Efficacy of adjuvant chemotherapy schedules for breast cancer according to body mass index: results from the phase III GIM2 trial.

BACKGROUND: The phase III GIM2 trial showed improved disease-free survival (DFS) and overall survival (OS) with adjuvant dose-dense (DD) as compared with standard-interval (SI) chemotherapy in women with node-positive early-stage breast cancer (BC). This exploratory analysis aimed to investigate the benefit of different schedules according to body mass index (BMI) in this trial. PATIENTS AND METHODS: This analysis explored the efficacy, in terms of DFS and OS, of different chemotherapy schedules according to BMI. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. RESULTS: Out of 2091 patients enrolled, 1925 with known baseline BMI were randomized in the DD versus SI comparison and therefore included in this analysis: 31.6% were overweight and 19.3% obese. Overweight and obesity were significantly associated with postmenopausal status, pT >2, and pN >2 tumors. After a median follow-up of 15.0 years (interquartile range 8.4-16.3 years), multivariable Cox survival models demonstrated no association of different BMI categories on DFS [adjusted hazard ratio (adjHR) 0.96, 95% confidence interval (CI) 0.80-1.15 and adjHR 1.11, 95% CI 0.91-1.35 for overweight and obese patients, respectively, compared to patients with normal BMI] or OS (adjHR 0.90, 95% CI 0.71-1.14 and adjHR 1.18, 95% CI 0.92-1.52 for overweight and obese patients, respectively). No significant interaction was found between BMI and treatment schedule in terms of DFS (Pfor interaction = 0.56) or OS (Pfor interaction = 0.19). The survival benefit of DD chemotherapy was observed irrespective of different BMI categories, with a more pronounced benefit for overweight and obese patients. CONCLUSION: In node-positive BC patients, DD schedule should be considered the preferred schedule irrespective of BMI.

Cardiopulmonary deconditioning and plasma volume loss are not sufficient to provoke orthostatic hypertension.

Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.

Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Effects of 30 days bed rest and exercise countermeasures on PBMC bioenergetics.

AIM: Altered mitochondrial function across various tissues is a key determinant of spaceflight-induced physical deconditioning. In comparison to tissue biopsies, blood cell bioenergetics holds promise as a systemic and more readily accessible biomarker, which was evaluated during head-down tilt bed rest (HDTBR), an established ground-based analog for spaceflight-induced physiological changes in humans. More specifically, this study explored the effects of HDTBR and an exercise countermeasure on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs). METHODS: We subjected 24 healthy participants to a strict 30-day HDTBR protocol. The control group (n = 12) underwent HDTBR only, while the countermeasure group (n = 12) engaged in regular supine cycling exercise followed by veno-occlusive thigh cuffs post-exercise for 6 h. We assessed routine blood parameters 14 days before bed rest, the respiratory capacity of PBMCs via high-resolution respirometry, and citrate synthase activity 2 days before and at day 30 of bed rest. We confirmed PBMC composition by flow cytometry. RESULTS: The change of the PBMC maximal oxidative phosphorylation capacity (OXPHOS) amounted to an 11% increase in the countermeasure group, while it decreased by 10% in the control group (p = 0.04). The limitation of OXPHOS increased in control only while other respiratory states were not affected by either intervention. Correlation analysis revealed positive associations between white blood cells, lymphocytes, and basophils with PBMC bioenergetics in both groups. CONCLUSION: This study reveals that a regular exercise countermeasure has a positive impact on PBMC mitochondrial function, confirming the potential application of blood cell bioenergetics for human spaceflight.

Consensus conference statement on fluorescence-guided surgery (FGS) ESSO course on fluorescence-guided surgery.

BACKGROUND: Fluorescence-guided surgery (FGS) has emerged as an innovative technique with promising applications in various surgical specialties. However, clinical implementation is hampered by limited availability of evidence-based reference work supporting the translation towards standard-of-care use in surgical practice. Therefore, we developed a consensus statement on current applications of FGS. METHODS: During an international FGS course, participants anonymously voted on 36 statements. Consensus was defined as agreement ≥70% with participation grade of ≥80%. All participants of the questionnaire were stratified for user and handling experience within five domains of applicability (lymphatics & lymph node imaging; tissue perfusion; biliary anatomy and urinary tracts; tumor imaging in colorectal, HPB, and endocrine surgery, and quantification and (tumor-) targeted imaging). Results were pooled to determine consensus for each statement within the respective sections based on the degree of agreement. RESULTS: In total 43/52 (81%) course participants were eligible as voting members for consensus, comprising the expert panel (n = 12) and trained users (n = 31). Consensus was achieved in 17 out of 36 (45%) statements with highest level of agreement for application of FGS in tissue perfusion and biliary/urinary tract visualization (71% and 67%, respectively) and lowest within the tumor imaging section (0%). CONCLUSIONS: FGS is currently established for tissue perfusion and vital structure imaging. Lymphatics & lymph node imaging in breast cancer and melanoma are evolving, and tumor tissue imaging holds promise in early-phase trials. Quantification and (tumor-)targeted imaging are advancing toward clinical validation. Additional research is needed for tumor imaging due to a lack of consensus.

European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

BACKGROUND: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021. RESULTS: A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications. CONCLUSIONS: Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Near-infrared fluorescence cholangiography assisted laparoscopic cholecystectomy (FALCON): an international multicentre randomized controlled trial.

AIM: To assess the added value of Near InfraRed Fluorescence (NIRF) imaging during laparoscopic cholecystectomy. METHODS: This international multicentre randomized controlled trial included participants with an indication for elective laparoscopic cholecystectomy. Participants were randomised into a NIRF imaging assisted laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. Primary end point was time to 'Critical View of Safety' (CVS). The follow-up period of this study was 90 postoperative days. An expert panel analysed the video recordings after surgery to confirm designated surgical time points. RESULTS: A total of 294 patients were included, of which 143 were randomized in the NIRF-LC and 151 in the CLC group. Baseline characteristics were equally distributed. Time to CVS was on average 19 min and 14 s for the NIRF-LC group and 23 min and 9 s for the CLC group (p 0.032). Time to identification of the CD was 6 min and 47 s and 13 min for NIRF-LC and CLC respectively (p < 0.001). Transition of the CD in the gallbladder was identified after an average of 9 min and 39 s with NIRF-LC, compared to 18 min and 7 s with CLC (p < 0.001). No difference in postoperative length of hospital stay nor occurrence of postoperative complications was found. ICG related complications were limited to one patient who developed a rash after injection of ICG. CONCLUSION: Use of NIRF imaging in laparoscopic cholecystectomy provides earlier identification of relevant extrahepatic biliary anatomy: earlier achievement of CVS, cystic duct visualisation and visualisation of both cystic duct and cystic artery transition into the gallbladder.

Application of indocyanine green (ICG)-guided surgery in clinical practice: lesson to learn from other organs-an overview on clinical applications and future perspectives.

Indocyanine green (ICG) fluorescence-guided surgery is a modality of intra-operative navigation that might support the surgeon with enhanced visualization of anatomical structures in real time. Over the last years, it has emerged as one of the most promising and rapidly developing technical innovations in surgery. The most popular current clinical applications include fluorescence cholangiography, bowel anastomotic perfusion assessment, fluorescence-guided lymphography for sentinel lymph-node identification and guided lymphadenectomy and the possible use in oncological surgery for the identification and localization of tumors and the diagnosis and treatment of peritoneal carcinosis. This paper provides an overview of the multiple fields of applications of ICG fluorescence-guided surgery in visceral and oncological surgery, discussing indications summarizing most recent and significative available literature and giving technical notes of use.

Portomesenteric vein thrombosis following sleeve gastrectomy: Case report focusing on the role of pathogenetic factors.

INTRODUCTION: Sleeve gastrectomy has currently become the most commonly performed bariatric. procedure worldwide according to the last IFSO survey, overtaking gastric bypass with. a share of more than 50% of all primary bariatric-metabolic surgery. Gastric leak, intraluminal bleeding, bleeding from the staple-line and strictures are the most common complications. Portomesenteric vein thrombosis (PMVT)after sleeve gastrectomy is. another complication that has been increasingly reported in case-series in recent.years, although it remains uncommon. In this case report is described an extended portomesenteric vein thrombosis after. sleeve gastrectomy interesting splenic vein too with a favorable course and an. uneventful follow-up. We try to search in this case for pathogenetic factors involved in. this complication. CASE REPORT: A 42-year old man, with a body mass index (BMI) of 45 kg/m2, with a medical history of Obstructive Sleep Apnea Sindrome (OSAS) underwent laparoscopic sleeve gastrectomy. Early postoperative course was uneventful. Six days after discharge he complained abdominal pain and was admitted at the Emergency Department. A CT scan with intravenous contrast showed an occlusion of the portal vein, of the intrahepatic major branches and an extension to the superior mesenteric vein and the splenic vein. The patient received heparin and oral anticoagulation together with intravenous hydration and proton pump inhibitors. Considering the favourable course the patient was discharged after six days with long-term oral anticoagulation therapy. Anticoagulation with acenocumarol was continued for six months after a CT scan showed resolution of the PMVT without cavernoma. He had no recurrence of symptoms. DISCUSSION: Porto-mesenteric thrombosis after sleeve gastrectomy is a rare complication but it has been increasingly reported over the last 10 years along with the extensive use of sleeve gastrectomy. Because PMVT is closely associated with sleeve gastrectomy in comparison with other bariatric procedures, we need to investigate what pathogenetic factors are involved in sleeve gastrectomy. Thrombophylic state, prolonged duration of surgery, high levels of pneumoperitoneum, thermal injury of the gastroepiploic vessels during greater curvature dissection, high intragastric pressure, inadequate antithrombotic prophylaxis and delayed mobilization of the patient after surgery have been reported as pathogenetic factors of portmesenteric vein thrombosis. Most of the cases presented in the literature such as our clinical case resolve with medical therapy, although portal vein thrombus extends into the superior mesenteric vein and the splenic vein. CONCLUSION: Portomesenteric venous thrombosis is a rare but serious complication of bariatric surgery, especially associated with sleeve gastrectomy. Diagnosis is based on CT examination with intravenous contrast, and initial therapy is anticoagulation. Etiologic factors reported in the literature include a long duration of surgery, a high degree of pneumoperitoneum, high intragastric pressure after sleeve gastrectomy and thermal injury to the short gastric vessels and gastroepiploic arcade. Limited operative time, controlled values of pneumoperitoneum, careful dissection with energy device of gastric greater curvature, appropriate prophylaxis with low molecular weight heparin may be useful tools to prevent and limit this complication. Nonetheless we have to search which factors may condition the evolution of an extended PMVT as that described in this case towards resolution or to a further worsening clinical state. Early diagnosis? Correct treatment? Undiscovered patientrelated factors?

Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.

PURPOSE: Benign Prostatic Hyperplasia (BPH) is a result of prostate inflammation, frequently occurring in metabolic syndrome (MetS). Low testosterone is common in MetS. A randomized clinical trial was designed to evaluate if 24 weeks of testosterone therapy (TTh) in BPH men with MetS and low testosterone improve urinary symptoms and prostate inflammation. METHODS: One-hundred-twenty men with MetS waitlisted for BPH surgery were enrolled. They were categorized into normal testosterone (TT ≥ 12 nmol/L and cFT ≥ 225 pmol/L; n = 48) and testosterone deficient (TD) (TT < 12 nmol/L and/or cFT < 225 pmol/L; n = 72) then randomized to testosterone gel 2% (5 g/daily) or placebo for 24 weeks. At baseline and follow-up, questionnaires for urinary symptoms and trans-rectal ultrasound were performed. Prostate tissue was collected for molecular and histopathological analyses. RESULTS: No differences in the improvement of urinary symptoms were found between TTh and placebo (OR [95% CI] 0.96 [0.39; 2.37]). In TD + TTh, increase in prostate but not adenoma volume was observed (2.64 mL [0.07; 5.20] and 1.82 mL [- 0.46; 0.41], respectively). Ultrasound markers of inflammation were improved. In a subset of 61 men, a hyper-expression of several pro-inflammatory genes was found in TD + placebo when compared with normal testosterone. TTh was able to counteract this effect. For 80 men, the inflammatory infiltrate was higher in TD + placebo than in normal testosterone (0.8 points [0.2; 1.4]) and TD + TTh men (0.9 points [0.2; 1.5]). CONCLUSIONS: Twenty-four weeks of TTh in TD men with BPH and MetS improves ultrasound, molecular and histological proxies of prostate inflammation. This does not result in symptom improvement.

Surgical coaching applied to laparoscopic TME for continuous professional development in rectal surgery: proof of concept.

BACKGROUND: Coaching is maturing as a strategy for surgeons' continuous professional development in different types of surgery. Laparoscopic total mesorectal excision (LAP TME) is one of the recognized difficult procedures in colorectal surgery. Aim of this trial is to introduce the surgical coaching as a tool for a continuous technical education of LAP TME for cancer in a consultant surgeon carrier. METHODS: Twelve Italian colorectal surgeons were enrolled as trainees in the AIMS Academy rectal cancer surgical coaching project and attended a face-to-face 90-min surgical coaching on a pre-edited 45-min-long video of a laparoscopic proctectomy according to pre-determined guidelines. At the end of the coaching, all mentors were asked to fill a questionnaire evaluating the trainee's skills. All trainees had to fill a post-coaching questionnaire addressing the appropriateness of the coaching with respect to their actual level. RESULTS: Trainees were more confident in performing the extra-pelvic part of the surgical procedures compared to the intra-pelvic dissection. The most challenging steps according to the trainees were the seminal vesicles identification and the pelvic floor dissection. Mentors found the trainees quite confident in the approach to the vascular structures, lymphadenectomy, stapler utilization and bleeding control. The sharpness and the efficacy of the dissection, the dissection of the surgical planes and the anastomosis fashioning were reported at a lower level of confidence. The higher grade of satisfaction reported by the trainee came from the attention that the mentors demonstrated towards them, from the availability of the mentors to take into consideration the surgical issues raised and from the willingness to apply the suggestions received during their next proctectomies. CONCLUSIONS: The surgical coaching applied to LAP TME should be considered as an innovative tool for continuous professional development.

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer (ERIGE trial). Clinical and pharmacogenetic results on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

BACKGROUND: The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance. PATIENTS AND METHODS: This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen. RESULTS: From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS. CONCLUSIONS: The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity. EUDRACT NUMBER: 2012-003505-10.

Thyroid surgery during coronavirus-19 pandemic phases I, II and III: lessons learned in China, South Korea, Iran and Italy.

OBJECTIVE: We compared demographic and clinic-pathological variables related to the number of surgeries for thyroid conditions or for cancer, morbidity, and fine needle aspiration (FNA) practices among Covid19 pandemic phases I, II, III and the same seasonal periods in 2019. METHODS: The prospective database of the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Changchun, China was used for this study. Covid19 emergency levels were stratified according to the World Health Organization: phase I (January 25-February 25, 2020), phase II (February 26-March 19), phase III (March 20-April 20). RESULTS: There were fewer outpatient FNAs and surgeries in 2020 than in 2019. There were no thyroid surgeries during phase I. There were also fewer surgeries for cancer with a significant reduction of advanced stage cancer treatments, mainly stage T1b N1a in phase II and T3bN1b in phase III. Operative times and postoperative stays were significantly shorter during the pandemic compared to our institutional baseline. In phase III, vocal cord paralysis (VCP) increased to 4.3% of our baseline numbers (P = 0.001). There were no cases of Covid19-related complications during the perioperative period. No patients required re-admission to the hospital. CONCLUSION: The Covid19 outbreak reduced thyroid surgery patient volumes. The decrease of Covid19 emergency plans contributed to unexpected outcomes (reduction of early stage cancer treatment, decreased operative times and hospital stays, increased VCP rate).

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Scrotal ultrasound reference ranges and associations with clinical, seminal, and biochemical characteristics.

BACKGROUND: Scrotal color Doppler ultrasound (CDUS) still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study to assess the CDUS characteristics of healthy fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report and discuss the scrotal organs CDUS reference ranges and characteristics in HFM and their associations with clinical, seminal, and biochemical parameters. METHODS: A cohort of 248 HFM (35.3 ± 5.9years) was studied, evaluating, on the same day, clinical, biochemical, seminal, and scrotal CDUS following Standard Operating Procedures. RESULTS: The CDUS reference range and characteristics of the scrotal organs of HFM are reported here. CDUS showed a higher accuracy than physical examination in detecting scrotal abnormalities. Prader orchidometer (PO)- and US-measured testicular volume (TV) were closely related. The US-assessed TV with the ellipsoid formula showed the best correlation with the PO-TV. The mean TV of HFM was ~ 17 ml. The lowest reference limit for right and left testis was 12 and 11 ml, thresholds defining testicular hypotrophy. The highest reference limit for epididymal head, tail, and vas deferens was 12, 6, and 4.5 mm, respectively. Mean TV was associated positively with sperm concentration and total count and negatively with gonadotropins levels and pulse pressure. Subjects with testicular inhomogeneity or calcifications showed lower sperm vitality and concentration, respectively, than the rest of the sample. Sperm normal morphology and progressive motility were positively associated with epididymal head size/vascularization and vas deferens size, respectively. Increased epididymis and vas deferens sizes were associated with MAR test positivity. Decreased epididymal tail homogeneity/vascularization were positively associated with waistline, which was negatively associated with intratesticular vascularization. CDUS varicocele was detected in 37.2% of men and was not associated with seminal or hormonal parameters. Scrotal CDUS parameters were not associated with time to pregnancy, number of children, history of miscarriage. CONCLUSIONS: The present findings will help in better understanding male infertility pathophysiology, improving its management.

Could fluorescence-guided surgery be an efficient and sustainable option? A SICE (Italian Society of Endoscopic Surgery) health technology assessment summary.

BACKGROUND: Indocyanine green fluorescence vision is an upcoming technology in surgery. It can be used in three ways: angiographic and biliary tree visualization and lymphatic spreading studies. The present paper shows the most outstanding results from an health technology assessment study design, conducted on fluorescence-guided compared with standard vision surgery. METHODS: A health technology assessment approach was implemented to investigate the economic, social, ethical, and organizational implications related to the adoption of the innovative fluorescence-guided view, with a focus on minimally invasive approach. With the support of a multidisciplinary team, qualitative and quantitative data were collected, by means of literature evidence, validated questionnaires and self-reported interviews, considering the dimensions resulting from the EUnetHTA Core Model. RESULTS: From a systematic search of literature, we retrieved the following studies: 6 on hepatic, 1 on pancreatic, 4 on biliary, 2 on bariatric, 4 on endocrine, 2 on thoracic, 11 on colorectal, 7 on urology, 11 on gynecology, 2 on gastric surgery. Fluorescence guide has shown advantages on the length of hospitalization particularly in colorectal surgery, with a reduction of the rate of leakages and re-do anastomoses, in spite of a slight increase in operating time, and is confirmed to be a safe, efficacious, and sustainable vision technology. Clinical applications are still presenting a low evidence in the literature. CONCLUSION: The present paper, under the patronage of Italian Society of Endoscopic Surgery, based on an HTA approach, sustains the use of fluorescence-guided vision in minimally invasive surgery, in the fields of general, gynecologic, urologic, and thoracic surgery, as an efficient and economically sustainable technology.

Fashioning enterotomy closure after totally laparoscopic ileocolic anastomosis for right colon cancer: a multicenter experience.

BACKGROUND: Laparoscopic right hemicolectomy is a commonly performed procedure. Little is known on how to perform the enterotomy closure after stapled side-to-side intracorporeal anastomosis. METHOD: A multicentric case-controlled study has been designed to compare different ways to fashion enterotomy closure: double layer versus single layer, sewn versus stapled, and robotic versus laparoscopic approach. Furthermore, additional characteristics including sutures' materials, interrupted versus running suture and the presence of deep corner suture has been investigated. RESULTS: We collected data for 1092 patients who underwent right hemicolectomy at ten centers. We analyzed 176 robotic against 916 laparoscopic anastomosis: no significant differences were found in terms of bleedings (p = 0.455) and anastomotic leak (p = 0.405). We collected data from 126 laparoscopic sewn single-layer versus 641 laparoscopic sewn double-layer anastomosis: a significant reduction was recorded in terms of leaks in double-layer group (p = 0.02). About double-layer characteristics, we found a significant reduction of bleedings (p = 0.008) and leaks (p = 0.017) with a running suture; similarly, a reduction of bleedings (p = 0.001) and leaks (p = 0.005) was observed with the usage of deep corner closure. The presence of a barbed suture thread seemed to significantly reduce both bleedings (p = 0.001) and leaks (p = 0.001). We found no significant differences in terms of bleedings (p = 0.245) and anastomotic leak (p = 0.660) comparing sewn versus stapled anastomosis. CONCLUSIONS: Fashioning a stapled ileocolic intracorporeal anastomosis, we can recommend the adoption of a double-layer enterotomy closure using a running barbed suture in the first layer. Totally, stapled closure and robotic assistance have to be considered a non-inferior alternative.

Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.

BACKGROUND: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. RESULTS: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.

Estado epiléptico refractario en UCIP. Experiencia en un hospital de la Provincia de Buenos Aires / Refractory status epilepticus in the PICU. Experience at a hospital in the Province of Buenos Aires

Introducción: El estado epiléptico (EE) es la emergencia neurológica más frecuente en pediatría. Los pacientes que no responden al tratamiento estándar con dosis adecuadas de benzodiacepinas seguido de una droga antiepiléptica aceptable son definidos como Estado epiléptico Refractario (ER). Objetivo: caracterizar la población de niños con EE que ingresan a UCIP y determinar qué factores son predictores de refractariedad en esta población. Métodos: Estudio de casos y controles, retrospectivo. Población: niños con EE internados en UCIP desde Febrero 2015 a Febrero 2017. Casos: Estado epiléptico Refractario (ER). Controles: Estado epiléptico No Refractario (ENR). Se calculó el Odds Ratio (OR) individual para las distintas variables en Med Calc. Resultados: Se internaron 35 pacientes de los cuales 12 fueron casos y 23 controles. Hubo fiebre en 77% de los pacientes. En el total de niños estudiados hubo 11% con antecedente de convulsión febril, 11% con antecedente de epilepsia y 9% con antecedente de malformación del SNC. Los niños con antecedente de convulsión febril tuvieron 2,5 veces mayor riesgo de ER (OR: 2,58; IC 95%: 1,17-5,68). Los niños con EE que tenían antecedentes de enfermedad neurológica previa presentaron riesgo de ER 2,6 veces mayor que el grupo control (OR 2,60; IC 95%: 1,24-5,42). Discusión: Dado el aumento en la mortalidad de los pacientes con ER sería importante disponer de más herramientas para predecir este desenlace e iniciar tratamiento oportuno. Resultaría útil entrenar a los padres de niños con antecedente de convulsión febril en la aplicación de medicación antiepiléptica prehospitalaria, esto podría prevenir la farmacorresistencia, el daño neurológico y las complicaciones que acarrea el ingreso a UCIP. (AU)

Introduction: Status epilepticus (SE) is the most common neurologic emergency in children. Patients that do not respond to standard treatment with adequate doses of benzodiazepines followed by an acceptable antiepileptic drug are defined as having refractory status epilepticus (RSE). Objective: To characterize the population of children with SE admitted to the PICU and to determine predictive factors for refractoriness in this population. Methods: A retrospective case-control study was conducted. Population: Children with SE admitted to the PICU between February 2015 and February 2017. Cases: Refractory status pilepticus (RSE). Controls: Non-refractory status epilepticus (NRSE). Individual Odds Ratio (OR) was calculated for different variables using Med Calc. Results: 35 patients were admitted of whom 12 were cases and 23 controls. Overall, 77% of the patients had fever. Of all the children, 11% had a history of febrile seizures, 11% had history of epilepsy and 9% had a CNS malformation. Children with a history of febrile seizures had a 2.5-fold higher risk of developing RSE (OR: 2.58; 95% CI: 1.17-5.68). Children with SE that had a history of neurologic disease had a 2.6-fold higher risk of developing RSE than controls (OR 2.60; 95% CI: 1.24-5.42). Discussion: Given the increased mortality in children with RSE, availability of tools to predict this outcome in order to initiate early treatment is important. It would be useful to train the parents of children with a history of febrile seizures in the prehospital administration of antiepileptic drugs as this may prevent pharmaco-resistance, neurologic damage, and complication related to PICU admission (AU)

Sperm selection with density gradient centrifugation and swim up: effect on DNA fragmentation in viable spermatozoa.

Subjects increasing sperm DNA fragmentation (sDF) during Density Gradient Centrifugation (DGC), a common sperm selection procedure in Assisted Reproduction Techniques (ARTs), experience a 50% lower probability of pregnancy. Hence, identification of these subjects is of clinical importance. Here, we investigated whether such subjects are identified with higher accuracy detecting DNA fragmentation in viable (viable sDF) instead of total spermatozoa (total sDF) and whether swim up, an alternative procedure to DGC, does not increase sDF. With DGC, we identified 10/20 subjects increasing total sDF, and 2 more subjects using viable sDF. With swim up, we identified 8/40 subjects increasing total sDF, and 8 more subjects using viable sDF. In addition, viable sDF reveals more accurately the increase of the damage when it occurs. Finally, a multivariate analysis demonstrated that the proportional increase of sDF was higher after DGC respect to swim up. In conclusion, viable sDF is a more accurate parameter to reveal the increase of the damage by selection both with swim up and DGC. Swim up increases sDF in some samples, although at a lesser extent than DGC, suggesting that it should be used to select spermatozoa for ARTs when possible.