Stewart Skinner

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial.

CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. MAIN OUTCOME MEASURES Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. RESULTS Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group. CONCLUSIONS Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. TRIAL REGISTRATION actr.org Identifier: ACTRN012605000159651.

Laparoscopic Adjustable Gastric Banding in Severely Obese Adolescents: A Randomized Trial

CONTEXT Adolescent obesity is a common and serious health problem affecting more than 5 million young people in the United States alone. Bariatric surgery is being evaluated as a possible treatment option. Laparoscopic adjustable gastric banding (gastric banding) has the potential to provide a safe and effective treatment. OBJECTIVE To compare the outcomes of gastric banding with an optimal lifestyle program on adolescent obesity. DESIGN, SETTING, AND PATIENTS A prospective, randomized controlled trial of 50 adolescents between 14 and 18 years with a body mass index (BMI) higher than 35, recruited from the Melbourne, Australia, community, assigned either to a supervised lifestyle intervention or to undergo gastric banding, and followed up for 2 years. The study was performed between May 2005 and September 2008. MAIN OUTCOME MEASURES Weight loss. Secondary outcomes included change in metabolic syndrome, insulin resistance, quality of life, and adverse outcomes. RESULTS Twenty-four of 25 patients in the gastric banding group and 18 of 25 in lifestyle group completed the study. Twenty-one (84%) in the gastric banding and 3 (12%) in the lifestyle groups lost more than 50% of excess weight, corrected for age. Overall, the mean changes in the gastric banding group were a weight loss of 34.6 kg (95% CI, 30.2-39.0), representing an excess weight loss of 78.8% (95% CI, 66.6%-91.0%), 12.7 BMI units (95% CI, 11.3-14.2), and a BMI z score change from 2.39 (95% CI, 2.05-2.73) to 1.32 (95% CI, 0.98-1.66). The mean losses in the lifestyle group were 3.0 kg (95% CI, 2.1-8.1), representing excess weight loss of 13.2% (95% CI, 2.6%-21.0%), 1.3 BMI units (95% CI, 0.4-2.9), and a BMI z score change from 2.41 (95% CI, 2.21-2.66) to 2.26 (95% CI, 1.91-2.43). At entry, 9 participants (36%) in the gastric banding group and 10 (40%) in the lifestyle group had the metabolic syndrome. At 24 months, none of the gastric banding group had the metabolic syndrome (P = .008; McNemar chi(2)) compared with 4 of the 18 completers (22%) in the lifestyle group (P = .13). The gastric banding group experienced improved quality of life with no perioperative adverse events. However, 8 operations (33%) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up. CONCLUSIONS Among obese adolescent participants, use of gastric banding compared with lifestyle intervention resulted in a greater percentage achieving a loss of 50% of excess weight, corrected for age. There were associated benefits to health and quality of life. TRIAL REGISTRATION ANZCTR Identifier: 12605000160639.

Microvascular structure of benign and malignant tumors of the colon in humans.

Studies of experimental tumors in rodents indicate that there are morphological abnormalities of the tumor microcirculation compared to normal tissues. The aim of this study was to examine the structure of the microvasculature in benign and malignant colonic tumors in humans using microvascular casting techniques. There were 15 adenocarcinomas, four benign sporadic adenomas, and three specimens from patients with familial adenomatous polyposis (FAP). A cast of the microvessels of these tumors was prepared by intraarterial administration of acrylic resin (Mercox) and the cast examined by scanning electron microscopy. Quantitative measures of the microvasculature were obtained from histological sections using stereological techniques in four carcinomas, two sporadic adenomas, and 12 adenomas from patients with FAP. Vascular casts of benign colonic adenomas showed that the microvasculature had a similar organization to normal colon. However, capillaries and venules were elongated and had increased diameters compared to normal. In adenomas greater than 3 mm in diameter, there was an increased density of microvessels in the spaces between tumor cells. Vascular casts of colonic carcinomas were characterized by a disorganized structure and increased density of microvessels. The organization of microvessels within carcinomas had a similar overall pattern to normal colon. However, the increased number and density of microvessels resulted in formation of nodular clusters of capillaries, formation of “sheets” of frequently anastomosing capillaries, or almost complete packing of the interstitial spaces of the tumor by capillaries in places. Most capillaries had a long and tortuous course and numerous capillary sprouts were identified. Tumor microvessels had greater mean diameters than normal. Extravasation of resin from microvessels in carcinomas was frequently seen. The vascular volume of carcinomas (23.1%±12.2), sporadic adenomas (16.3%±3.4), and adenomas >3 mm diameter in patients with FAP (17.7%±3.0) were significantly greater than in normal colon (11.0%±4.2). This study indicates that there is an increased vascular density in benign and malignant tumors of the colon compared to normal colon. The presence of profusely anastomotic microvessels and frequent capillary sprouts is evidence of active neovascularization and suggests control of tumor growth could be achieved by modifiers of angiogenesis.

A Prospective, Randomized, Controlled Clinical Trial of Placement of the Artificial Bowel Sphincter (Acticon Neosphincter) for the Control of Fecal Incontinence

BACKGROUNDSevere fecal incontinence remains a disabling condition for the patient and a major therapeutic challenge for the physician. A series of observational studies have indicated that placement of an artificial bowel sphincter is associated with marked improvement of continence and quality of life. We have performed a prospective, randomized, controlled trial to evaluate the effect of placement of an artificial bowel sphincter (Acticon Neosphincter®) on continence and quality of life in a group of severely incontinent adults.METHODSFourteen adults (male:female, 1:13; age range, 44–75 years) were randomized to placement of the artificial bowel sphincter or to a program of supportive care and were followed for six months from operation or entry into the study. The principal outcome measure was the level of continence, measured with the Cleveland Continence Score, which provides a scale from 0 to 20, representing perfect control through to total incontinence. Secondary outcome measures were perioperative and late complications in the artificial bowel sphincter group, and the changes in quality of life in both groups.RESULTSIn the control group, the Cleveland Continence Score was not significantly altered, with an initial value of 17.1 ± 2.3 and a final value of 14.3 ± 4.6 at six months. The artificial bowel sphincter group showed a highly significant improvement, changing from 19.0 ± 1.2 before placement to 4.8 ± 4.0 at six months after placement. One patient in the artificial bowel sphincter group had failure of healing of the perineal wound and explantation of the device (14 percent explantation rate). There were two other significant perioperative events of recurring fecal impaction initially after placement in one patient and additional suturing of the perineal wound in another. There were major improvements in the quality of life for all measures in the artificial bowel sphincter group. There was significant improvement in all eight subscales of the Medical Outcome Study Short Form-36 measures. The American Medical Systems Quality of Life score was raised from 39 ± 6 to 83 ± 14 and the Beck Depression Inventory showed reduction from a level of mild depression (10.8 ± 9.3) to a normal value (6.8 ± 8.7). No significant changes in any of the quality of life measures occurred for the control group.CONCLUSIONSThrough a prospective, randomized trial format, we have shown that placement of an artificial bowel sphincter is safe and effective when compared with supportive care alone. Perioperative and late problems are likely to continue to occur and between 15 percent and 30 percent of patients may require permanent explantation. For the remainder, the device is easy and discrete to use, highly effective in achieving continence, and able to generate a major improvement in the quality of life.

5-Aminosalicylic acid and olsalazine inhibit tumor growth in a rodent model of colorectal cancer

The ability of 5-aminosalicylic acid and olsalazine to inhibit colonic aberrant crypts and tumors was investigated in 1,2-dimethylhydrazine-treated rats. The effect of these drugs on the rates of tumor apoptosis and proliferation was studied as potential mechanisms for their action. 5-Aminosalicylic acid reduced the number of aberrant crypt foci by over one third, while olsalazine had no effect on this parameter. However, both agents effectively reduced tumor number and load, increased the rate of tumor apoptosis, and reduced the rate of tumor cell proliferation. In conclusion, 5-aminosalicylic acid and olsalazine are both ultimately effective chemopreventive agents in this model; however, only 5-aminosalicylic acid inhibited the formation of aberrant crypt foci. The inhibitory effect of these agents in tumors is related to the inhibition of proliferation and the induction of apoptosis.

Inhibition of β-Catenin Translocation in Rodent Colorectal Tumors: A Novel Explanation for the Protective Effect of Nonsteroidal Antiinflammatory Drugs in Colorectal Cancer

In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs reduce tumor mass by increasing the rate of tumor cell apoptosis and decreasing proliferation. We have examined β-catenin as a potential target for these agents in colorectal cancer. Carcinogen-treated rats were treated for 23 weeks with a range of nonsteroidal antiinflammatory drugs. Control animals received vehicle alone. Intracellular β-catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nucleii). The frequency of nuclear β-catenin staining correlated directly with the volume of tumor and inversely with the rate of apoptosis. In tumors from treatment groups, the cytoplasmic staining for β-catenin was unchanged; however, nuclear staining was absent except in the celecoxib group, where it was reduced to a median of 14%. Colorectal tumors from animals treated with NSAIDs show reduced levels of nuclear β-catenin immunoreactivity.

Sulindac inhibits colorectal tumour growth, but not prostaglandin synthesis in the rat

We have determined the dose‐response relationship between sulindac administration and inhibition of tumour growth in the rat. The effect of tumour‐inhibiting doses of sulindac on the production of prostaglandin E in tumours and macroscopically normal colon was then examined. Growth of pre‐existing tumours was significantly reduced following administration of sulindac at 0.1 (P= 0.004), 1 (P= 0.01), 3 (P < 0.001) and 10mg/kg b.d. (P= 0.002) for 4 weeks. There was no significant difference in prostaglandin E synthesis between tumours from control rats and those treated with sulindac at either 3 or 10mg/kg b.d. (P= 0.09 and 0.4, respectively). Prostaglandin E synthesis was reduced by 33 and 32% in macroscopically normal tissue from these treatment groups. These data show that sulindac inhibits tumour growth at low doses and do not support a role for the inhibition of prostaglandin synthesis, by sulindac, in the inhibition of tumour growth.

Non‐steroidal anti‐inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model

Standard non‐steroidal anti‐inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase‐2 (COX‐2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX‐2 inhibitors to inhibit colorectal cancer at clinically relevant doses.

Botulinum toxin therapy for chronic anal fissures: where are we at currently?

Botulinum toxin (Botox) injection for chronic anal fissure (CAF) is commonly performed, yet there remains no consensus on optimal dosage or frequency of injections required to achieve complete resolution of anal fissure. The aim of this study was to determine the effectiveness of Botox and side‐effect profile in the management of CAF.

Evaluation of pulmonary nodules and lung cancer with one-inch crystal gamma coincidence positron emission tomography/CT versus dedicated positron emission tomography/CT

Dedicated positron emission tomography (PET)/CT scanners using BGO and related detectors (d‐PET) have become standard imaging instruments in many malignancies. Hybrid gamma camera systems using NaI detectors in coincidence mode (g‐PET) have been compared to d‐PET but reported usefulness has been variable when gamma cameras with half‐inch to three‐fourth‐inch thick crystals have been used without CT. Our aim was to compare g‐PET with a 1‐in.‐thick crystal and inbuilt CT for lesion localization and attenuation correction (g‐PET/CT) and d‐PET/CT in patients presenting with potential and confirmed lung malignancies. One hour after 18F‐fluorodeoxyglucose (FDG), patients underwent BGO d‐PET/CT from jaw to proximal thigh. This was followed by one to two bed position g‐PET/CT 194 ± 27 min after FDG. Each study pair was independently analysed with concurrent CT. d‐PET/CT was interpreted by a radiologist experienced in both PET and CT, and g‐PET/CT by consensus reading of an experienced PET physician and an experienced CT radiologist. A TNM score was assigned and studies were then unblinded and compared. Fifty‐seven patients underwent 58 scan pairs over 2 years. Eighty‐nine per cent concordance was shown between g‐PET/CT and d‐PET/CT for the assessment of intrapulmonary lesions, with 100% concordance for intrapulmonary lesions >10 mm (36 of 36). Eighty‐eight per cent (51 of 58) concordance was shown between g‐PET/CT and d‐PET/CT for TNM staging. Coincidence imaging using an optimized dual‐head 1‐in.‐thick crystal gamma camera with inbuilt CT compares reasonably well with dedicated PET/CT for evaluation of indeterminate pulmonary lesions and staging of pulmonary malignancies and may be of some value when d‐PET/CT is not readily available.