James W. Ostroff

Endoscopic Sclerotherapy Compared with Percutaneous Transjugular Intrahepatic Portosystemic Shunt after Initial Sclerotherapy in Patients with Acute Variceal Hemorrhage: A Randomized, Controlled Trial

During the past 15 years, endoscopic sclerotherapy and, more recently, band ligation and such pharmacologic agents as octreotide have eclipsed surgical shunting as the preferred method for controlling acute variceal hemorrhage. The status of sclerotherapy for the long-term management of patients with bleeding varices, however, remains controversial. In a previous controlled clinical trial comparing endoscopic sclerotherapy with surgical portacaval shunting [1], we enrolled 64 adult patients with Child class C cirrhosis and active hemorrhage from esophageal varices. At the index hospitalization, patients randomly assigned to sclerotherapy required less blood transfusion and fewer days of hospitalization than did those randomly assigned to shunt surgery. During the initial follow-up period, which extended for a mean of 530 days after randomization, 75% of the patients treated with sclerotherapy were hospitalized for recurrent variceal hemorrhage but none of the patients who had had shunt surgery were rehospitalized [1]. Although patients treated with sclerotherapy had longer hospital stays and received more blood transfusions during short-term follow-up, a longer follow-up study [2] showed no difference in survival or overall health care costs between patients treated with sclerotherapy and those treated with surgical shunt. The transjugular intrahepatic portosystemic shunt (TIPS) procedure is a nonsurgical procedure in which an expandable metal prosthesis is used to connect an intrahepatic portal vein with an adjacent hepatic vein [3, 4]. In our initial report on 100 patients having this procedure [3], TIPS stent placement was technically successful in 96 patients and variceal hemorrhage was controlled in 88 of 94 patients [3]. Furthermore, the 30-day mortality rate was only 13% in patients treated with TIPS. These data, as well as those of other researchers who used radiographically placed portosystemic stents, suggest that TIPS might be more cost-effective than sclerotherapy; however, data comparing the two procedures are limited [5-10]. Therefore, we did a randomized, controlled trial in patients with massive acute variceal hemorrhage in an effort to compare the two therapies for the prevention of recurrent variceal hemorrhage. Methods From November 1991 through December 1995, we enrolled 49 adults who had cirrhosis and endoscopically documented bleeding from esophageal varices. We excluded an estimated additional 250 patients with bleeding varices whom we had seen during the study period (vide infra). Our study protocol was approved by the Committee on Human Research of the University of California, San Francisco. Patients who were admitted to San Francisco General Hospital, University of California Medical Center, and Veterans Affairs Medical Center (all located in San Francisco, California) with massive or submassive acute gastrointestinal tract hemorrhage from large esophageal varices were approached for consent and randomization within 24 hours of admission. Massive hemorrhage was defined as bleeding associated with shock (systolic blood pressure < 80 mm Hg). Submassive hemorrhage was defined as hemorrhage associated with postural vital sign changes (upright pulse rate increased by 20 beats per minute compared with supine pulse rate; upright systolic blood pressure decreased by 20 mm Hg compared with supine blood pressure). The 250 excluded patients were excluded for the following reasons: They were prisoners; they were younger than 18 or older than 75 years of age; they had had a cerebrovascular accident within 3 months before the onset of bleeding; they refused to accept blood products; or they had gastric variceal hemorrhage, electrocardiographic changes compatible with acute myocardial infarction, a Po 2 less than 70 mm Hg or an arterial pH of 7.20 or less on room air at the time of evaluation for eligibility, a serum creatinine level of 221 mol/L or more, a prothrombin time at least 5 seconds longer than control (despite the use of fresh frozen plasma), a platelet count less than 50 109/L, stage IV hepatic encephalopathy, cancer other than skin cancer, the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex, sepsis, pneumonia, peritonitis, clinical evidence of alcoholic hepatitis, a serum bilirubin concentration of 7 mg/dL or more, thrombosis of the portal vein, thrombosis of the hepatic veins, or thrombosis of the inferior vena cava as determined by Doppler ultrasonography. All patients received endoscopic sclerotherapy at the time of the initial endoscopic procedure that established the source of hemorrhage as esophageal varices. Patients were deemed eligible for participation if they presented with hemodynamically submassive or massive hemorrhage and were found to have large (>1 cm across) distal esophageal varices with cherry red spots, hematocystic spots, or red wale signs. Before randomization, all patients had patency of the portal venous system (main, right, and left portal veins and the splenic vein) and hepatic veins determined by real-time color and pulse-wave Doppler ultrasonography. After we obtained informed consent, we used serially numbered, sealed, opaque envelopes to randomly assign patients either to repeated sclerotherapy or to TIPS. If neither the patient nor the patients next of kin was able to give informed consent, a patient advocate was designated to consider the invitation to participate. Patients randomly assigned to sclerotherapy received treatment every 2 to 7 days during the initial hospitalization; treatment consisted of 0.5- to 2.0-mL injections of ethanolamine oleate solution per varix. Repeated endoscopy and sclerotherapy treatments were done weekly after discharge from the initial hospitalization. As much as 30 mL of ethanolamine oleate solution was used per treatment session. All visible varices were injected within the distal 7 to 10 cm of the esophagus. In patients who developed sclerotherapy-associated ulcers, repeated endoscopy was scheduled to be done 2 to 7 days after the notation of ulcers to assess interval healing. Patients assigned to the TIPS group had the procedure within 48 hours of randomization; the procedure was performed by one of six radiologists skilled in this procedure, as described elsewhere [3]. Catheterization of the hepatic vein was done through the right internal jugular vein. A tract between a suitable hepatic vein and a suitable portal vein was established by needle set (Ring TIPS set, Cook, Inc., Bloomington, Indiana), dilated with a balloon over a guidewire, and then maintained by one or more expandable metal mesh stents (Wallstent, Schneider, Inc., Minneapolis, Minnesota). The adequacy of the portosystemic shunt was documented by contrast injection and manometric measurement at the time of the initial procedure. A target portal vein-to-hepatic vein pressure gradient of 12 mm Hg or less was achieved in all cases. Persistent varices opacified at portal venography after adequate stenting were occluded by using embolization coils. Preprocedural data recorded prospectively included sex, age, vital signs at admission, physical examination findings at admission (including presence of encephalopathy and ascites), nutritional status, results of laboratory tests, and Child-Pugh score [11]. Prospectively identified outcome variables after randomization included death, rebleeding, liver transplantation, total transfusion requirements, onset and presence of encephalopathy, cost of managing variceal hemorrhage after randomization, total duration of hospitalization for variceal hemorrhage and any related encephalopathy, and complications of therapy. Nutritional status was defined as malnourished if the patient had gross muscle wasting, had cachexia, or had lost at least 10% of body weight during the previous 6 months. Bleeding after randomization was defined as bloody or coffee grounds emesis (hemetemesis, melenemesis) or liquid black stools (melena) with a decrease in hematocrit sufficient to warrant transfusion. Hepatic encephalopathy was defined clinically by the presence of asterixis, gross disorientation or agitation, or frank somnolence or coma in the absence of another identifiable cause. Presence of ascites was determined by both ultrasonography and clinical assessment (shifting dullness, fluid wave, gross distention) for all patients initially and for patients in the TIPS group having follow-up Doppler ultrasonography. For patients assigned to sclerotherapy, presence of ascites was subsequently determined by clinical criteria alone. Follow-up information was obtained through face-to-face interviews, telephone interviews, or chart reviews and was obtained from the patient, family, physician, or all three sources. The total cost of health care per patient was calculated as the sum of all real costs for inpatient and outpatient hospital care, including hospital expenditures and costs for professional services from the day of randomization until death or the last follow-up visit. In addition, all outpatient costs for endoscopic sclerotherapy, Doppler ultrasonography, and stent revision during the follow-up period were included. We used the actual cost to the hospital or medical staff, or both, of providing a service or procedure (rather than billing charges or collections). For example, the cost of an endoscopic sclerotherapy session was determined by summating the following: 1 hour of a gastroenterologists time plus benefits (derived from personnel pay records); 2 hours of a registered nurses time plus benefits; the invoice cost of disposable sclerotherapy catheters, bite blocks, and intravenous tubing; the pharmacy costs of all drugs, including the sclerosant agent; the estimated depreciation of an Olympus GIT-IT100 videoendoscope (Lake Success, New York); endoscopic processing costs; 1 hour of recovery room personnel time; and costs of recovery supplies. Outcome variables were compared, using the intention-to-tre

Thoracoscopic esophageal myotomy in the treatment of achalasia

We treated 24 patients with achalasia using thoracoscopic (22 patients) or laparoscopic (2 patients) esophagomyotomy. The only operative complications were mucosal lacerations, which occurred in 3 patients and required conversion to an open procedure in 2. Twenty-two (91%) patients were eating by the second postoperative day. Analgesics were only required for the management of pain from the chest tube, which remained in place for a median time of 24 hours. The median postoperative hospital stay was 3 days (range, 20 to 14 days). The myotomy proved to be incomplete in the first 3 patients, who required a second myotomy; this was done laparoscopically in 2. One patient had a paraesophageal hernia repaired 6 months after the myotomy, and 1 patient required an esophagectomy 1 year after the myotomy for a large nonfunctioning esophagus. Late follow-up showed that swallowing was excellent in 17 (71%) and fair to good in 4 (17%). Sixteen (66%) of these 24 patients have regained their original weight. Thus, excellent to good results were ultimately obtained in nearly 90% of the patients. These results suggest that esophageal myotomy performed using minimally invasive techniques appears to be the treatment of choice for achalasia.

Early predictors of severe lower gastrointestinal bleeding and adverse outcomes: a prospective study.

BACKGROUND & AIMS Unlike in upper tract bleeding, prognostic factors for ongoing or recurrent bleeding from the lower gastrointestinal tract have not been well-defined. The aim of this study was to identify risk factors for severe lower gastrointestinal bleeding and for significant adverse outcomes. METHODS All patients seeking attention at a university emergency department for gastrointestinal bleeding were prospectively identified during a 3-year period. Ninety-four of 448 (21%) admitted patients had lower gastrointestinal bleeding. Clinical predictors available in the first hour of evaluation were recorded. The primary outcome, severe lower gastrointestinal bleeding, was defined as gross blood per rectum after leaving the emergency department associated with either abnormal vital signs (systolic blood pressure < 100 mm Hg or heart rate > 100/min) or more than a 2-unit blood transfusion during the hospitalization. Significant adverse outcomes, including death, were tabulated. RESULTS Thirty-seven patients (39%) had severe lower gastrointestinal bleeding. Independent risk factors for severe lower gastrointestinal bleeding were initial hematocrit </=35% (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.2-16.7); presence of abnormal vital signs (systolic blood pressure < 100 mm Hg or heart rate > 100/min) 1 hour after initial medical evaluation (OR, 4.3; 95% CI, 1.4-12.5); and gross blood on initial rectal examination (OR, 3.9; 95% CI, 1.2-13.2). Nineteen patients (20%) experienced a significant adverse outcome, including 3 deaths. The main independent predictor of adverse outcomes was severe lower gastrointestinal bleeding (OR, 5.3; 95% CI, 1.7-16.5). CONCLUSIONS Risk factors are available in the first hour of evaluation in the emergency department to identify patients at risk for severe lower gastrointestinal bleeding. Severe lower gastrointestinal bleeding is a significant risk factor for global adverse outcomes.

THE MANAGEMENT OF T TUBE LEAKS IN ORTHOTOPIC LIVER TRANSPLANT RECIPIENTS WITH ENDOSCOPICALLY PLACED NASOBILIARY CATHETERS

Biliary tract problems remain an important cause of complication following orthotopic hepatic transplantation. We describe 12 liver transplantation patients who developed bile peritonitis secondary to a biliary leak after T tube removal. Each of these patients underwent an urgent ERCP that exhibited leakage outside the T tube tract and nondilated intrahepatic ducts. At the time of the ERCP, a nasobiliary catheter was inserted to divert the bile flow. All of these patients resolved their symptoms and closed their leak. We advocate endoscopic placement of a nasobiliary catheter as first-line therapy for significant T tube tract leaks after liver transplantation.

Gastrointestinal Bleeding in the Hospitalized Patient: A Case-Control Study to Assess Risk Factors, Causes, and Outcome

PURPOSE To determine the risk factors, etiology, and outcome of clinically important gastrointestinal bleeding that occurs after hospital admission (nosocomial gastrointestinal bleeding). PATIENTS AND METHODS Cases consisted of consecutive patients who developed gastrointestinal bleeding more than 24 hours after admission to the hospital. Cases were compared with two control populations: a set of hospitalized patients without gastrointestinal bleeding matched with cases for age, gender, and length of stay; and all patients admitted to the hospital with clinically important gastroduodenal ulcer bleeding during the study period. Case and controls were compared with respect to risk factors for gastrointestinal bleeding and outcomes. Data were obtained through a comprehensive review of medical records. RESULTS Clinically important nosocomial gastrointestinal bleeding occurred in 67 inpatients after a mean hospital length of stay of 14 +/- 10 days. The majority (64%) of the patients were not hospitalized in the intensive care unit at the onset of the bleeding. Seventy-two percent of the patients who developed bleeding had been receiving some form of bleeding prophylaxis. In a multivariate analysis, a prior intensive care unit stay (odds ratio 2.5; 95% confidence interval 1.0 to 6.1; P <0.05) and mechanical ventilation (OR 3.4; 95% CI 1.1 to 10.7; P = 0.03) were independent risk factors for the onset of bleeding. Nosocomial gastrointestinal bleeding was associated with poor outcome, with an associated mortality of 34%. Duodenal ulcer disease was the most common source of nosocomial gastrointestinal bleeding, accounting for 36% of cases overall. Nosocomial ulcer bleeders were less likely to have a previous history of ulcer disease (13% versus 50%; P <0.05) Helicobacter pylori infection (14% versus 62%; P <0.0001), chronic active gastritis (29% versus 91%; P <0.0001), or to be taking NSAIDs (48% versus 68%; P <0.08) than patients admitted to the hospital with ulcer bleeding. CONCLUSIONS Gastrointestinal bleeding remains an important complication of hospitalization, with a high associated mortality. Our current approaches to prevention of this complication are imperfect. Bleeding tends to occur after a prolonged hospital stay and is more likely to occur in patients with more severe underlying illnesses. Duodenal ulcer disease is the most common source of this bleeding. Nosocomial gastroduodenal ulcer disease is distinct in etiology from the ulcer disease that occurs in outpatients.

Magnetic resonance cholangiography of biliary strictures after liver transplantation: a prospective double-blind study.

To compare magnetic resonance cholangiography (MRC) with endoscopic retrograde cholangiography (ERC) in quantitatively evaluating biliary strictures in liver transplant recipients.

Predictors of endoscopic treatment outcomes in the management of biliary problems after liver transplantation at a high-volume academic center

BACKGROUND Biliary tract problems are the most common complications after liver transplantation. ERCP is increasingly being used to address posttransplantation biliary problems. OBJECTIVE To identify predictors of endoscopic treatment outcomes in the management of post-liver transplantation complications. SETTING AND PATIENTS All adult patients who underwent liver transplantation at the University of California, San Francisco between January 1999 and December 2008 were reviewed. DESIGN A multivariate regression analysis. MAIN OUTCOME MEASUREMENTS Identification of donor and recipient factors as well as technical considerations that predicted success or failure in the endoscopic management of posttransplantation biliary complications. RESULTS In 1062 patients who underwent liver transplantation, there were 224 biliary complications. ERCP was the primary treatment modality and was successful in the majority of patients treated. Patients with biliary complications who had take-back surgery for a nonbiliary indication during the first month after liver transplantation (odds ratio [OR], 0.32; P = .03), particularly for bleeding (OR, 0.18; P = .02), were less likely to respond to endoscopic therapy. Those who received a graft from a donor after cardiac death (OR, 0.15; P = .02) or a living donor (OR, 0.11; P < .01) were also less likely to respond to endoscopic therapy. Take-back surgery for a nonbiliary indication in the first month after liver transplantation was also identified as a novel risk factor for the development of biliary complications (OR, 1.80; P = .02). LIMITATIONS Retrospective design. CONCLUSIONS ERCP can be used to treat the majority of posttransplantation biliary problems. However, endoscopic therapy is less efficacious in the treatment of complications associated with ischemia.

Active cathepsins B, L, and S in murine and human pancreatitis.

Cathepsins regulate premature trypsinogen activation within acinar cells, a key initial step in pancreatitis. The identity, origin, and causative roles of activated cathepsins in pancreatic inflammation and pain are not defined. By using a near infrared-labeled activity-based probe (GB123) that covalently modifies active cathepsins, we localized and identified activated cathepsins in mice with cerulein-induced pancreatitis and in pancreatic juice from patients with chronic pancreatitis. We used inhibitors of activated cathepsins to define their causative role in pancreatic inflammation and pain. After GB123 administration to mice with pancreatitis, reflectance and confocal imaging showed significant accumulation of the probe in inflamed pancreas compared with controls, particularly in acinar cells and macrophages, and in spinal cord microglia and neurons. Biochemical analysis of pancreatic extracts identified them as cathepsins B, L, and S (Cat-B, Cat-L, and Cat-S, respectively). These active cathepsins were also identified in pancreatic juice from patients with chronic pancreatitis undergoing an endoscopic procedure for the treatment of pain, indicating cathepsin secretion. The cathepsin inhibitor K11777 suppressed cerulein-induced activation of Cat-B, Cat-L, and Cat-S in the pancreas and ameliorated pancreatic inflammation, nocifensive behavior, and activation of spinal nociceptive neurons. Thus pancreatitis is associated with an increase in the active forms of the proteases Cat-B, Cat-L, and Cat-S in pancreatic acinar cells and macrophages, and in spinal neurons and microglial cells. Inhibition of cathepsin activation ameliorated pancreatic inflammation and pain. Activity-based probes permit identification of proteases that are predictive biomarkers of disease progression and response to therapy and may be useful noninvasive tools for the detection of pancreatic inflammation.

Identification of psychogenic abdominal pain

Abstract Persistent abdominal pain can be a diagnostic challenge. This study compared the presence of 13 factors, which have been considered positive indicators of psychological etiology, in three patient populations: psychogenic abdominal pain (PAP), inflammatory bowel disease, and general medical-surgical. Four factors in the patient history that are particularly useful in differentiating PAP patients are: (1) past evidence of somatization; (2) the presence of a symptom model; (3) prominent guilt; and (4) a history of physical abuse by either a parent or spouse.

Zollinger-Ellison syndrome in a patient with normal screening gastrin level

SummaryA 59-year-old female presented with multifocal peptic ulcer disease and diarrhea. A fasting serum gastrin level obtained while the patient was receiving no antacid therapy was normal. A secretin stimulation test was positive. A small gastrinoma was found in the anterior duodenal wall at exploratory laparotomy. Normal fasting gastrin levels do occur in patients with overt Zollinger-Ellison syndrome and should not deter further investigation if clinical suspicion of this syndrome is high.