Adrian H. Ormsby

A Randomized Clinical Trial of Ciprofloxacin and Metronidazole to Treat Acute Pouchitis

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch–anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1 ± 2.3 to 3.3 ± 1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7 ± 2.3 to 5.8 ± 1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9 ± 1.2 versus 3.8 ± 1.7; p = 0.002), symptom score (2.4 ± 0.9 versus 1.3 ± 0.9; p = 0.03), and endoscopic score (3.6 ± 1.3 versus 1.9 ± 1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach

The histological distinction between intestinal metaplasia involving the distal esophagus (Barretts esophagus [BE]) and intestinal metaplasia of the stomach has important clinical implications and can be difficult even with the use of histochemical mucin stains. Cytokeratin (CK) 7 and 20 are cytoplasmic structural proteins that show restricted expression in normal and malignant epithelia of the gastrointestinal tract. The aim of this study was to determine the use of CK7 and 20 expression in the histological distinction of BE from gastric intestinal metaplasia. CK7 and 20 immunostaining was performed on randomly selected surgical resection (n = 31) and biopsy specimens (n = 34) from patients with long-segment BE and gastric resection specimens (n = 11) and gastric cardia biopsy specimens (n = 13) in patients with histological evidence of intestinal metaplasia. A unique pattern of immunoreactivity designated the Barretts CK7/20 pattern showed superficial CK20 staining and strong CK7 staining of both superficial and deep glands in 29 of 31 (94%) esophageal resection specimens and 34 of 34 (100%) esophageal biopsy specimens form patients with long-segment BE. A Barretts CK7/20 pattern was not observed in gastric cardia biopsy specimens (n = 13) or gastric resection specimens (n = 11) in patients with histological evidence of intestinal metaplasia. The sensitivity, specificity, and positive predictive value of a Barretts CK7/20 pattern for a diagnosis of long-segment BE was 97%, 100%, and 100%, respectively. CK7 and 20 reactivity patterns can reliably identify the location of intestinal metaplasia in the esophagus and stomach using histological material from both routine endoscopic biopsy and surgical resection specimens.

Dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of prospective evaluation after a minimum of ten years.

AbstractPURPOSE: Stapling of the ileal pouch-anal anastomosis with preservation of the anal transitional zone remains controversial because of concerns about the potential risk of dysplasia and cancer. The natural history and optimal treatment of anal transitional zone dysplasia ten or more years after surgery are unknown. This study establishes the risk of dysplasia in the anal transitional zone and the outcome of a conservative management policy for anal transitional zone dysplasia, with a minimum of ten years’ follow-up after ileal pouch-anal anastomosis. METHODS: A total of 289 patients undergoing anal transitional zone–sparing stapled ileal pouch-anal anastomosis for inflammatory bowel disease between 1986 and 1990 were studied. Patients undergoing anal transitional zone–sparing ileal pouch-anal anastomosis who were studied with serial anal transitional zone biopsies for at least ten years postoperatively were included (n = 178). Median follow-up was 130 (range, 120–157) months. RESULTS: Anal transitional zone dysplasia developed in 8 patients 4 to 123 (median, 9) months after surgery. There was no association with gender, age, preoperative disease duration, or extent of colitis, but the risk of anal transitional zone dysplasia was significantly associated with cancer or dysplasia as a preoperative diagnosis or in the proctocolectomy specimen. Dysplasia was high grade in two patients and low grade in six. Two patients with low-grade dysplasia on two or more occasions after detection of low-grade dysplasia underwent completion mucosectomy and perineal pouch advancement with neo–ileal pouch-anal anastomosis. One patient with high-grade dysplasia on two occasions was to undergo completion mucosectomy, but this was not technically feasible. Partial mucosectomy with vigorous anal transitional zone biopsy was performed with close postoperative surveillance. Biopsies were negative for dysplasia. The second recently diagnosed patient with high-grade dysplasia underwent examination under anesthesia with negative anal transitional zone biopsies and will be kept under close surveillance. No cancer in the anal transitional zone was found during the study period. The 4 other patients with low-grade dysplasia on 1 or 2 occasions were treated expectantly and have been dysplasia free for a median of 119 (range, 103–133) months. CONCLUSIONS: Anal transitional zone dysplasia after stapled ileal pouch-anal anastomosis is infrequent and is usually self-limiting. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone with a minimum of ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, mucosectomy with perineal pouch advancement and neo–ileal pouch-anal anastomosis is recommended.

Modified Pouchitis Disease Activity Index A Simplified Approach to the Diagnosis of Pouchitis

AbstractPURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn’s disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores’ diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.

The gastric cardia: fact or fiction?

Abstract OBJECTIVE: It is unclear whether the gastric cardia is present from birth or is metaplastic and develops as a result of gastroesophageal reflux disease. To this end, we evaluated the histology of the entire esophagogastric junction in consecutive pediatric autopsies to determine the presence and extent of cardiac mucosa. METHODS: The entire esophagogastric junction of 33 consecutive pediatric (≤18 yr) autopsies was examined. The precise location of the squamocolumnar junction and its relationship to the esophagogastric junction was noted in all cases. Slides were evaluated by two pathologists in a blinded fashion to look for cardiac mucosa, characterized by unequivocal periodic acid-Schiff (PAS)-positive mucous glands in a lobular configuration. Sections from the antrum and esophagogastric junction were examined for the presence of Helicobacter pylori. RESULTS: Three cases were excluded due to autolysis. The mean age of the 30 remaining patients was 6.3 yr (range: 16 days–18 yr). A regular-appearing squamocolumnar junction was identified at the esophagogastric junction in all 30 cases. Cardiac mucosa was present in all specimens (mean length: 1.8 mm; range: 1.0–4.0 mm), always on the gastric side of the esophagogastric junction. There was no significant association between patient age or gender and length of cardiac mucosa. None of the patients had a known history of gastroesophageal reflux disease or Barrett’s esophagus, and none were taking acid-suppressing medications before death. All were negative for Helicobacter pylori by Giemsa stain. CONCLUSIONS: In an unselected pediatric patient population with little or no propensity for gastroesophageal reflux disease, a short segment of cardiac mucosa was consistently present on the gastric side of the esophagogastric junction, independent of gender or age. These results support the concept that the gastric cardia is present from birth as a normal structure.

Irritable pouch syndrome: a new category of diagnosis for symptomatic patients with ileal pouch-anal anastomosis

OBJECTIVE: Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI). METHODS: Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch–anal anastomosis. Pouchitis was defined as a PDAI score of 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of 7 and the absence of cuffitis. RESULTS: Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis ( p 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of 1, whereas the remaining patients had persistent symptoms despite therapy. CONCLUSIONS: A substantial number of symptomatic patients after ileal pouch–anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications. (Am J Gastroenterol 2002;97:972–977.

The gastric cardia: fact or fiction|[quest]|

OBJECTIVE:It is unclear whether the gastric cardia is present from birth or is metaplastic and develops as a result of gastroesophageal reflux disease. To this end, we evaluated the histology of the entire esophagogastric junction in consecutive pediatric autopsies to determine the presence and extent of cardiac mucosa.METHODS:The entire esophagogastric junction of 33 consecutive pediatric (≤18 yr) autopsies was examined. The precise location of the squamocolumnar junction and its relationship to the esophagogastric junction was noted in all cases. Slides were evaluated by two pathologists in a blinded fashion to look for cardiac mucosa, characterized by unequivocal periodic acid-Schiff (PAS)-positive mucous glands in a lobular configuration. Sections from the antrum and esophagogastric junction were examined for the presence of Helicobacter pylori.RESULTS:Three cases were excluded due to autolysis. The mean age of the 30 remaining patients was 6.3 yr (range: 16 days–18 yr). A regular-appearing squamocolumnar junction was identified at the esophagogastric junction in all 30 cases. Cardiac mucosa was present in all specimens (mean length: 1.8 mm; range: 1.0–4.0 mm), always on the gastric side of the esophagogastric junction. There was no significant association between patient age or gender and length of cardiac mucosa. None of the patients had a known history of gastroesophageal reflux disease or Barretts esophagus, and none were taking acid-suppressing medications before death. All were negative for Helicobacter pylori by Giemsa stain.CONCLUSIONS:In an unselected pediatric patient population with little or no propensity for gastroesophageal reflux disease, a short segment of cardiac mucosa was consistently present on the gastric side of the esophagogastric junction, independent of gender or age. These results support the concept that the gastric cardia is present from birth as a normal structure.

Primary seminal vesicle carcinoma: an immunohistochemical analysis of four cases.

Primary adenocarcinoma of the seminal vesicles is an extremely rare neoplasm. Because prompt diagnosis and treatment are associated with improved long-term survival, accurate recognition of this neoplasm is important, particularly when evaluating limited biopsy material. Immunohistochemistry can be used to rule out neoplasms that commonly invade the seminal vesicles, such as prostatic adenocarcinoma. Previous reports have shown that seminal vesicle adenocarcinoma (SVCA) is negative for prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PAP); however, little else is known of its immunophenotype. Consequently, we evaluated the utility of cancer antigen 125 (CA-125) and cytokeratin (CK) subsets 7 and 20 for distinguishing SVCA from other neoplasms that enter the differential diagnosis.Four cases of SVCA—three cases of bladder adenocarcinoma and a rare case of adenocarcinoma arising in a mullerian duct cyst—were immunostained for CA-125, CK7, and CK20. Three of four cases of SVCA were CA-125 positive and CK7 positive. All four cases were CK20 negative. All bladder adenocarcinomas and the mullerian duct cyst adenocarcinoma were CK7 positive and negative for CA-125 and CK20. In addition, CA-125 immunostaining was performed in neoplasms that commonly invade the seminal vesicles, including prostatic adenocarcinoma (n = 40), bladder transitional cell carcinoma (n = 32), and rectal adenocarcinoma (n = 10), and all were negative for this antigen.In conclusion, the present study has shown that the CK7-positive, CK20-negative, CA-125–positive, PSA/PAP-negative immunophenotype of papillary SVCA is unique and can be used in conjunction with histomorphology to distinguish it from other tumors that enter the differential diagnosis, including prostatic adenocarcinoma (CA-125 negative, PSA/PAP positive), bladder transitional cell carcinoma (CK20 positive, CA-125 negative), rectal adenocarcinoma (CA-125 negative, CK7 negative, CK20 positive), bladder adenocarcinoma (CA-125 negative), and adenocarcinoma arising in a mullerian duct cyst (CA-125 negative).

The Location and Frequency of Intestinal Metaplasia at the Esophagogastric Junction in 223 Consecutive Autopsies: Implications for Patient Treatment and Preventive Strategies in Barrett's Esophagus

The frequency of intestinal metaplasia at the esophagogastric junction is as high as 36% in endoscopy studies; the majority of cases (approximately 67%) occur in short segments of esophageal columnar mucosa. The validity of these studies has been questioned, however, because of heterogenous underlying diseases prompting endoscopy. To determine the frequency and origin of intestinal metaplasia at the esophagogastric junction, we histologically evaluated the entire esophagogastric junction for the presence of intestinal metaplasia using Alcian blue/periodic acid-Schiff mucin stains in 223 consecutive autopsies. Precise localization of the Z line in relation to the esophagogastric junction and tongues of esophageal columnar-appearing mucosa were noted in each case. Mean patient age was 47 years; 69% of patients were male, and 63% were white. Twenty five of 223 cases (11%) had intestinal metaplasia at the esophagogastric junction. Only 2 of 25 cases (8%) had intestinal metaplasia in the esophagus; the remaining 23 cases (92%) had intestinal metaplasia in the gastric cardia. Male gender, advanced age, white ethnic origin, and short tongues of esophageal columnar mucosa were not associated with gastric cardia intestinal metaplasia. An association of distal gastric intestinal metaplasia (P <.01) and chronic gastritis (P <.01) with gastric cardia intestinal metaplasia suggests a role for Helicobacter pylori infection in this process. The frequency of intestinal metaplasia at the esophagogastric junction in an unselected autopsy population is low (11%) even after exhaustive histologic evaluation using Alcian blue mucin stains. Furthermore, intestinal metaplasia is confined to the gastric cardia in more than 90% of cases with no association to male gender, white ethnic origin, advanced age, or the presence of short segments of esophageal columnar-appearing mucosa at endoscopy. These results demonstrate that caution is warranted when applying the findings of endoscopy studies to the development of preventive and screening strategies aimed at identifying Barretts esophagus in an asymptomatic general population.

The utility of cytokeratin subsets in distinguishing Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma.

Aims: Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barretts‐related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co‐ordinate CK7 and 20 expression in the distinction of Barretts‐related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia.