Preliminary results of conservative combination radiotherapy and chemotherapy in early stages of Hodgkin''s disease

Heterogeneity of biological structure and function is an impediment to the analysis and treatment of human solid tumours. Its importance is frequently underestimated in clinico-pathological research. This article reviews the many facets of heterogeneity in tumour systems, and its importance to the interpretation of tumour biology.     

Topical topic. Use of chemotherapy for retinoblastoma

We studied the significance of debt as a risk factor for suicidal ideation and suicide attempts in a nation-wide sample (n = 4868) of the Finnish general population. Those experiencing difficulties in repaying their debts more often than others (37 vs. 16%, P<0.001) had a probable minor mental disorder (GHQ-12 score > or =3). Nevertheless, difficulties in repaying debts were found to be a factor independently associated with suicidal ideation (OR, 2.8; 95% CI, 1.9-4.2). The clinical implication of these findings is that individuals experiencing difficulties in repaying their debts may require psychiatric evaluation as well as socio-economic counselling.     

Clinicopathologic features of retinoblastoma after primary chemoreduction

BACKGROUND: Cytotoxic T cells can induce target cell lysis and apoptosis by different pathways. The interactions of CD95 antigen (Fas) with its ligand (CD95L) and of tumor necrosis factor (TNF)-alpha with its receptor (TNF-R1) lead to apoptotic cell death. Recently, conflicting studies have been published concerning the expression and the role of CD95L in allograft rejection and tolerance. METHODS: In this study, the intragraft expression of CD95/CD95L and TNF-alpha and the frequency and distribution of apoptotic cells were compared in a model of heterotopic cardiac allograft in the rat in which recipients were either not treated (acute rejection) or pretreated with donor-specific blood transfusion (tolerant). RESULTS: In the acutely rejected allografts, a peak in the expression of CD95L and TNF-alpha and in the number of apoptotic cells was observed during the first week after transplantation; apoptotic cells were confined to graft-infiltrating cells. In the tolerated allografts, however, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower. The expression of Fas was constitutive and was not modulated during acute rejection or tolerance. CONCLUSION: This down-regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing pathways in acute allograft rejection.     

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.     

Response to chemotherapy in cerebral primary lymphoma

INTRODUCTION: Primary central nervous system lymphomas (PCNSL) are infrequent, rapidly growing and generally limited to the central nervous system (CNS). In recent years there has been a threefold increase in cases occurring in immunocompetent individuals. Conventional treatment with corticosteroids and radiotherapy is effective, but over 80% relapse in less than a year. Chemotherapy has significantly improved the results of treatment. CLINICAL CASE: We present a case of PCNSL in an immunocompetent patient which was resistant to radiotherapy (RT). There was progression of the lymphoma three months after irradiation, and later multicentric progression one month after radiosurgery. The patient had complete radiological remission after systemic chemotherapy. The clinical improvement was obvious, since before chemotherapy was started the patient was in coma and had episodes of apnea. The therapeutic response obtained was consolidated by intensive chemotherapy and hemopoietic support. The condition is still in remission three years after completion of this treatment. CONCLUSIONS: There are no publications about the results of combined radiotherapy and chemotherapy in series of patients with PCNSL, since there are relatively few patients and many methods of treatment are tried.     

Superselective vagotomy. Preliminary results

Twelve patients suffering from an intractable duodenal ulcer are included in this review. Eleven were treated by superselective vagotomy without drainage, one had a selective vagotomy with pyloroplasty. A peroperative control of the gastric acidity after pentagastrin stimulation was used in all cases and permitted section of forgotten nerve fibers. Short-term results are satisfactory: after 2-6 months the clinical state of the patients is excellent (Visick I and II), basal acidity is decreased by 58 to 66% of preoperative value, the Hollander tests are negative except two. After more than 6 months, the few available results are satisfactory except one case of recurrent ulcer. The one case with a 1 year follow-up is excellent, clinically and as to acid secretion.     

The chemotherapy of adult primary brain tumors

Adult patients with primary malignant brain tumors are a heterogeneous group. Most patients will have high-grade astrocytomas and can be expected to obtain minimal benefit from current standard chemotherapy regimens. Intra-arterial chemotherapy, high-dose chemotherapy with autologous bone marrow rescue, and new chemotherapeutic agents designed to penetrate the blood-brain barrier have not resulted in significant advances to date. However, there are exciting new directions in the chemotherapy of high-grade astrocytomas which are entering clinical trials. Two potentially promising approaches include interstitial chemotherapy using surgically implanted polymers and the continuous infusion of combinations of active chemotherapeutic agents. Other therapeutic modalities such as radioactive seed implants, stereotactic radiosurgery, and gene therapy are also being evaluated. Hopefully, this intense activity by subspecialists with a wide range of interests and expertise will produce novel and effective treatments for the large number of patients with malignant astrocytomas. In contrast, patients with many of the less common neoplasms of the central nervous system may benefit from the addition of chemotherapy to their treatment. Primary germ cell tumors or lymphomas of the central nervous system are very sensitive to chemotherapy. The germ cell tumors respond to the cisplatin-containing regimens developed for testicular malignancies. The optimal chemotherapy for CNS lymphoma is not clear but exciting results have been reported with a combination of radiation, systemic and intrathecal methotrexate, and systemic cytosine arabinoside. Although limited, the available literature suggests that patients with anaplastic oligodendrogliomas may also benefit from chemotherapy at diagnosis or at relapse. Studies in children suggest a benefit for adjuvant chemotherapy and radiation therapy in poor risk patients with medulloblastomas although these findings have not been confirmed in adults. Finally, anecdotal reports suggest that chemotherapy may be useful in the very rare patient who presents with a pineal tumor or an ependymoma.     

The results of primary radiotherapy in vaginal carcinoma

The results of two previous and two recent studies of middle-aged males and females are presented to exemplify the clinical importance of lipoprotein(a) (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these studies various conventional and recently suggested risk factors were included and different methods for Lp(a) quantification were used. Lp(a) was a significant risk factor in all four studies. In the recent prospective case-control study, Lp(a) and cholesterol were found to act synergistically and predict primary acute myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/l increased the risk of acute myocardial infarction if the Lp(a) level was above 200 mg/l. The plasma apo A-I level was a protective factor. In the other recent case-control study, an Lp(a) level above 500 mg/l was a highly significant risk factor in Black and White US women with myocardial infarction or advanced coronary artery disease in addition to low density lipoprotein cholesterol levels above 130 mg/dl. A high apo A-I level was a protective factor. In these studies no other factors tested reached significance in multivariate logistic regression analysis. A hypothetical association between high Lp(a) levels and intracellular infection with Chlamydia pneumoniae is discussed. The results suggest that the Lp(a) level is useful in identifying high-risk individuals. Lowering low density lipoprotein cholesterol below 100 mg/dl (<2.6 mmol/l) seems to be most important in both males and females with high-risk Lp(a) levels.     

Ultrasonic welding of bones. Preliminary results

Experiments with ultrasonic applied welding, a method first developed in the USSR are reported. In standardized isolated bone preparations stability values could be obtained of 10% [and in one case of 40% (!)] of the stability of the nonfractured bone. With these values the requirements of the method of osteosynthesis are met. Results of in vivo experiments are expected.     

Efficacy of neoadjuvant chemotherapy in primary non-small cell lung cancer

PURPOSE: To examine the changes in ciliary body thickness after topical application of pilocarpine, cyclopentolate hydrochloride, and PhXA41, a prostaglandin F2alpha analog. METHOD: We used high-frequency Humphrey UBM840 ultrasound biomicroscope to examine 36 healthy young Japanese subjects. RESULTS: The mean ciliary body thickness increased from 0.67 +/- 0.07 mm to 0.073 +/- 0.08 mm (P < .01) after application of 2% pilocarpine; 1% cyclopentolate hydrochloride and 0.005% PhXA41 decreased the mean ciliary body thickness from 0.75 +/- 0.07 mm to 0.69 +/- 0.05 mm (P < .05) and from 0.78 +/- 0.06 mm to 0.75 +/- 0.06 mm (P < .01), respectively. CONCLUSIONS: Our ultrasound study clearly indicates that pilocarpine increased comparative thickness of the ciliary body by 8.3%, whereas PhXA41 decreased comparative thickness by 3.3% in a manner similar to cyclopentolate hydrochloride.     

"Eight drugs in one day" chemotherapy in a nonfamilial bilateral retinoblastoma with recurrent cerebrospinal fluid metastases

OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.     

High incidence of chromosome 8 monosomy and chromosome 7 trisomy in prostatic primary tumor and its related lymphatic metastasis. Preliminary results

SETTING: Chest Clinic, University Teaching Hospital, Zambia. OBJECTIVE: To study the pre-diagnosis economic impact, burden, and barriers to care-seeking for tuberculosis patients in urban Zambia. DESIGN: In-depth interviews conducted over a 9-week period with adult in-patients and out-patients registering with new pulmonary tuberculosis; data analysis using Epi Info. RESULTS: Interviews were completed by 202 patients: 64% normally worked, but 31% stopped due to their tuberculosis, with an average of 48 days off. The mean duration of illness prior to their tuberculosis registration was 63 days, with 64% of patients delaying in presenting to the Chest Clinic. Of these, 38% blamed money shortages for their delay. In seeking diagnosis, patients incurred a mean total cost equivalent to 127% of their mean monthly income (pounds sterling UK 40 [$US 59]); direct expenditures represented 60% of this cost. In addition, patients lost, on average, 18 work days prior to diagnosis. Care-givers incurred costs equivalent to 31% of the mean monthly income (pounds sterling UK 10 [$US 15]). CONCLUSION: The economic burden of tuberculosis on patients creates barriers to prompt diagnosis which may lead to continuing transmission of the infection. Important economic barriers include transportation expenditure, cost of 'special food', and lost income. These barriers may be reduced through interventions that reduce the number of health encounters, travel distances and duration of illness before diagnosis.     

Surgical results of persistent hyperplastic primary vitreous

PURPOSE: To evaluate the surgical success of patients with persistent hyperplastic primary vitreous (PHPV) and to identify preoperative indicators of visual outcome. DESIGN: Noncomparative case series. METHODS: The diagnosis of PHPV was made in 35 eyes of 27 patients from 1982 to 1994. In each case, anterior and/or posterior PHPV findings, preoperative testing, surgical procedures, and visual outcomes were documented. Twenty-nine of 35 eyes were managed surgically. Follow-up ranged from 2 months to 12 years. RESULTS: Of the 35 eyes, 2 (5.7%) had strictly anterior PHPV, 8 (22.9%) had strictly posterior PHPV, and 25 (71.4%) had components of both anterior and posterior disease. Initial lensectomy and vitrectomy was performed in 24 eyes (68.6%). Surgery was withheld in four eyes secondary to severity of disease with an unrecordable visual-evoked potential (VEP). Reoperation rate was 32.3% for membrane reproliferation, glaucoma, vitreous hemorrhage, retinal detachment, or strabismus. Best-corrected final visual acuity ranged from 20/60 to no light perception. Six eyes (17%) maintained Snellen visual acuity despite posterior PHPV with some degree of retinal dysplasia. CONCLUSIONS: Surgical treatment of PHPV can result in functional visual outcome despite posterior segment involvement. The degree of ocular malformation, however, will ultimately limit the amount of visual improvement. Preoperative testing, including VEP, may aid in determining surgical candidates.