Endoscopic En Bloc Versus Piecemeal Resection of Large Nonpedunculated Colonic Adenomas : A Randomized Comparative Trial.

BACKGROUND: Endoscopic resection of adenomas prevents colorectal cancer, but the optimal technique for larger lesions is controversial. Piecemeal endoscopic mucosal resection (EMR) has a low adverse event (AE) rate but a variable recurrence rate necessitating early follow-up. Endoscopic submucosal dissection (ESD) can reduce recurrence but may increase AEs. OBJECTIVE: To compare ESD and EMR for large colonic adenomas. DESIGN: Participant-masked, parallel-group, superiority, randomized controlled trial. (ClinicalTrials.gov: NCT03962868). SETTING: Multicenter study involving 6 French referral centers from November 2019 to February 2021. PARTICIPANTS: Patients with large (≥25 mm) benign colonic lesions referred for resection. INTERVENTION: The patients were randomly assigned by computer 1:1 (stratification by lesion location and center) to ESD or EMR. MEASUREMENTS: The primary end point was 6-month local recurrence (neoplastic tissue on endoscopic assessment and scar biopsy). The secondary end points were technical failure, en bloc R0 resection, and cumulative AEs. RESULTS: In total, 360 patients were randomly assigned to ESD (n = 178) or EMR (n = 182). In the primary analysis set (n = 318 lesions in 318 patients), recurrence occurred after 1 of 161 ESDs (0.6%) and 8 of 157 EMRs (5.1%) (relative risk, 0.12 [95% CI, 0.01 to 0.96]). No recurrence occurred in R0-resected cases (90%) after ESD. The AEs occurred more often after ESD than EMR (35.6% vs. 24.5%, respectively; relative risk, 1.4 [CI, 1.0 to 2.0]). LIMITATION: Procedures were performed under general anesthesia during hospitalization in accordance with the French health system. CONCLUSION: Compared with EMR, ESD reduces the 6-month recurrence rate, obviating the need for systematic early follow-up colonoscopy at the cost of more AEs. PRIMARY FUNDING SOURCE: French Ministry of Health.

Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study.

BACKGROUND: Fibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration. MATERIALS AND METHODS: We conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck's depression inventory were also studied. RESULTS: A significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method. CONCLUSION: A three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.

Evaluation of the Analgesia Nociception Index and videopupillometry to predict post-tonsillectomy morphine requirements in children: a single-centre, prospective interventional study.

Background: Tonsil surgery causes significant and challenging postoperative pain. The Analgesia Nociception Index (ANI) and videopupillometry are two techniques of interest to monitor nociception in adults and may predict postoperative morphine requirements. We hypothesised that these techniques could predict the need for morphine after tonsillectomy in children. The main objective was to assess the prognostic significance of ANI and videopupillometry, measured at the end of surgery, on morphine consumption determined by a Face, Legs, Activity, Cry, Consolability (FLACC) scale score >3 in the Post Anesthesia Care Unit (PACU). Methods: A single-centre, prospective, interventional study evaluating children between 2 and 7 yr old undergoing tonsil surgery was performed. ANI and videopupillometry with tetanic stimulation were measured under general anaesthesia 4 min after the end of the surgical procedure. Each child was evaluated every 10 min by a nurse using the FLACC scale in the PACU and blinded to the measurements performed in the operating theatre. Results: Eighty-nine children were analysed and 39 (44%) received morphine in the PACU. Neither ANI values nor videopupillometry values were predictive of postoperative morphine consumption (areas under the receiver operating characteristic curve 0.54, 95% confidence interval [CI; 0.42-0.65], and P=0.57; and 0.52, 95% CI [0.41-0.63], and P=0.69, respectively). Neither ANI values nor videopupillometry values were correlated to the maximum FLACC scale score in the PACU with ρ=0.04 (P=0.71) and ρ=0.06 (P=0.57), respectively. Conclusions: Neither ANI nor videopupillometry performed at the end of surgery can predict morphine consumption in the PACU in children undergoing tonsillectomy.

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study.

BACKGROUND: A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence. AIMS: To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up. METHODS: A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT. RESULTS: A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038). CONCLUSIONS: PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.

Home-Based Physical Activity in Patients With Breast Cancer: During and/or After Chemotherapy? Impact on Cardiorespiratory Fitness. A 3-Arm Randomized Controlled Trial (APAC).

OBJECTIVES: Physical activity (PA) programs are recommended for breast cancer care. However, their modalities remain to be discussed. This study determined the best time to begin a personalized or adapted program based on cardiopulmonary exercise test function. This randomized controlled trial evaluated the effect of home-based adapted PA (APA) performed during or after treatment on cardiorespiratory fitness (CRF) at 12 months. METHOD: The primary endpoint was the peak oxygen consumption (VO2peak) at 12 months (group A vs C and B vs C). Secondary endpoints included the 6-minute walking test, assessment of muscle strength, fatigue, quality of life, anxiety, and depression, and a questionnaire on PA levels. All tests were evaluated at baseline and at 6 and 12 months. A total of 94 patients with breast cancer were randomized to 3 different groups: group A, performing 6 months of APA during adjuvant care; group B, 6 months of APA after adjuvant care; and group C, 12 months of APA during and after specific care. The program combined 1 resistance session and 2 aerobic sessions per week. Analysis of variance was used for repeated measures, Student's t-test or the Mann-Whitney U-test for continuous variables, and χ2 test for binary or categorical variables. RESULTS: The study assessed 81 participants at 6 months and 73 at 12 months. The majority of patients completed more than 85% of the exercise sessions. The baseline for VO2peak and secondary outcomes did not differ among the groups. VO2peak increased during the exercise period and decreased during the chemotherapy period without APA, but at 12 months no significant difference was observed. The same variation was observed in the 6-minute walking test, with significance at 6 months between A+C versus B (P = .04), but no difference among the groups at 12 months. In the 3 groups, no decreases in other studied parameters were noted, except at 6 months in group B without APA. CONCLUSION: Home-based APA in breast cancer patients has a positive effect on CRF and physical functions, with no differences based on the timing of this program based on specific cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gouv.fr (NCT01795612). Registered 20 February 2013.

Pectoral I Block Does Not Improve Postoperative Analgesia After Breast Cancer Surgery: A Randomized, Double-Blind, Dual-Centered Controlled Trial.

BACKGROUND AND OBJECTIVES: General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique. We evaluated the efficacy of the first pectoral nerve block (Pecs I) in treating postoperative pain after breast cancer surgery. METHODS: A randomized, double-blind, dual-centered, placebo-controlled trial was performed. One hundred twenty-eight patients scheduled for unilateral breast cancer surgery were recruited. A multimodal analgesic regimen and surgeon-administered local anesthetic infiltration were used for all patients. Ultrasound-guided Pecs I was performed using bupivacaine or saline. The primary outcome was the patient pain score (numerical rating scale [NRS]) in the recovery unit 30 minutes after admission or just before the morphine administration (NRS ≥4/10). The secondary outcomes were postoperative opioid consumption (ie, in the recovery unit and after 24 hours). RESULTS: During recovery, no significant difference in NRS was observed between the bupivacaine (n = 62, 3.0 [1.0-4.0]) and placebo (n = 65, 3.0 [1.0-5.0]) groups (P = 0.55). However, the NRS was statistically significantly different, although not clinically significant, for patients undergoing major surgeries (mastectomies or tumorectomies with axillary clearance) (n = 29, 3.0 [0.0-4.0] vs 4.0 [2.0-5.0], P = 0.04). Morphine consumption during recovery did not differ (1.5 mg [0.0-6.0 mg] vs 3.0 mg [0.0-6.0 mg], P = 0.20), except in the major surgery subgroup (1.5 mg [0.0-6.0 mg] vs 6.0 mg [0.0-12.0 mg], P = 0.016). Intraoperative sufentanil and cumulative morphine consumption up to 24 hours did not differ between the 2 groups. Three patients experienced complications related to the Pecs I. CONCLUSIONS: Pecs I is not better than a saline placebo in the presence of multimodal analgesia for breast cancer surgery. However, its role in extended (major) breast surgery may warrant further investigation. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT01670448.

Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study.

BACKGROUND: Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. CONCLUSION/SIGNIFICANCE: Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803621.

Chemotherapy outcome predictive effectiveness by the Oncogramme: pilot trial on stage-IV colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) remains a major public concern. While conventional chemotherapeutic regimens have proved useful against advanced/metastatic diseases, progresses are to be made to effectively cure the large portion of patients not benefiting from these treatments. One direction to improve response rates is to develop chemosensitivity and resistance assays (CSRAs) efficiently assisting clinicians in treatment selection process, an already long preoccupation of oncologists and researchers. Several methods have been described to this day, none achieving yet sufficient reliability for recommended use in the clinical routine. METHODS: We led a pilot study on 19 metastatic CRC patients evaluating capacity of the Oncogramme, a standardized process using tumor ex vivo models, to provide chemosensitivity profiles and predict clinical outcome of patients receiving standard CRC chemotherapeutics. Oncogramme responses were categorized according to the method of percentiles to assess sensitivity, specificity and concordance. RESULTS: We report from a primary analysis a success rate of 97.4 %, a very good sensitivity (84.6 %), a below-average specificity (33.3 %), along with a global agreement of 63.6 % and a concordance between Oncogramme results and patients' responses (Kappa coefficient) of 0.193. A supplementary analysis, focusing on CRC patients with no treatment switch over a longer time course, demonstrated improvement in specificity and concordance. CONCLUSIONS: Results establish feasibility and usefulness of the Oncogramme, prelude to a larger-scale trial. Advantages and drawbacks of the procedure are discussed, as well as the place of CSRAs within the future arsenal of methods available to clinicians to individualize treatments and improve patient prognosis. TRIAL REGISTRATION: ClinicalTrials.gov database, registration number: NCT02305368.

Effects of home-based exercise training on VO2 in breast cancer patients under adjuvant or neoadjuvant chemotherapy (SAPA): a randomized controlled trial.

BACKGROUND: Breast cancer chemotherapy is associated with a decline in measured cardiorespiratory fitness and increased fatigue. Physical activity has emerged as a feasible intervention to limit these side effects. Quantitative evaluation is necessary to propose a better-adapted physical activity and to evaluate efficacy. AIM: We undertook a prospective study to assess the effects of a home-based adapted physical activity (APA) program on aerobic capacity, strength, and fatigue in women treated with adjuvant or neoadjuvant chemotherapy for breast cancer versus usual care. DESIGN: This was an open two-arm, randomized controlled trial. SETTING: Study included outpatient groups in the Department of Physiology and Medical Oncology of a hospital in France. POPULATION: Forty-four patients treated with adjuvant or neoadjuvant chemotherapy for breast cancer. METHODS: Patients were randomly assigned to a control group or an APA group. Intervention consisted of a 3-week, home-based, supervised, combined APA program (endurance and resistance training) during 27 weeks. The primary endpoint was cardiopulmonary function assessed by maximal peak oxygen consumption (VO2peak). Secondary endpoints included a 6-minute Walking Test (6MWT), and assessment of muscular strength, fatigue, quality of life, physical activity level, and anxiety/depression. RESULTS: At 27 weeks, VO2peak increased by 1.83±0.68 ml.min-1.kg-1 in the APA group (P=0.009) and decreased by 1.31±0.65 mL.min-1.kg-1 in the control group (P=0.046). The difference between the two groups was not significant (2.26±1.53 mL.min-1.kg-1, P=0.140) in intention-to-treat analysis, but it was significant in per protocol analysis (3.49±1.64 mL.min-1.kg-1, P=0.049). At 27 and 54 weeks, no significant differences were observed between the two groups for the cardiopulmonary exercise test, 6MWT, quadriceps strength, or quality of life. CONCLUSIONS: In breast cancer patients, a home-based supervised program during chemotherapy and radiotherapy treatment may be safe, feasible and increase VO2peak. In this study, heavy evaluation tests explain patient's non-adherence and do not permit to obtain statistically significant results between APA and control groups. CLINICAL REHABILITATION IMPACT: Aerobic home-based adapted physical activity is beneficial on aerobic capacity.