Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study

PurposeEmerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset.MethodsFifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control.ResultsIn total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26–1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56–415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84–46.70; p = 0.007) were independently associated with an increased risk of major complications.ConclusionA dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.     

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study

ObjectiveTo examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC).MethodsThe Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity).ResultsNulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast.ConclusionAmong young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman’s risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.     

Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis

PurposeTo use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).Patients and methodsWe enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.ResultsAfter multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52–0.81, P < 0.0001) and 0.58 (0.47–0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2–4 (ypT3–4) and postchemotherapy pathologic nodal stages N2–3 (ypN2–3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38–0.69, P < 0.0001), 0.60 (0.40–0.88, P = 0.0096), and 0.64 (0.48–0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0–4, ypN0–3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.ConclusionFor patients with breast cancer ypT3–4, ypN2–3, or pathologic stages IIIA–IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.     

Postoperative chemotherapy and radiation improve survival following cardiac sarcoma resection

ObjectiveCardiac sarcoma represents a rare and aggressive form of cancer with a paucity of data to produce outcome-driven evidence-based guidelines. Current surgical management consists of resection with postoperative therapy (chemotherapy, radiation, or both) offered on a selective, individualized basis. This study was designed to determine whether postoperative therapy was associated with improved overall survival after resection.MethodsThe National Cancer Database was used to identify patients with cardiac sarcoma between 2004 and 2015. Patient characteristics were stratified by treatment (surgical, nonsurgical, and none), and treatment was analyzed by stage. Overall survival, assessed with Kaplan–Meier methodology, was compared between patients who received postoperative therapy and those who did not following resection. Multivariable survival modeling using a Weibull model identified risk factors associated with survival while controlling for confounders.ResultsThe study included 617 patients diagnosed with cardiac sarcoma. Only 24% (149/617) of patients were diagnosed with early-stage disease. Angiosarcoma represented 48% (298/617) of cases and was the most commonly identified histologic subtype. 60% (372/617) underwent surgical resection and 58% (216/372) of those patients were treated with postoperative therapy. Following surgery, median survival was more than doubled for patients treated with postoperative therapy (19 months vs 8 months, P = .026). However, 5-year overall survival was similar between the groups. Multivariable analysis confirmed an improvement in survival with postoperative therapy (hazard ratio, 0.68; 95% confidence interval, 0.51-0.91, P = .009).ConclusionsPostoperative therapy is associated with better median survival following resection of cardiac sarcoma. However, at 5 years, the difference in overall survival is not statistically significant.     

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

BackgroundChemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX.MethodsWe compared three different doses of q3w nab-PTX (Standard: 260 mg/m² [SD260] vs Medium: 220 mg/m² [MD220] vs Low: 180 mg/m² [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was <0.75 or >1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded.ResultsOne hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180.ConclusionsIntravenous administration of low-dose nab-PTX at 180 mg/m² q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC.     

Incidental diagnosis of Covid-19 pneumonia on chest computed tomography

PurposeThe purpose of this study was to determine the prevalence and imaging characteristics of incidentally diagnosed COVID-19 pneumonia on computed tomography (CT).Materials and methodsThis retrospective study was conducted between March 20th and March 31st, 2020 at Cochin hospital, Paris France. Thoracic CT examinations of all patients referred for another reason than a suspicion of SARS-CoV-2 infection were reviewed. CT images were analyzed by a chest radiologist to confirm the presence of findings consistent with COVID-19 pneumonia and quantify disease extent. Clinical and biological data (C-reactive protein serum level [CRP] and white blood cell count) of patients with CT findings suggestive for COVID-19 pneumonia were retrieved from the electronic medical chart.ResultsDuring the study period, among 205 diagnostic CT examinations, six examinations (6/205, 3%) in 6 different patients (4 men, 2 women; median age, 57 years) revealed images highly suggestive of COVID-19 pneumonia. The final diagnosis was confirmed by RT-PCR. Three inpatients were suspected of extra thoracic infection whereas three outpatients were either fully asymptomatic or presented with fatigue only. All had increased CRP serum level and lymphopenia. Disease extent on CT was mild to moderate in 5/6 patients (83%) and severe in 1/6 patient (17%).ConclusionCumulative incidence of fortuitous diagnosis if COVID-19 pneumonia did not exceed 3% during the highest pandemic phase and was predominantly associated with limited lung involvement.     

Sleep disturbances and restless legs syndrome in postmenopausal women with early breast cancer given adjuvant aromatase inhibitor therapy

IntroductionWhether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturbances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue.MethodsBetween March 2014 and November 2017, validated questionnaires for assessing insomnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were administered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy.ResultsAI therapy significantly decreased the patients’ QoL, but did not influence insomnia, anxiety or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%).ConclusionAlthough AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.     

COVID-19: A qualitative chest CT model to identify severe form of the disease

PurposeThe purpose of this study was to identify clinical and chest computed tomography (CT) features associated with a severe form of coronavirus disease 2019 (COVID-19) and to propose a quick and easy to use model to identify patients at risk of a severe form.Materials and methodsA total of 158 patients with biologically confirmed COVID-19 who underwent a chest CT after the onset of the symptoms were included. There were 84 men and 74 women with a mean age of 68 ± 14 (SD) years (range: 24–96 years). There were 100 non-severe and 58 severe cases. Their clinical data were recorded and the first chest CT examination was reviewed using a computerized standardized report. Univariate and multivariate analyses were performed in order to identify the risk factors associated with disease severity. Two models were built: one was based only on qualitative CT features and the other one included a semi-quantitative total CT score to replace the variable representing the extent of the disease. Areas under the ROC curves (AUC) of the two models were compared with DeLong's method.ResultsCentral involvement of lung parenchyma (P < 0.001), area of consolidation (P < 0.008), air bronchogram sign (P < 0.001), bronchiectasis (P < 0.001), traction bronchiectasis (P < 0.011), pleural effusion (P < 0.026), large involvement of either one of the upper lobes or of the middle lobe (P < 0.001) and total CT score ≥ 15 (P < 0.001) were more often observed in the severe group than in the non-severe group. No significant differences were found between the qualitative model (large involvement of either upper lobes or middle lobe [odd ratio (OR) = 2.473], central involvement [OR = 2.760], pleural effusion [OR = 2.699]) and the semi-quantitative model (total CT score ≥ 15 [OR = 3.342], central involvement [OR = 2.344], pleural effusion [OR = 2.754]) with AUC of 0.722 (95% CI: 0.638–0.806) vs. 0.739 (95% CI: 0.656–0.823), respectively (P = 0.209).ConclusionWe have developed a new qualitative chest CT-based multivariate model that provides independent risk factors associated with severe form of COVID-19.     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Bilevel positive airway pressure for gastroscopy with sedation in patients at risk of hypoxemia: A prospective randomized controlled study

Study objectiveHypoxemia is one of the most frequent adverse events during sedated gastroscopy, and there is still no effective means to prevent and cure it. Therefore, we conducted this randomized trial to confirm our hypothesis that, compared with the nasal cannula group, bilevel positive airway pressure (BPAP) would decrease the incidence of hypoxemia in patients with obstructive sleep apnea (OSA) or overweight status undergoing gastroscopy.DesignIn a single-center, prospective, randomized controlled clinical trial, 80 patients aged 18–65 years and with OSA or overweight status who underwent gastroscopy with sedation were randomly assigned to two groups: the nasal cannula and BPAP groups. The primary outcome was the incidence of hypoxemia (75% < peripheral oxygen saturation [SpO2] < 90% for >5 sand <60 s).Main resultsCompared to the nasal cannula group, BPAP therapy significantly decreased the incidence of hypoxemia from 40.0% to 2.5% (absolute risk difference [ARD], 37.5% [95% confidence interval (CI), 21.6 to 53.4], p < 0.001), decreased subclinical respiratory depression from 52.5% to 22.5% (ARD, 30.0% [95% CI, 9.8 to 50.2], p = 0.006), and decreased severe hypoxemia from 17.5% to 0% (ARD, 17.5% [95% CI, 5.7 to 29.3], p = 0.006). The BPAP intervention also decreased the total propofol dosage and operation time and improved anesthesiologist's satisfaction.ConclusionBPAP therapy significantly decreased the incidence of hypoxemia in patients with OSA or overweight status who underwent gastroscopy.     

Intravenous amino acid therapy for kidney protection in cardiac surgery patients: A pilot randomized controlled trial

ObjectiveTo determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery.MethodsAdult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed.ResultsSixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P = .84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P < .0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P = .033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P = .046).ConclusionsCommencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials.     

Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non–small cell lung cancer: A phase II study

IntroductionCurrently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exist. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable non–small cell lung cancer (NSCLC).MethodsThis was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints were the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival, and adverse events (AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor.ResultsOf the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4). Median DFS was 33.5 months (95% CI, 19.7-47.3); median overall survival was not reached. Skin toxicity (24/35,68.6%) and gastrointestinal symptoms (17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, 4 patients experienced chylothorax (4/33,12.1%). Patients with MPR had a prolonged survival compared with those without (DFS, P = .019).ConclusionsNeoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.     

Prognosis stratification and postoperative radiation therapy utilization in adenoid cystic carcinoma of the breast

PurposeAdenoid cystic carcinoma of the breast (ACCB) is a rare malignancy with a favorable prognosis. Little information exists regarding the impact of postoperative radiation therapy (RT) on survival outcome in patients with ACCB. This study aimed to evaluate the clinical significance of postoperative RT in ACCB.MethodsData of patients with ACCB were extracted from the Surveillance, Epidemiology, and End Results database (2000–2019). Univariate and multivariable Cox regression analyses were performed to identify prognostic factors. In addition, a nomogram model was constructed and internally validated for discrimination and calibration. The value of postoperative RT was respectively accessed in each risk subgroup according to nomogram-deduced individualized score.ResultsA total of 689 eligible patients were included in the analysis. Partial mastectomy was associated with an increased risk of death compared with partial mastectomy plus postoperative RT (P = 0.020), but total mastectomy with or without postoperative RT was comparable (P = 0.624). Then, in-depth analysis was performed for patients receiving breast-conserving therapy (n = 485, the training set vs. the testing set = 340 vs. 145). Age at diagnosis, histological grade, and T stage were identified as prognostic factors for overall survival (OS) (All P < 0.05). A nomogram was constructed to provide predictive accuracy toward individual OS rates of ACCB and to divide patients into different risk subgroups. Notably, compared with non-RT, postoperative RT significantly improved OS in the high-risk subgroup (P = 0.006 for the training set, and P = 0.013 for the overall population) but not in the low-risk subgroup (P = 0.807 for the training set, and P = 0.293 for the overall population), suggesting that these patients may be able to exempt from postoperative RT.ConclusionA robust and effective nomogram was developed to predict prognosis and assist in treatment decisions in patients with ACCB undergoing partial mastectomy.     

Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

BackgroundThe role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood.MethodsA total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test.ResultsMedian follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048).ConclusionsHigher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.     

Contemporary treatment of keloids: A 10-year institutional experience with medical management,surgical excision,and radiation therapy

IntroductionWe evaluate a single center’s, decade-long experience utilizing 3 approaches to keloid treatment: corticosteroid medical management (MM), surgical excision (SE), and surgical excision + radiation therapy (SE + RT).Study designPatients undergoing keloid treatment were identified (2008–2017). Outcomes were symptomatology/cosmesis for MM, and recurrence and complications for SE and SE + RT. Logistic regression was used to determine factors associated with recurrence and complications.Results284 keloids (95 MM, 94 SE, 95 S E + RT) corresponded to patients with a median age of 39.1 (IQR: 26.1–53), 68.1% Black, and followed-up for 15.4 months (IQR: 5.6–30.7). For MM, 84.6% and 72.5% reported improvement in cosmesis and symptoms, respectively. SE and SE + RT recurrence were 37.2 and 37.9%, respectively. In adjusted analyses, higher radiation doses were associated with decreased recurrence whereas male gender (OR 3.3) and postoperative steroids (OR 9.5) were associated with increased recurrence (p < 0.01). There were more complications in the SE + RT group.ConclusionsMM resulted in at least some improvement. Recurrence rates after SE and SE + RT were similar. Female sex is protective, race does not affect outcomes.     

Outcomes of transapical mitral valve repair with neochordae implantation

ObjectiveTransapical off-pump beating-heart neochord implantation (NC) has shown encouraging early results in patients with degenerative mitral regurgitation. The aim of this study was to evaluate clinical and echocardiographic 5-year outcomes of patients who underwent NC.MethodsAll patients who underwent NC at our institution from November 2013 to March 2016 were included. Indications were severe symptomatic degenerative mitral regurgitation due to leaflet prolapse/flail. Patients were classified as having favorable anatomy (FA) and unfavorable anatomy (UA) on the basis of the extent and severity of mitral valve disease. All patients underwent clinical and echocardiographic follow-up at 1, 3, 6, and 12 months, and annually thereafter. Data were prospectively collected and retrospectively analyzed. Outcomes were on the basis of the Mitral Valve Academic Research Consortium guidelines.ResultsOne hundred consecutive patients were included in the analysis (FA: 81%; UA: 19%). Median age was 66 years (interquartile range, 58-76) and median European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was 1.4% (interquartile range, 0.7-2.3). Technical and procedural success were 98% and 94%, respectively. Thirty-day mortality was 2%. Device success was 94%, 92%, and 78%, at 30 days, 1-year, and 5 years, respectively. Patient success at 1 year was 92%. Median follow-up was 5.1 years. At 5 years, overall survival was 83% with no difference between FA and UA patients. Cumulative incidence of severe mitral regurgitation recurrence at 5 years was 14% (95% CI, 6.5%-22.8%) in FA patients and 63% (95% CI, 39.7%-86.2%) in UA patients, respectively (P < .001). Patients with FA compared with UA had a lower incidence of reintervention (14.7% vs 43.4%; P < .001).ConclusionsTransapical off-pump beating heart NC might represent an acceptable option in patients with degenerative mitral valve disease and FA.     

Comparative study on the manually-controlled variable-rate versus fixed-rate infusion of norepinephrine for preventing hypotension during spinal anesthesia for cesarean delivery

Study objectivePrevious studies have shown that prophylactic norepinephrine infusion is superior to intermittent bolus administration in preventing post-spinal hypotension. Nevertheless, it is still controversial whether manually-controlled variable-rate infusion is more effective than fixed-rate infusion. The purpose of the present study was to compare the efficacy of variable-rate infusion and fixed-rate infusion of norepinephrine for prophylaxis against maternal hypotension and maintaining hemodynamic stability during spinal anesthesia for cesarean delivery to determine more effective mode for clinical practice.DesignA prospective randomized, controlled study.SettingOperating room, Women's Hospital, Zhejiang University School of Medicine.PatientsA total of 161 parturients scheduled for elective cesarean delivery with spinal anesthesia were randomized into Group F (fixed-rate infusion) and Group V (variable-rate infusion).InterventionsParturients received prophylactic norepinephrine infusion concurrent with the intrathecal injection at rate started at 0.05 μg/kg/min. In Group F, norepinephrine was administered continuously at a fixed (on-off) rate, and a bolus of norepinephrine 5 μg or 10 μg was given when systolic blood pressure (SBP) decreased by 20% or more of baseline. In Group V, manually adjusted norepinephrine infusion within the range 0–0.14 μg/kg/min, according to SBP at 1-min intervals until delivery, aim to maintain values close to the baseline.MeasurementsDuring the study period, the incidence of maternal hypotension, hemodynamic performance, the number of physician interventions, reactive hypertension, bradycardia, nausea, vomiting, norepinephrine cumulative dose (before delivery), and neonatal outcomes were recorded.Main resultsThe incidence of maternal hypotension was significantly lower in Group V than that in Group F (9% versus 30%) (P < 0.001). No significant difference was found in the serial changes in SBP and heart rate (HR) for the first 15 min. Group V showed higher frequency of physician interventions compared with the Group F (P < 0.001). The incidence of hypertension, severe hypotension, nausea, vomiting, bradycardia, norepinephrine cumulative dose, and neonatal outcome were comparable between the two groups.ConclusionWhen norepinephrine was infused at an initial dose of 0.05 μg/kg/min for preventing hypotension during spinal anesthesia for cesarean delivery, due to technical limitations of inadequate dose design in this study, neither a variable-rate infusion (need more physician intervention) nor a fixed-rate infusion regimen (experience more transient hypotension) was optimal. However, in terms of clinical importance, how to prevent the parturients from experiencing more incidence of hypotension might be a greater concern for anesthesiologists.     

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

IntroductionPlatinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.Materials and methodsAll studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.ResultsFrom the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I² = 0%).ConclusionAccording to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.     

Association between background parenchymal enhancement and tumor response in patients with breast cancer receiving neoadjuvant chemotherapy

PurposeTo analyze the relationships between background parenchymal enhancement (BPE) of the contralateral healthy breast and tumor response after neoadjuvant chemotherapy (NAC) in women with breast cancer.Materials and methodsA total of 228 women (mean age, 47.6 years ± 10 [SD]; range: 24–74 years) with invasive breast cancer who underwent NAC were included. All patients underwent breast magnetic resonance imaging (MRI) before and after NAC and 127 patients underwent MRI before, during (after the 4th cycle of NAC) and after NAC. Quantitative semi-automated analysis of BPE of the contralateral healthy breast was performed. Enhancement level on baseline MRI (baseline BPE) and MRI after chemotherapy (final BPE), change in enhancement rate between baseline MRI and final MRI (total BPE change) and between baseline MRI and midline MRI (early BPE change) were recorded. Associations between BPE and tumor response, menopausal status, tumor phenotype, NAC type and tumor stage at diagnosis were searched for. Pathologic complete response (pCR) was defined as the absence of residual invasive cancer cells in the breast and ipsilateral lymph nodes.ResultsNo differences were found in baseline BPE, final BPE, early and total BPE changes between pCR and non-pCR groups. Early BPE change was higher in non-pCR group in patients with stages 3 and 4 breast cancers (P = 0.019) and in human epidermal growth factor receptor 2 (HER2)-negative patients (P = 0.020).ConclusionEarly reduction of BPE in the contralateral breast during NAC may be an early predictor of loss of tumor response, showing potential as an imaging biomarker of treatment response, especially in women with stages 3 or 4 breast cancers and in HER2 – negative breast cancers.     

Valve-sparing root replacement in patients with bicuspid aortopathy: An analysis of cusp repair strategy and valve durability

ObjectiveValve-sparing root replacement using reimplantation techniques is increasingly applied to bicuspid aortopathy. Long-term durability of cusp repair is unclear. We analyze midterm results using a conservative approach to cusp repair.MethodsFrom 2006 to 2018, 327 patients underwent valve-sparing reimplantation, 66 with bicuspid valves. Leaflets were analyzed after reimplantation. A majority (51/66) required no cusp repair. Fifteen patients had cusp repair limited to closure of unfused raphe or central plication. Patients were followed by echocardiography.ResultsMean age of patients was 44.7 ± 12.3 years. The cusp repair group had a higher incidence of preoperative moderate (10% vs 40%) or severe (4% vs 33.3%) aortic insufficiency (P < .001). There was no operative mortality or major complication. Mean follow-up was 51.6 ± 40.8 months. On postoperative echocardiography, incidence of none, trace, or mild aortic insufficiency was 41.3% (19/46), 43.5% (20/46), and 15.2% (7/46) in the no cusp repair group and 40% (6/15), 40% (6/15), and 20% (3/15) in the cusp repair group, respectively (P = .907). Few patients progressed in degree of aortic insufficiency. No patients required reoperation. At 5 years, freedom from any aortic insufficiency was 46.9% versus 15.8% (P = .013), and freedom from greater than trace aortic insufficiency was 59.1% versus 36.9% (P = .002) due to the higher rate of postoperative trace and mild aortic insufficiency with cusp repair. There was no difference in freedom from greater than mild aortic insufficiency (92.1% vs 100%; P = .33).ConclusionsValve-sparing root replacement is reliably performed with bicuspid aortic valves whether or not cusp reconstruction is necessary. Few patients progress to greater than mild aortic insufficiency. Need for reoperation is rare in midterm follow-up.