TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE STAINING OF MALIGNANT LYMPHOMAS IN PARAFFIN SECTIONS: A USEFUL METHOD FOR THE DIAGNOSIS OF LYMPHOBLASTIC LYMPHOMA

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3′ hydroxyl ends of oligo- or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno-fluorescence or -peroxidase staining. Until the recent development of the use of microwave-treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non-endemic Burkitt's lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T-cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T-cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT-positive. The specificity of the anti-TdT antibody used was confirmed by immunoblot and the specific 60 kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin-embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service. © 1997 John Wiley & Sons, Ltd.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.     

Chronic Toxicity Carcinogenicity Studies of Triethanolamine in B6C3F1 Mice

The chronic toxicity and carcinogenic potential of triethanolaminewas examined in B6C3F1 mice. Triethanolamine, dissolved in distilledwater at levels of 0 (control), 1, and 2%, was given to groupsof 50 males and 50 females ad libitum in drinking water for82 weeks. Neoplasms developed in all groups, including the controlgroup, but no dose-related increase of the incidence of anytumor was observed in treated groups of both sexes. There wereno adverse effects as regards survival of the mice, organ weights,and specific incidence of neoplasms in the treated, comparedto the control group. This chronic toxicity test provides noevidence of carcinogenic potential of triethanolamine in B6C3F1mice.     

Usefulness of contrast-enhanced ultrasound for the diagnosis of recurrent renal cell carcinoma in contralateral kidney

We studied contrast-enhanced ultrasound (CEU) for recurrence of renal cell carcinoma (RCC) at the contralateral kidney during postoperative follow up of localized renal cell carcinoma. CEU successfully detected all recurring cases, despite the fact that 5/6 cases were observed using conventional ultrasound; the remaining one case was not detected using conventional ultrasound. CEU using Levovisto successfully revealed renal tumors as RCC. Lesions were diagnosed as cystic renal tumors by Bosniac classification, and pathological findings demonstrated RCC, in accordance with the prior tumor.     

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide

Background and Aim: Controversies remain over the need for antiulcer treatment following 1‐week eradication triple therapy for Helicobacter pylori‐positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. Methods: The study was conducted in 52 H. pylori‐positive patients with an endoscopically‐proven open gastric ulcer. All patients received 1‐week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7‐week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and ¹³C‐urea breath test. Results: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non‐eradicated patients. The overall gastrointestinal symptom‐free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. Conclusions: The results suggested that the combination therapy for open gastric ulcer was safe, well‐tolerated and effective. However, data from a double‐blind placebo‐controlled study is necessary to confirm these findings.     

Two Cases of Malignancy-Associated Hypercalcemia Treated with Mithramycin

The hypocalcemic effect of mithramycin, an antitumor antibiotic,was studied in two consecutive hypercalcemic patients with malignancy.Case 1 was a 60-year-old woman with advanced breast cancer.Severe, generalized bone metastasis seemed to be the cause ofthe hypercalcemia. Serum calcium levels reached 14.6mg/dl (ionizedcalcium 3.84 mEq/I) despite continued therapy with saline (5liters/day) with frosemide (60mg/day, intravenously), high dosesof elcatonin (up to 440 MRC units/day) and prednisolone (30mg/day). Case 2 was a 49-year-old woman with recurrence of ovariancancer. Bone metastasis was not found on X-ray films. Hypercalcemiawas progressive in spite of extensive treatments with saline(2 liters/day) with frosemide (40 mg/day), indomethacin (150mg/day), elcatonin (160 MRC units/day) and prednisolone (30mg/day). Meantime, serum calcium rose to 14.6mg/dl (ionizedcalcium 3.57 mEq/I). In both cases, mithramycin (1.25 mg) wasthen administered intravenously. Serum calcium levels droppedto 9.6 and 9.4 mg/dl two days after the administration of mithramycinin case 1 and case 2, respectively. These observations indicate that mithramycin is more effectivethan any other drug tested for the treatment of hypercalcemiacaused by malignancy irrespective of the presence or absenceof bone metastasis. Therefore, it should be widely used forhypercalcemic emergency.     

A Case of Small Cell Carcinoma of the Lung Producing ADH, ACTH, MSH and Calcitonin: Successful Treatment of Severe Hyponatremia with Furosemide and Hypertonic Saline

A 48-year-old man with a small cell carcinoma of the lung presentedhyponatremia and was diagnosed as having the syndrome of inappropriateADH secretion. A plasma ADH bioassay confirmed this syndrome.During the clinical course, the patient developed a hyponatremiccrisis with a serum sodium of 108mEq/l. His hyponatremia wasrapidly corrected by infusing furosemide in conjunction withhypertonic saline. The postmortem studies demonstrated ADH bioactivityin the tumor tissues, as well as immunoreactive ACTH, ß-MSHand calcitonin. Tumor hypersecretion of ACTH appeared to bethe cause of the patient's hyperresponsiveness to exogenousACTH and of the bilateral adrenocortical hyperplasia observedat the time of autopsy. Therefore, this was a case of a multiple hormone-producing smallcell carcinoma of the lung, in which the severe clinical manifestationsof SIADH were successfully treated with furosemide and hypertonicsaline.     

Tamoxifen in Advanced Breast Cancer; Response Rate, Effect on Pituitary Hormone Reserve and Binding Affinity to Estrogen Receptor

Patients with advanced breast cancer were treated with antiestrogen,tamoxifen, 20 mg orally, twice a day. Of the evaluable 23 patients,one achieved complete response with a duration of 16 months,and five achieved partial response lasting from two to eightmonths, indicating that the response rate was 26%. In the fiveperi-and postmenopausal patients, basal and LH-RH stimulatedplasma LH levels decreased but stayed within the postmenopausalrange in three patients during the tamoxifen therapy. Basaland LH-RH stimulated FSH levels decreased also but stayed withinthe postmenopausal range in all five patients. In a premenopausalpatient, basal and stimulated plasma LH and FSH levels did notchange significantly during the tamoxifen therapy. The plasmaTSH responses did not change significantly. In three of thesix patients, basal and TRH-stimulated prolactin levels decreasedslightly during the tamoxifen therapy. These relatively inconsistentand small changes in the pituitary hormone secretion observedduring the tamoxifen therapy suggest that the anti-tumor effectof tamoxifen was not due to alteration of the pituitary hormonesecretion. The binding of tamoxifen for the estrogen receptorwas examined in the estrogen receptor assay system. The doseresponse curve for tamoxifen was parallel to that for estradiol,indicating that tamoxifen competes with estradiol for the estrogenreceptor. The affinity constants of tamoxifen for the estrogenreceptor in eight cytosols of human breast cancer tissues were(139 ±79) X 10^–10M (mean±SD), indicatingthat the binding affinity of tamoxifen was about 0.7% that ofestradiol. The affinity constants for nuclear receptors weresimilar to those for cytosol receptors. These data suggest thattamoxifen is a useful drug for treatment of advanced breastcancer, and that the anti-tumor effect could be related to itsbinding to estrogen receptors in tumor tissues, and not causedby altering the secretion of pituitary hormones.