Nuclear feulgen DNA content and nuclear size in human breast carcinoma.

Biopsy specimens from 29 patients with operable breast carcinomas were examined by Feulgen-DNA microspectrophotometry. A diploid DNA stemline was found in ten tumors, seven of which were stage I carcinomas. In 19 tumors, ten of which were stage II cancers, a non-diploid DNA stemline was observed. The diploid tumors were most often estrogen receptor-positive (nine of nine examined carcinomas), whereas 13 of 19 non-diploid tumors studied did not contain estrogen receptors. The mean nuclear size of the non-diploid tumor cells was increased compared with that of the diploid malignant cells. Three grade I carcinomas were diploid, whereas three grade III tumors were non-diploid. Of the 23 grade II carcinomas, seven were diploid and 16 non-diploid. Hum Pathol 13:626-630, 1982.

Characterization of bladder tumours by multiparameter flow cytometry with special reference to grade II tumours.

Sixty-three human transitional cell carcinomas of the urinary bladder were studied by multiparameter flow cytometry (FCM). The cellular DNA content, the cellular protein content, the fraction of cells in S phase, and the nuclear size were registered and correlated to histological grade (WHO) and histologically determined infiltration through the basement membrane. Aneuploidy was found in the great majority of grade III tumours, but in only 24% of grade II tumours. A new, combined variable, viz. the cellular DNA to protein ratio, indicated a possibility for further subdivision of the tumours. Grade II tumours, which constitute a rather heterogeneous group with regard to prognosis, could be classified in two subgroups: One group of diploid tumours with the FCM characteristics of grade I tumours, and another group of diploid and aneuploid tumours with the characteristics of grade III tumours. Infiltration was most frequently seen in the latter subgroup. The putative prognostic relevance of such a subdivision will be the subject of a future study. Compared to FCM measurement of DNA alone, multiparameter FCM, including measurement of the total cellular protein content, has given additional information that may be of prognostic value.

[Tetracycline sclerotherapy of hydroceles and spermatoceles]. / Tetracyklinsklerosering av hydroceler og spermatoceler.

40 patients were treated by aspiration and instillation of a 10% solution of tetracycline. 32 were cured after average 1.45 instillations. The dominating adverse effect was scrotal pain, reported by 55% of the patients. One patient experienced a transient vasovagal reaction due to the pain, and one patient was suspected of having a slight infection. No other adverse effect was registered, and 90% of the patients would prefer to have the same treatment rather than an operation if another treatment were found necessary. The treatment is given as an outpatient procedure at 1/10 of the cost of traditional operative treatment, and with comparable results.

Sarcoma following irradiation for breast cancer. Report of three unusual cases including one malignant mesenchymoma of bone.

Three cases of sarcoma developing after irradiation for breast cancer are reported. A malignant mesenchymoma in the sternum--a combination of osteogenic sarcoma and rhabdomyosarcoma--is the first documented case of its kind occurring after radiation therapy. Of the other two tumors one was an extraskeletal osteogenic sarcoma in the soft tissues of the thoracic wall and one a rhabdomyosarcoma in the axilla.

[Meckel's diverticulum. Symptoms, diagnosis and treatment]. / Meckels divertikkel. Symptomer, diagnose og behandling.

Meckel's diverticulum is a rare, but serious cause of acute abdominal pain. The prevalence of Meckel's diverticulum is 2% and lifetime risk of illness in a diverticulum is 4.2%. The risk declines with age and approaches zero after the age of 70. Morbidity after resection of symptomatic Meckel's diverticulum is 11.1-17.6% with 6.0-7.5% mortality. The morbidity rate for resection of incidentally discovered diverticulum is 1.2-8.9%. Symptoms and complications are related to age. Below the age of one year the most prevalent complication is gastrointestinal obstruction. Later in childhood the most dominating complication is peptic ulcer with serious gastrointestinal bleeding, while various kinds of gastrointestinal obstruction and diverticulitis are most prevalent in adults. The treatment of symptomatic Meckel's diverticulum is resection. However, the treatment of incidentally discovered Meckel's diverticulum is a subject of dispute. After a thorough study of the literature we conclude that resection should be the routine for all incidentally discovered Meckel's diverticulums in persons younger than 40. After this age resection should be reserved for patients with palpable stigmata of heterotopic tissue, diverticulums of some length and the presence of omphaloenteric- or omphalodiverticulare chords.

Tamsulosin, a selective alpha 1c-adrenoceptor antagonist: a randomized, controlled trial in patients with benign prostatic 'obstruction' (symptomatic BPH). The European Tamsulosin Study Group.

OBJECTIVE: To evaluate the efficacy and safety of tamsulosin 0.4 mg once daily (as a modified-release formulation) compared with placebo in patients with benign prostatic enlargement, lower urinary tract symptoms and prostatic 'obstruction' (symptomatic benign prostatic hyperplasia [BPH]). PATIENTS AND METHODS: Of 313 patients with symptomatic BPH enrolled in a 2-week placebo run-in period, 296 were subsequently randomized to receive either placebo (98 patients) or tamsulosin 0.4 mg once daily (198 patients) for 12 weeks. The primary variables assessed to determine efficacy were maximum urinary flow rate (Qmax) from free-flow measurements and the total Boyarsky symptom score. RESULTS: Tamsulosin produced greater improvements in Qmax (1.4 mL/s, 13.1%) than did placebo (0.4 mL/s, 3.8%) (P = 0.028) and a greater decrease in total symptom score (3.4 points, 35.8% reduction) than did placebo (2.2 points, 23.7% reduction) (P = 0.002). Significantly more tamsulosin-treated patients (67%) than placebo-treated patients (44%) had a > or = 25% decrease in total symptom score after 12 weeks (P < 0.001). Treatment with tamsulosin for 12 weeks also produced significant improvements in average urinary flow rate (P = 0.040), irritative (P = 0.013) and obstructive (P = 0.014) symptom scores and symptoms of nocturia (P = 0.022) and hesitancy (P = 0.004). Tamsulosin was tolerated well by the patients. The incidence of adverse events emerging during treatment was comparable in the tamsulosin- and placebo-treated groups (34% and 24% respectively, P = 0.109), as was the incidence of cardiovascular-related adverse events (5% and 7% respectively; P = 0.596). There were no significant differences in changes in blood pressure or pulse rates between the tamsulosin- and placebo-treated groups. CONCLUSION: Tamsulosin 0.4 mg once daily is safe, well tolerated and clinically effective in improving symptoms and urinary flow rate in patients with symptomatic BPH.

A complete pyelo-uretero-vesical duplication.

A complete pyelo-ureteral duplication with a palpable pelvic mass giving urinary infection and a slight urinary incontinence is reported. An intravenous pyelography demonstrated that the renal calyces on the left side were reduced in number compared to those present on the right side. Renal resection and a pyelo-ureteral resection was performed. A brief survey of the embryological basis for this anomaly is presented.

DNA cytometry of primary breast cancer. Comparison of microspectrophotometry and flow cytometry, and different preparation methods for flow cytometric measurements.

In 18 biopsy specimens from human breast carcinoma a comparison was made between DNA measurements obtained by microspectrophotometry (MSP) of Feulgen-stained nuclei in imprints and flow cytometry (FCM) of nuclei stained with ethidium bromide. For each specimen FCM was performed both with ethanol-fixed cells and unfixed cells. In addition, single cell suspensions were made from other 11 fresh mammary cancer biopsies. Parts of these suspensions were analysed both by MSP (Feulgen-stained smears) and FCM (ethanol-fixed, mitramycin-stained cells). The MSP histograms show selected tumour cells and tumour-like cells. This explains the higher proportion of cells with DNA content above the 2 c level. A good agreement was found between the results obtained by MSP and FCM with regard to the ploidy of the DNA stemline(s). FCM of fixed cells (multiple-step procedure) yielded a slightly lower proportion of diploid cells than FCM of the unfixed cells (one-step procedure), probably owing to loss of small cells during the different preparation steps. It is concluded that the results from DNA-histograms obtained from MSP and FCM can be compared as to DNA-stemline ploidy of the cell population but not as to the proportion of cells with non-diploid DNA-content.

Epirubicin combined with estramustine phosphate in hormone-resistant prostate cancer: a phase II study.

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EMP), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m(-2), every third week up to a cumulative dose of 500 mg m(-2). Biochemical response [> or = 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of > or = 3 weeks' duration] was demonstrated in 13 of 24 patients included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a > or = 50% serum PSA reduction. Subjective improvement (pain score, performance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (> or = 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 months for surviving patients (range 3.3-13.2). Eight patients experienced grade 3/4 leucopenia, with no indication of cumulative myelosuppression. Cardiovascular toxicity was experienced by four patients. Two patients developed angioedema twice, in one patient requiring hospitalization at the intensive ward. Based on this limited series, the combination of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warrant further investigations of the two drugs and, in particular, of the clinical significance of > or = 50% PSA decrease in patients with HRPC.

The adhesiveness of blood platelets before, during and after cardiopulmonary bypass.

The influence of cardiopulmonary bypass on the adhesiveness of blood platelets, using both bubble (Bentley and Rygg-Kyvsgaard) and membrane (Landé-Edwards) oxygenators, was investigated. With both types of oxygenators, there was a considerable fall in platelet adhesiveness during cardiopulmonary bypass, particularly with the Rygg-Kyvsgaard apparatus. The adhesiveness increased 30 minutes after bypass, but it was still not restored to the initial value.

Colony growth and chemosensitivity in vitro of human melanoma biopsies. Relationship to clinical parameters.

To study the usefulness of an in vitro colony-forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty-seven per cent of the tumors gave PEs greater than 1%, 45% gave PEs in the range 0.1-0.9%, whereas 11% of the tumors gave 0.01-0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay greater than 2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.

Studies on urinary bladder carcinoma by morphometry, flow cytometry, and light microscopic malignancy grading with special reference to grade II tumours.

Biopsies from 28 patients with urinary bladder carcinoma were investigated by flow cytometry and morphometry. Histopathological grading on 1.5 microns thick glycol methacrylate sections was also performed. Nuclear profile areas, nuclear volume densities and mitotic indices were usually larger in the higher grades of malignancy. All grade I tumours were diploid and all grade III tumours were aneuploid. Out of 13 grade II tumours 8 were diploid and 5 aneuploid. In these latter five cases nuclear profile areas were at the high end of the spectrum. The data show that flow cytometry and morphometry could be a valuable tool in the diagnosis of urinary bladder carcinoma. Our data also suggest that a subdivision of the grade II tumours might be possible and meaningful in the assessment of prognosis.

Does prophylactic breast irradiation prevent antiandrogen-induced gynecomastia? Evaluation of 253 patients in the randomized Scandinavian trial SPCG-7/SFUO-3.

OBJECTIVES: To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. METHODS: In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). RESULTS: Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P <0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P <0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P <0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked "very much" on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors' and patients' detection of breast problems was observed. CONCLUSIONS: The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness.

[Antibiotic prophylaxis in diagnostic and therapeutic urological interventions]. / Antibiotikaprofylax vid diagnostiska och terapeutiska urologiska ingrepp.

An enquiry into the use of antibiotic prophylaxis in conjunction with diagnostic or therapeutic urological procedures at hospitals in four Scandinavian countries showed manifest national differences to exist for most procedures. In transurethral resection, for instance, antibiotic cover was used at 79 percent of Finnish hospitals, but at only nine percent of Danish hospitals. Not only were dosage regimens characterized by wide national variation, but also the spectrum of antibiotics used, quinolones being most frequently used in Sweden, but ampicillin and pivampicillin in Denmark. For some procedures policy was more uniform in all countries, antibiotic cover rarely being used in connection with ureterocystoscopy (5 percent of hospitals), but often in conjunction with percutaneous stone surgery (72 per cent). In certain procedures where there is strong evidence suggesting the necessity of antibiotic prophylaxis, it was not always used-e.g., in transrectal prostate biopsy where it was used at only 62 per cent of hospitals. The interpretation of published findings and clinical experience would appear to differ markedly, and local traditions would seem to be strong determinants of clinical routines. The wide variation suggests that all patients do not receive optimal treatment. To improve routines, our knowledge of antibiotic preparations needs to be expanded by well executed studies, followed by general implementation of the results at the various centres. A series of consensus conferences should be arranged and the recommendations published as a first step toward a more uniform and probably better use of antibiotic prophylaxis in conjunction with diagnostic and therapeutic urological procedures.

Treatment of high-grade, high-stage prostate cancer with estramustine phosphate or diethylstilbestrol. A double-blind study. The SPCG-1 Study Group. Scandinavian Prostate Cancer Group.

Between 1984 and 1989, 197 patients with T1-4, NX, M1, G2-3 or G3 prostate cancer were randomized to treatment with 560 mg estramustine phosphate (EMP, Estracyt, Emcyt) or 3 mg diethylstilbestrol (DES) per day in a double blind study with stratification on presence or absence of cancer pain at start. A total of 194 patients were evaluated for efficacy of therapy. Time to progression (p = 0.054), to treatment failure (p = 0.036), cancer-specific survival (p = 0.068) as well as overall survival (p = 0.021) were longer in the DES group. There were more patients with prognostic parameters indicating bad prognosis in the EMP group. This trial was designed to study whether EMP had better effect than DES as the primary treatment of high-grade, disseminated prostate cancer. The results did not confirm this hypothesis. On the contrary, treatment with DES had relatively good effect on this very aggressive form of prostate cancer.

Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. Analysis of a multinational, multicentre, open-label study assessing the long-term efficacy and safety in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group.

OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with benign prostatic enlargement, lower urinary tract symptoms and benign prostatic obstruction (symptomatic BPH) for up to 60 weeks. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This 60-week interim analysis includes the patients (n = 244) randomized to tamsulosin in the two placebo-controlled trials. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Qmax) and total Boyarsky symptom score, that were observed during the placebo-controlled trials, were sustained throughout the long-term extension study. Mean Qmax improved from baseline (before initiation of tamsulosin) to endpoint by 13.7% (p < 0.001) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score improved by 36.2% from baseline to endpoint (p < 0.001). Similarly, the percentage of treatment responders, defined as an increase in Qmax of > or = 30% or a decrease in total symptom score of > or = 25%, remained constant throughout the 60-week period. At endpoint, 69% of patients demonstrated this clinically significant total Boyarsky symptom score response. During the 60-week study period, 51 patients (21%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which were dizziness and abnormal ejaculation, both occurring in 5% of patients. There were no clinically significant changes in blood pressure or pulse rate during the study. CONCLUSION: Long-term tamsulosin therapy is safe, well tolerated and improvements in urinary flow and symptoms are maintained for at least 60 weeks of treatment.

Primary breast cancer. Flow cytometric DNA pattern in relation to clinical and histopathologic characteristics.

Cell suspensions of 59 primary operable mammary carcinomas in women were subjected to flow cytometric DNA analyses. The results were correlated to histopathological grading, clinical staging, menopausal status and estrogen receptor status. Thirty-two tumors showed a DNA peak above +25% of murine lymphocyte level and were named distinct aneuploid (AN). Twenty-seven tumors did not show such a peak and were named near diploid (ND). Low histopathological malignancy grade was associated with a high frequency of ND tumors (P less than 0.05). Small tumors (T1) were predominantly ND (14/19), while larger tumors (T2-3) showed a high frequency of AN tumors (27/40) (P less than 0.01). Tumors occurring in post-menopausal women were often AN, while those arising in premenopausal women were frequently ND (P less than 0.06). No clear correlation was found between the DNA ploidy pattern and estrogen receptor status. There was a tendency that patients with AN tumors had a higher frequency of relapses during the first 4-5 years of follow-up than those with ND breast carcinomas.

Tamsulosin: 3-year long-term efficacy and safety in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction: analysis of a European, multinational, multicenter, open-label study. European Tamsulosin Study Group.

OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) treated for up to 3 years. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This analysis reports on 355 patients randomized originally to tamsulosin (n = 244) or placebo (n = 111) in the two placebo-controlled trials with follow-up data for up to 3 years. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Q(max)) and total Boyarsky symptom score that were observed during the placebo-controlled trials were sustained throughout the long-term extension study for up to 3 years in patients who remained on therapy. Mean Q(max) increased from baseline (range 0.7-1.8 ml/s; p < 0.05 vs. baseline) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score also improved from baseline (range -3.7 to -4.1 (or -39 to -44%); p < 0.001 vs. baseline). Similarly, the percentage of treatment responders, defined as an increase in Q(max) of >/=30% or a decrease in total symptom score of >/=25%, remained constant throughout the 3-year period. The number of patients who had a clinically significant total Boyarsky symptom score response ranged between 69 and 80%. During the 3-year study period, 95 patients (27%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which (occurring in

Delineation of subsets in human B-cell lymphomas by a set of monoclonal antibodies raised against B lymphoma cells.

Murine hybridoma antibodies to a human B-cell lymphoma were developed. After screening against normal T cells, monocytes, and granulocytes 11 antibodies that reacted with cells from other B-cell lymphomas remained, of which 10 showed individually distinct staining patterns, as tested by indirect fluorescence. When tested against lymphomas or cell lines, none of these antibodies revealed staining patterns suggesting reactivity with conventional B-cell surface markers, such as immunoglobulin, complement factor 3 receptors, or HLA-DR antigens. Only one of the antibodies (GB1) reacted with human serum, as determined by a blocking assay. The antibodies were found to belong to different immunoglobulin isotypes. Two antibodies (GB13 and GB14) reacted with greater than 5% of normal peripheral blood mononuclear cells. These reactions were mainly due to reactivity with B cells. The antibodies reacted only in a few cases with acute leukaemias, B-cell lines, and follicular lymphomas. On the other hand, distinct patterns of reactivity in different histological groups of diffuse lymphomas were obtained, suggesting that the antibodies may be useful in delineating phenotypic subsets among human B-cell lymphomas.

Cultivation of human breast carcinoma in soft agar. Experience with 237 fresh tumour specimens.

A total of 237 breast carcinomas have been studied with the Courtenay-Mills (C-M) soft agar method. Cell yields and plating efficiencies (PE) were recorded after various enzyme treatments. The highest cell yields and PEs were obtained with the combination of collagenase 0.5%, hyaluronidase 1000 IE ml-1 and DNase 0.1% and an incubation time of 2 h. Eighty percent of the specimens gave greater than 10 colonies, and 60% formed greater than 30 colonies permitting chemosensitivity studies. The C-M method gave significantly higher PEs than the Hamburger-Salmon (H-S) method. Hormone supplements (insulin, oestradiol, progesterone, hydrocortisone) and also reduced agar concentrations (less than 0.3%) gave marginal stimulation of colony formation. In chemosensitivity studies involving doxorubicin, vincristine and 4-OOH-cyclophosphamide, the C-M method gave dose-response relationships without plateaus.