Phosphoprotein-based biomarkers as predictors for cancer therapy.

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.

Using telemedicine on an acute care surgery service: improving clinic efficiency and access to care.

BACKGROUND: Telemedicine has been shown to improve patient access to medical care while potentially improving overall healthcare efficiency. It has not been consistently explored on an acute care surgery service as a method of increasing clinic availability and efficiency within a safety-net hospital system. Socioeconomic hardships associated with an in-person clinic visit can deter patients with limited resources. A virtual clinic for post-operative laparoscopic cholecystectomy patients was developed. We hypothesized that a virtual follow-up increases clinic efficiency and availability for new patients without compromising patient safety. METHODS: A retrospective review of patient and clinic outcomes before and after implementing virtual post-op visits for uncomplicated laparoscopic cholecystectomy patients on an acute care surgery service was performed. Providers called post-operative patients using a standardized questionnaire. Data included outpatient clinic composition (new vs. post-operative patients), elective operations scheduled, emergency department visits, and loss to follow-up rates. RESULTS: February to March 2017 was the baseline pre-intervention period, while February to March 2019 was post-intervention. Pre-intervention clinics consisted of 17% new and 50% post-op visits, in comparison to 31% new and 27% post-op visits in the post-intervention group (p < 0.01). Elective operations scheduled increased slightly from 8.4 to 11.5 per 100 patient visits, but was not statistically significant (p = 0.09). There was no change in the number of post-operative patients returning to the emergency department (p = 0.91) or loss to follow-up (p = 0.30) rates. CONCLUSIONS: Through the implementation of virtual post-operative visits for laparoscopic cholecystectomy patients, clinic efficiency improved by increasing new patient encounters, decreasing post-operative volume, and trending towards increased operations scheduled. This change did not compromise patient safety. Further implementation of telemedicine on an acute care surgery service is a promising method to expand services offered to an at-risk population and increase efficiency in a resource-limited environment.

Access to Paid Parental Leave for Academic Surgeons.

BACKGROUND: Parental leave is linked to health benefits for both child and parent. It is unclear whether surgeons at academic centers have access to paid parental leave. The aim of this study was to determine parental leave policies at the top academic medical centers in the United States to identify trends among institutions. METHODS: The top academic medical centers were identified (US News & World Report 2016). Institutional websites were reviewed, or human resource departments were contacted to determine parental leave policies. "Paid leave" was defined as leave without the mandated use of personal time off. Institutions were categorized based on geographical region, funding, and ranking to determine trends regarding availability and duration of paid parental leave. RESULTS: Among the top 91 ranked medical schools, 48 (53%) offer paid parental leave. Availability of a paid leave policy differed based on private versus public institutions (70% versus 38%, P < 0.01) and on medical center ranking (top third = 77%; middle third = 53%; and bottom third = 29%; P < 0.01) but not based on region (P = 0.06). Private institutions were more likely to offer longer paid leaves (>6 wk) than public institutions (67% versus 33%; P = 0.02). No difference in paid leave duration was noted based on region (P = 0.60) or rank (P = 0.81). CONCLUSIONS: Approximately, 50% of top academic medical centers offer paid parental leave. Private institutions are more likely to offer paid leave and leave of longer duration. There is considerable variability in access to paid parenteral leave for academic surgeons.

Rapid Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation (RAI) in Patients with Hyperthyroidism.

BACKGROUND: Time to hormonal control after definitive management of hyperthyroidism is unknown but may influence patient and physician decision making when choosing between treatment options. The hypothesis is that the euthyroid state is achieved faster after thyroidectomy than RAI ablation. METHODS: A retrospective review of all patients undergoing definitive therapy for hyperthyroidism was performed. Outcomes after thyroidectomy were compared to RAI. RESULTS: Over 3 years, 217 patients underwent definitive therapy for hyperthyroidism at a county hospital: 121 patients received RAI, and 96 patients underwent thyroidectomy. Age was equivalent (p = 0.72). More males underwent RAI (25% vs 15%, p = 0.05). Endocrinologists referred for both treatments equally (p = 0.82). Both treatments were offered after a minimum 1-year trial of medical management (p = 0.15). RAI patients mostly had Graves (93%), versus 73% of thyroidectomy patients (p < 0.001). Thyroidectomy patients more frequently had eye symptoms (35% vs 13%, p < 0.001), compressive symptoms (74% vs 15%, p < 0.001), or were pregnant/nursing (14% vs 0, p < 0.001). While the thyroidectomy patients had a documented discussion of all treatment modalities, 79% of RAI patients did not have a documented discussion regarding the option of surgical management (p < 0.001). Both treatment groups achieved an euthyroid state (71% vs 65%, p = 0.39). Thyroidectomy patients became euthyroid faster [3 months (2-7 months) versus 9 months (4-14 months); p < 0.001]. CONCLUSIONS: Thyroidectomy for hyperthyroidism renders a patient to an euthyroid state faster than RAI. This finding may be important for patients and clinicians considering definitive options for hyperthyroidism.

Antiplatelet and Anticoagulant Medications Significantly Increase the Risk of Postoperative Hematoma: Review of over 4500 Thyroid and Parathyroid Procedures.

PURPOSE: Antiplatelet and/or anticoagulant medication use is common. Abstinence a week before surgery may still result in altered hemostasis. The study aim was to report on perioperative antiplatelet and anticoagulant use in thyroidectomy and parathyroidectomy patients, and to determine the association with postoperative hematoma (POH) rates. METHODS: Retrospective review of a prospective endocrine surgery database was performed. Procedure extent was defined as unilateral, bilateral, or extensive. Antiplatelets were categorized as none, 325 mg aspirin (ASA), <325 mg ASA, clopidogrel, or other. Anticoagulants were categorized as none, oral, or injectable. RESULTS: A total of 4514 patients were identified. POH developed in 22 patients (0.5 %). Rates were similar between age, gender, and reoperative status. POH were seven times more common after thyroidectomy (0.8 vs. 0.1 %, p < 0.01). Unilateral procedures had lower POH rates than bilateral or extensive (0.1 vs. 0.9 vs. 0.8 %, p < 0.01). POH rates in patients receiving 325 mg ASA (0.8 %) or clopidogrel (2.2 %) were much higher than patients not receiving antiplatelets (0.5 %) or receiving <325 mg ASA (0.1 %, p = 0.04). Oral anticoagulants (2.2 %) and injectable anticoagulants (10.7 %) had much higher POH rates than patients not receiving anticoagulants (0.4 %, p < 0.01). Target organ, patient gender, procedure extent, antiplatelet use, and anticoagulant use were included on logistic regression to determine association with POH. Bilateral procedures, thyroidectomy, clopidogrel, oral, and injectable anticoagulants were all independently associated with POH. CONCLUSIONS: POH occur more frequently after thyroidectomy and during bilateral procedures. Patients requiring clopidogrel or any anticoagulant coverage are at much higher risk for POH. These higher-risk patients should be considered for observation to ensure prompt POH recognition and intervention.

Contralateral adrenal abnormalities in Conn's syndrome.

BACKGROUND: During the course of evaluation for primary hyperaldosteronism, cross-sectional imaging is obtained in efforts to identify patients with an aldosterone producing adenoma (APA). A subset of these patients will have a synchronous, contralateral adrenal abnormality. Adrenal vein sampling (AVS) further guides clinical decision making by identifying unilateral (APA) versus bilateral hypersecretion. In the subset of patients with contralateral adrenal abnormalities, it is unclear how this affects the durability of an adrenalectomy for APA. This study characterizes this group of patients to assess the efficacy of surgical intervention. METHODS: A retrospective review of patients undergoing adrenalectomy for APA based on AVS at a university practice. Preoperative and postoperative patient characteristics, laboratory evaluations, imaging results, and final pathology were noted. RESULTS: From 2000 to 2011, 103 patients with APA underwent unilateral adrenalectomy. Eighteen patients (17%) had discordant results between AVS and imaging. Most of these patients were male (78%), and the mean age was 57 ± 13 y. Median duration of follow-up was 3.5 y [1 y, 6 y]. All patients with initial hypokalemia were rendered normokalemic after the operation. Four patients increased their antihypertensive regimen during the follow-up period. These patients all had nodular hyperplasia on final pathology. CONCLUSIONS: In patients with bilateral adrenal abnormalities who have undergone unilateral adrenalectomy for primary hyperaldosteronism, patients with clear APAs on final pathology appear to have durable outcomes after resection. Conversely, nodular hyperplasia on final pathology may be a risk factor for ongoing aldosterone hypersecretion. An algorithm for biochemical surveillance in this subset of patients should be considered.

Early endocrine attending surgeon presence increases operating room efficiency.

BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR ≤10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR ≤10 min before attending arrival, and 99 patients were >10 min (3 ± 3 min versus 35 ± 14 min, P < 0.01). The ≤10 min procedures started sooner after patient arrival in OR (40 ± 11 versus 63 ± 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10 min groups, saving $2416 ± 477 and $1458 ± 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in ≤10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 ± 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.

All thyroid ultrasound evaluations are not equal: sonographers specialized in thyroid cancer correctly label clinical N0 disease in well differentiated thyroid cancer.

BACKGROUND: Ultrasound (US) is a standard preoperative study in thyroid cancer. Accurate identification of lymph node (LN) disease in the central neck by US is debated, leading some surgeons to perform prophylactic central dissection. The purpose of this study was to evaluate if US performed by a surgeon with specialization in thyroid sonography correctly determined clinical N0 status. METHODS: Retrospective identification of cN0 thyroid cancer patients from a prospectively maintained database was performed. Exclusion criteria included LN dissection with thyroidectomy or missing preoperative US. Demographics and outcomes were reviewed. Patients were categorized by who performed the thyroid US (surgeon vs. non-surgeon). Additional radioactive iodine (RAI) treatments or subsequent positive pathology defined recurrence. RESULTS: From 2005 to 2012, 177 patients met criteria. Forty-eight patients had surgeon US versus 129 patients with non-surgeon US. Groups were equivalent in age, gender, and tumor size. Forty-six percent had a preoperative diagnosis of cancer, whereas 19 % had benign and 35 % had indeterminate diagnoses. Surgeon US documented LN status more frequently (69 vs. 20 %, p < 0.01). RAI treatment and dose were equivalent. RAI uptake was lower with surgeon US (0.06 % ± 0.02 vs. 0.20 % ± 0.03, p < 0.01). Recurrence rates were higher in non-surgeon US (12 vs. 0 %, p = 0.01). Median time to recurrence was 11 months. CONCLUSIONS: Surgeons with thyroid US expertise correctly identify patients as N0, which may eliminate the need for prophylactic LN dissection without increasing risk of early recurrence. Because not all thyroid cancers are diagnosed preoperatively, US examination of the thyroid should include routine evaluation of the cervical LNs.

Justified follow-up: a final intraoperative parathyroid hormone (ioPTH) Over 40 pg/mL is associated with an increased risk of persistence and recurrence in primary hyperparathyroidism.

INTRODUCTION: After parathyroidectomy for sporadic primary hyperparathyroidism (PHPT), overall rates of persistence/recurrence are extremely low. A marker of increased risk for persistence/recurrence is needed. We hypothesized that final intraoperative parathyroid hormone (FioPTH) ≥40 pg/mL is indicative of increased risk for disease persistence/recurrence, and can be used to selectively determine the degree of follow-up. METHOD: A retrospective review of PHPT patients undergoing parathyroidectomy with ioPTH monitoring was performed. An ioPTH decline of 50 % was the only criteria for operation termination. Patients were grouped based on FioPTH of <40, 40-59, and >60 pg/mL. RESULTS: Between 2001 and 2012, 1,371 patients were included. Mean age was 61 ± 0.4 years, and 78°% were female. Overall persistence rate was 1.4°%, with a 2.9°% recurrence rate. Overall, 976 (71°%) patients had FioPTH < 40, 228 (16.6°%) had FioPTH 40-59, and 167 (12.2°%) had FioPTH ≥60. Mean follow-up was 21 ± 0.6 months. Patients with FioPTH <40 were younger, with lower preoperative serum calcium, PTH, and creatinine (all p ≤ 0.001). Patients with FioPTH <40 had the lowest persistence rate (0.2 %) versus patients with FioPTH 40-59 (3.5 %) or FioPTH ≥60 (5.4 %; p < 0.001). Recurrence rate was also lowest in patients with FioPTH <40 (1.3 vs. 5.9 vs. 8.2 %, respectively; p < 0.001). Disease-free status was greatest in patients with FioPTH <40 at 2 years (98.5 vs. 96.8 vs. 90.5 %, respectively) and 5 years (95.7 vs. 72.3 vs. 74.8 %, respectively; p < 0.01). CONCLUSIONS: Patients with FioPTH < 40 pg/mL had lower rates of persistence and recurrence, than patients with FioPTH 40-59, or ≥60. Differences became more apparent after 2 years of follow-up. Patients with FioPTH ≥40 pg/mL warrant close and prolonged follow-up.

Preventing postoperative hypocalcemia in patients with Graves disease: a prospective study.

BACKGROUND: Hypocalcemia occurs after total thyroidectomy (TT) for Graves disease via parathyroid injury and/or from increased bone turnover. Current management is to supplement calcium after surgery. This study evaluates the impact of preoperative calcium supplementation on hypocalcemia after Graves TT. METHODS: A prospective study of patients with Graves disease undergoing TT was performed. Patients with Graves disease managed over a 9-month period took 1 g of calcium carbonate (CC) three times a day for 2 weeks before TT. Those managed the previous year without supplementation served as historic controls. Age-, gender-, and thyroid weight-matched, non-Graves TT patients were procedure controls. Patient demographics, postoperative laboratory values, complaints, and medications were reviewed. Parathyroid hormone (PTH)-based postoperative protocols dictated postoperative CC and calcitriol use. RESULTS: Forty-five patients with Graves disease were treated with CC before TT, and 38 patients with Graves disease were not. Forty control subjects without Graves disease were identified. Age, gender, and thyroid weight were comparable. Preoperative calcium and PTH levels were equivalent. PTH values immediately after surgery, at postoperative day 1, and at 2-week follow-up were equivalent. Postoperative use of scheduled CC (p = 0.10) and calcitriol (p = 0.60) was similar. Postoperatively, patients with untreated Graves disease had lower serum calcium levels than pretreated patients with Graves disease or control subjects without Graves disease (8.3 mg/dL vs. 8.6 vs. 8.6, p = 0.05). Complaints of numbness and tingling were more common in nontreated Graves disease (26%) than in pretreated Graves disease (9%) or in control subjects without Graves disease (10%, p < 0.05). CONCLUSIONS: Calcium supplementation before TT for Graves disease significantly reduced biochemical and symptomatic postoperative hypocalcemia. Preoperative calcium supplementation is a simple treatment that can reduce symptoms of hypocalcemia after Graves TT.

Outcomes after subtotal parathyroidectomy for primary hyperparathyroidism due to hyperplasia: significance of whole vs. partial gland remnant.

INTRODUCTION: Primary hyperparathyroidism (PHPT) due to multigland hyperplasia is managed by subtotal parathyroidectomy (sPTX), with a partial gland left in situ. However, smaller, hyperplastic glands may be encountered intraoperatively, and it is unclear if leaving an intact gland is an equivalent alternative. This study evaluates the rates of permanent hypoparathyroidism and cure of PHPT patients with four-gland hyperplasia that were left with either a whole gland remnant (WGR) or a partial gland remnant (PGR) after sPTX. METHODS: We reviewed the outcomes of PHPT patients with hyperplasia who underwent sPTX at an academic institution. Surgeon intraoperative judgment determined remnant size (a WGR vs. a PGR). RESULTS: Between 2002 and 2013, 172 patients underwent sPTX for PHPT. There were 108 patients (62.8%) who had a WGR. Another 64 patients (37.2%) had a PGR. Mean age was 60 ± 14 years. There were 82.6% female patients. Cases with positive family history for PHPT were more likely to have a PGR (12.5 vs. 3.7%; p = 0.03). Patients had similar preoperative and postoperative laboratories. Individuals with a PGR tended to have larger glands encountered by surgeons intraoperatively (525 ± 1,308 vs. 280 ± 341 mg; p = 0.02). One patient with a WGR developed permanent hypocalcemia. Overall, the cure rate was 97.1%. A mean of 29 ± 28.7 months follow-up revealed a recurrence rate of 5.2%. Disease persistence and recurrence rates were similar in patients. CONCLUSION: PHPT due to hyperplasia is managed by sPTX, leaving WGR without increased rates of disease persistence/recurrence. Patients without family history for hyperparathyroidism and those with smaller glands may be the best candidates for this approach.

Preoperative impairment is associated with a higher postdischarge level of care.

BACKGROUND: Although preoperative risk factors have been shown to lead to postdischarge institutionalization, an association between preoperative risk factors, preoperative level of required care, and discharge to higher levels of care has not previously been demonstrated. MATERIALS AND METHODS: Using an institutional American College of Surgeons National Surgical Quality Improvement Program database, a retrospective review of elderly patients undergoing nonemergent inpatient general surgery procedures was performed with the goal of identifying preoperative risk factors that indicated the need for a higher level of care on hospital discharge. Univariate and multivariate analyses were performed on the patient population. RESULTS: Over a 4-y period, 585 patients (29%) within the database were aged ≥65 y. In this population, 12% of patients required discharge to a higher level of care compared with their preoperative origin. In patients aged ≥65 y, impaired cognition, decreased functional capacity, advanced age (≥79 y), high American Society of Anesthesiologists class, and long hospital length of stay were found in univariate analysis to be associated with postoperative discharge to a higher level of care, although all of these variables except decreased functional capacity were also associated with a higher discharge level of care in multivariate analysis. CONCLUSIONS: Cognitive and functional capacity scoring can be used as simple ways to indicate discharge to a higher level of care for older adults. Preoperative counseling in high-risk older adults needs to include the likelihood for discharge to a higher level of care, so that a possible referral to social work can be placed during discharge planning.

Kidney Disease Improving Global Outcomes guidelines and parathyroidectomy for renal hyperparathyroidism.

BACKGROUND: Patients with end-stage renal disease develop hypocalcemia, resulting in secondary hyperparathyroidism (SHPT). No clear criterions exist to aid in surgical decision making for SHPT. The 2009 Kidney Disease Improving Global Outcomes (KDIGO) guidelines provide target ranges for serum calcium, phosphate, and parathyroid hormone (PTH) levels in patients with end-stage renal disease. Parathyroidectomy can help achieve these targets. The study purpose was to examine how parathyroidectomy for SHPT impacts KDIGO targets during immediate and long-term follow-up and to evaluate KDIGO categorization with receipt of additional surgical intervention. METHODS: A retrospective review of a prospective parathyroidectomy database was performed. Included patients had SHPT, were on dialysis, and underwent parathyroidectomy. Calcium, phosphate, and PTH values were classified as below, within, or above KDIGO targets. RESULTS: Between 2000 and 2013, 36 patients with SHPT met criteria. Subtotal parathyroidectomy was performed in 89%, total parathyroidectomy in 11%. Follow-up time was 54 ± 7 mo. Eight patients (22%) required additional surgery. Twenty-eight patients (76%) were alive at the last follow-up. At the last-follow up, patients had phosphate (46%), and PTH (17%) above KDIGO ranges. Factors associated with reoperation were assessed. Patient PTH within or above target immediately postoperative had a higher rate of reoperation (P < 0.01). At the last follow-up, higher phosphate (P = 0.054) and PTH (P < 0.001) were associated with higher reoperation rates, but calcium (P = 0.33) was not. CONCLUSIONS: PTH and phosphate levels above KDIGO indices were associated with additional surgical intervention. Many patients had laboratory indices above range at the last follow up, suggesting more patients had persistent or recurrent disease than those who underwent reoperation. Patients may benefit from more aggressive medical and/or surgical management.

Surgeon and staff radiation exposure during radioguided parathyroidectomy at a high-volume institution.

INTRODUCTION: Radioguided parathyroidectomy (RGP) uses technetium-99 m sestamibi causing gamma ray emission during RGP to aid dissection and confirm parathyroid excision. Source (the patient) proximity and exposure duration determine degree of exposure. The purpose of this study was to quantify surgeon and staff radiation exposure during RGP. METHODS: Surgeons and assistants wore radiation dosimeters during RGP procedures at a high-volume endocrine surgery practice. Area dosimeters measured personnel potential exposure. Data were prospectively collected. Provider exposures were corrected for both duration of exposure and case volume. Institutional safety requirements uses 100 mrem/year as an indicator for radiation safety training, 500 mrem/year for personal monitoring, and a maximum allowed exposure of 4,500 mrem/year. RESULTS: A total of 120 RGP were performed over 6 months. Badges were worn in 82 cases (68 %). Three faculty and four assistants were included. Primary hyperparathyroidism was the diagnosis for 95 %. Median case volume per provider was 13 cases (range 6-45), with median exposure of 18 h (range 9-70). Mean provider deep dose exposure (DDE) was 22 ± 10 mrem. Corrected for exposure duration, mean DDE was 0.6 ± 0.2 mrem/h. Corrected for case volume, mean DDE was 0.8 ± 0.2 mrem/case. Anesthesia exposure was minimal, while mayo stand exposure was half to two thirds that of the surgeon and assistant. Based on institutional guidelines and above data, 125 RGP/year warrants safety training, 625 RGP/year warrants monitoring, whereas >5,600 RGP/year may result in maximum allowed radiation exposure to the surgeon. CONCLUSIONS: Surgeon and staff radiation exposure during RGP is minimal. However, high-volume centers warrant safety training.

Radioactive iodine remnant uptake after completion thyroidectomy: not such a complete cancer operation.

BACKGROUND: Given limitations in preoperative diagnostics, thyroid lobectomy followed by completion thyroidectomy (CT) for differentiated thyroid cancer (DTC) may be required. It is unclear whether resection quality by CT differs from that by total thyroidectomy (TT). Additional surgeon or patient factors may also influence the "completeness" of resection. This study evaluated how CT and surgeon volume influence the adequacy of resection as measured by radioactive iodine (RAI) remnant uptake. METHODS: A retrospective review of a prospectively collected thyroid database was queried for patients treated for DTC with TT or CT followed by RAI ablation. CT patients were matched 1:2 by age, sex, and tumor size to TT patients. Surgeon volume, time to completion, and continuity of surgeon care were reviewed. RESULTS: Over 18 years, 45 patients with DTC had CT and RAI. Mean age was 48 ± 2 years, and 76 % were female, with a tumor size of 2.7 ± 0.3 cm. CT had higher remnant uptake than TT (0.07 vs. 0.04 %; p = 0.04). CT performed by a high-volume surgeon had much lower remnant uptakes (0.06 vs. 0.22 %; p = 0.04). Remnant uptake followed a stepwise decrease with involvement of a high-volume surgeon for part or all of the surgical management (p = 0.11). Multiple regression analysis found CT (p = 0.02) and surgeon volume (p = 0.04) to significantly influence uptake after controlling for other factors. CONCLUSIONS: Single-stage TT provides a better resection based on smaller thyroid remnant uptakes than CT for patients with thyroid cancer. If a staged operation for cancer is necessary, surgeon volume may affect the completeness of resection.

Identifying predictors of a difficult thyroidectomy.

BACKGROUND: A Thyroidectomy Difficulty Scale (TDS) was previously developed that identified more difficult operations, which correlated with longer operative times and higher complication rates. The purpose of this study was to identify preoperative variables predictive of a more difficult thyroidectomy using the TDS. METHODS: A four item, 20-point TDS, was used to score the difficulty of thyroid operations. Patient and disease factors were recorded for each patient. Difficult thyroidectomy and non-difficult thyroidectomy (NDT) patients were compared. A final multivariate logistic regression model was constructed with significant (P<0.05) variables from a univariate analysis. RESULTS: A total of 189 patients were scored using TDS. Of them, 69 (36.5%) suffered from hyperthyroidism, 42 (22.2%) from Hashimotos, 34 (18.0%) from thyroid cancer, and 36 (19.0%) from multinodular goiter. Among hyperthyroid patients, the DT group had a greater number preoperatively treated with Lugols potassium iodide (81.6% DT versus 58.1% NDT, P=0.032), presence of ophthalmopathy (31.6% DT versus 9.7% NDT, P=0.028), and presence of (>4 IU/mL) antithyroglobulin antibodies (34.2% DT versus 12.9% NDT, P=0.05). Using multivariate analysis, hyperthyroidism (odds ratio [OR], 4.35, 95% confidence interval [CI], 1.23-15.36, P=0.02), presence of antithyroglobulin antibody (OR, 3.51, 95% CI, 1.28-9.66, P=0.015), and high (>150 ng/mL) thyroglobulin (OR, 2.61, 95% CI, 1.06-6.42, P=0.037) were independently associated with DT. CONCLUSIONS: Using TDS, we demonstrated that a diagnosis of hyperthyroidism, preoperative elevation of serum thyroglobulin, and antithyroglobulin antibodies are associated with DT. This tool can assist surgeons in counseling patients regarding personalized operative risk and improve OR scheduling.

Primary hyperparathyroidism across the ages: presentation and outcomes.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a disease process traditionally thought to present during middle age, but can occur at any age. The purpose of this study was to compare PHPT patient characteristics based on patient age at the time of surgical referral. METHODS: A retrospective review of a prospectively managed database of adult patients undergoing parathyroid surgery for PHPT was conducted. Patients with a negative family history, no previous parathyroid surgery, and ≥6-mo follow-up were included. Patients were grouped by age for comparison. RESULTS: From 2001-2012, 1372 patients met inclusion criteria. Age groups were as follows: ≤50 y, 51-60 y, 61-70 y, and >70 y. Female predominance increased with age (P>0.01). Baseline serum parathyroid hormone levels were higher at the extremes of age (P<0.001). Young patients had the highest serum calcium (P<0.01), urinary calcium (P<0.001), and T-score (P<0.001) measures, and greater incidence of vitamin D deficiency (P=0.03). The use of local anesthesia increased with age, whereas use of outpatient parathyroidectomy decreased with age (both P<0.01). Rates of disease persistence (2.3%-2.9%, P=0.95) and recurrence (2.1%-3.3%, P=0.75) were low, and did not differ. CONCLUSIONS: Patients at the extremes of age are referred with more elevated laboratory indices whereas those in the traditional age range have milder biochemical indices. This may result from differential surgical referral. Individuals with laboratory evidence of abnormal calcium and parathyroid hormone regulation should be evaluated for parathyroidectomy regardless of age because all ages can be successfully treated.

Markedly elevated thyroglobulin levels in the preoperative thyroidectomy patient correlates with metastatic burden.

BACKGROUND: Thyroglobulin (Tg) is a marker of tumor recurrence during thyroid cancer follow-up. While helpful in the postoperative setting, the clinical significance of preoperative Tg measurements remains unclear. The aim of the study was to determine if preoperative Tg levels are indicative of underlying malignancy or burden of metastatic disease. METHODS: A retrospective review of a prospectively collected database at an academic medical center of all thyroidectomy patients with a measured preoperative Tg level was conducted. Patients were grouped by Tg level into quartiles for initial univariate analysis, followed by multivariable analysis of variance. RESULTS: Between 2007 and 2012, 611 patients met criteria. Quartile breakdown was as follows: ≤19 ng/mL, 19.1-54 ng/mL, 54.1-151 ng/mL, and >151 ng/mL. Patients' age and gender were equivalent. Hashimoto's thyroiditis was most common in the lowest Tg group (24% versus 11%-12%, P < 0.01). While cancer was more common in the low Tg, metastatic disease was most common in the high Tg group. Specimen weight increased with increasing Tg levels (P < 0.01). Body mass index, gland weight, cancer, and Hashimoto's and metastatic disease were entered into a multivariable analysis. Only gland weight and metastatic disease correlated with Tg levels (both P < 0.001). All patients with Tg > 5000 ng/mL had metastatic disease (n = 6). CONCLUSIONS: Although preoperative Tg levels are not associated with a diagnosis of cancer, they are associated with the presence of metastatic disease. All patients with a Tg > 5000 ng/mL had significant disease burden. In patients with concern for metastatic disease, preoperative serum Tg may be a useful marker to aid decision making.

Novel thyroidectomy difficulty scale correlates with operative times.

BACKGROUND: The aim of this study was to evaluate a new thyroidectomy difficulty scale (TDS) for its inter-rater agreement, correspondence with operative times, and correlation with complications. METHODS: We developed a four item, 20-point TDS. Following cases where two board-certified surgeons participated, each surgeon completed a TDS, blinded to the other's responses. Paired sets of TDS scores were compared. The relationship between operative time and TDS scores was analyzed with linear regression. Multiple regression evaluated the association of TDS scores and other clinical data with operative times. RESULTS: A total of 119 patients were scored using TDS. In this cohort, 22.7% suffered from hyperthyroidism, 37.8% experienced compressive symptoms, and 58.8% had cancer. The median total TDS score was 8, and both surgeons' total scores exhibited a high degree of correlation. Overall, 87.4% of the two raters' total scores were within one point of each other. Patients with hyperthyroidism received higher median scores than euthyroid patients (10 vs. 8, p < 0.01). Similarly, patients who suffered a complication had higher scores than those without complications (10 vs. 8, p = 0.04). TDS scores demonstrated a linear relation with operative times (R2 = 0.36, p < 0.01). Cases with a score of ≥14 took 41.0% longer compared to cases with scores of ≤5 (p < 0.01). In the multiple regression analysis, TDS scores independently predicted the operative time (p < 0.01). CONCLUSION: The TDS is an accurate tool whose scores correlate with more difficult thyroidectomies as measured by complications and operative times.

Presentation, management, and outcomes of hyperparathyroidism in octogenarians and nonagenarians.

BACKGROUND: Various elective surgical procedures are routinely performed on patients ≥80 years of age. With primary hyperparathyroidism (PHPT), surgical management is the only treatment. The goal of this study was to compare presentation and outcome of patients ≥80 to that of those <80 years of age. METHODS: Retrospective review of a prospectively collected database of all parathyroidectomies for PHPT performed at a university hospital. Patients ≥80 years at the time of surgery compared with patients <80 years. RESULTS: Over 13 years, 1,826 patients underwent parathyroidectomy for PHPT. A total of 154 patients were ≥80 years at the time of surgery (8.4 %), ranging from 80 to 91 years. Patients ≥80 years had higher serum PTH, creatinine and vitamin D levels and lower T scores. Calcium levels were similar. Patients ≥80 years had a greater history of hypertension, coronary artery disease, congestive heart failure, and stroke. Psychiatric disease was less common. Patients ≥80 years had the procedure under local anesthesia only more often. Use of a unilateral approach was equivalent. Rates of adenoma, double adenoma, and hyperplasia were comparable. Patients ≥80 years were observed overnight more frequently. Stays >24 h and disease recurrence and persistence, as well as morbidity rates, were all equivalent. CONCLUSION: Disease presentation of PHPT in patients ≥80 is similar to <80. Despite increased comorbidities, parathyroidectomy is a safe procedure in this patient population with a noted equivalent complication rate to younger patients. Operative management remains the only treatment. Patient age should not be a deterrent to offer curative surgical intervention.