kruskal-Wallis ANOVA for nonparametric values. RESULTS: The control group had mean age 37 +/- 7.6 with mean 23 +/- 2.5 and no comorbidities. The mean age of the sample group was 40.36 +/- 13.7 with mean BMI 52 +/- 8.2. The neutrophil and monocyte relative frequencies of CD11b (monocytes and neutrophils), and CD16 (neutrophils only) were comparable to controls at baseline and did not change significantly with weight loss throughout the study period. However, a significant reduction of CD62L (L-selectin) expression was noted in monocytes and neutrophils at baseline (neutrophils 103 vs 240 gmf, p < 0.001) (monocytes 104 vs 246 gmf, P < 0.001) when compared to normal controls. Levels of L-selectin normalized by 6 months in both monocytes and neutrophils, and by 12 months had become abnormally elevated in monocytes (monocytes 391 gmf, P = 0.007); in neutrophils, there was an upward trend that did not reach significance. The expression of the LPS receptor CD14 in the study group was elevated significantly compared to controls at baseline (1129 vs 719 gmf, P = 0.004); this marker appeared to return to normal by 3 months. Monocyte CD14+/CD16+ subset percentage were also elevated significantly at baseline (14.3% vs 5.25%, P < 0.001), declined throughout the time period but was still significant at 1 year (8.8%, P < 0.001). Eosinophil percentages were elevated at baseline (3.3% obese vs 1.8% controls, P = 0.003) and remained so throughout the time period. CONCLUSION: Deficiencies in the immune system of morbidly obese individuals include elevated levels of eosinophils, monocyte CD14, and monocyte CD14+/CD16+ subsets, with depression of monocyte and neutrophil CD62L. These abnormal levels reverse rapidly with surgically-induced weight loss. RYGBP is not only a weight loss operation but also appears to be an immune restorative procedure.

Common phytochemicals are ecdysteroid agonists and antagonists: a possible evolutionary link between vertebrate and invertebrate steroid hormones.

Many plant compounds are able to modulate growth and reproduction of herbivores by directly interacting with steroid hormone systems. In insects, several classes of phytochemicals, including the phytoestrogens, interfere with molting and reproduction. We investigated whether the anti-ecdysone activity may be due to interaction with the ecdysone receptor (EcR) using a reporter-gene assay and a cell differentiation assay of an ecdysone-responsive cell line, Cl.8+. We tested rutin (delays molt in insects); four flavones: luteolin and quercetin (metabolites of rutin), and apigenin and chrysin; and three non-flavones, coumestrol and genistein (both estrogenic) and tomatine (alters molt in insects). None of the phytochemicals tested were ecdysone agonists in the reporter-gene assay, but the flavones were able to significantly inhibit EcR-dependent gene transcription. In the Cl.8+ cells, quercetin and coumestrol were mixed agonists/antagonists, while genistein, tomatine and apigenin showed a synergistic effect with ecdysteroid in the reduction of cell growth. We suggest that the rutin effects on molting in insects are most likely due to the metabolites, luteolin or quercetin, while tomatine acts via a non-EcR pathway. Flavones not only interact with EcR and estrogen receptor (ER), but also signal nitrogen-fixing bacteria to form root nodules. The NodD protein which regulates this symbiosis has two ligand-binding domains similar to human ERalpha. The evolutionary significance of these findings are discussed.

The effects of chrysomelid beetle grazing and plant competition on the growth of Rumex obtusifolius.

The interaction between grazing by Gastrophysa viridula and interspecific plant competition was investigated for Rumex obtusifolius growing in the field. During an eight-month growing season non-competing R. obtusifolius grew larger than competing plants although herbivore loads (beetle productivity per unit leaf area) were similar for competing and non-competing plants. However, grazing significantly reduced the growth of R. obtusifolius only in competing plants thus demonstrating a synergism between plant competition and invertebrate herbivory. The relevance of these findings for the distribution of plant species is discussed.

Laparoscopic repair of traumatic perforation of the urinary bladder.

Laparoscopy as a diagnostic modality in trauma has been reported. However, therapeutic laparoscopy for trauma remains a controversial subject. We present a case of laparoscopic repair of a traumatic bladder rupture. A 25-year-old man was brought to the emergency room after a head-on collision. Physical examination was unremarkable with the exception of gross hematuria upon insertion of a urinary catheter. Computed tomography scan of the abdomen demonstrated a small amount of free intraperitoneal fluid. An anteroposterior cystogram was obtained which showed no intraperitoneal or extraperitoneal leak. Repeat examinations of the abdomen revealed a mild tenderness in the lower abdomen. Because of the presence of unexplained free intraperitoneal fluid and equivocal signs of peritoneal irritation, exploratory laparoscopy was performed. Three 5-mm ports and a 5-mm laparoscope were used. Laparoscopic examination of the abdomen revealed a 4-cm rupture at the dome of the bladder. The laceration was sutured in two layers using an intracorporeal technique. The patient was discharged on the second postoperative day with indwelling urinary catheter. Eight days after the operation, a repeated cystogram revealed no evidence of leak. We believe that laparoscopic exploration for trauma in hemodynamically stable patients is feasible. The repair of simple intraabdominal injuries such as bladder rupture can be safely performed.

Repair of ventral hernias in morbidly obese patients undergoing laparoscopic gastric bypass should not be deferred.

BACKGROUND: There is no consensus regarding the optimal treatment of ventral hernias in patients who present for weight loss surgery. METHODS: Medical records of consecutive morbidly obese patients who underwent laparoscopic Roux-en-Y (LRYGB) gastric bypass with a secondary diagnosis of ventral hernia were reviewed. Only patients who were beyond 6 months of follow-up were included. RESULTS: The study population was 85 patients. There were three groups of patients according to the method of repair: primary repair (59), small intestine submucosa (SIS) (12), and deferred treatment (14). Average follow-up was 26 months. There was a 22% recurrence in the primary repair group. There were no recurrences in the SIS group. Five of the patients in the deferred treatment group (37.5%) presented with small bowel obstruction due to incarceration. CONCLUSION: Biomaterial mesh (SIS) repair of ventral hernias concomitant with LRYGB resulted in the most favorable outcome albeit having short follow-up. Concomitant primary repair is associated with a high rate of recurrence. All incarcerated ventral hernias should be repaired concomitant with LRYGB, as deferment may result in small bowel obstruction.

The effect of juvenile hormone on the response of the Drosophila imaginal disc cell line Cl 8+ to moulting hormone.

The Drosophila wing imaginal disc cell line Cl 8+ was used to investigate the interaction between juvenile hormone III (JH) and 20-hydroxyecdysone (20HE). Cell cultures were exposed to either or both hormones at a range of concentrations and cell growth was observed. JH was found to ameliorate the effects of 20HE on cell growth, even when added after the cells had been exposed to 20HE for 4 or 24h.

Adhesion of Drosophila imaginal disc cells in vitro.

We have used our imaginal disc cell lines to carry out in vitro studies on the cell-cell and cell-substrate adhesion of Drosophila leg and wing disc cells. Single cells were allowed to reaggregate in roller culture, and this process was found to be partially dependent on the presence of magnesium and calcium ions in the suspension medium. Varying rates of reaggregation were observed in cells from different stages of a passage, correlating with the pattern of morphogenesis which occurs during the passage. We have demonstrated that cloned cell lines can be produced showing certain selected characteristics, such as reduced cell adhesiveness.

Cell-cell and cell-substrate adhesion in cultured Drosophila imaginal disc cells.

Drosophila imaginal disc cell lines were used to investigate various aspects of cellular adhesion in vitro. The distribution of PS integrins and their involvement in cell-cell and cell-substrate adhesion were assessed with the monoclonal antibody aBG-1 against the betaPS subunit, and both forms of adhesion were found to be impeded by the presence of the antibody. Adhesion to a number of extracellular matrix components was investigated, and the cells were found to adhere to human fibronectin. This adhesion was inhibited by aBG-1. The adhesion molecule fasciclin III was also found in these cells. Given that the cells are competent to perform cell-cell and cell-substrate adhesion, it was thought that apical basal polarity might be restored when other suitable conditions were provided, i.e., an artificial basement layer with feeder cells to provide nutrients basally to the cells, and some features of apical-basal morphology were seen in cells cultured under these conditions.

Effect of age on the growth and response of a Drosophila cell line to moulting hormone.

Insect cell lines in culture are used for a variety of studies. In this laboratory imaginal disc cell lines have been established from primary cultures from third instar larvae, and used for a number of experiments. The effect of ageing on the morphology and physiology of Drosophila cell lines has received very little attention, although problems of genotypic or phenotypic changes in cell lines with age are recognized in other areas of animal cell culture. We tested our cell line Cl8+ for any difference in growth, morphology and response to 20-hydroxyecdysone (20HE) at different ages (passage numbers). The cells were found to multiply faster, adhere less firmly to the substrate and to lose the tendency to aggregate at higher passages. The response to 20HE in terms of cell numbers and induction of beta-galactosidase was similar at all passage numbers but morphological changes in hormone-treated cells were less obvious in the higher passages. Cell lines are likely to vary in the extent of ageing effects but workers are advised to be aware of the possibilities. We suggest the effects of age on cell lines should be established, and passage numbers noted in experimental reports.

A large-scale fumigation system for investigating interactions between air pollution and cold stress on plants.

A new large-scale closed chamber fumigation system with cooling facilities is described for studying effects of low concentrations of SO(2), NO(2) and O(3) and low temperatures on woody species and herbaceous plants. The system is based on modified hemispherical greenhouses with a forced air ventilation system. This provides a chamber environment with low spatial variability of pollutant gas concentrations and rapid air circulation which allows exposure of plants at near ambient temperatures and relative humidity. Large capacity cooling units come into operation when ambient temperatures fall below 0 degrees C, and these allow chamber temperatures to be lowered by an additional 4 to 8 degrees C in experiments designed to test whether exposure to pollutants enhances the frost sensitivity of plants.