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Objective: Laparoscopic splenectomy (LS) is relatively contraindicated in cirrhotic portal hypertension (CPH) patients with complicating hypersplenic splenomegaly (HS). This study aimed to evaluate the effectiveness and safety of incorporation of iodized oil and gelatin sponge embolization to conventional splenic artery embolization (cSAE) with coiling in CPH/HS patients undergoing LS.Patients and Methods: Between April 2012 and March 2014, eligible CPH/HS patients (n = 56) were assigned to preoperative modified SAE (mSAE) with LS (mSAE+LS group, n = 16), cSAE with LS (cSAE+LS group, n = 20) or LS alone (LS group, n = 20). Main outcome measures included frequency of conversion to laparotomy, operative time, intraoperative bleeding, and transfusion.Results: The three groups had similar baseline characteristics (all P > .05). mSAE and cSAE similarly decreased LS conversion frequency (mSAE+LS versus cSAE+LS versus LS, 0.0% versus 10.0% versus 30.0%, P = .030) and operative time (155 ± 23 minutes versus 170 ± 26 minutes versus 221 ± 42 minutes, P < .001) compared with LS alone. mSAE significantly reduced bleeding (178 ± 22 mL versus 250 ± 27 mL versus 328 ± 67 mL, P < .001) compared with cSAE and LS alone. The three groups had similar postoperative recovery times and surgical morbidities (all P > .05).Conclusions: In CPH/HS patients, preoperative SAE reduced LS conversion frequency and reduced operative time compared with LS alone, while mSAE further decreased volume of blood loss. [ABSTRACT FROM AUTHOR]

Background: Joint salvage surgery for patients with juxtaarticular osteosarcoma remains challenging, especially when the tumor invades the epiphysis. Because patients are surviving longer with current chemotherapy regimens, it is advantageous to retain native joints if possible, especially in young patients. However, the results using joint-preserving tumor resections in this context have not been well characterized.Questions/purposes: (1) What are the functional outcomes after limb salvage surgery at a minimum of 3 years? (2) What are the oncologic outcomes? (3) Is joint salvage surgery for epiphyseal tumors associated with an increased risk of local recurrence compared with metaphyseal tumors not invading the epiphysis? (4) What are the complications associated with joint salvage surgery?Methods: Between 2004 and 2013, we treated 117 patients with juxtaarticular osteosarcoma; of those, 43 (38%) were treated with joint salvage surgery, and 41 (95%) of the 43 patients are included in our study. The other two (5%) were lost to followup before 3 years (mean, 4.4 years; range, 3-11 years,). During the period in question, we generally performed joint salvage surgery in these patients when they had a favorable response to chemotherapy, did not have a pathologic fracture or extrusion of the tumor into the joint, and did not have a whole-epiphyseal osteolytic lesion, a large mass, or obvious neurovascular involvement. This report is a followup of an earlier study; the current study includes an additional nine patients, and additional followup of a mean of 19 months for the patients included in the earlier report. We ascertained overall survival and survival free from local recurrence which was estimated using the Kaplan-Meier method, functional status of the limb which was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system, and recorded reconstructive complications including infection, fracture, skin necrosis, and nonunion. We compared oncologic and functional outcomes between patients with (n = 28) and without tumor extension to epiphysis (n =13). We also compared oncologic and functional outcomes among patients with different adjuvant treatments including microwave ablation (n = 11), cryoablation (n = 12), and navigation-assisted osteotomy (n = 5). Complications were tallied using records from our institutional database.Results: The overall Kaplan-Mayer survival rate was 82% (95% CI, 104-128 months) at 5 years. The overall Kaplan-Meier survivorship from local recurrence was 91% at 5 years (95% CI, 115-133 months). Three patients had a local recurrence, but none had local recurrence in or close to the remaining epiphysis. The MSTS scores ranged from 22 to 30 points, with a median of 28. There were no differences in survival rate, local recurrence, or MSTS scores between patients with a tumor that did not invade the epiphysis and those in whom the tumor did invade the epiphysis. There were differences in MSTS scores among patients with epiphyseal tumor extension in which different adjuvant techniques, including microwave ablation, cryoablation, and navigation-assisted osteotomy, were used. Additional surgical procedures were recorded for 10 patients (24%). Osteonecrosis of the residual epiphysis was detected 13 patients (31%).Conclusions: Our findings suggest it is possible to salvage joints in selected patients with juxtaarticular osteosarcoma around the knee. The patients who have a favorable response to chemotherapy are the best candidates for this approach. Future studies might explore the role of adjuvant techniques of microwave ablation and cryoablation, particularly when the tumor invades the epiphysis, and whether resections can be facilitated with navigation.Level Of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]

Background: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02).Conclusions: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. [ABSTRACT FROM AUTHOR]

High-grade glioma (HGG), and particularly Glioblastoma (GBM), can exhibit pronounced intratumoral heterogeneity that confounds clinical diagnosis and management. While conventional contrast-enhanced MRI lacks the capability to resolve this heterogeneity, advanced MRI techniques and PET imaging offer a spectrum of physiologic and biophysical image features to improve the specificity of imaging diagnoses. Published studies have shown how integrating these advanced techniques can help better define histologically distinct targets for surgical and radiation treatment planning, and help evaluate the regional heterogeneity of tumor recurrence and response assessment following standard adjuvant therapy. Application of texture analysis and machine learning (ML) algorithms has also enabled the emerging field of radiogenomics, which can spatially resolve the regional and genetically distinct subpopulations that coexist within a single GBM tumor. This review focuses on the latest advances in neuro-oncologic imaging and their clinical applications for the assessment of intratumoral heterogeneity. [ABSTRACT FROM AUTHOR]

Background: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone.Methods: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.Findings: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group.Interpretation: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.Funding: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Objective: To conduct a phase II trial of the combination of carboplatin, prednisone, and everolimus in metastatic castrate-resistant prostate cancer (mCRPC) as mTOR inhibition can overcome resistance to chemotherapy in prostate cancer.Methods: Patients with progressive mCRPC pretreated with docetaxel-based regimen were eligible. Performance status of 0-1 and adequate bone marrow, renal, and liver function were required. Primary end point was time to progression. Treatment consisted of carboplatin (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral everolimus 5 mg once daily and prednisone 5 mg twice daily.Results: Twenty-six patients were enrolled with median age of 69 years with 8 patients of African American origin. Grade 3 or 4 thrombocytopenia or neutropenia in 4 of 6 initial patients required dose adjustment of carboplatin to AUC of 4 for subsequent patients. There were no pharmacokinetic interactions between carboplatin and everolimus. The median time to progression was 2.5 months (90% confidence interval [CI], 1.8-4.3 months), and median overall survival was 12.5 months (90% CI, 7.7-18.7 months). Of 10 patients, 8 that demonstrated positive nuclear phosphorylated AKT (pAKT) staining on immunohistochemistry progressed within 9 weeks, whereas 2 patients with negative staining continued without progression for prolonged durations of 30 and 48 weeks. TSC1 gene mutations did not correlate with clinical outcome.Conclusion: The addition of the mTOR inhibitor everolimus to carboplatin demonstrated minimal clinical efficacy in metastatic prostate cancer. pAKT testing warrants further evaluation as a predictive marker of response to everolimus therapy. [ABSTRACT FROM AUTHOR]