Operative start time may impact the quality of mesorectal excision in minimally invasive rectal surgery: retrospective analysis of 137 patients.

INTRODUCTION: Timing of major elective operations is a potentially important outcome variable. This study examined the impact of operative start time (OST) on pathologic and short-term outcomes of minimally invasive rectal surgery (MIRS). METHODS: All rectal tumors patients who underwent MIRS from May 2012 to April 2016 were identified. Peroperative outcomes and the oncological quality of surgical excision were compared between patients with OST before 13.00h and after. RESULTS: A total of 137 patients were included in the study (71 Romarobot-assisted and 66 conventional laparoscopic). Ninety-nine (72%) patients were operated before 13.00h and 38 after 13.00h. The majority of cases were low/middle rectal tumors (69%). Patient's baseline characteristics were quite similar in both groups. The rate of severe complication (p=0.460) or reoperation (p=0.614) was the same. Pathologic criteria (T or N stage, number of harvested lymph nodes, and presence of any positive margin) were the same between groups except for the quality of mesorectal excision (ME) that was significantly poorer for cases beginning after 13.00h (complete 91% vs 74%; p=0.016). The OST was found to be the only parameter associated with a poor quality of ME [OR 2.55 (1.08 - 6.36)]. CONCLUSION: Perioperative outcome after MIRS does not appear to be influenced by OST. Poorer quality of ME was observed and may thus raise important questions about the timing and sequence of case scheduling.

Medulloblastoma in childhood: What effects on neurocognitive functions?

PUPOSE: Medulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16-25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. PATIENTS AND METHODS: Participants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n=16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. RESULTS: The mean standard score Full-Scale Intelligence Quotient (FSIQ) (M=63, SD=12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M=67.7, SD=13.1), perceptual reasoning (M=63.5, SD=13.8) and processing speed (M=62.7, SD=15.5) were all found to be in the extremely low range, while xorking memory (M=75.5, SD=10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P=0.001 and P<0.001 respectively. CONCLUSION: Our study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.

Less Morbidity with Robot-Assisted Gastric Bypass Surgery than with Laparoscopic Surgery?

INTRODUCTION: Although several studies have compared totally robot-assisted gastric bypass (RA-GB) to laparoscopic gastric bypass (L-GB), the clinical benefit of the robotic approach remains unclear. MATERIALS AND METHODS: We compared perioperative outcomes of 82 consecutive patients undergoing RA-GB between 2013 and 2016 to 169 consecutive patients having undergone L-GB between 2009 and 2016. Secondary endpoints included duration of hospitalization, readmission rate, weight loss at 1 year, and the learning curve of RA-GB, assessed by operation times and complication rates. RESULTS: There were no statistically significant differences between groups concerning age (43.5 ± 11.2 vs. 42.2 ± 12.4 years), body mass index (42.4 ± 5.0 vs. 43.6 ± 7.2 kg/m2), or comorbidities. The rate of revision surgery was higher in L-GB group without reaching statistical significance. No statistically significant difference was observed for duration of operation (134 ± 35 vs. 135 ± 37 min), readmission rate at 90 days (4.9% vs. 8.9%), or percentage of excess weight loss at 1 year (RA-GB vs. L-GB) (76.8% ± 20.5 vs. 73.1% ± 23.5). There were fewer statistically significant complications overall in RA-GB (9.8% vs. 21.9%, p = 0.019). Median duration of hospital stay was shorter for RA-GB (3 vs. 4 days, p < 0.0001). The mean duration of operation for RA-GB decreased from 153 min in 2014 to 122 min in 2016; p = 0.004. CONCLUSION: In our experience, the robotic approach for gastric bypass was associated with fewer postoperative complications compared to traditional laparoscopic gastric bypass. Cost increment associated with RA-GB remains an important drawback that hampers its widespread.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30years of life: A French multicentre cohort study.

PURPOSE: Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. PATIENTS AND METHODS: This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC. RESULTS: A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. CONCLUSION: Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

Tandem high-dose chemotherapy strategy as first-line treatment of primary disseminated multifocal Ewing sarcomas in children, adolescents and young adults.

The prognosis of primary disseminated multifocal metastatic Ewing's sarcoma (PDMES) is poor even if a slight improvement has been achieved with high-dose alkylating agent-containing chemotherapy. To enhance treatment efficacy, we assessed the feasibility, safety and efficacy of a tandem high-dose chemotherapy (HDC) regimen. In a single institution, patients with PDMES received six courses of vincristine/ifosfamide/doxorubicin/etoposide induction therapy, followed by high-dose thiotepa, and then melphalan-busulfan, 8 weeks apart. Surgical resection of primary tumour was carried out between the two HDC regimens and 70 days after the last HDC regimen for post-operative radiotherapy or irradiation alone. From October 2002 to 2009, 13 of the 18 consecutive patients with PDMES (72%) received the full treatment programme. The other five patients experienced early progression and died. Among the 13 patients, 11 relapsed after the end of the treatment programme within 6 months (2.2-11.9) from end of therapy. Only two patients are still alive in first complete remission after 9 years. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 and 22%, respectively. The median EFS and OS duration from the diagnosis were 13.4 and 17.3 months, respectively. Neither major complications nor treatment-related death occurred. The tandem-HDC regimen was feasible, with expected side effects, but it did not improve the outcome of patients with PDMES.

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.

Educational trajectories after childhood cancer: When illness experience matters.

With the increase in survival from childhood cancer, research has increasingly focused on the educational and professional achievements of childhood cancer survivors. Yet, if large-scale studies provide an acute description of the current situation of childhood cancer survivors, little is known about their trajectories and the social processes shaping these trajectories. Using a qualitative methodology, drawing from a life course perspective, this study sought to describe the role of childhood cancer and its side effects in educational trajectories, as perceived by the participants. We investigated related processes of social adjustment to cancer, that is to say, choices or decisions that survivors related to the illness in the making of their career plans. Eighty long-term French childhood cancer survivors participating in the Euro2K longitudinal study were interviewed through in-depth, face-to-face interviews undertaken in 2011-2012. There were various types of impact described by respondents of the diagnosis of cancer on their trajectories. These varied according to gender. In women, childhood cancer tended to result in poor educational achievement, or in steering the individual towards a health care or child care occupation. This was justified by a desire to return the support that had been offered to them as patients. In men, however, childhood cancer led to a shift in career plans, because of physical sequelae, or because of concerns about their future health. Paradoxically, this limitation had a positive impact in their occupational achievement, as most of these men disregarded blue-collar jobs and chose more qualified white-collar occupations. Overall, findings suggest that childhood cancer influenced educational trajectories and, thus, socioeconomic status in adulthood, through mechanisms embedded in gender norms. These mechanisms could explain gender inequalities in educational achievement after childhood cancer reported in large-scale cohort studies.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005).

BACKGROUND: To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. PATIENTS AND METHODS: From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a multimodal therapy including ifosfamide-doxorubicin chemotherapy and radiotherapy, according to a risk stratification based on surgical stage, tumor size and site, and nodal involvement. RESULTS: With a median follow-up of 52.1 months (range 13.8-104.4 months), event-free survival (EFS) was 81.9% and 80.7%, and overall survival (OS) was 97.2% and 90.7%, at 3 and 5 years, respectively. The only significant prognostic variable at univariate analysis was the risk group: 3-year EFS was 91.7% for low-risk, 91.2% for intermediate-risk, and 74.4% for high-risk cases. In 24 low-risk patients (completely resected tumor ≤5 cm in size) treated with surgery alone, there were two local relapses and no metastatic recurrences. Among 67 high-risk patients (unresected, or axial tumor or nodal involvement), 66 underwent surgery after neoadjuvant chemotherapy. Response to chemotherapy was 55.2%, including 22.4% cases with complete or major partial remissions, and 32.8% with minor partial remissions. CONCLUSION: This study demonstrates that collaborative prospective studies on rare pediatric sarcomas are feasible even on a European scale, with excellent treatment compliance. The overall results of treatment were satisfactory, with higher survival rates than those previously published by pediatric groups. Nonetheless, larger, international projects are needed, based on a cooperative effort of pediatric and adult oncologists. CLINICAL TRIALS NUMBER: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.

Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups.

BACKGROUND: Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. PATIENTS AND METHODS: Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). RESULTS: Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. CONCLUSIONS: While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0-1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3-4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS.

Appendicitis and diverticulitis of the colon: misleading forms.

Appendicitis and diverticulitis of the colon are the two main causes of febrile acute abdomen in adults. Diagnosis from imaging (ultrasound and CT) is usually easy. However, an imaging procedure which is not suitable for the clinical situation and an examination performed with the wrong protocol are sources of error and must be avoided. Anatomical variants, inflammatory cancers, complicated forms (perforation, secondary occlusion of the small intestine, peripheral abscesses, fistulae, pylephlebitis, liver abscesses) and associated signs related to a peritoneal inflammatory reaction (reflex ileus, reactive ileitis or salpingitis) can also lead to a wrong diagnosis.

[Brachytherapy role in pediatric rhabdomyosarcomas]. / Place de la curiethérapie dans les rhabdomyosarcomes pédiatriques.

Brachytherapy in paediatric malignancies is rarely used, limited to expert institutions. The most frequent tumour sites treated with brachytherapy are gynaecological rhabdomyosarcomas, and prostate/bladder rhabdomyosarcomas. Ballistic advantages make brachytherapy technique the treatment of choice, with a high and selective protection of organs at risk. Techniques, brachytherapy modalities (low dose-rate, high dose-rate, pulsed dose-rate), doses and indications vary according to centres. Brachytherapy advantages are in relation with ballistic properties, allowing a very high dose to the target with normal tissue sparing. This review analyzes brachytherapy techniques, indications and results according to the two most frequent tumour sites: gynaecological and bladder/prostate tumours. This technique requires a muldisciplinary approach.

Imaging of intestinal involvement in endometriosis.

Deep gastrointestinal involvement in endometriosis is characterised by fibrous, retractile thickening of the intestinal wall. The most common location is the upper rectum, in contiguity with a lesion of the torus uterinus. As part of a preoperative assessment, it is essential to establish an accurate and exhaustive map of intestinal lesions so that the surgeon can plan his actions. Transvaginal sonography and MRI correctly analyse pelvic and rectal involvement. Given the frequency of multiple intestinal sites, particularly sigmoid and associated ileo-caecal lesions, water enema CT should be performed. The role of rectal endoscopic sonography is debated.