Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Laparoscopic hernia repair and bladder injury.

BACKGROUND: Bladder injury is a complication of laparoscopic surgery with a reported incidence in the general surgery literature of 0.5% and in the gynecology literature of 2%. We describe how to recognize and treat the injury and how to avoid the problem. CASE REPORTS: We report two cases of bladder injury repaired with a General Surgical Interventions (GSI) trocar and a balloon device used for laparoscopic extraperitoneal inguinal hernia repair. One patient had a prior appendectomy; the other had a prior midline incision from a suprapubic prostatectomy. We repaired the bladder injury, and the patients made a good recovery. CONCLUSION: When using the obturator and balloon device, it is important to stay anterior to the preperitoneal space and bladder. Prior lower abdominal surgery can be considered a relative contraindication to extraperitoneal laparoscopic hernia repair. Signs of gas in the Foley bag or hematuria should alert the surgeon to a bladder injury. A one- or two-layer repair of the bladder injury can be performed either laparoscopically or openly and is recommended for a visible injury. Mesh repair of the hernia can be completed provided no evidence exists of urinary tract infection. A Foley catheter is placed until healing occurs.

Trocar injuries in laparoscopic surgery.

BACKGROUND: Disposable trocars with safety shields are widely used for laparoscopic access. The aim of this study was to analyze risk factors associated with injuries resulting from their use as reported to the Food and Drug Administration. STUDY DESIGN: Manufacturers are required to report medical device-related incidents to the Food and Drug Administration. We analyzed the 629 trocar injuries reported from 1993 through 1996. RESULTS: There were three types of injury: 408 injuries of major blood vessels, 182 other visceral injuries (mainly bowel injuries), and 30 abdominal wall hematomas. Of the 32 deaths, 26 (81%) resulted from vascular injuries and 6 (19%) resulted from bowel injuries. Eighty-seven percent of deaths from vascular injuries involved the use of disposable trocars with safety shields and 9% involved disposable trocars with a direct-viewing feature. The aorta (23%) and inferior vena cava (15%) were the vessels most commonly traumatized in the fatal vascular injuries. Ninety-one percent of bowel injuries involved trocars with safety shields and 7% involved direct-view trocars. The diagnosis of an enterotomy was delayed in 10% of cases, and the mortality rate in this group was 21%. In 41 cases (10%) the surgeon initially thought the trocar had malfunctioned, but in only 1 instance was malfunction subsequently found when the device was examined. The likelihood of injury was not related to any specific procedure or manufacturer. CONCLUSIONS: These data show that safety shields and direct-view trocars cannot prevent serious injuries. Retroperitoneal vascular injuries should be largely avoidable by following safe techniques. Bowel injuries often went unrecognized, in which case they were highly lethal. Device malfunction was rarely a cause of trocar injuries.

A randomized prospective study of radially expanding trocars in laparoscopic surgery.

Trocar injury is one of the most serious and potentially preventable complications of laparoscopic surgery. Use of a blunt rather than a cutting trocar could be expected to lessen the likelihood of this injury. Therefore complications related to laparoscopic port design were studied by comparing conventional cutting trocars with radially expanding (blunt) trocars. A multicenter, prospective, randomized clinical trial was conducted in 250 adult patients undergoing elective laparoscopic procedures at tertiary care centers and community hospitals. The patients were randomly assigned to one of two groups: group C, conventional cutting trocars; or group S, radially expanding trocars. Sixteen surgeons performed 244 elective laparoscopic procedures; six patients were removed from the study. One hundred nineteen patients were assigned to group S and 125 to group C. The groups were similar with regard to age, sex, and type of procedure. The following data were collected: intraoperative complications related to the trocars, abdominal wall bleeding, visceral or vascular injury, other complications, fascial closure, procedure time, trocar site assessment at 4 and 24 hours postoperatively, and visual analog pain scores at 4, 8, 12, and 24 hours postoperatively. Fascial defects from 10 mm or larger trocars in group C were closed; the fascial defects in group S were not closed. The trocar sites were checked for incisional hernias at late follow-up. Mean operating time was not different between the two groups (group S, 92 +/- 73 minutes; group C, 100 +/- 74 minutes). There were no episodes of intraoperative cannula site bleeding in group S compared with 16 episodes in 13 patients (P < 0.001) in group C. Postoperative wound complications were fewer in group S (13 vs. 23; P < 0.05). Although the pain scores were generally lower in group S, the differences were not significant. Only 3% of the patients in group S had fascial defects of 10 mm or greater that had to be closed. Within a follow-up period of 6 to 18 months, there have been no incisional hernias in either group. This study shows that radially expanding trocars are safe and effective, and less likely than conventional trocars to result in intraoperative or postoperative complications. The defects created by the radially expanding trocars do not have to be routinely closed.

Laparoscopic repair of paraesophageal hiatal hernias.

BACKGROUND: Regardless of symptoms, paraesophageal hiatal hernias should be repaired in order to prevent complications. This study reports the University of California San Francisco experience with laparoscopic repair of paraesophageal hiatal hernias, emphasizing the technical steps essential for good results. PATIENTS AND METHODS: From May 1993 to September 1997, 55 patients, 27 women and 28 men, with a mean age of 67 years (range, 35-102 years) underwent laparoscopic repair of paraesophageal hernias at the University of California San Francisco. Symptoms, which had been present an average of 85 months before surgery, consisted mainly of pain (55%), heartburn (52%), dysphagia (45%), and regurgitation (41%). Of the four patients who presented with acute illness, two had gastric obstruction, one had severe dyspnea, and one had gastric bleeding. Endoscopy demonstrated esophagitis in 25 (69%) of 36 patients, and 24-hour pH-monitoring demonstrated acid reflux in 22 (67%) of 33 patients. Manometry detected severely impaired distal esophageal peristalsis in 17 (52%) of 33 patients. The preferred operation consisted of reduction of the hernia, excision of the sack and the gastric fat pad, closure of the enlarged hiatus without mesh, and construction of a fundoplication anchored by sutures within the abdomen. RESULTS: Of the 55 patients, the operations of 49 were completed laparoscopically using the following reconstructions: Guarner (270-degree) fundoplication (30 patients); Nissen fundoplication (10 patients); and gastropexy (9 patients). Five (9%) operations were converted to laparotomies. The average operating time was 219 minutes; the average blood loss was less than 25 mL; resumption of an unrestricted diet, 27 hours; and mean hospital stay, 58 hours. Intraoperative technical complications occurred in five (9%) patients. One patient died during surgery from a sudden pulmonary embolus. Two (4%) patients required a second operation for recurrent paraesophageal hernias. CONCLUSIONS: Laparoscopic repair of paraesophageal hiatal hernias is safe and effective, but the operation is difficult and good results hinge on details of the operative technique and the surgeon's experience. In this series, the crus could always be closed securely without using mesh. We realized early that a fundoplication should be a routine step, because it corrects reflux and is the best method to secure the gastroesophageal junction in the abdomen.

Partial fundoplication for gastroesophageal reflux.

BACKGROUND: About 20% of patients with gastroesophageal reflux disease (GERD) have severely impaired esophageal peristalsis in addition to an incompetent lower esophageal sphincter. In these patients a total fundoplication corrects the abnormal reflux, but it is often associated with postoperative dysphagia and gas bloat syndrome. We studied the efficacy of partial fundoplication in such patients. METHODS: A partial fundoplication (240 degrees -270 degrees ) was performed laparoscopically in 26 patients (11 men, 15 women; mean age 50.5 years) with GERD (mean DeMeester score: 92 +/- 16) in whom manometry demonstrated severely abnormal esophageal peristalsis. RESULTS: All operations were completed laparoscopically and the patients were dicharged an average of 39 h after surgery. The preoperative symptoms resolved or improved in all patients, and no patient developed dysphagia or gas bloat syndrome. Postoperative pH monitoring showed complete or nearly complete resolution of the abnormal reflux in every patient. CONCLUSIONS: Partial fundoplication is an excellent treatment for patients with GERD and weak peristalsis, for it corrects the abnormal reflux and avoids postoperative dysphagia.

Laparoscopic treatment of liver cysts.

Symptomatic simple liver cysts should be treated. In this report we describe the results of a straightforward, well-tolerated laparoscopic operation for this condition. Between 1990 and 1996 we performed 19 laparoscopic liver cyst excisions. The exposed portion of the cyst wall was excised and a piece of omentum was secured into the remaining cyst cavity to prevent recurrence. The average age of the patients was 65 years (range 30 to 81 years). Eight patients (42%) had single simple cysts, nine patients (47%) had multiple simple cysts, and two patients (11%) had polycystic liver disease. Fifty-three percent of the patients had previous abdominal operations, 47% had undergone previous needle aspirations, and one had previously undergone unsuccessful laparoscopic cyst decompression elsewhere. The indications for surgery included abdominal pain, mass, early satiety, malaise, bloating, and shortness of breath. Two patients underwent concurrent cholecystectomies, and one patient underwent concurrent laparoscopic Nissen fundoplication. Follow-up, which averaged 32 months (range 3 to 68 months), is complete in all patients. There was one treatment failure among the patients with simple cysts. Both patients with polycystic liver disease have had recurrent symptoms. The laparoscopic approach to simple liver cysts is relatively straightforward, and if certain technical principles are adhered to, the success rate is very high.

Comparison of laparoscopic imaging systems and conditions using a knot-tying task.

Pilot experiments to determine the important factors in the engineering of laparoscopic (videoscopic) imaging systems are described in this paper. In the first set of experiments, three videoscopic systems were compared by using a knot-tying task: monoscopic, monoscopic with digital contrast enhancement, and stereoscopic. Direct viewing was used as a control. In both experienced and novice subject groups, no difference was found in completion time or errors between the videoscopic conditions. Performance with direct viewing was significantly better, however, indicating that there are factors in videoscopic imaging that degrade perception or distort the relationship between vision and motor response. In the second set of experiments, the effects of contrast and spatial resolution were examined by varying working distance and camera exposure while experienced subjects tied knots on high- and low-contrast surfaces. Good contrast was found to be most important at longer working distances. This result shows that performance of knot tying, a complex task, is affected by contrast sensitivity, which is a fundamental property of human vision.

Radially expanding dilatation. A superior method of laparoscopic trocar access.

Trocars used in laparoscopic surgery occasionally produce serious complications, such as bleeding, visceral injury, or incisional hernia. We report the evaluation of a new, potentially safer laparoscopic access device in which the cutting obturator of a standard trocar is replaced by a blunt, radially expanding device. Conventional and radially expanding trocars were used in laparoscopic cholecystectomies in 12 pigs. Their abdominal walls were excised and the defects caused by the trocars were examined. The defects caused by the radially expanding devices were about 50% narrower (P < 0.001), and the incidence of abdominal wall bleeding was considerably less (0% vs 21%) with the radially expanding trocars. Since incisional hernias at trocar sites are related to the size of the abdominal wall defect, the use of radially expanding trocars should decrease the incidence of this complication. There should also be less risk of visceral injury.

Complex task performance in Cyberspace. Surgical procedures in a telepresence environment.

To assess the capabilities of our fully functional, prototype telepresence surgery system, experienced surgeons performed complete operative procedures on live, anesthetized pigs. Cholecystectomy, the prototypical procedure for evaluating the integration of surgical skills, was successfully performed in six animals. There were no aborted attempts or complications. Other procedures completed included gastrotomy and enterotomy closures, anastomosis of the small intestine, and nephrectomy. No specific training was required for using the telepresence surgery system, and the "feel" of the system was described as intuitive. Operative times were longer than required in conventional, open surgery, most likely the result of the four degrees of freedom available in the manipulators of the current-generation system. Force feedback and high-resolution, stereoscopic video input facilitated performance. Surgeons operating through a first-generation telepresence system can achieve technical results equivalent to those obtained in conventional surgery.

Assessing a virtual reality surgical skills simulator.

The Institute for Defense Analyses (IDA) was contracted to perform a military standard task analysis of laparoscopic cholecystectomy, and to study the effectiveness of a virtual reality surgical skills simulator as a tool for surgical training and as a method for recording psychomotor behavior. This report describes the purpose of the study, its design, initial results, and implications for the field of medical education.

Intraluminal surgery: a new arena for minimally invasive surgery.

Although surgery within the lumen of the gut has been performed for many years, this has traditionally involved a laparotomy and enterotomy. With the advances in flexible endoscopy, surgeons and gastroenterologists have been able to perform therapeutic procedures with instruments introduced through the working channel of flexible endoscopes. These procedures, however, have been mainly limited to technically minor ones, such as injection and cautery of bleeding ulcers and resection of polyps and small mucosal lesion. More recently, laparoscopic surgeons have been able to isolate the lumen of hollow organs as a separate working space and develop instrumentation and technique specifically for intraluminal surgery. This paper provides an overview of our approach, which includes development of a new device for intraluminal access and operations within the lumen of the stomach. Future application of this approach will also be discussed.

Ultrastructural observations on myelinated fibres in experimental diabetes: effect of the aldose reductase inhibitor ponalrestat given alone or in conjunction with insulin therapy.

Six groups of rats were studied over a 12-week period: onset and end controls, untreated diabetics, ponalrestat-treated diabetics, insulin-treated diabetics, and diabetics treated with ponalrestat and insulin. The concentrations of glucose, sorbitol and fructose significantly increased and that of myo-inositol significantly decreased in the sciatic nerve of untreated diabetic animals. Ponalrestat administration completely normalized sorbitol levels and partially corrected fructose and myo-inositol concentrations without altering nerve glucose levels. The biochemical abnormalities were also corrected in both the insulin-treated and insulin and ponalrestat-treated diabetic animals. Myelinated fibre cross-sectional areas and axonal areas were significantly less in the tibial nerve of diabetic animals as compared with age-matched controls. Insulin treatment partially corrected the reduction in fibre and axonal area but teased fibre preparations showed an excess of axonal degeneration as compared with controls, untreated diabetics and ponalrestat-treated diabetics. Ponalrestat given alone or in conjunction with insulin therapy did not correct the reduction in fibre or axonal area and single isolated fibres from diabetic animals treated with ponalrestat and insulin showed a marked excess of axonal degeneration, probably related to hypoglycaemia. The study fails to reveal any significant beneficial effect of aldose reductase inhibition on the structural abnormalities in peripheral nerve in experimental diabetes.