Measuring Decision-Making During Thyroidectomy: Validity Evidence for a Web-Based Assessment Tool.

BACKGROUND: Errors in judgment during thyroidectomy can lead to recurrent laryngeal nerve injury and other complications. Despite the strong link between patient outcomes and intraoperative decision-making, methods to evaluate these complex skills are lacking. The purpose of this study was to develop objective metrics to evaluate advanced cognitive skills during thyroidectomy and to obtain validity evidence for them. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from four institutions completed a 33-item assessment, developed based on a cognitive task analysis and expert Delphi consensus. Sixteen items required subjects to make annotations on still frames of thyroidectomy videos, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test," VCT). Seven items were short answer (SA), requiring users to type their answers, and scores were automatically calculated based on their similarity to a pre-populated repertoire of correct responses. Test-retest reliability, internal consistency, and correlation of scores with self-reported experience and training level (novice, intermediate, expert) were calculated. RESULTS: Twenty-eight subjects (10 endocrine surgeons and otolaryngologists, 18 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.96; n = 10) and internal consistency (Cronbach's α = 0.93). The assessment demonstrated significant differences between novices, intermediates, and experts in total score (p < 0.01), VCT score (p < 0.01) and SA score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.95, p < 0.01), between total case number and VCT score (ρ = 0.93, p < 0.01), and between total case number and SA score (ρ = 0.83, p < 0.01). CONCLUSION: This study describes the development of novel metrics and provides validity evidence for an interactive Web-based platform to objectively assess decision-making during thyroidectomy.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

De novo thyroid cancer following solid organ transplantation-A 25-year experience at a high-volume institution with a review of the literature.

BACKGROUND AND OBJECTIVES: We investigated the rate, stage, and prognosis of thyroid cancer in patients after solid-organ transplantations, and compared this to the general population. METHODS: We performed a retrospective review of patients who developed thyroid cancer after a solid-organ transplantation between January 1988 and December 2013 at a high volume transplant center. Standardized Incidence Ratio's (SIR) were calculated. Additionally, a systematic review of the literature was performed. RESULTS: A total of 10,428 patients underwent solid organ transplantation. Eleven patients (11.4 per 100,000 person-years) developed thyroid cancer: six men and five women with a mean age at diagnosis of thyroid cancer of 58 years. Ten patients underwent surgery and had stage I thyroid cancer. One patient had recurrent disease after a mean follow-up time of 78 months. The SIR varied between 0.75 and 2.3. Seventeen studies were included in the systematic review with a SIR ranging from 2.5 to 35. CONCLUSION: Rate of thyroid cancer is not significantly higher in patients who underwent solid organ transplantation compared to general population. Stage at presentation and prognosis also appear to be similar to that of the general population. Post-transplant screening for thyroid cancer remains debatable; however, when thyroid cancer is discovered, treatment should be similar to that of non-transplant patients. J. Surg. Oncol. 2017;115:105-108. © 2017 Wiley Periodicals, Inc.

Measuring intra-operative decision-making during laparoscopic cholecystectomy: validity evidence for a novel interactive Web-based assessment tool.

BACKGROUND: Errors in judgment during laparoscopic cholecystectomy can lead to bile duct injuries and other complications. Despite correlations between outcomes, expertise and advanced cognitive skills, current methods to evaluate these skills remain subjective, rater- and situation-dependent and non-systematic. The purpose of this study was to develop objective metrics using a Web-based platform and to obtain validity evidence for their assessment of decision-making during laparoscopic cholecystectomy. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from six institutions completed a 12-item assessment, developed based on a cognitive task analysis. Five items required subjects to draw their answer on the surgical field, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test", VCT). Test-retest reliability, internal consistency, and correlation with self-reported experience, Global Operative Assessment of Laparoscopic Skills (GOALS) score and Objective Performance Rating Scale (OPRS) score were calculated. Questionnaires were administered to evaluate the platform's usability, feasibility and educational value. RESULTS: Thirty-nine subjects (17 surgeons, 22 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.95; n = 10) and internal consistency (Cronbach's α = 0.87). The assessment demonstrated significant differences between novices, intermediates and experts in total score (p < 0.01) and VCT score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.83, p < 0.01) and between total case number and VCT (ρ = 0.82, p < 0.01), and moderate to high correlations between total score and GOALS (ρ = 0.66, p = 0.05), VCT and GOALS (ρ = 0.83, p < 0.01), total score and OPRS (ρ = 0.67, p = 0.04), and VCT and OPRS (ρ = 0.78, p = 0.01). Most subjects agreed or strongly agreed that the platform and assessment was easy to use [n = 29 (78 %)], facilitates learning intra-operative decision-making [n = 28 (81 %)], and should be integrated into surgical training [n = 28 (76 %)]. CONCLUSION: This study provides preliminary validity evidence for a novel interactive platform to objectively assess decision-making during laparoscopic cholecystectomy.

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.

Rare metastases of well-differentiated thyroid cancers: a systematic review.

BACKGROUND: A minority of metastatic well-differentiated thyroid cancer (WDTC) patients present with end-organ disease other than in the lung, bone or lymph nodes. These metastases tend to be overlooked because of their low incidence, and this results in delayed diagnosis. The purpose of this study was to perform a systematic review of the clinical and histologic features of unusual WDTC metastases. METHODS: A systematic literature search of bibliographic databases, reference lists of articles, and conference proceedings was performed up to 2013. Studies were included if they reported on adult patients with WDTC and pathology-proven metastases to end-organs other than lung, bone, or lymph nodes. A total of 238 studies were included in a qualitative analysis. Data is expressed as N (%) and median [interquartile range]. RESULTS: A total of 492 patients (median age, 62 years [50-70 years]) were identified in 197 case reports and 42 case series. There were 22 different end-organ metastatic sites documented with either papillary [255 (57 %)], follicular [172 (39 %)], or Hürthle-cell [18 (4 %)] histology. A total of 181 (41 %) patients presented with solitary metastasis and 54 (93 %) with elevated serum thyroglobulin. Positron emission tomography and whole-body radioactive iodine scans revealed hypermetabolic foci in 28 (97 %) and 50 (81 %) cases, respectively. Disease-free interval following the initial diagnosis of the primary thyroid cancer was highly variable, ranging from synchronous presentation [66 (33 %)] to metachronous disease after 516 months [mean 86 months (SD 90)]. CONCLUSIONS: WDTC can manifest with highly variable and unusual clinical features. Rare sites of metastases should be considered in the absence of the more common extra-cervical disease recurrence locations.

Primary hyperparathyroidism patients with positive preoperative sestamibi scan and negative ultrasound are more likely to have posteriorly located upper gland adenomas (PLUGs).

BACKGROUND: Standard preoperative imaging for primary hyperparathyroidism usually includes sestamibi scanning (MIBI) and ultrasound (US). In a subset of patients with a positive MIBI and a negative US, we hypothesize that the parathyroid adenomas are more likely to be located posteriorly in the neck, where anatomically they are more difficult to detect by US. METHODS: We retrospectively reviewed the records of 661 patients treated for primary hyperparathyroidism between 2004 and 2009 at a tertiary referral center. We included patients who for their first operation had a MIBI that localized a single lesion in the neck and an US that found no parathyroid adenoma. We excluded patients with persistent or recurrent hyperparathyroidism, and patients with MIBIs that were negative, that had more than one positive focus, or that had foci outside of the neck. Sixty-six cases were included in the final analysis. RESULTS: A total of 54 patients (83%) had a single adenoma, 4 (6%) had double adenomas, and 7 (11%) had hyperplasia. Thirty-three patients (51%) had a single upper gland adenoma; 19 of these (58%) were posteriorly located upper gland adenomas (PLUGs). PLUGs occurred more often on the right side than on the left (P = 0.048, Fisher's test). PLUGs were also larger than other single adenomas (mean 1.85 vs. 1.48 cm, P = 0.021, t-test). Seventy-six percent of patients successfully underwent a unilateral or focused exploration. Six patients (9%) had persistent disease, which is double our group's overall average (4-5%). CONCLUSIONS: Primary hyperparathyroid patients with preoperative positive MIBI and negative US are more likely to have PLUGs.

Changing paradigms in the treatment of malignant pheochromocytoma.

BACKGROUND: Pheochromocytomas and paragangliomas are intra- and extra-adrenal neoplasms that are rarely malignant. The treatment of those that are malignant has remained a challenge because little was known about the molecular pathways involved in its malignant transformation. Recently, however, the genetic and molecular changes involved in malignant pheochromocytoma have come to be understood. METHODS: The authors review the recent literature about the changing treatment options for malignant pheochromocytomas and paragangliomas. RESULTS: Traditional treatments for malignant pheochromocytoma remain unsuccessful. With the advances made in genomics and proteomics, novel pathways in pheochromocytoma carcinogenesis are becoming the targets of new treatment strategies and show promising results. CONCLUSIONS: Although several studies and clinical trials show great promise for improving the treatment of pheochromocytomas and paragangliomas, the hope is that future collaborative efforts will allow for prospective clinical trials using an evidenced-based approach.

The Role of the ThyroSeq v3 Molecular Test in the Surgical Management of Thyroid Nodules in the Canadian Public Health Care Setting.

Background: Although the current gold standard for diagnosing thyroid nodule malignancy is ultrasound-guided fine-needle aspiration (FNA) cytology, about 20-25% of cytological evaluations are considered indeterminate for malignancy. This limitation has led to the emergence of next-generation sequencing panels, for example, ThyroSeq v3 (TSv3), which recognize highly diagnostic genetic mutations of common thyroid carcinomas in FNA samples and classify them as test-negative or test-positive, helping optimize treatment for indeterminate thyroid nodules (ITNs). Our goals were to evaluate the benign call rate (BCR) of TSv3 and assess its diagnostic performance and clinical utility while highlighting the points of consideration for a public Canadian institution. Methods: This is a single-center study conducted at the Royal Victoria Hospital (McGill University Health Centre) in Montreal, Canada, between January and February 2019. Patients were offered TSv3 following the McGill algorithm for ITN workup, a novel protocol developed at our institution to select only diagnostic surgery candidates to minimize waste of public resources, considering the single-payer health care system. Patient demographics, cytopathology results, TSv3 data, treatment plan, and final histopathology result were reviewed. Results: A total of 50 ITNs underwent TSv3 testing; molecular analysis yielded 20 (40%) "positive" results and 24 (48%) "negative" results. Six (12%) results were classified as "currently negative" or "negative but limited." "Currently negative" results indicate a low-risk mutation that alone is insufficient for development of a malignant lesion. "Negative but limited" results indicate a sample that is nondiagnostic for malignancy due to low cell count. BCR was calculated as ("negative" and "currently negative")/total, resulting in a BCR of 58%. Twenty-three (46%) patients were scheduled for surgery and 27 (54%) patients continued with surveillance. Ninety-one percent (20 of 22) of the resected target nodules were malignant on final pathology. Conclusions: TSv3 proved beneficial in classifying ITNs as positive or negative, avoiding surgery in the latter cases. We found a lower reduction rate in surgery and BCR than the previously published studies, which is attributable to the criteria of the McGill algorithm. In the Canadian public health care system, preventing unnecessary surgery represents significant cost savings for the provincial government while also improving patient quality of life.

Defining the competencies for laparoscopic transabdominal adrenalectomy: An investigation of intraoperative behaviors and decisions of experts.

BACKGROUND: Safe performance of laparoscopic transabdominal adrenalectomy requires the application of a complex body of knowledge and skills, which are difficult to define, teach, and measure. This qualitative study aims to characterize expert behaviors, decisions, and other cognitive processes required to perform laparoscopic transabdominal adrenalectomy. METHOD: Hierarchical and cognitive task analyses for right and left laparoscopic transabdominal adrenalectomy were performed using semi-structured interviews and field observations of experts. Verbal data was supplemented with published literature, coded and thematically analyzed using constructivist grounded-theory by 2 independent reviewers. RESULTS: A conceptual framework was synthesized. Sixty-eight tasks, 46 cognitive behaviors, and 52 potential errors were identified and categorized into 8 procedural steps and 8 fundamental principles: anticipation, exposure, teamwork or communication, physiology, dissection techniques, oncologic margins, tactical modification, and error recovery. Experts emphasized the importance of creating a 3-dimensional mental model of the anatomy or pathology (eg, aberrant vessels, tumor location) that is consistently fine-tuned throughout the operation, with conscious awareness of danger zones (eg, medial arc). Despite variations in dissection techniques, experts highlighted 2 themes: macrodissection and microdissection, with emphasis on nonlinear motions and effective transitions between the 2 when appropriate. CONCLUSION: This study defines behaviors and competencies that are essential to performing laparoscopic transabdominal adrenalectomy effectively and safely.

Somatic mosaicism of androgen receptor CAG repeats in colorectal carcinoma epithelial cells from men.

BACKGROUND: The X-linked human androgen receptor gene (AR) contains an exonic polymorphic trinucleotide CAG. The length of this encoded CAG tract inversely affects AR transcriptional activity. Colorectal carcinoma is known to express the androgen receptor, but data on somatic CAG repeat lengths variations in malignant and normal epithelial cells are still sporadic. MATERIALS AND METHODS: Using laser capture microdissection (LCM), epithelial cells from colorectal carcinoma and normal-appearing mucosa were collected from the fresh tissue of eight consecutive male patients undergoing surgery (mean age, 70 y; range, 54-82). DNA isolated from each LCM sample underwent subsequent PCR and DNA sequencing to precisely determine AR CAG repeat lengths and the presence of microsatellite instability (MSI). RESULTS: Different AR CAG repeat lengths were observed in colorectal carcinoma (ranging from 0 to 36 CAG repeats), mainly in the form of multiple shorter repeat lengths. This genetic heterogeneity (somatic mosaicism) was also found in normal-appearing colorectal mucosa. Half of the carcinoma cases examined tended to have a higher number of AR CAG repeat lengths with a wider range of repeat size variation compared to normal mucosa. MSI carcinomas tended to have longer median AR CAG repeat lengths (n = 17) compared to microsatellite stable carcinomas (n = 14), although the difference was not significant (P = 0.31, Mann-Whitney test). CONCLUSIONS: Multiple unique somatic mutations of the AR CAG repeats occur in colorectal mucosa and in carcinoma, predominantly resulting in shorter alleles. Colorectal epithelial cells carrying AR alleles with shorter CAG repeat lengths may be more androgen-sensitive and therefore have a growth advantage.

Thyroid Nodule DNA Methylation Signatures: An Important Diagnostic Annotation.

Molecular profiling in thyroid cancer has made significant progress in part due to advances in somatic mutation profiling. Yet, differentiating benign from malignant thyroid nodules remains elusive. A unique set of DNA methylation signatures has the potential of improving thyroid cancer molecular diagnostics based on the DNA methylome.See related article by Yim et al., p. 544.

A thyroid gland with over 30 foci of papillary thyroid carcinoma with activating BRAF V600E mutation.

Multifocal papillary thyroid carcinoma (PTC) is common and the number of tumor foci rarely exceeds ten. The mechanism of multifocal disease is debated, with the two main hypotheses consisting of either intrathyroidal metastatic spread from a single tumor or independent multicentric tumorigenesis from distinct progenitor cells. We report the case of a 46-year-old woman who underwent total thyroidectomy and left central neck lymph node dissection after fine-needle aspiration of bilateral thyroid nodules that yielded cytological findings consistent with PTC. Final pathology of the surgical specimen showed an isthmic dominant 1.5 cm classical PTC and over 30 foci of microcarcinoma, which displayed decreasing density with increasing distance from the central lesion. Furthermore, all malignant tumors and lymph nodes harbored the activating BRAF V600E mutation. The present case highlights various pathological features that support a mechanism of intraglandular spread, namely a strategic isthmic location of the primary tumor, radial pattern of distribution and extensive number of small malignant foci and BRAF mutational homogeneity. Learning points: Multifocal papillary thyroid carcinoma (PTC) is commonly seen in clinical practice, but the number of malignant foci is usually limited to ten or less. There is no clear consensus in the literature as to whether multifocal PTC arises from a single or multiple distinct tumor progenitor cells. Strategic location of the dominant tumor in the thyroid isthmus may favor intraglandular dissemination of malignant cells by means of the extensive lymphatic network. An important pathological finding that may be suggestive of intrathyroidal metastatic spread is a central pattern of distribution with a reduction in the density of satellite lesions with increasing distance from the dominant focus. PTCs originating from the isthmus with intraglandular metastatic dissemination behave more aggressively. As such, a more aggressive treatment course may be warranted, particularly with regard to the extent of surgery.

Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism.

Importance: In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects. Objective: To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism. Design, Setting, and Participants: A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded. Main Outcomes and Measures: Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery. Results: On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater. Conclusions and Relevance: In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

Microsatellite instability in benign and malignant thyroid neoplasms.

BACKGROUND: Microsatellite instability (MSI) is a form of genomic instability that has recently been implicated in the pathogenesis of thyroid cancer. The purpose of this study was to further define the distribution of MSI in both normal and neoplastic thyroid follicular epithelium. DESIGN: Using laser capture microdissection, cells from both normal and tumor tissue were individually collected. Polymerase chain reaction amplification of the DNA was then performed using six dinucleotide and two mononucleotide microsatellite markers. RESULTS: Forty benign and malignant thyroid tumors were compared with their adjacent normal thyroid follicular tissue and were analyzed for MSI. Nine of 14 papillary thyroid carcinomas and 10/16 of follicular thyroid carcinomas demonstrated MSI at > or =30-40% of loci tested. For benign follicular adenomas, 9/10 demonstrated microsatellite stability or low-frequency MSI. CONCLUSION: MSI appears to play a role in thyroid pathogenesis as evidenced by the high frequency of MSI in malignant thyroid neoplasms. In addition our study showed a significant difference in MSI frequency between follicular adenomas and follicular carcinomas. More importantly, the technique of laser capture microdissection allows for more accurate selection of benign, malignant, and normal DNA.

Effects of Chronic Lymphocytic Thyroiditis on the Clinicopathological Features of Papillary Thyroid Cancer.

BACKGROUND: The effects of chronic lymphocytic thyroiditis (CLT) on the presentation and outcome of papillary thyroid carcinoma (PTC) have long been a topic of controversy. OBJECTIVE: To evaluate the effect of coexistent CLT on the clinicopathological features of PTC. DESIGN: Retrospective study. PATIENTS: All patients with PTC who had been followed by the 2 co-investigators (Juan Rivera and Richard J. Payne) between 2006 and 2011 were included. RESULTS: CLT was present in 35% (166) of the included patients and was associated with a higher proportion of patients with TNM stage I (p = 0.027) and fewer patients with persistent disease (p = 0.014) in comparison with the PTC-only group. Analysis of the data based on age (<45 or >45 years) revealed that in the older group, the presence of CLT was associated with fewer patients with persistent disease (p = 0.03) and capsular invasion (p = 0.05). However, in patients <45 years of age, the presence of CLT was associated with more capsular invasion (p = 0.003) and extrathyroidal extension (p = 0.004) compared with the PTC-only group. CONCLUSIONS: CLT in patients with PTC was associated with lower-stage disease and less disease persistence in patients >45 years of age. In patients <45 years, the presence of CLT appeared to be associated with unfavorable pathological features.

Unexpected discrepancies in hospital administrative databases can impact the accuracy of monitoring thyroid surgery outcomes in France.

OBJECTIVE: To determine the validity of hospital administrative databases compared to prospective collection of medical data assessing thyroid surgery complications. BACKGROUND: Administrative data are increasingly used to track surgical outcomes. METHODS: All patients undergoing thyroid surgery at three French university hospitals between April 2008 and April 2009 were prospectively included. Using diagnosis and procedural codes from hospital administrative database, we designed three indicators for measuring complications of thyroid surgery: recurrent laryngeal nerve palsy, postoperative hypoparathyroidism, and postoperative hemorrhage. Gold standard was obtained from a prospective collection of medical data after systematically screening each patient for the above-mentioned complications. Their ability to monitor surgical outcomes over time within individual hospitals was estimated using control charts. Spatial comparison between hospitals was performed by funnel plots. RESULTS: A total of 1909 patients were included. Complication rates extracted from administrative data were significantly lower compared to medical data (nerve palsy 2.4% vs. 6.7%, hypoparathyroidism 10.6% vs. 22.3%, p<0.0001). Indicator sensitivity was 30.4% for nerve palsy, 45.4% for hypoparathyroidism and 71.4% for postoperative hemorrhage. Corresponding positive predictive values were 84.4%, 95.1% and 68.2%. In two of the three hospitals, administrative data were not able to track temporal variations in complications rates. Regarding inter-hospital comparisons, 2 out of 3 hospitals were considered outliers according to administrative data despite having an average performance based on medical data. CONCLUSIONS: The ability of indicators extracted from administrative databases to measure thyroid surgery outcomes depends on the quality of underlying data coding. Validation in every center should be a prerequisite before implementing such metrics for tracking performance.

Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.

BACKGROUND: The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2. METHODS: Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters. RESULTS: A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann-Whitney test). CONCLUSIONS: These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.

Selective strategy for intensive monitoring after pheochromocytoma resection.

BACKGROUND: Guidelines recommend 24-48 hours of intensive monitoring after resection of pheochromocytoma. However, many patients do not require it. The objective of this study is to identify preoperative risk factors associated with postoperative hemodynamic instability (HDI) so as to select patients who may not require intensive postoperative monitoring. METHODS: Medical records of patients undergoing pheochromocytoma resection over a 12-year period were reviewed. Postoperative HDI was defined as systolic blood pressure of >200 or <90, heart rate >110 or <50 or needing active resuscitation. RESULTS: We included 41 patients; 49% had postoperative HDI but only 34% had HDI > 6 hours. Risk factors for HDI were preoperative mean arterial pressure (MAP) > 100 mm Hg (14% vs 45%), norepinephrine/normetanephrine levels >3x normal (44 vs 82%), and resection of another solid organ (0 vs 20%). Avoidance of planned postoperative monitoring for low-risk patients would have reduced estimated costs by 34%. CONCLUSION: Fewer than one-half of patients undergoing resection for pheochromocytoma benefit from intensive monitoring. High preoperative MAP, high norepinephrine/normetanephrine levels, and concomitant resection of another organ are risk factors for postoperative HDI. After a 6-hour interval of postoperative stability, selective rather than routine use of intensive monitoring may be an efficient strategy for monitoring lower risk patients.

Correction: Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

[This corrects the article DOI: 10.1371/journal.pone.0149723.].