Publications by authors named "Heather Wachtel"

51 Publications

Presentation, Management, and Outcomes of Urinary Bladder Paraganglioma: Results from a Multi-center Study.

J Clin Endocrinol Metab 2022 Jul 26. Epub 2022 Jul 26.

Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA.

Context And Objectives: Urinary bladder paraganglioma (UBPGL) is rare. We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL.

Methods: We conducted a multi-center study of consecutive patients with pathologically-confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality.

Results: 110 patients (56, 51% women) were diagnosed with UBPGL at a median age of 50 years (IQR, 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after initial diagnosis. Development of metachronous metastases was associated with younger age (Hazard ratio, HR 0.97, 95%CI 0.94-0.99), UBPGL size (HR of 1.69, 95%CI of 1.31-2.17), and a higher degree of catecholamine excess (HR of 5.48, 95%CI of 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR of 20.80, 95%CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality.

Conclusions: Only a minority of patients were diagnosed before biopsy/surgery, reflecting the need of better diagnostic strategies. All patients with UBPGL should be monitored life-long for development of recurrence and metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgac427DOI Listing
July 2022

Histopathology and Genetic Causes of Primary Aldosteronism in Young Adults.

J Clin Endocrinol Metab 2022 Jul 2. Epub 2022 Jul 2.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Context: Due to its rare incidence, molecular features of PA in young adults are largely unknown. Recently developed targeted mutational analysis identified aldosterone-driver somatic mutations in aldosterone-producing lesions, including aldosterone-producing adenomas (APAs), aldosterone-producing nodules (APNs), and aldosterone-producing micronodules, formerly known as aldosterone-producing cell clusters.

Objective: To investigate histologic and genetic characteristics of lateralized PA in young adults.

Methods: Formalin-fixed, paraffin-embedded (FFPE) adrenal tissue sections from 74 young patients with lateralized PA (<35 years-old) were used for this study. Immunohistochemistry (IHC) for aldosterone synthase (CYP11B2) was performed to define the histopathologic diagnosis. Somatic mutations in aldosterone-producing lesions were further determined by CYP11B2 IHC-guided DNA sequencing.

Results: Based on the CYP11B2 IHC results, histopathologic classification was made as follows: 48 APAs, 20 APNs, 2 multiple aldosterone-producing nodules (MAPNs), 1 double APN, 1 APA with MAPN, and 2 non-functioning adenomas (NFAs). Of 45 APAs with successful sequencing, 43 (96%) had somatic mutations, with KCNJ5 mutations being the most common genetic cause of young-onset APA (35/45, 78%). Of 18 APNs with successful sequencing, all of them harbored somatic mutations, with CACNA1D mutations being the most frequent genetic alteration in young-onset APN (8/18, 44%). Multiple CYP11B2-expressing lesions in patients with MAPN showed several aldosterone-driver mutations. No somatic mutations were identified in NFAs.

Conclusions: APA is the most common histologic feature of lateralized PA in young adults. Somatic KCNJ5 mutations are common in APAs, whereas CACNA1D mutations are often seen in APNs in this young PA population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgac408DOI Listing
July 2022

How Referring Providers Choose Specialists for Their Patients: a Systematic Review.

J Gen Intern Med 2022 Apr 19. Epub 2022 Apr 19.

Center for Surgery and Health Economics, University of Pennsylvania, Philadelphia, PA, USA.

Background: Physician referrals are a critical step in directing patients to high-quality specialists. Despite efforts to encourage referrals to high-volume hospitals, many patients receive treatment at low-volume centers with worse outcomes. We aimed to determine the most important factors considered by referring providers when selecting specialists for their patients through a systematic review of medical and surgical literature.

Methods: PubMed and Embase were searched from January 2000 to July 2021 using terms related to referrals, specialty, surgery, primary care, and decision-making. We included survey and interview studies reporting the factors considered by healthcare providers as they refer patients to specialists in the USA. Studies were screened by two independent reviewers. Quality was assessed using the CASP Checklist. A qualitative thematic analysis was performed to synthesize common decision factors across studies.

Results: We screened 1,972 abstracts and identified 7 studies for inclusion, reporting on 1,575 providers. Thematic analysis showed that referring providers consider factors related to the specialist's clinical expertise (skill, training, outcomes, and assessments), interactions between the patient and specialist (prior experience, rapport, location, scheduling, preference, and insurance), and interactions between the referring physician and specialist (personal relationships, communication, reputation, reciprocity, and practice or system affiliation). Notably, studies did not describe how providers assess clinical or technical skills.

Conclusions: Referring providers rely on subjective factors and assessments to evaluate quality when selecting a specialist. There may be a role for guidelines and objective measures of quality to inform the choice of specialist by referring providers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11606-022-07574-6DOI Listing
April 2022

Survival After Adrenalectomy for Metastatic Lung Cancer.

Ann Surg Oncol 2022 Apr 6;29(4):2571-2579. Epub 2022 Jan 6.

Department of Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA.

Background: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes.

Patients And Methods: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed.

Results: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002).

Discussion: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-11192-7DOI Listing
April 2022

New Operative Reporting Standards: Where We Stand Now and Opportunities for Innovation.

Ann Surg Oncol 2022 Mar 14;29(3):1797-1804. Epub 2021 Sep 14.

Department of Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Background: The American College of Surgeons Commission on Cancer's (CoC) new operative standards for breast cancer, melanoma, and colon cancer surgeries will require that surgeons provide synoptic documentation of essential oncologic elements within operative reports. Prior to designing and implementing an electronic tool to support synoptic reporting, we evaluated current documentation practices at our institution to understand baseline concordance with these standards.

Methods: Applicable procedures performed between 1 January 2018 and 31 December 2018 were included. Two independent reviewers evaluated sequential operative notes, up to a total of 100 notes, for documentation of required elements. Complete concordance (CC) was defined as explicit documentation of all required CoC elements. Mean percentage CC and surgeon-specific CC were calculated for each procedure. Interrater reliability was assessed via Cohen's kappa statistic.

Results: For sentinel lymph node biopsy, mean CC was 66% (n = 100), with surgeon-specific CC ranging from 6 to 100%, and for axillary dissection, mean CC was 12% (n = 89) and surgeon-specific CC ranged from 0 to 47%. The single surgeon performing melanoma wide local excision had a mean CC of 98% (n = 100). For colon resections, mean CC was 69% (n = 96) and surgeon-specific CC ranged from 39 to 94%. Kappa scores were 0.77, 0.78, -0.15, and 0.78, respectively.

Conclusions: We identified heterogeneity in current documentation practices. In our cohort, rates of baseline concordance varied across surgeons and procedures. Currently, documentation elements are interspersed within the operative report, posing challenges to chart abstraction with resulting imperfect interrater reliability. This presents an exciting opportunity to innovate and improve compliance by introducing an electronic synoptic documentation tool.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10766-9DOI Listing
March 2022

Data to inform counseling on parathyroidectomy for secondary hyperparathyroidism of renal origin.

Surgery 2022 01 6;171(1):63-68. Epub 2021 Sep 6.

Department of Surgery, Division of Endocrine and Oncologic Surgery, University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: The risk of postoperative hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism of renal origin may alter the course of treatment, including the hospital length of stay and readmission rates. We sought to identify additional patient or hospital factors that might contribute to hungry bone syndrome after parathyroidectomy in patients with secondary hyperparathyroidism of renal origin.

Methods: Patients who underwent a parathyroidectomy for secondary hyperparathyroidism of renal origin were identified in a geographically diverse, 10-state, discharge data set. Covariates included demographic data, payer status, 31 comorbidities, and hospital characteristics. The primary outcome variable of interest was hospital length of stay. Secondary outcomes were complications and 30-day readmission.

Results: Of 796 patients studied, 164 patients (20.6%) were diagnosed with hungry bone syndrome. There were no differences in the rates of hungry bone syndrome by race or number of comorbidities. The average age of hungry bone syndrome patients (45.7 years ± 13.9) was younger than that of non-hungry bone syndrome patients (50.7 ± 14.8; P < .001). Hungry bone syndrome was more common among obese patients than nonobese patients (25.0% vs 15.8%; P < .001). Parathyroid autotransplant was performed at similar rates in hungry bone syndrome and non-hungry bone syndrome patients (23.8% vs 23.1%; P = .821). Median length of stay was significantly longer for hungry bone syndrome patients (6 days, interquartile range: [4, 8] versus 3 days, interquartile range: [2-6]; P < .001). Similar 30-day readmission rates were observed (hungry bone syndrome: 41 (25%) versus non-hungry bone syndrome: 147 (23%); P = .640).

Conclusion: Hungry bone syndrome occurs in 1 of 5 patients after parathyroidectomy for secondary hyperparathyroidism of renal origin. Patients should be informed of the possibility of a relatively long (6 days) length of stay after surgery as well as the moderate possibility (>20%) of another hospitalization within the 30-day postdischarge period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2021.08.009DOI Listing
January 2022

Endocrine Surgical Procedures During COVID-19: Patient Prioritization and Time to Surgery.

J Surg Res 2021 12 24;268:459-464. Epub 2021 Jul 24.

Div. of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: We tracked endocrine surgery patients with treatment delays due to COVID-19 to investigate the relationship between physician assigned priority scoring (PAPS), the Medically Necessary, Time Sensitive (MeNTS) scoring system and delay to surgery.

Material & Methods: Patients scheduled for endocrine surgery or clinically evaluated during COVID-19-related elective surgery hold at our institution (2/26/20-5/1/20) were prospectively enrolled. PAPS was assigned based on categories of high, moderate, or low risk, consistent with the American College of Surgeons' priority system. MeNTS scores were calculated. The primary outcome was delay to surgery. Descriptive statistics were performed, and receiver operator characteristic (ROC) curves and area under the curve (AUC) values were calculated for PAPS and MeNTS.

Results: Of 146 patients included, 68% (n = 100) were female; the median age was 60 years (IQR:43,67). Mean delay to surgery was significantly shorter (P = 0.01) in patients with high PAPS (35 d), compared with moderate (61 d) and low (79 d) PAPS groups. MeNTS scores were provided for 105 patients and were analyzed by diagnosis. Patients with benign thyroid disease (n = 17) had a significantly higher MeNTS score than patients with thyroid disease which was malignant/suspicious for malignancy (n = 44) patients (51.5 versus 47.6, P = 0.034). Higher PAPS correlated well with a delay to surgery of <30 d (AUC: 0.72). MeNTS score did not correlate well with delay to surgery <30 d (AUC: 0.52).

Conclusion: PAPS better predicted delay to surgery than MeNTS scores. PAPS may incorporate more complex components of clinical decision-making which are not captured in the MeNTS score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302853PMC
December 2021

Correlation Between Plasma Catecholamines, Weight, and Diabetes in Pheochromocytoma and Paraganglioma.

J Clin Endocrinol Metab 2021 09;106(10):e4028-e4038

Hospital of the University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA.

Context: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes.

Objective: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control.

Design: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1].

Setting: Tertiary academic hospital.

Patients: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female.

Main Outcome Measures: The primary and secondary outcomes were weight and HbA1c, respectively.

Results: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c.

Conclusion: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475214PMC
September 2021

Therapeutic Outcomes with Surgical and Medical Management of Primary Aldosteronism.

Curr Cardiol Rep 2021 06 3;23(7):89. Epub 2021 Jun 3.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, 4 Silverstein Pavilion, Philadelphia, PA, 19104, USA.

Purpose Of Review: Primary aldosteronism (PA) is the most common cause of secondary hypertension and is significantly under-diagnosed. Delays in diagnosis and treatment can lead to cardiovascular morbidity and mortality. The goal of this study is to review the management of PA, with a focus on medical and surgical treatment outcomes.

Recent Findings: PA causes cardiovascular dysfunction in excess of degree of hypertension. Adrenalectomy demonstrates a therapeutic advantage over mineralocorticoid antagonist (MRA) therapy, after controlling for degree of hypertension and subtype of PA. Higher rates of atrial fibrillation, heart failure, stroke, and incidence of chronic kidney disease are observed in subjects treated with MRAs than in subjects treated with adrenalectomy. The therapeutic benefit of surgery may reflect definitive resolution of excess aldosterone. Complete mineralocorticoid blockade may achieve similar benefit to adrenalectomy. Adrenalectomy is the most effective treatment for unilateral PA. Biomarkers for MRA therapy might inform optimal medical therapy of bilateral adrenal hyperplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11886-021-01516-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341292PMC
June 2021

"Double-Down" Adrenal Vein Sampling Results in Patients with Apparent Bilateral Aldosterone Suppression: Utility of Repeat Sampling including Super-Selective Sampling.

J Vasc Interv Radiol 2021 05 27;32(5):656-665. Epub 2021 Mar 27.

Department of Radiology, Division of Interventional Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: To report outcomes of patients undergoing adrenal vein sampling (AVS) for primary aldosteronism with results indicating apparent bilateral adrenal suppression (ABAS), in which the adrenal aldosterone-to-cortisol ratios are decreased bilaterally ("double-down") compared to the non-adrenal sample, and evaluate repeat AVS results.

Materials And Methods: Between 2003 and 2020, 762 patients underwent AVS. Twenty patients (2.6%; male, 12; female, 8; age 50.3 ± 9.7 years) with ABAS on initial AVS were identified. Ten underwent repeat AVS. Super-selective AVS (SS-AVS) was employed in 6 of 10 repeat AVS (60%). Outcomes after AVS were analyzed. A lateralization index (LI) >4 was considered an indication for adrenalectomy.

Results: Repeat AVS was diagnostic in 70% of patients (n = 7), with 6 of 7 lateralizing with LI >4 (median LI = 32.3; range 4.6-54.8) and 1 of 7 nearly lateralizing (LI = 3.5). All 7 patients underwent adrenalectomy. ABAS was redemonstrated in 3 patients (30%): 2 with unilateral adenomas on cross-sectional imaging underwent adrenalectomy despite ABAS results and 1 was lost to follow-up. Four of 6 patients (66%) who underwent SS-AVS were diagnosed with unilateral disease (median LI = 43.3; range 23.9-54.8), with one patient's diagnosis reliant upon a single super-selective sample. In total, 9 patients underwent adrenalectomy after repeat AVS, all of whom had improved blood pressure control postoperatively. Ten patients did not undergo repeat AVS: 6 were lost to follow-up, 3 underwent medical management, and 1 underwent adrenalectomy.

Conclusions: AVS should be repeated when "double-down" ABAS results are encountered. Super-selective sampling may provide worthwhile diagnostic data when employed during repeat AVS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2020.12.029DOI Listing
May 2021

Genetics of pheochromocytoma and paraganglioma.

Curr Opin Endocrinol Diabetes Obes 2021 06;28(3):283-290

University of Colorado School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and the Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Aurora, Colorado, USA.

Purpose Of Review: This review summarizes our current understanding of germline and somatic genetics and genomics of pheochromocytomas and paragangliomas (PCC/PGL), describes existing knowledge gaps, and discusses future research directions.

Recent Findings: Germline pathogenic variants (PVs) are found in up to 40% of those with PCC/PGL. Tumors with germline PVs are broadly categorized as Cluster 1 (pseudohypoxia), including those with SDH, VHL, FH, and EPAS1 PVs, or Cluster 2 (kinase signaling) including those with NF1, RET, TMEM127, and MAX PVs. Somatic driver mutations exist in some of the same genes (RET, VHL, NF1, EPAS1) as well as in additional genes including HRAS, CSDE1 and genes involved in cell immortalization (ATRX and TERT). Other somatic driver events include recurrent fusion genes involving MAML3.

Summary: PCC/PGL have the highest association with germline PVs of all human solid tumors. Expanding our understanding of the molecular pathogenesis of PCC/PGL is essential to advancements in diagnosis and surveillance and the development of novel therapies for these unique tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MED.0000000000000634DOI Listing
June 2021

Double adenoma as a cause of primary hyperparathyroidism: Asymmetric hyperplasia or a distinct pathologic entity?

Am J Surg 2021 09 19;222(3):483-489. Epub 2021 Jan 19.

Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA; Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA. Electronic address:

Background: Primary hyperparathyroidism (PHPT) caused by double adenoma may carry a higher risk of failure to cure. We compared outcomes in single adenoma (SA), double adenoma (DA) and four-gland hyperplasia (HP).

Methods: Patients undergoing initial parathyroidectomy for PHPT were categorized by diagnosis. The primary outcome was persistent/recurrent disease postoperatively.

Results: Of 3408 patients, 81.3% had SA, 9.5% had DA, and 9.3% had HP. Rates of persistence/recurrence were 2.9%, 5.3%, and 4.5% in SA, DA, and HP, respectively (p = 0.281). Patients with persistence/recurrence had higher preoperative calcium (11.0 vs 10.7 mg/dl, p = 0.028) and PTH (96 vs 77 pg/ml, p = 0.015), and lower rates of IOPTH normalization (77% vs 96%, p < 0.001). On multivariable analysis, DA was associated with increased risk of persistent/recurrent disease (OR 3.0, p = 0.017).

Conclusions: Most patients with DA are cured with removal of two glands, but approximately 5% experience disease persistence/recurrence. Low-normal final IOPTH was associated with lower risk of persistent/recurrent disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjsurg.2021.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286973PMC
September 2021

A Framework for the Future.

Authors:
Heather Wachtel

Ann Surg 2020 12;272(6):e287

Hospital of the University of Pennsylvania, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003972DOI Listing
December 2020

Racial Disparities in Primary Hyperparathyroidism.

World J Surg 2021 Jan 25;45(1):180-187. Epub 2020 Sep 25.

Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street 4 Silverstein Pavilion, Philadelphia, PA, 19104, USA.

Background: Racial disparities in surgery are increasingly recognized. We evaluated the impact of race on presentation, preoperative evaluation, and surgical outcomes for patients undergoing parathyroidectomy for primary hyperparathyroidism (PHPT).

Methods: We performed a retrospective cohort study of patients undergoing parathyroidectomy for PHPT at a single center (1997-2015). Patients were classified by self-identified race, as African-American or White. The primary outcome was disease severity at referral. The secondary outcome was completeness of preoperative evaluation. Operative success and surgical cure were evaluated.

Results: A total of 2392 patients were included. The majority of patients (87.6%) were White. African-American patients had higher rates of comorbid disease as well as higher preoperative calcium (10.9 vs.10.8 mg/dl, p < 0.001) and PTH levels (122 vs. 97 pg/ml, p < 0.001). White patients were more likely to have history of bone loss documented by DXA and nephrolithiasis. African-American patients had lower rates of complete preoperative evaluation including DXA scan. Operatively, African-American patients had larger glands by size (1.7 vs. 1.5 cm, p < 0.001) and mass (573 vs. 364 mg, p < 0.001). We observed similar operative success (98.9 vs. 98.0%, p = 0.355) and cure rates (98.3 vs. 97.0%, p = 0.756).

Conclusions: At the time of surgical referral, African-American patients with PHPT have more biochemically severe disease and higher rates of incomplete evaluation. Operative success and cure rates are comparable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05791-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906108PMC
January 2021

Predicting Metastatic Potential in Pheochromocytoma and Paraganglioma: A Comparison of PASS and GAPP Scoring Systems.

J Clin Endocrinol Metab 2020 12;105(12)

University of Colorado School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and the Division of Biomedical Informatics and Personalized Medicine, Aurora, Colorado.

Purpose: The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.

Methods: The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).

Results: From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score.

Conclusion: Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553245PMC
December 2020

Tumor detection rates in screening of individuals with SDHx-related hereditary paraganglioma-pheochromocytoma syndrome.

Genet Med 2020 12 3;22(12):2101-2107. Epub 2020 Aug 3.

Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Aurora, CO, USA.

Purpose: Minimal data exist regarding the efficacy of screening protocols for individuals with SDHx germline pathogenic variants with hereditary paraganglioma-pheochromocytoma syndrome. This study aimed to evaluate the SDHx-related tumor detection rate in individuals undergoing clinical screening protocols.

Methods: A multicenter retrospective longitudinal observational study was conducted. Individuals with germline SDHx pathogenic variants underwent clinical whole-body imaging and biochemical testing.

Results: Two hundred sixty-three individuals with SDHx germline pathogenic variants completed 491 imaging screens. Individuals with SDHB germline pathogenic variants were most common (n = 188/263, 72%), followed by SDHD (n = 35/263, 13%) and SDHC (n = 28/263, 11%). SDHx-related tumors were found in 17% (n = 45/263) of the cohort. Most SDHx-related tumors were identified on baseline imaging screen (n = 39/46, 85%). Individuals with SDHD pathogenic variants had the highest tumor detection rate (n = 14/35, 40%). Of imaging screens identifying SDHx-related paraganglioma/pheochromocytoma, 29% (n = 12/41) had negative biochemical testing. Secondary actionable findings were identified in 15% (n = 75/491) of imaging screens.

Conclusion: Current SDHx screening protocols are effective at identifying SDHx-related tumors. Tumor detection rates vary by SDHx gene and screening has the potential to uncover actionable secondary findings. Imaging is an essential part of the screening process as biochemical testing alone does not detect all disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-0921-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710583PMC
December 2020

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

Ann Surg 2021 12;274(6):1073-1080

Massachusetts General Hospital, Department of Surgery, Boston MA.

Objective: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy.

Background: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined.

Methods: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards.

Results: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS.

Conclusions: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003876DOI Listing
December 2021

Single Gland, Ectopic Location: Adenomas are Common Causes of Primary Hyperparathyroidism in Children and Adolescents.

World J Surg 2020 05;44(5):1518-1525

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Primary hyperparathyroidism (PHPT) in children and adolescents is uncommon. Data-driven guidelines for management in pediatric patients are limited.

Methods: We performed a retrospective cohort analysis of all patients (1997-2017) with PHPT ≤ 21 years of age who underwent parathyroidectomy at three institutions. Clinical and demographic variables were analyzed. Primary operative outcome was cure (normocalcemia > 6 months after surgery); secondary outcome was operative success (intraoperative parathyroid hormone decrease of ≥ 50%).

Results: We identified 86 patients with a median age of 17 years (IQR: 14, 19); 64% (n = 55) were female. The mean preoperative serum calcium was 11.7 mg/dL, median parathyroid hormone (PTH) was 110 pg/mL, and median urine calcium was 4.1 mg/kg/24 h. Preoperatively, sestamibi scan localized in 41/71 patients (58%); neck ultrasound localized in 19/44 (43%). The most common pathology at surgery was a single ectopic parathyroid adenoma in 71% (n = 61). A high incidence of ectopic adenomas (25%, n = 22) was observed, most commonly intrathymic (n = 13), followed by tracheoesophageal groove (n = 5), carotid sheath (n = 2), and intrathyroidal (n = 2). Of 56 patients with retrievable data > 6 months postoperatively, cure was achieved in 55 of 56 patients (98%). One patient who presented to us with parathyromatosis require subsequent reoperation.

Conclusion: In this multi-institutional series of PHPT in children and adolescents, the majority were sporadic PHPT and were due to a single adenoma. We observed a high incidence of ectopic parathyroid adenomas, most commonly intrathymic. Given the high risk for ectopic adenoma in pediatric patients, parathyroid surgery in children and adolescents should be performed by experienced surgeons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-019-05362-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124981PMC
May 2020

Clinical presentation and surgical outcomes in primary aldosteronism differ by race.

J Surg Oncol 2020 Mar 19;121(3):456-464. Epub 2019 Dec 19.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension; early diagnosis and intervention correlate with outcomes. We hypothesized that race may influence clinical presentation and outcomes.

Methods: We conducted a retrospective analysis of patients with PA (1997-2017) who underwent adrenal vein sampling (AVS). Patients were classified by self-reported race as black or non-black. Improvement was defined as postoperative decrease in mean arterial pressure (MAP), antihypertensive medications (AHM), or both.

Results: Among patients undergoing AVS (n = 443), 287 underwent adrenalectomy. Black patients (28.2%) had higher body mass index (33.9 vs 31.8 kg/m ; P = .01), longer median duration of hypertension (12 vs 10 years; P = .003), higher modified Elixhauser comorbidity index (2 vs 1; P = .004), and lower median income ($47 134 vs $78 280; P < .001). Black patients had similar aldosterone:renin ratios (150 vs 135.6 [ng/dL]/[ng·mL· hr ]; P = .23) compared to non-blacks. At long-term follow-up, black patients had a similar requirement for AHM (1 vs 0; P = .13) but higher MAP (100.6 vs 95.3 mm Hg; P = .004).

Conclusion: Black patients present with longer duration of hypertension and more comorbidities. They are equally likely to lateralize on AVS, suggesting similar disease phenotype. However, black patients demonstrate less improvement with adrenalectomy; this may reflect a delay in diagnosis or concomitant essential hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.25806DOI Listing
March 2020

Challenges in obesity and primary aldosteronism: Diagnosis and treatment.

Surgery 2020 01 18;167(1):204-210. Epub 2019 Sep 18.

Department of Surgery, Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. Electronic address:

Background: Obese patients may have unrecognized primary aldosteronism due to high rates of concomitant hypertension. We hypothesized that obesity impacts the diagnosis and management of patients with primary aldosteronism.

Methods: We conducted a retrospective analysis of all primary aldosteronism patients (n = 418) who underwent adrenal vein sampling (1997-2017). Patients were classified by body mass index as obese (body mass index ≥35) or nonobese (body mass index <35) and diagnostic evaluation was compared between groups. Within the operative cohort (n = 285), primary outcomes were changes in both blood pressure and antihypertensive medications after adrenalectomy. Secondary outcome was clinical resolution by Primary Aldosteronism Surgery Outcomes criteria.

Results: Thirty-five percent of patients were obese. Obese patients were more likely to be male (67.8% vs 56.1%, P = .025), somewhat younger (51.5 vs 54.4 years old, P < .012), and require more preoperative antihypertensive medications (6.7 vs 5.7, P = .04) than nonobese patients. Obese patients had lesser rates of radiologic evidence of adrenal tumors (68.4 vs 77.9%, P = .038) despite similar rates of lateralization on adrenal vein sampling. In the operative subset, obese patients had somewhat smaller tumors on final pathology (1.1 vs 1.5 cm, P = .014) but similar rates of complete and partial clinical resolution (P = 1.000).

Conclusion: Obese primary aldosteronism patients have lesser rates of localization by imaging, likely due to smaller tumor size, however, experience similar benefit from adrenalectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2019.03.036DOI Listing
January 2020

Intraoperative Parathyroid Hormone Monitoring in Parathyroidectomy for Tertiary Hyperparathyroidism.

J Surg Res 2019 12 4;244:77-83. Epub 2019 Jul 4.

Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Tertiary hyperparathyroidism (THPT) is characterized by hypercalcemia and hyperparathyroidism after renal allograft. Limited data exist regarding the use of intraoperative parathyroid hormone (IOPTH) for THPT. We examined our series of parathyroidectomies performed for THPT to determine clinical outcomes with respect to IOPTH.

Materials And Methods: Patients who underwent parathyroidectomy for THPT (1999-2017) were identified for inclusion. Retrospective chart review was performed. Cure was defined as eucalcemia ≥6 mo after surgery. Statistical analysis was performed.

Results: Of 41 patients included in the study, 41% (n = 17) were female. The median duration of dialysis before renal allograft was 34 mo (interquartile interval [IQI]:6-60). Preoperatively, the median calcium level was 10.4 mg/dL (IQI:10.0-11.2), median parathyroid hormone was 172 pg/mL (IQI:104-293), and renal function was minimally abnormal with median glomerular filtration rate 58 mL/min/1.73 m2 (IQI:49-71). At surgery, the median final IOPTH was 40 pg/mL (IQI:29-73), and median decrease in IOPTH was 78% (IQI:72-87), with 88% (n = 36) of patients demonstrating >50% decrease. Median calcium level ≥6 mo after surgery was 9.4 mg/dL (IQI:8.8-9.7), and only one patient had recurrent hypercalcemia. Failure to achieve >50% decrease in IOPTH was not significantly associated with recurrent hypercalcemia (P = 1.000). With a median follow-up time of 41 mo (IQI:25-70), only three patients had graft failure. The positive predictive value of IOPTH for cure was 89% (95% confidence interval: 0.752-0.971), with 0% negative predictive value and 87% accuracy (95% confidence interval: 0.726-0.957).

Conclusions: Subtotal parathyroidectomy is a successful operation with durable cure of THPT. IOPTH fails to predict long-term cure in THPT despite minimally abnormal renal function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2019.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179078PMC
December 2019

A comparison of patient satisfaction when office-based procedures are performed by general surgery residents versus an attending surgeon.

Surgery 2019 07 2;166(1):116-122. Epub 2019 Apr 2.

Department of Surgery, Massachusetts General Hospital, Boston, MA. Electronic address:

Background: Patient satisfaction is an increasingly important quality metric nationwide. The impact that surgical trainees have on patient-reported satisfaction when they perform operations independently, however, has not been studied.

Methods: We conducted a prospective study at a single academic institution from October 2016 to June 2017. An office-based, postprocedure survey was developed by adapting questions from the validated Consumer Assessment of Healthcare Providers and Systems Surgical Care Survey. Top-box scoring was used to determine satisfaction for categorical questions and a comparison of the means was used for overall quality ratings (scale 0-10). Patients indicated whether their operation was completed by an attending surgeon or a postgraduate year 3 general surgery resident. The primary outcome measured was patient satisfaction with overall quality of care. Individual questions were grouped by phase of care and composite scores were measured as a secondary outcome.

Results: The survey response rate was 87.4% (n = 195). There were no differences in patient demographics or the types of procedures performed by residents or an attending surgeon. Excision of a soft tissue mass (ie, lipoma) accounted for 89.2% of all procedures performed (n = 174). There were no differences between preprocedure (resident = 92.5% vs attending = 94.2%) or postprocedure (resident = 95.3% vs attending = 97.7%) composite scores. There was, however, a significant difference in periprocedure satisfaction (resident = 78.7% vs attending = 90.7%, P = .02). There was no difference in overall ratings of quality of care given by patients who had their procedure performed by residents (9.8 ± 0.5) versus an attending surgeon (9.9 ± 0.3, P = .15). Finally, on adjusted analysis, resident care did not independently impact the likelihood of a "best possible care" rating for overall quality of care (odds ratio 0.84 ± 0.27, confidence interval 0.45-1.57, P = .58).

Conclusion: Patient satisfaction was very high when residents independently performed minor surgery operations in an office-based setting. Of note, there was no difference in satisfaction with overall quality of care compared with an attending surgeon. This study demonstrates that high resident operative autonomy and patient satisfaction are not mutually exclusive goals when postgraduate year 3 residents perform office-based outpatient procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2019.02.009DOI Listing
July 2019

Association of Outcome Definitions With Success Following Adrenalectomy for Primary Aldosteronism.

JAMA Surg 2019 04 17;154(4):e185843. Epub 2019 Apr 17.

Center of Surgery and Health Economics, Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2018.5843DOI Listing
April 2019

Primary aldosteronism with nonlocalizing imaging.

Surgery 2019 01 7;165(1):211-218. Epub 2018 Nov 7.

Department of Surgery, Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia.

Background: Unilateral primary aldosteronism is surgically curable. The goal of this study was to examine outcomes based on preoperative imaging findings.

Methods: We performed a retrospective analysis of patients with primary aldosteronism who underwent adrenal vein sampling. Patients were classified by imaging as localized (unilateral adrenal mass) or nonlocalized (no mass/bilateral masses). Outcomes were assessed as complete, partial, or absent clinical success.

Results: Of 446 patients, 74.9% were localized. There were no significant demographic or biochemical differences between groups; however the imaged tumor size was larger (median 1.3 vs 1.2 cm, P = .038), and rates of lateralizing adrenal vein sampling were higher (79.0% vs 62.2%, P < .001) in the localized group. Of 289 patients who underwent adrenalectomy, adenoma was the most common finding in both groups (79.7% vs 80.3% respectively, P = .447), but median tumor size was larger in localized patients (1.5 vs 1.0 cm, P < .001). Equivalent rates of partial (94.6% vs 91.7%, P = .456) and complete (8.7% vs 9.8%, P = .801) clinical success were observed. At long-term follow-up, nonlocalized patients experienced partial reversal of clinical improvement.

Conclusion: Primary aldosteronism patients with nonlocalizing imaging but lateralizing adrenal vein sampling benefit from adrenalectomy. Regardless of imaging findings, adrenal vein sampling is indicated to determine whether patients may be surgically curable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2018.04.077DOI Listing
January 2019

Circulating BRAF Levels Correlate with Treatment in Patients with Thyroid Carcinoma.

Thyroid 2018 03 27;28(3):328-339. Epub 2018 Feb 27.

1 Department of Surgery, Massachusetts General Hospital , Boston, Massachusetts.

Background: BRAF is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAF assay was reported. The objective of this study was to assess the correlation of BRAF circulating tumor RNA levels with surgical and medical treatment.

Methods: Circulating BRAF levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAF mutation undergoing BRAF-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAF analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAF values were assessed and compared to clinical characteristics and response to therapy.

Results: In a murine model of anaplastic thyroid carcinoma with BRAF mutation, blood BRAF RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAF-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAF levels declined postoperatively (median 370.0-178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAF declined following therapy and corresponded with radiographic evidence of partial response or stable disease.

Conclusions: This study shows the correlation of blood BRAF levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAF-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2017.0322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865613PMC
March 2018

PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma.

Endocr Pathol 2018 Mar;29(1):59-67

Department of Pathology, Massachusetts General Hospital, Warren 219, 55 Fruit Street, Boston, MA, 02114, USA.

Poorly differentiated thyroid carcinoma (PDTC) is an aggressive form of thyroid cancer that currently has limited effective treatment options. Immune checkpoint inhibitors (ICIs) have shown to be an effective treatment for a variety of carcinomas. In this study, we explore whether immune checkpoint pathways, such as programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1), are activated in a cohort of patients with PDTC to determine whether ICIs may be an effective therapy for these patients. PDTC from 28 patients were stained for IDO1, PD-L1, and CD8 using immunohistochemistry. Staining was scored using an H-score, and PD-L1 and IDO1 expression was correlated with clinicopathologic characteristics. Positivity for PD-L1 and IDO1 was set at an H-score cutoff of five. Twenty-five percent (n = 7/28) of the PDTC were positive for PD-L1 expression. Twenty-nine percent (n = 2/7) of the PD-L1 positive PDTCs also co-expressed IDO1. The expression of PD-L1 in PDTC was significantly associated with tumor size and multifocality, with a non-significant trend towards associations with older age, extrathyroidal extension, presence of metastasis, higher stage, increased number of CD8+ T cells, and decreased disease-free and overall survival. PD-L1 expression occurs in a subset of PDTC, and is associated with a subset of clinical features of aggressive thyroid disease. Given the limited effective treatments for this patient population, consideration for ICIs as monotherapy or in combination with an IDO1 inhibitor should be explored as a novel treatment modality for patients with PDTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12022-018-9514-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500591PMC
March 2018

Evaluating the projected surgical impact of reclassifying noninvasive encapsulated follicular variant of papillary thyroid cancer as noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Surgery 2018 01 13;163(1):60-65. Epub 2017 Nov 13.

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Institute for Technology Assessment, Boston, MA. Electronic address:

Background: The reclassification of noninvasive encapsulated follicular variant of papillary thyroid cancer to noninvasive follicular thyroid neoplasm with papillary-like nuclear features will reduce nonefficacious and potentially harmful care. Reclassification is estimated in 18.6% of patients with papillary thyroid carcinoma; we aimed to quantify the implications of this change.

Methods: Pathology reports from April 2006 to April 2016 were reviewed to isolate cases that would have been designated as neoplasm with papillary-like nuclear features. Of the 1,335 cases of papillary thyroid carcinomas, 194 cases (14.5%) met criteria. Cases in which neoplasm with papillary-like nuclear features was found in combination with other thyroid malignancies (n = 25) and cases of prior thyroid lobectomy (n = 5) were excluded. Demographic, pathologic, treatment, and follow-up data were assessed for the remaining 164 potential neoplasm with papillary-like nuclear features cases. Logistic regression analysis was performed to evaluate association between fine-needle aspiration result and index procedure.

Results: Of the 164 patients with tumors who met neoplasm with papillary-like nuclear features criteria, fine-needle aspiration results were nondiagnostic (2%), benign (18%), atypia/follicular lesion of undetermined significance (26%), follicular neoplasm or suspicious for follicular neoplasm (20%), suspicious for malignancy (19%), malignant (6%), and not obtained (9%). Eighty-five (52%) patients underwent total thyroidectomy. A "suspicious for malignancy" fine-needle aspiration result was associated with undergoing total thyroidectomy versus thyroid lobectomy (P = .006). Thyroid lobectomy was the index procedure for 79 patients (48%); of these patients, 54% (n = 43, 3.2% of all patients with papillary thyroid carcinomas) underwent subsequent total thyroidectomy, and 24% received postoperative radioactive iodine treatment. There were no recurrences among the 125 patients with >3 months of follow-up.

Conclusion: The reclassification of noninvasive encapsulated follicular variant of papillary thyroid cancer as neoplasm with papillary-like nuclear features will decrease nonefficacious treatment and reduce costs. However, the impact of this change with regard to extent of surgery was limited to 3.2% of patients with papillary thyroid carcinomas compared with the projected potential impact on 18.6%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2017.04.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736433PMC
January 2018

Eleven-Year Retrospective Report of Super-Selective Venous Sampling for the Evaluation of Recurrent or Persistent Hyperparathyroidism in 32 Patients.

Cardiovasc Intervent Radiol 2018 Jan 2;41(1):63-72. Epub 2017 Aug 2.

Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, 1 Silverstein, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Purpose: Parathyroid venous sampling (PAVS) is usually reserved for patients with persistent or recurrent hyperparathyroidism after parathyroidectomy with inconclusive noninvasive imaging studies. A retrospective study was performed to evaluate the diagnostic efficacy of super-selective PAVS (SSVS) in patients needing revision neck surgery with inconclusive imaging.

Materials And Methods: Patients undergoing PAVS between 2005 and 2016 due to persistent or recurrent hyperparathyroidism following surgery were reviewed. PAVS was performed in all patients using super-selective technique. Single-value measurements within central neck veins performed as part of super-selective PAVS were used to simulate selective venous sampling (SVS) and allow for comparison to data, which might be obtained in a non-super-selective approach.

Results: 32 patients (mean age 51 ± 15 years; 8 men and 24 women) met inclusion and exclusion criteria. The sensitivity and positive predictive value (PPV) of SSVS for localizing the source of elevated PTH to a limited area in the neck or chest was 96 and 84%, respectively. Simulated SVS, on the other hand, had a sensitivity of 28% and a PPV of 89% based on the predefined gold standard. SSVS had a significantly higher sensitivity compared to simulated SVS (p < 0.001).

Conclusion: SSVS is highly effective in localizing the source of hyperparathyroidism in patients undergoing revision surgery for hyperparathyroidism in whom noninvasive imaging studies are inconclusive. SSVS data had also markedly higher sensitivity for localizing disease in these patients compared to simulated SVS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00270-017-1757-3DOI Listing
January 2018

Racial Disparities in Initial Presentation of Benign Thyroid Disease for Resection.

Ann Surg Oncol 2016 08 29;23(8):2571-6. Epub 2016 Mar 29.

Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.

Background: Racial disparities exist in thyroidectomy outcomes. One contributing factor may be the disease state upon presentation to a surgeon. Minorities with thyroid cancer present at a later disease stage and with larger tumors. This relationship has not been examined for benign thyroid disease. We sought to examine the association between race, referral patterns, and disease severity for benign thyroid conditions.

Methods: We analyzed all patients receiving a thyroidectomy for benign disease in our institutional endocrine surgery registry. Patient demographics, disease history, disease severity, and postoperative outcomes were investigated. Univariate analysis compared black and white patients. Multivariable linear regression examined the relationship between race and time to surgical referral.

Results: Of the 1189 patients studied, the majority (86.0 %) were white. Black and white patients differed in median income and reason for referral. When compared with white patients, black patients more commonly presented with compressive symptoms (black: 45.0 % vs. white: 21.2 %, p < .01) and dysphagia (19.0 % vs. 10.1 %, p < .01), and after a longer disease duration [black: median 0 years (interquartile ratio, IQR, 0-5) vs. white: 0 years (IQR, 0-2)]. Blacks also had larger glands than white [median 71 grams (IQR, 33.5-155.3) vs. 24.3 grams (IQR, 15.0-50.2)]. With the exception of reintubation rate, there were no differences in postoperative outcomes.

Conclusions: Black patients with benign thyroid conditions have a longer time to surgical referral and present for surgical evaluation with more severe disease than white patients. Identification of these disparities is the first step in eliminating differences in patient care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-016-5199-yDOI Listing
August 2016
-->