Detection of enterovirus RNA in postoperative thyroid tissue specimens.

CONTEXT: Autoimmune thyroiditis is a very common disease. A genetic predisposition and environmental factors such as viruses are thought to contribute to the development of autoimmune thyroiditis. Enteroviruses, which are involved in other autoimmune diseases, are attractive candidates. OBJECTIVE: To investigate the presence of enteroviral genome sequences in postoperative thyroid tissues with lymphocytic infiltration, a common histological feature of thyroiditis. SUBJECTS AND METHODS: Postoperative thyroid specimens collected prospectively from 86 patients were blindly frozen at -80 degrees C. The presence of EV genome sequences in the samples was blindly investigated by real-time RT-PCR. Clinical data, histological findings and levels of anti-TPO antibodies were collected. RESULTS: EV-RNA detection was positive (up to 36 cycles) or weakly positive (37-39 cycles) in 22 out of 86 patients (25%). EV-RNA (positive or weakly positive signal) was detected in 5 out of 27 (18.5%) thyroid specimens with lymphocytic infiltration, and in 17 out of 59 (29%) thyroid specimens without lymphocytic infiltration (P = 0.4). No correlation was observed between EV-RNA detection in thyroid and the presence of anti-TPOAb. EV-RNA was detected in 3 out of 11 patients histologically diagnosed as thyroiditis (27.3%) and in 18 out of 74 patients (24.3%) with thyroid tumours (multinodular goitre, adenoma and carcinoma) (P = 0.5) and in one patient with a normal thyroid. CONCLUSION: EV-RNA can be detected in thyroid tissue from patients with various thyroid diseases, but there is no relationship between the presence of EV-RNA and thyroiditis. Further studies are needed to clarify the role of EV in thyroid diseases.

Technical and functional results after laparoscopic rectopexy to the promontory for complete rectal prolapse. Prospective study in 54 consecutive patients.

INTRODUCTION: Laparoscopic rectopexy for complete rectal prolapse offers short-term advantages compared with operations performed by laparotomy. The aim of this prospective study was to report technical and functional outcome after laparoscopic rectopexy to the promontory in consecutive patients operated on by a single surgeon. PATIENTS AND METHODS: From May 1996 to July 2004, 54 consecutive patients (47 women), median age 53 years (range: 16-84 years), underwent laparoscopic rectopexy to the promontory for complete rectal prolapse. Preoperative evaluation included physical examination, dynamic videoproctography and, in patients with constipation, colonic transit time (with radiopaque markers). Postoperative evaluation included the same examinations and a simple global quality-of-life questionnaire. RESULTS: Conversion to laparotomy was required for three patients during the learning curve. Median duration of operation was 157 minutes (range: 50-370). There was no mortality and morbidity was 5.5% (brachial plexus palsy in two patients and urinary tract infection in one). Median hospital stay was 3.5 days (range: 1-11). There were 4 recurrences (7.4%). Functional outcome at 12 months showed the presence of constipation in 20.3% of patients (persistence in eight and de novo in three) and the presence of outlet obstruction in 25.9% of patients (persistence in six and de novo in eight). Anal continence improved in 72.4% of the 29 patients who complained of this symptom. The global quality-of-life questionnaire showed a satisfactory result in 96% of patients. CONCLUSION: Laparoscopic rectopexy to the promontory is a safe and efficient procedure to treat complete rectal prolapse; morbidity is low. Functional outcome is at least equivalent to that obtained with open procedures in terms of continence, constipation and outlet obstruction.

[Larynx cancer in France: descriptive epidemiology and incidence estimation]. / Les cancers du larynx en France: éléments d'épidémiologie descriptive et estimation de l'incidence nationale.

The epidemiology of cancers is known in France through mortality data provided by Inserm and morbidity data obtained by French tumor registries. The purpose of this study was to compare the incidence of laryngeal cancers in 9 French departments and to give an estimate of this incidence for the whole of France, based on this data. Incidence and mortality data were collected over the period 1978-1997. The incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The estimated number of laryngeal cancers was 3,865 in males and 361 in females. There were pronounced contrasts in laryngeal cancer incidence between cancer registries. The incidence rate of laryngeal cancers were especially high in the Somme and Calvados department compared to those observed in Haut-Rhin and Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is among the countries which have the highest rates of incidence and mortality for laryngeal cancer in Europe.

ZD1839 (Iressa) modifies the activity of key enzymes linked to fluoropyrimidine activity: rational basis for a new combination therapy with capecitabine.

PURPOSE: The efficacy of new oral fluoropyrimidines, including capecitabine, is improved in cells expressing high levels of thymidine phosphorylase (TP) and low levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase. We used a human head and neck cancer cell line (CAL33) to examine the influence of cell cycle modifications on TS, TP, and dihydropyrimidine dehydrogenase activity. EXPERIMENTAL DESIGN: Cells were exposed to the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa(2)) and 5'-deoxy-5-fluorouridine (5'-DFUR), alone and in combination, for up to 96 h, and modifications in cell cycle, enzyme activity, and gene expression were examined. RESULTS: ZD1839 (24- to 72-h exposure) markedly reduced proliferation and caused a rapid increase in G(0)-G(1) and a decrease in S phase; a 40-fold decrease in TS activity at 24 h and a 2.5-fold increase in TP activity at 48 h were observed. A significant link between TP activity and expression was observed (r(2) = 0.98; P = 0.0068). Additional investigations pointed out an increased cellular production of 5-fluorouracil anabolites from 5'-DFUR when cells were preincubated with ZD1839. Dose-effect curves of ZD1839 and 5'-DFUR, alone and in combination, were examined. Combination indices for ZD1839 + 5'-DFUR were 0.58 +/- 0.1 and 0.63 +/- 0.1 for 50% survival and 25% survival, respectively. Additional investigations pointed out an increased cellular production of 5-fluorouracil anabolites from 5'-DFUR when cells were preincubated with ZD1839. CONCLUSIONS: These data demonstrate a strong synergistic interaction between ZD1839 and 5'-DFUR when ZD1839 is applied before or concurrently with 5'-DFUR. Such a drug combination would have two advantages: (a) the theoretical advantage of tumor selectivity of epidermal growth factor receptor-targeted therapy; and (b) the practical advantage of a combination therapy that could be administered p.o.

Oxaliplatin-5-fluorouracil and ionizing radiation. Importance of the sequence and influence of p53 status.

OBJECTIVES AND METHODS: The association oxaliplatin (OXA)-5-fluorouracil/folinic acid (FUFA) is currently a standard first-line treatment for advanced colorectal cancer. The main objective of this experimental study was to examine the cytotoxic effects resulting from the addition of ionizing radiation (Rgamma) to the combination OXA-FUFA on 2 human colon cancer cell lines (SW403, p53 wild type and WiDr, p53 mutated). A clinically relevant drug sequence was used consisting in OXA during 2 h followed by FUFA over 24 h. The impact of the position of radiation (1 and 4 Gy) was tested: radiation 2 h before drug application, in the middle of the drug application or 24 h after the drug application. RESULTS: Both cell lines exhibited similar dose response curves to Rgamma alone, WiDr being more radio-sensitive than SW403 (IC50: 4.8 Gy and 7 Gy, respectively). The effects of Rgamma-drug combinations were assessed using a conventional isobolographic method and by computing a potentiation factor (F) defined as the ratio of IC50 drug combinations/IC50 drug combinations combined with Rgamma. The results from both calculation methods concurred: the combination of OXA-FUFA with Rgamma led to additive-antagonistic effects for the p53 mutated cell line (WiDr), whatever the sequence. In contrast, for the p53 wild type cell line (SW403), additive-synergistic effects were observed with, in this case, an optimal position for Rgamma occurring when applied before or at mid-drug application. CONCLUSIONS: These results could be taken into consideration for an optimal design of clinical protocols associating Rgamma and OXA-FUFA.