Linda Youngwirth

In Patients with Thyroid Cancer of Follicular Cell Origin, a Family History of Nonmedullary Thyroid Cancer in One First-Degree Relative Is Associated with More Aggressive Disease

BACKGROUND About 5% of nonmedullary thyroid cancers (NMTCs) are familial. Most patients with a family history of thyroid cancer do not meet the definition of familial NMTC (FNMTC; two or more affected family members). The aim of this study was to determine whether patients with a family history of NMTC, but who do not meet the definition of FNMTC, have more aggressive disease. METHODS A database of 1502 thyroidectomies was reviewed and 358 patients with NMTC who did not have a family history of benign thyroid disease and who underwent thyroidectomy from January 1994 to December 2008 were identified. These included 324 (90%) patients with papillary thyroid carcinoma (PTC), 24 (7%) with follicular thyroid cancer, and 10 (3%) with anaplastic or Hürthle cell carcinoma. Among them, those with and without a family history of NMTC in first-degree relatives were compared. Then patients with only one affected family member were compared with FNMTC patients. RESULTS Thirty-seven (10%) patients had a family history of thyroid cancer, all to of which had PTC. Patients with a family history of NMTC had a similar tumor size than those without (2±0 vs. 2.1±0 cm, p=0.72) but they were significantly younger (43±3 vs. 49±1 years, p=0.04), and more likely to have multicentricity (48% vs. 22%, p=0.01), malignant lymph nodes (22% vs. 11%, p=0.02), and local invasion to surrounding tissues (5.4% vs. 0.6%, p=0.007). They also had a higher recurrence rate (24% vs. 12%, p=0.03) than patients without a family history. Interestingly, patients with only one affected family member were similar to FNMTC patients with respect to age (44±4 vs. 40±3 years, p=0.4), tumor size (2±0 vs. 1.9±0 cm, p=0.65), rate of multicentricity (44% vs. 52%, p=0.57), malignant lymph nodes (22% vs. 21%, p=0.93), local invasiveness (5.5% vs. 11%, p=0.59), and disease recurrence (28% vs. 21%, p=0.56). CONCLUSION Patients with NMTC having a family history of thyroid cancer have more aggressive disease, regardless of whether they meet the current definition of FNMTC regarding number of affected family members. Therefore, any positive family history should be considered a risk factor for more aggressive thyroid carcinoma.

Is There a Minimum Number of Thyroidectomies a Surgeon Should Perform to Optimize Patient Outcomes

Objective: To determine the number of total thyroidectomies per surgeon per year associated with the lowest risk of complications. Background: The surgeon volume–outcome association has been established for thyroidectomy; however, a threshold number of cases defining a “high-volume” surgeon remains unclear. Methods: Adults undergoing total thyroidectomy were identified from the Health Care Utilization Project-National Inpatient Sample (1998–2009). Multivariate logistic regression with restricted cubic splines was utilized to examine the association between the number of annual total thyroidectomies per surgeon and risk of complications. Results: Among 16,954 patients undergoing total thyroidectomy, 47% had thyroid cancer and 53% benign disease. Median annual surgeon volume was 7 cases; 51% of surgeons performed 1 case/y. Overall, 6% of the patients experienced complications. After adjustment, the likelihood of experiencing a complication decreased with increasing surgeon volume up to 26 cases/y (P < 0.01). Among all patients, 81% had surgery by low-volume surgeons (⩽25 cases/y). With adjustment, patients undergoing surgery by low-volume surgeons were more likely to experience complications (odds ratio 1.51, P = 0.002) and longer hospital stays (+12%, P = 0.006). Patients had an 87% increase in the odds of having a complication if the surgeon performed 1 case/y, 68% for 2 to 5 cases/y, 42% for 6 to 10 cases/y, 22% for 11 to 15 cases/y, 10% for 16 to 20 cases/y, and 3% for 21 to 25 cases/y. Conclusions: This is the first study to identify a surgeon volume threshold (>25 total thyroidectomies/y) that is associated with improved patient outcomes. Identifying a threshold number of cases defining a high-volume thyroid surgeon is important, as it has implications for quality improvement, criteria for referral and reimbursement, and surgical education.

Parathyroid Hormone Deficiency After Total Thyroidectomy: Incidence and Time

BACKGROUND Parathyroid hormone (PTH) deficiency or hypoparathyroidism after total thyroidectomy is not an uncommon postoperative complication. Patients who have PTH deficiency will develop profound hypocalcemia if not properly treated with oral calcium supplementation and activated vitamin D (1,25-dihydroxycholecalciferol or calcitriol). However, there is little published on the long-term outcomes of these patients. The aim of this study was to determine the incidence of PTH deficiency and the time course to resolution after total thyroidectomy. METHODS We identified 271 consecutive patients who underwent total thyroidectomy from January 2006 to December 2008. All patients had serum PTH levels tested 4 h after surgery and the morning after surgery. Patients were diagnosed with PTH deficiency if their serum PTH was <10 pg/mL. The outcomes of patients with PTH deficiency (group 1) were then compared with patients who did not have PTH deficiency (group 2). Patients in group 1 were evaluated for parathyroid function by measuring serum PTH levels as well as documenting usage of supplemental calcium and 1,25-dihydroxycholecalciferol. RESULTS Of the 271 patients, 33 (12%) were found to have PTH deficiency. In comparing PTH deficient patients (group 1) with patients in group 2, there were no differences in age, gender, thyroid pathology, the incidence of thyroiditis, or other factors that would predict hypoparathyroidism. Twenty-four patients (73%) had recovery of their PTH levels to > or =10 pg/mL at their 1 wk follow-up appointment, while 9 (27%) patients still had PTH levels <10 pg/mL. With long term follow-up, 27 (82%) patients had recovered with a PTH level of > or = 10 pg/mL, while 6 (18%) patients had a serum PTH level <10 pg/mL. However, three of the 33 patients in group 1 (9%) required long-term 1,25-dihydroxycholecalciferol, but only two of these patients had undetectable PTH levels. Thus, the overall rate of hypocalemia requiring 1,25-dihydroxycholecalciferol was <1% (two of 271 total patients). CONCLUSIONS We concluded that approximately 12% (33 of 271) of patients undergoing total thyroidectomy will develop PTH deficiency. Of the PTH deficient patients, 73% will return to normal parathyroid function within 1 wk of surgery. Furthermore, 82% of these PTH deficient patients will return to normal parathyroid function with long-term follow-up. Less than 1% (two of 271) of patients undergoing total thyroidectomy will require 1,25-dihydroxycholecalciferol for long-term hypocalcemia.

Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer

BACKGROUND Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. METHODS The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival. RESULTS In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer. CONCLUSION In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.

Tissue engineered vascular grafts: Origins, development, and current strategies for clinical application

Since the development of a dependable and durable synthetic non-autogenous vascular conduit in the mid-twentieth century, the field of vascular surgery has experienced tremendous growth. Concomitant with this growth, development in the field of bioengineering and the development of different tissue engineering techniques have expanded the armamentarium of the surgeon for treating a variety of complex cardiovascular diseases. The recent development of completely tissue engineered vascular conduits that can be implanted for clinical application is a particularly exciting development in this field. With the rapid advances in the field of tissue engineering, the great hope of the surgeon remains that this conduit will function like a true blood vessel with an intact endothelial layer, with the ability to respond to endogenous vasoactive compounds. Eventually, these engineered tissues may have the potential to supplant older organic but not truly biologic technologies, which are used currently.

Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: An analysis of 18 243 patients

Neoadjuvant therapy has theoretical benefits for pancreatic cancer; however, its association with perioperative outcomes remains controversial. This study sought to evaluate variation in use of neoadjuvant therapy and outcomes following pancreatic resection.

Defining a Hospital Volume Threshold for Minimally Invasive Pancreaticoduodenectomy in the United States

Importance There is increasing interest in expanding use of minimally invasive pancreaticoduodenectomy (MIPD). This procedure is complex, with data suggesting a significant association between hospital volume and outcomes. Objective To determine whether there is an MIPD hospital volume threshold for which patient outcomes could be optimized. Design, Setting, and Participants Adult patients undergoing MIPD were identified from the Healthcare Cost and Utilization Project National Inpatient Sample from 2000 to 2012. Multivariable models with restricted cubic splines were used to identify a hospital volume threshold by plotting annual hospital volume against the adjusted odds of postoperative complications. The current analysis was conducted on August 16, 2016. Main Outcomes and Measures Incidence of any complication. Results Of the 865 patients who underwent MIPD, 474 (55%) were male and the median patient age was 67 years (interquartile range, 59-74 years). Among the patients, 747 (86%) had cancer and 91 (11%) had benign conditions/pancreatitis. Overall, 410 patients (47%) had postoperative complications and 31 (4%) died in-hospital. After adjustment for demographic and clinical characteristics, increasing hospital volume was associated with reduced complications (overall association P < .001); the likelihood of experiencing a complication declined as hospital volume increased up to 22 cases per year (95% CI, 21-23). Median hospital volume was 6 cases per year (range, 1-60). Most patients (n = 717; 83%) underwent the procedure at low-volume (⩽22 cases per year) hospitals. After adjustment for patient mix, undergoing MIPD at low- vs high-volume hospitals was significantly associated with increased odds for postoperative complications (odds ratio, 1.74; 95% CI, 1.03-2.94; P = .04). Conclusions and Relevance Hospital volume is significantly associated with improved outcomes from MIPD, with a threshold of 22 cases per year. Most patients undergo MIPD at low-volume hospitals. Protocols outlining minimum procedural volume thresholds should be considered to facilitate safer dissemination of MIPD.

Radioactive Iodine Treatment Is Associated with Improved Survival for Patients with Hürthle Cell Carcinoma

BACKGROUND Hürthle cell carcinoma (HCC) is not typically iodine avid, raising questions regarding postoperative use of radioactive iodine (RAI). The aims of this study were to describe current practice patterns regarding the use of RAI for HCC and to assess its association with survival. METHODS The National Cancer Data Base 1998-2006 was queried for all patients with HCC who underwent total thyroidectomy. Inclusion was limited to T1 tumors with N1/M1 disease, and T2-4 tumors with any N/M disease. Patients were divided into two treatment groups based on receipt of RAI. Baseline patient characteristics were compared between the two groups. Survival was examined using Kaplan-Meier and Cox regression analyses. RESULTS A total of 1909 patients were included. Of these, 1162 (60.9%) received RAI, and 747 (39.1%) did not. Patients treated with RAI were younger (57 vs. 61 years for no RAI, p < 0.001), more often had private insurance (61.7% vs. 53.5% for no RAI, p < 0.003), and were more likely to be treated at an academic center (40.0% vs. 33.1% for no RAI, p < 0.001). Five- and 10-year survival rates were improved for patients who received RAI compared with those who did not (88.9 vs. 83.1% and 74.4 vs. 65.0%, respectively, p < 0.001). RAI administration was associated with a 30% reduction in mortality (hazard ratio = 0.703, p = 0.001). CONCLUSION Present guidelines are inconsistent with regard to indications for using RAI for HCC. This could explain why nearly 40% of HCC patients did not receive RAI. RAI is associated with improved survival, suggesting that it should be advocated for HCC patients with tumors >2 cm and those with nodal and distant metastatic disease.

Same thyroid cancer, different national practice guidelines: When discordant American Thyroid Association and National Comprehensive Cancer Network surgery recommendations are associated with compromised patient outcome.

BACKGROUND The American Thyroid Association (ATA) and National Comprehensive Cancer Network (NCCN) guidelines have discordant recommendations for managing patients with differentiated thyroid cancer (DTC). We hypothesized that physician adherence to either of the 2009 extent of surgery guidelines of the ATA or NCCN was associated with improved survival, and that practice is most standardized nationally when guidelines are concordant. METHODS Adult patients undergoing surgery for DTC were included from the National Cancer Database. Multivariable modeling was used to identify factors associated with nonadherence to the 2009 ATA or NCCN guidelines (2010-2011) and hypothetically examine the association of retrospective adherence to guidelines with survival (1998-2006). RESULTS A total of 39,687 patients with DTC were included; 2,249 were not treated in accordance with ATA or NCCN guidelines. Factors independently associated with nonadherence were discordance between ATA and NCCN recommendations, black race, and treatment at nonacademic centers (P < .01). After adjustment, care not in accordance with either set of guidelines was associated with compromised survival (hazard ratio 1.16, P = .02). CONCLUSION A minority of patients received surgery for DTC not aligned with guidelines; nonadherent care was associated with compromised survival. Discordance in recommendations between guidelines is associated with reduction in adherent care, suggesting that standardizing guidelines could decrease confusion, increase adherence, and thereby may improve outcomes.

Lymphovascular invasion is associated with survival for papillary thyroid cancer

Data are limited regarding the association between tumor lymphovascular invasion and survival for patients with papillary thyroid cancer (PTC). This study sought to examine lymphovascular invasion as an independent prognostic factor for patients with PTC undergoing thyroid resection. The National Cancer Data Base (2010-2011) was queried for patients with PTC who underwent total thyroidectomy or lobectomy. Patients were classified into two groups based on the presence/absence of lymphovascular invasion. Demographic, clinical and pathological features were evaluated for all patients. A Cox proportional hazards model was utilized to identify factors associated with survival. Results show that 45,415 patients met inclusion criteria; 11.6% had lymphovascular invasion. Patients with lymphovascular invasion were more likely to have larger tumors (2.8cm vs 1.5cm, P<0.01), metastatic lymph nodes (74.1% vs 32.5%, P<0.01), and distant metastases (3.0% vs 0.5%, P<0.01). They were also more likely to receive radioactive iodine (69.3% vs 44.9%, P<0.01). Unadjusted overall 5-year survival was lower for patients who had tumors with lymphovascular invasion (86.6% vs 94.5%) (log-rank P<0.01). After adjustment, increasing patient age (HR=1.06, P<0.01), male gender (HR=1.68, P<0.01), presence of metastatic lymph nodes (HR=1.77, P<0.01), distant metastases (HR=3.49, P<0.01), and lymphovascular invasion (HR=1.88, P<0.01) were associated with compromised survival. For patients with lymphovascular invasion, treatment with RAI was associated with reduced mortality (HR=0.43, P<0.01). The presence of lymphovascular invasion among patients with PTC is independently associated with compromised survival. Patients who have PTC with lymphovascular invasion should be considered higher risk, and adjuvant RAI should be more strongly considered.