Room for Improvement: The Impact of Guideline-Recommended Extended Thromboprophylaxis in Patients Undergoing Abdominal Surgery for Colorectal and Anal Cancer at a Tertiary Referral Center.

BACKGROUND: Venous thromboembolism occurs in approximately 2% of patients undergoing abdominal and pelvic surgery for cancers of the colon, rectum, and anus and is considered preventable. The American Society of Colon and Rectal Surgeons recommends extended prophylaxis in high-risk patients, but there is low adherence to the guidelines. OBJECTIVE: This study aims to analyze the impact of venous thromboembolism risk-guided prophylaxis in patients undergoing elective abdominal and pelvic surgeries for colorectal and anal cancers from 2016 to 2021. DESIGN: This was a retrospective analysis. SETTING: The study was conducted at a multisite tertiary referral academic health care system. PATIENTS: Patients who underwent elective abdominal or pelvic surgery for colon, rectal, or anal cancer. MAIN OUTCOME MEASURES: Receipt of Caprini-guided venous thromboembolism prophylaxis, 90-day postoperative rate of deep vein thrombosis, pulmonary embolism, venous thromboembolism, and bleeding events. RESULTS: A total of 3504 patients underwent elective operations, of whom 2224 (63%) received appropriate thromboprophylaxis in the inpatient setting. In the postdischarged cohort of 2769 patients, only 2% received appropriate thromboprophylaxis and no thromboembolic events were observed. In the group receiving inappropriate thromboprophylaxis, at 90 days postdischarge, the deep vein thrombosis, pulmonary embolism, and venous thromboembolism rates were 0.60%, 0.40%, and 0.88%, respectively. Postoperative bleeding was not different between the 2 groups. LIMITATIONS: Limitations to our study include its retrospective nature, use of aggregated electronic medical records, and single health care system experience. CONCLUSION: Most patients in our health care system undergoing abdominal or pelvic surgery for cancers of the colon, rectum, and anus were discharged without appropriate Caprini-guided venous thromboembolism prophylaxis. Risk-guided prophylaxis was associated with decreased rates of inhospital and postdischarge venous thromboembolism without increased bleeding complications. See Video Abstract . MARGEN DE MEJORA EL IMPACTO DE LA TROMBOPROFILAXIS RECOMENDADA POR LAS DIRECTRICES EN PACIENTES SOMETIDOS A CIRUGA ABDOMINAL POR CNCER COLORRECTAL Y ANAL EN UN CENTRO DE REFERENCIA TERCIARIO: ANTECEDENTES:El tromboembolismo venoso ocurre en aproximadamente el 2% de los pacientes sometidos a cirugía abdominal y pélvica por cánceres de colon, recto y ano, y se considera prevenible. La Sociedad Estadounidense de Cirujanos de Colon y Recto recomienda una profilaxis prolongada en pacientes de alto riesgo, pero el cumplimiento de las directrices es bajo.OBJETIVO:Este estudio tiene como objetivo analizar el impacto de la profilaxis guiada por el riesgo de tromboembolismo venoso (TEV) en pacientes sometidos a cirugías abdominales y pélvicas electivas por cáncer colorrectal y anal entre 2016 y 2021.DISEÑO:Este fue un análisis retrospectivo.AJUSTE:El estudio se llevó a cabo en un sistema de salud académico de referencia terciaria de múltiples sitios.PACIENTES:Pacientes sometidos a cirugía abdominal o pélvica electiva por cáncer de colon, recto o ano.PRINCIPALES MEDIDAS DE RESULTADO:Recepción de profilaxis de tromboembolismo venoso guiada por Caprini, tasa postoperatoria de 90 días de trombosis venosa profunda, embolia pulmonar, tromboembolismo venoso y eventos de sangrado.RESULTADOS:Un total de 3.504 pacientes se sometieron a operaciones electivas, de los cuales 2.224 (63%) recibieron tromboprofilaxis adecuada en el ámbito hospitalario. En el cohorte de 2.769 pacientes después del alta, solo el 2% recibió tromboprofilaxis adecuada en la que no se observaron eventos tromboembólicos. En el grupo que recibió tromboprofilaxis inadecuada, a los 90 días después del alta, las tasas de trombosis venosa profunda, embolia pulmonar y tromboembolia venosa fueron del 0,60%, 0,40% y 0,88%, respectivamente. El sangrado posoperatorio no fue diferente entre los dos grupos.LIMITACIONES:Las limitaciones de nuestro estudio incluyen su naturaleza retrospectiva, el uso de registros médicos electrónicos agregados y la experiencia de un solo sistema de atención médica.CONCLUSIÓN:La mayoría de los pacientes en nuestro sistema de salud sometidos a cirugía abdominal o pélvica por cánceres de colon, recto y ano fueron dados de alta sin una profilaxis adecuada de TEV guiada por Caprini. La profilaxis guiada por el riesgo se asoció con menores tasas de tromboembolismo venoso hospitalario y dado de alta sin un aumento de las complicaciones de sangrado. (Traducción-Dr. Aurian Garcia Gonzalez ).

Venous Thromboembolism Prophylaxis in Otolaryngologic Patients Using Caprini Assessment.

OBJECTIVE: The aim was to determine the utilization of Caprini guideline-indicated venous thromboembolism (VTE) prophylaxis and impact on VTE and bleeding outcomes in otolaryngology (ORL) surgery patients. METHODS: Elective ORL surgeries performed between 2016 and 2021 were retrospectively identified. Logistic regression models were used to examine the association between patient characteristics and receiving appropriate prophylaxis, inpatient, 30- and 90-day VTE and bleeding events. RESULTS: A total of 4955 elective ORL surgeries were analyzed. Thirty percent of the inpatient cohort and 2% of the discharged cohort received appropriate risk-stratified VTE prophylaxis. In those who did not receive appropriate prophylaxis, overall inpatient VTE was 3.5-fold higher (0.73% vs. 0.20%, p = 0.015), and all PE occurred in this cohort (0.47% vs. 0.00%, p = 0.005). All 30- and 90-day discharged VTE events occurred in those not receiving appropriate prophylaxis. Inpatient, 30- and 90-day discharged bleeding rates were 2.10%, 0.13%, and 0.33%, respectively. Although inpatient bleeding was significantly higher in those receiving appropriate prophylaxis, all 30- and 90-day post-discharge bleeding events occurred in patients not receiving appropriate prophylaxis. On regression analysis, Caprini score was significantly positively associated with likelihood of receiving appropriate inpatient prophylaxis (odds ratio [OR] 1.05, confidence interval [CI] 1.03-1.07) but was negatively associated in the discharge cohort (OR 0.43, CI 0.36-0.51). Receipt of appropriate prophylaxis was associated with reduced odds of inpatient VTE (OR 0.24, CI 0.06-0.69), but not with risk of bleeding. CONCLUSION: Although Caprini VTE risk-stratified prophylaxis has a positive impact in reducing inpatient and post-discharge VTE, it must be balanced against the risk of inpatient postoperative bleeding. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1169-1182, 2024.

Caprini assessment utilization and impact on patient safety in gynecologic surgery.

PURPOSE: Postoperative venous thromboembolism (VTE) can potentially be associated with significant morbidity, mortality, and healthcare costs. The aim of this study was to determine the utilization of Caprini guideline indicated VTE in elective gynecologic surgery patients and its impact on postoperative VTE and bleeding complications. METHODS: This was a retrospective cohort study of elective gynecologic surgical procedures performed between January 1, 2016, and May 31, 2021. Two study cohorts were generated: (1) those who received and (2) those who did not receive VTE prophylaxis based on Caprini score risk stratification. Outcome measures were then compared between the study cohorts and included the development of a VTE up to 90-days postoperatively. Secondary outcome measures included postoperative bleeding events. RESULTS: A total of 5471 patients met inclusion criteria and the incidence of VTE up to 90 days postoperatively was 1.04%. Overall, 29.6% of gynecologic surgery patients received Caprini score-based guideline VTE prophylaxis. 39.2% of patients that met high-risk VTE criteria (Caprini > 5) received appropriate Caprini score-based prophylaxis. In multivariate regression analysis, the American Society of Anesthesiologists (ASA) score (OR 2.37, CI 1.27-4.45, p < 0.0001) and Caprini score (OR 1.13, CI 1.03-1.24, p = 0.008) predicted postoperatively VTE occurrence. Increasing Charlson comorbidity score (OR 1.39, CI 1.31-1.47, P < 0.001) ASA score (OR 1.36, CI 1.19-1.55, P < 0.001) and Caprini score (OR 1.10, CI 1.08-1.13, P < 0.001) were associated with increased odds of receiving appropriate inpatient VTE prophylaxis. CONCLUSION: While the overall incidence of VTE was low in this cohort, enhanced adherence to risk-based practice guidelines may provide more patient benefit than harm to postoperative gynecologic patients.

A Parathyroid Hormone-Guided Calcium and Calcitriol Supplementation Protocol Reduces Hypocalcemia-Related Readmissions Following Total Thyroidectomy.

OBJECTIVE: To determine the effect of a 4-hour postoperative serum parathyroid hormone (PTH)-guided calcium (Ca) and calcitriol supplementation protocol on the incidence of hypocalcemia and hospital readmissions in patients undergoing total thyroidectomy. METHODS: This was a single-institution, retrospective chart review of patients who underwent total thyroidectomy; 148 and 389 of the patients underwent surgery prior to and after the protocol implementation, respectively. The risk of hypocalcemia was stratified as low (PTH level of >30 pg/mL), medium (15-30 pg/mL), and high (<15 pg/mL), using serum PTH values obtained 4 hours postoperatively. Hypocalcemia was defined as a total serum Ca level of <8 mg/dL. Baseline demographic and operative characteristics and postoperative outcome were recorded for both groups. The Fisher exact test and Wilcoxon rank sum test were used to compare the characteristics of the 2 groups. A multivariate logistic regression model was applied to account for potentially confounding variables. RESULTS: Postoperative hypocalcemia occurred significantly less frequently in the protocol group compared with that in the preprotocol group (10.3% vs 20.9%, P = .002). The reduction in hypocalcemia in the protocol group was observed in both patients with (16.3% vs 25.6%) and without (8.4% vs 19.3%) cervical lymph node dissection. The protocol group had a significantly lower incidence of hospital readmission events than the preprotocol group (1.0% vs 4.7%, P = .013). CONCLUSION: Compared with a historical cohort, a PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients undergoing total thyroidectomy.

The Impact of Caprini Guideline Indicated Venous Thromboembolism Prophylaxis in Colorectal Surgery Patients: Experience of a Single Health System.

BACKGROUND: Venous thromboembolism (VTE) is the most common cause of preventable mortality following colorectal surgery (CRS), occurring in about 2% of patients. As a result, prophylaxis including discharge chemoprophylaxis is recommended. While VTE risk assessment tools are available, the consistent adoption and utilization of these tools remains elusive. Our study objectives were to determine the utilization and impact of risk adjusted VTE prophylaxis in CRS patients. STUDY DESIGN: CRS cases performed between 1/1/2016 and 5/31/2021 were retrospectively analyzed. Caprini score and implemented VTE prophylaxis measures were determined. The primary outcome measure was receiving Caprini guideline indicated VTE prophylaxis. Secondary outcomes included VTE and bleeding. Categorical variables were compared by chi-square and Fisher's exact tests, and continuous variables by Kruskal-Wallis test. Logistic regression models were used to determine predictors of receiving appropriate VTE prophylaxis or experiencing postoperative VTE and bleeding. RESULTS: 10,422 CRS cases were analyzed and 90.6% were high risk for VTE. In-hospital appropriate prophylaxis rates in low, moderate, high, and very high-risk category patients were 91.2%, 56.1%, 61.0%, and 63.1%, respectively. Inpatient VTE was reduced by 75% in those receiving appropriate VTE prophylaxis. At discharge, 5.8% of patients received appropriate prophylaxis, in whom there were no VTE events at 30- and 90 days from discharge. Increasing Caprini score positively correlated with VTE risk in both the inpatient and discharge cohorts, but inversely correlated with the likelihood of receiving appropriate prophylaxis at discharge (OR .31, P <.0001). CONCLUSION: Caprini guideline indicated VTE prophylaxis in CRS patients reduced VTE events without increasing bleeding complications.

Localization and surgical approach to mediastinal parathyroid glands.

BACKGROUND: Hyperactive parathyroid glands (PTGs) are in the mediastinum 4.3% of the time. Historically, localization and resection of these glands can be challenging. METHODS: We searched all operative notes involving a thoracic surgeon and a preoperative diagnosis of hyperparathyroidism from 2001 to 2019. RESULTS: Eighty-five cases were reviewed, of which 63 were included. Only 14 patients (22%) had de novo hyperparathyroid operations. Seventeen patients (27%) had single-photon emission computed tomography with computed tomography fusion (SPECT-CT) as the only preoperative localization test (excluding chest radiography and ultrasound), and all were resected successfully. The initial surgical approach was transcervical for 16 (27%) patients, however only 7 remained transcervical. 4 (6%) patients had an exploration in which the target lesion was resected but it was not parathyroid tissue. CONCLUSION: Most patients presenting with mediastinal PTG have had prior HPT surgery. The trend toward more focused HPT surgery may mean more de novo mediastinal PTG resections. An unambiguous functional and anatomic localization test, such as a spect-ct scan, is the best predictor of a successful resection. Ambiguous or discordant scans should be approached cautiously, and additional confirmatory tests are recommended. For suspected PTG located in the thymus, the thoracic surgeon should choose the most familiar approach to achieve complete thymectomy.

Addressing the Challenge of COVID-19: One Health Care Site's Leadership Response to the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols.

Results of surgical resection of carotid body tumors: A twenty-year experience.

This study examines whether surgical resection of carotid body tumors (CBTs) is acceptable in light of potential significant neurologic complications. This IRB-approved retrospective study analyzed data from 24 patients undergoing surgical treatment for CBTs between April 1998 and April 2017 at Mayo Clinic (Florida campus only). For patients who underwent multiple CBT resections, only data from the first surgery was used in this analysis. CBT resection occurred in 24 patients with the following demographics: fourteen patients (58.3%) were female, median age was 56.5 years, median BMI was 29. A prior history of neoplasm was found in ten patients (41.7%). A known family history of paraganglioma was present in five patients (20.8%). Two patients were positive for succinate dehydrogenase mutation (8.3%). Multiple paragangliomas were present in seven patients (29.2%). There was nerve sacrifice in three patients (12.5%) during resection. Carotid artery reconstruction and patch angioplasty occurred in one patient (4.2%). Complete resection occurred in 24 patients (100.0%). Postoperatively, one patient (4.2%) suffered stroke. No mortalities occurred within or beyond 30 days of surgery. Persistent cranial nerve injury occurred in two patients (8.3%) with vocal cord paralysis. There was no recurrence of CBT through last follow-up. Five patients (20.8%) were diagnosed with other neoplasms after resection, including basal cell carcinoma, contralateral carotid body tumor, glomus vagale, and glomus jugulare. There was 100% survival at 1 year in patients followed for that time (n = 17). Surgical treatment remains the first-line curative treatment to relieve symptoms and ensure non-recurrence. While acceptable, neurologic complications are significant and therefore detailed preoperative informed consent is mandatory.

ThyroSeq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules.

OBJECTIVE: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules. METHODS: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy. RESULTS: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy. CONCLUSION: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules. ABBREVIATIONS: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia.

Oropharyngeal Stenosis Leading to an Unanticipated Difficult Airway in a Patient After Uvulopalatopharyngoplasty: A Case Report and Review of the Literature.

Oropharyngeal stenosis can manifest as a rare complication after surgery for obstructive sleep apnea or tonsillectomy. Scar tissue formation from oropharyngeal stenosis may impede tracheal intubation or laryngeal mask airway insertion. We report the case of an asymptomatic adult woman found to have oropharyngeal stenosis after induction of anesthesia and discuss the management of this challenging scenario. We also contrast oropharyngeal stenosis with nasopharyngeal stenosis, another rare complication of uvulopalatopharyngoplasty.

Comprehensive Genomic Profiling of a Rare Thyroid Follicular Dendritic Cell Sarcoma.

We previously reported an extremely rare case of follicular dendritic cell sarcoma (FDCS) presented as a thyroid mass. Given the rarity of this disease, there are no personalized and molecularly targeted treatment options due to the lack of knowledge in the genomic makeup of the tumor. A 44-year-old white woman was diagnosed with an extranodal FDCS in thyroid. The patient underwent a total thyroidectomy, central compartment dissection, parathyroid re-implantation, and adjuvant radiation therapy. Tumor DNA sequencing of 236 genes by FoundationOne panel found truncating mutations in PTEN and missense mutations in RET and TP53. However, patient-matched germline DNA was not sequenced which is critical for identification of true somatic mutations. Furthermore, the FoundationOne panel doesn't measure genomic rearrangements which have been shown to be abundant in sarcomas and are associated with sarcoma tumorigenesis and progression. In the current study, we carried out comprehensive genomic sequencing of the tumor, adjacent normal tissues, and patient-matched blood, in an effort to understand the genomic makeup of this rare extranodal FDCS and to identify potential therapeutic targets. Eighty-one somatic point mutations were identified in tumor but not in adjacent normal tissues or blood. A clonal truncating mutation in the CLTCL1 gene, which stabilizes the mitotic spindle, was likely a driver mutation of tumorigenesis and could explain the extensive copy number aberrations (CNAs) and genomic rearrangements in the tumor including a chr15/chr17 local chromothripsis resulted in 6 expressed fusion genes. The fusion gene HDGFRP3→SHC4 led to a 200-fold increase in the expression of oncogene SHC4 which is a potential target of the commercial drug Dasatinib. Missense mutations in ATM and splice-site mutation in VEGFR1 were also detected in addition to the TP53 missense mutation reported by FoundationOne.

MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma.

CONTEXT AND OBJECTIVE: Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. DESIGN AND PATIENTS: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. RESULTS: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. CONCLUSION: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

Clinical and molecular features of Hürthle cell carcinoma of the thyroid.

CONTEXT: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. DESIGN: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. RESULTS: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III-IV (females, 74%; males, 91%) compared with patients with TNM stage I-II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. CONCLUSION: Widely invasive HCC with TNM stage III-IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.

Management of cervical thoracic duct cyst with cyst-venous anastomosis.

INTRODUCTION: Cervical thoracic duct cyst (CTDC) is a rare cause of lateral neck mass. Surgical excision with ligation of the cervical thoracic duct is the current standard for definitive management with symptomatic patients. We report the first case of an alternative method of management performing a cyst venous anastomosis for decompression. PRESENTATION OF CASE: A 77 year old female presented with a six month history of left arm pain, swelling and a left-sided cystic neck mass. She was treated with cyst-venous anastomosis between the cyst wall and the left internal jugular vein. At two year follow-up, she has had resolution of pain and no recurrence of the mass. DISCUSSION: Many potential etiologies have been proposed for CTDC, though surgical management of this rare problem has consistently required cyst excision and thoracic duct ligation. Few innovative modes of therapy have been developed to address this problem in a less invasive manor. Maintaining a more natural thoracic duct anatomy decreases the likely of complications associated with duct ligation. CONCLUSION: Cyst-venous anastomosis for the management of CTDC provides an effective, novel form of treatment which maintains the integrity of the thoracic duct and avoids potential complications associated with duct ligation.

RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma.

CONTEXT: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. OBJECTIVE: RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. DESIGN: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2-3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. PATIENTS: BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. RESULTS: RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. CONCLUSION: BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of these newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-MUT and BRAF-WT tumors.

Analysis of postoperative bleeding and risk factors in transoral surgery of the oropharynx.

IMPORTANCE: With an increasing incidence of oropharyngeal carcinoma and prevalence of transoral surgical techniques, postoperative bleeding, with its associated risk factors, deserves evaluation. OBJECTIVE: To classify and review postoropharyngectomy hemorrhage rates and associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: Single-institution, multicenter retrospective medical chart review analyzing surgical procedures in 906 patients treated with transoral surgery for oropharyngeal carcinoma at a tertiary care, academic referral center from 1994 to 2012. Tumor stage, previous treatment, resection method, and transcervical external carotid branch ligation were analyzed in relationship to postoperative hemorrhage rate, and severity. A novel classification system was created, grading bleeding episodes as minor, intermediate, major, or severe based on management method and related sequelae. RESULTS: Postoperative bleeding occurred in 5.4% of patients (49 of 906) with 67.3% of these (33 of 49) requiring operative intervention. Severe bleeding episodes were very rare (1.1% of patients). Transcervical external carotid system vessel ligation was performed with the primary resection in 15.6% of patients with no overall difference in bleeding rate or severity of bleeding in patients who underwent ligation vs those who did not (P = .21 and P = .66, respectively). Vessel ligation was performed more frequently in patients with a higher T stage (P = .002). In previously treated patients, severity of bleeding was decreased if vessels were ligated (P > .05). Higher T-stage tumors had a higher bleeding rate (P = .02). Bleeding rates were similar between those treated with laser (5.6%) and robotic (5.9%) oropharyngectomy (P = .80); however, patients with significantly higher T-stage tumors were treated with laser vs robot techniques (P < .001). CONCLUSIONS AND RELEVANCE: Transoral resection of oropharyngeal carcinoma is safe, and severe life-threatening hemorrhage is rare. Although transcervical vessel ligation did not result in an overall decrease in bleeding rate, there is a trend toward reduced postoropharyngectomy bleeding severity with ligation. We recommend ligation for higher T-stage tumors, primary tonsil tumors, and patients undergoing revision surgery.

Predictors of accuracy in preoperative parathyroid adenoma localization using ultrasound and Tc-99m-Sestamibi: a 4-quadrant analysis.

PURPOSE: To compare the accuracy of preoperative parathyroid adenoma localization in patients with primary hyperparathyroidism (pHPT) due to a single adenoma using a detailed 4-quadrant analysis and to identify patient and tumor characteristics associated with accurate preoperative localization. MATERIALS AND METHODS: Retrospective review of 203 patients who underwent parathyroidectomy for pHPT due to a single adenoma between 2008 and 2011. Results from preoperative ultrasound and Tc-99m-sestamibi were compared to operative findings to determine accuracy of localization studies. Associations between clinicopathologic features and accurate preoperative adenoma localization were evaluated. RESULTS: Ultrasound was performed on 198 patients, sestamibi on 177 patients, and both on 172 patients. Accurate localization occurred significantly more often for ultrasound than sestamibi (63% vs. 41%, P<0.001). For ultrasound, accurate localization was found in patients with larger or heavier adenomas, those with adenomas located inferiorly, patients not having a reoperative procedure, and patients with higher post-operative serum calcium levels. For sestamibi, greater adenoma size or weight, adenomas located inferiorly, and patients with associated thyroid cancer on pathology were most predictive of accurate preoperative localization. CONCLUSIONS: Our results provide evidence that ultrasound is more accurate in localizing parathyroid adenomas in patients with pHPT due to a single adenoma when compared to sestamibi scan using 4-quadrant location analysis and may be the preferred preoperative imaging modality in these patients. No significant preoperative patient factors were associated with accurate localization by ultrasound or sestamibi, but adenoma size, weight, and location in an inferior position were predictive of accurate preoperative localization.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

PURPOSE: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. CONCLUSION: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

OBJECTIVES: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all 3 Mayo Clinic campuses (Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased 7 times within 2 years. The number of active therapeutic endocrine malignancies clinical trials also increased from 1 in 2005 to 5 in 2009, with all 3 Mayo campuses participating. CONCLUSIONS: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.