Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?

Exome sequencing (ES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for ES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex etiologies. The phenotypic spectrum of OFCs may include overt clefts and several subclinical phenotypes, such as discontinuities in the orbicularis oris muscle (OOM) in the upper lip, velopharyngeal insufficiency (VPI), microform clefts or bifid uvulas. We hypothesize that expanding the OFC phenotype to include these phenotypes can clarify inheritance patterns in multiplex families, making them appear more Mendelian. We performed exome sequencing to find rare, likely causal genetic variants in 31 multiplex OFC families, which included families with multiple individuals with OFCs and individuals with subclinical phenotypes. We identified likely causal variants in COL11A2, IRF6, SHROOM3, SMC3, TBX3, and TP63 in six families. Although we did not find clear evidence supporting the subclinical phenotype hypothesis, our findings support a role for rare variants in the etiology of OFCs.

Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?

Whole-exome sequencing (WES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for WES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex etiologies. The phenotypic spectrum of OFCs may include overt clefts and several subclinical phenotypes, such as discontinuities in the orbicularis oris muscle (OOM) in the upper lip, velopharyngeal insufficiency (VPI), microform clefts or bifid uvulas. We hypothesize that expanding the OFC phenotype to include these phenotypes can clarify inheritance patterns in multiplex families, making them appear more Mendelian. We performed whole-exome sequencing to find rare, likely causal genetic variants in 31 multiplex OFC families, which included families with multiple individuals with OFCs and individuals with subclinical phenotypes. We identified likely causal variants in COL11A2, IRF6, KLF4, SHROOM3, SMC3, TP63 , and TBX3 in seven families. Although we did not find clear evidence supporting the subclinical phenotype hypothesis, our findings support a role for rare variants in the etiology of OFCs.

Longer examination time improves detection of gastric cancer during diagnostic upper gastrointestinal endoscopy.

BACKGROUND & AIMS: It is not clear how the duration of upper endoscopy affects the detection of cancer or premalignant lesions that increase the risk for gastric cancer. We investigated whether the length of time spent performing esophagogastroduodenoscopy (EGD) affects the detection of important pathologic features of the stomach. METHODS: We collected data from 837 symptomatic patients, during a 3-month period in 2010, who underwent a first diagnostic EGD at a tertiary university hospital in Singapore. Endoscopists were classified as fast or slow based on the mean amount of time it took them to perform a normal EGD examination. We used logistic regression to compare between groups the numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers detected, using histologic analysis of biopsy samples collected during endoscopy as the standard. RESULTS: Of 224 normal endoscopies, the mean duration was 6.6 minutes (range, 2-32 min). When we used 7 minutes as the cut-off time, 8 endoscopists were considered to have short mean examination times (mean duration, 5.5 ± 2.1 min; referred to as fast endoscopists), and 8 endoscopists were considered to have long mean examination times (mean duration, 8.6 ± 4.2 min; referred to as slow endoscopists). Eleven cancers and 81 lesions considered to pose risks for cancer were detected in 86 patients; 1.3% were determined to be cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95% confidence interval, 1.52-4.12), regardless of whether they were endoscopy staff or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions (cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25-10.38). CONCLUSIONS: Endoscopists with mean EGD examination times longer than 7 minutes identified a greater number of high-risk gastric lesions than faster endoscopists. Examination time may be a useful indicator of quality assessment for upper endoscopy. Studies are required to test these findings in different populations.

Predicting mortality in patients with bleeding peptic ulcers after therapeutic endoscopy.

BACKGROUND & AIMS: Despite advances in management of patients with bleeding peptic ulcers, mortality is still 10%. This study aimed to identify predictive factors and to develop a prediction model for mortality among patients with bleeding peptic ulcers. METHODS: Consecutive patients with endoscopic stigmata of active bleeding, visible vessels, or adherent clots were recruited, and risk factors for mortality were identified in this deprivation cohort by using multiple stepwise logistic regression. A prediction model was then built on the basis of these factors and validated in the evaluation cohort. RESULTS: From 1993 to 2003, 3220 patients with bleeding peptic ulcers were treated. Two hundred eighty-four of the patients developed rebleeding (8.8%); emergency surgery was performed on 47 of these patients, whereas others were managed with endoscopic retreatment. Two hundred twenty-nine of these sustained in-hospital death (7.1%). In patients older than 70 years, presence of comorbidity, more than 1 listed comorbidity, hematemesis on presentation, systolic blood pressure below 100 mm Hg, in-hospital bleeding, rebleeding, and need for surgery were significant predictors for mortality. Helicobacter pylori-related ulcers had lower risk of mortality. The receiver operating characteristic curve comparing the prediction of mortality with actual mortality showed an area under the curve of 0.842. From 2004 to 2006, data were collected prospectively from a second cohort of patients with bleeding peptic ulcers, and mortality was predicted by using the model developed. The receiver operating characteristic curve showed an area under the curve of 0.729. CONCLUSIONS: Among patients with bleeding peptic ulcers after endoscopic hemostasis, advanced age, presence of listed comorbidity, multiple comorbidities, hypovolemic shock, in-hospital bleeding, rebleeding, and need for surgery successfully predicted in-hospital mortality.

Closure of a gastrotomy after transgastric tubal ligation by using the Eagle Claw VII: a survival experiment in a porcine model (with video).

BACKGROUND: Transgastric access to the peritoneal cavity presents new opportunities for novel endoscopic surgery. Secure closure of the gastrotomy site is critical to the success of transgastric endoscopic surgery. OBJECTIVE: To study the safety and efficacy of closure of a gastrotomy by using the Eagle Claw VII endoscopic suturing device after transgastric bilateral tubal ligation. DESIGN: A prospective survival study in a porcine model with ten 30-kg pigs. INTERVENTIONS: The gastrotomies were made by using a needle-knife and balloon dilation. Bilateral fallopian tube ligation was performed with detachable snares, and the tubes were transected by using the needle-knife. The gastrotomies were closed with endoscopic suturing by using the Eagle Claw VII. MAIN OUTCOME MEASUREMENTS: Included the survival of the pigs, security of the closure, number of plicating sutures used, operative time, peritoneal contamination, and histopathologic confirmation of the full-thickness healing of the gastrotomy. RESULTS: Transgastric fallopian-tube ligation was performed in 10 pigs, and all of the gastrotomies were successfully closed by using the Eagle Claw VII endoscopic suturing device. The operative time for bilateral tubal ligation was 38.2 minutes (range 18-50 minutes), whereas, the operative time for gastrotomy closure was 25.5 minutes (range 15-35 minutes). Three endoscopic sutures were necessary to achieve a secure gastrotomy closure. All the pigs survived and tolerated a full diet 24 hours after the operation. A postmortem confirmed full-thickness healing for all gastrotomies, with no evidence of leakage. One pig had an overtube-related esophageal perforation, which was successfully managed with endoscopic clip closure. LIMITATIONS: The porcine gastric wall is thicker than the human gastric wall, and the posterior wall of the porcine stomach becomes the anterior-inferior wall after gaseous distention. Hence, all the gastrotomies were made through the posterior wall. The tissue tolerance and healing of the porcine stomach may be different from that of the human stomach. CONCLUSIONS: Endoscopic suturing by using the Eagle Claw VII device is a feasible method for gastrotomy closure after a natural orifice transluminal endoscopic surgery procedure.

Pilot study of transesophageal endoscopic epicardial coagulation by submucosal endoscopy with the mucosal flap safety valve technique (with videos).

BACKGROUND: We previously demonstrated that the thoracic cavity could be safely accessed by submucosal endoscopy with the mucosal flap safety valve (SEMF) technique. OBJECTIVES: To evaluate the technical feasibility of transesophageal access to the heart and epicardial ablation. DESIGN: One-week survival study with 5 porcine models. SETTINGS: Animal laboratory with general anesthesia. INTERVENTIONS: High-pressure carbon dioxide injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. A myotomy was performed inside the submucosal space. The thoracic cavity was endoscopically accessed through the myotomy site. A pericardial window was created with a needle-knife. A spot coagulation of the epicardium was performed with a heat probe and a hook-knife. The myotomy site was sealed with the overlying mucosal flap, and the mucosal entry site was closed with clips. MAIN OUTCOME MEASUREMENTS: An endoscopy and a necropsy were performed to study the esophagus, mediastinum, pericardial space, and cautery locations on the epicardium one week after the procedure. RESULTS: Epicardial coagulation was successfully performed within 30 minutes in 4 of the 5 pigs. Follow-up endoscopy demonstrated completely sealed myotomy sites by the overlying mucosal flap. There was no gross contamination or signs of contamination in the thoracic cavity. The pericardial space was normal in appearance. The epicardial coagulation sites were healing, without exudative ulceration. CONCLUSIONS: The SEMF technique allowed endoscopic access to the upper mediastinum, the pericardium, and the epicardium via the esophagus, along with a minimal intervention on the epicardium.

Concurrent chemoradiotherapy or endoscopic stenting for advanced squamous cell carcinoma of esophagus: a case-control study.

BACKGROUND: We evaluated the role of chemoradiotherapy (CRT) for patients with inoperable squamous esophageal cancer. METHODS: Patients with locally advanced or metastatic squamous esophageal carcinoma who received CRT were recruited. The CRT consists of continuous infusion of 5-fluorouracil at 200 mg/m(2)/day, and cisplatin at 60 mg/m(2) on days 1 and 22, with concurrent radiotherapy for a total of 50 to 60 Gy in 25 to 30 fractions over 6 weeks. Efficacy was assessed by endoscopy and computed tomographic scan before and 8 weeks after completion of the treatment program. Median survival and the need for palliative esophageal stenting were compared with another group of patients who received endoscopic stenting. RESULTS: From 1996 to 2003, a total of 36 consecutive patients (33 male, mean +/- SD age 63.2 +/- 9.5 years) with T4 disease (81%) with or without cervical nodal metastasis (50%) received CRT, while 36 patients treated with endoscopic stenting alone were recruited as controls. Both groups were comparable in demographics, pretreatment dysphagia score, comorbidities, and tumor characteristics. CRT was completed in 32 patients (89%). There was no treatment-related mortality. Tumor volume was greatly reduced after CRT in 19 patients. Four patients (11%) received salvage esophagectomy 9 to 42 months after CRT. Compared with the stenting group, CRT statistically significantly improved 5-year survival (15% vs. 0%, P = .01), median survival (10.8 months vs. 4.0 months, P < .005), and need for stenting (22% vs. 100%, P = .005). CONCLUSIONS: Palliative CRT can effectively improve the symptoms of dysphagia in patients with inoperable squamous esophageal carcinoma. It results in better survival compared with endoscopic stenting in these patients.

Hand-assisted laparoscopy on a shoestring.

BACKGROUND: Hand-assisted laparoscopic surgery is useful in difficult laparoscopic operations. Expensive and cumbersome devices are necessary to ensure airtightness between the surgeon's hand and the abdominal wall so that pneumoperitoneum can be maintained. METHOD: A simple method of maintaining pneumo-peritoneum in hand-assisted laparoscopic surgery was carried out by tying a strong nylon suture in a criss-cross fashion on one end of the incision. Airtightness was maintained by tightening the suture around the wrist and wedging the dorsum of the hand against the abdominal wall. RESULT: The method was used successfully to remove a pyonephrotic left kidney in a 28-year-old man from Papua New Guinea. CONCLUSION: Hand-assisted laparoscopic operations can be carried out expediently and inexpensively without specialized equipment by simply tying a shoestring suture at one end of the wound.

Transgastric cholecystectomy: transgastric accessibility to the gallbladder improved with the SEMF method and a novel multibending therapeutic endoscope.

BACKGROUND: Transgastric cholecystectomy is thought to technically and anatomically challenge a single entry flexible endoscopic approach. OBJECTIVES: To examine the feasibility of a transgastric-only cholecystectomy, endoscope performance in an upper-abdominal operation, and the usefulness of an offset gastrotomy. STUDY DESIGN: Animal survival study. SETTING: Animal research laboratory. PATIENTS: Six domestic pigs. MAIN OUTCOME MEASUREMENTS: Transgastric access to the gallbladder and technical feasibility of unassisted transgastric cholecystectomy. INTERVENTIONS: A cephalad submucosal tunnel was created in the anterior gastric wall with a high-pressure CO2 injection. An EMR-cap myotomy was performed distally within the submucosal space and created an offset gastrotomy. An endoscope was inserted into the peritoneal cavity through the myotomy. Access to the gallbladder was compared by using a multibending therapeutic endoscope (R-scope), with a standard double-channel endoscope. A cholecystectomy was performed by using both types of endoscopes. The myotomy site was sealed with the overlying mucosal flap. The mucosal entry point was closed with clips or tissue anchors. RESULTS: A standard double-channel endoscope could access the gallbladder in 2 of 4 attempts. A multibending endoscope accessed the gallbladder in all 4 attempts, including 2 pigs in which the standard scope failed to access the gallbladder. In 4 pigs, a cholecystectomy was completed. Two pigs died during surgery, with air embolization observed in 1. Two pigs survived a planned 1-week survival period. CONCLUSIONS: Transgastric cholecystectomy is technically feasible. Transgastric access to the gallbladder may be improved by using submucosal endoscopy with an offset exit gastrotomy by means of the mucosal flap safety-valve technique and a multibending gastroscope.

Use of a variable-stiffness colonoscope decreases the dose of patient-controlled sedation during colonoscopy: a randomized comparison of 3 colonoscopes.

BACKGROUND: The variable-stiffness colonoscope incorporates different degrees of stiffness of the insertion tube, which can be adjusted during the examination. Whether its use can lead to reduced procedure-related pain and sedative use is unknown. OBJECTIVE: Our purpose was to compare the use of 3 types of colonoscope with different shaft stiffnesses in relation to procedure-related pain and sedative consumption. DESIGN: Prospective randomized trial. SETTING: Endoscopy unit of a university-affiliated hospital. PATIENTS: Consecutive patients undergoing ambulatory colonoscopy. INTERVENTIONS: Random assignment was made of patients into 3 groups to receive colonoscopic examinations by one of the 3 types of colonoscope: conventional standard adult size, 1.3-m; 1.6-m; and the new variable-stiffness adult size, full-length (1.6-m) colonoscope. A mixture of propofol and afentanil, delivered by a patient-controlled syringe pump, was used for sedation in all groups. MAIN OUTCOME MEASURES: Outcome measures included dose of patient-controlled sedation consumed, pain score, cecal intubation rate, cecal intubation time, requirement of abdominal pressure and change of patients' positions during colonoscopy, and endoscopists and patients' satisfaction scores according to a visual analog scale. RESULTS: A total of 335 patients were randomized. Patients in group 3 used significantly less propofol (in milligrams per kilograms, mean [SD]) compared with the other 2 groups (group 1: 1.00 [0.75], group 2: 0.93 [0.62], and group 3: 0.75 [0.65]; P = .02; 1-way analysis of variance). The mean (SD) pain score was also lower in group 3. LIMITATIONS: The endoscopists were not blinded. CONCLUSION: The use of the new variable-stiffness adult-size colonoscope significantly reduced procedure-related pain and doses of sedative medications during colonoscopy.

A novel safe approach to the peritoneal cavity for per-oral transgastric endoscopic procedures.

BACKGROUND: We have previously reported the feasibility and safety of per-oral transgastric endoscopic procedures in a porcine model. OBJECTIVE: Our purpose was to evaluate the safety and feasibility of a PEG-like approach to the peritoneal cavity. SETTINGS: Acute experiments on 50-kg pigs under general anesthesia. DESIGN AND INTERVENTIONS: After per-oral intubation, the endoscope was positioned into the body of the stomach, the anterior abdominal wall was transilluminated and punctured with a needle, and a guidewire was inserted into the stomach through the needle. The guidewire was grasped with endoscopic forceps and pulled through the biopsy channel of the endoscope. A sphincterotome was inserted into the gastric wall over the guidewire. Gastric incision was performed and the endoscope was advanced into the peritoneal cavity. The peritoneal cavity was insufflated and endoscopic peritoneoscopy was performed. Then the animal was euthanized and necropsy was performed. MAIN OUTCOME MEASURES: Safety of transgastric entrance to peritoneal cavity. RESULTS: The PEG-like approach was used in 12 pigs. The average procedure time was 11.4 +/- 3.7 minutes. There was only 1 complication related to the access: bleeding from the gastric wall incision was documented when a pure cut (without coagulation) current was used for incision of the gastric wall. There were no complications in the other 11 pigs. The necropsy did not reveal any damage to organs adjacent to the stomach. LIMITATIONS: Gastric wall incision is located on anterior gastric wall. CONCLUSIONS: The PEG-like transgastric approach to the peritoneal cavity appears technically simple and safe.

Technical feasibility of endoscopic gastric reduction: a pilot study in a porcine model.

BACKGROUND: Gastric restrictive procedures are widely used for the surgical treatment of morbid obesity. OBJECTIVE: Our purpose was to determine the technical feasibility of endoscopic gastric reduction in a live porcine model. SETTING: Acute experiments on 50-kg pigs under general anesthesia. DESIGN AND INTERVENTIONS: After per-oral intubation, the endoscope was inserted into the stomach. A fishing line was sutured to the gastric wall along the fundus approximately 5 cm below the gastroesophageal junction with a prototype endoscopic suturing device (Olympus, Eagle Claw). Then the fishing line was tied to create a small proximal pouch. A flexible sheath was placed on one side of fishing line and additional knots were tied, forming a ring at the outlet of the gastric pouch. The ring was anchored to gastric wall with additional stitches, completing the gastric reduction. Then the animals were killed for postmortem examination. MAIN OUTCOME MEASUREMENTS: The feasibility of endoscopic gastric reduction. RESULTS: We performed 4 acute experiments. It required 12 to 14 stitches in each animal to create gastric reduction. There were no technical problems during the procedures. Postmortem examination demonstrated an approximately 30-mL gastric pouch separated from the rest of the stomach by the line of stitches. There were no complications during the procedure. LIMITATIONS: We have not performed survival experiments to determine how long our gastric reduction will last. CONCLUSIONS: Endoscopic gastric reduction is technically feasible on a live porcine model.

Pilot study of the porcine uterine horn as an in vivo appendicitis model for development of endoscopic transgastric appendectomy.

BACKGROUND: Iatrogenic inflammation of the porcine uterine horn may serve as an in vivo appendicitis model for the development of endoscopic transgastric appendectomy. OBJECTIVE: Five female pigs. STUDY DESIGN: Animal study. SETTINGS: General anesthesia. MAIN OUTCOME MEASUREMENTS: Anatomical appearance and technical feasibility. INTERVENTIONS: Three pigs were used to identify an injectable material that would inflame the uterine horn, and 2 pigs were used for a pilot appendectomy. Three types of materials were individually injected into the bilateral uterine horns, and the ideal material to inflame the uterine horn was injected into the right uterine horn for the last 2 pigs. After 24 hours, the injected uterine horns of the first 3 pigs were assessed and a pilot appendectomy was performed in the last 2 pigs. RESULTS: Ethanolamine oleate (EO) injected uterine horns demonstrated similarities to the inflamed human appendix. Simulations of the appendectomy were successfully performed by using the EO model. LIMITATIONS: Suboptimal existing tools. CONCLUSIONS: This preliminary study demonstrated the technical feasibility to create a model for acute appendicitis by using the porcine uterine horn and transgastric appendectomy.

Immediate endoscopic closure of colon perforation by using a prototype endoscopic suturing device: feasibility and outcome in a porcine model (with video).

BACKGROUND: Perforation is an uncommon but potentially devastating complication of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal closure of a perforation would avoid the morbidity and mortality associated with general anesthesia, laparotomy, and surgical repair. OBJECTIVES: To evaluate the feasibility and safety of full-thickness endoscopic closure of colonic perforations with a prototype endoscopic suturing device, the Eagle Claw, in a porcine model. DESIGN: Endoscopic animal experimental study of closure of colon perforation by using a porcine model. SUBJECTS: Ten pigs were included in the study. INTERVENTIONS: The Eagle Claw was used to close small perforations (1.5 to 2 cm) of the colon created by needle-knife with the animal under general anesthesia by using the endoluminal route. All animals received intravenous antibiotics and were allowed to eat after 24 hours. MAIN OUTCOME MEASUREMENTS: The animals were monitored daily for signs of sepsis and peritonitis. On day 7, they were euthanized. The peritoneal cavity was examined for fecal peritonitis, and the colon perforation site was checked for wound dehiscence and pericolic abscess formation. RESULTS: Endoscopic closure of the colon perforation was successful in 7 animals, and they recovered well without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation at the site of perforation, and the perforation healed well. Closure was successful in 1 animal, but necropsy revealed dehiscence of the colon perforation site. Endoscopic closure was unsuccessful in 2 animals, and these were euthanized immediately. CONCLUSIONS: Closure of acute perforation of the colon is feasible with the Eagle Claw endoscopic suturing device in a porcine model.

The endoscopic transilluminator: an endoscopic device for identification of the proximal jejunum for transgastric endoscopic gastrojejunostomy.

BACKGROUND: Localization of the proximal jejunum is important for creation of gastrojejunal anastomosis to palliate gastric outlet obstruction or for treatment of obesity with gastric bypass. OBJECTIVE: To facilitate identification of the proximal jejunum during transgastric endoscopic gastrojejunostomy with the use of an endoscopic transilluminator (ET). DESIGN AND SETTING: Acute experiments in a live porcine model. INTERVENTIONS: The ET is a 3500-mm long, 6F radio-opaque tube with a fiberoptic core that lights up at its distal end. When situated in the intestinal lumen, it transilluminates the bowel wall. With the animal under general anesthesia with endotracheal intubation, a colonoscope was advanced to the proximal jejunum. A plastic tube (3500-mm long, 3.5 mm in diameter) was passed through the biopsy channel and placed into the small bowel. The colonoscope was withdrawn, leaving the tube in place. The ET was introduced into the jejunum through the tube. A gastric wall incision was made and the endoscope was advanced to the peritoneal cavity. The transilluminated loop of the proximal jejunum was identified and gastrojejunal anastomosis was made by use of a previously reported endoscopic technique. MAIN OUTCOME MEASUREMENTS: Identification of the proximal jejunum. RESULTS: Eleven pigs (average weight 55 kg) had ET placement. In all of the pigs, placement of the ET was performed easily to the proximal small bowel, and the proximal jejunum was successfully localized by either direct visualization of the transilluminated loop only or with the aid of fluoroscopy. The tip of the ET was usually located about 50 to 70 cm distal to the ligament of Treitz. There were no complications related to the use of ET. LIMITATIONS: The device has not yet been evaluated in humans. CONCLUSIONS: The ET is a safe instrument and can be used to identify the proximal jejunum to facilitate endoscopic gastrojejunostomy.

Endoscopic plication of massively bleeding peptic ulcer by using the Eagle Claw VII device: a feasibility study in a porcine model.

BACKGROUND AND OBJECTIVE: We examined the efficacy of endoscopic plication when using Eagle Claw VII in a porcine bleeding ulcer model. ANIMAL MODEL PREPARATION: The right gastroepiploic artery (diameter 1.5-2 mm) was isolated and was tunneled to small gastrotomies at either the lesser or greater curvature of the stomach. INTERVENTIONS: We applied the Eagle Claw VII to achieve hemostasis. MAIN OUTCOME MEASUREMENTS: The survival of the pigs after endoscopic plication for hemostasis, time to achieve hemostasis with Eagle Claw VII, recurrent bleeding, number of successful plication, and number of suture remained. RESULTS: Endoscopic plication was performed on bleeding gastric ulcers in 6 pigs. The time to achieve hemostasis was 6 minutes 56 seconds +/- 3 minutes 50 seconds. There was no complication. A total of 14 plications were performed. All animals survived for 1 week without recurrent bleeding. At the postmortem, 10 of the plication sutures remained. LIMITATION: Our model cannot simulate the chronicity of peptic ulcer. CONCLUSIONS: In this porcine model, the Eagle Claw VII effectively stopped bleeding from arteries 2 mm in size.

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.

Multicenter prospective randomized trial comparing standard esophagectomy with chemoradiotherapy for treatment of squamous esophageal cancer: early results from the Chinese University Research Group for Esophageal Cancer (CURE).

We conducted a prospective randomized trial to compare the efficacy and survival outcome by chemoradiation with that by esophagectomy as a curative treatment. From July 2000 to December 2004, 80 patients with potentially resectable squamous cell carcinoma of the mid or lower thoracic esophagus were randomized to esophagectomy or chemoradiotherapy. A two- or three-stage esophagectomy with two-field dissection was performed. Patients treated with chemoradiotherapy received continuous 5-fluorouracil infusion (200 mg/m2/day) from day 1 to 42 and cisplatin (60 mg/m2) on days 1 and 22. The tumor and regional lymphatics were concomitantly irradiated to a total of 50-60 Gy. Tumor response was assessed by endoscopy, endoscopic ultrasonography, and computed tomography scan. Salvage esophagectomy was performed for incomplete response or recurrence. Forty-four patients received standard esophagectomy, whereas 36 were treated with chemoradiotherapy. Median follow-up was 16.9 months. The operative mortality was 6.8%. The incidence of postoperative complications was 38.6%. No difference in the early cumulative survival was found between the two groups (RR = 0.89; 95% confidence interval, 0.37-2.17; log-rank test P = 0.45). There was no difference in the disease-free survival. Patients treated with surgery had a slightly higher proportion of recurrence in the mediastinum, whereas those treated with chemoradiation sustained a higher proportion of recurrence in the cervical or abdominal regions. Standard esophagectomy or chemoradiotherapy offered similar early clinical outcome and survival for patients with squamous cell carcinoma of the esophagus. The challenge lies in the detection of residue disease after chemoradiotherapy.

Endoscopic gastrojejunostomy with survival in a porcine model.

BACKGROUND: We have previously reported the feasibility and the safety of an endoscopic transgastric approach to the peritoneal cavity in a porcine model. We now report successful performance of endoscopic gastrojejunostomy with survival. METHODS: All procedures were performed on 50-kg pigs, with the pigs under general anesthesia, in aseptic conditions with sterilized endoscopes and accessories. The stomach was irrigated with antibiotic solution, and a gastric incision was performed with a needle-knife and a sphincterotome. A standard upper endoscope was advanced through a sterile overtube into the peritoneal cavity. A loop of jejunum was identified, was retracted into the stomach, and was secured with sutures while using a prototype endoscopic suturing device. An incision was made into the jejunal loop with a needle-knife, and the filet-opened ends of the jejunal wall were secured to the gastric wall with a second line of sutures, completing the gastrojejunostomy. OBSERVATIONS: Two pigs survived for 2 weeks. Endoscopy and a radiographic contrast study performed after gastrojejunostomy revealed a patent anastomosis with normal-appearing gastric and jejunal mucosa. Postmortem examination demonstrated a well-healed anastomosis without infection or adhesions. CONCLUSIONS: The endoscopic transgastric approach to create a gastrojejunostomy is technically feasible and can be performed, with survival, in a porcine model.