Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer.

BACKGROUND: Local occurrence of prostate cancer (PCa) after external beam radiation (EBRT) may benefit from definitive local therapy. OBJECTIVE: To evaluate the safety and efficacy of salvage high-intensity focal ultrasound (HIFU) in local PCa recurrence after EBRT and to determine prognostic factors for optimal patient selection. DESIGN, SETTING, AND PARTICIPANTS: Between 1995 and 2006, patients with a local PCa recurrence after EBRT were retrospectively included. INTERVENTION: All patients received salvage HIFU with the Ablatherm device. MEASUREMENTS: Prognostic factors (pre-EBRT risk group, androgen-deprivation [AD] use, pre-HIFU prostate-specific antigen [PSA], Gleason score and positive biopsy percentage) were studied in univariate and multivariate analyses. Progression was defined as positive biopsy and/or last PSA > nadir + 2 ng/ml and/or adjuvant therapy introduction. All complications were recorded. RESULTS AND LIMITATIONS: Some 194 HIFU sessions for 167 patients were performed. Local cancer control was achieved with negative biopsy results in 122 (73%) patients. The median PSA nadir was 0.19 ng/ml. The mean follow-up period was 18.1 mo (range: 3-121 mo). Seventy-four patients required no hormone therapy. The actuarial 5-yr overall survival rate was 84%. The actuarial 3-yr progression-free survival rate was significantly lower in three circumstances: (1) worsening of the pre-EBRT stage with 53%, 42%, and 25% for low-, intermediate-, and high-risk patients, respectively, (2) increase in the pre-HIFU PSA, and (3) use of AD during PCa management. In multivariate analyses, the risk ratio for intermediate- and high-risk patients were 1.32 and 1.96, respectively. The risk ratio was 2.8 if patients had received AD. No rectal complications were observed. Urinary incontinence accounted for 49.5% of the urinary sphincter implantations required in 11% of patients. This is a retrospective study in which the role of the PSA doubling time and the time until recurrence was not evaluated. CONCLUSIONS: Salvage HIFU is a curative treatment option for local relapse after EBRT with acceptable morbidity. Careful patient selection is imperative depending upon the aforementioned prognostic factors

Are protocol graft biopsies after pediatric liver transplantation useful? Experience in a single center over 20 years

Abstract Background The role of protocol liver biopsies (PLB) in the follow‐up of pediatric liver transplant recipients remains questionable. This single‐center retrospective study aimed to evaluate their clinical impact on the long‐term management of pediatric liver transplant recipients. Methods We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT). Results A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1‐year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03). Conclusion Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5‐year protocol

Three Consecutive Pregnancies in a Patient with Chronic Autoimmune Thyroid Disease Associated with Hypothyroidism and Extremely High Levels of Anti-Thyrotropin Receptor Antibodies

International audienceBackground: Thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAb) can be present in chronic autoimmune thyroiditis. Transplacental TRAb transfer can lead to fetal thyroid dysfunction and serious complications. Patient Findings: We report the case of a woman with autoimmune hypothyroidism and extremely high TRAb levels, with blocking and stimulating activities (biological activities characterized with Chinese hamster ovary cells expressing TSHR). At week 22 of her first pregnancy, sonography detected fetal growth retardation and cardiac abnormalities (extreme tachycardia, right ventricular dilatation, pericardial effusion). The mother's TRAb level, assayed later, was 4030 IU/L (n < 10). Delivered via caesarean section gestational week 30, the newborn girl had several malformations, signs of malnutrition, goiter and hyperthyroidism associated with elevated TRAb (1200 IU/L). The newborn died 26 days after delivery. Faced with persistently high TRAb levels and a desire to become pregnant again, the woman was treated with three consecutive 740-MBq activities of iodine-131, which resulted in a decrease in TRAb to 640 IU/L. The patient had two subsequent pregnancies 16 and 72 months after the radioiodine administration. During the close follow-ups, fetal development was normal, and initial TRAb levels during the two pregnancies were 680 and 260 IU/L, respectively, which initially decreased but then increased in late pregnancy. In both cases, labor was induced at 34 weeks. The newborns, mildly hyperthyroid at birth, required carbimazole treatment at days 5 and 2, respectively. The mild hyperthyroidism despite high TRAb levels was likely due to the concomitant presence of stimulating and blocking TRAb. The two girls, now aged 12 and 8 years, are in good health. The mother has no detectable thyroid gland tissue and is euthyroid on levothyroxine (175 μg/d). Her TRAb level gradually decreased to 136 IU/L. Summary and Conclusions: This remarkable case illustrates the severe consequences of untreated fetal hyperthyroidism and the need to assay and follow-up TRAb levels in women of reproductive age with autoimmune thyroiditis

За кадры. 1971. № 61 (1575)

Рядовые студенческой гвардии / М. БорисоваКонференции в Оксфорде / С. П. БугаевДонести до каждого / А. АлександровичБольше доверия! / Г. КуницынВ звании студента утвержден / П. СеменовПоложение о проведении в комсомольской организации ТПИ Ленинского зачета "Решения XXIV съезда КПСС - в жизнь"Осенние мелодии / А. МеркушеваПриглашает оперная студияВ братской Монголии / И. Т. Лозовски

Prévention du carcinome rénal : l’approche nutrigénétique

La fréquence du cancer du rein (RCC), 3 % des cancers humains, augmente dans les pays industrialisés, laissant supposer l’intervention de facteurs toxiques (xénobiotiques et/ou alimentation, trichloréthylène, tabagisme et obésité). Le RCC survient le plus souvent sous forme sporadique mais est également retrouvé dans un contexte familial : la maladie de von Hippel-Lindau (VHL). L’existence, d’une part, d’une grande hétérogénéité intra- et inter-familiale dans le contexte du VHL et, d’autre part, la susceptibilité variable à des carcinogènes chimiques dans les formes sporadiques, laisse supposer, en outre, la participation de gènes modificateurs conditionnels. Afin d’identifier des sous-groupes d’individus particulièrement exposés ou, au contraire, protégés du fait de certains génotypes, nous avons collecté une série de 460 tumeurs et de patients appartenant à 79 familles VHL et développé un outil informatique, l’« universal mutation database » (UMD) pour les mutations du gène VHL, permettant de rechercher des corrélations. Les mutations du gène VHL à l’origine à la fois des RCC sporadiques et de la maladie de VHL sont de nature différente : 1) dans les tumeurs sporadiques, 83 % des mutations du gène VHL sont des mutations aboutissant à un décalage du cadre de lecture (délétion, insertion, non-sens = « frameshift »). Les 17 % restant comprennent des transversions (3/4) et des transitions (1/4). Cette proportion élevée de transversions suggère fortement l’implication de substances carcinogènes (fumée de tabac) dont l’impact est largement conditionné par la variabilité génétique de l’activité des enzymes de biotransformation ; 2) pour les formes familiales, les mutations de type faux sens prédominent dans 65 % des cas. Cette différence permet de définir un facteur pronostique de développer un RCC pour les patients VHL en fonction de la nature de la mutation germinale dont ils sont porteurs. Afin de repérer les génotypes conférant un risque élevé en présence de substances potentiellement carcinogènes, nous avons établi le génotype des patients pour 8 gènes (une cinquantaine de génotypes) impliqués dans le métabolisme des xénobiotiques. Cette étude fait apparaître une relation significative entre le développement d’un RCC et des combinaisons d’allèles comprenant : CYPIA1 ("variant"), NAT2 et NAT1 (acétyleurs lents) et GSTM1 (allèle nul). D’éventuelles associations entre les génotypes "à risque" et le profil des mutations somatiques observées chez les patients, mais aussi à différents stades tumoraux, pourraient aider à 1) préciser la nature de certains profils de mutagenèse en relation avec l’activité ou la déficience de telle ou telle enzyme du métabolisme des xénobiotiques et sous l’effet de tel ou tel carcinogène ; 2) montrer que, dans le contexte du VHL, certaines combinaisons d’allèles de ces différents gènes confèrent un risque particulier de développer certains types de tumeur. Ainsi, suivre "à la trace" des substances potentiellement carcinogènes, à la fois par l’empreinte laissée au niveau de l’ADN, ainsi qu’à travers les allèles conditionnellement délétères de gènes participant à leur détoxication, devrait permettre une meilleur prévention grâce à une alimentation personnalisée pour les individus présentant ces génotypes