Prognostic impact of Bacillus Calmette-Guérin interruption at the time of induction and consolidation.

CONTEXT: Intravesical Bacillus Calmette-Guérin (BCG) is a cause of bladder and systemic toxicity that is difficult to prevent and is responsible for treatment drop out in bladder cancer patients. More recently, BCG shortage has become the main cause of incomplete treatment. AIMS: The aim of this study was to examine the impact on long-term prognosis of bladder cancer patients following discontinuation of BCG instillations. SETTINGS AND DESIGN: In this retrospective study, data were examined from 333 consecutive nonmuscle invasive bladder cancer patients treated from 2005 to 2015 by transurethral resection (TUR) and had undergone adjuvant BCG therapy after TUR. SUBJECTS AND METHODS: Rate of complete cure, the reason for the interruption, toxicity, and the associations between discontinuance of BCG therapy, tumor characteristics, association with carcinoma in situ and tumor recurrence or progression were analyzed. STATISTICAL ANALYSIS USED: Recurrence and progression-free survival rate curves were estimated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Differences among groups were considered as statistically significant when P < 0.05. RESULTS: Overall, 303 patients were eligible for analysis. Median follow up was 36 (confidence interval: 7-120) months. A total of 55 (18.1%) had <6 installations (Group I); 87 (28.7%) completed induction and 1-year maintenance (Group III); and 161 (53.1%) completed the induction course, but not the 1-year maintenance (Group II). Grade III-IV toxicity rates were significantly higher in Group I than Group II and III. Interruption for BCG shortage was the main cause of interrupting BCG in Group II. Multivariate analysis showed that discontinuation of BCG induction therapy was an independent predictor for tumor recurrence (P < 0.001) and 1-year BCG maintenance therapy for tumor progression (P = 0.005). CONCLUSIONS: Discontinuation of BCG therapy has a significantly deleterious effect on tumor recurrence and progression rates. Although BCG toxicity is a major cause of drop out, BCG shortage became a major cause of discontinuation. All effort must be done today to restore normal production of BCG worldwide.

Basic homopolyamino acids, histones and protamines are potent antagonists of angiogenin binding to ribonuclease inhibitor.

A radio-ribonuclease inhibitor assay based on the interaction of 125I-angiogenin with ribonuclease inhibitor (RI) was used to detect pancreatic-type ribonucleases and potential modulators of their action. We show that highly basic proteins including the homopolypeptides poly-arginine, poly-lysine and poly-ornithine, core histones, spermatid-specific S1 protein and the protamines HP3 and Z3 were strong inhibitors of angiogenin binding to RI. A minimum size of poly-arginine and poly-lysine was required for efficient inhibition. The inhibition likely resulted from direct association of the basic proteins with the acidic inhibitor, as RI bound to poly-lysine and protamines while 125I-angiogenin did not. Antagonists of the angiogenin-RI interaction are potential regulators of either angiogenin-triggered angiogenesis and/or intracellular RI function, depending on their preferential target.

Prevention of second primary tumours with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. Results of a multicentric double-blind randomised study.

Patients who are cured from head and neck carcinomas remain at high risk for developing a second primary in the head and neck area. It is now clear that retinoids exert a prophylactic action on the development of epithelial cancers when tested on laboratory animals and on human premalignant lesions. They are now used in the chemoprevention of epithelial cancers in randomised trials evaluating their efficacy. We prospectively studied 316 patients who developed squamous cell carcinoma of the head and neck, classified as T1/T2, N0/N1 < or 3 cm, M0 according to the UICC TNM classification. Patients were randomly assigned to receive orally, either etretinate (a loading dose of 50 mg/day for the first month, followed by a dose of 25 mg/day in the following months) or a placebo for 24 months. Adjuvant treatment began no later than 15 days after surgery and/or the initiation of radiotherapy. The 5-year survival rate and disease-free survival rate are similar in the two groups. There are no significant differences regarding either local, regional and distant relapses. After a median follow-up of 41 months (range 0-81), 28 patients in the etretinate group and 29 in the placebo group developed a second cancer with, respectively, 12 and 13 in the head and neck region. Adjuvant treatment was definitively discontinued mainly due to toxicity in 33% of patients in the etretinate group versus 23% in the placebo group (P < 0.05). Etretinate, a second-generation retinoid, does not prevent second primary tumours in patients who have been treated for squamous cell carcinoma of the oral cavity and oropharynx.

In vivo and in vitro studies of angiogenin--a potent angiogenic factor.

Angiogenin is a potent blood-vessel-inducing polypeptide with a molecular weight of 14,000 that has a unique ribonucleolytic activity. First isolated from the conditioned medium of tumour cells, angiogenin has since been purified from normal plasma, which suggested that its propensity to induce neovascularization should be strictly controlled. Modulation of that activity might involve interaction of angiogenin with cell-surface receptors and extracellular matrix of endothelial cells, tight-binding inhibition of both its ribonucleolytic activity and cell binding property by ribonuclease inhibitor, as well as the overall influence of divalent copper, a modulator of angiogenesis.

Secretion of ribonucleases by normal and immortalized cells grown in serum-free culture conditions.

The requirement of serum in cell culture is a major limitation for studies on secreted ribonucleases (RNases) because serum contains a high amount of ribonucleolytic activity. Defined culture condition is thus of interest to improve our knowledge of the RNase biology. We report here that cells from three different types and origins, Chinese hamster lung fibroblasts, bovine smooth muscle cells, and human endothelium-derived EA.hy926 cells, proliferate consistently in the presence of a basal medium supplemented with bovine serum albumin, high-density lipoproteins, basic fibroblast growth factor, insulin, and transferrin. Using a new quantitative radio-RNase inhibitor assay, two distinct ribonucleolytic assays, and a radioimmunoassay against angiogenin, it is shown that RNases became apparent in media conditioned by cell monolayers. Both the hamster lung fibroblast and the EA.hy926 cell lines secreted larger amounts of RNase inhibitor-interacting factors and RNase activity than normal smooth muscle cells. The serum-free medium represents an alternative way to grow these cells and allows investigation of biosynthesis and functions of RNases in culture. It should be useful to identify and quantitate unambiguously specific members of the RNase family secreted by normal versus tumor cells in culture.

Isolation and partial purification of lipid-linked oligosaccharides from calf pancreas.

Lipid-linked oligosaccharides containing at least five mannose residues (0.7 nmol/g of tissue) were isolated from calf pancreas by chloroform-methanol-water extraction and purification on DEAE-cellulose and Sephadex LH-20, and affinity chromatography on concanavalin A-Sepharose in the presence of nonionic detergent. The addition, prior to the chromatographic steps, of 14C-labeled lipid-linked oligosaccharides (synthesized in vitro by calf pancreas microsomes in the presence of GDP-D-[14C]mannose and UDP-D-[14C]glucose, respectively) as internal standards, indicated a final yield ranging from 38 to 50%. Analysis of the oligosaccharide residues by liquid chromatography of the lipid-free preparation, monitored by u.v. absorbance and radioactivity measurement of the tritiated compounds, indicated a heterogeneous mixture of oligosaccharides. Its components, ranging from Man5(GlcNAc)2 to Glc3Man9(GlcNAc)2, cochromatographed with the 14C-labeled derivatives from in vitro synthesis. Calf pancreas contains lipid intermediates bearing at least six mannose residues, such as Man9(GlcNAc)2-P-P-lipid, in almost equal or even higher amounts than Glc3Man9(GlcNAc)2-P-P-dolichol.

[Angiogenin: involvement in angiogenesis and tumour growth]. / L'angiogénine: implications dans l'angiogenése et le développment tumoral.

Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo. Angiogenin is normally present in plasma but overexpressed in cancer patients. The possible involvement of angiogenin in the development of cancer is suggested by its overexpression in patients with a variety of tumours and the observation that angiogenin antagonists prevent the growth of human tumour xenografts in athymic mice. This 14.1-kDa protein has 35% amino acid sequence identity with human pancreatic ribonuclease and displays ribonucleolytic activity. As only angiogenin is able to induce angiogenesis, its biological activities are thought to result from structural characteristics. Although the structural characteristics of angiogenin have been extensively studied, the understanding of its physiological role and of how its properties are expressed is still to be deciphered. This article reviews some of the biological, biochemical and structural properties of angiogenin.

[Birdshot chorioretinopathy associated with tamoxifen retinal toxicity]. / Un cas d'association de choriorétinopathie de type Birdshot et de toxicité rétinienne du tamoxifène.

We report a case of Birdshot retinochoroidopathy associated with ocular toxicity due to tamoxifen. Adverse drug effects were suspected due to the presence of yellow-white dots in the paramacular region and the fovea and by modifications of the retinal epithelial pigments. Ocular toxicity should be suspected as it may be reversible if recognized and stopped early. Other adverse ocular effects are described and the pathogenic mechanism of tamoxifen retinopathy analyzed.

[Giant cell tumor of the cricoid bone. Apropos of a case]. / Tumeur a cellules géantes du cricoïde. A propos d'un cas.

The authors report about one case of giant-cell tumor of the cricoid bone (osteoclastoma, myeloplaxic tumor). The diagnosis is difficult as the clinical and radiological symptoms are not specific. A detailed iconography sums up the clinicopathological characteristics of this tumor. The authors emphasize the necessity to perform wide exeresis surgery through total laryngectomy.

[Actinomycosis in otorhinolaryngology. Apropos of a case with localization in the nasal cavity]. / L'actinomycose en ORL. A propos d'un cas localisé aux fosses nasales.

The authors report an atypical case of actionomycosis implanted in the nasal cavity and occurring twenty years after septum surgery. Treatment by penicillin and surgical excision gave a good result. Cervicofacial actinomycosis is caused by actinomyctes which usually lives as a saprophyte in the oral cavity. A trauma is often found in the previous history. Diagnosis with tumors and abscess may be difficult. The histopathological examination shows typical aspects of the granuloma (gram+ and Grocott+) and the bacteriological isolation of the germ is difficult to obtain. Penicillin associated with surgical excision is the best therapy, but high doses must be used for a long time. The literature is reviewed without finding such a case.

[Analysis of prognostic factors in cervicofacial carcinology using the Cox model. An example of piriform sinus cancer]. / L'analyse des facteurs pronostiques en carcinologie cervico-faciale par le modèle de Cox. Un exemple à propos du cancer du sinus piriforme.

Analysis of prognosis factors was performed on a surgical series of 34 of piriform sinus cancer, based on the use of a multivariate study according to the Cox model. The presentation is essentially didactic emphasizing the main points: how to collect data, what data to collect, and what judgment criterion to use. The authors detail the interpretation to be drawn from the analysis results using Cox model.

[High frequency jet ventilation in heated gas saturated in water vapor without a reserve of medical gas under pressure. An original method]. / Jet ventilation à haute fréquence en gaz réchauffés et saturés en vapeur d'eau sans réserve de gaz médical sous pression. Une méthode originale.

A prototype of high frequency jet ventilator is compared with a classic device: Gambro Soxijet ventilator. The advantages of the prototype are: no need of pressured medical gas; warming and saturated moisture of the gas. A powerful compressor (2 M3.H-1 flow--3 bar pressure) draws up the moistened and warmed gases and injects them into a double pneumatic capacity. The first capacity is pressure limited by a relief valve (3 bar). Exhausted gases flow back to the pump. A miniature pressure regulator, placed between the two capacities, rules the driving pressure. Gas mixture is injected through a solenoid valve controlled by an electronic twin-timer. Results of both devices are similar. However, our prototype seems to be very convenient for developing countries where medical gases under high pressure are not often available.

[Stereomodel-assisted fibula free flap harvest and mandibular reconstruction: A technical note. Literature review of CAS and CAM applied to mandibular reconstruction]. / Reconstruction de la mandibule par lambeau libre de péroné assistée par une maquette tridimensionnelle : note technique. Revue de la littérature des techniques de CAO et FAO appliquées à la reconstruction mandibulaire.

PURPOSE: Mandibular reconstruction with fibula free flap harvest is currently the reference technique. Various preoperative processes have been developed to optimize this reconstruction. We report our experience with a simple, inexpensive, preoperative technique requiring a 3D printer, a device for maintaining mandibular reduction, a paper-cutting guide. TECHNICAL NOTE: Stereomodels of the mandible were obtained from computed tomography scan data and printed 3D in ABS. It allowed planning mandibular osteotomies, determine the angle between two bone fragments, and preoperatively modeling the osteosynthesis plate. A paper-cutting guide, and a simple device for maintaining mandibular reduction were also built. Two patients were operated on with this technique, with follow-up at 6 and 8 months. Reconstructions were successful with good clinical outcome in terms of mandibular contour and reconstructed segments positions. DISCUSSION: Preoperative planning of reconstruction may be used for mandibular osteotomies, fibular osteotomies, maintaining mandibular reduction, osteosynthesis, or placing implants for dental rehabilitation. The most complex procedures can virtually plan all these steps, but they are expensive and long to implement. Nevertheless, such procedures are quite expansive and require time not always compatible with carcinoma. Using a mandibular stereomodel is fast, easy, and cheap.

Review: Human trophoblast fusion and differentiation: lessons from trisomy 21 placenta.

The syncytiotrophoblast layer plays a major role throughout pregnancy, since it is the site of numerous placental functions, including ion and nutrient exchange and the synthesis of steroid and peptide hormones required for fetal growth and development. Inadequate formation and regeneration of this tissue contributes to several pathologies of pregnancy such as intrauterine growth restriction and preeclampsia, which may lead to iatrogenic preterm delivery in order to prevent fetal death and maternal complications. Syncytiotrophoblast formation can be reproduced in vitro using different models. For the last ten years we have routinely purified villous cytotrophoblastic cells (CT) from normal first, second and third trimester placentas and from gestational age-matched Trisomy 21 placentas. We cultured villous CT on plastic dishes to follow the molecular and biochemical aspects of their morphological and functional differentiation. Taking advantage of this unique collection of samples, we here discuss the concept that trophoblast fusion and functional differentiation may be two differentially regulated processes, which are linked but quite distinct. We highlight the major role of mesenchymal-trophoblast cross talk in regulating trophoblast cell fusion. We suggest that the oxidative status of the trophoblast may regulate glycosylation of proteins, including hCG, and thereby modulate major trophoblast cell functions.