Concurrent chemotherapy with carboplatin + 5-fluorouracil and radiotherapy in advanced squamous cell head and neck carcinoma: a retrospective single institution's study.

AIMS AND BACKGROUND: [corrected] The purpose of the study was to analyze the long-term follow-up of a single institution's experience with a regimen of concomitant carboplatin + 5-fluorouracil (CBDCA + 5-FU) infusion and radiotherapy. STUDY DESIGN: Fifty-eight patients with locally advanced squamous cell head and neck cancer treated with combined chemoradiotherapy between March 1990 and October 1998 were reviewed retrospectively. According to the TNM tumor staging, 6 patients had stage II, 21 stage III and 31 stage IV tumors. The chemotherapy regimen consisted of the combination of 5-FU and CBDCA, for a total of 3 cycles. Both drugs were given as 4-day continuous intravenous infusions during the first and fourth week of radiation therapy: 5-FU at 1000 mg/m2 per day and CBDCA at 75 mg/m2 per day. Radiation was given in single daily fractions of 1.8 to 2 Gy, to a total dose of 66 to 70 Gy. RESULTS: After the completion of chemotherapy and radiotherapy, 34 patients (58.6%) achieved clinical and radiological (computerized tomography and/or magnetic resonance imaging) complete remission, 15 patients (25.9%) partial remission >50%, 5 patients (8.6%) partial remission <50%, and 4 patients (6.8%) had no response. Toxicity was intensive but tolerable. After a median follow-up of 25 months, overall survival and recurrence-free survival estimated for the whole patient population was 52% at 3 years, and the median length of recurrence-free survival was 23 months. CONCLUSIONS: Our regimen combining standard single daily fraction radiation with the conventional dose of CBDCA and 5-FU was given without dose modification regardless of the severity of the adverse effects. It gave a clinical complete response at the primary site in 58.6% of patients. With a 52% projected 3-year overall survival, our series compares favorably with similar studies in the literature. Therefore, our results with concomitant CBDCA/5-FU infusion and radiotherapy are encouraging and suggest that CBDCA can be substituted for cisplatin with a good therapeutic index.

[The exclusive radiotherapy of tumors of the paranasal sinuses. A retrospective analysis of 73 cases]. / La radioterapia esclusiva dei tumori dei seni paranasali. Analisi retrospettiva di 73 casi.

Seventy-three cases of paranasal sinus tumors observed between 1980 and 1991 were retrospectively analyzed. Our series consisted of 50 men and 23 women aged 43 to 83 years. Histology demonstrated 33 squamous cell carcinomas, 20 adenocarcinomas, 10 undifferentiated carcinomas, 3 mucoepidermoid carcinomas, 3 adenoid-cystic carcinomas, 2 osteosarcomas, 1 fibrosarcoma and 1 melanoma. All patients were untreated. The lesions from maxillary sinus consisted of 3 T2, 13 T3 and 39 T4 tumors; 50 cases were N0 and 5 N+. "Central" neoplasms consisted of 6 stage I, 7 stage II and 5 stage III lesions. All patients underwent irradiation (with 60Co) with two angled fields or three fields -2 opposing lateral and 1 anterior. Critical structures were shielded when possible and wedges were used to optimize dose distribution. Locoregional lymph nodes were treated in N+ cases only. Dose distribution was studied on CT images. All patients received a total dose of 54-72 Gy (mean: 61.4, median: 62 Gy) with 1.8-2 Gy/day fractions for 5 days/week. After irradiation 27/73 (30.8%) complete responses were observed. Local control at 6 months was obtained in 17/73 cases (23.3%) and it was correlated with the total dose. Actuarial survival rates at 3 and 5 years were 27.9% and 21.8%, respectively. At the multivariate analysis, the only significant variable was the stage; no correlations were found with sex, histology and site. During follow-up, lymph node metastases were observed in 4/66 initially N0 cases. Distant metastases were found in 10/73 patients (13.7%) and secondary lesions in 8/73 (11%). Severe complications were observed in 7/73 cases (9.6%).

[Post-radiotherapy complications in malignant tumors of the nasopharynx. Analysis of 141 cases]. / Complicanze postradioterapiche nei tumori maligni della rinofaringe. Analisi di 141 casi.

This study was aimed at retrospectively analyzing the incidence and severity of the complications occurred in 141 patients affected with nasopharyngeal carcinomas treated with exclusive radiotherapy from 1960 to 1986. The acute complications were analyzed (85/141 grade II-III mucositis which generally came to a complete remission) which occurred during and immediately after radiation treatment. The late damage was then studied which occurred in 74/141 patients (52.5%) and which may worsen patients' quality of life. Finally, the incidence and severity of damage were correlated with some parameters: sex, age, performance status, risk factors (tabagism, alcoholism, diabetes), stage, total dose, fractionation, and processing techniques for treatment planning.

[Multiple duodenal and ampullary carcinoids and von Recklinghausen's neurofibromatosis]. / Carcinoidi duodeno-ampollari multipli e neurofibromatosi di Recklinghausen.

A clinical case of multiple duodenal carcinoid involving the ampulla in a woman with von Recklinghausen's neurofibromatosis (VRNF) is described. The Authors review the literature of the 20 cases previously reported and discuss the significance of such an association. Carcinoid tumors of the duodenum represent 2-5% of all carcinoid found in the general population. While VRNF-associated duodenal carcinoids are not otherwise distinctive, they tend to be associated to pheochromocytoma. Duodenal carcinoid need to be investigated systematically for their immunocytochemical profile, especially for chromogranins (CG), neuron specific enolase (NSE) and somatostatin.

[Solitary ulcer of the colon associated with mucosal melanosis]. / Ulcera solitaria del colon associata a melanosi mucosa.

The authors report on a case of solitary ulcer of the large bowel associated with mucosal melanosis, stressing the peculiar nature of this rare pathology and its differentiation from solitary ulcer of the rectum. The pathogenesis of the disease is still unknown and histological data from biopsies performed at various time intervals in chronic cases show, in this case as in other cases of solitary ulcer of the rectum, that histological findings vary over time; in the case reported on here, histology revealed a transition from a chronic inflammatory situation to one of mucosal melanosis after three months. Diagnosis is reached by exclusion and is based on colonoscopy plus biopsy. Useful techniques in complicated cases are selective angiography (for haemorrhage) or CAT (for perforations, abscesses). Treatment is conservative in uncomplicated cases, with suitable follow-up in the form of check colonoscopies and targeted biopsies. Surgical treatment is confined to those cases--by no means infrequent--complicated by haemorrhage, perforation and abscesses.

Adaptive character of liver glucokinase.

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.

Sigmoidal kinetics of glucokinase.

Glucokinases obtained from the liver of several species of mammals and amphibians exhibit sigmoidal saturation functions for glucose. Hill coefficients (nH) are about 1.5, and half-saturation values (K0.5) lie between 1.5 and 8.5 mmol/l. The nH and K0.5 values are constant throughout the purification steps of rat glucokinase. A dimeric form of rat glucokinase appearing in aged preparations exhibits michaelian kinetics. Sigmoidal kinetics is considered as an adaptive feature of glucokinases to increase the efficiency of the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.