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.

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.

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.

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.

Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.

BACKGROUND: CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure and change in quality of life (QoL) or pain compared with gemcitabine alone. PATIENTS AND METHODS: A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21). RESULTS: Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The objective response rate with CG was 12% versus 14% with PG when investigator-assessed and 1% versus 6%, respectively, when assessed centrally. Time to treatment failure did not differ between the two arms (P = 0.304). QoL scores at 2 months were worse with CG than with PG. Pain response rates were similar between the two groups. There was an increased incidence of neutropenia and thrombocytopenia with CG. CONCLUSIONS: Adding CI-994 to gemcitabine in advanced pancreatic carcinoma does not improve overall survival, response rate or time to progression; CG produced decreased QoL and increased hematological toxicity and appears inferior to single-agent gemcitabine.

Cholangiocarcinoma: advocate an aggressive operative approach with adjuvant chemotherapy.

Cholangiocarcinoma presents many challenges. Prognosis is thought to be determined by conventional predictors of survival; margin status, pathologic criteria, stage, and comorbid disease. Ninety-four patients, 57 males and 37 females, underwent resections for cholangiocarcinoma between 1989 and 2000. Thirty-two patients (34%) had distal tumors, 10 had midduct lesions, and 52 had proximal/intrahepatic lesions. Thirty-four patients underwent pancreaticoduodenectomies, 23 bile duct resections alone, and 37 bile duct and concomitant hepatic resections. Tumor location did not influence mean survival (distal, 28 months +/- 23; midduct, 28 months +/- 21; and proximal, 31 months +/- 36). Operation undertaken did not alter survival (bile duct resection, 30 months +/- 37; pancreaticoduodenectomy, 27 months +/- 23; and concomitant bile duct/hepatic resection, 32 months +/- 32). TNM stage failed to predict survival: 5 stage I (29 months +/- 22), 12 stage II (41 months +/- 33), 12 stage III (33 months +/- 19), and 64 stage IV (27 months +/- 32). Tumor size did not influence survival: T1-2 (32 months +/- 33) versus T3-4 lesions (29 months +/- 25). Mean survival with negative margin (n = 67) was 34 months +/- 33, whereas microscopically positive (n = 13, 23.9 months +/- 25) or grossly positive (n = 14, 20.4 months +/- 20) margins were predictive of significantly shorter survival (P < 0.03). Adjuvant treatment (n = 41) was associated with significantly longer survival (40.5 months +/- 36) than those who received no further therapy (n = 53; 24 months +/- 24) (P = 0.05). TNM stage, tumor size, operation undertaken, and location were not associated with duration of survival after resection. Margin status was associated with duration of survival, though extended survival is possible even with positive margins. Advanced stage should not preclude aggressive resection. Without specific contraindications, an aggressive operative approach is advocated followed by adjuvant therapy.

Laparoscopic management of symptomatic achalasia associated with epiphrenic diverticulum.

BACKGROUND: We evaluated outcome after laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication. METHODS: Patients with symptomatic achalasia and epiphrenic diverticula underwent laparoscopic diverticulectomy, Heller myotomy, and partial fundoplication. Intraoperative endoscopy and postoperative esophagography were performed in all patients. Patients graded preoperative and postoperative dysphagia and heartburn on a Likert scale. RESULTS: Anterior fundoplication was performed in five patients and posterior fundoplication in one. Mean follow-up was 9 months (range, 1-17 months). One intraoperative complication occurred--an esophagotomy that was laparoscopically repaired. There were no postoperative leaks. Patient-reported dysphagia decreased from 4.5 +/- 0.8 (mean +/- SD) to 1.8 +/- 1.7 ( p < 0.05 matched pair analysis). Heartburn decreased from 4.3 +/- 0.8 to 1.3 +/- 1.3 ( p < 0.05). All patients reported improvement in symptoms after operation. CONCLUSION: Laparoscopic esophageal diverticulectomy, Heller myotomy, and partial fundoplication with intraoperative endoscopy safely reduce dysphagia associated with achalasia and esophageal diverticula while limiting symptoms of gastroesophageal reflux.

Videoscopic heller myotomy as first-line therapy for severe achalasia.

To many nonsurgeons myotomy is considered an excessively invasive treatment for achalasia and has become a salvage procedure when esophageal dilation and botulinum toxin (botox) injections fail. We sought to examine our experience with videoscopic Heller myotomy to determine whether preoperative therapy predicts perioperative complications and long-term outcome. Videoscopic Heller myotomy was undertaken in 111 patients with achalasia between June 1992 and May 2000. Intraoperative endoscopy was used in all patients. Fundoplication was used selectively for patients with large hiatal hernias or as part of repair of esophageal perforation. Patients were asked to grade their dysphagia and reflux symptoms before and after myotomy on a scale of 0 (no symptoms) to 5 (severe symptoms). Patients were also asked to rate their outcome as excellent (no symptoms), good (greatly improved), fair (slightly improved), or poor (not improved) compared with their preoperative status. Patients were stratified on the basis of preoperative intervention (botox, pneumatic dilation, botox and pneumatic dilation, or no botox or dilation) and compared. Previous pneumatic dilation and/or botox injection had been undertaken before operation in 88 (79%) patients whereas 23 (21%) patients had no invasive preoperative therapy. The overall mean preoperative dysphagia score was 4.8+/-0.8 and mean preoperative reflux score was 3.3+/-2.1. Groups of patients undergoing preoperative interventions were similar to those patients not undergoing preoperative interventions in terms of preoperative symptoms, dysphagia scores, and reflux scores. Postoperative complications (13%) and perforations (8%) were slightly more common in patients who had undergone preoperative botox or dilation (P = not significant). Subjectively, operative myotomy was more difficult in patients who had preoperative botox or dilation. Patients had significant improvement in dysphagia, dysphagia score, reflux score, emesis/ regurgitation, and chest pain (P < 0.05) regardless of preoperative intervention. After myotomy patients who had never undergone botox or pneumatic dilation were less likely to have mild dysphagia compared with those with previous botox injections (30% vs 53%; P = 0.09), previous dilations (30% vs 54%; P = 0.09), or both (30% vs 59%; P = 0.04). As well, dysphagia scores were better if no preoperative therapy had been undertaken: botox 0.8+/-1.3, dilation 1.0+/-1.4, botox and dilation 1.0+/-1.3, and no therapy 0.3+/-0.7 (P < 0.05). Overall 97 per cent of patients stated that their symptoms were improved although more patients tended to have excellent or good outcomes if no preoperative intervention was undertaken (91%) compared with patients undergoing preoperative botox (86%), dilation (83%), or both (82%) (P = not significant). We conclude that videoscopic Heller myotomy is safe and efficacious particularly in patients who have not undergone previous endoscopic interventions. The difference in patients' outcomes based on preoperative therapy may be related to a less difficult operation in patients who forgo endoscopic therapy and elect to undergo early myotomy. Although videoscopic Heller myotomy provides good outcomes as a salvage procedure after failed dilations and/or botox injections for achalasia we advocate it as first-line therapy in reasonable operative candidates.

Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy.

The role of adjuvant chemoradiation therapy (CT/XRT) in the treatment of cholangiocarcinoma is controversial. We undertook this study to determine whether CT/XRT is appropriate after resection of cholangiocarcinomas. One hundred ninety-two patients with cholangiocarcinomas were treated from 1988 to 1999. After resection, patients were assigned a stage (TNM) and were stratified by location of the tumor as intrahepatic, perihilar, and distal tumors. Data are presented as mean +/- standard deviation. Of 192 patients 92 (48%) underwent resections of cholangiocarcinomas. Thirty-four patients had liver resections, 25 had bile duct resections, and 33 underwent pancreaticoduodenectomies. Thirty-four patients had adjuvant CT/XRT, three had adjuvant chemotherapy, four had neoadjuvant CT/XRT, and 50 had no radiation or chemotherapy. Mean survival of resected patients with adjuvant CT/XRT was 42 +/- 37.0 months and without CT/XRT it was 29 24.5 months (P = 0.07). Mean survival of patients with distal tumors receiving or not receiving CT/XRT was 41 +/- 21.8 versus 25 +/- 20.1 months, respectively, (P = 0.04). Adjuvant chemoradiation improves survival after resection for cholangiocarcinoma (P = 0.07) particularly in patients undergoing resection for distal tumors (P = 0.04). Benefits of adjuvant CT/XRT are apparent when stratified by location of cholangiocarcinomas rather than staging.

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.

Delay in treatment of biliary disease during pregnancy increases morbidity and can be avoided with safe laparoscopic cholecystectomy.

Recent reports indicate that laparoscopic cholecystectomy in pregnancy is safe. The aim of this study was to evaluate whether delays in definitive treatment of symptomatic cholelithiasis increase morbidity. We reviewed the records of 16 women who underwent laparoscopic cholecystectomy during pregnancy between 1992 and 1999. Mean age was 24 +/- 5 years (mean +/- standard error). Symptom onset was during the first trimester in nine patients, second trimester in six patients, and third trimester in one patient. Patients had abdominal pain (93%), nausea (93%), emesis (80%), and fever (66%) for a median of 45 days (range 1-195 days) before cholecystectomy. Nine of 11 women who underwent cholecystectomy more than 5 weeks after onset of symptoms experienced recurrent attacks necessitating 15 hospital admissions and four emergency room visits. Moreover four women who developed symptoms in the first and second trimesters but whose operations were delayed to the third trimester had 11 hospital admissions and four emergency room visits; three of those four (75%) women developed premature contractions necessitating tocolytics. Cholecystectomy was completed laparoscopically in 14 women. There was no hospital infant or maternal mortality or morbidity. We recommend prompt laparoscopic cholecystectomy in pregnant women with symptomatic biliary disease because it is safe and it reduces hospital admissions and frequency of premature labor.

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.

Management of medically refractory ascites.

BACKGROUND: Medically refractory ascites is a clinical entity for which there exists few effective therapeutic options. Available treatment modalities include diuresis and sodium restriction, peritoneovenous shunt, liver transplant, transjugular intrahepatic portosystemic shunts and surgical shunts, and large-volume paracentesis. Herein we review the current therapeutic options for medically refractory ascites focusing on indications, benefits, and drawbacks of each specific therapy. DATA SOURCES: Data and recommendations are based on the authors' cumulative experience with complicated cirrhotic and cancer patients and on past and current literature addressing intractable ascites. CONCLUSIONS: The absence of a single, effective therapy in the management of refractory ascites speaks to the complex nature of this complication. Although most patients will respond to medical management, thoughtful application of available therapeutic options in patients who fail, as described herein, not only makes decisions regarding their care easier but also provides the best palliation in a vexing clinical scenario.

Frequency with which surgeons undertake pancreaticoduodenectomy determines length of stay, hospital charges, and in-hospital mortality.

Others have suggested that in certain technically challenging operations, outcome and experience are related. Because pancreaticoduodenectomy is a technically complex procedure, this study was undertaken to evaluate mortality, length of hospital stay, and hospital charges when compared to volume of experience. The database of the State of Florida Agency for Health Care Administration was queried for pancreaticoduodenectomies undertaken during a recent 33-month period. Length of stay, hospital charges, and in-hospital mortality were stratified by the frequency of pancreaticoduodenectomy. A total of 282 surgeons performed 698 pancreaticoduodenectomies over 33 months. Eighty-nine percent of surgeons performed one pancreaticoduodenectomy per year or less and accounted for 52% of the procedures. Overall mortality rate was 5.1%. Average hospital charges were $72,171.64. The more frequently pancreaticoduodenectomy was undertaken, the shorter the hospital stay (P = 0.025, regression analysis) and the lower the hospital charges (P = 0.008, regression analysis) and in-hospital mortality (P = 0.036, log likelihood ratio test). Surgeons who undertake pancreaticoduodenectomy more frequently have patients with shorter hospital stays, lower hospital charges, and lower in-hospital mortality rates, independent of hospital volume. Variations exist among surgeons and among different areas of the state. Data regarding cost and mortality are available for use in programs of cost and quality improvement.

Laparoscopic revision of failed antireflux operations.

BACKGROUND: A small number of patients fail fundoplication and require reoperation. Laparoscopic techniques have been applied to reoperative fundoplications. We reviewed our experience with reoperative laparoscopic fundoplication. METHODS: Reoperative laparoscopic fundoplication was undertaken in 28 patients, 19 F and 9 M, of mean age 56 years +/- 12. Previous antireflux procedures included 19 open and 12 laparoscopic antireflux operations. RESULTS: Symptoms were heartburn (90%), dysphagia (35%), and atypical symptoms (30%%). The mean interval from antireflux procedure to revision was 13 months +/- 4.2. The mean DeMeester score was 78+/-32 (normal 14.7). Eighteen patients (64%) had hiatal breakdown, 17 (60%) had wrap failure, 2 (7%) had slipped Nissen, 3 (11%) had paraesophageal hernias, and 1 (3%) had an excessively tight wrap. Twenty-five revisions were completed laparoscopically, while 3 patients required conversion to the open technique. Complications occurred in 9 of 17 (53%) patients failing previous open fundoplications and in 4 of 12 patients (33%) failing previous laparoscopic fundoplications and included 15 gastrotomies and 1 esophagotomy, all repaired laparoscopically, 3 postoperative gastric leaks, and 4 pneumothoraces requiring tube thoracostomy. No deaths occurred. Median length of stay was 5 days (range 2-90 days). At a mean follow-up of 20 months +/- 17, 2 patients (7%) have failed revision of their fundoplications, with the rest of the patients being essentially asymptomatic (93%). CONCLUSIONS: The results achieved with reoperative laparoscopic fundoplication are similar to those of primary laparoscopic fundoplications. Laparoscopic reoperations, particularly of primary open fundoplication, can be technically challenging and fraught with complications.

New directions in systemic therapy of pancreatic cancer.

BACKGROUND: The aggressiveness of pancreatic adenocarcinoma makes it a deadly disease, with its incidence rate and fatality rate almost equal. Surgery represents the only means to provide cure to patients with pancreatic cancer, though the 5-year survival is less than 10%. METHODS: We review the data on surgical and systemic therapies and provide more details on a newer biologically based medical approach. RESULTS: Neoadjuvant chemotherapy protocols are confined to one or two institutions, and adjuvant chemotherapy and chemoradiation therapy protocols are far from being standardized. Chemoradiation therapy for locally advanced pancreatic cancer offers limited benefits. Protocols that include gemcitabine and 5-fluorouracil, while comparing favorably to historical controls, offer median survivals at approximately 8 months. CONCLUSIONS: More effective protocols with combinations of approaches agents are needed to improve the treatment of pancreatic cancer.

Videoscopic Heller myotomy for achalasia--results beyond short-term follow-up.

BACKGROUND: Heller myotomy has long been utilized for patients failing nonoperative management of achalasia. Videoscopy has been advocated to decrease the morbidity of Heller myotomy; however, few reports document outcome beyond 1 year after videoscopic Heller myotomy. PURPOSE: To determine perioperative morbidity, relief of dysphagia, and the incidence of postoperative reflux symptoms following videoscopic Heller myotomy with follow-up to over 4 years. METHODS: Patients with achalasia documented by barium esophogram and esophageal manometry underwent videoscopic Heller myotomy beginning in 1992. Intraoperative peroral endoscopy was utilized to guide the cephalad and caudad extent of myotomy. A barium esophogram was undertaken in the immediate postoperative period to evaluate for subclinical leak and assess esophageal emptying. RESULTS: Seventy-eight patients underwent videoscopic Heller myotomy. The mean age was 51 years +/- 19 (range 14 to 91). Most (62%) patients had undergone pneumatic dilation prior to surgical consultation and 54% had previous botox injections. All patients complained of dysphagia and 40% had symptoms of heartburn prior to myotomy. After myotomy, 91% of patients stated that their swallowing was improved with myotomy. Thirteen patients (18%) experience heartburn more than once per week after myotomy. The average length of stay was 2 +/- 2 days, with 72% of patients spending 2 days or fewer in the hospital. Six (7.7%) major complications occurred: five esophageal perforations and one enterotomy without long-term sequellae. Three procedures (3.8%) were converted to "open" procedures. No deaths occurred. We conclude that videoscopic Heller myotomy is safe and efficacious, with low morbidity and mortality. Videoscopic myotomy provides relief beyond the short term for dysphagia due to achalasia with minimal reflux symptoms. We advocate videoscopic Heller myotomy in the treatment of severe dysphagia due to achalasia not adequately palliated by or amenable to nonoperative management.