Lohse, Christine M.

OBJECTIVE Detection of vestibular schwannoma (VS) growth during observation leads to definitive treatment at most centers globally. Although ≥ 2 mm represents an established benchmark of tumor growth on serial MRI studies, 2 mm of linear tumor growth is unlikely to significantly alter microsurgical outcomes. The objective of the current work was to ascertain where the magnitude of change in clinical outcome is the greatest based on size. METHODS A single-institution retrospective review of a consecutive series of patients with sporadic VS who underwent microsurgical resection between January 2000 and May 2020 was performed. Preoperative tumor size cutpoints were defined in 1-mm increments and used to identify optimal size thresholds for three primary outcomes: 1) the ability to achieve gross-total resection (GTR); 2) maintenance of normal House-Brackmann (HB) grade I facial nerve function; and 3) preservation of serviceable hearing (American Academy of Otolaryngology–Head and Neck Surgery class A/B). Optimal size thresholds were obtained by maximizing c-indices from logistic regression models. RESULTS Of 603 patients meeting inclusion criteria, 502 (83%) had tumors with cerebellopontine angle (CPA) extension. CPA tumor size was significantly associated with achieving GTR, postoperative HB grade I facial nerve function, and maintenance of serviceable hearing (all p < 0.001). The optimal tumor size threshold to distinguish between GTR and less than GTR was 17 mm of CPA extension (c-index 0.73). In the immediate postoperative period, the size threshold between HB grade I and HB grade > I was 17 mm of CPA extension (c-index 0.65). At the most recent evaluation, the size threshold between HB grade I and HB grade > I was 23 mm (c-index 0.68) and between class A/B and C/D hearing was 18 mm (c-index 0.68). Tumors within 3 mm of the 17-mm CPA threshold displayed similarly strong c-indices. Among purely intracanalicular tumors, linear size was not found to portend worse outcomes for all measures. CONCLUSIONS The probability of incurring less optimal microsurgical outcomes begins to significantly increase at 14–20 mm of CPA extension. Although many factors ultimately influence decision-making, when considering timing of microsurgical resection, using a size threshold range as depicted in this study offers an evidence-based approach that moves beyond reflexively recommending treatment for all tumors after detecting ≥ 2 mm of tumor growth on serial MRI studies.

Objective To report perioperative, renal functional and oncologic outcomes for patients undergoing partial or radical nephrectomy for cT2 renal masses. Methods Retrospective review of patients who underwent partial ( n = 72) or radical nephrectomy ( n = 379) for cT2 renal masses from 2000 to 2016. After propensity adjustment using inverse probability weighting, the following were compared by surgery (partial or radical nephrectomy): complications, renal function measured by estimated glomerular filtration rate as continuous and as <60 mL/min/1.73 m 2 at 1 and 3 years postoperatively and overall, metastases‐free survival and cancer‐specific survival in patients with renal cell carcinoma. Results After propensity adjustment, clinical and radiographic features were well‐balanced between groups. Overall and severe complications were more common for partial compared with radical nephrectomy, although not statistically significant (19 vs 13%, P = 0.14 and 4 vs 2%, P = 0.3, respectively). Estimated glomerular filtration rate change at 1 and 3 years was more pronounced in radical compared with partial nephrectomy (median −16 vs −5 and −14 vs −2, respectively, P < 0.001). A greater proportion of radical nephrectomy patients had an estimated glomerular filtration rate <60 at 1 and 3 years (55 vs 17% and 48 vs 17%, respectively, P < 0.01). In renal cell carcinoma patients, overall, metastases‐free and cancer‐specific survival were not significantly different between groups (median survivor follow up 7.1 years, interquartile range 3.6–11.4). Conclusions Partial nephrectomy appears to be a relatively safe and a potentially effective treatment for cT2 renal masses, conferring better renal functional preservation compared with radical nephrectomy. These data support continued use of partial nephrectomy for renal masses >7 cm in appropriately selected patients.

BACKGROUND: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. OBJECTIVE: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS: Immunohistochemistry staining for Bim was performed on paraffin-embedded tumor tissue blocks from patients with metastatic ccRCC who underwent nephrectomy between 1990-2004. Associations of Bim expression with cancer-specific survival (CSS) and overall survival (OS) from date of metastasis were evaluated using multivariable Cox regression models, adjusting for age, sex, and metastases-score. RESULTS: 525 patients with metastatic ccRCC, of whom 169 (32%) had metastases at time of nephrectomy were studied. After multivariable adjustment, high Bim expression remained associated with worse CSS (HR = 1.31; 95% CI 1.07–1.59; p = 0.008) and OS (HR = 1.28; 95% CI 1.06–1.55; p = 0.01). The interaction between Bim and PD-L1 was not statistically significant for CSS ( p = 0.68) or OS ( p = 0.57), suggesting that the associations between Bim and survival outcomes were not significantly different based on tumor PD-L1 expression. CONCLUSION: High Bim expression in PTLs at nephrectomy is prognostic of worse CSS and OS in patients with metastatic ccRCC, irrespective of tumor PD-L1 expression. The role of earlier PD-1/PD-L1-directed therapy warrants evaluation in these patients.

Objectives: Clinicians need to identify which patients presenting with S. aureus bacteremia (SAB) have underlying cardiovascular implantable electronic device (CIED) infection and therefore need device extraction. The goal of this study was to identify clinical predictors of CIED infection in patients presenting with SAB. Methods: We retrospectively reviewed all cases of SAB in CIED recipients at Mayo Clinic from Jan 2001 to Dec 2011. CIED infection was defined using clinical, microbiologic and echocardiographic criteria. Patients who presented with clinical signs of CIED pocket infection were excluded. A multivariable model was developed to identify independent predictors of CIED infection. Model discrimination was summarized using the area under a receiver operating characteristics curve (AUC). Results: Among the 131 patients with SAB and CIED, 45 (34%) had underlying CIED infection. Permanent pacemaker (PPM) devices (OR 3.90, 95% CI 1.65-9.23, p=0.002), >1 device-related procedure (OR 3.30, 95% CI 1.23-8.86, p=0.018), and duration of SAB ≥4 days (OR 5.54, 95% CI 3.32-13.23, p <0.001) were independently associated with an increased risk of CIED infection. The AUC for this multivariable model was 0.79 indicating good discriminatory capacity to separate SAB patients with and without CIED infection. Various combinations of these three features and the corresponding predicted probabilities of CIED infection are summarized in Table. Conclusions: An individual patient’s risk of underlying CIED infection can be calculated based on the type of device, number of device-related procedures, and duration of SAB. Patients without any of these high-risk features have very low risk of underlying CIED infection and may be monitored closely without immediate device extraction.

AbstractBackgroundCalciphylaxis is a debilitating dermatological condition associated with high rates of morbidity and mortality. Palliative care offers a multidisciplinary approach to addressing symptoms and goals of care in patients with serious medical diagnoses. Involvement of palliative services for calciphylaxis is infrequently reported in the literature. The purpose of this report is to assess rates of palliative and pain consultation for patients with calciphylaxis.MethodsThis is a comprehensive, single‐institution retrospective chart review of 121 eligible patients with a diagnosis of calciphylaxis treated at Mayo Clinic in Rochester, Minnesota, from 1999 to 2016. Inclusion criteria were an indisputable diagnosis of calciphylaxis based on clinical, histopathologic, and radiographic features. One hundred twenty‐one patients met inclusion criteria.ResultsFifty‐one patients (42%) received either a palliative (n = 15) or pain (n = 20) consultation, or both (n = 16). Patients with a palliative care consultation were younger compared with those without (mean ages 57 vs. 62 years, P = 0.046). In 104 patients (86%), psychiatric symptoms were not assessed.ConclusionsIn this cohort of patients with calciphylaxis, the majority do not receive palliative and pain care consultations. Psychiatric complications are inconsistently addressed. These observations highlight practice gaps in the care of patients with calciphylaxis.

Objective: Active treatment of small- or medium-sized vestibular schwannoma during wait-and-scan management is currently recommended at most centers globally once growth is detected. The primary aim of the current study was to characterize the natural history of growing sporadic vestibular schwannoma during observation. Study Design: Cohort study. Setting: Four tertiary referral centers across the United States and Denmark. Patients: Patients with two prior MRI scans demonstrating ≥2 mm of linear growth who continued observational management. Intervention: Observation with serial imaging. Main Outcome Measure: Subsequent linear growth-free survival (i.e., an additional ≥2 mm of growth) following initial growth of ≥2 mm from tumor size at diagnosis. Results: Among 3,402 patients undergoing observation, 592 met inclusion criteria. Median age at initial growth was 66 years (IQR 59–73) for intracanalicular tumors (N = 65) and 62 years (IQR 54–70) for tumors with cerebellopontine angle extension (N = 527). The median duration of MRI surveillance following initial detection of tumor growth was 5.2 years (IQR 2.4–6.9) for intracanalicular tumors and 1.0 year (IQR 1.0–3.3) for cerebellopontine angle tumors. For intracanalicular tumors, subsequent growth-free survival rates (95% CI; number still at risk) at 1, 2, 3, 4, and 5 years following the initial MRI that demonstrated growth were 77% (67–88; 49), 53% (42–67; 31), 46% (35–60; 23), 34% (24–49; 17), and 32% (22–47; 13), respectively. For cerebellopontine angle tumors, subsequent growth-free survival rates were 72% (68–76; 450), 47% (42–52; 258), 32% (28–38; 139), 26% (21–31; 82), and 22% (18–28; 57), respectively. For every 1 mm increase in magnitude of growth from diagnosis to tumor size at detection of initial growth, the HRs associated with subsequent growth were 1.64 (95% CI 1.25–2.15; p < 0.001) for intracanalicular tumors and 1.08 (95% CI 1.01–1.15; p = 0.02) for cerebellopontine angle tumors. Conclusions: Growth detected during observation does not necessarily portend future growth, especially for slowly growing tumors. Because early treatment does not confer improved long-term quality of life outcomes, toleration of some growth during observation is justifiable in appropriately selected cases.

6049 Background: In the head and neck, human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) has a better prognosis and more tumor infiltrating lymphocytes (TILs) compared to its HPV(-) counterpart. Within HPV(+)OPSCC, the prognostic value of TILs in the primary tumor and in metastatic lymph nodes is not well understood. Methods: This is a matched case-control study at a tertiary care center of HPV(+)OPSCC patients who underwent primary surgery between 05/2007–12/2016. Cases developed locoregional recurrence or distant metastases during follow-up, while controls did not during a similar duration of follow-up. Pairs were matched on age, American Joint Committee on Cancer (AJCC) 8th edition pathologic stage, sex, year of surgery, degree of adjuvant treatment, comorbidities, and smoking status. One representative H&E slide of the primary tumor and lymph node (when nodal disease was present) from each patient was independently reviewed by two pathologists (JG, MR) blinded to outcome, for tumor TILs (tTILs) density (defined as % TILs), presence/absence of desmoplastic stroma, and when stroma was present, for stromal TILs (sTILs) density (defined as relative crowding of TILs). The Brandwein-Gensler pattern of invasion (POI) score was used to grade the primary tumor. Interrater agreement was assessed using Cohen’s kappa. Associations between TILs and time to disease progression were assessed using Cox proportional hazards regression models. Results: 41 case-control pairs (N=82) were included in the study: 38 (46%) were AJCC pStage I, 37 (45%) were pStage II, and 7 (9%) were pStage III; 22 (27%) underwent surgery alone, 15 (18%) underwent surgery with adjuvant radiotherapy, and 45 (55%) underwent surgery with adjuvant chemoradiation. Interrater agreement was fair for tTILs density in the primary tumor ( k=0.24) and lymph node ( k=0.23), moderate for desmoplastic stroma in the primary tumor ( k=0.58) and lymph node ( k=0.64), moderate for sTILs density in the primary tumor ( k=0.58) and lymph node ( k=0.48), and fair for the POI score ( k=0.17). tTILs density ≥10% (HR 0.35, 95% CI 0.14-0.90, p=0.028) and a moderate/dense sTILs density (HR 0.15, 95% CI 0.04-0.68, p=0.014) in the primary tumor were significantly associated with decreased risk of disease progression. An aggressive POI score of III or IV was significantly associated with increased risk of disease progression (HR 4.00, 95% CI 1.34-11.96, p=0.013). None of the study measures in the lymph node were significantly associated with disease progression. Conclusions: In HPV(+)OPSCC, a higher density of tumor and stromal TILs and nonaggressive POI in the primary tumor specimen may indicate a lower risk of disease progression. TILs may serve as a powerful prognostic marker for the adaptive immune response to this disease.

Objective: Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses. Study Design: Retrospective cohort. Setting: Tertiary referral center. Patients: Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included. Interventions: Metformin use among patients with observed sporadic VS. Main Outcome Measures: Tumor growth, defined as an increase in volume of at least 20% from the initial MRI. Results: A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40–1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34–1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth. Conclusion: Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.

Objective: To investigate potential associations between the Predictive Gagging Survey (PGS) with patient experience of gag and discomfort as well as provider perception of patient gag and level of laryngeal visualization during flexible laryngoscopy with stroboscopy (FL-S). Methods: A total of 53 adult patients undergoing FL-S were recruited for this prospective non-controlled study. PGS was completed before FL-S. Patients rated perceived level of gag and discomfort on a 10-point severity scale after FL-S. Additionally, providers completed a Gagging Severity Index (GSI) reflecting their impression of patient gag and level of laryngeal visualization following FL-S. Spearman rank correlation coefficients were used to assess associations. Results: There was a positive association with PGS score and patient perception of gagging (0.34; P = .013) and patient perception of discomfort (0.38; P = .005). No significant association was found between PGS score and provider GSI (−0.12; P = .39) or level of laryngeal visualization (0.15; P = .29). A negative association was found between level of laryngeal visualization and patient perception of gagging (−0.34; P = .012) and discomfort (−0.44; P = .001). No significant differences were found between current and former smokers compared to never smokers for GSI or patient-perceived gag or discomfort. Conclusions: While not predictive of GSI or level of laryngeal visualization, the PGS was found to be a useful tool in predicting patient experience of gagging and discomfort during FL-S, further reinforcing the subjective experience of this procedure. Use of the PGS may be helpful in identifying specific candidates who may struggle with subjective discomfort or gagging during FL-S for future studies considering interventions to manage and meaningfully decrease discomfort. Having such an instrument is important given the low number of individuals who struggle with discomfort during the exam.

Abstract Background How significant asymmetries in otolith organ function in the presence of symmetrical and asymmetrical semicircular canal function influence skull vibration-induced nystagmus testing (SVINT) has not been well described. Purpose The aim of the study is to examine the agreement between SVINT and caloric testing, ocular vestibular-evoked myogenic potentials (oVEMP), and cervical vestibular-evoked myogenic potentials (cVEMP) for detecting asymmetric vestibular function. Research Design This is a retrospective study of patients presenting with the chief complaint of vertigo, dizziness, or imbalance. Study Sample A total of 812 patients were studied with a median age at testing of 59 years (interquartile range 46‐70; range 18‐93) and included 475 (59%) women. Intervention Either the monothermal warm caloric test or alternate binaural bithermal caloric test, oVEMP, and cVEMP tests were administered to all patients. All patients underwent the SVINT prior to vestibular laboratory testing. Data Collection and Analysis Agreement between tests categorized as normal versus abnormal was summarized using percent concordance (PC). Sensitivity and specificity values were calculated for SVINT compared with other tests of vestibular function. Results There was higher agreement between ipsilateral and contralateral SVINT with the caloric test (PC = 80% and 81%, respectively) compared with oVEMP (PC = 63% and 64%, respectively) and cVEMP (PC = 76% and 78%, respectively). Ipsilateral and contralateral SVINT showed higher sensitivity for the caloric test (sensitivity = 47% and 36%, respectively) compared with oVEMP (sensitivity = 26% and 21%, respectively), or cVEMP (sensitivity = 33% vs. 27%, respectively). Specificity of SVINT was high (>80%) for all assessments of vestibular function. Conclusion The presence of SVIN is a useful indicator of the asymmetry of vestibular function between the two ears when making judgments about semicircular canal asymmetry but is less sensitive to asymmetries in otolith organ function.