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Background: Esophageal variceal banding may be less likely to cause bacteremia than sclerotherapy. The existing data about the frequency of bacteremia after esophageal variceal banding are conflicting, and few studies include both banding and sclerotherapy., Aims: We conducted a prospective randomized controlled trial to compare the frequency of bacteremia after esophageal variceal banding and sclerotherapy., Methods: Over a 2-year period, patients with liver disease admitted for upper gastrointestinal bleeding or for outpatient elective variceal therapy were enrolled. New patients were randomized preprocedure to either banding or sclerotherapy, and subsequent sessions utilized the initial procedure. The groups consisted of banding, sclerotherapy, and endoscopy without variceal therapy. Subjects underwent endoscopy by one out of three gastroenterologists. Blood cultures were obtained 5 min before and 30 min after endoscopy to check for bacteremia., Results: Postendoscopic blood cultures were positive following 4 out of 139 (2.9%) sessions: 1 sclerotherapy and 3 control sessions. All postendoscopic positive blood cultures were found following emergency sessions (4/92, 4.3%). One pre-endoscopic blood culture was positive in a patient with emergency banding. The rates of positive postendoscopic blood cultures among groups with emergency banding (0/22, 0%), emergency sclerotherapy (1/41, 2.3%), and emergency control (3/29, 10.3%) were not significantly different. Postendoscopic positive blood cultures were not found after elective sessions with either banding or sclerotherapy., Conclusions: Postendoscopic bacteremia was infrequent following emergency endoscopy in patients with esophageal variceal bleeding. Bacteremia was not found after esophageal variceal banding, although this was not significantly less frequent than after sclerotherapy. Postendoscopic bacteremia was not associated with elective variceal therapy.

Background: Supraomohyoid neck dissection (SOHND) is currently used as a staging procedure for patients with clinically negative nodes in the neck who are at increased risk (>20%) for metastatic disease., Objective: To assess the potential role of SOHND in patients with clinically positive nodes at levels I, II, or III. We evaluated, in particular, whether selective neck dissection in patients with clinically positive nodes results in decreased regional control and/or diminished survival., Patients and Methods: We retrospectively reviewed the charts of all patients who underwent SOHND from January 1, 1971, to December 31, 1997. The oral cavity and oropharynx represented the primary sites in the majority of the patients. Two-year follow-up information was available on all patients., Results: During the study period, 69 patients underwent 84 SOHNDs. Of the 69 patients, there were 30 patients with clinically negative nodes and 39 patients with clinically positive nodes in the neck. The overall regional control rates were 88% vs 71% for pathologically negative vs positive nodes, respectively, with or without adjuvant radiation therapy. Adjuvant radiation therapy significantly improved regional control in patients with pathologically positive nodes but not in patients with NO disease (P = .005). Similar results were noted in patients with both clinically and pathologically positive nodes., Conclusions: Supraomohyoid neck dissection in patients with pathologically positive nodes in the neck is inadequate therapy for regional control without postoperative radiation therapy. However, in patients with pathologically positive nodes in the neck, SOHND with postoperative radiation therapy can achieve regional control comparable to that of comprehensive neck dissection and postoperative radiation therapy.

In an effort to generate a good mouse model for human colorectal cancer, we generated mice which carry a mutation in the adenomatous polyposis coli (Apc) gene. Mice which are heterozygous for the mutation, designated Apc1638, develop colonic polyps and tumors of the small intestine. Neoplasms were found in 96% of animals studied, and they included adenomas, adenocarcinomas, and polypoid hyperplasias. The mice developed an average of 3.3 tumors, with the highest number in duodenum, followed by jejunum, stomach, ileum, and colon. Focal areas of dysplasias were observed in the colonic mucosa in 50% of mice which were 10 months old or older. These results suggest that mice carrying the Apc1638 mutation can serve as a good model to study the initiation, progression, and inhibition of gastrointestinal tumors.

Native cellular fluorescence (NCF) is being investigated as an intermediate endpoint biomarker for chemoprevention. Oral epithelial cells were cultured under three conditions to identify a spectral pattern for epithelial differentiation: cells maintained in serum-free keratinocyte growth medium were the least differentiated (KGM cells); cells switched to DMEM/F12 plus 10% FCS were intermediate in differentiation (DMEM/F12/FCS cells); DMEM/F12/FCS cells switched to serum-free DMEM/F12 plus 0.8 M NaCl to induce cornified envelopes were the most differentiated (DMEM/F12/NaCl cells). The differentiation status was characterized using immunohistochemistry and electron microscopy. NCF analysis was able to distinguish terminally differentiated epithelial cells (DMEM/F12/NaCl) from those less differentiated cells (KGM, DMEM/F12/FCS) in several emission (lambda ex 340 nm, lambda em 360-660 nm; lambda ex 365 nm, lambda em 400-700 nm; lambda ex 420 nm, lambda em 440-800 nm) and excitation scans (lambda ex 200-360 nm; lambda em 380 nm, lambda ex 240-430 nm; lambda em 450 nm, lambda ex 250-460 nm, lambda em 480 nm; lambda ex 270-500 nm, lambda em 520 nm). The ability to discriminate terminal differentiation in this in vitro model supports the concept of using NCF as an intermediate biomarker to monitor in vivo mucosal differentiation.

Objective: To determine if a single-step noninvasive stable isotope method of assessing digestive function could separate normal subjects from subjects with pancreatic insufficiency (maldigestion) or small bowel dysfunction (malabsorption) and to see if subjects with maldigestion could be simultaneously separated from subjects with malabsorption., Methods: Forty (40) normal volunteers, 18 adults with cystic fibrosis and four adults with celiac sprue, ingested a liquid test meal along with bentiromide, [13C6]PABA, and xylose (PABAX test). Serum was collected at 1 h and analyzed for PABA, [13C6]PABA, and xylose by stable isotope dilution methods using gas chromatography mass spectrometry., Results: All subjects with cystic fibrosis had abnormal pancreatic function test results, whereas three of four adults with sprue had normal values of pancreatic function. All subjects with sprue had abnormal small bowel absorption tests, whereas all adults with cystic fibrosis had apparently normal intestinal function., Conclusion: The one-step, 1-h PABAX test can reliably separate normal subjects from those with either maldigestion or malabsorption and can also separate subjects with maldigestion from those with malabsorption.

Objective: To identify alterations in the biochemical composition and histoarchitectural structure of the lining epithelium that signal malignant transformation in carcinogen-exposed upper aerodigestive mucosa by quantitation of native cellular fluorescent properties., Design: Case series., Setting: Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY., Patients and Methods: Thirty-one patients with previously untreated mucosal neoplasias of the oral cavity and pharynx were studied by means of a hand-held fiberoptic probe attached to a xenon lamp-based fluorescent spectrometer. Fluorescence analyses of the lesions and contralateral normal sites were performed in each patient on the basis of specific emission and excitation wavelengths. Differences between normal tissue and neoplastic mucosa were tested for statistical significance by paired t test and Hotelling's T2 test., Results: The ratios of fluorescence intensities of neoplastic mucosa and contralateral normal sites were significantly different in three of the four fluorescence scans (excitation of 300 nm and emission of 320 to 580 nm; excitation of 340 nm and emission of 360 to 660 nm; and excitation of 200 to 360 nm and emission of 380 nm) when analyzed individually (P < .05). The ratios in the scans with excitation of 240 to 430 nm and emission of 450 nm were not significantly different. All four scans, when analyzed together, demonstrated significant differences between normal and neoplastic tissues (P < .01)., Conclusions: Neoplastic mucosa of the upper aerodigestive tract within an individual patient will express native cellular fluorescent properties in vivo that differ from those of normal upper aerodigestive epithelia. This may represent a noninvasive screening method for head and neck squamous cell cancers.

Background: Change in epithelial thickness is part of the neoplastic transformation process of the upper aerodigestive tract. The quantitation of native cellular fluorescence (NCF) may represent a noninvasive means of distinguishing such a change., Patients and Methods: Nineteen patients with squamous neoplasms and 12 surgical specimens from cancer patients were analyzed for NCF using a hand-held fiber optic probe attached to a fluorescent spectrometer. Tumors and normal sites were analyzed for fluorescence, and tissue samples were obtained. Ratios of intensities of various emitted wavelengths were computed to quantitate and compare various spectral patterns. These ratios were then correlated with mucosal thickness., Results: The 330 nm peak in the excitation scan (lambda Ex 200 to 360 nm, lambda Em 380 nm) was lost in the tumors compared with the normal sites. The 390 nm peak in the emission scan (lambda Ex 340 nm, lambda Em 360 to 660 nm) was also lost. The 290 nm/330 nm ratio in the in-vivo excitation scan (lambda Ex 200 to 360 nm, lambda Em 380 nm) correlated with changes in epithelial thickness. The 390/450 ratio in the emission scan (lambda Ex 340 nm, lambda Em 360 to 660 nm) correlated negatively with the mean epithelial thickness., Conclusions: Native cellular fluorescence analysis can identify changes in neoplastic tissues, including changes in epithelial thickness.

A gas chromatography/mass spectrometric (GC/MS) isotope dilution assay for xylose was developed using tertbutyldimethylsilyl-derivatized xylose and [13C]1xylose, and applied to human serum samples. A calibration curve in serum using this assay showed < 3% variation (< 10 mg/L) for any given point. The correlation coefficient for xylose measurements made on 27 sera between a colorimetric method performed by a national commercial reference laboratory and the GC/MS method developed here was .952. However, xylose determinations of 10 of 27 samples differed by > 10% (up to 150 mg/L) when colorimetric values were compared to GC/MS. Two of these samples had borderline-low xylose values by GC/MS, but were well within the normal range by colorimetric analysis. gas chromatography/mass spectrometric isotope dilution assay appears to be an accurate method to measure xylose in serum. These data also suggest that further prospective studies comparing GC/MS to colorimetric methods are indicated for subjects undergoing oral xylose testing.

Neoplastic progression in patients with chronic ulcerative colitis (UC) is characterized by the development of epithelial dysplasia, which is accompanied by genetic abnormalities that can be detected by flow cytometric and molecular biologic methods. Distribution of and correlation between histologic abnormalities, DNA content, and loss of heterozygosity for a p53 allele (p53 LOH) in the colons of nine UC patients were analyzed. Loss of a p53 allele was found in 85% (22/26) of biopsy specimens classified histologically as carcinoma, 63% (25/40) of biopsy specimens with high grade dysplasia, and 33% (7/21) of biopsy specimens with low grade dysplasia. Loss of heterozygosity for p53 was also found in 9% (5/57) of biopsy specimens indefinite for dysplasia and in 1/18 biopsy specimens negative for dysplasia, showing that this genetic change may occur early in the histological progression towards carcinoma. Aneuploid DNA contents were more common than p53 LOH in regions with negative, indefinite or low grade dysplastic histology; moreover, p53 LOH was detected only in aneuploid cells and not in diploid epithelium. Aneuploidy alone was not as specific a marker for the concomitant presence of dysplasia or carcinoma in a biopsy sample as aneuploidy combined with p53 LOH. These findings show that aneuploidy may precede both p53 LOH and epithelial dysplasia. Two UC patients' colons contained geographically separated clones of cells with different aneuploidies that also showed loss of different p53 alleles, suggesting that neoplasia may arise within different populations of cells in separate areas of the same colon.

Allelic deletions of the p53 gene previously were demonstrated by Southern hybridization to occur in high frequency in sporadic colon carcinomas and in a variety of other human tumors. We have examined the frequency of allelic loss of the p53 gene in carcinoma and dysplasia arising in patients with chronic ulcerative colitis who are heterozygous for the codon 72 polymorphism in exon 4 of the p53 gene. Cells derived from carcinoma and dysplasia specimens from 10 patients who were heterozygous at this locus were sorted by flow cytometry on the basis of DNA content. The p53 exon 4 region was amplified from diploid and aneuploid populations, via a polymerase chain reaction (PCR), and digested with BstUI. Three of three carcinomas, four of six dysplasias, and one patient who was indefinite for dysplasia demonstrated evidence of allelic loss of the p53 gene. Seven of ten cases of sporadic colon carcinoma, analyzed for comparative purposes, exhibited loss of a p53 allele. These results demonstrate that PCR analysis, followed by restriction endonuclease digestion of a polymorphic locus, can provide a rapid, definitive method for analyzing loss of heterozygosity in small numbers of cells from colonic mucosa. Such loss precedes cancer in ulcerative colitis and can be present in its earliest histologically identifiable precursor.