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Perforated Meckel's diverticulum (MD) is a rare complication of pregnancy. Its diagnosis, however, must be considered in all cases of intra-abdominal disease, as its presentation is similar to appendicitis. Prompt diagnosis and appropriate treatment is imperative in these cases due to the high rate of perforation leading to fetal and maternal morbidity and mortality. The usual lesion affecting a patient with MD and a review of the literature on other unusual causes of an acute abdomen in pregnancy is presented in the following report.

Background: Hepatic cystic lesions are rare; however, their management and treatment is dependent on early recognition and diagnosis., Methods: In this report, the authors discuss a 72-year-old woman who presented to their clinic for treatment of a hepatocystadenoma., Results: The history, physical examination, and diagnostic modalities lead to surgical intervention despite an unclear diagnosis., Conclusions: This case illustrates an unusual hepatic lesion in which the diagnosis was not known until the time of laparotomy. However, diagnostic modalities were important in establishing the need for surgical intervention. The authors offer a pertinent review of the literature and discuss current treatment modalities.

The aim of this study was to determine factors that predict mortality in patients with traumatic inferior vena cava (IVC) injuries and to review the current management of this lethal injury. A 7-year retrospective review of all trauma patients with IVC injuries was performed. Factors associated with mortality were assessed by univariate analysis. Significant variables were included in a multivariate regression analysis model to determine independent predictors of mortality. Statistical significance was determined at P < or = 0.05. A literature review of traumatic IVC injuries was performed and compared with our institutional experience. Thirty-six IVC injuries were identified (mortality, 56%; mechanisms of injury, 28% blunt and 72% penetrating). There was no difference in mortality based on mechanism of injury. Injuries with closer proximity to the heart were associated with increased mortality (P < 0.001). Univariate analysis demonstrated that nonsurvivors had a higher injury severity scale, a lower systolic blood pressure in the emergency department, a lower Glasgow coma score (GCS), and were more likely to have thoracotomies performed in the emergency department or operating room. Multivariate analysis revealed that only GCS (P = 0.03) was an independent predictor of mortality. Typical factors predicting mortality were identified in our cohort of patients, including GCS. The mechanism of injury is not associated with survival outcome, although mortality is higher with injuries more proximal to the heart. The form of management by IVC level is reviewed in our patient population and compared with the literature.

Background: The implementation of new therapeutic options for the management of metastatic colon cancer mandates a revisit to apoptosis and its role in colon cancer tumorigenesis with an emphasis on the mechanisms leading to chemotherapeutic resistance and immune system evasion of colon cancer cells., Data Sources: Literature regarding molecular apoptosis mechanisms and the role of apoptosis in colon cancer progression are reviewed by this article., Conclusion: Programmed cell death has rapidly emerged as a potential target for cancer treatment at various stages of tumor progression. Chemoprevention, immuno-regulation, and metastasis are prospective targets by which apoptotic mechanisms could be utilized in the prevention and management of tumorigenesis. Understanding how defects in the death receptor pathway of apoptosis permit colon cancer cells to escape the immune system would allow for treatment options whereby the body's immune system could again recognize and eliminate unwanted cells.

Background: Portal vein thrombosis is rare following Roux-en-Y gastric bypass (RYGBP). Its natural history is dependent on the etiology of the thrombosis. Iatrogenic injuries at bariatric operations resulting in portal vein thrombosis are lethal complications typically necessitating a liver transplant, whereas postoperative portal vein thrombosis without an injury to the portal vein has a benign course. There are currently no data on management or prognostic factors of portal vein thrombosis after bariatric operations., Methods: 3 patients referred for liver transplantation secondary to portal vein injury following bariatric surgery between 2000 and 2003 are presented., Results: 2 super-obese (BMI>or=50 kg/m2) and 1 morbidly obese (BMI 44 kg/m2) patients sustained portal vein injuries during bariatric surgery (RYGBP 2, VBG 1) by experienced bariatric surgeons. In each case, the portal injury was identified and repaired. Thrombosis followed reconstruction in all 3 patients. All 3 underwent emergency liver transplantation, but died of sepsis and multi-organ failure following transplantation. Review of the literature found no cases of traumatic portal vein injuries following bariatric operations and 2 cases of postoperative portal vein thrombosis: 1 following LRYGBP (BMI 46) and one after a Lap-Band (BMI 41)., Conclusion: Injury to the portal vein resulting from difficulty in discerning the anatomy of the intra-abdominal structures in the morbidly obese, is a lethal complication of bariatric surgery. Super-obese patients submitting to bariatric surgery should lose weight, undergo a two-stage bariatric procedure, or undergo laparoscopic RYGBP to minimize the risk of portal injury. Postoperative portal vein thrombosis has a benign course and can be managed conservatively.

The aim of our study is to determine factors that predict morbidity and mortality in patients with traumatic duodenal injury (DI). A retrospective review from July 1996 to March 2003 identified 52 patients admitted to our trauma center (age 24.4 +/- 2.1 years, ISS = 18.8 +/- 1.76). The mortality rate for patients with duodenal injury was 15.4 per cent (n = 8). The mechanisms of injury were blunt (62%), gun shot wound (GSW) (27%), and stab wound (SW) (11%). There was no difference in mortality based on mechanism of injury. Management was primarily nonoperative [n = 30 (57%)]. Of those with perforation (n = 22), 64 per cent underwent primary repair (n = 14), 23 per cent duodenal resection (n = 5), 9 per cent duodenal exclusion (n = 2), and one patient pancreaticoduodenectomy. The method of initial surgical management was not related to patient outcome. Univariate analysis demonstrated that nonsurvivors were older, more, hypotensive in the emergency department, had a more negative initial base deficit, had a lower initial arterial pH, and had a higher Injury Severity Score. Nonsurvivors were also more likely to have an associated inferior vena cava (IVC) injury. Multivariate regression analysis revealed age, initial lowest pH, and Glasgow Coma Score to be independent predictors of mortality, suggesting that the physiologic presentation of the patient is the most important factor in predicting mortality in patients with traumatic DIs.

Mesenteric fibromatosis (MF) is a rare, benign tumor commonly associated with Gardner's syndrome. The signs and symptoms in patients with MF are insidious. Patients may present with abdominal pain or discomfort when the tumors reach large sizes, which is typical at the time of diagnosis. Differentiating MF from other neoplasms such as gastrointestinal stromal tumors may present a diagnostic dilemma, especially in patients without any history of familial adenomatous polyposis. In the present report, we discuss a young girl who presented with MF. A pertinent review of the literature is also presented. This case is peculiar in that MF presented at a young age in a patient without history of familial adenomatous polyposis and occurred in the omentum with local invasion to the stomach.

Although the avocado is known as a rich source of monounsaturated fatty acids, there has been far less attention given to its content of other bioactive substances including carotenoids, which might contribute to cancer preventive properties similar to those attributed to other fruits and vegetables. The yellow-green color of the avocado prompted us to study the carotenoid content of this fruit using established methods in our laboratory. The California Hass avocado (Persea americana Mill.) was selected for study, because it is the most commonly consumed variety in the southwest United States. These avocados were found to contain the highest content of lutein among commonly eaten fruits as well as measurable amounts of related carotenoids (zeaxanthin, alpha-carotene, and beta-carotene). Lutein accounted for 70% of the measured carotenoids, and the avocado also contained significant quantities of vitamin E. An acetone extract of avocado containing these carotenoids and tocopherols was shown to inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines in vitro. Incubation of PC-3 cells with the avocado extract led to G(2)/M cell cycle arrest accompanied by an increase in p27 protein expression. Lutein alone did not reproduce the effects of the avocado extract on cancer cell proliferation. In common with other colorful fruits and vegetables, the avocado contains numerous bioactive carotenoids. Because the avocado also contains a significant amount of monounsaturated fat, these bioactive carotenoids are likely to be absorbed into the bloodstream, where in combination with other diet-derived phytochemicals they may contribute to the significant cancer risk reduction associated with a diet of fruits and vegetables.

Context: Pancreatic schwannomas are rare neoplasms. These tumors vary in size and two thirds are partially cystic which grossly mimic pancreatic cystic lesions. Computed tomography and magnetic resonance imaging are the primary initial imaging modalities. Definitive diagnosis is typically made at the time of laparotomy following biopsy. Surgical resection is the mainstay of treatment., Case Report: A 69-year-old woman presented with abdominal pain in the epigastric and left upper quadrant. The patient had no systemic symptom and laboratory results including tumor markers were negative. A CT scan of the abdomen showed a 5 cm mass arising from the head of the pancreas. Needle biopsy revealed a mass consistent with schwannoma. At laparotomy, a large pancreatic head mass was found to encase the superior mesenteric artery, and portal vein confluence. Frozen biopsy showed schwannoma. Curative resection was deferred due to extensive vascular involvement and favorable tumor biology. A gastrojejunostomy was performed and radiation therapy was instituted post-operatively., Conclusions: Only 24 cases of pancreatic schwannoma had been previously reported. Definitive diagnosis is obtained with routine histology. Most tumors are benign and surgical resection is curative. The role of radiation therapy in the management of unresectable tumors is still unclear.

Background: Bowel obstruction has been frequently reported after laparoscopic Roux-en-Y gastric bypass (LRYGBP). The aim of this study was to review our experience with bowel obstruction following LRYGBP, specifically examining its etiology and management and to strategize maneuvers to minimize this complication., Methods: We retrospectively reviewed the charts of 9 patients who developed postoperative bowel obstruction after LRYGBP. Each chart was reviewed for demographics, timing of bowel obstruction from the primary operation, etiology of obstruction, and management., Results: 9 of our initial 225 patients (4%) who underwent LRYGBP developed postoperative bowel obstruction. The mean age was 46 +/- 12 years, with mean BMI 47 +/- 9 kg/m(2). 6 patients developed early bowel obstruction, and 3 patients developed late bowel obstruction. The mean time interval for development of early bowel obstruction was 16 +/-16 days. The causes for early bowel obstruction included narrowing of the jejunojenunostomy anastomosis (n=3), angulation of the Roux limb (n=2), and obstruction of the Roux limb at the level of the transverse mesocolon (n=1). The mean time interval for development of late bowel obstruction was 7.4 +/- 0.5 months. The causes for late bowel obstruction included internal herniation (n=2) and adhesions (n=1). 6 of 9 bowel obstructions (66%) were considered technically related to the learning curve of the laparoscopic approach. Eight of the 9 patients required operative intervention, and 6 of the 8 reoperations were managed laparoscopically. Management included laparoscopic bypass of the jejunojejunostomy obstruction site (n=5), open reduction of internal hernia (n=2), and laparoscopic lysis of adhesion (n=1)., Conclusions: Bowel obstruction is a frequent complication after LRYGBP, particularly during the learn ing curve of the laparoscopic approach. Specific measures should be instituted to minimize bowel obstruction after LRYGBP as most of these complications are considered technically preventable.

Among Roux-en-Y gastric bypass (RYGB) patients, large male patients carry the greatest risk for severe, life-threatening complications. The higher complication rate is partly related to large amounts of intra-abdominal fat that increases the technical difficulty of the RYGB. In order to minimize the risk for complications, we established a staged approach for weight loss surgery for high-risk, super-obese patients. Patients with intra-abdominal fat at exploration which precluded the performance of RYGB underwent jejunoileal bypass (JIB). Following an initial period of weight loss (6-24 months), they were converted to a RYGB during a second operation. Twenty-four patients underwent initial JIB that was associated with a major complication rate of 8.3 per cent (2/24) and no mortality. Eight patients lost 53.4 +/- 6.3 kg prior to their conversion to RYGB (mean, 14.1 months). There was one major complication (12%) and no deaths (0%). Following RYGB, an additional period of weight loss resulted in overall excess weight loss (EWL) totaling 62 per cent. A two-step procedure is a safe and effective approach for minimizing complications for high-risk patients undergoing RYGB. The initial JIB was associated with low morbidity and no mortality, and the follow-up RYGB procedure was a technically simple operation that could be performed with few complications.

Background: Obesity, which is epidemic in the United States, is associated with increased morbidity and mortality. The combination of diet, exercise, and a behavior-modification program often does not result in ideal body weight., Objective: The aim of this study was to determine the efficacy of phentermine (Phen) alone compared with phentermine plus fenfluramine (Phen-Fen), when used in combination with a very-low-calorie diet (VLCD) for weight loss in an outpatient obesity center., Methods: We analyzed data collected at the UCLA outpatient University Obesity Center between 1993 and 1999. Data for patients who attended the center for at least 12 weeks and at least 4 visits, who were taking Phen or Phen-Fen, and whose body mass index (BMI) was ≥30 kg/m(2) were included in this retrospective study., Results: During the study period, 3200 visits were recorded. Of 1133 potential participants, 446 patients were included in the analysis (309 women, 137 men; mean [SD] age, 46.7 [11.4] years; mean [SEM] body weight, 109.6 [26.7] kg; mean [SEM] BMI, 38.0 [7.6] kg/m(2)). Of these, 128 women and 60 men (mean [SEM] body weight at baseline, 103.4 [24.0] kg and 124.9 [28.2] kg, respectively) received Phen alone; 181 women and 77 men (mean [SEM] body weight at baseline, 102.5 [21.4] kg and 124.9 [30.2] kg, respectively) received Phen-Fen. No statistically significant differences were found between the Phen and Phen-Fen groups in mean age, body weight, or BMI for women or men at baseline. No significant differences in the time of weight loss were found when a VLCD was used with Phen alone compared with the Phen-Fen combination for either sex even at 12 weeks. For women, the mean total body weight loss was 7.4% in the Phen group and 8.7% in the Phen-Fen group, but these differences were not significant. For men, the mean total body weight loss was 7.8% in the Phen group and 8.2% in the Phen-Fen group, but these differences were not significant. No significant differences in BMI, severe adverse events, or dropout rate were found between the 2 treatment groups for men or women., Conclusions: This outpatient study did not detect any significant difference between adjunctive uses of Phen compared with Phen-Fen pharmacotherapy when used with VLCD over 12 weeks. Phen can be used to achieve significant weight loss when combined with VLCD. The tolerability and positive physical response further suggest that Phen is a valuable medication for obesity management in the outpatient setting.

This study evaluated the effects of various levels of dietary calcium on polyp formation, vitamin D homeostasis, and fecal bile acids in the Apcmin mouse. Female Apcmin mice were randomized to three groups and fed a purified diet with either half or double the level of calcium in control AIN-93G. Serum 25-OH-D and fecal bile acids were measured at weeks 0 and 12 of treatment. Mice were killed for polyp scoring by two observers blinded to treatment after 12 weeks. Results show there was no difference in polyp number or tumor load with dietary calcium in any treatment group. Serum 25-OH-D was reduced and total fecal bile acids were increased in animals that received the high calcium diet. We have previously shown that vitamin D supplementation diminishes polyp load; the lack of effect of an altered calcium diet seen here may be due to a disturbance in vitamin D homeostasis.

The current chemotherapeutic modalities for advanced colorectal cancer are limited. DNA-platinating drugs such as cisplatin have poor efficacy against this malignancy. The aim of this study was to identify genes that render survival advantage after cisplatin treatment in metastatic colon cancer. Cell lines SW480 (primary colon cancer) and SW620 (metastatic lesion from the same patient) were obtained from ATCC. Apoptosis was measured by FACS analysis of cisplatin-treated (0.01-10 micro g/ml) and untreated cells. Simultaneous analysis of approximately 1200 cDNAs was performed by microarray technique on untreated and treated cells from lines. Microarray results were confirmed by RT-PCR. The SW620 cell line was more resistant to apoptosis induced by cisplatin. Western blot analysis revealed equal expression of pro-caspases 3, 8, and 9 in both cell lines. Microarray analysis identified 15 genes and 9 expressed sequence tags (ESTs) significantly altered both by cell type (metastatic vs. non-metastatic) and treatment vs. non-treatment. Several of these transcripts are well-characterized genes including MCT, GAD67, P19, GSTM3, Cyclin D1, ATM, and CO-029 that have been implicated in various malignancies. In the present study, we have identified a set of genes responsible for apoptosis resistance following treatment with cisplatin in the late stages of carcinogenesis. Targeting these genes may increase chemotherapy effectiveness in advanced colon cancer and reduce toxicity in normal tissue.

Anastomotic leaks after Roux-en-Y gastric bypass (RYGB) potentially result in considerable morbidity and mortality. In the present report we describe our experience with the management of gastrojejunal anastomotic leaks. Tachycardia and fever are considered early signs of anastomotic disruption. Patients weighing less than 350 pounds underwent radiographic testing to diagnose gastrojejunal disruption. Those with severe leaks or patients too large for radiographic evaluation underwent exploratory laparotomy. For severe anastomotic disruptions a retrograde transanastomotic jejunal sump drain was placed. Twenty-four (1.3%) anastomotic leaks occurred in 1789 RYGBs. Five of the leaks were classified as severe and required retrograde sump tube placement. There was one mortality and all of the other patients completely recovered. Aggressive and early intervention for anastomotic disruption after RYGB is necessary to ensure the best possible outcomes for patients with this complication. A high index of suspicion for leaks in postoperative RYGB patients with tachycardia is required if patients are to have good outcomes when complications develop.

Background: Anastomotic disruption after surgical intervention is an infrequent complication, but may lead to severe morbidity and mortality when it occurs. Of the various gastric procedures, the Roux-en-Y gastric bypass (RYGB) has one of the highest risks for anastomotic leakage. Consequently, a nasogastric tube (NGT) is frequently placed when these operations are performed. Most studies examining the outcomes for patients without postoperative NGTs have been relatively small with groups of patients undergoing a variety of operations. Assessing the incidence of anastomotic leaks by routine elimination of postoperative NGTs requires a large number of patients. In this study, we assessed the safety and efficacy of routine elimination of NGTs in a large cohort of patients undergoing a single operation., Methods: We reviewed our experience with 1067 patients who underwent RYGB at the UCLA medical center. Fifty-six patients had NGTs routinely placed before the implementation of a standard protocol, which eliminated postoperative NGT decompression. The complication rate for the RYGB patient cohort with and without postoperative NGT was compared., Results: We found no difference in the complication rates between the 2 groups (Fisher exact test; P =.21)., Conclusions: Our findings suggest that routine placement of an NGT after RYGB is unnecessary.

Purpose: To determine preoperative risk factors predictive of adverse outcomes after gastric bypass surgery., Summary Background Data: Gastric bypass results in sustained weight loss for seriously obese patients, but perioperative complications can be formidable. Preoperative risk assessment is important to establish the risk-benefit ratio for patients undergoing these operations., Methods: Data for 10 risk factors predictive of adverse outcomes were collected on 1,067 consecutive patients undergoing gastric bypass surgery at the UCLA Medical Center from December 1993 until June 2000. Univariate analyses were performed for individual risk factors to determine their potential significance as predictors for complications. All 10 risk factors were entered into a logistic regression model to determine their significance as predictors for complications. Sensitivity analysis was performed., Results: Univariate analysis revealed that male gender and weight were predictive of severe life-threatening adverse outcomes. Multistep logistic regression yielded only male gender as a risk factor. Male patients were heavier than female patients on entry to the study, accounting for weight as a potential risk factor. Patients older than 55 years had a threefold higher mortality from surgery than younger patients, although the complication rate, 5.8%, was the same in both groups. Sensitivity analysis demonstrated that the risk for severe life-threatening adverse outcomes in women increased from 4% for a 200-lb female patient to 7.5% for a 600-lb patient. The risk increased from 7% for a 200-lb male patient to 13% for a 600-lb patient., Conclusions: Large male patients are at greater risk for severe life-threatening complications than smaller and/or female patients. Risk factors thought to be predictive of adverse outcomes, such as a history of smoking or diabetes, proved not to be significant in this analysis. Older patients had the same complication rate but a threefold higher mortality, suggesting that they lack the reserve to recover from complications when they occur.

PC-SPES is a mixture of eight herbs with antiproliferative activity in prostate cancer cell lines and antitumor effects in animal models of prostate cancer. In addition, evidence of clinical efficacy in advanced prostate cancer has been reported. PC-SPES has also been shown to have antitumor activity against several other cancer cell lines including breast and neuroepithelial cancer, melanoma, and leukemia cell lines. Because of these findings, we investigated the effects of PC-SPES in vitro in colon cancer cell lines SW480, SW620, and DLD-1 and in vivo in the Apc(min) mouse, a murine model for intestinal carcinogenesis. For the in vitro studies, colon cancer cell lines were exposed to an ethanolic extract of PC-SPES compared with a diluent control [ethanol < or = 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 micro l/ml) caused a 95% inhibition of cell proliferation of the DLD-1 colon cancer cell line, and similar results were observed in the SW480 and SW620 colon cancer cell lines. Cell cycle analysis demonstrated a drastic (> or =60%) accumulation of cells in the G(2)-M phase with a concomitant decrease of cells in the G(0)-G(1) phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 micro l/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of beta-tubulin in the SW620 cell line exposed to PC-SPES. Terminal deoxynucleotidyl transferase-mediated nick end labeling analysis revealed an increase in apoptotic colon cancer cells incubated with PC-SPES. For the in vivo studies, female 4-5-week-old Apc(min) mice were randomized to two groups: a PC-SPES-treated group (n = 11) received 250 mg/kg/day (0.2 ml) PC-SPES via gastrointestinal gavage; and a control group (n = 10) received 0.2 ml of the vehicle solution (1.5% carboxymethylcellulose with 0.2% Tween 20) via gastrointestinal gavage. Both groups were treated five times a week for 10 weeks. After treatment, the gastrointestinal tract was dissected for polyp scoring by two observers blinded to treatment. The Apc(min) mice given PC-SPES had a 58% reduction in tumor number and a 56% decrease in tumor load. No effect on either food intake or body weight was observed in the treated versus sham groups. The present study is the first to report the potent activity of PC-SPES against colon cancer. Both cell cycle arrest and apoptosis occurred after treatment with PC-SPES. This suggests that the components of this herbal mixture, either independently or in combination, acted in colon cancer, resulting in a drastic effect on tumor initiation and tumor progression.

Background: Biliopancreatic diversion (BPD) has been advocated for the treatment of morbid obesity. This procedure has the theoretical advantage that patients retain normal eating capacity and lose weight irrespective of their eating habits. However, vitamin deficiencies may develop because BPD causes malabsorption., Objective: This report describes a 40-y-old mother and her newborn infant, who developed vitamin A deficiency as a result of iatrogenic maternal malabsorption after BPD. Our primary objective is to show that BPD patients need close follow-up and lifelong micronutrient supplementation to prevent nutrient deficiencies in themselves and their offspring., Design: The medical records of the mother and infant were reviewed, and their clinical course was followed until 10 mo postpartum. The mother was also interviewed on several occasions about her medical care, follow-up, and supplemental vitamin use., Results: The mother developed night blindness with undetectable serum vitamin A concentrations in the third trimester of her pregnancy. Her vitamin A deficiency was untreated until she delivered her infant. At delivery, the infant also had vitamin A deficiency. He may have permanent retinal damage, but this is still unclear because the ophthalmologic examination performed at 2 mo of age was inconclusive., Conclusions: Complications of BPD may take many years to develop, and the signs and symptoms may be subtle. Because of the malabsorption that results from BPD, patients need lifelong follow-up and appropriate vitamin supplementation to prevent deficiencies. These nutrient deficiencies can also affect the offspring of female BPD patients.

Continuous positive airway pressure (CPAP) is used to prevent apneic arrest and/or hypoxia in patients suffering from obstructive sleep apnea. This modality has not been universally accepted for patients following upper gastrointestinal surgery because of concerns that pressurized air will inflate the stomach and proximal intestine, resulting in anastomotic disruption. This study was performed to assess the safety and efficacy of postoperative CPAP for patients undergoing a gastrojejunostomy as part of a Roux-en-Y gastric bypass (RYGB) procedure. A total of 1067 patients (837 women [78%] and 230 men [22%]) were prospectively evaluated for the risk of developing anastomotic leaks and pulmonary complications after the RYGB procedure. Of the 1067 patients undergoing gastric bypass, 420 had obstructive sleep apnea and 159 were dependent on CPAP. There were 15 major anastomotic leaks, two of which occurred in CPAP-treated patients. Contingency table analysis demonstrated that there was no correlation between CPAP utilization and the incidence of major anastomotic leakage (P = 0.6). Notably, no episodes of pneumonia were diagnosed in either group. Despite the theoretical risk of anastomotic injury from pressurized air delivered by CPAP, no anastomotic leaks occurred that were attributable to CPAP. There were no pulmonary complications in a patient population that is at risk for developing them postoperatively. CPAP is a useful modality for treating hypoventilation after RYGB without increasing the risk of developing postoperative anastomotic leaks.

Both calcium and vitamin D are thought to be able to inhibit colon carcinogenesis. To better define the effects of vitamin D, we studied 1alpha,25-(OH)(2)-D(3) and a noncalcemic synthetic analogue of vitamin D(3) (VD(3)) in the Apc(min) mouse. Female Apc(min) mice 4-5 weeks old were randomized to four groups: a VD(3)-treated group (n = 11) were given injections of 0.01 microg of 1alpha,25-(OH)(2)-D(3) i.p. three times per week; an analogue-treated group (n = 10) received 5 microg of 1alpha,25-(OH)(2)-16-ene-19-nor-24-oxo-D(3) i.p. three times per week; and a control group (n = 12) received sham injections of PBS. A sulindac-treated group (n = 10) was used as a positive control. Doses of these compounds were chosen based on previous toxicity studies in mice and rats. After 10 weeks of treatment, mice were killed and two observers (S. H., R. W. I.), blinded to treatment, scored polyp number and size. Tumor number was not affected with 1alpha,25-(OH)(2)-D(3) or vitamin D analogue administration. A significant decrease in total tumor load (sum of all polyp areas) over the entire gastrointestinal tract was seen in the analogue (36% decrease; P < 0.05) and the VD(3) groups (46%; P < 0.001). There was a significant decrease in polyp number (49%; P < 0.001) and polyp area (70%; P < 0.001) in the sulindac group. Reverse transcription-PCR of the total RNA derived from intestinal tissue revealed expression of the vitamin D receptor throughout the small intestine and the colon. Serum calcium levels in the analogue group were not elevated at week 4 of treatment and only moderately elevated (22%) by week 8 (P < or =0.001). In contrast, serum calcium in the VD(3) group was significantly elevated (P < or =0.001) at weeks 4 (23%) and 8 (45%). Food intake and growth rate were significantly lower in the VD(3) group (26%, P < 0.001, and 27%, P < 0.001, respectively) at week 10. In contrast, food intake and growth rate were similar for the control, sulindac, and analogue groups. Our results indicate that a noncalcemic analogue of vitamin D can significantly decrease intestinal tumor load in Apc(min) mice without severe toxic side effects and suggest that these compounds may have utility as chemopreventive agents in groups at high-risk for colon cancer.