Search

The flat adenoma may be a more aggressive pathway in colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort were reclassified histopathologically as flat or polypoid and compared with initial and surveillance pathology.A total of 933 sessile adenomas detected during 1980-1990 were reclassified as follows: (1) adenoma thickness (AT):or =1.3 mm, and (2) adenoma ratio (AR): adenoma thickness2x normal mucosa thickness. Logistic regression was used to assess whether flat adenomas had an effect on risk for high-grade dysplasia initially, and a Cox proportional hazards model assessed the risk for advanced adenomas at surveillance.The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR measures of adenoma flatness were 95% concordant. By the AT measure, flat adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were found to be no more likely to exhibit high-grade dysplasia than sessile (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was 1.91 (95% confidence interval [CI], 0.66-5.47; P = 0.23) for sessile (polypoid) vs. flat adenomas and 1.78 (95% CI, 0.63-5.02; P = 0.28) for pedunculated vs. flat adenomas adjusted for size, villous component, and location, and corrected for correlation of risk within an individual patient. Patients with flat adenomas at initial colonoscopy were not at greater risk for advanced adenomas at surveillance compared with those with polypoid adenomas only, the odds ratio was 0.76 (95% CI, 0.4-1.42; P = .39), adjusted for multiplicity, age, and family history of colorectal cancer.Flat adenomas identified in the National Polyp Study cohort at baseline were not associated with a higher risk for high-grade dysplasia initially, or for advanced adenomas at surveillance.

Background After patients have undergone colonoscopic polypectomy, it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance. Methods As part of the National Polyp Study, we offered colonoscopic examination and double-contrast barium enema for surveillance to patients with newly diagnosed adenomatous polyps. Although barium enema was performed first, the endoscopist did not know the results. Results A total of 973 patients underwent one or more colonoscopic examinations for surveillance. In the case of 580 of these patients, we performed 862 paired colonoscopic examinations and barium-enema examinations that met the requirements of the protocol. The findings on barium enema were positive in 222 (26 percent) of the paired examinations, including 94 of the 242 colonoscopic examinations in which one or more adenomas were detected (rate of detection of adenomas, 39 percent; 95 percent confidence interval, 33 to 45 percent). The proportion of examinations in which ...

Background The adenoma–adenocarcinoma sequence in colorectal cancer suggests an increased risk of colorectal cancer in the families of patients with adenomatous polyps. Methods A random sample of participants in the National Polyp Study who had newly diagnosed adenomatous polyps were interviewed for information on the history of colorectal cancer in their parents and siblings. The risk of colorectal cancer in family members was analyzed according to the characteristics of the patients with adenomas and in comparison with a sample of patients' spouses, who served as controls. Results Among the patients with adenomas, 1199 provided information on whether they had a family history of colorectal cancer. After the exclusion of families for which information was incomplete and of 48 patients who had been referred for colonoscopy solely because they had a family history of colorectal cancer, there were 1031 patients with adenomas, 1865 parents, 2381 siblings, and 1411 spouse controls. The relative risk of colore...

A case is presented of an elderly man with a striking and unusual form of colonic schistosomiasis consisting of extensive large nodules on the serosal surface of the distal large bowel. The nodules were composed almost entirely of Schistosoma mansoni ova surrounded by thick bands of fibrous tissue. Although the English language literature describes various manifestations of intestinal and abdominal schistosomiasis, nowhere is there an adequate description of this unusual presentation, which might be confused with subserosal metastic malignancy or diverticulosis during surgical examination.

Background The current practice of removing adenomatous polyps of the colon and rectum is based on the belief that this will prevent colorectal cancer. To address the hypothesis that colonoscopic polypectomy reduces the incidence of colorectal cancer, we analyzed the results of the National Polyp Study with reference to other published results. Methods The study cohort consisted of 1418 patients who had a complete colonoscopy during which one or more adenomas of the colon or rectum were removed. The patients subsequently underwent periodic colonoscopy during an average follow-up of 5.9 years, and the incidence of colorectal cancer was ascertained. The incidence rate of colorectal cancer was compared with that in three reference groups, including two cohorts in which colonic polyps were not removed and one general-population registry, after adjustment for sex, age, and polyp size. Results Ninety-seven percent of the patients were followed clinically for a total of 8401 person-years, and 80 percent returned...

Measurement of the relative contributions of morphology alone; minimal essential clinical data; immunohistologic reactivity of a prototypic tumor marker, carcinoembryonic antigen (CEA); and the process by which a pathologist can identify the origin of a metastatic adenocarcinoma of unknown primary site is the subject of this report. To standardize the case material, we used an image digitizing and archival system to present 100 metastatic adenocarcinomas of known primary site as unknowns to two pathologists. The images were selected to show only gland-forming areas of the carcinomas and excluded all normal tissue elements. They were viewed, initially without, and then with, identification of gender and metastatic site. Subsequently, the results of immunoperoxidase staining for CEA, assessed independently by a third pathologist, were provided. Our analysis showed that, overall, the correct primary site was chosen as choice 1, 2, or 3 in 72% and 76%, and as choice 1 in 49% and 47% of cases, respectively. Accuracy was highest for prostatic, ovarian, and breast carcinomas, and lowest for upper-gastrointestinal tract, biliary tract, and pancreatic adenocarcinoma. Statistical analysis showed the largest increments in accuracy in the choice 1 prediction in each tumor category were achieved by provision of minimal essential clinical data. Knowledge of CEA status did not affect overall accuracy; however, it increased the odds of making the correct diagnosis for ovarian, colorectal, and endometrial (both pathologists) carcinomas, and for prostatic, pulmonary and esophago-gastric adenocarcinomas (one pathologist). The study exemplifies a model for the objective measurement of the contribution of ancillary studies, such as immunoperoxidase markers, to the accuracy of pathologic diagnosis.

The relationship of villous to tubular adenomas is poorly understood and often difficult to characterize morphologically. A villous growth pattern in colorectal adenomas has been associated with a higher frequency of high-grade dysplasia. We compared phenotypic markers using immunoperoxidase techniques in paired samples of villous (75% to 100% villous) and pure tubular adenomas matched for size and degree of dysplasia, which were selected by review of 1,000 polyps from our files. The following monoclonal antibodies were used: CAM 5.2 and AE1/AE3 to cytokeratins; B18, D14, B7.1, and B7.8 to four distinct carcinoembryonic antigen epitopes; Leu-M1 and LN3 to HLA-DR antigen; LN2 to invariant chain class II major histocompatibility complex; LN1 and MB2 to B-cell markers; UCHL1 and MT1 to T-cell markers; Leu-7 to natural killer cells; Mac 387 to macrophages; S-100 to Langerhans-type cells; and a polyclonal antibody to secretory component. LN3 reactivity correlated with villous morphology and secretory component correlated with tubular morphology. Combined HLA-DR and secretory component expression discriminated between tubular and villous growth patterns in 12 of 15 pairs of adenomas (P less than .001). LN2 was expressed more frequently than LN3, but did not correlate with growth pattern. Neuroendocrine cells (Leu-7) were more frequent in tubular adenomas. Carcinoembryonic antigen epitopes did not relate to growth pattern. We did not confirm previously reported differences in cytokeratin expression. We concluded that among the markers tested, HLA-DR expression, which may have an immunologic basis, is most characteristic of colorectal adenomas that exhibit a villous growth pattern.

The National Polyp Study (NPS) is a multicenter prospective randomized trial designed to evaluate follow-up surveillance strategies in patients who have undergone polypectomy for the control of large bowel cancer. The study design was developed by a joint research committee from American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the American College of Gastroenterology. Subjects who met the eligibility criteria were randomized into two different treatment arms. Eligibility criteria included: removal of one or more adenomas; complete colonoscopy; no prior polypectomy, inflammatory bowel disease, or familial polyposis; and no history of colon cancer. The treatment arms consisted of a frequent follow-up (1 and 3 years after initial polypectomy) and a less frequent follow-up (3 years). Follow-up examinations included fecal occult blood tests, air-contrast barium enema, and colonoscopy. The latter was done on 9112 referred patients at the seven participating centers from November 1980 until February 1990 who had no history of polypectomy, colon cancer, familial polyposis, or inflammatory bowel disease. Of these patients, 4763 (52.3%) had no polyps; 549 (6.0%) had an invasive cancer; 776 (8.5%) had nonadenomatous polyps; 208 (2.3%) had incomplete examinations; 184 (2.0%) had other findings; and 2632 (28.9%) had one or more adenomas, of which 1418 (53.9%) were randomized to one of the two treatment arms. This article reports the background, rationale, objectives, methods, and organization of this study and includes patient characteristics on initial presentation. Future data provided by the NPS may help in the development of recommendations for surveillance guidelines for such patients. This study also provides a framework to address questions regarding the natural history of adenomas and their relationship with colorectal cancer.

The term biologic marker (biomarker) of colorectal cancer refers in this article to an early preclinical phenotypic characteristic that relates to the risk for developing this cancer. Putative biologic markers in the normal colorectal mucosa of patients at risk include abnormal cell proliferation as determined by kinetic studies, ornithine decarboxylase activity, and polyamine synthesis. Alterations of mucin synthesis have been studied using both histochemical stains and lectin-binding techniques. Blood group and related carbohydrate antigens also have been evaluated as potential biomarkers in the normal mucosa

The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p

Immunohistologic techniques were used to study the expression of colorectal carcinoma-associated antigens in colonic polyps and to compare this with expression in the normal colonic epithelium. Forty-nine polyps were studied using monoclonal antibodies to 16 different blood group and differentiation antigens and carcinoembryonic antigen epitopes. With the Lewis(a) antigen and the two epitopes of CEA recognized by 3D6 and COL-4 expression in polyp tissue was the same as that in the normal colon. Five types of alteration of antigen expression in polyps were seen. The blood group antigens A, B, and Lewis(b), which are expressed only on the right side of the normal adult colon, were detected in both neoplastic and nonneoplastic polyps from the distal colon. The Lewis(x) antigen and the antigen epitopes detected by the antibodies COL-12, CA19-9, ME491, and GA73.3 showed an increased frequency of expression in all types of polyps in comparison with the normal colonic epithelium, while H-type 2, ND4, and the antigen epitope detected by CO29.11 showed a slightly decreased frequency of expression in polyp tissue. The X-like antigen which was expressed in only 7% of normal colon specimens showed increased frequency of expression in polyp tissue with significantly greater expression in neoplastic than hyperplastic lesions (P = 0.003). The TAG-72 antigen was detected only in adenomas with severe dysplasia (P = 0.01), correlating well with premalignant histology. These findings have helped us clarify the variation of antigen expression in colonic polyps and allowed us to define which antigens are worthy of further investigation as markers of possible malignant transformation.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.

The results of histopathologic study and the preoperative circulating carclnoeiribryontc anttgen levels were correlated with each other and with the postoperative clinical course in 45 surgically treated patients with cancer of the colon. Histopathologic evaluation of the tumor included the depth of bowel wall involvement according to the Dukes classification, the histologic differentiation of cells on the basis of Broders' grades of malignancy, evidence of lymphocyte and plasma cell infiltration within and surrounding the primary tumor, and evidence of blood vessel, lymphatic, and perineural invasion. All these parameters, including the serum carcinoetnbryonic antigen level, had prognostic value. Low serum carcinoembryonic antigen levels in patients wiith colonic cancer suggested tumor localized within the bowel wall; the highest values were found in patients with tumors that had spread beyond the bowel wall. An inverse correlation was noted between the degree of tumor differentiation and carcino-embryonic antigen levels in the same patient. Carcinoembryonic antigen levels tended to be elevated when blood vessel, lymphatic, and perineural invasion was present. An inverse correlation was also noted between the preoperative carcinoembryonic antigen level and the degree of lymphocyte and plasma cell.

Preliminary indirect immunofluorescence studies on the zinc glycinate marker (ZGM) were compared with carcinoembryonic antigen (CEA) immunofluorescence, ZGM, detected in 26 of 29 human colon adenocarcinomas, was associated with the epithelial component of the malignant glands. Fluorescence was generally less strong and more granular for ZGM than for CEA and was found in intraglandular spaces, luminal border areas, and cytoplasm. ZGM concentration and tissue localization appeared to be related to tumor differentiation. ZGM was also detected in benign colon mucosae (adjacent to and distant from the carcinomas) from patients with colon carcinoma, but differed from CEA in that it was present in the deep crypt portion only. Gastric, pancreatic, esophageal, and anal adenocarcinomas, as well as benign gastric pyloric and small bowel mucosae had detectable ZGM. CEA, but not ZGM, was observed in 20 nongastrointestinal carcinomas to date. Studies are under way to determine whether ZGM is a marker associated with colon and gastrointestinal adenocarcinoma specifically or undifferentiated crypt cells of the colon and digestive tract in general.

Preoperative plasma CEA levels were measured in 93 selected patients with histologically defined colorectal adenomata removed at fibroptic colonoscopy in order to determine whether CEA levels are elevated in patients with colonic polyps, or vary with different histologic patterns. None of the patients had inflammatory bowel disease, previous history of carcinoma, or evidence of liver disease. Fifteen percent of the patients had elevated CEA levels (greater than or equal to 2.5 ng/ml; Hansen method), and two-thirds of these were between 2.5 and 4.0 ng/ml. Increased association of elevated CEA levels was noted with old age, villous adenomas (2- to 4-fold), and increased tumor size (greater than 2.3-cm diameter; 2-fold), but not with foci of dysplasia or carcinoma in situ as such. One-half (7/14) of the patients with elevated CEA levels showed the following: two patients had villous tumors with carcinoma in situ, one had a villous adenoma, two had mixed villous and tubular adenomas (with a high proportion of villous pattern), and two were subsequently shown to have carcinoma elsewhere in the colon. It is uncertain that the polyps were the source of the elevated circulating CEA levels; other factors including smoking and patient selection need to be considered. This preliminary study suggests that patients with colorectal adenomata and elevated circulating CEA may be at higher risk for the development of carcinoma. Further follow-up studies of the malignant potential of the polyp-bearing colon are essential.

Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor.

The possibility that the disposition of cholesterol, which is influenced by the quality of dietary fat, may be associated with either vascular lipidosis or colon cancer was evaluated in this study. Rats were fed diets containing cholesterol plus a) saturated fat, 20% coconut oil, to elevate serum cholesterol and promote vascular lipidosis or b) polyunsaturated fat, 20% safflower oil, to minimize serum cholesterol elevations and retard the development of vascular lipidosis. The relationships of these diets to gastrointestinal tract tumors induced by 1,2,-dimethylydrazine (DMH) was evaluated. Serum cholesterol levels in rats fed the coconut oil diet and given DMH were markedly elevated and were associated with moderate to severe vascular and aortic sudanophilia. Conversely, rats fed the safflower oil diet and given DMH had modest elevations in serum cholesterol levels and minimal vascular and aortic sudanophilia. Significantly, greater numbers of large bowel tumors induced by DMH were found in rats fed the safflower oil diet than in those fed the coconut oil diet. It was suggested that the polyunsaturated fat diet promoted the decrease in serum cholesterol levels concomitant with an increase in fecal neutral and acid sterols, which in turn augmented tumorigenesis by DMH in these animals compared with those fed the saturated fat diet. Thus, in the animal model used, the interaction of dietary fat (quality or quantity) with endogenous or dietary cholesterol determines whether or not diet will be a contributing factor in a) the development of vascular lipidosis or b) augmentation of small and large bowel tumorigenesis.

A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first-degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old (a) an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, (b) either colonoscopy or barium enema may reduce mortality by ~85%, (c) a 3–5-yr frequency for endoscopies or barium enemas preserves 70%–90% of the effectiveness of an annual frequency, and (d) beginning screening at age 50 reduces effectiveness by 5%–10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies.

Assessment of the influence of nutritional substrates on the disposition of ingested ethanol from the blood requires, first, an understanding of the influence that these may exert upon ethanol absorption from the gastrointestinal tract. In this report, the effects of various carbohydrates on the intestinal absorption of ethanol were studied. When carbohydrates (50 mM) were perfused simultaneously with ethanol (50 mM) in vivo in the rat small bowel, ethanol absorption increased up to 34% (P less than 0.005) above controls receiving ethanol alone. Of the monosaccharides, fructose, 3-O-methylglucose, glucose, or galactose added to an ethanol perfusate, only glucose or galactose increased ethanol absorption over control animals receiving ethanol alone. Of the disaccharides tested, sucrose and maltose, but not lactose, enhanced ethanol absorption. Addition of varying concentrations of maltose to an ethanol perfusate augmented ethanol absorption in a direct proportion to the quantity of glucose absorbed, rather than to the quantity of maltose hydrolyzed. Augmentation of ethanol absorption by carbohydrates appears to be dependent upon sugar-active transport. Ethanol, dissolved in intraluminal water, may cross the mucosa in water absorbed during sugar-active transport. This quantity of ethanol is absorbed in addition to that which normally crosses the mucosa by diffusion down its concentration gradient.

Immunoperoxidase and immunofluorescence staining for carcinoembryonic antigen (CEA) was performed on paraffin and frozen sections, respectively, of colonic carcinomas (70), liver and lymph node metastases (20), mesenteric nodes (150), mucosa adjacent to carcinoma (40), colonic resection margins (20), normal colon (ten), and colorectal polyps (64) in order to assess its potential diagnostic value. On the basis of this study of the immunocytochemical localization of CEA in colorectal tissues, conclusions were as follows. (1) Localization of CEA to glycocalyx of surface epithelial cells is a normal finding in the colon and is similar in normal colon and mucosa distant and adjacent to infiltrating carcinoma. (2) Although strongly positive cell surface and intraluminal staining frequently correlates with the presence of carcinoma in neoplastic polyps, it is not by itself a reliable diagnostic criterion. (3) Failure to demonstrate CEA in a gland-forming carcinoma makes a diagnosis of colorectal carcinoma unlikely. (4) Poorly differentiated colorectal carcinoma usually contains much less demonstrable surface CEA, but may occasionally stain cytoplasm strongly. (5) Although lymph node micrometastases from colorectal carcinoma are readily demonstrated by immunoperoxidase staining for CEA, screening of hematoxylin and eosin-stained sections by a competent pathologist appears to be adequate for their detection.

A myxoma of the mandibles in an adult female Macaca mulatta is described. The left mandible was markedly enlarged by the tumor, which extended from the symphysis to the temporomandibular joint. The tumor had extended a short distance across the symphysis into the right mandible. It was composed of a glistening mucinous material. Radiographs of the tumor showed a large expansile radiolucent lesion of the left mandible without soft tissue involvement. Light microscopy demonstrated capillaries, stellate shaped cells with processes up to 15 mu long, very few other cell types, and an amorphous ground substance. Electron microscopic examination revealed similarity to the myxoma of bone of man. The oxytalan fibers discovered in this myxoma have not been found in myxomas before and suggest the tumor is odontogenic in origin. The incidence of spontaneous neoplasia in general and that of spontaneous oral tumors in particular in nonhuman primates are reviewed.

The incidence and clinicopathologic features of early gastric cancer encountered among surgical specimens from gastric resections for carcinoma in a recent three-year period, 1977 to 1979, at the Mallory Institute of Pathology were studied and compared with those of a pre-endoscopic period 10 years earlier, 1967 to 1969. It was found that early gastric cancer now comprises a greatly increased proportion of lesions leading to gastric resection, mainly as a result of endoscopy and biopsy of gastric ulcers of benign appearance. In the recent period, there were six early gastric cancers in a total of 22 gastric resection specimens compared with one in 27 gastric resections performed for carcinoma in the pre-endoscopy period. Five of the six patients in the recent period are alive without evidence of disease four to five years following surgical resection. The single patient in the earlier period died postoperatively. Applying the classification of the Japanese Endoscopic Society, there were three depressed or ulcerated lesions (type lic or III), three elevated or polypoid lesions (type I or IIa), and a single flat lesion (type IIb). All three ulcerated lesions were Interpreted as benign peptic ulcers on conventional upper gastrointestinal studies. Findings on endoscopic biopsy were positive in all cases (six of six). Although not encountered frequently in the United States, early gastric cancer, nonetheless, appears to be indistinguishable from the disease as it is described in Japan in terms of its pathologic morphology, growth patterns, coexistent or related lesions of the stomach, and curability by surgical resection. If early gastric cancer is to be recognized more frequently, knowledge of the disease and a high index of suspicion on the part of physicians are essential.

1. Two cases of granular-cell lesions (myoblastoma) involving stomach and colon, respectively, are reported.

Summary Human post-mortem gastrointestinal tissue can be used for the study of the mast cell. There is no appreciable decrease in the number of mast cells between the fourth through the ninth hours after death. A distinct distributional pattern of mast cells occurs throughout the different levels and layers of the gastrointestinal tract.

Using a radioimmunoassay for carcinoembryonic antigen(s), positive assays were obtained in 40 of 88 patients with severe alcoholic liver disease but in none of 14 patients with nonalcoholic liver disease. None of these patients had evidence of gastrointestinal malignancy. Lower levels of serum carcinoembryonic antigen(s) usually were seen in patients with alcoholic liver disease than in patients with colonic or pancreatic cancer. The patients with liver disease and carcinoembryonic antigen-positive sera usually had active alcoholic liver disease with decompensated Laennec’s cirrhosis and were readily distinguished clinically from patients suspected to have gastrointestinal malignancy.

Electron microscopic study of hepatoma tissue from a patient with mildly active alcohol-associated cirrhosis has demonstrated the ultrastructural nature of the two forms of hepatoma hyaline inclusions described by Norkin and Campagna-Pinto (Cytoplasmic hyaline inclusions in hepatoma. Arch Pathol 86:25-32, 1968). The reticular form of hepatoma hyalin is identical to alcoholic hyalin of Mallory. The globular deposits of hepatoma hyalin have a fibrillar internal structure also indistinguishable from that of the classical alcoholic hyalin of Mallory, except for closer packing of fibrils. Physical continuity of globular and reticular forms of hepatoma hyalin and a close association of globular hyalin with microbodies is demonstrated.

Liver biopsy specimens from patients with liver disease associated with alcoholism were studied by light and electron microscopy to demonstrate the distinguishing features of alcoholic hyalin and "megamitochondria" (giant mitochondria). Alcoholic hyalin is a fibrillar material and megamitochondria are readily identifiable organelles. They are separate and distinct entities, and there is no valid reason for confusing one with the other.

Presentation of Case A fifty-nine-year-old housewife was referred to the Tufts Hematology Clinic for evaluation of anemia. Nine months before she had noted the gradual onset of weakness and fatigue...

Laser energy produced by controlled fluorescence in crystals or gases possesses a number of remarkable special properties, particularly those of coherence and high power density. Laser energy is non-ionizing unlike x-ray irradiation and may produce exceedingly high power densities. Three groups of Syrian hamsters with various cell type malignant tumors were subjected to laser radiation. A specific selective destructive biologic effect which differed significantly from that caused by heat alone and x-ray irradiation was observed. The ultimate effect of laser energy on certain malignant tumors is gross dissolution of the tumor with no tumor cells observed by histologic examination.

Cirrhosis and hepatoma at Boston City Hospital have progressively increased in frequency, especially cirrhosis associated with chronic alcoholism. Alcoholic cirrhosis or fatty nutritional cirrhosis (FNC) increased from 31% (1917-1926) to 61% (1955-1968) of all types of cirrhoses. One third of 98 subjects dying of hepatoma had FNC. The occurrence of hepatoma associated with postnecrotic cirrhosis increased twofold and threefold in subjects with hemochromatosis. Chronic alcoholism was considered the pathogenetic agent implicated in the production of FNC, hemochromatosis, and post-necrotic cirrhosis in 56 of our 98 patients dying of hepatoma. An average of 8 years ensued from the onset of alcoholic cirrhosis to the appearance of hepatoma in 23 alcoholic patients.

Summary A study of the ultrastructure of the human colonic mucosa revealed a remarkably well developed, hairy extraneous coat on the luminal surface of the epithelial cells. Mucosal biopsies for this study were obtained from the rectosigmoids of eight patients. The surface of the microvilli and the intermicrovillous plasmalemma is covered with hairlike fibrils extending from the outer leaflet of the plasmalemma into the lumen. This layer measures up to 1.5 p, in thickness and is best developed on the surface epithelium and less well developed on the crypt epithelium. The extraneous coat appears to be an integral part of the epithelial cell, but its site of origin and its precise function remain speculative.

Summary Chronic liver injury was produced in rats by feeding a choline deficient diet for 1 year. The pathologic findings in the liver varied in severity from fatty liver to cirrhosis. The serum amylase activity decreased only when cirrhosis was produced and was maintained at normal values in earlier stages. No abnormalities were observed in the histology of the pancreas in any of the diseased animals. Liver amylase activity increased considerably, and this increase was associated with fat accumulation in the liver. In contrast to serum amylase, serum glutamic-pyruvic transaminase (SGPT) activity was increased in the fatty liver stage and returned toward normal with increased severity of the injury. In spite of the elevated serum levels, the liver transaminase did not show a significant decrease in activity. Moreover, absence of a reduced liver transaminase activity was interpreted as evidence against an increased permeability as a sole explanation for the high serum levels unless there is an accompanying increased rate of enzymatic synthesis to replace the released enzyme.

This paper describes a large circumferential benign tumor of the jejunum indistinguishable from villous adenoma of the colon. The lesion was recognized and resected 21/2 years after the onset of symptoms. The clinical course of the patient was characterized by intermittent bowel obstruction and preoperatively by hemorrhage and intussusception, all common clinical features of jejunal tumors. The lesion is considered to represent a previously undescribed villous adenoma of the small bowel.

In recent years a singular type of renal tubular nephropathy has been recognized in association with hypokalemia consisting of a characteristic patchy vacuolar change usually localized to the epithelial cells of the proximal convoluted tubules. Most vacuoles are supranuclear, compressing the nuclei toward "the basement membrane. Affected tubules usually fail to stain for fat, although some fat-positive vacuoles have been reported in experimentally induced lesions in rats.! The picture of vacuolar nephropathy has been seen in a number of gastrointestinal diseases associated with diarrhea; for example, ulc~rative colitis, regional enteritis, diverticulitis, gastroenterocolitis, acute enteritis, bacillary dysentery, sprue (idiopathic or malabsorption syndrome), and Whipple's disease.2 6 The importance of this clinical entity lies in the fact that the lesion is probably a reversible one if recognized and treated promptly. The purpose of this paper is to present a patient with massive intestinal resection, who survived for 6 years, with development of hypokalemic vacuolar nephropathy. This clinical sequence has not been previously reported.

SummaryThe substitution of 20% alcohol for drinking water of Buffalo rats maintained on an adequate diet demonstrated significant decreases in glucose-6-phosphate dehydrogenase, formiminotransferase, malic and citrate cleavage enzyme activities. This is in contrast to the Charles River and other strains of rats. Liver studies using labeled glucose and acetate indicated that the Buffalo rat is capable of synthesizing approximately twice as much lipid from glucose compared with the Charles River rat. The results suggest that the Buffalo rat has a sensitivity to alcohol related to certain aspects of lipid metabolism not seen in the Charles River rat or other strains.

A case of progressive systemic sclerosis with extensive morphologic and functional abnormalities of the gastrointestinal tract is reported. Cutaneous manifestations were mild throughout the course but there was severe and progressive gastrointestinal involvement with episodes of fecal obstruction, malabsorption and atony, with death by spontaneous perforation of a diseased portion of the colon. At autopsy an additional morphologic finding not heretofore described was abundant deposits of ceroid (lipofuscin) pigment in the smooth muscle of the gut. The morphologic and functional abnormalities of gastrointestinal scleroderma illustrated by this case are discussed.

The relationship of dietary cholesterol to bowel tumorigenesis is controversial. Lui and associates (1) used food disappearance data and age specific mortality rates for colon cancer in a descriptive epidemiologic study. By cross classification of data they observed that dietary cholesterol independently exhibited a significant direct effect with colon cancer mortality but fat and fiber did not. In a case control study of colo-rectal cancer by Jain, et al (2) multivariate analysis, with major nutrients controlled, revealed a dose responsive direct relationship for each sex between dietary cholesterol intake and colorectal cancer.

We used monoclonal antibody B72.3 to study the expression of the colorectal carcinoma-associated antigen TAG-72 in premalignant colonic lesions with the immunoperoxidase technique. This antigen, which is rarely detectable in the normal colonic epithelium, was expressed in 13 of 19 adenomas with moderate to severe dysplasia and nine of nine cases of inflammatory bowel disease. The antibody reacted with the normal-appearing mucosa adjacent to a carcinoma in 10 of 12 cases, although only eight of the tumors expressed the antigen. The expression of the TAG-72 antigen in the colonic epithelium may be an early marker of malignant transformation.

Iron deficiency has been shown to affect a number of systems including the immune system, the gastrointestinal system, the erythron, and the utilization of at least one essential nutrient and perhaps others. A number of studies have indicated that in irondeficient animals and humans there is decreased killing by polymorpholeucocytes (1,2), but phagocytosis may not be altered. Additionally, in iron-deficient humans, it is shown to depress the response of T cells to mitogens.(3)

Ultrastructural studies in our laboratory have previously shown that alcoholic hyalin and megamitochondria are separate and distinct entities within the hepatic cytoplasm of patients with liver disease associated with alcoholism.1 Alcoholic hyalin presents as aggregates of fibrillar material without a limiting membrane and without special association with any organelle. Enlarged mitochondria or megamitochondria are easily identified, regardless of their size or shape because of their characteristic outer membranes and cristae. Hyalin and megamitochondria are also identifiable in thick Epon sections stained by a modified basic fuchsin-crystal violet stain. We were able, therefore, to make direct correlations of the morphology of any specific structure by studying thick sections with a light microscope and the adjacent thin sections with the electron microscope.

IN 1962 Wangensteen and his associates1 reported the achievement of "physiological gastrectomy" by gastric freezing. At that time these investigators presented results on 24 patients with duodenal ulcers who were subjected to a one-hour period of gastric freezing. In this group of patients there was excellent subjective relief of symptoms, significant decreases in gastric secretory response and disappearance of duodenal-ulcer craters. In parallel animal studies these workers found that isolated gastric pouches, whether Pavlov, Heidenhain or antral, when frozen for an hour (with inflowing coolant at temperatures of -17 to -20°C.), became unresponsive to physiologic stimuli. They postulated that the . . .