[Management of native kidneys in renal transplant recipients with autosomal dominant polycystic kidney]. / Gestion des reins natifs chez les patients transplantés rénaux dans le cadre d'une polykystose rénale autosomique dominante.

Autosomal dominant polycystic kidney disease (ADPKD) is responsible for 10 % of end-stage renal failure cases in Europe and the majority of these patients will have their renal failure treated with kidney transplantation. In this context, native kidneys will have a negligible function but maybe the source of a series of complications, whether due to polycystosis or immunosuppression. These complications include urinary tract infections, renal neoplasms, high blood pressure and abdominal pain and must be managed specifically for this particular context. Native nephrectomy may also be considered to prevent these complications, but it is a serious procedure and the risk-benefit ratio must be carefully assessed. There are still no clear and consensual guidelines on the indications for this nephrectomy or on the ideal timing of it in relation to the transplant procedure. Nevertheless, a review of the various data in the literature allows us to suggest an algorithm to help the therapeutic decision.

La polykystose rénale autosomique dominante (ADPKD) est responsable de 10 % des insuffisances rénales terminales en Europe et la majorité de ces patients verront leur insuffisance rénale traitée par transplantation rénale. Dans ce contexte, les reins natifs auront une fonction négligeable, mais pourront, en revanche, être à l'origine d'une série de complications, que ce soit à la faveur de la polykystose ou de l'immunosuppression. Ces complications comprennent notamment les infections urinaires, les néoplasies rénales, l'hypertension artérielle et les douleurs abdominales. Elles doivent être prises en charge de façon spécifique à ce contexte particulier. Une néphrectomie native peut également être envisagée afin de prévenir ces complications, mais il s'agit d'une intervention lourde dont le rapport risque-bénéfice doit être soigneusement évalué. Il n'existe pas encore de directives claires et consensuelles sur les indications de cette néphrectomie ni sur le «timing¼ idéal de celle-ci par rapport à l'opération de transplantation. Cependant, une revue des différentes données de la littérature permet de proposer un algorithme aidant à la décision thérapeutique.

Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX.

BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.

p53 status and response to radiotherapy in rectal cancer: a prospective multilevel analysis.

The aim of this study was to evaluate, in a prospective study, the predictive role of p53 status analysed at four different levels in identifying the response to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70 patients were staged and endoscopic forceps biopsies from the tumour area were taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis, immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated after surgery by both pathologic downstaging and histologic tumour regression grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%); and p53 antibodies were detected in 11 patients (16.7%). In the multilevel analysis of p53 status, gene mutations correlated with both nuclear protein overexpression (P < 0.0001) and loss of heterozygosity (P = 0.013). In all, 29 patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%) were classified as tumour regression grade 1. Whatever the method of evaluation of treatment response, no correlation between p53 alterations and response to radiotherapy was observed. Our results do not support the use of p53 alterations alone as a predictive marker for response to radiotherapy in rectal carcinoma.

[Laparoscopic surgery versus laparotomy. Comparative analysis of stress markers]. / Coelio-chirurgie comparée à la laparotomie. Analyse comparative des marqueurs du stress.

The place of laparoscopic surgery continues to increase in the field of surgery in our specialty. Although the advantages would seem to be obvious, it seemed to us interesting to quantify, if possible, the parameters of operative stress and compare laparoscopic surgery with conventional surgery. Markers studied are Prolactin, Cortisol, Adrenaline, Nor-Adrenaline, Dopamine and the Beta-Endorphins. The only marker that shows any difference in the two procedures in our study is Beta-Endorphin which is significantly less raised in laparoscopic surgery directly after the operation (p less than 0.01). This was very specific for pain, which is one of the benefits of this technique and shown in this parameter which confirms the clinical impression. The curves of the changes in the different markers have been analysed and discussed.

Fast double antibody radioimmunoassay of human granulocyte myeloperoxidase and its application to plasma.

The haem enzyme myeloperoxidase (MPO) (EC 1.11.1.7) with a spectral A430/A280 ratio greater than 0.7 and a specific activity of 125 U/mg was purified from isolated human neutrophils. To obtain a radioimmunoassay (RIA) for this enzyme, a specific antiserum against human neutrophil MPO was raised in rabbits and used at an initial dilution of 1/10,000. MPO labelled with 125iodine by a technique of self-labelling in the presence of H2O2, had a specific activity of 24 mCi/mg. After incubation at room temperature (2 h) and separation by double antibody precipitation in the presence of polyethylene glycol, the sensitivity of the RIA was 21 ng/ml. The RIA showed good precision and accuracy with intra- and interassay coefficients of variation of less than 7% for MPO concentrations ranging from 100 to 800 ng/ml, and satisfactory recoveries of known amounts of exogenous MPO in plasma. For the measurement of MPO in blood, the best sampling technique was to collect blood into EDTA. Rapid centrifugation (within 20 min) was necessary for blood collected into heparin. Mean MPO values in normal individuals were 340 +/- 98 ng/ml in EDTA plasma (n = 152) and 332 +/- 82 ng/ml in heparinized plasma (n = 34). When MPO was measured 12-6 h after injury in critically ill patients high values (above 1000 ng/ml) were found in 6/15 patients with multiple injuries. In patients with sepsis (n = 22), MPO values were always above 1000 ng/ml.

[Celioscopy with peridural anesthesia. Techniques, indications, results in 220 cases]. / La coelioscopie sous anesthésie péridurale. Techniques, indications, résultats à propos de 220 cas.

The authors used epidural anaesthesia to carry out laparoscopy in 220 patients. The chief indications for the laparoscopies were GIFT (intratubal transfer of gametes) and tubal sterilization. The technique used was slightly different according to the indications for the use but they had to be sure of anaesthetising up to T4. In 90% of cases the patients tolerated the procedure well. No change in ventilation or in metabolic measurements. As far as fertilization was concerned studies carried out in various parameters failed to show any untoward side effects due to the use of local anaesthetics. Finally so long as the anaesthesia is only used for a short length of time this technique seems to be suitable for day cases.

Casein and other tumor markers in relation to cancer of the breast.

Five tumor markers can be simultaneously determined in the serum by radioimmunoassay: carcinoembryonal antigen (CEA), alpha-fetoprotein (alpha-FP), human chorionic gonadotropin (HCG), beta-subunit of HCG (beta-HCG) and kappa-casein. In a series of 935 healthy subjects, these antigens remain detectable or are detected within very precise limits. At the start of the clinical evolution of breast cancer, the incidence of pathological concentrations is increased as compared with the highest level observed in normal subjects. This high incidence is mainly due to a concomitant determination of CEA, kappa-casein, HCG and beta-HCG. The alpha-FP test is never positive, while the kappa-casein concentration is particularly high in the first clinical stages of breast cancer and with metastases. The concomitant determination of these tumor markers may be a biological element contributing to the diagnosis of neoplasia, although it is neither an absolute nor a specific criterium. Indeed, a pathological concentration of at least one antigen was observed in 5.5% of the subjects presenting with benign mastopathy. When metastases occur (25 patients), the incidence of pathological concentrations of at least one antigen increases: 88%, the absolute values of these levels increasing simultaneously. The determination of the antigen concentration therefore allows an evaluation of the extension of the disease. Surgical removal reduces the incidence of positivity of these antigens to 34%. Persistence of pathological levels seems to be related to a possibility of relapse or metastatic spreading. Finally, chemotherapy and radiotherapy applied on a tumor which is not excised, does not decrease the incidence of positivity of the tumoral markers, although their levels seem to fluctuate with the clinical evolution.