Phase III Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection for Colon Cancer: An Intergroup Trial of the ECOG-ACRIN Cancer Research Group (E1292).

BACKGROUND: Studies suggest that adjuvant chemotherapy should be initiated at the earliest possible time. The Eastern Cooperative Oncology Group (ECOG) and Intergroup evaluated the effect of perioperative fluorouracil (5-FU) on overall survival (OS) for colon cancer. PATIENTS AND METHODS: This phase III trial randomized patients to receive continuous infusional 5-FU for 7 days starting within 24 h after curative resection (arm A) or no perioperative 5-FU (arm B). Patients with Dukes' B3 and C disease received adjuvant chemotherapy per standard of care. The primary endpoint of the trial was overall survival in patients with Dukes' B3 and C disease. The secondary objective was to determine whether a week of perioperative infusion would affect survival in patients with Dukes' B2 colon cancer with no additional chemotherapy. RESULTS: From August 1993 to May 2000, 859 patients were enrolled and 855 randomized (arm A: 427; arm B: 428). The trial was terminated early due to slow accrual. The median follow-up is 15.4 years (0.03-20.3 years). Among patients with Dukes' B3 and C disease, there was no statistically significant difference in OS [median 10.3 years (95% CI 8.4, 13.2) for perioperative chemotherapy and 9.3 years (95% CI 5.7, 12.3) for no perioperative therapy, one-sided log-rank p = 0.178, HR = 0.88 (95% CI 0.66, 1.16)] or disease-free survival (DFS). For patients with Dukes' B2 disease, there was also no significant difference in OS (median 16.1 versus 12.9 years) or DFS. There was no difference between treatment arms in operative complications. One week of continuous infusion of 5-FU was tolerable; 18% of arm A patients experienced grade 3 or greater toxicity.

Partially covered esophageal stents cause bowel injury when used to treat complications of bariatric surgery.

BACKGROUND: We hypothesized that an esophageal nitinol stent that is mainly silicone-covered but partially uncovered may allow tissue ingrowth and decrease the migration rate seen with fully covered stents and still allow safe stent removal. The aim of this study was to evaluate the first human results of using partially covered stents for anastomotic complications of bariatric surgery. METHODS: This was a retrospective evaluation of all patients with staple-line complications after bariatric surgery who received a partly covered stent at a single tertiary-care bariatric center. The stents varied in length from 10 to 15 cm and in diameter from 18 to 23 mm. RESULTS: From April 2009 to April 2010, eight patients received partially covered stents on 14 separate occasions. The indications were gastrojejunal stricture in four, acute leak in two, acute leak followed by a later stricture in one, and a perforated anastomotic ulcer in one patient. Single stents were placed in 12 sessions and two overlapping stents in two sessions. At the time of stent deployment, one patient had the uncovered proximal end of the stent in the stomach, with all others in the distal esophagus. Immediate symptom improvement occurred in 12/14 stent placements. Oral nutrition was initiated for 10/14 stent treatments within 48 h. Stents were removed after 25 ± 10 days. Minor stent displacement occurred with 9/13 stents, with the proximal end of the stent moving into the stomach, though the site of pathology remained covered. The stents were difficult to remove when tissue ingrowth was present. One patient required laparoscopic removal and one required two endoscopy sessions for removal. At the time of removal of ten stents, where the proximal end was found in the stomach, four had gastric ulceration, three had gastric mucosa replaced by granulation tissue, and three had normal gastric mucosa. In four cases where the proximal portion of the stent stayed in the esophagus, the esophageal deployment zone had abnormalities: three with granulation tissue and one with denuding of the esophageal mucosa. The distal uncovered portion of the stent in the Roux limb never became embedded in the mucosa and caused minimal injury. CONCLUSIONS: A partially covered stent was successful in keeping the site of the pathology covered and provided rapid symptom improvement and oral nutrition in most patients. The proximal end of the stent generally moved from the esophagus to the stomach, probably due to esophageal peristalsis. The proximal uncovered portion of the stent causes significant bowel mucosal injury and sometimes becomes embedded in the esophagus or the stomach, making removal difficult. We no longer use partially covered stents.

In search of the best peritoneal adhesion model: comparison of different techniques in a rat model.

BACKGROUND: Adhesion-related complications after abdominal surgery result in significant morbidity and costs. Results from animal studies investigating prevention or treatment of adhesions are limited due to lack of consistency in existing animal models. The aim of this study was to compare quality and quantity of adhesions in four different models and to find the best model. MATERIALS AND METHODS: This study was approved by the University of Missouri Animal Care and Use Committee (ACUC). Forty female rats were randomly assigned to four different groups of 10 animals each. Adhesion created was performed utilizing the four techniques: Group 1 - parietal peritoneum excision (PPE), Group 2 - parietal peritoneum abrasion (PPA), Group 3 - peritoneal button creation (PBC), and Group 4 - cecal abrasion (CA). Rats were allowed to recover and necropsy was performed on postoperative d 14. Adhesions were scored by an established quantitative and qualitative scoring systems. The midline incision served as the control in each animal. RESULTS: The four groups were not equal with respect to both quantity score (P<0.001) and quality score (P=0.042). The PBC group had the highest quantity of adhesions. The highest quality of adhesion was seen in the PPE group. A multivariate analysis carried out to quantify the performance of each model clearly demonstrated that PBC exhibited the best results in terms of both quantity and quality. CONCLUSIONS: The button technique (PBC) is most consistent and reproducible technique for an intra-abdominal adhesion model. This model can help in the study and development of substances to prevent adhesion formation in the future.

Transvaginal cholecystectomy by using a prototype flexible clip applier.

BACKGROUND: Currently, no endoscopic clips have been proven to be effective in ligating the cystic duct in natural orifice transluminal endoscopic surgery (NOTES) hybrid cholecystectomy. OBJECTIVE: To determine the safety and feasibility of a prototype endoscopic flexible clip applier, which is the only flexible device that deploys a zero-gap clip. DESIGN: Pilot study in a survival porcine model. Necropsy was performed at 2 weeks postprocedure. SETTING: University of Missouri animal laboratory, Columbia, Missouri. INTERVENTION: Transvaginal cholecystectomy was performed on 6 survival pigs using the NOTES Toolbox 1.0. MAIN OUTCOME MEASUREMENTS: Safety and feasibility of the described instrument. Investigators were asked to fill out a standardized, blinded questionnaire on the ease of use and functionality of the flexible clip applier. RESULTS: Clipping of the cystic duct was achieved with the flexible clip applier in all 6 pigs. The mean time for completion of clipping of the cystic duct was 9 minutes. Multiple attempts were required to successfully fire the clip in 2 of 6 pigs. We were unable to visualize the tip of the clip before deployment. Difficulty releasing the clip from the applier once fired and challenges in clip loading were encountered. The clips were visualized in place at necropsy, with no bile leakage, evidence of infection, or injury to surrounding structures seen in any cases. LIMITATIONS: Preclinical animal model. CONCLUSION: The prototype flexible clip applier showed adequate safety and was feasible in clipping the cystic duct in all animals. Design efforts to improve clip visualization, loading, and release are underway.

Transvaginal repair of a large chronic porcine ventral hernia with synthetic mesh using NOTES.

BACKGROUND: Ventral incisional hernias still remain a common surgical problem. We tested the feasibility of transvaginal placement of a large synthetic mesh to repair a porcine hernia. METHODS: Seven pigs were used in this survival model. Each animal had creation of a 5-cm hernia defect and underwent a transvaginal repair of the defect with synthetic mesh. A single colpotomy was made using a 12-cm trocar for an overtube. The mesh was cut to size and placed through the trocar. A single-channel gastroscope with an endoscopic atraumatic grasper was used for grasping sutures. Further fascial sutures were placed every 5 cm. RESULTS: Mesh repair was feasible in all 7 animals. Mean operative time was 133 minutes. Technical difficulties were encountered. No gross contamination was seen at the time of necropsy. However, 5 animals had positive mesh cultures; 7 had positive cultures in the rectouterine space in enrichment broth or on direct culture. CONCLUSION: Transvaginal placement of synthetic mesh to repair a large porcine hernia using NOTES is challenging but feasible. Future studies need to be conducted to develop better techniques and determine the significance of mesh contamination.

Lessons learned establishing an animal model for endoscopic stent placement to treat gastrojejunal anastomotic leaks after gastric bypass.

BACKGROUND: Anastomotic leaks after Roux-en-Y gastric bypass (RYGB) cause significant morbidity and mortality. Placement of enteral stents may be an improvement to the current treatment, which is withholding of oral intake and total parenteral nutrition. METHODS: We established an open RYGB porcine model with a leak at the gastrojejunostomy in three pigs. A pilot study was then performed in five pigs, where Polyflex stents were placed across the leaking anastomosis and fixed with transmural sutures to the Roux limb. After 2 weeks, endoscopy, fluoroscopy, and necropsy were performed. RESULTS: One pig without stent died on the second postoperative day (POD) due to a volvulus unrelated to the leak. In the other two pigs, leaks with large abscesses were found at necropsy. Stents were placed in five pigs but required open surgical manipulation of the delivery system. One pig died on POD 3 due to a perforation in the posterior gastric wall likely caused by the rigid delivery system. One pig died from gastrojejunostomy leakage on POD 5. The leaks were healed in the remaining three pigs after 2 weeks. In one pig, a perforation of the jejunum 4 cm distal to the anastomosis was found. Stent migration to some extent was seen in all pigs. CONCLUSION: Stent placement and fixation were feasible but had a high complication rate for treatment of a leaking gastrojejunal anastomosis in the open porcine model. The stent may have contributed to healing the leak in some pigs. Further studies should focus on improving stent delivery, sealing of the leak, and prevention of stent migration.

Transgastric placement of biologic mesh to the anterior abdominal wall.

BACKGROUND: Incisional hernia repairs have a risk of wound complications that may be decreased using a natural orifice transluminal endoscopic surgery (NOTES) approach. The aim of this study was to determine the feasibility and safety of transgastric mesh placement to the anterior abdominal wall in a porcine model as a precursor to future studies of NOTES ventral hernia repair. METHODS: The procedure was done under sterile conditions with a double lumen endoscope using a plastic overtube. The endoscope was placed in the stomach preloaded with an overtube. Entrance of the endoscope and overtube into the peritoneal cavity was performed with the percutaneous endoscopic gastrostomy (PEG) technique. A 13 x 15 cm Surgisis Gold mesh with four corner sutures was delivered through the overtube. Transfascial suture passer and endoscopic grasper were used to externalize the sutures and attach the mesh to the anterior abdominal wall. The gastrotomy was closed with a transabdominal gastropexy. The pigs were sacrificed at 2 weeks. RESULTS: Mesh placement was performed in five pigs. Operative time was 215 min (standard deviation, SD 99 min). The most difficult portion of the procedure involved manipulating the gastric overtube, likely exposing the mesh to bacteria in the stomach. Culture-positive abscesses were present at the mesh in 3/5 animals. The mesh appeared intact in 4/5 animals; one of the infected meshes had delamination of 50% of the mesh. Adhesions to the mesh surface varied from 2% to 100%. At 2 weeks, median mesh size was 116 cm2 (range 96-166 cm2) and median contraction was 41% (range 15-51%). Histologic evaluations demonstrated marked inflammation and fibrosis progressing into the mesh material. CONCLUSIONS: Totally endoscopic transgastric delivery and fixation of a biologic mesh to the anterior abdominal wall is feasible. Challenges remain in designing systems for mesh delivery that exclude gastric content. Once these problems can be surmounted NOTES ventral hernia repair may become an option in man.

Colonic sterilization for natural orifice translumenal endoscopic surgery (NOTES) procedures: a comparison of two decontamination protocols.

BACKGROUND: This study aimed to evaluate the effect of two different sterilization protocols on the bacterial counts in the swine colon as preparation for natural orifice translumenal endoscopic surgery (NOTES) surgery. METHODS: In this study, 16 swine were randomized to two different colonic sterilization protocols: low colonic irrigation using 300 ml of a 1:1 dilution of 10% povidone-iodine (Betadine) with sterile saline, followed by 1 g of cefoxitin dissolved in 300 ml of saline or two consecutive 300-ml irrigations using a quaternary ammonium antimicrobial agent (Onamer M). Colonic cultures were taken before colonic cleansing after a decontamination protocol and after completion of the NOTES procedure. The Invitrogen live/dead bacterial viability kit was used to assess for change in the bacterial load. A qualitative culture of peritoneal fluid was obtained at the end of the NOTES procedure. Colon mucosal biopsies obtained immediately after the sterilization procedure and at the 2-week necropsy point were evaluated for mucosal changes. RESULTS: Protocol 1 resulted in an average 93% decrease in live colonic bacteria versus 90% with protocol 2 (nonsignificant difference). After a NOTES procedure, group 1 had a 62% increase in live bacteria and group 2 had a 31% increase (nonsignificant difference). Peritoneal cultures also were obtained. Bacteria were isolated from the peritoneal fluid of all the animals, and two or more species were isolated from 75% of the animals. There was no evidence of peritoneal infection at necropsy. Reactive epithelial changes and mild inflammation were the only pathologic abnormalities. No changes were noted at histologic evaluation of colonic mucosa after 2 weeks, demonstrating that these were temporary changes. CONCLUSION: Colonic irrigation with Betadine and antibiotics are as effective for bacterial decontamination of the swine colon as a quaternary ammonium compound. The results of this study support the use of either protocol. Despite thorough decontamination, peritoneal contamination occurs. The significance of this for humans is unknown.

Endoscopic colotomy closure for natural orifice transluminal endoscopic surgery using a T-fastener prototype in comparison to conventional laparoscopic suture closure.

BACKGROUND: Safe and efficient endoscopic closure of a colotomy is essential for transcolonic peritoneal access or endoscopic full-thickness resection of the colon, if open or laparoscopic surgery is to be avoided. OBJECTIVE: To compare the feasibility and safety of colotomy closure with the newly developed Tissue Approximation System (TAS, Ethicon Endo-Surgery, Inc.) to conventional laparoscopic suture closure. DESIGN: Prospective randomized survival animal study involving 16 pigs. SETTING: University hospital. INTERVENTIONS: Pigs were randomized for closure of a 2- to 3-cm full-thickness colotomy with the TAS or with a conventional laparoscopic running suture. MAIN OUTCOME MEASUREMENTS: Success of colotomy closure, time of colotomy closure, postoperative infection, and complication rates. RESULTS: Colotomies were successfully closed in all animals. Median closure time (range) was 39.5 minutes (25-95 min) in the TAS group and 23 minutes (16-40 min) in the laparoscopic group (P = .0134). There were no postoperative infections or complications. LIMITATIONS: Closure with the TAS was performed under laparoscopic vision. There was no control group without closure of the colotomy site. CONCLUSIONS: Colotomies are safely closed with the TAS with comparable results to laparoscopic closure. The TAS may serve as a useful tool to close full-thickness colon defects or colotomy sites made for transluminal endoscopic procedures.

Gastrotomy creation and closure for NOTES using a gastropexy technique (with video).

BACKGROUND: Safe and efficient gastrotomy creation and closure is pivotal for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To test a method of transgastric access and closure with commercially available devices. DESIGN: An animal survival study. SETTING: University hospital. PATIENTS: Fifteen pigs. INTERVENTIONS: By using a surgical suture passer, under endoscopic guidance, 3 percutaneous stay sutures were placed, in a triangular fashion, through the gastric wall. A gastrotomy was created with a dilation balloon, which was introduced over a guidewire through the gastric wall in the center of the 3 sutures. After performing a NOTES procedure, the gastrotomy was closed by tying the sutures. Necropsies were performed after 2 to 4 weeks. MAIN OUTCOME MEASUREMENTS: Success and time of gastrotomy creation and closure, and intraoperative and postoperative complications. RESULTS: Gastrotomies were successfully created and closed in all the animals. The median time to create a gastrotomy was 19 minutes (range 11-85 minutes), and the median closure time was 1 minute (range 1-45 minutes). One pig died on postoperative day 1 because of peritonitis caused by a leaking gastrotomy site that extended beyond the stay sutures. There were no other gastrotomy-related complications. All gastrotomies were well healed at the necropsy. LIMITATION: No control group. CONCLUSIONS: We evaluated a simple method by using the principles of the PEG technique combined with a gastropexy, which is familiar to the majority of endoscopists. Strict attention to the gastrotomy site is needed, because one leak was from the gastrotomy site that extended beyond the stay sutures.

Improving rates for screening colonoscopy: Analysis of the health information national trends survey (HINTS I) data.

BACKGROUND: Colonoscopy is an effective modality for colorectal cancer screening. The objectives of this study were to identify colorectal cancer knowledge and barriers to screening colonoscopy in the general US population. METHODS: Data was obtained from the health information national trends survey (HINTS I). The dataset (n = 6369) examined the influence of age, race, gender, education, income, media usage, and interactions with health care providers on knowledge, attitudes, and behavior regarding colonoscopic screening for colorectal cancer. RESULTS: The term 'colonoscopy' was recognized by 80% of participants (over the age of 35), however only 35% of respondents perceived it as a major method for colon cancer screening. Hispanics had the least awareness of colonoscopic screening (16% versus 39% non-Hispanic). Female gender, education, and income all correlated with knowledge and use of colonoscopic screening. There was a positive correlation between media usage and having a colonoscopy (r = 0.095, p < 0.01). Having a health care provider was strongly correlated with having undergone a colonoscopy (r = 0.249, p < 0.01). Reasons for not having a colonoscopy were 'no reason' (29%), 'doctor didn't order it' (24%), and 'didn't know I needed the test' (15%). Personalized materials were the preferred media for receiving cancer-related information. CONCLUSIONS: Knowledge of and participation in screening colonoscopy is low in the US population, especially among Hispanics. The most important immediate action is to increase physician referral for screening colonoscopy. Education materials focused on specific sociodemographic segments and targeted communication campaigns need to be developed to encourage screening.

Integrated flexible endoscopy training during surgical residency.

BACKGROUND: New advances in endoscopic surgery make it imperative that future gastrointestinal surgeons obtain adequate endoscopy skills. An evaluation of the 2001-02 general surgery residency endoscopy experience at the University of Missouri revealed that chief residents were graduating with an average of 43 endoscopic cases. This met American Board of Surgery (ABS) and Accreditation Council for Graduate Medical Education (ACGME) requirements but is inadequate preparation for carrying out advanced endoscopic surgery. Our aim was to determine if endoscopy volume could be improved by dedicating specific staff surgeon time to a gastrointestinal diagnostic center at an affiliated Veterans Administration Hospital. METHODS: During the academic years 2002-05, two general surgeons who routinely perform endoscopy staffed the gastrointestinal endoscopy center at the Harry S. Truman Hospital two days per week. A minimum of one categorical surgical resident participated during these endoscopy training days while on the Veterans Hospital surgical service. A retrospective observational review of ACGME surgery resident case logs from 2001 to 2005 was conducted to document the changes in resident endoscopy experience. The cases were compiled by postgraduate year (PGY). RESULTS: Resident endoscopy case volume increased 850% from 2001 to 2005. Graduating residents completed an average of 161 endoscopies. Endoscopic experience was attained at all levels of training: 26, 21, 34, 23, and 26 mean endoscopies/year for PGY-1 to PGY-5, respectively. CONCLUSIONS: Having specific endoscopy training days at a VA Hospital under the guidance of a dedicated staff surgeon is a successful method to improve surgical resident endoscopy case volume. An integrated endoscopy training curriculum results in early skills acquisition, continued proficiency throughout residency, and is an efficient way to obtain endoscopic skills. In addition, the foundation of flexible endoscopic skill and experience has allowed early integration of surgery residents into research efforts in natural orifice transluminal endoscopic surgery.

Prognostic indicators of quality of life after cholecystectomy for biliary dyskinesia.

Approximately 30 per cent of patients who undergo cholecystectomy for biliary dyskinesia will continue to have symptoms after surgery. Quality of life has not been evaluated but may be decreased in these patients. The purpose of this study was to measure quality of life after laparoscopic cholecystectomy in these patients to better define optimal treatment of biliary dyskinesia. All patients with biliary dyskinesia (defined as the absence of gallstones, and a gallbladder ejection fraction of <35%) who underwent cholecystectomy at our institution from January 31, 2000 to January 31, 2005 were identified. Preoperative data including ultrasound, biochemical data, and pathology were retrieved by chart review. Postoperative assessment included the Gastrointestinal Quality of Life Index and a symptom survey. The postoperative quality of life was compared with historic standards. The quality of life was also compared with preoperative variables to determine if any variables predicted outcome. A total of 66 patients were identified as fitting the inclusion criteria. Forty-three patients were reached by phone and 30 agreed to participate. Patients were noted to have good recall as to preoperative symptoms when the retrospective survey of symptoms was compared with the medical record. The mean +/- SD postoperative quality of life in the study population was 113 +/- 20. This is higher than in historic patients with gallbladder disease before (84 +/- 19) and after (102 +/- 13) cholecystectomy. Quality of life in the study group was lower than the healthy control (125 +/- 13). Patients having both postprandial nausea and vomiting before surgery had a lower quality of life (P < 0.029) after surgery as compared with those without these preoperative symptoms. When adjusted for nausea and vomiting, the quality of life in study patients (119 +/- 14) was similar to normal controls. No other symptom, laboratory, pathologic, or sonographic data were predictive of a lower quality of life. Cholecystectomy is beneficial for most patients with biliary dyskinesia. Nausea and vomiting were negative predictors of quality of life after cholecystectomy. These patients with nausea and vomiting may have a global gastrointestinal motility disorder and are less likely to benefit from cholecystectomy.

Management of anastomotic leaks after Roux-en-Y bypass using self-expanding polyester stents.

BACKGROUND: To analyze the outcomes of a series of endoscopically placed polyester self-expanding polyflex stents (SEPSs) for the management of anastomotic leaks after Roux-en-Y bypass. Anastomotic leaks after gastric bypass cause significant morbidity and mortality. Covered polyester SEPSs might have a role in the treatment of these leaks. METHODS: A retrospective chart review was performed from January 2006 to November 2006 that included all acute and chronic leaks treated with SEPSs. RESULTS: A total of 6 patients were treated with stents, with a mean procedure time of 22 minutes. Of these 6 patients, 5 had acute postoperative leaks and 1 had a chronic fistula. Five patients started oral intake 1-6 days after their procedure. All acute leaks had complete healing at a median of 44 days. The patient with a chronic gastrocutaneous fistula required revisional surgery for fistula closure. In addition, 5 patients had stent migration, and 3 required stent replacement. CONCLUSION: An endoscopically placed SEPS provides a less-invasive alternative to treat acute anastomotic leaks after Roux-en-Y bypass while simultaneously allowing oral intake. The results of this case series have demonstrated this treatment to be safe and effective.

Laparoscopic resection of colon cancer and synchronous liver metastasis.

The recommended surgical approach to synchronous colorectal metastasis has not been clarified. Simultaneous open liver and colon resection for synchronous colorectal carcinoma has been shown beneficial when compared to staged resections. A review of the literature has shown the benefits of both laparoscopic colon resection for colorectal cancer and laparoscopic left lateral segmentectomy in liver disease. We present the case of a 60-year-old male with sigmoid colon carcinoma and a synchronous solitary liver metastasis localized to the left lateral segment. Using laparoscopic techniques, we were able to achieve simultaneous resection of the sigmoid colon and left lateral liver segment.

Management of postsurgical leaks in the bariatric patient.

Postsurgical leaks after bariatric procedures are a significant cause of morbidity and mortality. They usually arise from anastomotic and staple line failures that are attributed to surgical technique, ischemia, and patient comorbid conditions. Timely diagnosis from subtle clinical clues is the key to appropriate management. Traditional treatment consists of adequate control of the intra-abdominal infection via surgical or percutaneous drainage maneuvers, antibiotics, and nutrition support via parenteral or feeding tube routes. Recently, endoscopically placed covered esophageal stents have been used to exclude the leak site, allowing oral nutrition and speeding healing.