Comparison of perioperative adverse events following suburethral sling placement using synthetic mesh, autologous rectus fascia, and autologous fascia lata in a national surgical registry.

AIMS: To assess and compare 30-day perioperative adverse events following suburethral sling surgery using synthetic mesh, autologous rectus fascia, and autologous fascia lata in women. METHODS: This was a retrospective cohort study of patients who underwent fascial or synthetic sling placement for stress urinary incontinence between 2008 and 2021 using the American College of Surgeons' National Surgical Quality Improvement Program database. Current Procedural Terminology codes were used to identify patients undergoing each type of sling procedure. Multivariable regression analysis with stepwise regression was used to assess the odds of composite adverse events (e.g., urinary tract infection, surgical site infection, pulmonary embolism, and other reportable events) between cohorts. RESULTS: Of the 41 533 female patients who underwent isolated suburethral sling placement without concurrent procedures, 41 292 (99.4%) received a synthetic mesh sling, and 241 (0.6%) received an autologous facial sling. In the fascial sling cohort, 160 (66.4%) underwent rectus fascia harvest and 81 (33.6%) underwent fascia lata harvest. Sling surgeries involving autologous fascia were associated with increased odds of adverse events compared to those involving synthetic mesh, even after adjusting for confounders (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 2.56-5.15). Compared to fascial slings from rectus fascia, slings from fascia lata were associated with increased odds of composite adverse events (aOR: 2.11, 95% CI: 1.03-4.04). However, with the exclusion of urinary tract infections, the adverse event rate was similar between slings using the two fascial harvest techniques (aOR: 1.93, 95% CI: 0.81-4.63). CONCLUSIONS: In this retrospective database study, suburethral sling surgeries using autologous fascia were independently associated with a 3.6-fold increase in odds of 30-day perioperative adverse events compared to sling surgeries using synthetic mesh.

A visiting otolaryngology team in northern Ontario - demographics, clinical presentation and barriers to access.

CONTEXT: Approximately 20% of Canadians reside in rural or remote communities where access to medical specialties such as otolaryngology remains challenging due to long wait times and distance to services. The purpose of this study was to characterize patient demographics, common clinical diagnoses, and barriers to accessing otolaryngology services, in a remote Northern Ontario setting. A secondary objective was to describe a care model that provides multi-subspecialty otolaryngology services to a remote community. ISSUE: A team of academic otolaryngologists provided annual (2020-2021) subspecialty services in otology, neurotology, rhinology, head and neck oncology, and pediatrics to a remote hospital with admitting, general anesthesia and surgical resources. Data regarding patient demographics, otolaryngology-related diagnosis, wait times and distance travelled were recorded. Data were obtained for 276 patients treated in the clinic. The median age was 47 years (range 0-85 years). The most common otolaryngological conditions were hearing loss (n=62) and nasal obstruction (n=34). Nearly 30% of patients traveled further than 150 km to access care, and 62% waited 3-6 months for a consultation. LESSONS LEARNED: This is the first study to characterize the demographics and range of otolaryngological disorders encountered in a remote Northern Ontario setting. The results have identified specific otolaryngology needs and barriers to access to care. The data can be used to guide healthcare providers and administrators on resource allocation to optimize the delivery of otolaryngology services.

Statewide geographic variation in hysterectomy approach for pelvic organ prolapse: a county-level analysis.

BACKGROUND: There are no definitive guidelines for surgical treatment of pelvic organ prolapse. Previous data suggests geographic variation in apical repair rates in health systems throughout the United States. Such variation can reflect lack of standardized treatment pathways. An additional area of variation for pelvic organ prolapse repair may be hysterectomy approach which could not only influence concurrent repair procedures, but also healthcare utilization. OBJECTIVE: This study aimed to examine statewide geographic variation in surgical approach of hysterectomy for prolapse repair and concurrent use of colporrhaphy and colpopexy. STUDY DESIGN: We conducted a retrospective analysis of Blue Cross Blue Shield, Medicare, and Medicaid fee-for-service insurance claims for hysterectomies performed for prolapse in Michigan between October 2015 and December 2021. Prolapse was identified with International Classification of Disease Tenth Revision codes. The primary outcome was variation in surgical approach for hysterectomy as determined by Current Procedural Terminology code (vaginal, laparoscopic, laparoscopic assisted vaginal, or abdominal) on a county level. Patient home address zip codes were used to determine county of residence. A hierarchical multivariable logistic regression model with vaginal approach as the dependent variable and county-level random effects was estimated. Patient attributes, including age, comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, morbid obesity), concurrent gynecologic diagnoses, health insurance type, and social vulnerability index were used as fixed-effects. To estimate variation between counties in vaginal hysterectomy rates, a median odds ratio was calculated. RESULTS: There were 6974 hysterectomies for prolapse representing 78 total counties that met eligibility criteria. Of these, 2865 (41.1%) underwent vaginal hysterectomy, 1119 (16.0%) underwent laparoscopic assisted vaginal hysterectomy, and 2990 (42.9%) underwent laparoscopic hysterectomy. The proportion of vaginal hysterectomy across 78 counties ranged from 5.8% to 86.8%. The median odds ratio was 1.86 (95% credible interval, 1.33-3.83), consistent with a high level of variation. Thirty-seven counties were considered statistical outliers because the observed proportion of vaginal hysterectomy was outside the predicted range (as defined by confidence intervals of the funnel plot). Vaginal hysterectomy was associated with higher rates of concurrent colporrhaphy than laparoscopic assisted vaginal hysterectomy or laparoscopic hysterectomy (88.5% vs 65.6% vs 41.1%, respectively; P<.001) and lower rates of concurrent colpopexy (45.7% vs 51.7% vs 80.1%, respectively; P<.001). CONCLUSION: This statewide analysis reveals a significant level of variation in the surgical approach for hysterectomies performed for prolapse. The variation in surgical approach for hysterectomy may help account for high rates of variation in concurrent procedures, especially apical suspension procedures. These data highlight how geographic location may influence the surgical procedures a patient undergoes for uterine prolapse.

Variation in diagnosis of urinary incontinence in women by provider and patient demographic factors.

INTRODUCTION: Urinary incontinence (UI) among women is under-recognized in primary care setting. We hypothesized that UI is, therefore, more commonly diagnosed by specialists. Our aim was to determine the rate of UI diagnosis by provider and patient demographics, and whether these factors affect the likelihood of UI diagnosis. METHODS: Retrospective study using electronic medical records from 2010 to 2019. Ambulatory patient encounters by adult females were identified. Encounters with new diagnosis of UI (stress, urgency, mixed, or unspecified) were identified using ICD 9 and 10 codes. The following data were extracted: diagnosing provider specialty and sex, patient age, BMI, race, estimated household income, insurance coverage and type, and primary care provider (PCP). Rate of UI diagnosis was calculated using proportions. Univariable comparison and multivariable logistic regression were performed. RESULTS: 576,110 patient encounters were captured. 14,378 patient encounters had UI diagnosis (2.5%). UI population had the following characteristics: Mean age of 60.1 ± 15.5 years, 65.6% identified as white, 75.7% had a PCP, and 87.9% had insurance. UI diagnosis rate was < 1% for PCPs. Multivariable logistic regression showed that urogynecologists and female providers were more likely to diagnose UI; patient demographics associated with UI diagnosis included older age, elevated BMI, white race, commercial insurance, and having a PCP. Estimated household income did not have a significant effect. CONCLUSION: Diagnosis of UI is seldom made by PCPs. Race, insurance, and having a PCP may affect the likelihood of receiving UI diagnosis. Continued efforts to promote equity in recognizing UI may be warranted.

Variations in structural support site failure patterns by prolapse size on stress 3D MRI.

INTRODUCTION AND HYPOTHESIS: Our objective was to develop a standardized measurement system to evaluate structural support site failures among women with anterior vaginal wall-predominant prolapse according to increasing prolapse size using stress three-dimensional (3D) magnetic resonance imaging (MRI). METHODS: Ninety-one women with anterior vaginal wall-predominant prolapse and uterus in situ who had undergone research stress 3D MRI were included for analysis. The vaginal wall length and width, apex and paravaginal locations, urogenital hiatus diameter, and prolapse size were measured at maximal Valsalva on MRI. Subject measurements were compared to established measurements in 30 normal controls without prolapse using a standardized z-score measurement system. A z-score greater than 1.28, or the 90th percentile in controls, was considered abnormal. The frequency and severity of structural support site failure was analyzed based on tertiles of prolapse size. RESULTS: Substantial variability in support site failure pattern and severity was identified, even between women with the same stage and similar size prolapse. Overall, the most common failed support sites were straining hiatal diameter (91%) and paravaginal location (92%), followed by apical location (82%). Impairment severity z-score was highest for hiatal diameter (3.56) and lowest for vaginal width (1.40). An increase in impairment severity z-score was observed with increasing prolapse size among all support sites across all three prolapse size tertiles (p < 0.01 for all). CONCLUSIONS: We identified substantial variation in support site failure patterns among women with different degrees of anterior vaginal wall prolapse using a novel standardized framework that quantifies the number, severity, and location of structural support site failures.

Sporadic pituitary adenoma with somatic double-hit loss of MEN1.

PURPOSE: Pituitary adenomas commonly arise in patients with MEN1 syndrome, an autosomal dominant condition predisposing to neuroendocrine tumor formation, and typically diagnosed in patients with a relevant family cancer history. In these patients with existing germline loss of MEN1 on one allele, somatic loss of the second MEN1 allele leads to complete loss of the MEN1 protein, menin, and subsequent tumor formation. METHODS: Whole exome sequencing was performed on the tumor and matching blood under an institutional board approved protocol. DNA extraction and analysis was conducted according to previously described methods. RESULTS: We describe a 23 year-old patient with no significant past medical history or relevant family history who underwent surgical resection of a symptomatic and medically resistant prolactinoma. Whole exome sequencing of tumor and blood samples revealed somatic loss of MEN1 at both alleles, suggesting a double hit mechanism, with no underlying germline MEN1 mutation. CONCLUSION: To our knowledge, this is the first case of pituitary adenoma to arise from somatic loss of MEN1 and in the absence of an underlying germline MEN1 mutation.

Predictors of same-day discharge following benign minimally invasive hysterectomy.

BACKGROUND: Same-day discharge following minimally invasive hysterectomy has been shown to be safe and feasible in select populations, but many nonclinical factors influencing same-day discharge remain unexplored. OBJECTIVE: To develop prediction models for same-day discharge following minimally invasive hysterectomy using both clinical and nonclinical attributes and to compare model concordance of individual attribute groups. STUDY DESIGN: We performed a retrospective study of patients who underwent elective minimally invasive hysterectomy for benign gynecologic indications at 69 hospitals in a statewide quality improvement collaborative between 2012 and 2019. Potential predictors of same-day discharge were determined a priori and placed into 1 of 7 attribute groupings: intraoperative, surgeon, hospital, surgical timing, patient clinical, patient socioeconomic, and patient geographic attributes. To account for clustering of same-day discharge practices among surgeons and within hospitals, hierarchical multivariable logistic regression models were fitted using predictors from each attribute group individually and all predictors in a composite model. Receiver operator characteristic curves were generated for each model. The Hanley-McNeil test was used for comparisons, 95% confidence intervals for the areas under the receiver operator characteristic curve were calculated, and a P value of <.05 was considered significant. RESULTS: Of the 23,513 patients in our study, 5062 (21.5%) had same-day discharge. The composite model had an area under the receiver operator characteristic curve of 0.770 (95% confidence interval, 0.763-0.777). Among models using factors from individual attribute groups, the model using intraoperative attributes had the highest concordance for same-day discharge (area under the receiver operator characteristic curve, 0.720; 95% confidence interval, 0.712-0.727). The models using surgeon and hospital attributes were the second and third most concordant, respectively (area under the receiver operator characteristic curve, 0.678; 95% confidence interval, 0.670-0.685; area under the receiver operator characteristic curve, 0.655; 95% confidence interval, 0.656-0.664). Models using surgical timing and patient clinical, socioeconomic, and geographic attributes had poor predictive ability (all areas under the receiver operator characteristic curve <0.6). CONCLUSION: Clinical and nonclinical attributes contributed to a composite prediction model with good discrimination in predicting same-day discharge following minimally invasive hysterectomy. Factors related to intraoperative, hospital, and surgeon attributes produced models with the strongest predictive ability. Focusing on these attributes may aid efforts to improve utilization of same-day discharge following minimally invasive hysterectomy.

Geometric analysis of the urethral-vaginal interface curvature in women with and without stress urinary incontinence: A pilot magnetic resonance imaging study.

AIMS: To evaluate differences in the curvature of the urethral-vaginal interface in women with and without stress urinary incontinence (SUI) using geometric morphometric analysis techniques. METHODS: We conducted a pilot case-control study using magnetic resonance imaging (MRI) scans of 18 women with and without SUI. The urethral-vaginal interface at the level of the mid-urethra was fitted with a second-order polynomial regression. The chord length and chord-to-vertex length of the resulting parabolic curve were used to calculate the arc length and radius of a circular arc fitted to the interface curvature. Demographic characteristics and Pelvic Organ Prolapse Quantification (POP-Q) parameters were collected. Subjects were stratified by those with and without SUI, as well as by those with and without anterior wall prolapse beyond 2 cm proximal to the hymen (Aa > -2 cm). RESULTS: The radius of the urethral-vaginal interface curvature was not found to be different between subjects with and without SUI (8.8 vs. 9.2 mm, p = 0.53); however, this value was smaller in subjects with Aa > -2 (8.4 vs. 11.9 mm, p = 0.03). The chord length, chord-to-vertex length, and arc length comprising the urethral-vaginal interface curvature were similar between subjects with and without SUI, and between subjects with and without Aa > -2 cm (p > 0.05 for all). CONCLUSIONS: In this pilot study population, the radius of the urethral-vaginal interface curvature at the mid-urethra was smaller among women with anterior vaginal wall prolapse beyond 2 cm proximal to the hymen. A difference in the urethral-vaginal interface curvature among women with and without SUI was not found.

Position and orientation of vaginal pessaries in situ on magnetic resonance imaging.

INTRODUCTION AND HYPOTHESIS: We hypothesize that there are differences in the position and orientation of ring and Gellhorn pessaries in situ on magnetic resonance imaging (MRI). METHODS: This was a retrospective cohort study comparing MRI findings in 25 women with pessaries in situ at the time of imaging. Scanner coordinates for anatomic and pessary landmarks were obtained and transformed to 3D Pelvic Inclination Correction System coordinates using MATLAB software. The normal vector to the pessary disc was computed and compared to the positive y-axis in the sagittal and coronal planes to determine XY and YZ disc angles, respectively. Comparisons between groups were made using Wilcoxon rank, Fisher's exact, and Brown-Forsythe tests. RESULTS: Twenty-one women with ring pessaries and four women with Gellhorn pessaries met inclusion criteria for the study. Women with ring pessaries were younger (68.4 vs. 80.7 years, p = 0.003) but had similar BMI, vaginal parity, history of hysterectomy, and anatomic characteristics. Ring pessaries had a smaller diameter (59.5 vs. 79.3 mm, p = 0.004) and were positioned further posterior with respect to the inferior pubic point (midpoint X position 42.6 vs. 29.5 mm, p = 0.004). There were significant differences in the magnitude and variance of the XY disc angle (57.0 ± 14.0 vs. -1.2 ± 2.8 degrees, p = 0.002 for magnitude, p = 0.012 for variance) but not the YZ disc angle (3.3 ± 30.6 vs. 1.5 ± 7.7 degrees, p > 0.05 for both) between groups. CONCLUSIONS: We found differences in the position and orientation between ring and Gellhorn pessaries in situ using an anatomic 3D reference system. These findings provide insight into the mechanism of action of vaginal pessaries.

Racial Disparities in Sterilization Procedure Performed at Time of Cesarean Section.

OBJECTIVES: While bilateral tubal ligation has historically been performed for sterilization at cesarean delivery (CD), recent data supports the use and safety of opportunistic bilateral salpingectomy during CD to decrease lifetime ovarian cancer risk. Prior studies have described racial disparities in sterilization rates, but there is a paucity of data regarding racial disparities in type of sterilization procedure. Our objective was to determine differences in sterilization procedure type performed at CD by race (Black vs. non-Black) to evaluate for equity in bilateral salpingectomy utilization. STUDY DESIGN: We performed a retrospective cohort study of patients included in the American College of Surgeons National Surgical Quality Improvement Program database who underwent sterilization at time of CD from January 2019, to December 2020, identified using Current Procedural Terminology codes. Patients without documented race were excluded. Multivariable logistic regression was used to determine odds of undergoing bilateral salpingectomy compared with bilateral tubal ligation by race while controlling for confounders. RESULTS: Of 28,147 patients who underwent CD, 3,087 underwent concurrent sterilization procedure, and 2,161 met inclusion criteria (Black: n = 279; non-Black: n = 1,882). Black patients were significantly more likely to have hypertension (10.8% vs. 5.3%, p < 0.01), bleeding disorders (3.9% vs. 1.3%, p < 0.01), preoperative anemia (hemoglobin < 11 g/dL; 36.9% vs. 21.3%, p < 0.01), and be of American Society of Anesthesiologist class 3 or higher (29.4% vs. 22.5%, p = 0.01) than non-Black patients. After adjusting for differences, Black patients were almost 50% less likely than non-Black patients to undergo bilateral salpingectomy compared with bilateral tubal ligation for sterilization at CD (adjusted odds ratio = 0.52, 95% confidence interval: 0.36-0.75). CONCLUSION: Despite evidence that bilateral salpingectomy decreases ovarian cancer risk and is safe at CD, there is a racial disparity in bilateral salpingectomy utilization. While the cause of this disparity is unclear, further research is warranted to determine root causes and equitable solutions. KEY POINTS: · Opportunistic salpingectomy is recommended for primary prevention of ovarian cancer in patients undergoing pelvic surgery who have completed childbearing.. · Black patients were almost 50% less likely to undergo bilateral salpingectomy compared with bilateral tubal ligation than non-Black patients even after controlling for possible confounders.. · Further research is needed to determine root cause of the racial disparity in bilateral salpingectomy utilization rate..

Pelvic cross-sectional area at the level of the levator ani and prolapse.

INTRODUCTION AND HYPOTHESIS: Intraabdominal pressure acts on the pelvic floor through an aperture surrounded by bony and muscular structures of the pelvis. A small pilot study showed the area of the anterior portion of this plane is larger in pelvic organ prolapse. We hypothesize that there is a relationship between prolapse and anterior (APA) and posterior (PPA) pelvic cross-sectional area in a larger, more diverse population. STUDY DESIGN: MRIs from 30 prolapse subjects and 66 controls were analyzed in this case-control study. The measurement plane was tilted to approximate the level of the levator ani attachments. Three evaluators made measurements. Patient demographic characteristics were compared using Wilcoxon rank-sum and Fisher's exact tests. A multivariable logistic regression model identified factors independently associated with prolapse. RESULTS: Controls were 3.7 years younger and had lower parity, but groups were similar in terms of race, height, and BMI. Cases had a larger APA (p < 0.0001), interspinous diameter (ISD) (p = 0.001), anterior-posterior (AP) diameter (p = 0.01), and smaller total obturator internus muscle (OIM) area (p = 0.002). There was no difference in the size of the PPA(p = 0.12). Bivariate logistic regression showed age (p = 0.007), parity (p = 0.009), ISD (p = 0.002), AP diameter (p = 0.02), APA (p < 0.0001), and OIM size (p = 0.01) were significantly associated with prolapse; however, PPA was not (p = 0.12). After adjusting for age, parity, and major levator defect, prolapse was significantly associated with increased anterior pelvic area (p = 0.001). CONCLUSIONS: We confirm that a larger APA and decreasing OIM area are associated with prolapse. The PPA was not significantly associated with prolapse.

Pre-operative headaches and obstructive hydrocephalus predict an extended length of stay following suboccipital decompression for pediatric Chiari I malformation.

PURPOSE: For young children and adolescents with Chiari malformation type I (CM-I), the determinants of extended length of hospital stay (LOS) after neurosurgical suboccipital decompression are obscure. Here, we investigate the impact of patient- and hospital-level risk factors on extended LOS following surgical decompression for CM-I in young children to adolescents. METHODS: The Kids' Inpatient Database year 2012 was queried. Pediatric CM-I patients (6-18 years) undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree patient comorbidities or post-operative complications correlated with extended LOS. RESULTS: A total of 1592 pediatric CM-I patients were identified for which 328 (20.6%) patients had extended LOS (normal LOS, 1264; extended LOS, 328). Age, gender, race, median household income quartile, and healthcare coverage distributions were similar between the two cohorts. Patients with extended LOS had significantly greater admission comorbidities including headache symptoms, nausea and vomiting, obstructive hydrocephalus, lack of coordination, deficiency anemias, and fluid and electrolyte disorders. On multivariate logistic regression, several risk factors were associated with extended LOS, including headache symptoms, obstructive hydrocephalus, and fluid and electrolyte disorders. CONCLUSIONS: Our study using the Kids' Inpatient Database demonstrates that presenting symptoms and signs, including headaches and obstructive hydrocephalus, respectively, are significantly associated with extended LOS following decompression for pediatric CM-I.

Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases.

PURPOSE: Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare pre-treatment patient characteristics and outcomes between the two treatment options. METHODS: Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018. Pre-treatment factors and treatment responses were compared between those treated with LITT versus bevacizumab. RESULTS: Twenty-five patients underwent LITT and 13 patients were treated with bevacizumab. The LITT cohort had a longer overall survival (median 24.8 vs. 15.2 months for bevacizumab, p = 0.003) and trended to have a longer time to local recurrence (median 12.1 months vs. 2.0 for bevacizumab), although the latter failed to achieve statistical significance (p = 0.091). LITT resulted in an initial increase in lesional volume compared to bevacizumab (p < 0.001). However, this trend reversed in the long term follow-up, with LITT resulting in a median volume decrease at 1 year post-treatment of - 64.7% (range - 96.0% to + > 100%), while bevacizumab patients saw a median volume increase of + > 100% (range - 63.0% to + > 100%), p = 0.010. CONCLUSIONS: Our study suggests that patients undergoing LITT for RN have longer overall survival and better long-term lesional volume reduction than those treated with bevacizumab. However, it remains unclear whether our findings are due only to a difference in efficacy of the treatments or the implications of selection bias.

Laser interstitial thermal therapy for treatment of cerebral radiation necrosis.

Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with arteriovenous malformations and brain metastases but possibly also affecting patients treated with radiosurgery for meningioma. The pathophysiology of radiation necrosis is still not well understood but is most likely a secondary local tissue inflammatory response to brain tissue injured by radiation. Radiation necrosis in brain metastases patients may present radiographically and behave clinically like recurrent tumor. Differentiation between radiation necrosis and recurrent tumor has been difficult based on radiographic changes alone. Biopsy or craniotomy therefore remains the gold standard method of diagnosis. For symptomatic patients, corticosteroids are first-line therapy, but patients may fail medical management due to intolerance of chronic steroids or persistence of symptoms. In these cases, open surgical resection has been shown to be successful in management of surgically amenable lesions but may be suboptimal in patients with deep-seated lesions or extensive prior cranial surgical history, both carrying high risk for peri-operative morbidity. Laser interstitial thermal therapy has emerged as a viable, alternative surgical option. In addition to allowing access to tissue for diagnosis, thermal treatment of the lesion can also be delivered precisely and accurately under real-time imaging guidance. This review highlights the pertinent studies that have shaped the impetus for use of laser interstitial thermal therapy in the treatment of radiation necrosis, reviewing indications, outcomes, and nuances toward successful application of this technology in patients with suspected radiation necrosis.

Perioperative adverse events in women over age 65 undergoing robot-assisted sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Pelvic floor disorders are common among and disproportionately affect older women. There are limited data regarding perioperative adverse events in older women undergoing robot-assisted sacrocolpopexy (RASC) specifically. The aim of this study was to compare the rate of perioperative adverse events in younger (age <65 years) versus older (age >65 years) women who underwent RASC. METHODS: We conducted a retrospective cohort study of women who underwent RASC between 2013 and 2018. Postoperative adverse events were categorized according to the Clavien-Dindo classification. Our primary outcome was the rate of intraoperative adverse events and postoperative adverse events with Clavien-Dindo grade II or greater. Outcomes were compared using univariate and multivariate analysis. RESULTS: Of the 327 patients included in the study, 227 were <65 years of age and 100 were ≥65 years of age. Women ≥65 years of age had higher rates of hypertension, higher American Society of Anesthesiologist (ASA) class, and higher Charlson Comorbidity Index (CCI) scores compared with women <65 years of age; these were not associated with increased likelihood of adverse events. The overall rate of any perioperative adverse event was 18.3%. There was no statistically significant difference in the overall rate of perioperative adverse events between younger and older women (18.5% vs 18.0%, p = 0.91). CONCLUSIONS: There is no difference in rate of adverse events between women ≥65 years of age undergoing RASC and their younger counterparts.

Laser-interstitial thermal therapy compared to craniotomy for treatment of radiation necrosis or recurrent tumor in brain metastases failing radiosurgery.

PURPOSE: Many publications report laser-interstitial thermal therapy (LITT) as a viable alternative treatment to craniotomy for radiation necrosis (RN) and re-growing tumor occurring after stereotactic radiosurgery (SRS) for brain metastases. No studies to-date have compared the two options. The aim of this study was to retrospectively compare outcomes after LITT versus craniotomy for regrowing lesions in patients previously treated with SRS for brain metastases. METHODS: Data were collected from a single-institution chart review of patients treated with LITT or craniotomy for previously irradiated brain metastasis. RESULTS: Of 75 patients, 42 had recurrent tumor (56%) and 33 (44%) had RN. Of patients with tumor, 26 underwent craniotomy and 16 LITT. For RN, 15 had craniotomy and 18 LITT. There was no significant difference between LITT and craniotomy in ability to taper off steroids or neurological outcomes. Progression-free survival (PFS) and overall survival (OS) were similar for LITT versus craniotomy, respectively: %PFS-survival at 1-year = 72.2% versus 61.1%, %PFS-survival at 2-years = 60.0% versus 61.1%, p = 0.72; %OS-survival at 1-year = 69.0% versus 69.3%, %OS-survival at 2-years = 56.6% versus 49.5%, p = 0.90. Craniotomy resulted in higher rates of pre-operative deficit improvement than LITT (p < 0.01). On subgroup analysis, the single factor most significantly associated with OS and PFS was pathology of the lesion. About 40% of tumor lesions needed post-operative salvage with radiation after both craniotomy and LITT. CONCLUSIONS: LITT was as efficacious as craniotomy in achieving local control of recurrent irradiated brain metastases and facilitating steroid taper, regardless of pathology. Craniotomy appears to be more advantageous for providing symptom relief in those with pre-operative symptoms.

Erythrocytosis in hepatocellular carcinoma portends poor prognosis by respiratory dysfunction secondary to mitochondrial DNA mutations.

Erythrocytosis is a common paraneoplastic syndrome associated with hepatocellular carcinoma. Although increased erythropoietin (EPO) is found in these patients, the clinical significance and molecular mechanisms underlying this observation are unclear. We demonstrate an inverse relationship between EPO production and overall prognosis in our cohort of 664 patients as well as in data from The Cancer Genome Atlas. In the subset of hepatocellular carcinoma patients with erythrocytosis, we identified somatic mutations of mitochondrial DNA, resulting in impairment of respiratory metabolism, which sequentially led to depletion of α-ketoglutarate, stabilization of hypoxia inducible factor-α, and expression of target genes such as EPO. Cell lines and patient-derived xenograft models were used to demonstrate that EPO promoted cancer stem cell self-renewal and expansion in an autocrine/paracrine manner through enhanced Janus kinase/signal transducer and activator of transcription signaling both in vitro and in vivo. Furthermore, to explore the therapeutic targeting of EPO-induced tumor changes, we found that blocking EPO signaling with soluble EPO receptor extracellular domain Fc fusion protein could inhibit tumor growth both in vitro and in vivo. CONCLUSION: These findings suggest clinical and therapeutic implications for erythrocytosis in hepatocellular carcinoma. There is an underlying link between mitochondrial function and hypoxia inducible factor alpha signaling, revealing a mechanism of erythrocytosis in a subset of hepatocellular carcinoma patients who may benefit from treatment involving EPO signaling interference. (Hepatology 2017;65:134-151).

Integration of Metabolomics and Transcriptomics Reveals Major Metabolic Pathways and Potential Biomarker Involved in Prostate Cancer.

Prostate cancer is a highly prevalent tumor affecting millions of men worldwide, but poor understanding of its pathogenesis has limited effective clinical management of patients. In addition to transcriptional profiling or transcriptomics, metabolomics is being increasingly utilized to discover key molecular changes underlying tumorigenesis. In this study, we integrated transcriptomics and metabolomics to analyze 25 paired human prostate cancer tissues and adjacent noncancerous tissues, followed by further validation of our findings in an additional cohort of 51 prostate cancer patients and 16 benign prostatic hyperplasia patients. We found several altered pathways aberrantly expressed at both metabolic and transcriptional levels, including cysteine and methionine metabolism, nicotinamide adenine dinucleotide metabolism, and hexosamine biosynthesis. Additionally, the metabolite sphingosine demonstrated high specificity and sensitivity for distinguishing prostate cancer from benign prostatic hyperplasia, particularly for patients with low prostate specific antigen level (0-10 ng/ml). We also found impaired sphingosine-1-phosphate receptor 2 signaling, downstream of sphingosine, representing a loss of tumor suppressor gene and a potential key oncogenic pathway for therapeutic targeting. By integrating metabolomics and transcriptomics, we have provided both a broad picture of the molecular perturbations underlying prostate cancer and a preliminary study of a novel metabolic signature, which may help to discriminate prostate cancer from normal tissue and benign prostatic hyperplasia.