The role of repeated biopsies in prognosis of prostate cancer

INTRODUCTION: The treatment of prostate cancer is still controversial. One of the most common treatment form is the use of LHRH analogs, but its way of action is still not cleared enough. AIMS: The aim of this study was to determine the predictive value of some histological and immuno-histochemical parameters based on repeated biopsies taken from prostate carcinoma patients. PATIENTS/METHOD: At the time of diagnosis by needle biopsy the TNM stage, serum PSA level, Gleason's grade, apoptotic and mitotic index, as well as Ki67, p53 and bcl2 expression were investigated in 60 prostate carcinoma patients. Anti-androgen therapy supplemented with surgical or chemical castration (with LHRH analogs) was administered. Serum PSA-test and needle biopsy were repeated 13-14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53 and bcl2 expression. RESULTS: Forty-seven patients were alive at the end of the study (average 23.46 +/- 8.6 months) and thirteen patients died (average 25.3 +/- 14.8 months). Initial TNM stage and Gleason's score proved to be of prognostic value. Decrease in mitotic index and increase in apoptotic index during therapy proved to predict favourable long-term response to androgen ablation therapy. Similarly, lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to a favourable effect of antiandrogen and especially of LHRH analog treatment. Since the ratio between Ki67 percentage and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio may be recommended as a histologically detectable predictive factor. However, bcl2 expression did not show significant correlation with the outcome of the disease. CONCLUSION: Histological evaluation of parameters such as mitotic and apoptotic index as well as Ki67 and p53 expression in repeated biopsies during treatment may contribute to predicting the value of the actual treatment and may be useful to institute alterations in therapy.     

Tumor-like tracheal and lung diseases in biopsy samples

Tumor like miscellaneous lung diseases are rare conditions. They can be confused with benign and malignant tumors. We describe the clinicopathological features some of this conditions i.e.: two cases of osteoplastic tracheopathy, one inflammatory tracheal polyp, two cases of tumor mimicking foreign body aspiration, and one case of tracheobronchial amyloidosis.     

Amyopathic dermatomyositis

Dermatomyositis is a systemic autoimmune disease which belongs to the group of idiopathic inflammatory myopathies. The disease is rare with an incidence of 0.1-1/100,000 and a prevalence of 1-6/100,000. Women are affected twice as often as men. In some patients the disease presents with dermatologic changes weeks to months before the myopathy arises. It was observed that in some patients the myositis develops much later and sometimes not at all. Therefore, the term of dermatomyositis sine myositis used in earlier literature has been changed to amyopathic dermatomyositis. The most important question is whether the patient needs systemic therapy with its possible side effects yet possibly preventing the appearance of myositis or only local therapy for the skin manifestations is necessary. The goal of this article is to summarize the latest findings in amyopathic dermatomyositis.     

Activation of the 10-Hz sympathetic generator during the second phase of severe hypoxia-hypercapnia and Cushing reaction

Under urethane anesthesia, as in freely moving cats, the sympathetic nerve discharge (SND) contains a 10-Hz component, either as a single peak in the autospectra or in addition to the cardiac-related or 2-6-Hz rhythm. In this study, we examined the changes in these rhythmic SND components during the reaction to asphyxia and to sudden elevation in the intracranial pressure (Cushing reaction). In all cats included in this study, resting SND was dominated by 2-6-Hz rhythm, but a peak at 10 Hz was also present in the coherence functions. During asphyxia or Cushing reaction, the 2-6-Hz component exhibited the usual two-phase pattern of activation followed by suppression. In phase 2, however, the SND did not desynchronize, as in chloralose-urethane anesthetized cats [Am. J. Physiol. 256 (1989) R120; J. Physiol. (London) 469 (1993) 37], and the massive SND activation and the resulting pressor reaction was due to strengthening of the 10-Hz rhythm. After the ischemic reaction, the 10-Hz component diminished and 2-6-Hz rhythm recovered. These findings suggest that two-phase response to hypoxia-hypercapnia is not due to hypoxic neuronal damage but represents a physiological sympathetic reaction involving different patterns of SND.     

A fully recombinant partial prothrombin complex effectively bypasses fVIII in vitro and in vivo

The development of inhibitory antibodies is a serious complication in hemophilic patients, severely compromising therapeutic success. Bleeding episodes in affected patients are controlled by treatment with a plasma-derived prothrombin complex concentrate (PCC), activated PCC (APCC) or recombinant activated factor VII. We hypothesized that a recombinant two-component agent consisting of recombinant prothrombin (rfII) and activated factor X (rfXa) would have substantial fVIII bypassing activity and could be a safe alternative therapeutic option. To test this hypothesis we assembled an agent in vitro solely consisting of rfII and rfXa at a molar ratio of 37,500:1. These factors are believed to be responsible for the activity of APCC preparations. Recombinant fX, used as the source for fXa generation, and rfII were purified from serum-free and protein-free conditioned media of stably transfected CHO and BHK tissue culture cells, respectively. Activation of rfX to rfXa was accomplished by the plant protease ficin, obviating the need for a protease derived from a human or animal source. We found that in vitro the complex reduced the abnormally prolonged activated partial thromboplastin time (APTT) of a high-titer fVIII inhibitor plasma similar to an APCC preparation. Furthermore, addition of increasing amounts of rfII/rfXa to inhibitor plasma resulted in a linear dose-dependent increase in the rate of thrombin generation. In a rabbit fVIII inhibitor model, treatment with rfII/rfXa statistically significantly reduced the intensity of the abnormal cuticle bleeding. In the Wessler test, rfII/rfXa showed no thrombogenicity. These data show that a well-defined, particularly safe and efficacious agent with fVIII bypassing activity can be generated from recombinant fII and fXa.     

Effect of some new thioglycosides on endotoxin-induced disseminated intravascular coagulation in rabbits

Disseminated intravascular coagulation (DIC) is a systemic thrombohemorrhagic disorder seen in association with many clinical situations, e.g. sepsis, malignancy, obstetrical complications and intravascular hemolysis. In our model, disseminated intravascular coagulation was induced in rabbits by two consecutive intravenous bolus injections of endotoxin from Escherichia coli, 80 and 40 μg/kg. The control group was treated with 0.9% saline. The activity of thioglycosides was compared to unfractionated heparin (UFH) and efegatran with and without administration of endotoxin. Drugs were administered in the following doses: heparin 50 and 100 IU/kg/h i.v. infusion; efegatran 0.25 and 0.5 mg/kg/h i.v. infusion; GYKI 39521 (RGH-1875) as well as GYKI 39541 (RGH-1962) 12.5 and 25 mg/kg per os. Thioglycosides did not modify coagulation parameters in this model [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT)] as compared with endotoxin/vehicle group. The changes in TFPI level after administration of thioglycosides and heparin were similar in the mentioned model to those without endotoxin. Endotoxin-induced changes of leukocyte count were not affected by GYKI 39521 and GYKI 39541 treatment in our model. Diminution of fibrinogen level and platelet count was prevented by GYKI 39521 and GYKI 39541. Fibrin degradation products and fibrinolysis were significantly decreased by GYKI 39521 and GYKI 39541. The thioglycosides may have a lower risk of bleeding in the treatment of disseminated intravascular coagulation than heparin.     

Preliminary experiences with sentinel lymph node detection in cases of vulvar malignancy

Lymph node status is the most important prognostic factor in vulvar malignancy. The aim of this pilot study was to explore the clinical significance of radionuclide lymphoscintigraphy in the management of vulvar neoplasms. Eight patients with squamous cell carcinoma and two patients with malignant melanoma of the vulva were studied with 100 MBq technetium-99m nanocolloid (Sentiscint, OSSKI, Budapest) 1 day before surgery. The location of the sentinel lymph node was checked by a single-head gamma camera-computer system (MB 9200, Mediso, Budapest). Vulvectomy with bilateral inguinofemoral lymphadenectomy was performed in each case. At lymphadenectomy, the sentinel lymph node was separately removed and histologically studied. Three of the ten patients had positive sentinel lymph nodes (micrometastasis). Five months later one of them had local recurrence of the vulvar cancer, and another had inguinal recurrence of the tumour 6 months postoperatively; the third patient was operated on only recently. Our preliminary results are impressive and suggest that lymphoscintigraphy is an easy and reliable method for detection of the sentinel lymph node in vulvar malignancy.     

Wernicke-encephalopathy in children with cancer

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology-Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy-induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progestrone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy. © 1994 Wiley-Liss, Inc.