Biomarkers of human colonic cell growth are influenced differently by a history of colonic neoplasia and the consumption of acarbose.

The nutritional effects of butyrate on the colonic mucosa and studies of transformed cells suggest that butyrate has anti-colon cancer effects. If butyrate has antineoplastic effects, mucosal growth contrasts between normal subjects and those with a history of colonic neoplasia would parallel changes in growth characteristics caused by butyrate in a colon neoplasia population. To test this hypothesis, rectal biopsies from a survey of colonoscopy patients (n = 50) with and without a history of colonic neoplasia (controls) were compared. Similarly, rectal biopsies were compared from subjects (n = 44) with a colon neoplasia history in an acarbose-placebo crossover trial. Control subjects in the colonoscopy survey had higher bromodeoxyuridine (BrdU) uptake than subjects with a history of neoplasia (P = 0.05). The control subjects also had a higher correlation of BrdU and Ki-67 labeling (P = 0.003). Both findings were paralleled by acarbose use. Acarbose augmented BrdU uptake (P = 0.0001) and improved the correlation of BrdU and Ki-67 labeling (P = 0.013). Acarbose also augmented fecal butyrate (P = 0.0001), which was positively correlated with Ki-67 labeling (P = 0.003). p52 antigen had an earlier pattern of crypt distribution in subjects with a history of colon neoplasia but was not affected by acarbose use. Lewis-Y antigen was expressed earlier in the crypt with acarbose but had similar expression in the colonoscopy survey groups. The use of acarbose to enhance fecal butyrate concentration produced mucosal changes paralleling the findings in control subjects as opposed to those with neoplasia, supporting the concept of an antineoplastic role for butyrate.

Dietary guar gum alters colonic microbial fermentation in azoxymethane-treated rats.

To assess the effects of guar gum on colonic microbial fermentation and cancer development, azoxymethane-treated rats were fed a partially hydrolyzed guar or control diet. Anaerobic fecal incubations were conducted at 8-wk intervals, either without added substrate or with cornstarch or hydrolyzed guar as substrates. Short-chain fatty acids in colonic contents and colonic carcinoma areas were measured at 27 wk. Fecal in vitro fermentation rates were higher for guar-fed rats than for control rats [three-way ANOVA (diet, time, in vitro substrates), P = 0.002]. Fecal in vitro butyrate production was greater for guar-fed rats than for control rats after 3-11 weeks of diet treatment (three-way ANOVA, P = 0.027). Butyrate concentrations of colonic contents at 27 wk were higher in guar-fed than in control rats and higher in the cecum than in the post-cecal colon (two-way ANOVA, P = 0.0001). A regression equation predicting colonic carcinoma area (r2 = 0.279) using propionate and butyrate concentrations of the contents of the post-cecal colon showed propionate as a positive predictor (P < 0.001) and butyrate as a negative predictor (P = 0.033). Our results show that patterns of short-chain fatty acid production may affect the results of fiber-carcinogenesis experiments. Dietary addition of hydrolyzed guar is associated with fecal fermentation low in propionate and high in butyrate; short-chain fatty acid concentrations are greater proximally than distally. These results suggest that butyrate protects against colonic neoplasia, whereas propionate enhances it, and demonstrate that colonic microbiota adapt to produce more butyrate if given time and the proper substrate.

Bronchopulmonary bacillary angiomatosis.

A man with prior AIDS developed acute febrile interstitial pneumonitis, hilar and paratracheal adenopathy, and bronchial polyps. The polyps were histologically typical for bacillary angiomatosis and complete symptomatic and radiographic response to oral clarithromycin was seen. The clinical presentation of bacillary angiomatosis includes pulmonary disease and in particular bronchial polyps; clarithromycin is an effective oral antibiotic.

Peptide YY ameliorates cerulein-induced pancreatic injury in the rat.

Peptide YY (PYY), a known inhibitor of both pancreatic secretion and the release of cholecystokinin (CCK), may play a role in the pathophysiology of acute pancreatitis (AP). Supramaximal stimulation of the pancreas with CCK, or its analogue cerulein, induces edematous AP. We previously documented significant decreases in plasma PYY in sodium taurocholate-induced AP in the anesthetized pig, with exogenous PYY suppressing plasma amylase activity. We hypothesized that PYY may ameliorate cerulein-induced pancreatic injury in a conscious animal model. Thirty-two male Sprague-Dawley rats underwent chronic cannulation of the jugular vein and carotid artery for drug infusion and blood sampling. The animals were allowed to recover from anesthesia for a minimum of 16 hours, after which they were randomized to one of four (n = 8) treatment groups (cerulein 10 micrograms/kg/h, PYY 400 pmol/kg/h, cerulein+PYY, and control-saline 2 mL/kg/h). All treatments were administered by intravenous infusion over the first 6 hours of the experiment. Blood samples were taken prior to infusion and at 1, 3, 6, 9, and 24 hours into the study; the rats were then killed and the pancreata removed for weighing and histologic examination. All pancreatic specimens were graded in a blinded fashion for vacuolization, edema, inflammation, and necrosis. The mean basal plasma amylase level for all animals was 1,171 +/- 100 U/L and was not significantly different between groups. Infusion of cerulein resulted in significant increases in plasma amylase levels at 3, 6, 9, and 24 hours (4,827 +/- 1,022 U/L at 24 hours). In the group receiving both cerulein and PYY, the hyperamylasemia was attenuated with a return to basal values at 24 hours (1,206 +/- 103 U/L). There was significant pancreatic weight gain (1.99 +/- 0.07 g versus 1.03 +/- 0.07 g) and a worsened histologic picture in cerulein-treated animals compared with control animals (worsened edema, necrosis, and vacuolization). The addition of PYY to cerulein resulted in significantly lower pancreatic weight (1.27 +/- 0.11 g) than in the non-PYY-treated rats receiving cerulein. Pancreatic weight was not significantly different in this group compared with the control group. In addition, pancreatic histologic findings were significantly improved in those rats receiving PYY (decreased vacuolization and necrosis). Amylase levels, pancreatic weight, and morphologic findings were not significantly changed compared with basal values in the control or PYY alone treated groups. e conclude that as an inhibitor of pancreatic exocrine secretion, PYY ameliorates cerulein-induced pancreatic injury in the conscious rat.

Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease.

BACKGROUND: Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. METHODS: Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. RESULTS: Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. CONCLUSIONS: The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC.

Immunohistochemical analysis of small cell tumors of the thyroid gland: an Eastern Cooperative Oncology Group study.

The majority of small cell anaplastic tumors of the thyroid gland are generally believed to be non-Hodgkin's lymphomas, including most of those formerly classified as small cell carcinomas. Using a panel of antibodies capable of detecting epithelial, neuroendocrine, and B and T cells in paraffin-embedded tissue sections, we studied 68 thyroid neoplasms in which the original diagnosis was small cell carcinoma or lymphoma. Sixty-three of the tumors were identified as lymphomas of B-cell origin on the basis of L26 reactivity used in conjunction with light chain restriction and MB2 immunostaining. Two additional tumors were classified as lymphomas of indeterminate phenotype. Immunophenotyping indicated an epithelial origin in the remaining three tumors. No cases of medullary carcinoma were detected by immunostaining. Histologic review revealed a predominance of large cell and immunoblastic lymphomas, with low-grade lymphomas of mucosa-associated lymphoid tissue histology accounting for only five cases. Our findings indicate that the majority of small cell anaplastic tumors of the thyroid are B-cell lymphomas. Although primary small cell carcinoma of the thyroid may rarely occur, this diagnosis should not be made without immunohistologic confirmation.

Antigen diffusion and uptake: a caveat in immunohistochemical interpretation.

Thyroglobulin was demonstrated by monoclonal immunohistochemistry in the cytoplasm of renal cell carcinoma cells metastatic to the thyroid gland. This was attributed to release of thyroglobulin from injured native thyroid with diffusion and uptake by tumor cells. Previously reported cases of this process in tumors in thyroid, skeletal muscle, and lymphoid tissue are reviewed. Interpretation of the significance of demonstrated antigens in tumor cells, especially those that are constituents of invaded native tissues and only focally present, should be interpreted with caution and in conjunction with other histologic evidence.

Primary lymphoma of the penis with rationale of treatment.

Appropriate care of a patient with primary lymphoma of the penis requires consideration of the diagnoses, thorough evaluation, and knowledge of the various therapeutic approaches. A patient is presented with brief review of similar cases together with the rationale for the use of radiation therapy and chemotherapy rather than surgery.

Malakoplakia of the prostate.

Malakoplakia of the prostate is a rarely reported granulomatous inflammatory disorder which may clinically mimic carcinoma of the prostate gland. A case of a 70-year-old man, with long follow-up, is reported. Histologic diagnosis allows for effective antibiotic treatment.

Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.

Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.

The effect of tamoxifen on cervical squamous maturation in Papanicolaou stained cervical smears of post-menopausal women.

Using cervical smears obtained as part of routine gynaecological examinations, a retrospective study of the effects of the drug tamoxifen on squamous epithelial maturation of the cervix of post-menopausal women being treated for advanced breast cancer was made. The degree of squamous epithelial maturation was quantitated by using the Maturation Index and the Maturation Value. Although tamoxifen is a synthetic, non-steroidal compound classified as anti-oestrogenic, the findings indicate that this drug commonly produces a level of squamous maturation indicative of oestrogenic stimulation in Papanicolaou stained cervical smears from post-menopausal patients receiving this drug. Knowledge of the oestrogenic effect of tamoxifen in the cervix can obviate clinical concern about endometrial carcinoma.

An improved method of cell recovery following bronchial brushing.

Cytologic examination of bronchial brush specimens is effective in diagnosing bronchogenic carcinoma. A major problem is loss of cells and cellular detail associated with the direct smear technique (DST). A more recent method, the Saccomanno brush wash (SBW), uses a narrow-mouthed vial to scrape cells off the brush directly into fixative. We sampled 12 directly visualized airway tumors using standard brush technique. The same brush was then agitated in a SBW vial, which was centrifuged, the cell pellet being smeared over a predetermined area of a slide. Designated areas of each slide were counted and total malignant cells per slide extrapolated. DST slides had significantly fewer cells than SBW slides, and cellular detail was better with SBW in seven cases, DST in one case, and equal in four cases. SBW appears preferable for handling of bronchial brush specimens.

Inflammatory pseudotumor of the spleen.

Inflammatory pseudotumor of the spleen, an extremely rare benign inflammatory mass lesion, which clinically and radiologically mimics a neoplasm, is presented. The case is compared to the two cases previously reported in the literature. Possibilities of etiology and pathogenesis are considered.

Scrotal lymphangioma.

Congenital malformations of the intrascrotal lymphatic system may form cystic masses. A case of a lymphangioma arising in Colles fascia is presented. This rare clinical entity should be included in the differential diagnosis of cystic lesions of the external male genitalia. Total surgical excision is the treatment of choice.