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To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)

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Endoscopic sphincterotomy is the procedure of choice for choleducolithiasis post-cholecystectomy, and in poor-surgical-risk patients with the gallbladder still present. Sphincterotomy indications have been expanded to include acute biliary pancreatitis, acute cholangitis, and choleducolithiasis removal prior to definitive surgery. This paper will review the available literature and make recommendations on these new indications.

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The purpose of this paper is to illustrate the clinical usefulness of simultaneous fluoroscopy and manometry, as analyzed by the manofluorogram, in the evaluation of dysphagia. Four quantitative parameters calculated from the manofluorogram are analyzed and compared in six representative cases of dysphagia. The manofluorogram adds diagnostic information which cannot be obtained by barium swallow or standard manometry.

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A case of Salmonella enteritis which resulted in a chronic typhoid carrier state is reported. The recurrent cholangitis progressed to sclerosing cholangitis, with subsequent development of cholangiocarcinoma. Although epidemiological studies demonstrate an increased risk of developing hepatobiliary cancer in chronic typhoid carriers, a documented case has never been reported.

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A total of 20 patients with inflammatory bowel disease (IBD) (Crohn's disease, ulcerative colitis) were evaluated with regard to the role of infectious agents and host response. Patients were selected based upon oral manifestations of their disease, 10 with periodontal disease and 10 without. Microbiologic studies of the periodontal flora of IBD-affected patients revealed a unique microflora composed predominantly of small, motile, gram-negative rods, which were most consistent with the genus Wolinella. Further studies of the host response of these patients revealed a serum-mediated defect in neutrophil chemotaxis in all 10 patients with periodontal disease. Neutrophil phagocytosis was normal. In vitro studies of neutrophil function in response to Wolinella extracts and culture supernatants revealed inhibition of neutrophil chemotaxis in a dose-response fashion. The organism was chemokinetic for neutrophils but not chemotactic. The data suggest that unusual microorganisms colonizing the oral cavity of IBD patients potentially play a role in the pathogenesis of the disease as infectious agents or modifiers of the host response or both.

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Various surgical procedures have addressed the disabling pain of chronic pancreatitis. Pain control must be weighed against the surgical morbidity and metabolic consequences of operation. Although ductal drainage works well for patients with dilated ducts, a new procedure was devised to avoid the diabetic morbidity of near-total pancreatectomy or pancreaticoduodenectomy in patients with small duct pancreatitis. Five patients have undergone the splenopancreatic flap procedure. The head of the pancreas is resected in a manner similar to near-total pancreatectomy, while the body and tail are denervated by dissection from their bed, with retrograde perfusion from the splenic hilus. All patients are alive a mean of 9 months after operation, and none is diabetic. Only one patient requires narcotic analgesics. Although none is asymptomatic, all have shown significant weight gain, and four of five are vocationally rehabilitated. Flap viability and the absence of transgastric varices have been documented by angiography and CT scanning. Although the durability of pain relief and islet cell function is unknown, these results suggest that this procedure may offer an alternative to major resection in chronic pancreatitis.

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Forty-five percutaneous needle biopsies of pancreatic masses were performed in 41 patients in whom there was clinical or radiological concern for the diagnosis of cancer. Computed tomography (CT) was the imaging technique used in 41 of the 45 biopsies. An overall sensitivity of 85%, specificity of 100%, and accuracy rate of 88% were achieved, with serious complications in three of the 45 attempts (6.7%). These figures show that percutaneous pancreatic biopsies have the potential for greater accuracy than has been previously reported and are relatively safe when compared with surgery.

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These preliminary results of a new approach for the control of pain in chronic pancreatitis are presented with the hope that others experienced in this field will test this concept.

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The National Cooperative Gallstone Study, a double-masked, placebo-controlled, therapeutic trial of chenodiol (chenodeoxycholic acid), provided an opportunity to study the natural history of cholelithiasis in patients who choose nonsurgical management. The major component of the study comprised 916 patients, 305 of whom were randomly assigned to receive a placebo for 24 months. Among these 305 patients, the probability of having biliary tract pain during the 24 months of prospective evaluation was significantly increased if the patient had had a history of biliary tract pain in the 12 months before entry into the study (69% versus 31%). Thirty-eight percent of patients had stone growth (greater than 0.5 cm3), and 18% had a spontaneous decrease in stone volume. Despite the high incidence of biliary tract pain, nonelective cholecystectomy was required in only 4% of patients during the 24 months.

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The National Cooperative Gallstone Study (NCGS) was a cooperative, randomized, controlled trial of a drug, chenodiol, for the medical dissolution of gallstones. The design and procedures of the NCGS were complex, having developed as a result of extensive involvement of many experts in the field of gallstone disease and biliary lipids. During the design and implementation of the protocol, many important issues required consideration and resolution. The aim of this article is to review these issues and the deliberations surrounding their resolution and provide personal conclusions and recommendations that may be helpful to other investigators involved in cooperative, controlled trials.

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Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.

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During the National Cooperative Gallstone Study, therapy with chenodiol, 750 or 375 mg/d, for 2 years resulted in confirmed, complete gallstone dissolution in 14% and 5% of patients, respectively, and partial dissolution (greater than 50%) in 27% and 18%. The present study was done to determine the frequency with which complete dissolution occurs in patients having partial dissolution of gallstones who receive additional therapy. Eighty-six of one hundred thirty-eight eligible patients continued to receive 750 mg/d (61 patients) or 375 mg/d (25 patients) of chenodiol for 1 year. Patients whose oral cholecystogram at the end of the year showed further (greater than 50%) dissolution continued to receive chenodiol, (28 patients at 750 mg/d and 11 patients at 375 mg/d) for a second year (total duration of therapy, 4 years). A final oral cholecystogram was taken at the end of the fourth year. Complete dissolution occurred in 23% and 16% of patients receiving chenodiol, 750 or 375 mg/d, respectively, for an additional 1 or 2 years.

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The net absorption and retention of energy, fat, nitrogen, and six elements (potassium, phosphorus, calcium, magnesium, sodium, and chloride) from two intrajejunally infused enteral formulas were compared to solid food. Undernourished patients (group 1) underwent two consecutive 7-day balance studies on a predigested protein-low fat (elemental) formula and an intact protein-standard fat (polymeric) formula, the initial diet selected randomly. Periods were isocaloric and isonitrogenous, but differed in the amounts of remaining elements. The undernourished patients in group 2 ate a solid food standard hospital diet for the 7-day balance study in an amount equal in energy and protein to group 1. There were no major differences in the nutrient absorption between the three diets. Nitrogen balance was similar for the two formulas (mean +/- SD) (elemental 6.1 +/- 3.5 g/day; polymeric 4.8 +/- 3.2 g/day) and solid food (5.2 +/- 3.5 g/day), and the balance for the six remaining elements was approximately proportional to the amount supplied. Subjective tolerance of both formulas was good, with a tendency for superior tolerance of the polymeric formula. We conclude that for the nutrients investigated, 1) intrajejunally administered enteral formulas are capable of renourishing hospitalized patients with an efficacy similar to that of solid food, and 2) predigestion of the formula does not improve absorption.

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Can normal nutritional status, as indicated by albumin, transferrin and lean body mass values, be maintained during a 100 lb weight loss after gastric partitioning? Fifteen morbidly obese patients with normal nutritional status were fed three diets before (diet A) and after (diets B and C) gastric partitioning, and changes in albumin, transferrin, and lean body mass were monitored. Diets A and C were compositionally equal and contained 40 to 60 g of protein and 600 to 900 calories administered in six to eight equally divided portions per day. Diet B contained 20 to 40 g of protein and 600 to 800 calories per day and was given through a gastrostomy tube for three months after surgery while oral input was limited to noncaloric liquids. Results showed that weight loss was more rapid before surgery with diet A, than after surgery with diet B or C (diet A versus diet B, p less than 0.05; diet A versus diet C, p less than 0.05). Lean body mass was maintained with each diet, but transferrin (p less than 0.01) and albumin (p less than 0.05) decreased while patients were fed diet B. When gastrostomy tube feedings were discontinued, diet C restored albumin and transferrin to preoperative values (diet C versus diet B, p less than 0.05, diet C versus diet A, p greater than 0.1). Total postoperative weight loss averaged 106 +/- 20 lb after 2 years. These data show that in carefully selected patients with morbid obesity who demonstrate compliance to diet A before surgery, a 100 lb weight loss may be achieved while nutritional competence is maintained.

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Two patients with malabsorption syndrome and weight loss refractory to conventional pharmacologic and dietary therapy were evaluated on a metabolic ward. Baseline studies indicated moderate to severe protein-energy malnutrition, and severe energy, fat, and nitrogen malabsorption. Metabolic balance studies on low-fat elemental formulas infused nasoenterally over 18-hour periods indicated improved retention of nitrogen, phosphorus, calcium, magnesium, and energy when compared with a solid food diet. Because this dietary modification appeared to correct their malabsorption, both patients learned to insert the nasoenteral tube themselves, and a low-calorie solid-food diet combined with nocturnal tube feedings was continued at home. During the next 9 to 12 months, both patients had increases in body weight, and in the mass of fat-free tissue, skeletal muscle, and fat. This therapeutic approach may correct life-threatening semistarvation in selected patients.

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Biliary lipid classes (bile acids, phospholipids, cholesterol) as well as individual biliary bile acids were measured in duodenal bile samples obtained before treatment from 284 white men and 264 white women participating in the National Cooperative Gallstone Study. The patients had radiolucent gallstones present in visualizing gallbladders. Calculated biliary cholesterol saturation was significantly higher in women (143 +/- 43, mean +/- SD, vs. 132 +/- 39 for men). Chenodeoxycholic acid was the major biliary bile acid in both sexes (40.0 +/- 9.9 in men; 38.8 +/- 9.3 in women, NS). Cholic acid was the second most common bile acid, constituting 32.9 +/- 8.8 in men and 31.8 +/- 8.9 in women (NS). When other demographic and clinical characteristics, including serum lipids, were related with biliary lipid composition, only percent ideal body weight correlated significantly. The partial correlation coefficient adjusted for percent ideal body weight indicated that the proportion of chenodeoxycholic acid correlated negatively with the mole fraction of cholesterol in bile in men, but not in women. Multiple regression analyses showed that bile saturation could not be predicted reliably from any clinical, chemical, or radiologic measurement in either sex. Published data for biliary lipid composition in individuals with biliary disease showed considerable overlap with the National Cooperative Gallstone Study data reported here, suggesting that cholesterol gallstone disease is not caused solely by increased biliary cholesterol saturation.

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