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Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 19 recordsLinked to original sources

The association of benign prostatic hyperplasia and cancer of the prostate.

There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.

Adult

Prostatic intraepithelial neoplasia (PIN): current concepts.

Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts, ductules and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered to be a precursor to invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterized by basal cell layer disruption, basement membrane disruption, progressive loss of secretory differentiation markers, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognizing PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma.

Adult

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