Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

BackgroundBreast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) vs. ET alone.MethodsCompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2– ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.ResultsA total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study.ConclusionsResults from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2− ABC, including populations of interest (NCT02941926).Trial registrationClinicalTrials.gov NCT02941926     

Frailty measured by risk analysis index and adverse discharge outcomes after adult spine deformity surgery: analysis of 3104 patients from a prospective surgical registry (2011–2020)

Background ContextMeasurement of frailty with the Risk Analysis Index (RAI) has demonstrated improved outcome prediction compared to other frailty indices across the surgical literature. However, the generalizability and clinical utility of preoperative RAI scoring for prediction of postoperative morbidity after adult spinal deformity surgery is presently unknown. Thus, recent studies have called for an RAI analysis of spine deformity outcomes.PurposeThe present study sought to evaluate the discriminatory accuracy of preoperative frailty, as measured by RAI, for predicting postoperative morbidity among adult spine deformity surgery patients using data queried from a large prospective surgical registry representing over 700 hospitals from 49 US states and 11 countries.Study Design/SettingSecondary analysis of a prospective surgical registry.Patient SampleAmerican College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2011–2020).Outcome MeasuresThe primary endpoint was “adverse discharge outcome” (ADO) defined as discharge to a non-home, non-rehabilitation nursing/chronic care facility.MethodsAdult spine deformity surgeries were queried from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2011–2020) using diagnosis and procedure codes. The relationship between increasing preoperative RAI frailty score and increasing rate of primary endpoint (ADO) was assessed with Cochran-Armitage linear trend tests. Discriminatory accuracy was tested by computation of concordance statistics (with 95% confidence interval [CI]) in receiver operating characteristic (ROC) curve analysis.ResultsA total of 3104 patients underwent spine deformity surgery and were stratified by RAI score: 0–10: 22%, 11–15: 11%, 16–20: 29%, 21–25: 26%, 26–30: 8.0%, 31–35: 2.4%, and 36+: 1.4%. The rate of ADO was 14% (N=439/3094). The rate of ADO increased significantly with increasing RAI score (p<.0001). RAI demonstrated robust discriminatory accuracy for prediction of ADO in ROC analysis (C-statistic: 0.71, 95% CI: 0.69–0.74, p<.001). In pairwise comparison of ROC curves (DeLong test), RAI demonstrates superior discriminatory accuracy compared to the 5-factor modified frailty index (mFI-5; p<.001).ConclusionPreoperative frailty, as measured by RAI, is a robust predictor of postoperative morbidity (measured by ADO) after adult spine deformity surgery. The frailty score may be translated directly to the bedside with a user-friendly risk calculator, deployed here: https://nsgyfrailtyoutcomeslab.shinyapps.io/spineDeformity     

Evaluation of sentinel lymph node biopsy after previous breast surgery for breast cancer: GATA study

AimSentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context.Patients and methodsFrom 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy.ResultsThe detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%.ConclusionPrevious conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement.Clinical trial registration numberNCT00293865.     

Morbidity in Breast Cancer Patients with Sentinel Node Metastases Undergoing Delayed Axillary Lymph Node Dissection (ALND) Compared with Immediate ALND

Background Patients with sentinel lymph node (SLN) metastases need delayed completion axillary lymph node dissection (ALND) if intraoperative assessment of SLN is not employed. This study was designed to compare morbidity in patients undergoing complete ALND in the first (and only) operation versus those undergoing the two-step procedure (SLN biopsy followed by delayed completion ALND). Methods Secondary analysis of the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) randomized trial compared 83 patients with SLN metastases who proceeded to delayed completion ALND (two-step ALND) with 96 node-positive patients who underwent ALND as the only axillary procedure (one-step ALND). Outcome variables were assessed at baseline and at 3, 6, and 12 months after surgery. Results The 83 SLN-positive patients undergoing completion ALND were younger (p = 0.038) compared with the one-step ALND group. There was no difference in lymphedema, sensory loss, intercostobrachial (ICB) nerve division rates, impairment of shoulder movement, infection rate, or time to resumption of normal day-to-day activities after surgery between the two groups. Median axillary operative time for completion ALND in the two-step group was significantly higher than one-step ALND (33 min vs. 25 min, p = 0.004). The median hospital stay for the second surgery in the two-step group was similar to one-step ALND (6 days). The total median hospital stay (first and second surgery) was significantly higher for the two-stage procedure (10 vs. 6 days, p < 0.001). Conclusion A two-stage axillary node dissection procedure in patients with SLN metastases has similar arm morbidity to one-stage ALND. The second surgery is associated with increased axillary operative time and total hospital stay.     

The impact of social media presence,age, and patient reported wait times on physician review websites for sports medicine surgeons

BackgroundWhen choosing physicians, patients often review options online via physician review websites, which may influence decisions on providers.PurposeThe purpose of this study is to investigate the impacts of social media usage, age, and patient reported wait times on online ratings for three popular review websites.Study designCross-sectional study.MethodsThe American Orthopaedic Society for Sports Medicine database was used to extract demographic information for all listed sports medicine surgeons in Florida. Overall ratings, number of ratings and comments, and patient reported wait-times were recorded from three leading review websites (Healthgrades.com, Vitals.com, Google.com). Professionally focused SM accounts were searched for each physician on Facebook.com, Twitter.com, Instagram, and LinkedIn.com.Results102 orthopaedic sports medicine surgeons were included. At least one form of social media was used by 62.4% of our cohort. Those with social media had higher overall online physician ratings out of 5.00 across all review websites (Google:4.65vs4.44, p = 0.05; Healthgrades:4.41vs4.15, p = 0.03; Vitals:4.43vs4.14, p = 0.01). In bivariate analysis, older age was associated with lower ratings on Health Grades (Absolute difference (AD) −0.26, p < 0.0001), and social media was linked to higher ratings (Google: AD 0.21, p = 0.05; Healthgrades: AD 0.26, p = 0.03; Vitals: AD 0.29, p = 0.008). Longer wait times were associated with lower ratings in a dose-dependent manner in both bivariate and multivariable analysis.ConclusionsSocial media use among sports medicine surgeons correlated with higher overall physician ratings. Potentially, younger surgeons increase social media use because of a heightened concern for online image, whereas older surgeons may have less value in using online platforms to capitalize on an online presence. Older age and increased patient reported wait times in office had a negative correlation with online reviews, which highlights that factors beyond the surgeon's skill sets can influence overall ratings.     

乳腺癌前哨淋巴结活检替代腋窝清扫术前瞻性非随机对照临床研究

目的：探讨前哨淋巴结活检术（sentinel lymph node biopsy，SLNB）替代腋淋巴结切除术（axiHary lymph node dissection．ALND）的可行性。方法：联合应用亚甲蓝和^99mTc标记的硫胶体进行SLNB。2001年12月起山东省肿瘤医院乳腺病中心两个治疗组收治的临床T1.2N0M0乳腺癌病人进入本前瞻性非随机对照临床研究。A组病人SLNB后均行ALND。B组病人签署知情同意书，不同意SLNB替代ALND病人（B1组）治疗同A组；同意SLNB替代ALND病人（B2组）依据SLN状况，SLN阴性仅行SLNB，SLN阳性行ALND。结果：2001年12月-2005年6月共入组642例病人，其中A组114例（17．8％），B组528例（82.2％），B1组195例，B2组333例。B2组病人SLN阴性240例仅行SLNB；SLN阳性93例，其中87例接受ALND，另6例SLN镜下微小转移灶者中4例仅行SLNB，2例接受SLNB加区域淋巴结放疗。SLNB替代ALND者各项术后并发症显著低于ALND者（均P〈0．05）。B2组244例仅行SLNB病人中位随访26个月（7-48个月），2例病人发现区域淋巴结复发（0．82％），与ALND腋淋巴结阴性组病人（0％）相比差异无统计学意义（P〉0．05）。SLN术中冰冻快速病理诊断准确率98．5％，假阴性率5．4％。结论：SLNB可以缩小手术范围、减少病人术后并发症。SLN术中冰冻快速病理诊断具有较高的准确性，能够满足临床需要。     

Clinical application of axillary reverse mapping in patients with breast cancer: A systematic review and meta-analysis

BackgroundThe axillary reverse mapping (ARM) technique, identify and preserve arm nodes during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), was developed to prevent breast-cancer related lymphedema (BCRL) remains controversial.MethodsA comprehensive search of Medline Ovid, Pubmed, Web of Science and the Cochrane CENTRAL databases was conducted from the inception till January 2020. The key word including “breast cancer”, “axillary reverse mapping”, and “lymphedema”. Stata 15.1 software was used for the meta-analysis.ResultsAs a result, twenty-nine related studies involving 4954 patients met our inclusion criteria. The pooled overall estimate lymphedema incidence was 7% (95% CI 4%–11%, I² = 90.35%, P < 0.05), with SLNB showed a relatively lower pooled incidence of lymphedema (2%, 95% CI 1%–3%), I² = 26.06%, P = 0.23) than that of ALND (14%, 95% CI 5%–26%, I² = 93.28%, P < 0.05) or SLNB and ALND combined (11%, 95% CI 1%–30%). The ARM preservation during ALND procedure could significantly reduce upper extremity lymphedema in contrast with ARM resection (OR = 0.27, 95% CI 0.20–0.36, I² = 31%, P = 0.161). Intriguingly, the result favored ALND-ARM over standard-ALND in preventing lymphedema occurrence (OR = 0.21, 95% CI 0.14–0.31, I² = 43%, P = 0.153). The risk of metastases in the ARM-nodes was not significantly lower in the patients who had received neoadjuvant chemotherapy, as compared to those without neoadjuvant treatment (OR = 1.20, 95% CI 0.74–1.94, I² = 49.4%, P = 0.095).ConclusionsARM was found to significantly reduce the incidence of BCRL. The selection of patients for this procedure should be based on their axillary nodal status. Preoperative neoadjuvant chemotherapy has no significant impact on the ARM lymph node metastasis rate.     

A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY)

Study objectiveTo evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.DesignMulticenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).SettingOperating room.PatientsTwo separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery).InterventionRandomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).MeasurementsThe primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [C_max], time to C_max) and safety of liposomal bupivacaine, respectively.Main resultsBaseline characteristics were comparable across groups. Mean C_max after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean C_max in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to C_max of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.ConclusionsPlasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000–4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302     

Subsequent axillary surgery after sentinel lymph node biopsy: Results from the BreastSurgANZ Quality Audit 2006–2010

ObjectivesTo use data from the BreastSurgANZ Quality Audit (BQA) to examine the patterns of completion axillary lymph node dissection (cALND) after sentinel lymph node (SLN) biopsy in women treated for early breast cancer in Australia and New Zealand and to compare it to the Australian and New Zealand guidelines in cases of both positive and negative SLN results.Materials and methodsPatients were sub grouped as having primary tumours ≤3 cm and >3 cm and further analysed according to year of surgery, SLN status and final nodal status where cALND was recorded. Multivariate analysis was performed examining tumour size, grade, presence of lymphovascular invasion (LVI), HER2 and oestrogen receptor status, patient age and number of positive sentinel nodes as predictors for subsequent axillary surgery.Results14879 patients were identified from 2006 to 2010. 79.8% of patients with a positive SLN result underwent cALND. Age >70 years and a greater number of involved SLN predicted no cALND among SLN positive patients. 10.3% of patients who had a negative SLN result underwent cALND. Younger age, higher grade, lymphovascular invasion and tumour size >3 cm predicted cALND among SLN negative patients.ConclusionsAccording to the BQA from 2006 to 2010 the Australian and New Zealand guideline recommendations for SLN positive patients to have cALND and SLN negative patients not to have cALND were adhered to in 79.8% and 89.7% of cases respectively.     

Anticholinergic burden of long-term medication is an independent risk factor for the development of postoperative delirium: A clinical trial

BackgroundPostoperative delirium (POD) is a common complication after surgery.ObjectiveWe sought to determine the association between preoperative anticholinergic load calculated using the anticholinergic drug scale (ADS) and POD in cancer patients over 65 years of age.DesignA retrospective sub-investigation of a randomised controlled interventional trial.SettingTwo tertiary university hospitals.PatientsOverall, patients aged 65 years and older scheduled for surgical treatment of gastrointestinary, genitourinary or gynaecological cancers.Main outcome measuresThe primary outcome was the interaction between anticholinergic drug scale and occurrence of postoperative delirium. Patient clinical parameters and ADS scores were assessed preoperatively. POD screening was conducted for a total of 7 days following surgery using validated measures. Independent associations between ADS and POD were assessed using multivariate logistical regression analyses.ResultsA total of 651 patients (mean age, 71.8 years; 68.5% males) were included. Of those, 66 patients (10.1%) developed POD. The ADS score was independently associated with the occurrence of POD (higher ADS per point OR 1.496; 95% CI 1.09–2.05; p = 0.01). Additionally, age (per year OR 1.06; CI 95% CI 1.01–1.11; p = 0.03) and ASA state (OR 2.16; 95% CI 1.22–3.83; p = 0.01), as well as stay on ICU (yes vs. no OR 2.8; 95% CI 1.57–4.998; p < 0.01), were independently associated with POD.ConclusionsADS assessment according to chronic medication use is a cost-effective, non-invasive method of identifying elderly cancer patients at risk for POD.Trial registry: www.clinicaltrials.gov. Identifier NCT01278537.Ethics: IRB of Charité University-Medicine Berlin, Germany; EA2/241/08.     

Impact of sentinel lymph node mapping on relative charges in patients with early-stage breast cancer

Background: The introduction of SLNB has allowed accurate staging in early-stage breast carcinomas and has minimized the number of unnecessary ALNDs. Intraoperative frozen-section analysis is a fundamental component of the sentinel lymph node biopsy (SLNB) procedure. Some patients have positive nodes on frozen-section analysis and thus undergo a conventional axillary lymph node dissection (ALND) at the time of the SLNB. A few patients have negative nodes on frozen-section analysis but have subsequent evidence of metastases on final pathologic examination. The purpose of our study was 2-fold: to compare the hospital-related charges of patients undergoing staging by SLNB with those of patients undergoing conventional ALND and to assess whether the different outcomes associated with SLNB adversely affect the charges incurred with this procedure. Methods: Our study group consisted of 100 patients with T1 breast cancer and breast conservation therapy who underwent either SLNB or ALND from July 1, 1997, to June 30, 1998. We identified the first 50 consecutive patients to undergo SLNB during this period. We chose a similar cohort of 50 patients for ALND. Mean hospital-related charges for the SLNB patients were categorized and compared with those for the ALND patients. Results: Results for the two groups were analyzed using a two-sample Wilcoxon rank-sum test. Charges for the OR and hospital stay were less for the SLNB group (P<.05). Frozen-section analysis in the SLNB group contributed to the significant difference in charges for pathologic evaluation. Overall, the two groups showed no significant difference in total hospital-related charges. Conclusions: When SLNB is used for T1 tumors, a small percentage of patients (10% in our study) will return to the operating room for an ALND. This small percentage does not increase the charges related to SLNB, however, as the reduced stay for most patients offsets this subgroup’s contribution to the total hospital-related charges. Thus, in patients with clinical stage I breast cancer, SLNB does not cause significantly higher hospital-related charges compared with conventional ALND.     

Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial

Study objectiveDelirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment.The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery.DesignThe Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial.SettingPerioperative care.Patients182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia.InterventionsPre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo.MeasurementsAssessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay.Main resultsNone of the three study arms – haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups.ConclusionsThe study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular.Trial registrationClinicalTrials.gov NCT02433041; registered on April 7, 2015.     

Trends in axillary surgery and clinical outcomes among breast cancer patients with sentinel node metastasis

BackgroundThere is a lack of studies examining the long-term trend and survival of axillary surgery for breast cancer patients with sentinel node metastasis, especially for the patients with 3–5 node metastases.MethodsBreast cancer patients with 1–5 sentinel node metastases from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. Our study presented the trend of axillary surgery and assessed the long-term survival of sentinel lymph node biopsy (SLNB) alone vs axillary lymph node dissection (ALND) for those patients.ResultsOf the 41,996 patients diagnosed with T_1-2 breast cancer after lumpectomy and radiation included, 34,940 had 1-2 sentinel node metastases and 7056 had 3-5 sentinel node metastases. The percentage of patients undergoing SLNB alone increased from 22.4% in 2000 to 81.0% in 2016 for patients with 1–2 sentinel node metastases, and quadrupled from 5.2% in 2009 to 20.6% in 2016 for those with 3–5 sentinel node metastases. Completion of ALND did not benefit the long-term survival of 1–2 sentinel node metastasis patients (hazard ratio [HR] = 1.02, P = 0.539), but improved the long-term survival of 3–5 node metastasis patients (HR = 0.73, P < 0.001). Subgroup analysis demonstrated the inferiority of SLNB to ALND in all subgroups of 3–5 sentinel node metastases.ConclusionFor patients with T_1-2 breast cancer after lumpectomy and radiation, SLNB alone was an efficient and safe surgical choice for 1–2 sentinel node metastases but not for 3–5 sentinel node metastases. It is worth noting that for patients with 3–5 node metastasis, the proportion of omitted ALND quadrupled after 2009.     

Outcomes of individualized goal-directed therapy based on cerebral oxygen balance in high-risk patients undergoing cardiac surgery: A randomized controlled trial

Study objectiveTo investigate whether optimizing individualized goal-directed therapy (GDT) based on cerebral oxygen balance in high-risk surgical patients would reduce postoperative morbidity.DesignThis was a prospective, randomized, controlled study.SettingThe study was performed in the First Affiliated Hospital of Anhui Medical University, Hefei, China, from April 2017 to July 2018.Patients146 high-risk adult patients undergoing valve replacements or coronary artery bypass surgery with cardiopulmonary bypass (CPB) were enrolled.InterventionPatients were randomized to an individualized GDT group or usual care group. Individualized GDT was targeted to achieve the following goals: A less than 20% decline in the regional cerebral oxygen saturation (rScO₂) level from baseline; a less than 20% decline in the mean arterial pressure (MAP) from baseline, as well as a bispectral index (BIS) of 45–60 before and after CPB and 40–45 during CPB.MeasurementsThe primary outcome was a composite endpoint of 30-day mortality and major postoperative complications.Main results128 completed the trial and were included in the modified intention-to-treat analysis. Early morbidity was similar between the GDT (25 [39%] of 65 patients) and usual care groups (33 [53%] of 63 patients) (relative risk 0.73, 95% CI 0.50–1.08; P = 0.15). Secondary analysis showed that 75 (59%) of 128 patients achieved individual targets (irrespective of intervention) and sustained less morbidity (relative risk 3.41, 95% CI 2.19–5.31; P < 0.001).ConclusionsIn high-risk patients undergoing cardiac surgery, individualized GDT therapy did not yield better outcomes, however, the achievement of preoperative individual targets may be associated with less morbidity.Trial registrationClinicaltrials.gov identifier: NCT03103633. Registered on 1 April 2017.     

Sensory morbidity after sentinel lymph node biopsy and axillary dissection: a prospective study of 233 women

Background We prospectively compared the sensory morbidity and lymphedema experienced after sentinel node biopsy (SLNB) and axillary dissection (ALND) over a 12-month period by using a validated instrument. Methods Patients undergoing breast-conserving therapy completed the Breast Sensation Assessment Scale (BSAS) at baseline and 3, 6, and 12 months after surgery. Repeated-measures analysis of variance was used to compare ALND and SLNB over the 12-month period. Upper- and lower-arm circumference measurements at baseline and 12 months were used to assess lymphedema. Results SLNB was associated with substantial sensory morbidity, although significantly less than ALND, over time on all four subscales and the summary score. A statistically significant improvement in sensory morbidity occurred for both groups in the first 3 months, with no further change thereafter. For both types of axillary surgery, younger patients had significantly higher BSAS scores than older patients. There was no significant difference in arm circumference between patients with SLNB and ALND at 12 months. Conclusions Among women undergoing breast-conserving therapy, SLNB has significant sensory morbidity, although approximately half that of ALND. Sensory morbidity improves in the first 3 months after surgery, but patients continue to report sensory morbidity at 1 year. Longitudinal follow-up is required to further assess lymphedema.     

Role of frozen section in sentinel lymph node biopsy for breast cancer in the era of the ACOSOG Z0011 and IBCSG 23-10 trials

Background

Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN) were evaluated to avoid the need for deferred axillary lymph node dissection (ALND) in patients with early breast cancer (EBC). However, FS has low sensitivity for detecting micro-metastases (<2 mm), resulting in patients who later undergo deferred ALND. The aim of the study was to determine the best clinical approach for selecting patients who would derive real benefit from ALND, as well as to minimize the functional and psychological damage caused by delayed surgery, and the risk of undertreating EBC patients.

Sentinel node biopsy in breast cancer

Background: Sentinel lymph node biopsy (SNB) in breast cancer may be used in place of axillary lymph node dissection (ALND) if SNB accurately stages the axilla. This study assessed the success and accuracy of axillary SNB with isosulfan blue (ISB) and technetium-99 sulfur colloid (TSC) compared to ALND. Methods: Forty-two women with T1 or T2 breast cancer underwent SNB and ALND. Sixty to 90 minutes before anesthetic induction, a mixture of 3 mL ISB and 1 mCi TSC was injected around the primary cancer or prior biopsy site. Intraoperatively, the SLN was identified using a gamma detector (Neoprobe 1000) or by visualization of the blue-stained lymph node and afferent lymphatics. The SLN was excised separately, and a level I/II ALND was completed. The histologic findings of the axillary contents and SLN were compared. Results: An axillary SLN was found in 38 of 42 (90%) cases. SLN localization rate and predictive value were the same for women who had and those who had not undergone excisional biopsy before the date of SNB. Fifteen of 42 (36%) patients had lymph node metastases. The SLN was positive in all women with axillary metastases (negative predictive value, 100%). Conclusions: If confirmed by larger series, a negative SNB may eliminate the need for ALND for select women with breast cancer. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Transversus abdominis plane block with liposomal bupivacaine versus continuous epidural analgesia for major abdominal surgery: The EXPLANE randomized trial

ObjectiveCompare transversus abdominis plane (TAP) blocks with liposomal bupivacaine were to epidural analgesia for pain at rest and opioid consumption in patients recovering from abdominal surgery.BackgroundERAS pathways suggest TAP blocks in preference to epidural analgesia for abdominal surgery. However, the relative efficacies of TAP blocks and epidural analgesia remains unknown.MethodsPatients having major abdominal surgery were enrolled at six sites and randomly assigned 1:1 to thoracic epidural analgesia or bilateral/4-quadrant TAP blocks with liposomal bupivacaine. Intravenous opioids were used as needed. Non-inferiority margins were a priori set at 1 point on an 11-point pain numeric rating scale for pain at rest and at a 25% increase in postoperative opioid consumption.ResultsEnrollment was stopped per protocol at 3rd interim analysis after crossing an a priori futility boundary. 498 patients were analyzed (255 had TAP blocks and 243 had epidurals). Pain scores at rest in patients assigned to TAP blocks were significantly non-inferior to those given epidurals, with an estimated difference of 0.09 points (CI: −0.12, 0.30; noninferiority P < 0.001). Opioid consumption during the initial 3 postoperative days in TAP patients was not non-inferior to epidurals, with an estimated ratio of geometric means of 1.37 (CI: 1.05, 1.79; non-inferiority P = 0.754). However, the absolute difference was only 21 mg morphine equivalents over the 3 days. Patients with epidurals were more likely to experience mean arterial pressures <65 mmHg than those given TAP blocks: 48% versus 31%, P = 0.006.ConclusionPain scores at rest during the initial three days after major abdominal surgery were similar. Patients assigned to TAP blocks required more opioid then epidural patients but had less hypotension. Clinicians should reconsider epidural analgesia in patients at risk from hypotension.Trial Registration: ClinicalTrials.gov Identifier: NCT02996227.     

Is breast cancer sentinel lymph node mapping valuable for patients in their seventies and beyond?

BACKGROUND: Axillary lymph node dissection (ALND) is performed less commonly for the axillary staging of elderly patients because it is felt to uncommonly alter therapy. Sentinel lymph node (SLN) dissection can accomplish axillary staging with less morbidity, but it is unclear if it alters subsequent therapy. METHODS: Review of a prospectively collected breast cancer SLN mapping database. Medical records were reviewed to supplement the database. RESULTS: Among 730 breast cancer SLN mapping patients, 261 (35.8%) were >or=70 years of age (range 70 to 95). The overall SLN identification rate was 98.8% among those <70 and 97.1% for those >or=70 (P=.11) and 100% and 99.4%, respectively (P=.25), among the most recent 500 patients. SLN metastases were detected by hematoxalin and eosin staining (H&E) in 24.2% of those <70 and 13.4% of those >/=70 (P<.01) and by immunohistochemistry staining (IHC) only in 4.6% and 5.0% of patients, respectively. No elderly patients with histologically negative SLNs underwent ALND, but 88.9% of patients with H&E metastases and 84.6% with IHC metastases underwent ALND. Of the H&E-positive women, 88% underwent adjuvant systemic therapy versus 55% of H&E-negative women (P<.01). Hormonal therapy was administered to 86.9% of SLN-positive women and 54.3% of SLN-negative women (P<.01) and cytotoxic chemotherapy was administered to 24% of SLN-positive patients versus 2.8% of SLN-negative patients (P<.01). SLN status was associated with significantly different rates of systemic therapy for patients with tumors <1 cm and 1 to 2 cm, but not with tumors >2 cm. Mean follow-up was 15.4 months. No patient experienced local or regional recurrence. Distant metastases occurred in 8.2% of patients with SLN metastases and in no patients with negative SLNs (P<.01). CONCLUSIONS: The results of SLN mapping and biopsy in elderly patients significantly influences subsequent therapy decisions, including ALND, hormonal therapy, and cytotoxic chemotherapy. SLN biopsy should be recommended to elderly breast cancer patients.     

Preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea

Study objectiveObstructive sleep apnea (OSA) is known to be associated with postoperative cardiovascular events in patients undergoing major non-cardiac surgery. The objective of the study is to determine whether preoperative oximetry-derived hypoxemia predicts postoperative cardiovascular events in surgical patients with unrecognized obstructive sleep apnea.Design and settingThe study was a planned post hoc analyses of a multicenter prospective cohort study.PatientsThe inclusion criteria were patients ≥45 years old undergoing major non-cardiac surgery with cardiovascular risk factors.Interventions and measurementsAll patients underwent pre-operative pulse oximetry (PULSOX-300i, Konica-Minolta Sensing, Inc). The severity of OSA was classified based on oxygen desaturation index (ODI) (mild: ≥5 to <15, moderate: ≥15 to <30, and severe OSA: ≥30 events/h). The 30 days cardiovascular events were a composite of myocardial injury, cardiac death, congestive heart failure, thromboembolism, atrial fibrillation, and stroke.Main resultsFor 1218 patients with mild, moderate, or severe OSA (mean age: 67.2 ± 9.3 years; body mass index: 27.0 ± 5.3 kg/m²), the rate of postoperative cardiovascular events was 16.4%, 25.2%, and 29.8% respectively. The multivariable analysis showed that preoperative oxygen desaturation index (ODI) ≥30 events per hour {adjusted hazard ratio (aHR) 1.63 [95% confidence interval (CI): 1.05–2.53]}, and cumulative time spent during sleep with oxygen saturation below 80% (CT80) ≥10 min {aHR 1.79 [95% CI: 1.28–2.50]} were independent predictors of 30-day postoperative cardiovascular events.ConclusionsPreoperative ODI ≥30 events per hour and CT80 ≥ 10 min are associated with increased risk of postoperative cardiovascular events. Preoperative screening using oximetry helps in risk stratification for unrecognized sleep apnea.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01494181