Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

Single-site robotic cholecystectomy (SSRC): an initial review of safety and feasibility.

AIM: This report comprehensively reviews the findings from initial experiences with single-site robotic cholecystectomy (SSRC) across the world, and reports the feasibility of this new approach and novel platform. It attempts to be impartial in evaluating this novel robotic platform and approach. METHODS: A search utilizing MEDLINE®/PubMed® and Google Scholar was undertaken to identify articles about SSRC. Eleven articles met our criteria and were reviewed. Data collected included: patient demographic, preoperative, intraoperative, and postoperative data. Data are presented as weighted means±pooled standard deviations. RESULTS: Age and BMI was 46±13.1 years and 26±4.2 kg/m2, respectively. Operative time was 80±24.1 minutes; robotic console time was 38±16.9 minutes; and docking time was 7±3.1 minutes. Blood loss ranged from 0-150 mL. Ninety-eight percent of SSRC undertaken were completed robotically without the addition of other trocars/incisions, 2% of operations had additional trocars added, and three operations (<1%) were converted to "open". Postoperative hospital stay was 26 hours. Pain ratings, determined 2-3 weeks postoperatively, ranged from 0-2 on a Likert scale. CONCLUSION: This study serves as an overall analysis and review of SSRC. Existing reports of initial experiences with SSRC documents the operation is safe, feasible, and easily learned by surgeons from a broad spectrum of geographic areas. However, a detailed cost analysis is necessary in order to determine what the future holds for this novel approach.

Evolution of segmental anesthesia for Laparo-Endoscopic Single Site (LESS) cholecystectomy.

AIM: Transumbilical Laparo-Endoscopic Single Site (LESS) surgery promises improved cosmesis, quick recovery, reduced postoperative pain and shorter length of hospital stay. Since only a simple umbilical incision is used, LESS surgery can be completed with segmental epidural anesthesia. This study describes the evolution of our technique of LESS cholecystectomy from a combination of spinal and epidural anesthesia to thoracic epidural alone and presents our experience with its safety, the observed morbidity, and the reported patient satisfaction. METHODS: In August 2009, a prospective evaluation of LESS cholecystectomy with regional anesthesia was undertaken. We recruited patients with chronic cholecystitis or symptomatic cholelithasis. Blood loss, operative time, complications, and length of hospital stay were measured. Preoperatively and 14 days postoperatively, outcome and symptom resolution were scored. RESULTS: Fifteen consecutive patients underwent LESS cholecystectomy; first with combined spinal-epidural (CSE), and then with thoracic epidural anesthesia alone. Immediate postoperative pain and discomfort were well tolerated. VAS scores upon admission to PACU were 0.4 (1.7±2.2). At postoperative day 14, the patients scored high values for "Satisfaction", 10 (10±1.0) and "Cosmesis", 10 (9.3±1.5). CONCLUSION: LESS cholecystectomy with epidural anesthesia can be undertaken safely. Patient satisfaction and cosmesis are particularly prominent amongst our patients. Our experience supports further utilization of epidural anesthesia for selected patients undergoing LESS cholecystectomy.

BMI affects presenting symptoms of achalasia and outcome after Heller myotomy.

BACKGROUND: Obesity has reached epidemic proportions in the United States and worldwide. The impact of obesity on health is increasingly recognized; however, its impact on achalasia has not been established. METHODS: The present study was undertaken to determine the impact of body mass index (BMI) on the symptoms of achalasia and outcome after myotomy. In our institution, 262 patients have undergone laparoscopic Heller myotomy and scored their symptoms before and after myotomy on a Likert scale (frequency: 0 = never to 10 = every time I eat/always; severity 0 = not bothersome to 10 = very bothersome). Patients were stratified by BMI > or = 30 kg/m2 or BMI < 30 kg/m2, and preoperative symptom scores and postmyotomy outcomes were compared. RESULTS: Patients with BMI > or = 30 had higher symptom scores for frequency of choking and vomiting before myotomy (p < 0.05). All symptom scores improved significantly after myotomy, except heartburn frequency and severity for patients with BMI > or = 30. By regression analysis, increasing BMI tended to exacerbate the frequency of choking and vomiting before myotomy and the frequency of heartburn after myotomy. Among the patients with BMI > or = 30 kg/m2, 73% reported excellent or good outcomes compared to 91% for patients with BMI < 30 kg/m2 (p = 0.02, Fisher's exact test). However, 96% of patients with BMI > or = 30 kg/m2, as well as 93% of patients with BMI < 30 kg/m2 would still elect to have the operation if they were asked to make the decision over again. CONCLUSIONS: Although some preoperative symptoms are exacerbated by elevated BMI, all symptoms of achalasia are improved with myotomy, even when undertaken for obese patients.

Outcomes promote reoperative Heller myotomy for symptoms of achalasia.

BACKGROUND: Heller myotomy is accepted as first-line therapy for achalasia, yet for a small number of patients, symptoms persist or recur after myotomy. This study was undertaken to report our results with reoperative laparoscopic Heller myotomy for recurrent symptoms of achalasia. METHODS: We have undertaken laparoscopic Heller myotomy in 275 patients and reoperative myotomy in 12 patients for recurrent dysphagia, of which three had their initial myotomy undertaken by us. For each, studies prior to reoperative Heller myotomy documented a nonrelaxing lower esophageal sphincter without stricture. Patients scored symptoms before and after reoperative myotomy. RESULTS: Before reoperative myotomy, 75% underwent dilation and 42% underwent Botox injection. Ten of twelve reoperative myotomies were undertaken and completed laparoscopically. Median follow-up is 24.1 months (29.0 months + 25.89). Symptom frequency and severity scores improved significantly after reoperative myotomy. Frequency of vomiting and frequency and severity of heartburn were improved after reoperative myotomy, but not to a significant extent. However, they were not particularly notable prior to surgery, compared to obstructive symptoms, such as dysphagia. Excellent or good outcomes were reported in 73%, and notably, 91% stated that they would have the operation again after having been through the process firsthand and knowing their outcomes. CONCLUSION: Patient outcomes promote the application of reoperative Heller myotomy for recurrent or persistent symptoms of achalasia following Heller myotomy.

Upright, supine, or bipositional reflux: patterns of reflux do not affect outcome after laparoscopic Nissen fundoplication.

INTRODUCTION: This study was undertaken to determine if the body position in which gastroesophageal reflux occurs before fundoplication--i.e., pattern of reflux--affects symptoms before or after laparoscopic Nissen fundoplication. METHODS: A total of 417 patients with gastroesophageal reflux disease (GERD) underwent pH studies, and the severity of reflux in the upright and supine positions was determined. The percent time with pH less than 4 was used to assign patients to one of four groups: upright reflux (pH < 4 more than 8.3% of time in upright position, n = 80), supine reflux (pH < 4 more than 3.5% of time in supine position, n = 73), bipositional reflux (both supine and upright reflux, n = 163), or neither (n = 101). Before and after laparoscopic Nissen fundoplication, the frequency and severity of symptoms of reflux (e.g., dysphagia, regurgitation, choking, heartburn, chest pain) were scored on a Likert scale (0 = never/not bothersome to 10 = always/very bothersome). For each patient, symptom scores before versus after fundoplication were compared using the Wilcoxon matched pairs test; comparisons of symptom scores among patients grouped by reflux patterns were made using Kruskal-Wallis test. RESULTS: Before fundoplication, the patterns of reflux did not affect the frequency or severity of reflux symptoms. After laparoscopic fundoplication, all symptoms of bipositional reflux improved, and essentially all symptoms of isolated supine or upright reflux or neither improved. CONCLUSIONS: Preoperatively, regardless of the patterns of reflux, symptoms among patients were similar. After fundoplication, symptoms of GERD improved for all patterns of reflux. Laparoscopic fundoplication imparts dramatic and broad relief of symptoms of GERD, regardless of the patterns of reflux. Application of laparoscopic Nissen fundoplication is encouraged.

Postmyotomy recollection of premyotomy symptoms of achalasia is very accurate, supporting longitudinal studies of symptom improvement.

BACKGROUND: Recollection of preoperative symptom frequency and severity may change postoperatively, thus invalidating longitudinal studies. This study was undertaken to compare symptoms of achalasia before myotomy to patients' postoperative recollection of premyotomy symptoms. METHODS: A total of 173 patients, 54% male, of median age 48 years, have undergone laparoscopic Heller myotomy and have been followed through a prospectively maintained registry. Preoperatively, patients scored the frequency and severity of their symptoms on a Likert scale: 0 (never/very bothersome) to 10 (always/very bothersome). Similarly, after laparoscopic Heller myotomy, patients scored the frequency and severity of their symptoms, and re-scored their preoperative symptoms. Data are presented as median, mean +/- SD. RESULTS: Before myotomy, dysphagia, regurgitation, choking, chest pain, vomiting, and heartburn were particularly notable; symptom scores nearly globally improved after myotomy (p < 0.05 for all, Wilcoxon matched pairs test), especially obstructive symptoms. Postmyotomy recollection of premyotomy symptom frequency and severity was neither substantively nor consistently different from premyotomy scoring. CONCLUSIONS: Before myotomy, patient symptom scores reflected the deleterious impact of achalasia. After myotomy, patient symptom scores dramatically improved, reflecting the favorable impact of laparoscopic Heller myotomy. Even years after myotomy, patient recollection of premyotomy symptom severity and frequency is very accurate and supports longitudinal studies of symptom improvement after myotomy.

Addition of matrix metalloproteinase inhibition to conventional cytotoxic therapy reduces tumor implantation and prolongs survival in a murine model of human pancreatic cancer.

Matrix metalloproteinases (MMPs) participate in basement membrane degradation, a critical step in invasion of cancer cells. We have previously shown that MMP inhibition of pancreatic cancers improves survival and decreases MMP production in vivo. The purpose of this study was to determine whether BB-94 was better than cytotoxic therapy and would increase the efficacy of cytotoxic therapy (gemcitabine) in a murine model of human pancreatic cancer. A human pancreatic adenocarcinoma cell line (HPAC) was injected into the pancreata of BALB/c nu/nu mice. The mice were randomized 7 days after cancer cell injection to receive vehicle control, BB-94, gemcitabine, or gemcitabine and BB-94 until death or sacrifice at 84 days. At necropsy, tumors were harvested, and the relative enzyme activities of MMP-2 and MMP-9 were determined by gelatin zymography. Active MMP-2 levels in serum were determined using an ELISA technique. Combination treatment with gemcitabine and BB-94 significantly reduced implantation rates and improved survival in mice with documented orthotopic tumors compared with either therapy alone or control. Tumor levels of active and latent MMP-2 were higher than those of MMP-9 in both treated and control mice. There was a significant reduction of tumor MMP-2 activity in mice treated with BB-94, gemcitabine, or gemcitabine and BB-94. Serum levels of active MMP-2 were reduced in all treated groups, with the greatest reduction occurring in mice treated with gemcitabine and BB-94. Combination therapy with gemcitabine and BB-94 reduces cancer implantation and improves survival compared to treatment with BB-94, gemcitabine, or vehicle control alone. MMP production was reduced in all treated groups, reflecting reduced tumor progression, which was particularly seen with combination therapy with gemcitabine and BB-94. This study supports combining MMP inhibition with cytotoxic therapy (gemcitabine) for patients with pancreatic cancer.

Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial.

PURPOSE: The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. PATIENTS AND METHODS: Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. RESULTS: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P =.19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with gemcitabine and marimastat 5 and 10 mg (P <.003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat-treated patients, respectively. The major toxicity of marimastat was musculoskeletal (44% of marimastat patients, compared with 12% of gemcitabine patients; musculoskeletal toxicity was severe in only 8% of marimastat patients). CONCLUSION: The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.

Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies.

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.

Financial status does not predict weight loss after bariatric surgery.

BACKGROUND: Lower socioeconomic status and poor funding are thought to be associated with suboptimal outcome after bariatric surgery. We undertook this study to determine if funding status is a predictor of outcome in patients undergoing bariatric surgery. METHODS: The medical records of 131 consecutive patients who underwent vertical banded gastroplasty (VBG) for clinically severe obesity (BMI >40 kg/m2) were reviewed. Patients were divided into three groups based on insurance status: (1) commercially insured/traditional indemnity programs; (2) entitlement programs (Medicare), and (3) medically indigent (Medicaid or no funding). Data is mean +/- SD. Data was analyzed using ANOVA and Student t-test. RESULTS: The three groups had similar preoperative weight. Mean BMI was 39 +/- 13, 42 +/- 15, 41 +/- 11 at 1 year, and 40 +/- 13, 43 +/- 16, 45 +/- 16 at 2 years postoperatively for the insured, entitlement, and indigent groups, respectively. CONCLUSION: After standard preoperative evaluation and screening, patients loss weight following VBG independent of insurance status. Source of funding should, therefore, not preclude patients from undergoing bariatric surgery. Patients with limited financial resources can expect similar outcomes as patients with commercial insurance.

Outcome of gastric restriction procedures: weight, psychiatric diagnoses, and satisfaction.

BACKGROUND: Weight losses following bariatric surgery have varied widely, depending on length of follow-up and various pre-surgical characteristics of patients undergoing surgery. METHODS: One hundred thirty one patients had a detailed presurgical psychiatric evaluation. Patients were assessed clinically for 2 years after surgery and at follow-up a mean of 5.7 years after surgery. RESULTS: Mean presurgical body mass index (BMI) was 52.9 kg/m2; therefore, many patients had 'super obesity'. Two-thirds of the patients were located a mean of 5.7 years after surgery. The mean change in BMI at follow-up was 25% and the mean weight loss was 27%. One-third had excellent or good weight outcomes using the Griffen criteria. Five patients had died by follow-up. There was no relationship between age, gender, or fat content presurgically and weight loss at follow-up, although presurgical weight was associated with greater weight loss at follow-up. Weight regain began 2 years after surgery. There was no relationship between the presence or absence of a presurgical psychiatric diagnosis and weight loss at follow-up. There was also no relationship between the presence of a presurgical psychiatric diagnosis and various mental health parameters at follow-up. Satisfaction with the surgery was marginally associated with weight loss but significantly associated with improved mental and physical health. CONCLUSIONS: Mean weight losses were less than have been previously reported with gastric restriction procedures but the follow-up was longer than usually reported and many patients had 'super obesity' prior to surgery. The implications of 'super obesity' for weight loss are discussed.

Bariatric surgery and multiple personality disorder: complexities and nuances of care.

BACKGROUND: Multiple personality disorder (MPD) can occur in patients with morbid obesity in need of bariatric surgery, though few reports noting this association exist in the literature. Herein we address MPD in morbid obesity, in the context of a patient presenting to us seeking surgical treatment of her morbid obesity. METHODS: A 31-year-old morbidly obese (BMI 49 kg/m2) Hispanic female presented in early 1994 requesting bariatric surgery. She had been a victim of violent sexual abuse as a young girl. Subsequently, she developed at least three personalities, including one male personality. RESULTS: Although she has lost nearly 45 kg after gastroplasty, her care has been complicated by her named multiple personalities. While MPD are infrequent and unfamiliar to most care providers, successful outcomes can be promoted with a proper approach. CONCLUSIONS: This patient's care illustrates that: (1) all personalities must agree to proposed operative intervention; (2) consent must be obtained from the 'true' patient; and (3) postoperative care and follow-up must address all personalities for an optimal outcome.

Outcome following bariatric surgery in super versus morbidly obese patients: does weight matter?

BACKGROUND: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. METHODS: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. RESULTS: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m2 and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m2 and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m2 (61% EBW) versus 34 kg/m2 (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. CONCLUSIONS: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.

Body composition and source of weight loss after bariatric surgery.

BACKGROUND: Little is known about the composition and source of weight loss after bariatric surgery for morbid obesity. PURPOSE: This study was undertaken to determine changes in weight, body mass index (BMI), lean body weight (LBW), fat weight (FW) and left ventricular cardiac mass (LVM) following vertical banded gastroplasty (VBG). METHODS: After VBG for morbid obesity, 26 women and four men (mean age = 39.1 years) were weighed and had body composition analysis undertaken at intervals. Thirteen patients underwent echocardiography preoperatively and 1 year postoperatively to determine change in LVM and LVM index. RESULTS: Over 12 months there was significant weight loss for all weight parameters examined (p < 0.05). Fat weight loss was most significant; total weight loss and reduction of BMI were significant but less so than fat loss (Wilcoxon's signed ranks test). LBW loss had the smallest contribution to weight loss (p < 0.0001). There was a significant loss of LVM and posterior cardiac wall thickness (p < 0.05). CONCLUSIONS: VBG can lead to loss of lean body weight and left ventricular mass, and more dramatically, fat weight, body weight, and BMI. Cardiac mass and lean body mass are preferentially conserved relative to body fat with weight loss after VBG.

Clinical predictors of sleep apnea in patients undergoing bariatric surgery.

BACKGROUND: Sleep apnea is a frequent and unappreciated condition of morbidly obese patients. If unrecognized it could lead to significant postoperative complications. A clinical tool to assess the severity of sleep apnea is not available. We prospectively determined whether the Epworth Sleepiness Scale (ESS) or body mass index (BMI) predict the severity of sleep apnea in morbidly obese patients. METHODS: 66 consecutive patients evaluated for bariatric surgery from June to November 1999 were examined and prospectively administered a health questionnaire including the ESS. Patients with an ESS > or =6 were referred for polysomnography with calculation of Respiratory Disturbance Index (RDI). Sleep apnea was graded as mild (RDI 6-20), moderate (RDI 21-40) and severe (RDI>40). Clinical variables such as BMI and ESS score were compared using regression analysis. Data are mean +/- SEM. RESULTS: 4 men and 23 women (27/66) who scored >6 on the ESS completed a sleep study. Mean ESS was 13+/-4.5. Sleep apnea was mild in 13 patients, moderate in 7, severe in 6, and absent in 1. Mean age was 43+/-9.5 years. BMI was 52+/-10 kg/m2. Linear regression analysis did not demonstrate correlation between ESS score and severity of sleep apnea (r2=0.03, p>0.05). Multiple regression analysis demonstrated no correlation between BMI, patient snoring, and RDI score. CONCLUSIONS: Sleep apnea is frequent in candidates screened for bariatric surgery. ESS is a useful tool to investigate daytime sleepiness and other manifestations of sleep apnea. However, the ESS does not predict the severity of sleep apnea. Clinical suspicion of sleep apnea should prompt polysomnography.

Lymphocyte dysfunction in injured adults with elevated Candida antigen titers.

BACKGROUND: Lymphocytes play an important role in the activation of polymorphonuclear neutrophil (PMN) antimicrobial functions. This study was undertaken to evaluate the ability of lymphocytes from severely injured adults with elevated Candida antigen titers to activate the anticandidal function of normal PMNs. METHODS: Lymphocytes from 13 injured adults with elevated Candida antigen titers (titer+) were isolated and incubated with or without heat-killed C. albicans. After a 48-hour incubation, cell culture supernatants were harvested and tested for the ability to activate the anticandidal function of normal PMNs. Lymphocytes from 13 volunteers and 13 injury-matched patients with negative Candida antigen titers (titer-) were studied for comparison. RESULTS: The patients with titer+ and titer- were well matched in terms of age, sex, Injury Severity Score, units of blood transfused, and length-breadth of antibiotic therapy. Patients with titer+ had a higher incidence of bacterial infections than did patients with titer-. Only 2 of the 13 patients with titer+ had a positive Candida culture. Lymphocytes from the volunteers and patients with titer- released large amounts of a PMN-activating factor(s) when exposed to C. albicans. Lymphocytes from the patients with titer+ were defective in their ability to release this activating factor(s) after exposure to C. albicans. CONCLUSIONS: Although culture evidence of Candida was uncommon, injured adults with elevated Candida antigen titers have lymphocyte dysfunction and often suffer documented bacterial infections.

Does the direction of portal blood flow determine outcome with small-diameter prosthetic H-graft portacaval shunt?

BACKGROUND: Partial portal decompression, as attained by small-diameter prosthetic H-graft portacaval shunting, continues to gain popularity because of favorable outcomes. This study was undertaken to determine whether the direction of preshunt or postshunt portal blood flow or reversal in the direction of portal flow occurred with shunting effect outcome after small-diameter prosthetic H-graft portacaval shunt. METHODS: In 56 consecutive patients the direction of portal flow was determined before and after shunting. The direction of portal blood flow before and after shunting and changes in the direction of portal flow that occur with shunting were correlated with 30-day and 1-year survival, as well as with the rate of postshunt encephalopathy. RESULTS: Portal pressures significantly decreased in all with shunting. Whether or not stratified by Child's classification, neither the preshunt nor postshunt direction of portal flow affected 30-day or 1-year survival or incidence of encephalopathy. Eleven patients (significant at p < 0.001, fisher's exact test) had reversal of portal blood flow with shunting without an increase in 30-day or 1-year survival or incidence of encephalopathy. CONCLUSIONS: Small-diameter prosthetic H-graft portacaval shunts significantly reduce portal pressure and lead to reversal of portal flow in significant numbers. Significant hepatic dysfunction is uncommon after shunting. Neither the direction of preshunt or postshunt portal blood flow nor the reversal of portal blood flow with shunting has an effect on clinical outcome after small-diameter prosthetic H-graft portacaval shunt.

The physiologic effects of ileal reservoirs and efferent conduits complementing ileoanal anastomosis: an experimental study in dogs.

S-shaped ileal reservoirs (SSRs) and double-barreled ileal reservoirs (DBRs) of equal size were placed 6 or 2 cm from the anus and evaluated over 1 year for their ability to improve the functional incontinence noted after an ileoanal anastomosis (IAA). Compared to straight IAA, both reservoirs prolonged intestinal transit (235 minutes versus 135 minutes, P less than 0.001) and alleviated frequency without causing nutritional abnormalities. The capacity of the reservoirs was greater than that of a comparable length of distal ileum in dogs (n = 6) with straight IAA (304 +/- 16 ml versus 102 +/- 2 ml, P less than 0.001). The SSRs (n = 9), in contrast to the DBRs (n = 10), developed excessive volume capacity (360 +/- 30 ml versus 254 +/- 104 ml, P less than 0.01) and obstructive complications. Reservoirs with 6 cm efferent conduits (n = 13), in contrast to those with a 2 cm efferent conduit (n = 6), underwent marked dilatation (334 +/- 24 ml versus 238 +/- 13 ml, P less than 0.005). Electromyography and manometry revealed the DBRs to be more contractile than the SSRs but less than ileum proximal to the anus in dogs with a straight IAA. Ileal reservoirs improve results after IAA. Reservoirs should be complaint and yet contractile (e.g., DBR) so as to discourage excessive dilatation, which is the harbinger of obstruction. Ileal conduits facilitate reservoir placement, but if longer than 2 cm they excessively impeded reservoir emptying, predisposing to excessive reservoir dilatation and obstruction. A DBR with a 2 cm efferent conduit results in continence without obstructive problems.

Postoperative ascitic leaks: the ongoing challenge.

BACKGROUND: The leak of ascitic fluid from surgical incisions is thought to be associated with a very high mortality rate. There have been few reports, however, focusing on the clinical characteristics, management, or mortality rates of this condition. METHODS: During a 10-year period, 18 patients with postoperative ascitic fluid leaks were treated. All patients had ascites before surgery and all had liver disease; in 13 of the 18 patients alcoholic liver disease was the cause of ascites. RESULTS: Ten of the 18 patients died (56%). Midline incisions were more often associated with recalcitrant leaks and fatal complications than were transverse incisions. CONCLUSIONS: Early consideration of fascial dehiscence and prompt repair is emphasized. The most effective predictor of survival was cessation of the leak.