A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.     

Radiobiological studies of pi-meson at TRIUMF using mouse L5178Y cells

Radiobiological parameters, cell killing, induction of mutations resistant to 6-thioguanine and to methotrexate, and DNA scissions were investigated at the plateau region and peak region of the pion beams of TRIUMF under a preclinical beam condition. The relative biological effectiveness (RBE) of four parameters at the plateau region were nearly 1 using gamma-rays or X rays as the standard radiations. RBE values at the peak regions were varied from one biological parameter to the other. The RBE of cell killing was dependent upon radiation dose; an RBE of 1.9 decreased gradually to 1.2 with an increased radiation dose. The RBE of mutations resistant to 6-thioguanine was dose-dependent and decreased from 1.7 to 1.3 when the dose was increased, while the RBE of mutations resistant to methotrexate was a constant, 1.0. The RBE of DNA scission was a constant 0.7. The radiobiological significance of cell killing and of mutagenesis in pion radiotherapy will be discussed.     

The role of paraaortic node irradiation in the treatment of cancer of the cervix

One hundred and twenty-seven patients with previously untreated carcinoma of the uterine cervix underwent pretreatment laparotomy between 1971 and 1980. Thirty-one were found to have paraaortic metastasis. Twenty-seven patients received paraaortic node external supervoltage radiation to the entire paraaortic chain, 4400 cGy, over 4 1/2 weeks, with 600-800 cGy, boost over 1 week, limited to the area of metastasis as marked at laparotomy. Twenty-nine percent (8/27) of the patients with paraaortic node metastases who were irradiated have survived 5 years or more. These patients have FIGO stages IB, IIA, or IIB; all have epidermoid carcinoma. Three of five patients (60%) with microscopic metastasis and five of twenty-two patients (23%) with gross metastasis in the paraaortic lymph nodes are long-term survivors. None of our long-term survivors have suffered late complications. There have been no fatalities from treatment related complications. We present a radiation technique for paraaortic radiation in these patients, and discuss the indications for paraaortic node radiation in cancer of the cervix.     

Systematic classification of alleles of the glycophorin A (MN blood group) gene

Ten alleles (five M and five N alleles) of the MN blood group system with normal antigenicity were found by sequencing the glycophorin A (GPA) gene. This study demonstrates the systematic classification of these alleles to major or minor variations of the standard alleles. GPA-specific fragments ranging from 150 to 3.8 kb in length were amplified from the templates, and exons 1–7 and introns 1–6 were sequenced. The data were analyzed phylogenetically to classify these alleles into major groups or clusters. The ten alleles were grouped into four major clusters M10X (M101–M103), M20X (M201 and M202), N10X (N101–N104) and N20X (N201), where X represents a digit indicating minor variations. This grouping was supported by phylogenetic analysis. The cluster system of GPA alleles is highly informative for genetic screening.     

Optimal diabetes management during medical weight loss for cardiovascular risk reduction

Obesity has long been recognized as a significant risk factor for type 2 diabetes. Both obesity and type 2 diabetes are associated with an increase in cardiovascular risk. As cardiovascular disease continues to be the number one killer in the USA and western adult populations, the rise in prevalence of obesity and type 2 diabetes is alarming. This is especially disturbing in the tripling of overweight children and adolescents, accompanied by the increase in prevalence of pediatric type 2 diabetes. Optimal strategies for long-term diabetes management aim at effectively controlling, reducing and ultimately preventing obesity. This review explores the clinical recommendations in place, new clinical investigations, diet therapy, medical nutrition therapy, meal replacements, behavior therapy, exercise therapy, pharmacotherapy and surgical therapy as strategies to achieve weight-loss success in diabetic patients and ultimately reduce cardiovascular disease.