Management of huge epiphrenic esophageal diverticula.

Epiphrenic diverticula occur in association with motor disorders of the distal esophagus, including achalasia and diffuse esophageal spasm. Four patients with huge symptomatic epiphrenic diverticula are presented to emphasize the need for complete radiographic and manometric studies of the esophagus to document this motor dysfunction prior to performing combined diverticulectomy and esophagomyotomy. Each patient had achalasia with symptoms extending from 4 to 25 years. Diverticulectomy and esophagomyotomy were performed in every patient. One patient had previously undergone diverticulectomy alone, with prompt recurrence of the lesion. During a follow-up period extending from 2 to 10 years, three patients were alive and well. One patient developed recurrent dysphagia due to reflux esophagitis and stricture requiring dilatation. It is essential that esophagomyotomy be part of the initial operative procedure. In selected patients, an antireflux procedure may also be indicated.

Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions.

There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high-grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma.

Cryolumpectomy for carcinoma of the breast.

Cryosurgery and surgical en bloc excision in preventing the local recurrence of mammary adenocarcinoma were studied in BALB/cfC3H (supplied by the Cancer Research Institute, University of California Berkeley) syngeneic mice carrying virus induced mammary adenocarcinomas transplanted into the fourth mammary fat pad. Cryosurgical procedures involving multiple freeze-thaw cycles to minus 180 degrees C. followed by tumor excision substantially reduced the local recurrence rate of carcinoma of the mammary gland in the mouse. The use of cryolumpectomy in the treatment of early carcinoma of the breast in humans is presented herein.

Risk factors for gallbladder perforation.

Perforation of the gallbladder is a potentially lethal problem due in part to a delay in diagnosis. In an effort to improve our management of these patients, we reviewed all patients seen at the UCLA affiliated hospitals between 1955 and 1983 who had perforation of the gallbladder. Fifty-one patients were reviewed and perforations categorized as either acute (type I) in 16 (31%), subacute (type II) in 20 (39%), or chronic (type III) in 15 (29%). A history suggestive of chronic gallstone disease was obtained in 0% of patients with type I, in 35% of patients with type II, and 60% of patients with type III perforations. The incidence of severe systemic diseases was significantly greater (p less than 0.01) in patients with type I as compared to type III perforation. Based on these data, clinical profiles have been developed for patients at risk of developing acute versus chronic gallbladder perforation. Awareness of these groupings forms the basis for early recognition and treatment of acute gallbladder perforation.

Altered gallbladder concentration of biliary lipids during early cholesterol gallstone formation.

Whether gallbladder absorptive function is altered during formation of cholesterol gallstones is unclear. We tested the hypothesis that alterations in biliary lipid composition present during early cholesterol gallstone formation enhance gallbladder absorption, as manifested by an increase in the ratio of gallbladder to hepatic bile lipid concentrations. Prairie dogs received either control or a 0.4% cholesterol-enriched chow for two or six weeks. The bile acid pool of each animal was labeled with [14C]cholic acid. Gallbladder and hepatic bile were analyzed for lipid composition with calculation of indices for cholesterol saturation, gallbladder stasis, and gallbladder absorption. Animals maintained on cholesterol-enriched chow for two weeks had a significant increase, as compared to controls, in the ratio of gallbladder to hepatic bile concentrations of cholesterol (8.66 +/- 1.09 vs 5.76 +/- 0.48), phospholipids (4.76 +/- 0.42 vs 3.21 +/- 0.34), bile acids (6.42 +/- 2.20 vs 3.54 +/- 0.46), and total lipid content (6.22 +/- 0.94 vs 3.64 +/- 0.43). These changes occurred at a time when gallbladder stasis is present and cholesterol crystals are forming, but prior to stone formation. Similar findings were noted in six-week cholesterol-fed prairie dogs. We propose the uniformly increased ratios of biliary lipids result from enhanced gallbladder absorption of water and sodium. The resulting increase in solute concentration may promote nucleation and, therefore, may be an important etiologic factor in cholesterol gallstone formation.

Pancreatic polypeptide enhances postcontractile gallbladder filling in the prairie dog.

The hypothesis that pancreatic polypeptide promotes postcontractile gallbladder filling was tested in the prairie dog model. Fifteen animals underwent laparotomy with catheter placement into the gallbladder, distal common bile duct (vent), and femoral vein. The gallbladder was perfused with [14C]polyethylene glycol labeled lactated Ringer's solution at 0.03 ml/min and vent effluent was collected at 2.5-min intervals. All animals received a 20-min intravenous infusion of cholecystokinin-octapeptide, 2.5 ng/kg X min, immediately followed by 60-min infusions of either lactated Ringer's solution or bovine pancreatic polypeptide (PP), 10 or 50 ng/kg X min. Gallbladder emptying and intragallbladder pressure were similar for all three groups after cholecystokinin-octapeptide. When lactated Ringer's was administered after cholecystokinin-octapeptide, gallbladder filling increased by 15.6% with a minimal change in gallbladder pressure. In contrast, infusion of PP10 resulted in a significant (p less than 0.02) increase in gallbladder filling, 64.1% +/- 17.1%, and a significant (p less than 0.05) decrease in intragallbladder pressure, as compared to controls. Similar findings were noted with PP50. These data indicate that exogenous PP significantly increases gallbladder filling after cholecystokinin-induced gallbladder contraction. This enhanced filling results from gallbladder relaxation as manifested by decreased intraluminal pressure. These findings coupled with the observation that serum PP levels remain elevated for up to 6 h after a meal suggest that PP may play a role in the regulation of postprandial gallbladder filling.

In vivo gallbladder absorption: a new dual-isotope technique.

Available methods for measuring in vivo gallbladder absorption preclude the use of animals in which hepatic bile enters the gallbladder via accessory or aberrant channels. However, accessory bile ducts are present in many of the animal models currently used in gallstone research. The aim of this study, therefore, was to evaluate a new dual-isotope technique that corrects for accessory bile flow and to compare data on electrolyte and water absorption with those derived from the standard, single-isotope technique. Prairie dogs underwent gallbladder exclusion by cystic duct ligation and common bile duct cannulation. Carbon 14-polyethylene glycol-labeled lactated Ringer's solution was instilled into the gallbladder while tritiated cholic acid was administered intravenously to label the bile acid pool. There is no correlation between water or electrolyte absorption and time, nor between water and electrolyte absorption, when these parameters are calculated by the standard, single-isotope technique. In contrast, use of the dual-isotope technique quantifies accessory bile duct flow and yields a linear increase in water and electrolyte absorption, both of which are time dependent. These data suggest that the dual-isotope technique provides a means to accurately measure in vivo gallbladder absorption in animals with or without accessory bile ducts.

Carbohydrate diet-induced calcium bilirubinate sludge and pigment gallstones in the prairie dog.

Epidemiologic studies suggest that consumption of diets rich in carbohydrates may, in part, be responsible for the increasing incidence of pigment gallstone disease. The mechanism by which these dietary components lead to pigment stone formation remains obscure. Furthermore, investigative efforts in this area have been hampered by the lack of a suitable animal model. The present study was undertaken to study the role of complex carbohydrates in pigment gallstone formation in the prairie dog. Two groups of eight animals each were maintained on either a control, nonlithogenic chow, or a high carbohydrate (35% sucrose, 32% rich starch) diet for 2 months. Neither crystals nor gallstones were observed in any of the control animals. All of the carbohydrate fed animals (P less than 0.005 vs control) had calcium bilirubinate crystals and sludge, while microscopic, black stones were present in six of these eight animals (P less than 0.05 vs control). Although hepatic bile bilirubin was unchanged in the carbohydrate-fed group, these animals had a significant increase in hepatic bile calcium (P less than 0.005) and phospholipids (P less than 0.005) when compared to controls. Carbohydrate-fed animals also had a significant increase in gallbladder bile concentrations of phospholipids (P less than 0.001), calcium (P less than 0.001), unconjugated (P less than 0.005), conjugated (P less than 0.005), and total bilirubin (P less than 0.001) as compared to controls. These data indicate that in the prairie dog, carbohydrate feeding results in increased biliary concentrations of phospholipids, calcium and bilirubin, and formation of calcium bilirubinate crystals, sludge and microscopic gallstones.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary leiomyosarcoma of gallbladder seen on computed tomography and ultrasound.

Neoplasms of the gallbladder are relatively rare and their preoperative diagnosis that much rarer; leiomyosarcoma of the gallbladder is one of the most infrequent types. The authors had the opportunity to diagnose such a neoplasm preoperatively (although the histological diagnosis was not made). The ultrasound and computed tomographic appearance has not been published before. Leiomyosarcoma showed a dilated gallbladder with an irregularly thickened wall and a polypoid protrusion into the lumen.

Decreased morbidity and mortality after pancreatoduodenectomy.

In two 5 year periods (1975 to 1979 and 1980 to 1984), 96 patients underwent pancreatoduodenal resection, which included 74 partial pancreatic resections and 22 total pancreatectomies. Thirty-seven of these patients had resections with preservation of the pylorus. Substantial reductions in perioperative mortality (2 percent versus 10 percent) and morbidity (26 percent versus 49 percent) (p less than 0.05) were achieved in the latter period. Pylorus preservation, with a mortality and morbidity of 3 percent and 27 percent, respectively, did not increase operative risk or compromise long-term survival in patients with malignant disease. In comparison, relatively high mortality and morbidity rates (14 percent and 59 percent) accompanied total pancreatectomy without improved long-term survival. Five year actuarial survival for nonpancreatic periampullary adenocarcinomas was 58 percent. Thus, we recommend pancreatoduodenectomy with preservation of the pylorus for resection of periampullary tumors. These patients, whose only possibility for cure is a major pancreatic resection, should not be denied this opportunity on the basis of reports from a previous era.

Gallbladder absorption increases during early cholesterol gallstone formation.

The hypothesis that the presence of cholelithogenic bile during the early stages of cholesterol gallstone formation promotes gallbladder absorption of water and electrolytes was tested in a prairie dog gallstone model. An increase in gallbladder transport of water and sodium was observed in cholesterol-fed prairie dogs at a time when cholesterol crystals were present, but before gallstone formation. These data suggest that in the presence of cholesterol-saturated bile, in vivo gallbladder absorption is increased during the early stages of cholesterol gallstone formation. The resulting increase in the solute concentration may promote nucleation and, therefore, be an important etiologic factor in cholesterol gallstone formation.

Lactomer copolymer absorbable staples in gastrointestinal surgery.

We performed a series of experimental studies to determine the clinical feasibility of using lactomer copolymer absorbable staples in gastrointestinal surgery. The stapling properties, reliability of suture and wound healing, and degree of inflammatory response were compared to similar properties of standard metal staples and polyglactin sutures. The absorbable staples were used in partial gastric transection, Billroth II gastrojejunostomy, and to close the ileum and ascending colon as part of an ileocecal resection. There were no deaths or complications in the nine experimental animals. At sacrifice 2 and 4 weeks after operation, the absorbable staples were intact with little or no macroscopic or microscopic evidence of absorption. The mucosal and submucosal layers were completely healed at 2 weeks, but muscular and serosal layers, although in excellent approximation, were incompletely joined. Inflammatory reactions around the lactomer staples and polyglactin sutures were comparable, but greater than that observed around metal staples. The studies suggest that staple techniques using absorbable materials are feasible and safe in gastrointestinal surgery.

Cryolumpectomy for breast cancer: an experimental study.

The effects of cryosurgical procedures and surgical excision in preventing the local recurrence of mammary adenocarcinoma were studied in BALB/cfC3H mice carrying syngeneic, virus-induced mammary adenocarcinomas transplanted into the fourth mammary fat pad. In this report we present evidence demonstrating that cryosurgical procedures involving multiple freeze-thaw cycles followed by tumor excision markedly reduce the local recurrence rate of mouse mammary cancer. Surgical resection without cryotreatment resulted in an 80% local recurrence rate; in contrast, cryotreatment consisting of three freeze-thaw cycles before excision prevented local tumor recurrence in 70% of the animals. The use of cryotherapy and local excision (cryolumpectomy) in the treatment of human breast cancer is discussed.

The Kock pouch as a urinary reservoir. Pitfalls and perspectives.

The Kock continent urinary reservoir is a feasible alternative to traditional methods of urinary diversion in properly motivated patients who are anxious to exchange a convenient external appliance for frequent reservoir catheterization. The major shortcomings are increased operative time, loss of a long segment of small bowel, and an approximate 10 percent incidence of major reoperation. Long-term results are unknown. Facility with the operation requires extensive experience and attention to detail. Most complications are related to inadequate fixation of the intussuscepted valves and improper placement of a short terminal segment in the abdominal wall. Early repair of malfunctioning valves and distal segments that are difficult to catheterize is essential to prevent more severe acute complications. Whether the Kock pouch will replace the standard methods of urinary diversion must be determined by more extensive clinical experience and long-term results.

Chronic intestinal pseudo-obstruction. Management with total parenteral nutrition and a venting enterostomy.

A variety of remedies have been suggested for patients with chronic intestinal pseudo-obstruction. However, none of these treatments have been particularly effective, and many of these patients have died of malnutrition. Therefore, in an effort to maintain nutrition and avoid repetitive nasogastric intubation, 22 patients (12 adults and ten children) with chronic intestinal pseudo-obstruction were managed with long-term total parenteral nutrition (TPN), and 20 also received a "venting" enterostomy. Only two patients had to undergo revision of their gastrostomies. Prior to referral, these 22 patients required 56 admissions for obstruction (1.2 admissions per patient-year). Since the initiation of TPN and placement of a venting enterostomy, these 22 patients required only 17 hospitalizations for obstruction in a total of 80 patient years (0.2 admissions per patient-year). We conclude that patients with chronic intestinal pseudo-obstruction who receive TPN at home and have a venting enterostomy can be safely managed for prolonged periods and require fewer hospitalizations for obstruction.

Effect of pancreatic polypeptide on gallbladder filling.

Recent studies suggest that pancreatic polypeptide (PP) alters gallbladder pressure and reduces delivery of bile to the duodenum. Whether this peptide influences gallbladder emptying and/or filling is not clear. Using the prairie dog model, we tested the hypothesis that exogenous PP induces gallbladder filling. Animals maintained on control diets underwent laparotomy with placement of catheters into the gallbladder and common bile duct. The gallbladder was perfused with [14C]polyethtyleneglycol ([14C]PEG)-labeled lactated Ringer's solution (LR) at 0.1 ml/min. Effluent from the common bile duct was collected at 5-min intervals during 30-min intravenous infusions of LR, LR + 2% serum albumin, and LR + 2% serum albumin + bovine PP (10 and 50 ng/kg/min). Gallbladder pressure was continuously recorded. Total and incremental fillings were calculated based on volume and [14C]PEG concentration changes. Infusion of PP, 50 ng/kg/min, induced significant gallbladder filling. The filling response was progressive and peaked during the final 10 min of peptide infusion. These findings coupled with the observation that serum PP levels are increased for up to 6 hr postprandially suggest that PP may play an important role in the regulation of interdigestive gallbladder filling.

Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease.

Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.

Ileal resection-induced gallstones: altered bilirubin or cholesterol metabolism?

Ileal resection has been shown to increase the risk of cholelithiasis. Earlier studies in humans suggested that ileal resection increases the cholesterol saturation index. Recent data from patients on long-term parenteral nutrition and from animals, however, have suggested that ileal resection predisposes to pigment gallstone formation. We therefore tested the hypothesis that ileal resection alters bile calcium and bilirubin metabolism without affecting the cholesterol saturation index. Adult male prairie dogs underwent either sham laparotomy (eight prairie dogs) or ileal resection (16 prairie dogs). All animals were fed a trace cholesterol (nonlithogenic) diet before and for 4 weeks after operation. Pigment gallstones were present in 44% of the ileal-resected animals and in none of the sham animals (p less than 0.05). Calcium bilirubinate crystals were present in 94% of the ileal-resected animals and in none of the sham animals (p less than 0.01). Gallbladder bile calcium (25.6 +/- 2.4 versus 17.2 +/- 1.1 mg/dl; p less than 0.05) and total bilirubin (29.3 +/- 4.0 versus 9.4 +/- 1.8 mg/dl; p less than 0.01) concentrations were significantly greater in ileal-resected animals. The cholesterol saturation index of gallbladder bile, however, was no different in ileal-resected (0.53 +/- 0.04) and in sham-operated animals (0.50 +/- 0.04). Although initial studies suggested that the cholesterol saturation index of hepatic bile was increased after ileal resection, a second set of experiments demonstrated that this phenomenon resulted from washout of bile salts that were already in extremely low concentrations in hepatic bile. We conclude that alterations in bilirubin, but not cholesterol, metabolism result in pigment gallstone formation after ileal resection.

Parenteral nutrition-induced gallbladder disease: a reason for early cholecystectomy.

Patients who receive long-term parenteral nutrition have an increased incidence of both calculous and acalculous cholecystitis. In an attempt to establish guidelines for the clinical management of patients with TPN-induced gallbladder disease, we have reviewed the records of 35 patients who have undergone cholecystectomy for this problem since 1976 at the UCLA Medical Center. The mean age of the 23 adult and 12 children who had cholecystectomy was 29.1 years. Forty percent of these patients required emergency cholecystectomy. The overall operative morbidity was 54 percent, and the hospital mortality was 11 percent. Significant factors contributing to this high rate of complications included a delay in diagnosis, especially in the young children, and increased operative difficulty due to extensive adhesions and intraoperative hemorrhage. Our analysis suggests that patients receiving long-term TPN should have a program of ultrasound surveillance for gallstone formation, elective cholecystectomy when stones first appear, and consideration of cholecystectomy at the time of laparotomy performed for other reasons. Whether TPN-induced gallstones can be prevented through daily stimulated gallbladder emptying awaits the results of future studies.