Endoscopic circumferential esophageal mucosectomy in a porcine model: an assessment of technical feasibility, safety, and outcome.

BACKGROUND AND STUDY AIMS: Endoscopic mucosectomy has been performed for early cancers and dysplastic lesions < or = 2 cm in diameter. The feasibility and safety of mucosectomy for circumferential lesions of the esophagus is uncertain. The aim of this study was to determine the technical feasibility, as well as the short and long-term complication rates, with circumferential endoscopic mucosectomy of the distal esophagus in the pig. MATERIALS AND METHODS: Circumferential endoscopic mucosectomy of the distal 3 cm of the esophagus was performed in four pigs, using a cap mucosectomy device. The animals were sacrificed after 30, 50, 70, and 90 days to assess mucosal regeneration and stricture formation. RESULTS: The procedure time for circumferential endoscopic mucosectomy was 15-30 min. Circumferential endoscopic mucosectomy was technically feasible and without short-term complications. Videotapes of all resections were reviewed to ensure that complete removal of the mucosa was achieved. All mucosectomy specimens underwent histological evaluation. The specimens included the mucosa alone in three of the pigs. Some of the specimens in the fourth pig included a superficial layer of muscularis propria. This pig failed to thrive. Macroscopic examination of the dissected esophageal specimens from the healthy pigs revealed a well-healed, normal-appearing esophagus, whereas a stenosis of 4 x 10 mm was observed in the distal esophagus of the pig that failed to thrive. CONCLUSIONS: Circumferential endoscopic mucosectomy of the porcine distal esophagus is feasible and safe. An adequate submucosal saline cushion is essential to prevent stenosis due to deep injury.

Nitric oxide and chronic HCV and HIV infections.

High concentrations of nitric oxide (NO) are generated by the inducible form of the enzyme nitric oxide synthase (iNOS), which is expressed in activated macrophages and in hepatocytes. Increased expression of iNOS in hepatocytes or macrophages might be expected in chronic HCV liver disease and HIV infections. This might in turn be reflected in increased serum NO levels in these two conditions. In view of the discrepant findings in published reports, we measured serum NO levels in a large number of chronic HCV-infected patients and patients with chronic HIV infections with or without AIDS-related opportunistic infection. We also localized HCV and iNOS antigens by immunohistochemistry, in liver biopsy tissue from patients with chronic HCV-related hepatitis, HCV-related cirrhosis, and HCV-related hepatocellular carcinoma. A group of 121 subjects with serological evidence of HCV with or without HIV infection were studied. These were compared with 14 controls without HIV or HCV disease (group A). Among the subjects with HCV, 35 were negative for HIV (group B), 66 were HIV positive (group C), and 20 had AIDS-related opportunistic infection (group D). The serum NO concentration was determined by the Brucine method. A well-characterized commercially available antibody (HCV88) directed against a synthetic NS3 peptide fragment of HCV, which localizes to the hepatocyte nuclei, and an antibody to human macrophage iNOS, were both used to detect these proteins in liver biopsy tissue by immunohistochemistry. Mean serum NO values in HIV negative/HCV negative control patients (group A) (54.6+/-12 microM) were similar to those in HIV negative/HCV positive patients (group B) (55.0+/-13 microM) and HIV positive without AIDS-related disease/HCV positive patients (group C) (47.2+/-25 microM). By contrast, the mean serum NO (70.1+/-24 microM) was significantly increased in HCV-positive patients with AIDS-related infection (group D) compared to controls (P = 0.02). HCV NS3 and iNOS antibody staining hepatocytes were not detected in any of the control non-HCV-infected biopsy samples. In early chronic HCV hepatitis (fibrosis scores F0-F2), HCV NS3 antigen localized focally to only a small number of hepatocytes. In cirrhosis (fibrosis score F4) with or without hepatocellular carcinoma, the majority of hepatocyte nuclei stained positively with HCV NS3 antibody. The majority of hepatocytes in chronic HCV hepatitis expressed iNOS, irrespective of histological disease severity. The staining was present uniformly in the cytoplasm. In chronic HCV and HIV coinfection, the pattern and number of iNOS staining cells were similar to that in patients with chronic HCV infection alone. In conclusion, there is widespread expression of iNOS in hepatocytes in chronic HCV liver disease, irrespective of liver disease stage. However, elevated NO levels in serum were related only to active AIDS-related bacterial, protozoan, and fungal infections, rather than to chronic viral infection with HCV or HIV alone. NO may play a role in the local control of chronic viral infections at tissue level, but this is not reflected in serum levels.

Clinical application of a new colonoscope with variable insertion tube rigidity: a pilot study.

BACKGROUND: Colonic loop formation can prolong colonoscopy, increase patient discomfort, and preclude complete examination. A colonoscope with variable insertion tube rigidity may facilitate colonoscopy. Our aim was to determine whether the use of a colonoscope with variable insertion tube rigidity reduces insertion time and improves patient acceptance of colonoscopy. METHODS: Fifty patients were randomly assigned to undergo colonoscopy with a conventional colonoscope or a variable rigidity colonoscope (VRC). Patient acceptance, dosage of medication, use of abdominal pressure, and patient repositioning were assessed. Statistical analysis was performed by the 2-sample Wilcoxon rank sum test and an extension of Fisher exact test. RESULTS: The groups were comparable with respect to age, gender, and medications required during colonoscopy. The cecum was reached in all 25 patients who underwent colonoscopy with the VRC, including 1 patient in whom the cecum was not reached at a previous colonoscopy with a conventional instrument. In the conventional colonoscopy group, the cecum was not reached in 4 patients (2 poor preparation, 2 loop formation). There was no significant difference between the 2 groups with respect to insertion time. In the group that underwent colonoscopy with the variable rigidity instrument, less abdominal pressure was required (p = 0.05), and nursing assessment of patient discomfort was more favorable (p = 0.05). There were no complications and no significant differences in the intubation time to cecum or in repositioning, patient acceptance, or patient assessment of abdominal pain. CONCLUSION: The use of a variable rigidity colonoscope reduced the frequency of abdominal pressure but did not affect intubation time to cecum, repositioning, patient acceptance, or patient assessment of abdominal pain.

Endoscopic surveillance and ablative therapy for periampullary adenomas.

OBJECTIVES: Periampullary adenomas are an increasingly recognized condition, both in those with familial adenomatous polyposis syndromes (FAP) as well as sporadic cases. Endoscopic management has been advocated for these lesions without differentiating between these two patient groups regarding aim of therapy. The aims of this study were to determine the safety and effectiveness of endoscopic surveillance and ablative therapy of periampullary adenomas in patients with both sporadic and FAP-associated lesions. METHODS: Retrospective analysis of 59 patients with FAP and 32 with sporadic lesions who were all enrolled in a program of endoscopic surveillance and ablative therapy. Median follow-up was 24 months (range, 1-134 months). RESULTS: Ampullary ablative therapy has resulted in return to normal histology in 44 and 34% of sporadic and FAPassociated lesions, respectively. Complications of endoscopic therapy were mild in 12 patients and severe in 3 patients: the latter category involved one occurrence of asymptomatic duodenal stenosis and one occurrence of postcoagulation syndrome--both after Nd-YAG laser therapy-and necrotizing pancreatitis after ampullary biopsy in one patient. Thirteen patients have been referred for surgical intervention. There has been no mortality and no cases of advanced malignancy missed by endoscopy. CONCLUSIONS: Endoscopic surveillance and ablative therapy of periampullary lesions is safe and can be effective, although eradication of ampullary tissue requires multiple ablative sessions.

An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities.

OBJECTIVE: The role of liver biopsy in the management of patients with nonspecific chronic liver enzyme abnormalities is not well established. The aim of this study is to determine whether liver histology changes the clinical impression formed before liver biopsy and the preliminary management plan. METHODS: Consenting asymptomatic adult patients with persistent (> or = 6 months) liver test abnormalities were enrolled. Patients with a strong suspicion for a specific liver disease were excluded. A presumptive diagnosis and a preliminary management plan were documented before a liver biopsy. After the liver biopsy, the patients were reassessed to determine the effect of the biopsy on the diagnosis and management plan. RESULTS: A total of 36 patients were enrolled: 15 men and 21 women, with a median age of 51 yr. The prebiopsy diagnoses were nonalcoholic steatohepatitis (24), autoimmune hepatitis (3), primary biliary cirrhosis (2), primary sclerosing cholangitis (2), and miscellaneous (5 patients). The liver biopsy changed the diagnosis in 14% of cases. Lifestyle recommendations were not significantly altered by the biopsy. The liver biopsy affected the frequency of liver test monitoring in 13 patients (36%). Treatment recommendations were affected in 12 cases, 10 of whom were offered investigational therapy. CONCLUSIONS: Although a liver biopsy may help to definitively establish the final diagnosis in patients, the results alter the presumptive prebiopsy diagnosis infrequently, and no proven therapy exists for the vast majority of these patients. Therefore, the risks and benefits of a liver biopsy should be carefully weighed, especially in settings in which investigational therapies are unavailable.

Postpolypectomy lower GI bleeding: descriptive analysis.

BACKGROUND: Postpolypectomy hemorrhage may warrant intensive care monitoring, transfusions, and surgery. We sought factors predicting significant bleeding requiring blood transfusion and the benefits of critical care monitoring. METHODS: Patients with postpolypectomy bleeding between April 1989 and November 1996 were identified from a comprehensive GI bleeding database. Data included age, gender, medical history, medications, polyp characteristics, and polypectomy technique. Outcomes assessed included bleeding cessation, transfusion requirements, recurrent bleeding, length of stay, and death. RESULTS: There were 83 patients with a median age of 73 years (range 18 to 88 years; 56 men, 27 women). Comorbid conditions were common (71.1% cardiovascular, 43.4% musculoskeletal, 14.5% hematologic, 6.0% renal). Within 3 days of presentation, 32.5% had taken aspirin, 10.8% nonsteroidal anti-inflammatory drugs, 12.0% warfarin, and 12.0% corticosteroids; and within 1 day, 10.8% intravenous heparin, 7.2% subcutaneous heparin, and 7.2% dipyridamole. Fifty-seven percent of patients were hemodynamically stable. Sessile cecal polyps greater than 2 cm in diameter bled more commonly. The median number of units transfused was equal between critical care and noncritical care patients. Using age in the logistic regression model, no other variable was predictive of transfusion. Eighty patients (96.4%) received endoscopic therapy, 1 required embolization and 2 hemicolectomy. There was no significant difference in outcomes for patients managed in an intensive care unit versus a general medical floor. CONCLUSIONS: Postpolypectomy bleeding appears to have a predictable presentation and outcome. Advanced age seems to be predictive of transfusion requirement. Patient monitoring in an intensive care setting is not absolutely necessary.

Unsedated small-caliber esophagogastroduodenoscopy (EGD) versus conventional EGD: a comparative study.

BACKGROUND & AIMS: Significant portions of the cost and complications of esophagogastroduodenoscopy (EGD) are related to sedation. This study aimed to assess the feasibility, acceptability, and accuracy of unsedated small-caliber transoral EGD (sc-EGD). METHODS: A 4-phase study was performed in healthy volunteers and patients. Phases 1 and 2 involved assessment of the technical feasibility of sedated sc-EGD and the tolerability of unsedated sc-EGD, respectively, in volunteers. Subsequently, the technical feasibility, tolerability, and diagnostic accuracy of sedated and unsedated sc-EGD were determined by having each patient undergo sc-EGD (Pentax EG-1840) with (phase 3) and without (phase 4) sedation, followed by sedated conventional EGD (c-EGD) (Olympus GIF-100 or GIF-Q140) by a staff endoscopist blinded to the findings of the sc-EGD. The t test for paired samples was used for statistical analysis. A P value of <0.05 was considered significant. RESULTS: Sedated and unsedated sc-EGD were technically feasible and tolerable in all volunteers. In patients, compared with sedated c-EGD, sedated and unsedated sc-EGD were 96% and 97% accurate, respectively. The overall acceptability of unsedated sc-EGD was only slightly worse than that of sedated c-EGD (median, 2 vs. 1 on a scale of 1-10). After unsedated sc-EGD, 98% of patients expressed willingness to undergo the procedure again. No complications were observed during any phase of the study. CONCLUSIONS: Unsedated sc-EGD is technically feasible, tolerable, and accurate. It can potentially decrease the costs and complications of sedated conventional EGD.

Management and long-term prognosis of Dieulafoy lesion.

BACKGROUND: The Dieulafoy lesion is an important cause of gastrointestinal (GI) hemorrhage. Optimal treatment and long-term outcome are unknown. This study aimed to characterize the presentation of the Dieulafoy lesion and to summarize the results and report the long-term outcome of endoscopic therapy. METHODS: Data regarding diagnosis, treatment and outcomes were derived from our GI Bleed Team database, patient records and follow-up correspondence. RESULTS: Ninety Dieulafoy lesions were identified in 89 patients after a mean of 1.9 endoscopies. Their mean age was 72 years. Thirty-four percent of lesions were extragastric. Median transfusion requirement was 5 units. Two patients exsanguinated and 3 required surgery; all others were initially successfully treated endoscopically (with or without epinephrine injection): heat probe (71 patients), band ligation (3), hemoclip (1), laser (2), bipolar probe (4), sclerotherapy (2) and epinephrine alone (2). Gastric perforation occurred in 1 patient following sclerotherapy. Thirty-day mortality was 13%, 4 related to hemorrhage and 5 related to comorbidity. During median follow-up of 17 months, 34 patients (42%) died. One patient had recurrent bleeding 6 years after operation. CONCLUSIONS: Dieulafoy lesion is relatively common and often extragastric. Endoscopic therapy is safe and effective. Long-term recurrence was not evident following endoscopic ablation. Follow-up after ablative therapy appears unnecessary.

Self-expanding metal stents in the palliation of neoplasms of the cervical esophagus.

BACKGROUND/AIMS: Self-expanding metal stents (SEMS) represent a major advancement in the palliative treatment of dysphagia caused by neoplasms of the esophagus. Malignant cervical stenoses are a challenge for palliative techniques, due to their close relationship with the cricopharynx. METHODOLOGY: Six patients with a malignant stricture of the upper esophagus, within 2 cm of the cricopharyngeal muscle, were treated with a self-expanding metal stent. All patients had a circumferential squamous cell carcinoma histologically proven. Patients were intubated under general anesthesia, and the procedure was carried out under simultaneous endoscopic and fluoroscopic control. RESULTS: All patients had a remarkable improvement of dysphagia and none of them reported a foreign body sensation. In 3 patients, an insufficient expansion of the stent, detected 24 hours later, required a balloon dilation in two of them, whereas, for the third patient, it was necessary to introduce a second stent. Neoplastic in- and overgrowth occurred in 4 (67%) patients after 1, 2, 4 and 8 months, respectively. These complications were managed by placing a second stent in 3 patients; in the fourth patient, a neoplastic involvement of the cricopharynx did not allow for an endoscopic examination. Improvement of dysphagia was observed only in the patient who received a covered Cook-Z stent. In the other 2 patients, a percutaneous endoscopic gastrostomy was performed. The only major complication occurred in the patient who received three metal stents, as he complained of severe cervical pain. CONCLUSIONS: Our experience shows that uncovered self-expanding metal stents provide a good palliation in this subgroup of patients. Tumour ingrowth, overgrowth, and the progressive impairment of the swallowing mechanism due to a proximal submucosal infiltration remain complications difficult to solve.

The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease.

OBJECTIVE: The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is often greater than 2:1 in alcoholic hepatitis. The purpose of this study was to determine whether this ratio may be used to distinguish nonalcoholic steatohepatitis (NASH) from alcoholic liver disease. METHODS: Patients with NASH were matched with controls with alcoholic liver disease based on age, gender, and date of diagnosis. The diagnosis of alcoholic liver disease was based on exclusion of other causes and a significant history of alcohol consumption. The diagnosis of nonalcoholic steatohepatitis was based on exclusion of other causes of liver disease and a liver biopsy showing > 10% steatosis and inflammation. The two sided Student t test was used for statistical analysis. RESULTS: From 1990 to 1996, 70 patients with NASH were matched with 70 subjects with alcoholic liver disease. Patients with NASH had a mean AST to ALT ratio of 0.9 (range 0.3-2.8, median 0.7) and subjects with alcoholic liver disease a mean ratio of 2.6 (range 1.1-11.2, median 2.0). The mean AST levels were 66 U/L and 152 U/L, and the mean ALT levels 91 U/L and 70 U/L, in the nonalcoholic steatohepatitis and alcoholic liver disease groups, respectively. Although the absolute aminotransferase levels were significantly different in the two groups (p < 0.05), the greatest difference was observed in the AST to ALT ratio (p < 0.000001). Subset analysis of patients with NASH revealed mean AST to ALT ratios of 0.7, 0.9, and 1.4 for subjects with no fibrosis, mild fibrosis, or cirrhosis, respectively. The differences among these ratios were statistically significant (p < 0.05). CONCLUSIONS: The AST to ALT ratio appears to be a useful index for distinguishing nonalcoholic steatohepatitis from alcoholic liver disease. Although values < 1 suggest NASH, a ratio of > or = 2 is strongly suggestive of alcoholic liver disease.

Clinical application of a new disposable lithotripter: a prospective multicenter study.

BACKGROUND: Mechanical lithotripsy has become a well-accepted method of bile duct stone fragmentation and removal. The Olympus lithotripter (Olympus American, Melville, NY) is the standard reusable lithotripter at the institutions that participated in this study. A disposable device with a preassembled pistol grip may perform equally well and facilitate operation. METHODS: Twenty patients with bile duct stones were evaluated as part of a multicenter prospective study. Data were obtained regarding stone size and number, bile duct diameter, and configuration, ease of cannulation, basket function, stone capture and crushing success, and complications. RESULTS: The maximum stone size averaged 16.5 +/- 1.2 mm (range 10 to 30 mm). Sixteen patients had multiple stones (median 5, range 2 to 12). The mean bile duct diameter was 20.5 +/- 1.5 mm (range 12 to 38 mm). Cannulation was successful in all within 5 attempts. Basket deployment failed in 1 patient because of stone size and the basket was misshapen in 14. Bile duct clearance was complete in 16 subjects (80%), incomplete in 2 patients, and failed in 2 patients. Abnormal duct configuration (sigmoid, stricture) was noted in 2 of 4 patients with failed capture and 7 of 16 patients with successful clearance. No statistically significant difference was observed between the bile duct diameter, maximum stone size, number of stones, and successful clearance. CONCLUSION: The disposable lithotripter is easy to use and, compared with the published results for the reusable lithotripter, performs almost as well.

Vascular disorders of the small bowel.

Approximately 5% of all patients with gastrointestinal hemorrhage, and up to 38% of subjects with iron deficiency anemia without overt gastrointestinal bleeding, do not have a bleeding site identified after routine evaluation by esophagogastroduodenoscopy and colonoscopy. The source of bleeding in these subjects is often the small intestine. Most vascular lesions of the small bowel present as chronic gastrointestinal bleeding, which may severe in some cases. Depending on the underlying disease, other systemic signs and symptoms may be present. The diagnosis and often therapy are heavily dependent upon endoscopic techniques, and in some cases nonendoscopic methods.

Elevated levels of 92-kd type IV collagenase (matrix metalloproteinase 9) in giant cell arteritis.

OBJECTIVE: To determine if circulating gelatinase activity and matrix metalloproteinase 9 (MMP-9) (gelatinase B, or 92-kd type IV collagenase) antigenic levels are elevated in sera of patients with giant cell arteritis (GCA), and to ascertain if MMP-9 messenger RNA (mRNA) is deposited in situ at sites of disease involvement. METHODS: Serum samples were collected from 12 patients with GCA and 12 healthy volunteers. Vascular tissue was obtained at the time of temporal artery biopsy. Type IV collagenase activity was determined by gelatin substrate zymography and the quantitative biotinylated gelatin substrate degradation assay. A double-sandwich immunoassay utilizing 2 different isotypes of monoclonal antibodies generated against MMP-9 was used for measuring serum MMP-9 antigenic levels. Finally, to localize sites of MMP-9 mRNA transcription in inflamed arteries, the method of reverse transcriptase in situ polymerase chain reaction (RTisPCR) was utilized. RESULTS: Serum gelatinase activity and MMP-9 titers were significantly increased in patients with GCA (mean +/- SEM 198.9 +/- 36.9 micrograms gelatin/hour/ml serum, versus 21.2 +/- 4.0 in controls; P = 0.0006). The differences in antigenic MMP-9 levels were even more prominent (3005.4 +/- 900.6 ng/ml and 31.6 +/- 9.8 ng/ml in GCA and control sera, respectively; P = 0.007). By RTisPCR, MMP-9 mRNA was mainly detected in cytoplasm of cells resembling smooth muscle cells and fibroblasts in regions of fragmented elastic tissue in the lamina media. CONCLUSION: Gelatinase activity, and specifically MMP-9 levels, are substantially elevated in sera of patients with GCA. Detection of MMP-9 mRNA in the lamina media of inflamed vasculature suggests that degradation of intercellular matrix, particularly elastic fibers, may play a key role in the pathogenesis of GCA. Further studies are needed to determine if the circulating MMP-9 level could be utilized as a clinical marker of disease activity.

Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker.

In an attempt to find a potentially useful serum marker in rheumatoid arthritis (RA) which reflects underlying pathogenic mechanisms, we measured the circulating levels of matrix-degrading metalloproteinase-9 (MMP-9), also termed gelatinase B, in sera and synovial fluid (SF) from patients with RA and also quantitated the deposition and local synthesis of MMP-9 in RA synovium. Clinical samples, subjected to gelatin substrate zymography, antigenic immunoassay, and a quantitative substrate degradation assay, revealed elevated 92- and 72-kDa proenzyme forms of MMP-9 and MMP-2 in RA sera and SF compared with healthy controls. Immunostaining on fresh RA synovial specimens revealed MMP-9 within vascular walls in fibroblast-like cells and macrophages; mRNA synthesis was detected using reverse transcriptase in situ PCR. In summary, MMP-9 levels are substantially elevated in the sera and SF from patients with RA. The RA synovium is a source of this MMP-9 production, with abundant mRNA and protein observed within several different type of rheumatoid synovial cells.