Methotrexate in Crohn's disease: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND/AIMS: Immunosuppression with methotrexate may be useful in the treatment of Crohn's disease. We tested the efficacy of methotrexate in refractory Crohn's disease in a randomized, controlled trial. METHODOLOGY: Randomized, double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn's disease, 33% of whom had previously failed therapy with 6-mercaptopurine. Patients were given placebo or oral methotrexate 15 mg/week, or adjusted up to 22.5 mg/week, for up to 1 year or until treatment failure. Outcome was assessed by reduction in prednisone dosage, Crohn's Disease Activity Index, hospital admission, and laboratory parameters. RESULTS: Four patients were dropped from the study for non-compliance and one because of intercurrent illness, and 28 patients could be evaluated. Fewer methotrexate-treated patients (6/13 or 46%) had flares of Crohn's disease as compared to placebo-treated patients (12/15 or 80%), but this did not achieve statistical significance (p<0.1). There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients (3/13 or 23%) as compared to the placebo-treated patients (0/15 or 0%) (p<0.2). Laboratory indices of inflammation did not differ between the two groups. CONCLUSIONS: The methotrexate-treated group showed a trend toward fewer Crohn's disease flares, balanced by an increased number of significant side effects.

Prospective multicenter trial of esophageal Z-stent placement for malignant dysphagia and tracheoesophageal fistula.

BACKGROUND: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. METHODS: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. RESULTS: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/- SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). CONCLUSIONS: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed.

The use of EUS to diagnose malignant portal venous system invasion by pancreatic cancer.

BACKGROUND: CT scanning and mesenteric angiography are insensitive tests diagnosing vascular invasion by pancreatic cancer. Endoscopic ultrasound (EUS) has been proposed as an alternative. The sensitivity, specificity, and accuracy of specific EUS criteria for diagnosing malignant invasion of the branches of the portal venous system have not been determined. METHODS: This is a prospective blinded evaluation of EUS and angiography to diagnose malignant invasion of the portal venous system by pancreatic cancer in 45 patients, 28 of whom underwent surgery. Surgical staging was used as the gold standard for determining the accuracy of EUS and angiography. RESULTS: Four EUS criteria were studied and the overall accuracy rates were as follows: irregular venous wall (87%), loss of interface (78%), proximity of mass (73%), and size (39%). Although "irregular venous wall" was the most accurate, it suffered from a low sensitivity rate (47%) because of its relative inability to detect superior mesenteric vein invasion (sensitivity of 17%). The angiographic criteria had accuracy rates of 73% to 90% with low sensitivity rates (20% to 77%). The clean resection rate was 86% when all tests were used, 78% if EUS was used without angiography, and 60% if only angiography was used. CONCLUSION: EUS is highly sensitive for detecting portal and splenic vein invasion by pancreatic cancer, but may be insensitive for superior mesenteric vein involvement.

Endoscopic retrograde pancreatography: imaging findings.

Endoscopic retrograde pancreatography (ERP) is commonly used in the diagnosis and management of pancreatic disorders. The aim of this pictorial essay is to provide an overview of the common appearances of normal anatomy, anatomic variants, and pancreatic diseases at ERP.

Endoscopic laser lithotripsy of large bile duct stones.

Experimental work has established that the Candela (Candela Laser Corporation, Wayland, MA) flashlamp excited dye laser (wavelength, 504 nm) is a highly effective method for fragmenting biliary stones and has minimal potential for injuring the bile duct wall. This technique was evaluated in 25 complex patients whose stones, usually because of large size, did not respond to standard nonoperative treatment. The laser imaging was applied through a quartz fiber and aimed either under direct vision with choledochoscopes passed percutaneously or through a special "mother" duodenoscope or under fluoroscopic guidance at standard duodenoscopy. Laser treatment resulted in some fragmentation of stones in 23 cases. Subsequently, it proved that it was possible to clear the bile duct of stones in 20 patients, 12 of them receiving successful treatment during the same endoscopic procedure. There were no significant complications. This endoscopic technique seems to be a useful new alternative to surgery in patients with large and difficult bile duct stones.

Evaluation and treatment of the dominant dorsal duct syndrome (pancreas divisum redefined).

The controversial association of pancreatitis and pancreas divisum was studied in 100 patients (77 women, 23 men, median age 35) with episodic acute pancreatitis (49%) or "pancreatic pain" (51%). Seventy-one had classic pancreas divisum (type 1); 23 had only a dorsal duct with an absent Wirsung's duct (type 2); and 6 had a filamentous connection between the two duct systems (type 3). Accessory papilla sphincteroplasty was performed in 88 patients, with a mean follow-up of 53 months. The orifice was stenotic at the mucosal level in 66 patients. Seventy percent of patients have shown improvement: 85% if the accessory papilla was stenotic, compared with 27% if it was not (p less than 0.0001); and 82% with discrete attacks, compared with 56% with chronic pain (p = 0.002). Judged against intraoperative calibration of accessory papilla orifice diameter, ultrasonography with secretin stimulation was 78% sensitive for accessory papilla stenosis, with 3% false-positive results. Ultrasonography with secretin stimulation was the best predictor of surgical success: positive = 92% success (attacks or pain) versus negative = 40% success (64% with attacks; 21% with pain). There have been seven restenoses with six reoperations. We conclude that (1) pancreas divisum is but one variety of pancreatic anatomy characterized by a dominant dorsal duct and dependence on secretion through the accessory papilla; (2) accessory papilla stenosis appears to be a necessary cofactor to produce a morbid state, whether episodic pancreatitis or pancreatic pain; (3) presentation with pancreatitis and a positive result on the ultrasound-secretin test are the best predictors of successful accessory papilla sphincteroplasty.

Hepatic imaging and advanced endoscopic techniques.

Diseases of the liver and biliary tract can be diagnosed and potentially treated by a variety of radiologic modalities and endoscopic techniques. The imaging modalities of ultrasonography, computed tomography, nuclear scintigraphy and magnetic resonance are emphasized in this article. The current status of endoscopic retrograde cholangiopancreatography, sphincterotomy, biliary endoprostheses, cholangioscopy, endoscopic ultrasound, and laser lithotripsy is discussed.

Endoscopic palliation of obstructive esophagogastric malignancy.

To investigate the efficacy of alternative endoscopic palliative therapies for obstructive esophagogastric malignancy, the experience of 53 patients treated between 1979 and 1986 was analyzed. Forty-seven patients had placement of intraesophageal prostheses. Ten patients had prostheses placed after neodymium:YAG laser therapy. In four of these patients, prosthesis placement was planned as part of the initial therapy. Twelve patients initially received laser therapy. In six, recurrent tumor was treated with intraesophageal prostheses 3 to 24 weeks after laser treatment. Comparing neodymium:YAG laser therapy to placement of the prosthesis, both techniques provided similar improvement in dysphagia. Patients receiving prostheses required less additional treatment for dysphagia. Life table analysis comparing survival rates from diagnosis to death showed no difference. The palliation provided by prostheses and neodymium:YAG laser appears to be quite similar; however, the prosthesis seems to be more lasting and require fewer resources.

Biliary granular cell tumor: a little-known curable bile duct neoplasm of young people.

Two granular cell tumors of the biliary tree are described, one in a 37-year-old black woman with obstructive jaundice and the other in a 26-year-old white woman with abdominal pain. These are rare soft tissue tumors that have an excellent prognosis when surgically excised. Almost all reported cases have been in young women, the majority of whom have been black. Because granular cell tumors of the biliary tract are uniformly resectable and curable, they should be considered and distinguished from cholangiocarcinoma or localized sclerosing cholangitis, particularly if the patient is young, female, and black.

Successful treatment of nonhealing biliary-cutaneous fistulas with biliary stents.

Biliary-cutaneous fistulas occasionally complicate biliary tract surgery. Distal biliary obstruction, extensive loss of bile duct wall, or infection may contribute to the failure of such fistulas to heal. Five cases are reported of high-volume persistent fistulas that healed promptly after placement of endoscopic (4 cases) or percutaneous (1 case) biliary stents. Biliary stent placement eliminated the need for difficult reoperations in these complex patients and offers a promising therapeutic approach to this problem.

Villous tumors of the duodenum.

Nineteen cases of villous tumors of the duodenum are reported. They have a predilection for the ampullary region, tend to present with obstructive jaundice, especially if malignancy is present, and have a high prevalence of cancer (12 of 19, or 63%). Even when biopsies are available, the diagnosis of cancer is frequently missed (5 of 9 proven cancers, 56% false-negative rate), and it may be impossible to assess the presence of carcinoma in situ or invasive carcinoma without complete excision of the lesion. The authors' experience suggests that some small benign ampullary villous adenomas or those with carcinoma in situ can be excised locally but that pancreaticoduodenectomy is preferable in the fit patient for better local control both of extensive benign lesions and cancers without distant metastases.

Gastric and duodenal fistulas in Crohn's disease.

We report gastric or duodenal fistulas in 6 patients with Crohn's colitis or ileocolitis. Two patients had duodenocolic fistulas, 1 had a duodenoileal fistula, 2 had gastrocolic fistulas, and 1 had gastric and duodenal fistulas from an ileocolic anastomosis. In each case the fistula originated from the lower bowel segment, and no patient in this series had primary gastroduodenal Crohn's disease. These cases illustrate the range of manifestations of fistulas to the stomach and duodenum in Crohn's disease, and emphasize that the predominant symptoms determining surgical intervention usually arise from the diseased ileum and colon, rather than from the fistula. Our experience demonstrates the simplicity and safety of excision of the fistula with primary closure of the stomach or duodenum when the stomach and duodenum are otherwise normal by endoscopic examination.

Objective evaluation of ampullary stenosis with ultrasonography and pancreatic stimulation.

Ultrasonography can detect changes in pancreatic and bile duct sizes after pancreatic stimulation by secretin or morphine and prostigmine. The effects of the two pharmacologic regimens on pancreatic duct dilatation were comparable and correlated with papillary stenosis determined at surgery, but the morphine and prostigmine combination produced more false-positive responses than did secretin. After administration of intravenous secretin (1 unit/kg), the pancreatic duct dilated in 83 percent of 12 symptomatic patients found at surgery to have a stenotic sphincter of Oddi and in 72 percent of 17 symptomatic patients found to have a stenotic accessory papilla associated with the pancreas divisum anomaly. Comparable dilatation occurred in 14 percent of 14 control subjects without suspected ampullary disease and in none of 10 patients with surgically disproved stenosis (p less than 0.001). The morphine and prostigmine combination produced more false-positive results in both the pancreatic duct and bile duct. Concomitant elevation of the serum amylase level and reproduction of pain were found to be of no discriminatory value. In patients whose pancreatic duct dilated preoperatively during secretin stimulation, dilatation did not occur after surgical sphincteroplasty. A positive test result was associated with a 90 percent success rate in preventing recurrent pancreatitis and ameliorating pain. A negative test result was associated with a 29 percent success rate. Ultrasonography of the pancreatic duct with secretin stimulation may provide objective criteria to supplement clinical judgment in selecting patients for sphincteroplasty to treat stenosis of either the sphincter of Oddi or the accessory papilla in pancreas divisum.

Severe esophageal strictures: indications for balloon catheter dilatation.

Bougienage of esophageal strictures is a traditional method of therapy for patients who present with a stricture sufficiently large to permit passage of a mercury-weighted rubber bougie. However, when the residual lumen is smaller than 12 mm diameter, bougie dilatation acquires a prohibitively high risk of esophageal perforation. Twenty patients who had severe esophageal strictures have undergone surgical repair or Eder-Puestow dilatation assisted by guidewire. Fluoroscopic balloon catheter dilatation obviated surgery and allowed subsequent standard bougienage both in hospital and at home performed by the patient. We discuss indications, technique, results, and complications.

Epstein-Barr viral hepatitis: an unusual case and review of the literature.

We report a patient with icteric hepatitis and abdominal pain caused by Epstein-Barr virus in the absence of other common features of infectious mononucleosis. The peak alanine aminotransferase was 289 IU/I. Hemolytic anemia and urinary retention complicated the patient's course. Patients with infectious mononucleosis commonly have hepatic involvement but isolated symptomatic hepatitis is unusual. Although rare cases of liver failure have been reported, there is no evidence that Epstein Barr virus causes chronic liver disease. The clinical and histological features of Epstein Barr virus-induced hepatitis are reviewed.

Angiodysplasia. Clinical presentation and colonoscopic diagnosis.

Angiodysplasia is a recently recognized important cause of lower intestinal bleeding in older patients. Although angiography is an established procedure for the diagnosis of angiodysplasia, colonoscopy is being used increasingly for evaluation of lower intestinal bleeding. In order to define the nature of bleeding due to angiodysplasia and the appropriate role of colonoscopy, 80 patients diagnosed by angiography, pathology, or colonoscopy were reviewed. Bleeding attributable to angiodysplasia varied from acute life-threatening hemorrhage to occult blood in stools. Thirteen patients with angiodysplasia had no bleeding and were identified incidentally by colonoscopy performed for other indications. Eighty-nine percent of the lesions were located in the right colon and there was a mean of 1.5 angiodysplastic lesions per patient. The sensitivity of colonoscopy compared to angiography and pathology was 68% overall and 81% when the colon was completely examined and lesions were located in the colon. The predictive value of a positive colonoscopic diagnosis was 90% in this population. Colonoscopy should be employed as an initial study in patients with chronic or mild acute rectal bleeding.

The cause and treatment of pancreatitis associated with pancreas divisum.

Recurrent pancreatitis is more prevalent in the 4% of people with pancreas divisum (nonfused dorsal and ventral ducts), and it has been proposed that the pancreatitis is caused by stenosis at the orifice of the dorsal duct. We have treated 40 patients with pancreas divisum and proven or probable pancreatitis. The diagnoses were made by endoscopic pancreatography showing a foreshortened (less than 6 cm) ventral duct (Wirsung) and confirmed by postoperative pancreatograms showing the separate main duct (Santorini) emptying via the accessory papilla. Of these, 32 patients (25 men, 7 women, median age 30) had recurrent acute pancreatitis (22) or persistent pain (10) without chronic inflammation or fibrosis. Twenty-nine have been treated by transduodenal sphincteroplasty of the accessory papilla; 22 were stenotic (0.75 mm or less) and 7 nonstenotic. Among 25 patients observed for longer than 6 months after surgery, the relief of pain and pancreatitis has been good in 17, fair in 1, and poor in 7. There was no difference between accessory papillotomy alone (10-0-3) v papillotomies of both accessory and major papillae (7-1-4). Patients with stenosis (16-1-1) fared better (p less than 0.001) than those without stenosis (1-0-6). Those presenting with discrete attacks (12-1-2) also fared better (p less than 0.05) than those presenting with chronic pain (5-0-5). The other eight patients (two women, six men, median age 28) had chronic pancreatitis proven by pancreatography and surgical biopsy. In this group, treatment by sphincteroplasty of the accessory papilla failed, and seven patients eventually required a pancreaticojejunostomy (3), distal pancreatectomy (2), or total pancreatectomy (2). In pancreas divisum, pancreatitis is caused by stenosis at the accessory papilla of Santorini. There may be progression from recurrent acute pancreatitis to irreversible fibrosis in some cases. Sphincteroplasty is effective for recurrent acute pancreatitis, but ductal drainage or resection becomes necessary once chronic pancreatitis is established. A preoperative test for stenosis of the accessory papilla is needed to identify patients whose symptoms are genuinely caused by their pancreas divisum.