Open adrenalectomy through a makuuchi incision: A single institution's experience.

BACKGROUND: Surgical techniques for adrenalectomy have evolved substantially over the last century. Although minimally invasive approaches are favored for benign disease, open adrenalectomy remains the gold standard for large tumors and those concerning for malignancy. Most reports describe the use of midline, subcostal, or thoracoabdominal incisions for open adrenalectomy. We studied our experience with the Makuuchi incision, designed to optimize exposure and minimize denervation of the abdominal wall. METHODS: All open adrenalectomies at the University of Rochester from 2009 to 2017 were retrospectively reviewed. Patient demographic characteristics, intraoperative details, and postoperative complications were investigated. Surgical site infection and hernia rates of Makuuchi incision were compared with non-Makuuchi incision patients and with published standards. The study was approved by the university Institutional Review Board. RESULTS: A total of 41 adrenalectomies were performed via Makuuchi incision. Population statistics included a mean age of 51.7 (19-86) years, a mean body mass index of 29.7 (17.3-45.8), and a mean tumor diameter of 8 cm (3.1-26 cm). Fourteen (34%) required multivisceral resection. Twenty-one (51%) were previous or current smokers, and 9 (22%) had hypercortisolemia. Median duration of stay was 6 days (4-73). Incisional hernia occurred in 5 patients (12%) and surgical site infection in 3 patients (7%), 2 patients had Cushing syndrome and 1 was immunosuppressed. Pain was managed with patient-controlled epidural anesthesia or patient-controlled anesthesia with postoperative day 1 daily morphine equivalents equating to 0.5 mg of hydromorphone q2h. Among 15 non-Makuuchi incision patients, there were 2 hernias (13%), 2 surgical site infections (13%), and 1 case of postoperative pneumonia. CONCLUSION: The Makuuchi incision is well tolerated and affords outstanding exposure of the adrenals and adjacent viscera. Incisional hernia and surgical site infection rates were favorable compared with published rates for midline or subcostal incisions, despite an obese population with a high incidence of hypercortisolism and immunosuppression.

Have Recent Modifications of Operating Room Attire Policies Decreased Surgical Site Infections? An American College of Surgeons NSQIP Review of 6,517 Patients.

BACKGROUND: After a Department of Health site visit, 2 teaching hospitals imposed strict regulations on operating room attire, including full coverage of ears and facial hair. We hypothesized that this intervention would reduce superficial surgical site infections (SSIs). STUDY DESIGN: We compared NSQIP data from all patients undergoing operations in the 9 months before implementation (n = 3,077) to time-matched data 9 months post-implementation (n = 3,440). Univariate and multivariable analyses were used to examine patient, clinical, and operative factors associated with SSIs. Power analysis was performed using pre-intervention SSI rates. RESULTS: Despite a shift toward more clean cases, there were more SSIs post-implementation (33 vs 30 [1%]; p = 0.95). There were no differences in length of stay, complications, or mortality between the 2 time periods. Overall, SSI increased with wound class: 0.6%, 0.9%, 2.3%, and 3.8% in clean, clean-contaminated, contaminated, and infected cases, respectively. Limiting the review to clean or clean-contaminated cases, incisional SSIs increased from 0.7% (20 of 2,754) to 0.8% (24 of 3,115) (p = 0.85). A multivariable analysis showed that implementation of these policies was not associated with decreased SSIs (odds ratio 1.2; 95% CI 0.70 to 1.96; p = 0.56). The largest predictors of SSIs were preoperative infection, operative time >75th percentile, open wounds, and dirty/contaminated wounds. A hypothetical analysis revealed that a sample size of 485,154 patients would be required to demonstrate a 10% SSI reduction among patients with clean or clean-contaminated wounds. CONCLUSIONS: Implementation of stringent operating room attire policies do not reduce SSI rates. A study to prove this principle further would be impractical to conduct.

Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer.

Purpose: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR/PI3K or combined RAF/MEK inhibition but experienced a dramatic response when both drug regimens were combined.Experimental Design: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed. Meta-analysis of DNA and RNA sequencing studies of ATC was performed.Results: Sequencing revealed truncal BRAF and PIK3CA mutations, which are known to activate the MAPK and PI3K/AKT pathways, respectively. Meta-analysis demonstrated 10.3% cooccurrence of MAPK and PI3K pathway alterations in ATC. These tumors display a separate transcriptional profile from other ATCs, consistent with a novel subgroup of ATC.Conclusions: BRAF and PIK3CA mutations define a distinct subset of ATC. Blockade of the MAPK and PI3K pathways appears necessary for tumor response in this subset of ATC. This identification of synergistic activity between targeted agents may inform clinical trial design in ATC. Clin Cancer Res; 23(9); 2367-73. ©2016 AACR.

Prevalence of Contralateral Tumors in Patients with Follicular Variant of Papillary Thyroid Cancer.

BACKGROUND: Thyroid lobectomy alone is being performed increasingly for patients with encapsulated follicular variant of papillary thyroid carcinoma (fvPTC). However, the prevalence of contralateral disease in these patients is unknown. We investigated the presence of synchronous disease in fvPTC to improve decision making about the extent of surgical resection and need for surveillance. STUDY DESIGN: We performed a retrospective review of patients who underwent thyroid surgery from October 2009 to February 2013 with a diagnosis of fvPTC as their primary lesion. We collected information on patient demographics, nodule size, multifocality, fine-needle aspiration results, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis. Tumors were divided into noninvasive and invasive/infiltrative fvPTC categories. Characteristics of solitary and bilateral fvPTC were compared. RESULTS: We identified 124 patients with final pathology demonstrating fvPTC. The most common fine-needle aspiration diagnosis was "suspicious for malignancy" (n = 53). Sixty-five contralateral tumors were identified in 44 of 124 patients (35.5%) and included fvPTC (n = 40), classical PTC (n = 22), tall cell PTC (n = 2), and follicular carcinoma (n = 1). Fifty contralateral tumors were 1 to 5 mm, 10 measured 6 to 9 mm, and 5 were ≥10 mm. Contralateral disease correlated significantly with lymphovascular invasion (p = 0.037) and larger primary lesions (p = 0.020). There was no significant difference noted in extrathyroidal extension or lymph node metastasis. Both noninvasive and invasive/infiltrative fvPTC demonstrated similar rates of contralateral disease. CONCLUSIONS: Bilateral disease is common in fvPTC, primarily in the form of papillary microcarcinomas. Future monitoring of the contralateral lobe should be discussed with fvPTC patients who do not undergo completion thyroidectomy.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

Identification of Novel Oncogenic Mutations in Thyroid Cancer.

BACKGROUND: Thyroid cancer patients frequently have favorable outcomes. However, a small subset develops aggressive disease refractory to traditional treatments. Therefore, we sought to characterize oncogenic mutations in thyroid cancers to identify novel therapeutic targets that may benefit patients with advanced, refractory disease. STUDY DESIGN: Data on 239 thyroid cancer specimens collected between January 2009 and September 2014 were obtained from the Dana Farber/Brigham and Women's Cancer Center. The tumors were analyzed with the OncoMap-4 or OncoPanel high-throughput genotyping platforms that survey up to 275 cancer genes and 91 introns for DNA rearrangement. RESULTS: Of the 239 thyroid cancer specimens, 128 (54%) had oncogenic mutations detected. These 128 tumors had 351 different mutations detected in 129 oncogenes or tumor suppressors. Examination of the 128 specimens demonstrated that 55% (n = 70) had 1 oncogenic mutation, and 45% (n = 48) had more than 1 mutation. The 351 oncogenic mutations were in papillary (85%), follicular (4%), medullary (7%), and anaplastic (4%) thyroid cancers. Analysis revealed that 2.3% (n = 3 genes) of the somatic gene mutations were novel. These included AR (n = 1), MPL (n = 2), and EXT2 (n = 1), which were present in 4 different papillary thyroid cancer specimens. New mutations were found in an additional 13 genes known to have altered protein expression in thyroid cancer: BLM, CBL, CIITA, EP300, GSTM5, LMO2, PRAME, SBDS, SF1, TET2, TNFAIP3, XPO1, and ZRSR2. CONCLUSIONS: This analysis revealed that several previously unreported oncogenic gene mutations exist in thyroid cancers and may be targets for the development of future therapies. Further investigation into the role of these genes is warranted.

Bethesda Categorization of Thyroid Nodule Cytology and Prediction of Thyroid Cancer Type and Prognosis.

BACKGROUND: Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk. METHODS: All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy. RESULTS: A total of 1291 malignancies were identified, with primary cytology AUS in 130 cases, FN in 241 cases, SUSP in 411 cases, and M in 509 cases. AUS, SUSP, and M cytology were progressively associated with an increasing risk of high-risk disease (p < 0.001), LNM (p < 0.001), ETE (p < 0.001), and margin positivity (p < 0.001). Notably, 71% of malignancies with AUS cytology were follicular variants of papillary thyroid cancer compared with 63% with SUSP cytology and only 20% with M cytology. In contrast, high-risk malignancies were diagnosed in only 4% with AUS cytology, but 9% and 27% with SUSP and M cytology, respectively. FN conveyed a significantly increased risk of follicular thyroid carcinoma compared with all other types (28% vs. 2%; p < 0.001). A composite endpoint of recurrence, distant metastases, and death similarly increased as cytology progressed from AUS to SUSP to M (p < 0.001). CONCLUSION: In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence. These data extend the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy.

Defining competencies for safe thyroidectomy: An international Delphi consensus.

BACKGROUND: Current methods for teaching and assessing competencies that characterize expert intraoperative performance are inconsistent, subjective, and lack standardization. This mixed-methods study was designed to define and establish expert consensus on the most important competencies required to perform a thyroidectomy safely. METHODS: Cognitive task analyses for thyroidectomy were performed with semistructured interviews of experts in thyroid surgery. Verbal data were transcribed verbatim, coded, and categorized according to themes that were synthesized into a list of items. Once qualitative data reached saturation, 26 experts were invited to complete 2-round online Delphi surveys to rank each item on a Likert scale of importance (1-7). Consensus was predefined as a Cronbach's α ≥ 0.80. RESULTS: Sixty items were synthesized from 5 interviews and categorized into 8 sections: preparation (n = 8), incision/exposure (n = 11), general considerations (n = 4), middle thyroid vein (n = 1), superior pole (n = 5), inferior pole (n = 5), posterolateral dissection (n = 19), and closure (n = 7). Eighteen (69%) experts from 3 countries participated in the Delphi survey. Consensus was achieved after 2 voting rounds (Cronbach's α = 0.95). Greatest weighted sections included "Superior Pole Dissection" and "Posterolateral Dissection." CONCLUSION: Consensus was achieved on defining the most important competencies for safe thyroidectomy. This blueprint serves as the basis for instructional design and objective assessment tools to evaluate performance.

Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study.

BACKGROUND: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. METHODS: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. RESULTS: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. CONCLUSION: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

BACKGROUND: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. METHODS: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. RESULTS: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. CONCLUSIONS: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.

Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis.

BACKGROUND: Neoadjuvant therapy-based protocols for potentially resectable pancreatic adenocarcinoma (PAC) have not been directly compared with adjuvant protocols in large prospective randomized trials. This study aimed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model. METHODS: A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo- and/or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC. Base-case probabilities were derived from the published data of 21 prospective phases 2 and 3 trials (3708 patients) between 1997 and 2014. The primary outcome measures determined in an intent-to-treat fashion were overall and quality-adjusted survival rates. One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes. RESULTS: The median overall survival and 2-year survival rates for the patients in the standard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm. Quality-adjusted survival was 18.4 and 19.8 months, respectively. Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 %, the neoadjuvant strategy is no longer the favored option. CONCLUSIONS: The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer. However, the benefits in terms of overall and quality-adjusted survival are modest.

In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes.

UNLABELLED: The phosphatases PTEN and INPP4B have been proposed to act as tumor suppressors by antagonizing PI3K-AKT signaling and are frequently dysregulated in human cancer. Although PTEN has been extensively studied, little is known about the underlying mechanisms by which INPP4B exerts its tumor-suppressive function and its role in tumorigenesis in vivo. Here, we show that a partial or complete loss of Inpp4b morphs benign thyroid adenoma lesions in Pten heterozygous mice into lethal and metastatic follicular-like thyroid cancer (FTC). Importantly, analyses of human thyroid cancer cell lines and specimens reveal INPP4B downregulation in FTC. Mechanistically, we find that INPP4B, but not PTEN, is enriched in the early endosomes of thyroid cancer cells, where it selectively inhibits AKT2 activation and in turn tumor proliferation and anchorage-independent growth. We therefore identify INPP4B as a novel tumor suppressor in FTC oncogenesis and metastasis through localized regulation of the PI3K-AKT pathway at the endosomes. SIGNIFICANCE: Although both PTEN and INPP4B can inhibit PI3K-AKT signaling through their lipid phosphatase activities, here we demonstrate lack of an epistatic relationship between the two tumor suppressors. Instead, the qualitative regulation of PI3K-AKT2 signaling by INPP4B provides a mechanism for their cooperation in suppressing thyroid tumorigenesis and metastasis.

False negative cytology in large thyroid nodules.

BACKGROUND: Controversy exists regarding the accuracy of fine-needle aspiration (FNA) in large thyroid nodules. Recent surgical series have documented false-negative rates ranging from 0.7 to 13 %. We examined the accuracy of benign FNA cytology in patients with thyroid nodules ≥3 cm who underwent surgical resection and identified features characteristic of false-negative results. METHODS: We retrospectively studied all thyroidectomy specimens between January 2009 and October 2011 and identified nodules ≥3 cm with corresponding benign preoperative FNA cytology. We collected clinical information regarding patient demographics, nodule size, symptoms, sonographic features, FNA results, and final surgical pathology. For comparison, we analyzed nodules <3 cm from this cohort also with benign FNA cytology. RESULTS: A total of 323 nodules with benign preoperative cytology were identified. Eighty-three nodules were <3 cm, 94 nodules were 3-3.9 cm, and 146 nodules were ≥4 cm in size. The false-negative rate was 11.7 % for all nodules ≥3 cm and 4.8 % for nodules <3 cm (p = 0.03). Subgroup analysis of nodules ≥3 cm revealed a false-negative rate of 12.8 % for nodules 3-3.9 cm and 11 % for nodules ≥4 cm. Age ≥55 years and asymptomatic clinical status were the only patient characteristics that reached statistical significance as risk factors. Final pathology of the false-negative specimens consisted mainly of follicular variant of papillary thyroid cancer and follicular thyroid cancer. CONCLUSIONS: When referred for thyroidectomy, patients with large thyroid nodules demonstrate a modest, yet significant, false-negative rate despite initial benign aspiration cytology. Therefore, thyroid nodules ≥3 cm may be considered for removal even when referred with benign preoperative cytology.

Hypoglycemia after resection of pheochromocytoma.

BACKGROUND: Hypoglycemia after resection of pheochromocytoma is a rare and poorly understood complication thought to be secondary to rebound hyperinsulinemia and increased peripheral glucose uptake. We examined the incidence of this complication and aimed to identify predisposing risk factors. METHODS: Patients who underwent pheochromocytoma resection between 1993 and 2013 at 2 large academic medical centers were identified retrospectively from a research patient data registry. The primary end point was postoperative hypoglycemia defined as blood glucose <55 mg/dL. RESULTS: A total of 213 patients underwent resection of pheochromocytoma for a total of 215 operations. Nine patients (4.2%) experienced postoperative hypoglycemia, with 8 of 9 episodes occurring in the first 24 hours. Patients who developed hypoglycemia were more likely to have greater preoperative 24-hour urinary metanephrine (4,726 vs 2,461 µg/24 h, P = .05) and experienced longer operative times (270 vs 142 minutes, P < .01) with larger neoplasms (7.6 vs 4.6 cm, P = .02). Postoperatively, patients with hypoglycemia required intensive care level monitoring more frequently (88.9% vs 34.5%, P < .01), but there was no difference in duration of hospital stay (5 vs 3 days, P = .10). CONCLUSION: Our data demonstrate that hypoglycemia is a rare complication after resection of pheochromocytoma and may be more common in patients with epinephrine-predominant neoplasms and longer operative times.

Risk scoring can predict readmission after endocrine surgery.

BACKGROUND: Hospitals and surgeons simultaneously are pressured to decrease readmissions and duration of stay. We hypothesized that readmissions after endocrine surgery could be predicted by using a novel risk-score. METHODS: The National Surgical Quality Improvement Program database was queried for cervical endocrine operations performed during 2011 and 2012. The primary end point was unplanned readmission within 30 days. Multivariable logistic regression was used to create and validate a scoring system to predict unplanned readmissions. RESULTS: Overall, 34,046 cases were included with a readmission rate of 2.8% (n = 947). The most frequent reasons for readmission were hypocalcemia (32.4%) surgical-site infection (8.4%), and hematoma (8.0%) (2012 data only). The readmission risk score was created using the following factors: thyroid malignancy, hypoalbuminemia, renal insufficiency, American Society of Anesthesiologists class, and duration of stay >1 day. Predicted readmission rate by number of risk factors was 1.7 % for 0 risk factors, 3.2% for 1 risk factor (5-11 points), 5.8% for 2 risk factors, 10.5% for 3 risk factors, and 18.0% for 4 risk factors. The model had good predictive ability with c = 0.646. CONCLUSION: Readmissions after cervical endocrine operations can be predicted. This risk score could be used to direct resource use for preoperative, inpatient, and outpatient care delivery to reduce readmissions.

Response and acquired resistance to everolimus in anaplastic thyroid cancer.

Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors.