Characterization of preneoplastic and neoplastic lesions in the rat pancreas

Nodules of acinar cells with increased proliferative potential develop in the pancreas of carcinogen-treated rats and in untreated aged rats. Large nodules are classed as adenomas. Phenotypic and genotypic characteristics of nodule cells were compared with normal pancreas and transplantable acinar cell carcinomas by several methods. Nuclei of acinar cells from normal pancreas, adenomas, and three carcinomas in situ had normal diploid DNA content as determined by flow cytometry. One of two primary carcinomas had a hypodiploid DNA content. Two of three transplantable carcinomas were aneuploid with a DNA content in the tetraploid range. Explants from nodules and adenomas failed to grow in soft agar, whereas several carcinomas were positive in this assay. A primary carcinoma was serially transplanted, but transplantation of nodules or adenomas failed. Transfection of DNA from carcinomas in situ yielded a higher frequency of NIH 3T3 transformants than DNA from adenomas. DNAs from the transformants did not contain ras sequences. These studies indicate that cells from nodules and adenomas have low growth potential and lack critical phenotypic and genotypic characteristics of transformed malignant cells that were present in some primary and transplanted carcinomas.     

Palliative radiotherapy for brain metastases

Several studies have confirmed that results of different hypofractionated radiotherapy schedules for palliative purpose are similar to those of conventional higher doses. From 1992 to 1993, 56 consecutive patients with brain metastases were irradiated at our Institution. Three different schedules were used ranging between 18 and 40 Gy. Overall survival, clinical and radiological responses were evaluated with regard to schedules and prognostic characteristics of patient population. There were no significant differences between the treatments, even though patients with shorter estimated life expectancy were more likely to be irradiated with more hypofractionated radiotherapy. Short, cost effective treatments appear to be the best therapeutic option both for institution and patients in most palliative cases.     

Functional Base of Tongue Fat Injection in a Patient with Severe Postradiation Dysphagia

Lipofilling is a well-established technique in reconstructive plastic surgery. It is used primarily in recontouring of the body and face to correct post-traumatic and congenital defects. The regenerative properties of adipose tissue have allowed the use of the lipofilling technique for the treatment of burn sequelae and irradiated breast to improve tissue quality and elasticity. We report on the case of a patient treated with radiation therapy for a nasopharyngeal carcinoma who presented with severe postradiation dysphagia. The lipofilling technique was successfully used to improve abnormal swallowing. The technical details and functional outcomes are discussed.     

Randomized Multicentric Italian Study on two Treatment Regimens for Marrow Relapse in Childhood Acute Lymphoblastic Leukemia

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluahle patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.     

Health status of young children with cancer following discontinuation of therapy

This paper reports late effects and health status of 198 children who had cancer or leukemia diagnosed under 2 years of age and their therapies electively withdrawn. This series (92 neuroblastoma [NBL], 57 Wilms' tumor [WT], 46 acute lymphoblastic leukemia [ALL], and 3 non-Hodgkin's lymphoma) was followed for 1-12 years after discontinuation of therapy. Thirty-three children were diagnosed before 1973, 92 between 1973 and 1977, and 73 after 1977 in 16 Italian Pediatric Oncology Centers. As of December 1983, 176 children were reported to be alive and without evidence of primary cancer by physicians responsible for their care. One child died from a second primary tumor, two from late recurrences of the primary cancer, and three from other causes; eight were alive with evidence of primary cancer; and eight were lost to follow-up. Kyphoscoliosis was found in 22 children and other musculoskeletal anomalies in 8. Neurological sequelae were observed in 8 out 35 children with ALL treated with radiotherapy (RT) and intrathecal methotrexate. All but one were in continuous complete remission when they developed seizures (three cases), leukoencephalopathy (three cases), or intracerebral calcifications (two cases). One child had cardiomyopathy and subsequently died from cardiac failure: he had received doxorubicin (400 mg/m2) and mediastinal RT (13 Gy) for NBL. Growth impairments were observed in children with NBL and WT.     

U.v.-enhanced reactivation of u.v.-irradiated herpes virus by primary cultures of rat hepatocytes

Carcinogen treatment of cultured mammalian cells prior to infectionwith u.v.-irradiated virus results in enhanced virus survivaland mutagenesis suggesting the induction of SOS-type processes.In this paper, we report the development of a primary rat hepatocyteculture system to investigate cellular responses to DNA damagewhich may be relevant to hepato-carcinogenesis in vivo. We haveobtained data demonstrating that enhanced reactivation of u.v.-irradiatedHerpes simplex virus type 1 (HSV-1) occurs in hepatocytes irradiatedwith u.v. Cultured hepatocytes were pretreated with u.v. atthe time of enhanced DNA synthesis. These treatments causedan inhibition followed by a recovery of DNA synthesis. At varioustimes after pretreatment, the hepatocytes were infected withcontrol or u.v.-irradiated HSV-1 at low multiplicity, and virussurvival was measured by direct plaque assay. U.v.-irradiatedHSV-1 exhibited the expected two-component survival curve incontrol or u.v. pretreated hepatocytes. The magnitude of enhancedreactivation of HSV-1 was dependent on the u.v. dose to thehepatocytes, the time of infection following u.v. pretreatment,and the level of DNA synthesis at the time of pretreatment.These results suggest that u.v. treatment of rat hepatocytescauses the induction of SOS-type functions that may have a rolein the initiation of hepatocar-cinogenesis.     

Italian registry of patients off therapy after childhood acute lymphoblastic leukemia. Results after first phase of data collection

The Italian Registry of Off-Therapy patients after childhood tumors now includes 760 subjects with acute lymphoblastic leukemia. These patients were all removed from treatment by December 31, 1981, and were followed in 35 different institutions. All the children have received multiple-drug treatment, combined, in 79.7% of the cases, with cranial irradiation. Thirty-nine (5%) experienced a relapse before treatment suspension. Total duration of antileukemic therapy ranges between 18 and 131 months (median, 38). At the last updating (December 31, 1981), 699 subjects were alive, 6 were lost to follow-up, and 55 had died. Life-table analysis shows that 90.8% were alive and 77% were alive in continuous complete remission at 36 months, whereas at 66 months, the cumulative proportions were 88% and 75.5%, respectively. One hundred thirty-six of 760 relapses after therapy suspension were reported: 83 in male patients and 53 in female patients (P less than 0.01). The longest interval between relapse and treatment suspension was 64 months. Six of 55 died in continuous complete remission 3 to 44 months after treatment suspension. Five births of apparently normal babies to female patients have been reported. A general outline of the project and the future program are given.