Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Metformin in Conjunction With Stereotactic Radiotherapy for Early-stage Non-small Cell Lung Cancer: Long-term Results of a Prospective Phase II Clinical Trial.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is increasingly detected in early stages and there is interest in improving outcomes with stereotactic body radiotherapy (SBRT). As metformin affects NSCLC signaling pathways, it might alter the metabolism of NSCLC treated with SBRT. This study investigated the long-term outcomes of a phase II clinical trial evaluating metformin in conjunction with SBRT for early-stage NSCLC. PATIENTS AND METHODS: The trial evaluated patients with American Joint Commission on Cancer (AJCC) 7th edition Stage I-II, cT1-T2N0M0 NSCLC who were randomized 6:1 to receive metformin versus placebo in conjunction with SBRT. The outcomes analyzed included local failure (LF), progression-free survival (PFS), overall survival (OS), and Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicities. RESULTS: There were 14 patients randomized to the metformin arm and one to the placebo. Median follow-up was four years. In the metformin group, the median PFS was 4.65 years [95% confidence interval (CI)=0.31-5.93] and median survival was 4.97 years (95%CI=3.05-4.61). Five year PFS was 27.8% (95%CI=5.3-57.3%) and OS was 46.0% (95%CI=16.0-71.9%). The one patient randomized to placebo was alive and without progression at five years. There were no LFs in the primary SBRT treatment volumes and no CTCAE version 4 Grade ≥3 adverse events. CONCLUSION: Outcomes of SBRT and metformin for early-stage NSCLC were similar to historic controls. These findings along with the results of the NRG-LU001 and OCOG randomized trials do not support the therapeutic use of metformin for NSCLC.

A phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations.

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.

The Effect of Metformin on Vestibular Schwannoma Growth: A Systematic Review and Meta-analysis.

OBJECTIVES: To systematically review and evaluate metformin's potential impact on vestibular schwannoma (VS) growth. DATA SOURCES: PubMed, Cochrane Library, and Embase. REVIEW METHODS: A retrospective cohort study was performed on sporadic VS patients undergoing initial observation who had at least two magnetic resonance imaging studies. Patients were stratified by metformin use during the observation period. Primary endpoint was VS growth, defined as at least a 2 mm increase in diameter. Survival free of tumor growth was evaluated between groups. Systematic review and meta-analysis were performed to produce a pooled odds ratio [OR]. Study heterogeneity was assessed and post-hoc power analysis was performed. RESULTS: A total of 123 patients were included, of which 17% were taking metformin. Median patient age was 56.6 years (range, 25.1-84.5). There were no statistically significant differences between the groups. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29-1.29). Furthermore, logistic regression analysis did not demonstrate a statistically significant difference between groups in the odds of VS growth (OR = 0.46, 95% CI = 0.17-1.27). Systematic review identified 3 studies. Meta-analysis suggested that metformin reduces the odds of developing VS growth (pooled OR = 0.45, 95% CI = 0.29-0.71). Studies demonstrated low between-study heterogeneity. Power analysis demonstrated a sample size of 220 patients with equal randomization would be required to prospectively identify a true difference with 80% power. CONCLUSIONS: Metformin use may reduce the odds of VS growth. A randomized trial would be ideal to identify an unbiased estimate of metformin's effect on VS growth. Laryngoscope, 133:2066-2072, 2023.

Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer.

PREVENTION RELEVANCE: Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

BACKGROUND: There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). OBJECTIVE: To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution (Vd). METHODS: Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. RESULTS: In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups (P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups (P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. CONCLUSION AND RELEVANCE: Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.

Impact of treatment modality on pelvic floor dysfunction among uterine cancer survivors.

OBJECTIVE: Pelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications. METHODS: We used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact Questionnaire-7. Treatment type, body mass index, comorbidities, and number of vaginal births were obtained from medical records. A zero-inflated negative binomial regression model was used to assess the association of treatment regimens and covariates relative to the non-cancer cohort. RESULTS: A total of 309 surveys were analyzed. The median age of the patients at surgery was 58 years (range 20-87) and the median age at survey completion was 66 years (range 34-92). Most participants reported experiencing at least one symptom of pelvic floor dysfunction (76% by Pelvic Floor Distress Inventory-2). The type of treatment had no effect on overall pelvic floor dysfunction on multivariate analysis (all p>0.05). Worse urinary-related symptoms were associated with higher body mass index at surgery (OR 1.41), higher age at time of survey (OR 1.07), and higher numbers of vaginal births (OR 1.43) (all p<0.05). CONCLUSIONS: Overall, pelvic floor dysfunction did not significantly vary by treatment modality. Our findings suggest complex interactions among age, body mass index, and parity as to how uterine cancer treatment affects pelvic floor quality of life, which should be considered in the choice of treatment strategy and patient counseling.

Outcomes and Predictors of 28-Day Mortality in Patients With Solid Tumors and Septic Shock Defined by Third International Consensus Definitions for Sepsis and Septic Shock Criteria.

BACKGROUND: Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce. RESEARCH QUESTION: What are the independent predictors of 28-day mortality in critically ill adults with solid tumors and septic shock? STUDY DESIGN AND METHODS: Cohort of solid tumor patients admitted to the ICU with septic shock. Demographic and clinical characteristics were gathered from the electronic health records. We developed a reduced multivariate logistics regression model to identify independent predictors of 28-day mortality and used Kaplan-Meier plots to assess survival. RESULTS: A total of 271 patients were included. The median age was 62 years (range, 19-94 years); 57.2% were men and 53.5% were White. The most common underlying malignancies were lung (19.2%), breast (7.7%), pancreatic (7.7%), and colorectal (7.4%) cancers. Most patients (84.5%) harbored metastatic disease. Twenty-eight days after ICU admission, 188 patients (69.4%) had died. Nonsurvivors showed a higher rate of advanced cancer, longer hospital stays before ICU admission, and higher Sequential Organ Failure Assessment scores at admission and throughout the ICU stay (P < .001 for all). The multivariate analysis identified metastatic disease (OR, 3.17; 95% CI, 1.43-7.03), respiratory failure (OR, 2.34; 95% CI, 1.15-4.74), elevated lactate levels (OR, 3.19; 95% CI, 1.90-5.36), and Eastern Cooperative Oncology Group performance scores of 3 or 4 (OR, 2.72; 95% CI, 1.33-5.57) as independent predictors of 28-day mortality. Only 38 patients (14%) were discharged home without medical assistance. INTERPRETATION: The 28-day mortality rate of patients with solid tumors and septic shock was considerably high. Factors associated with worse survival included advanced oncologic disease, poor performance status, high lactate level, and concomitant acute respiratory failure. Early goals-of-care discussions should be considered for frail patients with septic shock and advanced metastatic disease without denying access to the appropriate level of care.

Outcomes and Predictors of 28-Day Mortality in Patients With Hematologic Malignancies and Septic Shock Defined by Sepsis-3 Criteria.

BACKGROUND: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. METHODS: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. RESULTS: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18-89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03-1.20), respiratory failure (OR, 3.12; 95% CI, 1.49-6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10-1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26-0.69), serum albumin (OR, 0.51; 95% CI, 0.31-0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24-0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. CONCLUSIONS: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.

Revisiting an Old Conundrum: A Systematic Review and Meta-Analysis of Intravesical Therapy for Treatment of Urothelial Carcinoma of the Prostate.

BACKGROUND: The optimal management of non-invasive (mucosal and/or ductal) urothelial carcinoma of the prostate remains elusive and there is a paucity of data to guide treatment. OBJECTIVE: Our objective was to systematically review and synthesize treatment responses to conservative management of non-invasive prostatic urothelial carcinoma using intravesical therapy. METHODS: A systematic literature search using MEDLINE, EMBASE, Cochrane Library, SCOPUS, and Web of Science databases from inception to November 2019 was performed. Risk of bias assessment was performed using the Newcastle-Ottawa scale for non-randomised studies. Pooled estimates of complete response in the bladder and prostate and prostate only were performed using a random effects model. Pre-specified subgroup analyses were generated to assess differences in complete responses for: BCG therapy vs other agents, ductal vs mucosal involvement, CIS vs papillary tumors and TURP vs no TURP. RESULTS: Nine studies including 175 patients were identified for inclusion in the systematic review and meta-analysis. All were retrospective case series and most evaluated response to BCG therapy. The pooled global complete response rate for intravesical therapy was 60%(95%CI: 0.48, 0.72), and for prostate 88%(95%CI: 0.81, 0.96). Pre-specified analyses did not demonstrate statistically significant differences between subgroups of interest. CONCLUSIONS: Management of non-invasive prostatic urothelial carcinoma using intravesical therapy yields satisfactory results. Caution should be taken in treating patients with papillary tumors and ductal involvement, as data for these populations is limited. TURP may not improve efficacy, but is required for staging. Current recommendations are based on low quality evidence, and further research is warranted.

Temporal Bone Osteoradionecrosis: An 18-year, Single-Institution Experience.

OBJECTIVES/HYPOTHESIS: To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease's natural history, prognostic factors, management, and outcomes. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease. RESULTS: TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, three-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful. CONCLUSIONS: TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2578-2585, 2021.

The Reality of Randomized Controlled Trials for Assessing the Benefit of Proton Therapy: Critically Examining the Intent-to-Treat Principle in the Presence of Insurance Denial.

PURPOSE: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial. METHODS AND MATERIALS: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients <65 years. All scenarios considered an age distribution with mean ± standard deviation: 55 ± 15 years, rates of insurance denial ranging from 0%-40%, and a sample of N = 300 patients (150 per arm). Clinical success rates were defined as 70% for proton therapy and 50% for intensity modulated radiation therapy. The average treatment effect, bias, and power were compared after applying 5000 simulations. RESULTS: Increasing rates of insurance denial demonstrated inherent weaknesses among all 3 analytical approaches. With clinical success independent of age, a per-protocol analysis demonstrated the least bias and loss of power. When clinical success was dependent on age, the per-protocol and ITT analyses resulted in a similar trend with respect to bias and loss of power, with both outperforming the as-treated analysis. CONCLUSIONS: Insurance denial leads to misclassification bias in the ITT analysis, a missing data problem in the per-protocol analysis, and covariate imbalance between treatment arms in the as-treated analysis. Moreover, insurance denial forces the critical appraisal of patient features (eg, age) affected by the denial and potentially influencing clinical success. In the presence of insurance denial, our study suggests cautious reporting of ITT and as-treated analyses, and placing primary emphasis on the results of the per-protocol analysis.

The Impact of Thoracic Epidural Analgesia Versus Four Quadrant Transversus Abdominis Plane Block on Quality of Recovery After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Surgery: A Single-Center, Noninferiority, Randomized, Controlled Trial.

BACKGROUND: Recovery after CRS-HIPEC influenced by several factors, including pain and opioid consumption. We hypothesized that 4Q-TAP blocks provide not inferior quality of recovery compared with TEA after CRS-HIPEC. We conducted a randomized, controlled trial to determine whether 4-quadrant transversus abdominis plane (4Q-TAP) block analgesia was noninferior to thoracic epidural (TEA) among patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). METHODS: Patients 18 years or older who underwent a CRS-HIPEC surgery were randomly assigned to have either TEA or 4Q-TAP blocks. The primary outcome of this study was the change in quality of recovery 2 days after surgery. Secondary outcomes included quality of recovery on Days 1, 3, 5, 7, 10, and 30 postoperatively, opioid consumption, pain intensity, length of stay, and postoperative complications. Analyses were performed on a per-protocol basis. RESULTS: Sixty-eight patients were included in the analysis. The difference between 4Q-TAP and TEA in the mean QoR-15 change from surgery at postoperative Days 1, 2, and 3 was 0.80 (P = 0.004), -4.5 (P = 0.134), and 3.4 (P = 0.003), respectively. All differences through postoperative day 30 were significantly within the noninferiority boundary of -10 except at postoperative Day 2 (P = 0.134). Length of stay, opioid-related adverse events, and frequency and grade of complications were not significantly different between TEA and 4Q-TAP patients. CONCLUSIONS: Despite the significantly higher use of opioids after CRS-HIPEC in patients with 4Q-TAP blocks, their short-term quality of recovery was not inferior to those treated with TEA. Patients undergoing CRS-HIPEC can be effectively managed with 4Q-TAP blocks.

Effect of hydrocortisone versus methylprednisolone on clinical outcomes in oncology patients with septic shock.

BACKGROUND: Corticosteroids are used as adjunctive treatment of critical illness-related corticosteroid insufficiency in patients with septic shock. This study aims to compare the impact of hydrocortisone versus methylprednisolone on duration of septic shock in critically ill oncology patients. METHODS: Single-center, retrospective cohort study of adult patients receiving hydrocortisone ≥200 mg/day or methylprednisolone ≥40 mg/day with septic shock. The primary outcome was time to shock reversal defined as time to systolic blood pressure ≥90 mmHg without vasopressors for ≥24 h. RESULTS: Eighty-eight patients were included, 49 patients received hydrocortisone and 39 patients received methylprednisolone. Solid tumor malignancy was more common in the hydrocortisone group, while hematological malignancy was more common in the methylprednisolone group (p = 0.009). Time to shock reversal was similar between hydrocortisone and methylprednisolone groups (72.4 versus 70.4 h; p = 0.825). Intensive care unit mortality occurred in 51.02% versus 53.85% of patients in hydrocortisone versus methylprednisolone, respectively (p = 0.792). Patients who received methylprednisolone had higher rates of mechanical ventilation (89.74% versus 55.1%, p < 0.001) and longer intensive care unit and hospital lengths of stay (4.2 versus 11.4 days and 14.3 versus 25.7 days; p < 0.001) compared to hydrocortisone. No differences were seen in incidence of steroid-related adverse effects between groups. CONCLUSIONS: In oncology patients with septic shock, the use of hydrocortisone versus methylprednisolone does not appear to affect time to shock reversal.

Safety of the LMA®Gastro™ for Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) patients typically receive either tubeless anesthesia or general endotracheal anesthesia (GETA). Patients receiving propofol-based total intravenous anesthesia (TIVA) are at higher risk of sedation-related adverse events (SRAEs) than patients receiving GETA, primarily due to the need for additional airway maneuvers. The increasing use of non-operating room (OR) anesthesia and the perception of a higher incidence of adverse outcomes in non-OR areas has led to the development of devices to improve safety while maintaining efficiency. The purpose of this study was to evaluate if the LMA Gastro™ could be used as a safe alternative to tubeless anesthesia for successfully completing ERCPs. METHODS: Eligible subjects were identified within the patient population at MD Anderson Cancer Center. Inclusion criteria consisted of adult patients (≥18 years old) scheduled for elective ERCP with TIVA. This was a prospective observational study in which the following data were collected: number of attempts and time to successful supraglottic airway (SGA) placement, vital signs, peripheral oxygen saturation (SpO2), median end-tidal CO2, practitioner satisfaction, and any complications. RESULTS: A total of 30 patients were included in this study. The overall rate of successful SGA placement within 3 attempts was 96.7% (95% confidence interval [CI], 82.8-99.9) or 29/30. The rate of successful ERCP with SGA placement within 3 attempts was 93.3% (95% CI, 77.9-99.2) or 28/30. Both the gastroenterologist and anesthesiologist reported satisfaction with the device in 90% of the cases (in 66.7% of the cases both anesthesiologist and gastroenterologist scored the device a 7/7 for satisfaction). Patients maintained an SpO2 of 95%-100% from induction to discharge, with the exception of 1 patient who had an SpO2 of 93%. The median end-tidal CO2 during the procedure for all patients was 35 mm Hg. Observed aspiration did not occur in any patient. Symptoms of hoarseness (13.3%), mouth soreness (6.7%), sore throat (6.6%), and minor bleeding/cuts/redness/change in taste to the tongue (3.3%) were determined through patient questioning before postanesthesia care unit (PACU) discharge. CONCLUSIONS: Our study suggests that the LMA Gastro might be a safe alternative for ERCP procedures. There was a high level of practitioner satisfaction. Only minor complications, such as hoarseness, mouth or throat soreness, or minor trauma to the tongue were experienced by patients. Similar incidences of complications may occur with GETA and tubeless anesthesia. The procedure was well tolerated by all patients; all patients maintained adequate oxygenation and required only minimal blood pressure support.

Oncologic Safety and Surveillance of Autologous Fat Grafting following Breast Conservation Therapy.

BACKGROUND: Autologous fat grafting is a useful adjunct following breast reconstruction. The impact of autologous fat grafting on oncologic safety and surveillance remains questionable, particularly following breast conservation therapy. METHODS: The authors performed a retrospective review of patients who underwent delayed fat grafting following breast conservation therapy between 2006 and 2016. A control group of conservatively managed patients without grafting was matched for cancer stage, age, body mass index, and follow-up. Outcomes included locoregional recurrence and oncologic surveillance. RESULTS: Seventy-two patients were identified per cohort. There were no differences in median age (50 years versus 51 years; p = 0.87), body mass index (28.2 kg/m versus 27.2 kg/m; p = 0.38), or length of follow-up (61.9 months versus 66.8 months; p = 0.144) between controls and grafted patients, respectively. Overall, four patients in each cohort experienced recurrence (5.6 percent; p = 1.00) with similar cumulative incidence estimates observed (log-rank test, p = 0.534). There were no significant differences in palpable mass (9.7 percent versus 19.4 percent; p = 0.1), fat necrosis (34.7 percent versus 33.3 percent; p = 0.86), calcifications (37.5 percent versus 34.7 percent; p = 0.73), or indication for breast biopsy (15.3 percent versus 22.2 percent; p = 0.23) between breast conservation and breast conservation therapy plus autologous fat grafting cohorts, respectively. CONCLUSIONS: Overall, the authors found no difference in recurrence rates after breast conservation with or without delayed fat grafting. Furthermore, there were no differences in the rates of fat necrosis, palpable mass, and abnormal radiographic findings. This study represents the longest follow-up to date in in a large matched study of autologous fat grafting with breast conservation therapy demonstrating oncologic safety and no interference with follow-up surveillance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Pleural Fluid Cytokine Levels at Baseline and Over Time are Associated With Time to IPC Removal: An Exploratory Study.

BACKGROUND: The behavior of pleural fluid cytokine (PFCs) levels and their association with pleurodesis after indwelling pleural catheter (IPC) placement is unknown. OBJECTIVE: A prospective exploratory study was conducted to obtain preliminary data on PFC levels after IPC placement. METHODS: The PFC panel consisted of 4 cytokines [interleukin -8 (IL-8), vascular endothelial growth factor, total (but not activated) transforming growth factor betas, and basic fibroblast growth factor], measured across 5 time points (T0: insertion; T1: 24 to 48 h; T2: 72 to 96 h; T3: 1 wk; and T4: 2 wk). Profile plots were used to identify patterns of change of PFC levels. Correlation matrices for each PFC over time were computed, and area under the curve (AUC) categories were used to compare the cumulative incidence of IPC removal. Auto pleurodesis was defined as elective catheter removal because of decreased drainage within 90 days of insertion. RESULTS: A total of 22 patients provided complete data. Except for IL-8, the majority of PFCs demonstrated strong positive correlations across measurement time points. Patients with high AUCs for IL-8, basic fibroblast growth factor, and vascular endothelial growth factor had a higher cumulative incidence of IPC removal by 90 days than did patients with low AUCs. CONCLUSION: This is the first study to evaluate longitudinal changes of pleural cytokine levels with respect to the likelihood of IPC removal and provide early evidence that the cytokine profile may be associated with the outcome of pleurodesis induced by IPCs. However, this is an exploratory study and further studies are needed to assess if these findings can be validated in further studies.

PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC.

BACKGROUND AND OBJECTIVE: Analysis of programmed death ligand-1 (PD-L1) in tumour samples is necessary to identify candidates for anti-PD-L1/PD-L1 therapy. Because PD-L1 is evaluated by immunohistochemistry (IHC), an adequate amount of tumour tissue is a prerequisite for PD-L1 testing. To examine whether pleural fluid might be an alternative to biopsy/resection specimens for IHC evaluation of PD-L1 in patients with non-small cell lung carcinoma (NSCLC), we compared PD-L1 by IHC between histological specimens and matched pleural fluid. METHODS: A retrospective cohort study of patients with NSCLC who underwent core biopsy of a lung mass/surgical resection with PD-L1 IHC and had a pleural fluid cell block (CB) available for PD-L1 staining was conducted. PD-L1 was categorized as negative (PD-L1 in <1% of tumour cells), moderately positive (PD-L1 in ≥1% to <50%), strongly positive (PD-L1 ≥ 50) or inadequate for PD-L1 testing (<100 tumour cells in the CB). Weighted Cohen's kappa was calculated to evaluate the agreement between PD-L1 on biopsy/resection specimen and pleural fluid for variables with more than two categories. RESULTS: Of the 115 patients included in this study, 82 (71.3%) had at least 100 tumour cells and were included in the analysis. Of these, 80 (97.6%) had adenocarcinoma. For PD-L1 of histological specimens versus pleural fluid categorized as negative, moderately positive or strongly positive, the weighted kappa statistic was 0.76 (95% CI: 0.64-0.88), and the concordance was 0.78 (95% CI: 0.68-0.86). CONCLUSION: Correlation and concordance are high between PD-L1 in histological specimens and matched pleural fluid. Evaluation of PD-L1 in pleural fluid should be considered in patients unable to undergo histological biopsies.

Secondary spontaneous pneumothorax in cancer patients.

BACKGROUND: Malignancy-associated secondary spontaneous pneumothorax (MSSP) poses significant challenges due to limited survival. By assessing risk factors associated with a MSSP recurrence, there is potential to identify patients who could benefit from early intervention intended to prevent recurrence. METHODS: We performed a retrospective cohort study of patients with MSSP. The primary outcome was time to MSSP recurrence. We used a competing risk model to identify risk factors associated with MSSP recurrence. RESULTS: A total of 2,532 patients were diagnosed with pneumothorax, with 114 having MSSP but only 96 were evaluable for the time-to-recurrence analysis. Of the 96 patients, 9 (9.4%) patients experienced recurrent MSSP, and 58 (60.4%) patients died during the study's follow-up period. The estimated cumulative incidence (CI) of MSSP considering death as a competing risk was 10.1% at 15 months. The univariable model identified the following covariates as associated with MSSP recurrence: mediastinal shift (HR 12.30, 95% CI: 3.44-43.91, P<0.001), distance from lung apex to thoracic cupola (HR 1.02, 95% CI: 1.00-1.03, P=0.003), and distance between visceral and chest wall at the hilum (HR 1.02, 95% CI: 1.00-1.03, P=0.026). CONCLUSIONS: Although the incidence of MSSP recurrence was found to be low, clinical factors such as sarcoma, the associated mediastinal shift, greater distance from lung apex to thoracic cupola, greater distance between visceral and chest wall at the hilum were found to be risk factors for MSSP recurrence.