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Background: The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care., Methods: We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589., Findings: From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p<0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012., Interpretation: Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial., Funding: French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bone is the third metastatic site after liver and lungs. Bone metastases occur in one out of three lung cancers and are usually of osteolytic aspect. Osteolytic bone metastases are responsible of long bone and vertebral fractures leading to restricted mobility, surgery and medullar compression that severely alter quality of life and that have a huge medico-economic impact. In the recent years, Bone Metastatic Multidisciplinary Tumour Board (BM 2 TB) have been developed to optimize bone metastases management for each patient in harmony with oncology program. In this review, we will go through all the different aspects of bone metastases management including diagnosis and evaluation (CT scan, Tc 99m-MDP bone scan, 18 FDG-PET scan and biopsy for molecular diagnosis), systemic bone treatments (zoledronic acid and denosumab) and local treatments (interventional radiology and radiotherapy). Surgical strategies will be discussed elsewhere. Based on the last 2017-Lung Cancer South East French Guidelines, we present a practical decision tree to help the physicians for decision making in order to reach a personalized locomotor strategy for every patient., (Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Allogeneic bone marrow transplantation is being used to treat hematologic malignancies after induction. The efficacy of this procedure is due to both myeloablative conditioning and graft versus leukemia (GvL). However, the disadvantages of allogenic transplantation include graft versus host disease (GvH), the susceptibility of patients to opportunistic infections, and relapse from the original tumor. Since 1995 is used conditioning regimen which are deeply immunosuppressive and non myeloablative. The therapeutic toxicity related to myeloablation and drug side effects should be reduced. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft versus tumor (GvT), like GvL, will have a significant anti-tumoral effect. According to the literature, the feasibility of this procedure seems demonstrated. The fist available results in renal carcinomas are encouraging. However, the efficacy of this procedure remains uncertain for other potential indications. After presenting the published results, we will discussed the actual difficulties and the future potential developments.

Introduction: Tamoxifen--a non steroidal triphenylethyl compound--in addition to having antiestrogenic properties may provoke weak estrogenic effects, the well known "paradoxical effects" on the female genital tractus. Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma; subsequent attention has been drawn through high risk histologic subtypes including poorly differentiated patterns and uterine sarcomas., Exegesis: We report two cases of uterine sarcoma arising in postmenopausal women taking tamoxifen, 20 mg daily during 38 and 42 months, for breast carcinoma: one leiomyosarcoma and one endometrial stromal sarcoma; both cases were asymptomatic and detected by pelvic sonography., Conclusion: Further studies will be required to establish if there is a relationship between long term tamoxifen exposure and highly aggressive types of cancer of the uterine corpus exhibiting adverse histologic features such as uterine sarcomas. There is no consensus regarding uterine surveillance of women receiving tamoxifen. We advocate an annual gynecologic examination plus imaging by means of transvaginal ultrasonography.

Objectives: To evaluate the place of ovarian transposition by laparoscopy in an effort to preserve ovarian function without compromising oncological safety among young women requiring intravaginal brachytherapy before surgery for cervical cancer., Material and Methods: The series was represented by 20 cases, all FIGO stage I squamous cell malignant diseases of the cervix. Mean age: 32 years (range 23-40). Oophoropexy (7 instances) or lateral high ovarian transposition (13 instances) was performed by laparoscopy, just before brachytherapy using cesium 137., Results: Continued hormonal function was achieved in 58% of the available cases, 50% (3/6) after oophoropexy, 68% (8/11) after ovarian transposition. Mean follow-up was 8.5 years (range 5-13). The mean radiation dose absorbed by the displaced ovary was 2.6 Gy (range 1. 2-5.9)., Conclusion: Ovarian transposition through laparoscopy before brachytherapy should be advised for selected stage I squamous type malignant tumor size 2 cm without lymphatic/vascular channel invasion by neoplastic emboli and without lymph node involvement. This procedure has been abandoned in our institution, instead of this, primary surgical treatment is accomplished (laparoscopically-assisted vaginal) radical hysterectomy is associated with orthotopic ovarian conservation.

Study Aim: The aim of this study was to report a series of 80 patients treated by unilateral neck exploration for a sporadic primary hyperparathyroidism., Patients and Method: Between April 1992 and November 1998, 80 patients (65 women and 15 men, mean age: 63.5 years) with a single gland enlargement localized by ultrasonography, were operated on through a short unilateral neck incision, under general anesthesia in 72 cases and local in eight cases. The enlarged gland was removed with intraoperative pathological examination and intraoperative monitoring of parathyroid hormone., Results: Mean duration of surgery was 25 minutes. There was no postoperative mortality or morbidity. Mean duration of hospital stay was two days. The enlarged gland was an adenoma in 75 cases and an hyperplasia in five. Adequate intraoperative parathyroid hormone decrease was observed. Postoperative calcemia was normal in 78 patients (97.5%). Among 76 surviving patients, with a 31-month follow-up, there was only a suspicion of persistent hyperparathyroidism in two patients., Conclusions: Minimal invasive approach by unilateral neck exploration may be performed with safety and efficiency in patients with a single gland enlargement under intraoperative monitoring of parathyroid hormone.

Objectives: Assess the importance of systematic surgical exploration of the tumor focus in case of complete clinical response to neoadjuvant chemotherapy for operable breast cancer., Patients and Methods: Between 1985 and 1997, first intention chemotherapy (4 to 6 cures) was given to 433 breast cancer patients with resectable tumors measuring > or = 3 cm but who required mammectomy. Complete clinical response was observed in 112 patients (26%); 31 of them had normal mammography and ultrasound examinations (7%). Local treatment in this favorable context varied: 82 patients underwent surgery (71 conservative procedures, 11 radical procedures) and 30 patients received radiation therapy alone., Results: Complete histological response was obtained in 22 cases accounting for 6% of the entire series, 27% of the complete clinical responses, and 45% of the complete clinical and imaging responses. The incidence of local recurrence at a mean 107 month follow-up was compared between patients given complementary surgical or radiation therapy after complete clinical response. Recurrence was observed in 10 of the 82 operated patients versus 8 of the 30 nonoperated patients (12% versus 27%, NS)., Conclusion: Complete clinical response after neoadjuvant chemotherapy does not rule out the need for surgical resection of the tumor focus because the risk of neoplastic reliquats remains high (3 out of 4 cases) and because the surgical specimen provides important histological information for prognosis (in vivo chemosensitivity test). lumpectomy also contributes to reducing the risk of local recurrence.

Background: Leiomyomatosis is a benign smooth muscle tumor which can provoke serious complications in case of intracaval or intracardiac extension., Case Report: A 61-year-old woman had undergone hysterectomy at the age of 45 years for a hemorrhagic fibroma. She underwent surgery for infiltrative breast cancer 3 months before hospitalization and was taking tamoxifen 30 mg/day. In the cancer context, the diagnosis of cavo-cardiac metastatic thrombus was proposed but not confirmed at pathology. The diagnosis of uterine tissue intravascular leiomyomatosis was established on the basis of pathology findings and immunohistochemistry results., Discussion: Five other cases of leiomyomatosis after hysterectomy have been reported in the literature.

The role of axillary lymph node dissection for microinvasive ductal carcinoma in situ of the breast was analyzed in a series of 60 consecutive cases. Forty-four cases were subclinical mammographically-detected carcinomas revealed by the clusters of microcalcifications. Although pathologists differ in their criteria for microinvasion, the maximal size considered in this retrospective study was 2 mm. Axillary lymph node involvement was found in 3 cases (i.e. 5%) which harbored poor histologic features: comedocarcinoma subtype, high nuclear grade, and size of the ductal carcinoma in situ greater than 3 cm, requiring total mastectomy. While there is no need for axillary dissection in women with pure ductal carcinoma in situ, the management is quite different in proven microinvasion. Owing to the weakness of prognostic information given by cellular, biochemical and molecular features, instead of lymph node status, axillary dissection is still recommended in microinvasive ductal carcinoma in situ.

ATM mutations predispose cells to malignancy by promoting chromosomal instability. We have identified a family with multiple cancers that segregates a mutant allele of ATM, IVS61+2insTA, which causes skipping of exon 61 in the mRNA, as well as a previously undescribed polymorphism, IVS61+104C(54):T(46). The mutation was inherited by two sisters, one who developed breast cancer at age 39 and the second at age 44, from their mother, who developed kidney cancer at age 67. Molecular studies were undertaken to determine the role of the ATM gene in the development of cancer in this family. Studies of irradiated lymphocytes from both sisters revealed elevated numbers of chromatid breaks, typical of A-T heterozygotes. Studies on lymphoblastoid cell lines established from these individuals revealed abnormal p53 induction and apoptosis after DNA damage. Loss of heterozygosity (LOH) in the ATM region of chromosome 11q23.1 showed that the normal ATM allele was lost in the breast tumor of the older sister. LOH was not seen at the BRCA1 or BRCA2 loci. BRCA2 is not likely to be a cancer-predisposing gene in this family because each sister inherited different chromosomes 13 from each parent. The sisters share their maternal BRCA1 allele, although no mutation in this gene was detected in the family. Our findings suggest that haploinsufficiency at ATM may promote tumorigenesis, even though LOH at the locus supports a more classic two-hit tumor suppressor gene model., (Copyright 1999 Wiley-Liss, Inc.)

Subclinical mammographic abnormalities discovered through screening are subjected to excisional surgical biopsy in order to prove or rule out malignant disease of the breast by histological examination. Close attention should be paid by the surgeon to avoid cosmetically disfiguring scar and failure in excision removal exhibited on postoperative mammogram. Indications for surgical assessment are selected upon suspicious patterns of opacities, clusters of microcalcifications or architectural distortions. Good communication between the radiologist, the surgeon and the pathologist is required for proper management of non palpable lesion. The most adequate lumpectomy technique should be performed with regard to the oncologic risk and cosmetic outcome.

Purpose: Retrospective analysis of the results of radiotherapy in localized prostatic adenocarcinoma. Complications were excluded., Patients and Methods: Six-hundred-and-ten T1-T2 adenocarcinomas of the prostate were treated with continuous courses of external beam radiation therapy in 19 participating Institutes between January 1983 and January 1988. The mean follow-up was 10.4 years; the mean age of patients at the beginning of radiotherapy was 68.5 years., Results: A 10-year, local control had been achieved in 86% of T1-T2 (81.4% for T2). The 5- and 10-year metastatic relapse rates were 25.3% and 30% (29% and 38.1% for T2), respectively. At 10 years, 62.4% of T1-T2 were recurrence-free; overall survival rate was 45.8% and cause-specific survival rate was 70.5%; 29.9% of T1-T2 patients were alive and disease-free. T category (TNM), pathologic grade, pelvic lymph node status, local tumor control, and obstructive ureteral symptoms were correlated with survival. The influence of pelvic nodes radiation, dose, overall treatment time, previous endocrine treatment, and transuretral resection was not significant for disease-free survival (alive and disease-free) and other endpoints., Conclusion: There was no difference between the French series (1975-1982 and 1983-1988). The results of the literature are comparable to ours. As far as prognostic factors are concerned, this report provides evidence that the explainable variables which influence survival depend on the tumor and patient status.

We report a case of epidural metastasis with left renal vein invasion. This nonsymptomatic venous involvement was detected by ultrasonography and confirmed at CT and MR imaging. Such an unusual cause of renal vein tumor thrombus occurred through a lumbar vein which represents one of its usual collateral branches.

Objective: To assess the characteristic features of ovarian carcinoma mucocellular secondary to breast cancer., Methods: A retrospective pathology evaluation of ovariectomy specimens was conducted to compare the histological types with the original pathology diagnosis of breast cancer., Results: Ten cases of ovarian carcinoma mucocellular were observed. Histologically, the ovarian stroma presented voluminous mucin-containing vacuoles in epitheliomatous cells with peripheralized nuclei. In 7 out of 10 cases, the primary breast cancer was invasive lobular carcinoma., Discussion: These pathology findings are in agreement with comparative studies on the metastatic behavior of different histological types of breast cancer: invasive lobular carcinoma differs from invasive ductal carcinoma by its tropism for gastrointestinal and internal genital organs.

We report a study of 41 radical hysterectomies performed through laparoscopic approach for carcinoma of the cervix uteri. According to the FIGO staging, the tumors were classified as 12 stages Ia2, 24 stages Ib, 4 stages IIa and 1 stage IIb. 17 patients were treated by exclusive surgical procedure. 24 patients received a combination of radiation therapy and surgery 2 patients had a tumor of the cervical stump after subtotal hysterectomy. The mean duration of the procedure was 270 minutes. The post-op stay was 6.5 days. There was no major operative and postoperative complication. Only one patient required a blood transfusion. The intravenous pyelogram control was correct in all cases. At this time, with a 4 to 76 months follow-up, no recurrence was observed. This experience suggests the faisability of the laparoscopic radical hysterectomy. This approach seems to be convenient in young and non obese women with a tumor less than 4 cm in the greatest diameter.

Objectives: To evaluate the efficacy and morbidity of surgical treatment of carcinoma of the penis. This series of patients was derived from a retrospective multicentre study (1959-1989), initially concerning 506 patients, all treatments combined., Methods: One hundred and sixty-eight patients treated by surgery or surgery followed by external radiotherapy between 1959 to 1989 were included. The mean follow-up is 14.4 years and the mean participation is 4.7 years. Total or partial amputation was performed as first-line treatment in 89 patients (53%) and as second-line treatment in 11 patients (7%). Thirty-two patients received external radiotherapy as a complement to surgery. Inguinal lymph node dissection was performed as first-line treatment in 68 patients (41%) and secondarily in 19 patients (11%). Postoperative inguinal radiotherapy was performed in 52 patients. Monofactorial statistical analysis of prognostic factors is proposed., Results: The 5-year local control rate was 84%; it was independent of the stage of the tumour; the survival of the patients dying from any cause was 53%, the progression-free survival was 69% and the survival of patients dying from cancer of the penis was 75%. The vital prognosis is statistically significant related to the lymph node status. No significant relationship was observed between lymph node status and tumour stage. 61 complications involving the penis were observed in 40 patients (24%). Thirty-seven patients developed complications secondary to the lymph node dissection (24 cases of oedema of the lower limbs and 13 cases of inguinal sclerosis)., Conclusion: Surgical treatment ensured a local control globally comparable to that obtained with brachytherapy, but unlike this technique, the local control is independent of the stage. Brachytherapy should not always be performed in favour of mutilation for advanced tumours because the iatrogenic effects of brachytherapy are increased in these cases. An approach to the treatment of lymph nodes is proposed based on the authors' experience and the data of the literature.

We report the case of 68-year-old woman with an adenocarcinoma of the right colon. The family history also suggested that she might also be at risk of ovarian or endometrial cancer. Thus despite the lack of gynecologic symptoms, abdominal hysterectomy and bilateral salpingo-oophorectomy was proposed at the time of the right colectomy endometrial carcinoma was discovered at surgery. This finding and the family pedigree were consistent with the diagnosis of familial Lynch II syndrome. Appropriate biomolecular analyses were undertaken. This case shows the importance of family history taking in patients with cancer. The surgeon should be aware of such situations and correlate indications and procedures with the genetic risk of the patients.

The study concerns 265 patients with axillary lymph node dissection for non-palpable breast cancer. The mammographically detected breast tumors were: 36 ductal carcinomas in situ (DCIS), 23 microinvasive carcinomas, 206 invasive carcinomas of which 179 were invasive ductal cancers (IDC), 25 invasive lobular cancers (ILC) and 2 mucinous invasive carcinomas. The histologic size of the invasive component was < or = 5 mm in 38 cases, 6-10 mm in 84 cases, 11-15 mm in 53 cases, 16-20 mm in 16 cases, > 20 mm in 15 cases. Axillary dissection was performed immediately during the initial surgical procedure in 209 patients (79%) or secondarily in 56 (21%) according to the results of intraoperative examination of surgical specimens on frozen sections. Axillary lymph node involvement was not found in DCIS, microinvasive carcinomas or invasive carcinomas < or = 5 mm in size. Among all 206 invasive breast carcinomas, lymph node involvement was found in 7.8% (16/206) of cases. There were 9/84 (10.7%) in tumors > 10 mm, 7/122 (5.8%) in tumors < or = 10 mm. Thus, it is concluded that lymph node involvement is unlikely to be found in patients with non palpable breast cancers, specially those with carcinoma in situ, microinvasive breast tumors and invasive breast cancer with less than 5 mm maximum diameter size. Axillary dissection may be avoided in these patients. However, the use of new prognostic factors of lymph node involvement may help in the definition of patient group.