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Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 289 records · Page 16Linked to original sources

When is intervention warranted?

A chemoprevention trial in prostate cancer would be a formidable but potentially rewarding study. The current status of knowledge of drug interactions with, biomarkers of, and even the natural history of prostate cancer is insufficient to study all levels of men at risk. Currently, the most promising group to study is group I--those men with a high probability of developing prostate cancer but who do not currently have evidence of the disease. This could be a placebo-controlled, prospective and randomized study with the endpoint being clinically-detected prostate cancer. In addition, much may be gained from short-term pilot studies of "chemo-active" agents on morphologic and other biomarkers of prostate cancer initiated immediately before surgical removal. It is hoped that such studies may provide rationale for future efforts directed at preventing progression of premalignant or early prostate cancer lesions.

Anticarcinogenic Agents↗

Natural history of early bladder cancer.

Non-invasive transitional cell carcinoma (TCC) occurs as two distinct growth patterns, papillary and non-papillary (flat), which display significant differences in biologic potential. Papillary carcinoma usually presents as a low-grade lesion which frequently recurs multiple times prior to invasion; conversely, non-papillary (flat) carcinoma in situ is usually high-grade at presentation (carcinoma in situ) and frequently associated with invasion. These lesions may occur together, although papillary cancer is more easily visualized cystoscopically due to its exophytic growth; flat carcinoma in situ is often cystoscopically invisible. This report reviews existing data concerning the prognostic value of pathologic grading and staging of non-invasive and early invasive TCC. Emphasis is placed on those studies reporting surgical treatment rather than other forms of treatment.

Carcinoma in Situ↗

Paneth cell-like change of the prostate gland. A histological, immunohistochemical, and electron microscopic study.

Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally observed in one case of normal glandular epithelium, two cases of glandular and stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four cases of prostatic adenocarcinoma. The distinctive cells were characterized by bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained material. The cytoplasmic granules in the benign prostatic epithelium were periodate-Schiff's procedure (PAS)-positive and diastase resistant and immunohistochemically negative for lysozyme, neuron-specific enolase, chromogranin, and serotonin. The eosinophilic granules in the prostatic intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically positive for chromogranin, serotonin, and neuron-specific enolase, and negative for lysozyme. By electron microscopy the eosinophilic granules represented exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro-endocrine granules in the malignant epithelium. The lesion represents a prostatic epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common histological manifestation of two different phenomena: (a) a PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, and (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC lies in its differentiation from other possible prostatic cytoplasmic inclusions.

Acid Phosphatase↗

Dysplasia and cancer complicating strictures in ulcerative colitis.

Previous studies have found a widely variable prevalence of dysplasia and cancer in colonic strictures in patients with ulcerative colitis. Consequently, therapeutic recommendations are conflicting. To better assess the prevalence, we reviewed the clinical and pathological findings in all 27 patients with ulcerative colitis complicated by stricture who were entered into our Inflammatory Bowel Disease Registry. A true stricture was defined as a persistent localized narrowing of the colon found on air-contrast barium enema or on colonoscopy. Upon careful review, 12 of 27 patients were found to have transient colonic spasm, not a stricture, and were excluded. The remaining 15 patients with true strictures represented 3.2% of all ulcerative colitis patients in the registry. Strictures were identified at 13.3 +/- 9.9 years following the diagnosis of ulcerative colitis. Eleven patients had multiple strictures that were principally located in the left colon. Of the 15 patients, 11 had dysplasia and two had cancer found on colonoscopic biopsy. Ultimately, six patients had carcinoma found at colonoscopy or colectomy (three modified Dukes' stage A, one stage B, and two stage D). All cancers were at the site of a stricture. These findings indicate that a true colonic stricture in ulcerative colitis is frequently associated with dysplasia and cancer, which can be diagnosed with colonoscopic biopsy. A stricture should be considered a strong risk factor for cancer, requiring intensive colonoscopic surveillance. If dysplasia is discovered, or if the stricture cannot be adequately biopsied, consideration should be given to total colectomy.

Adult↗

Isolated granulomatous gastritis in an adolescent.

This is a case of a 14 1/2-year-old black male with isolated granulomatous gastritis. The case is unusual in several aspects. For the first time this disorder has been seen in the pediatric age group. The symptoms and signs were more acute and severe than previously reported, and the inflammatory process involved the entire gastric mucosa. Several findings suggested an (auto)immune pathogenesis. The patient had a good clinical and histologic response to prednisone therapy, but the disease recurred after two years when therapy was discontinued.

Adolescent↗

Humoral hypercalcemia complicating adenosquamous carcinoma of the proximal colon.

Hypercalcemia as a complication of carcinoma of the colon is uncommon (1). It usually occurs in the presence of anorectal or rectal carcinoma that metastasizes to the lumbosacral vertebrae (2-4). Hypercalcemia complicating colon carcinoma in the absence of bone metastases--so-called humoral hypercalcemia of malignancy or paraneoplastic hypercalcemia--is rare. Only two such cases associated with adenocarcinoma of the colon (5,6) and two cases associated with adenosquamous carcinoma of the distal colon (rectum and sigmoid) (7) have been reported. We describe the first reported case of an adenosquamous carcinoma of the cecum and ascending colon that was accompanied by severe humoral hypercalcemia. The hypercalcemia was associated with a parathyroid hormone (PTH)-like substance.

Adenocarcinoma↗

Alterations in glycoconjugate expression following malignant transformation of human oropharyngeal squamous mucosa.

Malignant transformation of the squamous mucosa in the human oropharynx may be accompanied by alterations in carbohydrate production. Glycoconjugate expression was assessed by examining lectin-binding patterns and ABH isoantigen expression in human biopsy specimens from nine cases of carcinoma in situ and ten cases of invasive squamous cell carcinoma as well as adjacent normal squamous mucosa. Ten different fluorescein-conjugated lectins were used. Each lectin binds to specific nonreducing end-terminal carbohydrate residues. Wheat germ agglutinin and peanut agglutinin displayed intense cytoplasmic and/or membrane binding in more than 90% of the carcinoma in situ and squamous cell carcinoma specimens. However, only 40% of normal squamous epithelium specimens displayed intense cytoplasmic and/or membrane binding with wheat germ agglutinin and peanut agglutinin. Bandieraea simplicifolia I and Helix pomatia exhibited weak binding in less than 35% of normal and neoplastic tissues. Weak canavalia ensiformis binding was identified infrequently in the superficial layers of normal squamous mucosa, but was not found in neoplastic epithelium. None of the cases displayed binding for Dolichos biflorus, Ulex europaeus I, Sophora japonica, Glycine maximus, or Ricinus communis. Monoclonal antibodies directed against ABH blood group isoantigens showed increased cytoplasmic immunoreactivity for anti-H in dysplastic and neoplastic tissues, when compared with normal squamous mucosa. These findings indicate that wheat germ agglutinin and peanut agglutinin and H isoantigen are useful markers of malignancy in squamoproliferative lesions of the oropharynx, apparently reflecting alterations in expression of N-acetyl-D-glucosamine and galactose-related sugars, which appear following malignant transformation.

ABO Blood-Group System↗

Effects of ammonium acetate and sodium cholate on N-methyl-N'-nitro-N-nitrosoguanidine-induced colon carcinogenesis of rats.

This study was conducted to determine the effects of ammonium acetate alone or in combination with sodium cholate upon N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced colon carcinogenesis in rats. Ammonia, acetate, and deconjugated bile acids are produced by microbial enzymes in the gastrointestinal lumen. One hundred twenty male Sprague-Dawley rats, weighing 196 +/- 2 g at 8 wk of age, were given four intrarectal doses of MNNG (2 mg/dose) over 2 wk. They were then randomly assigned among four treatment groups, each containing 30 rats. The groups were arranged in a 2 x 2 factorial design and given intrarectal infusions of the agents under study in 0.3 ml of double-distilled water 3 times weekly for 52 wk beginning 4 wk after the initial MNNG treatment. The experimental treatments were: double-distilled water as control; ammonium acetate (24.8 mg of ammonia); sodium cholate (2 mg of cholic acid); and a combination of ammonium acetate and sodium cholate. Ammonium acetate treatment increased the number of rats with fecal blood 4-fold after 56 wk, and this was associated with a higher incidence of adenocarcinomas with a polypoid morphology. The incidence and total number of carcinomas in situ (high grade dysplasia) increased with ammonium acetate treatment. Ammonium acetate increased the total number of adenocarcinomas. Sodium cholate had no significant main effects on the incidence or morphology of colon lesions. The data support the conclusion that ammonium acetate treatment acted as a promoting agent in MNNG-induced colon carcinogenesis.

Acetates↗

Neuroendocrine innervation of the hepatic vessels in the rat and in man.

An extensive array of nerve fibers ramify around the afferent blood vessels of the liver and the extrahepatic and intrahepatic biliary pathways, and are thought to be involved in regulation of blood flow. Although the role of sympathetic innervation is established, little is known about the location or role of regulatory peptidergic innervation in the liver. We examined the anatomic distribution of a wide variety of regulatory peptides and several neural antigens by in situ immunohistochemistry in the rat and in man. A rich peptidergic plexus of nerve fibers and ganglion cells was observed around the arterial vessels in both species, with intense immunoreactivity for neuron-specific enolase, neurofilaments, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. S-100 protein immunoreactivity was seen principally in large nerve bundles, suggesting that the majority of nerves in this area were unmyelinated. In contrast, the portal vessels revealed very little peptidergic innervation. No staining was observed with antibodies directed against insulin, glucagon, gastrin, serotonin, met-enkephalin-Arg-Gly-Leu, cholecystokinin, or growth hormone. These findings indicate the presence of a rich, although selective, peptidergic plexus surrounding afferent hepatic blood vessels. This plexus may play an important role in regulation of hepatic blood flow.

Animals↗

Atypical spindle cell lesions of the prostate.

This report is a review of the spectrum of prostatic spindle cell lesions that are usually benign, but have morphologic features suggestive of high-grade malignancy. The problem is complicated further by the extreme rarity and heterogeneity of such lesions. Sixteen cases of atypical prostatic spindle cell proliferations are reported, and the differential diagnosis with malignancy is reviewed.

Adult↗

Premalignant lesions of the prostate.

Two putative premalignant lesions of the prostate have been identified. Prostatic intraepithelial neoplasia (PIN) is characterized by proliferation and anaplasia of cells lining ducts and acini. Atypical adenomatous hyperplasia (AAH) consists of a localized proliferation of small round glands without cytologic atypia. PIN and AAH may be confused with well-differentiated carcinoma as well as florid hyperplasia, basal cell hyperplasia, transitional metaplasia, seminal vesicular epithelium, and atypia due to inflammation, infarction, and radiation. These premalignant lesions appear to have a high predictive value for carcinoma, and their presence on prostatic biopsy warrants further search for concurrent invasive adenocarcinoma. The use of strict morphologic criteria and uniform nomenclature will ensure standardization in the diagnosis of premalignant lesions of the prostate.

Anaplasia↗

Expression of opioid peptides in tumors.

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.

Antibodies, Monoclonal↗

Gastric adenocarcinoma after gastric lymphoma.

Three men and one woman developed intestinal-type moderately or poorly differentiated gastric adenocarcinoma 4 to 15 years after the diagnosis of gastric lymphoma. Treatment of the lymphomas had included partial gastrectomy and follow-up radiotherapy and/or chemotherapy. Review of the literature reveals an additional 12 patients who developed adenocarcinoma 3.5 to 34 years (median, 14.5 years) after diagnosis of gastric lymphoma. In the total series of 16 patients, only four were women, who tended to be younger (median age, 36.5 years) than the men (median, 48.5 years) when lymphoma was diagnosed. Patients with gastric lymphoma seem to have an increased incidence of gastric adenocarcinoma. Carcinoma after gastric lymphoma often arises in the distal stomach and appears to occur irrespective of the type of therapy for the lymphoma.

Adenocarcinoma↗

Prostatic intra-epithelial neoplasia and early invasion in prostate cancer.

Prostatic intra-epithelial neoplasia (PIN, or intraductal dysplasia) is considered a precursor of invasive carcinoma, characterized by proliferation and anaplasia of cells lining prostatic ducts and acini. The highest grade of PIN, Grade 3, is thought to represent carcinoma in situ. To quantitate the degree of disruption of the basal cell layer in human prostatic ducts and acini as a potential marker of early invasion in PIN, a monoclonal antibody to keratin proteins of 49, 51, 57, and 66 kd which selectively labels the prostatic basal cell layer was used. A total of 1093 acini with PIN were identified in 14 cases with invasive carcinoma. Tumor cells consistently failed to be decorated with this antibody. The frequency of disruption of the basal cell layer increased with increasing grades of PIN, with disruption present in 0.7% of cases of PIN 1, 15% of cases of PIN 2, and 56% of cases of PIN 3. The amount of disruption of the basal cell layer also increased with increasing grades of PIN, with loss of more than one third of the basal layer in 52% of foci of PIN 3 compared with less than 2% in lower grades of PIN. Disruption of the basal layer was more common in acini adjacent to invasive carcinoma than in distant acini. These findings suggest that early invasion in prostate cancer is characterized by disruption of the basal layer, and that invasion occurs commonly in association with foci of high-grade prostatic intra-epithelial neoplasia.

Antibodies, Monoclonal↗

Solitary plasmacytoma of bone: treatment, progression, and survival.

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

Adult↗

Epithelioid hemangioendothelioma (histiocytoid hemangioma) of the palate.

The first case of epithelioid hemangioendothelioma involving the oropharynx is described. A 25-year-old woman developed a mass on the palate which noted to enlarge during the first trimester of pregnancy. Biopsy revealed a cellular tumor initially considered to be of epithelial origin. Vascular differentiation of the tumor was confirmed, however, by positive lectin histochemistry for Ulex europaeus, by evidence of immunoreactivity for factor VIII-related antigen, and by ultrastructural identification of endothelial features. The patient remains free of tumor 21 months after complete excision. Because of the potential for misdiagnosis, epithelioid hemangioendothelioma should be considered in the differential diagnosis of oropharyngeal malignancies. The effect of pregnancy on the development and growth of vascular tumors such as epithelioid hemangioendothelioma remains uncertain.

Adult↗