Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. I. Preparation of antisera against the zinc glycinate marker.

Antisera against the zinc glycinate marker (ZGM) were produced in New Zealand White rabbits with induced tolerance to normal tissue components and CEA, and in mature, previously uninoculated rabbits for use in immunofluorescent histologic localization of ZGM in colon cancers and other tissues. Analysis of the antisera by immunodiffusion and counterimmunoelectrophoretic techniques showed them to be specific for ZGM when tested with ZGM, carcinoembryonic antigen, normal tissue extracts, or cell elements of normal blood.

Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. II. Immunofluorescence microscopy.

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.

Psammomatous somatostatinomas of the duodenum.

The presence of psammoma bodies in carcinoid tumors of the gastrointestinal tract is a rare occurrence; it has also been reported to be associated with features of somatostatin production by the tumor cells. The morphologic features of three such tumors arising in the duodenum were studied by a combination of histochemical, immunocytochemical, and ultrastructural techniques in an effort to delineate their secretory profile and further subclassify them. All tumors showed a mixed architectural pattern with prominent areas of glandular differentiation. The psammoma bodies were almost exclusively located within the glandular lumina. In each instance, the majority of tumor cells showed histochemical and immunocytochemical features of somatostatin-containing cells, and one tumor studied ultrastructurally showed numerous large- and small-sized intracytoplasmic secretory granules, both of which contained somatostatin. In contrast to other endocrine tumors of the duodenum that frequently have a multihormonal secretory profile, psammomatous duodenal carcinoids are associated with the exclusive presence of somatostatin within tumor cells. While many more of such examples of this uncommon tumor need to be systematically investigated for their immunocytochemical and ultrastructural characteristics, duodenal somatostatinomas need to be included in the differential diagnosis of psammomatous tumors.

Esophageal intramural pseudodiverticulosis: a report of two cases with analysis of similar, less extensive changes in "normal" autopsy esophagi.

Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon cause of dysphagia. In this report, we describe two cases we encountered at autopsy. In both cases, the pseudodiverticula represented dilated excretory ducts of submucosal mucous glands. In addition, we retrospectively examined histologic sections of esophagus taken randomly from 100 autopsies, and prospectively studied 20 esophagi in a standardized fashion. Our findings suggest that the early pathologic changes of EIPD are more common than is appreciated in the literature. We found submucosal chronic inflammation surrounding mucous glands in more than 60% of esophagi at autopsy. Excretory duct dilatation and small pseudodiverticula were also commonly found, their prevalence related to the number of sections of esophagus studied. The finding of chronic inflammation associated with the earliest degrees of duct dilatation and pseudodiverticula formation suggests that inflammation may play a role in the etiology of this disorder.

Prognostic factors in colon carcinoma: correlation of serum carcinoembryonic antigen level and tumor histopathology.

The results of histopathologic study and the preoperative circulating carcinoembryonic antigen 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 carcinoembryonic antigen level, had prognostic value. Low serum carcinoembryonic antigen levels in patients with 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 carcinoembryonic 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 infiltration in the primary tumor. Round cell infiltration was interpreted as an indication of the host's immune response against the tumor. Thus, on the basis of clinical follow-up of the patients it is concluded that all morphologic parameters evaluated have prognostic value, that preoperative serum carcinoembryonic antigen levels have prognostic value, that all prognostic parameters correlate with each other appropriately, and that the combined parameters are more reliable than any single one alone.

Transformation of lymphoma to amyloidoma following radiation therapy.

A 62-year-old man presented with a localized upper-extremity small cell lymphoma with plasmacytoid features and an associated IgM lambda serum immunoglobulin level of 1,730 g/dl. The tumor was treated with 5,960 rad over 47 days. On completion of radiation therapy, the tumor had regressed only minimally, and the monoclonal immunoglobulin level had decreased by 63 per cent; repeat biopsy revealed that the lymphoma had been replaced by a virtually acellular mass of amyloid. It is postulated that radiation therapy accelerated the tissue conversion of lambda light chain into the beta-pleated sheet structure characteristic of amyloid fibrils.

Bacteriologic status of necrotic tissue in necrotizing pancreatitis.

To confirm the accuracy of guided percutaneous aspiration (GPA) in distinguishing sterile from infected pancreatic necrosis, we have performed Brown-Brenn tissue Gram stains on pancreatic and peripancreatic necrotic tissue removed operatively in 15 patients. In eight patients judged to have sterile necrosis on the basis of negative cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery was also free of bacteria. In seven patients judged to have infected necrosis on the basis of positive cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery harbored a considerable number of bacteria. We conclude that GPA targeted to areas of necrosis accurately distinguishes infected necrosis from sterile necrosis, and in infected necrosis, the solid necrotic tissue as well as the fluid component contains bacteria. We therefore believe that infected necrosis is not likely to be eradicated by catheter drainage and should be treated by surgical debridement.

Induction bleomycin infusion in head and neck cancer.

Twenty-one male patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with an induction regimen of bleomycin 15 mg/m2 I.V. bolus followed by a continuous 24-hour I.V. infusion at a dose of 15 mg/m2/day for 7 days. One week following induction therapy, patients were reevaluated for response and then received definitive therapy with surgery and/or radiation therapy. The chemotherapy yielded a major response rate of 33% (one CR, six PR). Toxic manifestations of this regimen were mild, consisting of fever, alopecia, rash, and mucositis. There was no pulmonary toxicity detected. The response rate obtained with bleomycin infusion is inferior to the combination of cis-platinum with a bleomycin infusion as induction therapy in previously untreated patients with squamous cell carcinoma of the head and neck.

Silicone-induced endocarditis. A complication of transvenous cardiac pacing catheterization.

We report a case of silicone-induced endocarditis as a newly recognized complication of transvenous cardiac pacing catheterization. Silicone was found embedded in thrombotic vegetations on the tricuspid valve of a patient who had a long-standing pacing catheter in the right side of his heart. Scanning electron microscopy and energy-dispersive x-ray analysis confirmed the presence of silicone in the vegetations and in the catheter tip.

Chemoprevention of head and neck cancer. Potential use of retinoids.

Research on retinoid treatment of neoplastic lesions will ultimately determine the long-term effect of these substances on cancer development. However, until specific indications are firmly established through clinical trials, retinoid compounds cannot be routinely recommended.

Multiple primary malignancies in patients with alcoholic liver disease. A report of two cases.

Two patients, each with three primary malignant neoplasms are presented. In an effort to identify a possible common denominator of induction of these tumors, it was found that both patients were alcoholics with liver disease, and that both had impaired delayed hypersensitivity reactions. The possibility of an increased susceptibility to cancer among alcoholics with liver disease is noted and the need for careful follow-up of these patients is suggested.

The prevalence of Barrett's esophagus in patients with chronic peptic esophageal strictures.

Both Barrett's esophagus and peptic stricture of the esophagus are consequences of chronic reflux esophagitis. Barrett's esophagus appears to be a premalignant condition, and continued histologic surveillance for dysplasia and carcinoma has been recommended for affected patients. While patients with peptic esophageal strictures and persistent reflux are at risk for the development of Barrett's epithelium, such patients often do not receive continued histologic surveillance if Barrett's epithelium is not identified on the initial endoscopic evaluation. Using endoscopic and peroral aspiration biopsy techniques, we studied the prevalence of Barrett's esophagus in 25 patients with chronic peptic esophageal strictures in whom Barrett's epithelium had not been identified previously. We found Barrett's esophagus in 11 (44%) of our 25 patients. One patient who did not have Barrett's esophagus was found to have an undifferentiated esophageal carcinoma. We conclude that patients with chronic peptic esophageal strictures frequently have Barrett's esophagus. A program of continued histologic surveillance seems advisable for such patients.

The increasing frequency of adenocarcinoma of the esophagus.

Adenocarcinoma of the esophagus has been considered an uncommon tumor, accounting for fewer than 8% of all cases of esophageal cancer. To determine the current frequency of adenocarcinoma of the esophagus, we reviewed data from the tumor registries of the Commonwealth of Massachusetts, the University Hospital (UH), and the Boston VA Medical Center (BVAMC). From 1982 to 1984, 868 esophageal cancers were reported in Massachusetts, of which 231 (27%) were adenocarcinomas. In comparison with squamous cell carcinomas of the esophagus, esophageal adenocarcinomas occurred more frequently in males (P less than 0.01) and were uncommon among blacks (P less than 0.01). From 1980 to 1986, 262 cases of esophageal cancer were seen at the UH and the BVAMC, of which 81 (31%) were adenocarcinomas. An analysis of the latter group to identify true esophageal adenocarcinomas (tumors confined to the esophagus without gastric involvement) yielded 47 cases. Thus, true esophageal adenocarcinoma accounted for 18% of esophageal malignancies at our hospitals, a frequency threefold to fivefold higher than that found in four prior studies that used comparable anatomic diagnostic criteria. We conclude that adenocarcinoma of the esophagus is now being recognized at a substantially higher frequency than reported in the past.

Sequential germ cell tumor without prior involvement of the testes.

We report on a patient who presented with a metastatic germ cell tumor and had a normal testicular examination. A complete response ensued following combination chemotherapy. A sequential germ cell tumor of the testes developed 20 months after the chemotherapy was stopped. This occurrence of clinically evident disease in the testes is consistent with either a second primary tumor or with recurrent disease from an occult focus not eradicated by prior systemic chemotherapy. Our case is compared to other cases of sequential germ cell tumors reported in the literature.

Chemotherapy for primary retroperitoneal yolk sac tumor: report of a case.

A case of primary extragonadal yolk sac tumor occurring in the retroperitoneum of a young adult male was studied. The chemotherapy of this tumor has not previously been described for cases of extragonadal origin. A combination of cyclophosphamide, vinblastine, bleomycin, cis-diamminedichloroplatinum, actinomycin-D, and chlorambucil was used. A partial response and dramatic prolongation of survival was achieved, compared with previously reported cases.

Prognostic factors in colon carcinoma: correlation of serum carcinoembryonic antigen level and tumor histopathology.

Preoperative serum CEA values showed prognostic usefulness and correlated with established histopathologic prognostic parameters. CEA levels provide an additional useful prognostic index of a complex immunopathologic process. The best prognostic appraisal of the individual patient can be achieved by a complete assessment of all participating factors.

The reticular pattern as a radiographic sign of the Barrett esophagus: an assessment.

A two-part retrospective study was conducted to assess the value of a reticular pattern as a sign of columnar-lined esophagus. Radiographic, endoscopic, and histologic findings were reviewed in 124 patients with known Barrett esophagus; then all barium esophagrams done at our institution during a 3 1/2 month period were reviewed and presence of a reticular pattern was correlated with available endoscopic and histologic data. In patients with known Barrett esophagus, the reticular pattern was found in 26% of double-contrast examinations. Twelve of these patients underwent careful esophageal mapping biopsies: the pattern was in squamous mucosa with ulceration in two, in columnar epithelium with ulceration in six, and in columnar epithelium without ulceration in four. In the group of 314 unselected patients who had double-contrast examinations, the reticular pattern was found in 26 (8%). Thirteen of the 26 had had endoscopy and biopsy: the site of the pattern was located in a squamous carcinoma in one, in squamous epithelium adjacent to squamous carcinoma in three, in squamous epithelium with esophagitis in five (two of whom had columnar mucosa distally), in normal squamous mucosa in one, and in columnar epithelium with esophagitis in three. The reticular pattern is a strong indicator of important esophageal disease, but is not specific for Barrett esophagus.

CEA levels in patients with colorectal polyps.

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.