Long-term outcomes for older patients with papillary thyroid carcinoma: should another age cutoff beyond 45 years be added?

BACKGROUND: Although an age cutoff of 45 years has often been adopted to stratify cancer risk in papillary thyroid carcinoma (PTC), both cancer-specific survival (CSS) and disease-specific survival (DFS) continue to worsen beyond this cutoff. This study aimed to determine whether advanced age (i.e., >60 years) at diagnosis was an independent predictor of CSS and DFS in older (≥45 years) patients. METHODS: This study analyzed 407 PTC patients with a minimal follow-up period of 7 years. Standard protocol was followed. Both CSS and DFS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables shown to be significant by the log-rank test were entered into the Cox regression analysis. RESULTS: During a median follow-up period of 15.1 years, 51 patients (12.5 %) died of PTC, whereas 80 (20.5 %) experienced at least one recurrence. For CSS, age beyond 60 years (hazard ratio [HR], 3.027; 95 % confidence interval [CI] 1.369-6.690; p = 0.006), tumor size greater than 4 cm (HR 2.043; 95 % CI 1.141-4.255; p = 0.049), central nodal metastases (HR 2.726; 95 % CI 1.198-6.200; p = 0.017), lateral nodal metastases (HR 5.247; 95 % CI 2.987-9.216; p < 0.001), and distant metastases (HR 4.297; 95 % CI 1.726-2.506; p = 0.002) were independent predictors. For DFS, only tumor size greater than 4 cm (HR 1.733; 95 % CI 1.030-3.058; p = 0.049), central nodal metastases (HR 2.362; 95 % CI 1.010-5.523; p = 0.047), and lateral nodal metastases (HR 4.383; 95 % CI 2.388-8.042; p < 0.001) were independent predictors. CONCLUSIONS: Advanced age was an independent predictor of CSS, and cancer-related death risk showed a continuing increase beyond the age of 60 years. However, advanced age was not an independent predictor of DFS. Therefore, having another age cutoff appears justifiable for stratifying risk of cancer-related death but less justifiable for disease recurrence. Tumor size as well as central and lateral nodal metastases independently predicted CSS and DFS.

Bilateral Pheochromocytomas in MEN2A Syndrome: A Two-Institution Experience.

BACKGROUND: Bilateral pheochromocytoma (PHEO) is more frequently found in patients with multiple endocrine neoplasia 2A carrying a RET germline mutation located in codon 634 (C634). However, it is unclear whether different amino acid substitutions within C634 cause differences in bilateral PHEOs expression. We aimed to answer this by pooling data from two Asian institutions. METHODS: Sixty-seven patients had confirmed C634 germline mutation. Age-dependent penetrance of bilateral PHEO was calculated from date of birth to the date when bilateral PHEO was first diagnosed or when the contralateral gland became a PHEO (if the patient already had one adrenal gland removed). Age-dependent penetrance was estimated by the Kaplan-Meier method and compared by log-rank test. RESULTS: The 4 different amino acid substitutions included C634R (arginine) (n = 19, 28.4 %), C634Y (tyrosine) (n = 36, 38.8 %), C634G (glycine) (n = 4, 6.0 %), and C634W (tryptophan) (n = 8, 11.9 %). The age-related penetrance of PHEO was similar between C634R, C634Y, C634G, and C634W (by age 40, 69.8, 55.2, 25.0, and 56.2 %, respectively) (p = 0.529). However, the age-related penetrance of bilateral PHEO in C634R was significantly higher than C634Y (by age of 40, 59.3 % vs. 25.2 %, p = 0.046) or C634Y, C634G, and C634W combined (59.3 % vs. 21.5 %, p = 0.024). Nevertheless, the accumulative risk of bilateral PHEOs across all four C634 mutations almost approached 100 % over time. CONCLUSION: The accumulative risk of bilateral PHEOs almost reached 100 % but its onset was significantly earlier in C634R mutation. These findings implied that those with C634R mutation might benefit from earlier screening of contralateral PHEO than other C634 mutations after an unilateral adrenalectomy.

High pre-operative urinary norepinephrine is an independent determinant of peri-operative hemodynamic instability in unilateral pheochromocytoma/paraganglioma removal.

BACKGROUND: Peri-operative hemodynamic instability (HDI) may increase peri-operative morbidity in pheochromocytoma/paraganglioma (PPGL) patients. OBJECTIVE: This study aimed to determine which tumor-related risk factors could lead to peri-operative HDI in unilateral or single PPGL removal. METHODS: Before surgery, 66 PPGL patients had at least two sets of 24 h urine collected for fractionated catecholamine analysis. At surgery, an arterial line was inserted to record systolic blood pressure (SBP), diastolic BP, and mean arterial BP (MAP). Peri-operative HDI was defined as hypertension (SBP > 160 mmHg) and/or hypotension (SBP < 90 mmHg and/or MAP < 60 mmHg) for >10 consecutive minutes either intra-operatively or within the first 12 h after surgery. Urinary fractionated catecholamines and other variables were compared between those with peri-operative HDI (group I) and those without (group II). RESULTS: A total of 15 (22.7 %) patients belonged to group I, while 51 patients belonged to group II. One (1.5 %) patient died 9 days after surgery. Relative to group II, group I had significantly higher urinary norepinephrine (NE) (5,488.0 vs. 1,980.0 nmol/L, p < 0.001), urinary normetanephrine (5,130.9 vs. 3,853.4 nmol/L, p = 0.045), maximum SBP at operation (188.2 vs. 167.4 mmHg, p = 0.037), but lower MAP after operation (78.9 vs. 91.8 mmHg, p = 0.026). Urinary NE (OD 1.02, 95 % confidence interval [CI] 1.01-1.03, p = 0.046) was an independent risk factor for peri-operative HDI. The urinary NE level significantly correlated with maximum intra-operative SBP and MAP (r 0.692, p < 0.001; and r 0.669, p < 0.001, respectively) and inversely correlated with maximum post-operative MAP (r -0.305, p = 0.040). CONCLUSIONS: High pre-operative urinary NE was an independent tumor-related factor for peri-operative HDI and significantly correlated with sustained intra-operative hypertension and post-operative hypotension.

Should an involved but functioning recurrent laryngeal nerve be shaved or resected in a locally advanced papillary thyroid carcinoma?

BACKGROUND: The issue of whether an involved but functioning recurrent laryngeal nerve (RLN) should be shaved or resected in locally advanced papillary thyroid carcinoma (PTC) remains controversial. Our study aimed to compare the early and late outcomes between those who underwent shaving and those who underwent resection and also to identify independent prognostic factors in this subset of patients. METHODS: Of the 77 patients with 1 RLN involved by PTC, 39 (50.6%) underwent RLN preservation (group I) while 38 (49.4%) underwent RLN resection (group II). Early and late vocal cord function (as assessed by flexible laryngoscopy) and disease status were compared between the 2 groups. A multivariate Cox proportional hazards model was carried out to identify independent factors. RESULTS: Baseline characteristics were comparable between the 2 groups. Although temporary vocal cord palsy rate was similar between the 2 groups (p=0.532), 5 patients in group II (13.2%) suffered temporary bilateral vocal cord palsies with 1 requiring a tracheostomy lasting for 1 month. After a median follow-up of 113.8 months, 1 patient from each group developed new onset vocal cord palsy. Presence of distant metastases (hazard ratio [HR]=5.892, 95% CI=1.971-17.604, p=0.001) and incomplete surgical resection in non-RLN concomitant sites (HR=2.491, 95% CI=1.181-5.476, p=0.024) were the 2 independent predictors for a poor cancer-specific survival. CONCLUSIONS: Our data suggested that shaving could preserve the normal functionality in most of the involved RLNs (>90%) in the short to medium term. In the presence of distant metastases or incomplete resection in other non-RLN concomitant sites, the argument for shaving over resection appears even stronger.

Evaluating the prognostic factors associated with cancer-specific survival of differentiated thyroid carcinoma presenting with distant metastasis.

BACKGROUND: Because patients with differentiated thyroid carcinoma (DTC) presenting with distant metastasis (DM) have a particularly poor prognosis, examining the prognostic factors in this group is essential. We aimed to evaluate the prognostic factors affecting cancer-specific survival (CSS) in DTC patients presenting with DM. METHODS: Of the 1227 DTC patients, 51 (4.2 %) presented with DM at diagnosis. All patients underwent a total thyroidectomy, followed by radioiodine (RAI) ablation and postablation whole body scan (WBS). Patients were considered to have an osseous metastasis if one of the metastatic sites involved a bone, while RAI avidity was determined by any visual uptake in a known metastatic site on the first WBS. Factors predictive of CSS were determined by univariate and multivariate analyses by the Cox proportional hazard model. RESULTS: In univariate analysis, older age (relative risk [RR] 1.050, 95 % confidence interval [CI] 1.010-1.091, P = 0.014), DM discovered before WBS (RR 3.401, 95 % CI 1.127-10.309, P = 0.030), follicular thyroid carcinoma (RR 3.095, 95 % CI 1.168-8.205, P = 0.025), osseous metastasis (RR 4.695, 95 % CI 1.379-15.873, P = 0.013), non-RAI avidity (RR 3.355, 95 % CI 1.280-8.772, P = 0.014), and external beam radiotherapy to DM (RR 3.241, 95 % CI 1.093-9.614, P = 0.034) were significant poor prognostic factors for CSS. In the multivariate analysis, after adjusting for other factors, osseous metastasis (RR 6.849, 95 % CI 1.495-31.250, P = 0.013) and non-RAI avidity (RR 7.752, 95 % CI 2.198-27.027, P = 0.001) were the two independent poor prognostic factors for CSS. Older age almost reached statistically significance (RR 1.055, 95 % CI 0.996-1.117, P = 0.068). CONCLUSIONS: DTC patients presenting with DM accounted for 4.2 % of all patients. Because osseous metastasis and RAI avidity were independent prognostic factors, future therapy should be directed at improving the treatment efficacy of osseous and/or non-RAI-avid metastases.

Evaluating the morbidity and efficacy of reoperative surgery in the central compartment for persistent/recurrent papillary thyroid carcinoma.

BACKGROUND: Although reoperative surgery in the central compartment (RCND) is indicated for bulky or progressive persistent/recurrent papillary thyroid carcinoma (PTC), its associated morbidity and disease outcomes remain unclear. We evaluated RCND outcomes by comparing them with those of patients who underwent primary central neck dissection (CND). METHODS: After matching for age, sex, tumor size, and initial tumor stage, the morbidity and outcomes of 50 consecutive patients who underwent RCND were compared with data from 75 patients who underwent primary therapeutic CND during the same period. Matching was performed blind to the morbidity and disease outcome of each patient. A stimulated thyroglobulin (sTg) <2 ng/ml was considered undetectable. RESULTS: Relative to primary CND, the incidence of extranodal extension (p = 0.010) and size of metastatic lymph nodes (p < 0.001) were significantly greater in the RCND group. Postoperative hypoparathyroidism and vocal cord palsy rates were comparable in the groups. There were two esophageal injuries in the RCND group and none in the primary CND group. The secondary CND group achieved a significantly lower undetectable postablation sTg rate (12.0 vs. 52.0 %, p = 0.001) and worse 10-year disease-free survival (35.6 vs. 91.8 %, p = 0.001) and cancer-specific survival (82.0 vs. 98.5 %, p = 0.001) than the primary CND group. CONCLUSIONS: Although RCND for persistent/recurrent PTC was performed with morbidity comparable to that seen with primary CND, it was associated with some serious complications. Short- and long-term disease control appeared moderate with approximately one-tenth of patients having an undetectable sTg level 6 months after ablation and one-third remaining clinically disease-free after 10 years.

Impact of routine unilateral central neck dissection on preablative and postablative stimulated thyroglobulin levels after total thyroidectomy in papillary thyroid carcinoma.

BACKGROUND: Prophylactic central neck dissection (CND) remains controversial in papillary thyroid carcinoma (PTC). Because postsurgical stimulated thyroglobulin (sTg) level is a good surrogate for recurrence, the study aimed to evaluate the impact of prophylactic CND on preablative and postablative sTg levels after total thyroidectomy. METHODS: Of the 185 patients retrospectively analyzed, 82 (44.3%) underwent a total thyroidectomy and prophylactic CND (CND-positive group) while 103 (55.7%) underwent total thyroidectomy only (CND-negative group). All patients had no preoperative or intraoperative evidence of lymph node metastases. Clinicopathological characteristics, postoperative outcomes, and preablative and postablative sTg levels were compared between the two groups. Preablative sTg level was taken at the time of radioiodine ablation, while postablative sTg level was taken 6 months after ablation. A multivariable analysis was conducted to identify factors for preablative athyroglobulinemia (sTg<0.5 µg/L). RESULTS: Relative to the CND-negative group, the CND-positive group had larger tumors (15 mm vs. 10 mm, P < 0.005), more extrathyroidal extension (26.8% vs. 14.6%, P<0.003), more tumor, node, metastasis system stage III disease (32.9% vs. 9.7%, P < 0.001), and more temporary hypoparathyroidism (18.3% vs. 8.7%, P=0.017). Fourteen patients (17.1%) in the CND-positive group were upstaged from stages I/II to III as a result of prophylactic CND. The CND-positive group experienced lower median preablative sTg (<0.5 µg/L vs. 6.7 µg/L, P < 0.001) and a higher rate of preablative athyroglobulinemia (51.2% vs. 22.3%, P = 0.024), but these differences were not observed 6 months after ablation. Prophylactic CND was the only independent factor for preablative athyroglobulinemia. CONCLUSIONS: Although performing prophylactic CND in total thyroidectomy may offer a more complete initial tumor resection than total thyroidectomy alone by minimizing any residual microscopic disease, such a difference becomes less noticeable 6 months after ablation.

Eucalcemic parathyroid hormone elevation after parathyroidectomy for primary sporadic hyperparathyroidism: risk factors, trend, and outcome.

BACKGROUND: Patients with eucalcemic parathyroid hormone elevation (ePTH) after parathyroidectomy for primary hyperparathyroidism (HPT) may be at risk of recurrence. We aimed to examine risk factors, trend of PTH level, and outcome of patients with ePTH 6 months after parathyroidectomy. METHODS: A total of 161 primary HPT were analyzed. The 6-month postoperative calcium and PTH levels were obtained. ePTH was defined as an elevated PTH level in the presence of normocalcemia. At 6 months, 98 had eucalcemic normal PTH and 63 (39.1%) had ePTH. Perioperative variables, PTH trend, and outcome were compared between 2 groups. Multivariable analyses were performed to identify independent preoperative and operative/postoperative risk factors for ePTH. RESULTS: Among preoperative factors, advanced age (odds ratio [OR] = 1.042, P = .027) and low 25-hydroxyvitamin D(3) (25OHD(3)) (OR = 1.043, P = .009) were independently associated with ePTH, whereas among operative/postoperative factors, high 10-min intraoperative PTH level (OR = 1.015, P = .040) and high postoperative 3-month PTH (OR = 1.048, P < .001) were independently associated with ePTH. After a mean follow-up of 38.7 months, recurrence rate was similar between the 2 groups (P = 1.00). In the first 2 postoperative years, 75 (46.6%) had ePTH on at least 1 occasion and 8 (5.0%) had persistently ePTH on every occasion. CONCLUSIONS: Advanced age, low 25OHD(3), high 10-min intraoperative PTH, and high postoperative 3-month PTH were independently associated with ePTH at 6-month. Although 39.1% of patients had ePTH at 6 months, more than 50% had at least 1 ePTH within the first 2 years of follow-up. Recurrence appeared similar between those with or without ePTH at 6 months.

Significance of metastatic lymph node ratio on stimulated thyroglobulin levels in papillary thyroid carcinoma after prophylactic unilateral central neck dissection.

BACKGROUND: Prognostic significance of metastatic central lymph node ratio (CLNR) in papillary thyroid carcinoma (PTC) remains unknown. Because postsurgical detectable stimulated thyroglobulin (DsTg) after radioiodine ablation may imply persistent or recurrent disease, we evaluated the association between CLNR and rate of DsTg in patients with PTC who underwent unilateral prophylactic central neck dissection. METHODS: To be eligible for analysis, the prophylactic central neck dissection specimen had to contain ≥3 central lymph nodes (CLNs) with ≥1 harboring metastasis. Of 129 specimens, 51 (39.5%) were eligible. CLNR was calculated as follows: (number of metastatic CLNs/number of CLNs retrieved)×100. They were categorized into group 1 (CLNR<33.34%) (n=14), group 2 (CLNR 33.34-66.67%) (n=15), and group 3 (CLNR>66.67%) (n=22). Postablation sTg level was measured 6 months after radioiodine ablation. A multivariate analysis was conducted to identify factors for postablation DsTg. RESULTS: Young age, palpable neck swelling, large tumor size, advanced tumor, node, metastasis system (TNM) stage, and large number of metastatic CLNs were significantly associated with high CLNR (P<0.05). Compared to groups 1 and 2, group 3 had significantly higher DsTg rate (P=0.018). Those who developed subsequent recurrence had significantly higher DsTg rate than those who did not (100% vs. 39.1%, P=0.013). In the multivariate analysis for postablative DsTg, after adjusting for age, palpable neck swelling, tumor size, TNM stage, and number of metastatic CLNs, CLNR was the only independent factor (odds ratio 1.15, 95% confidence interval 1.01-1.31, P=0.036). CONCLUSIONS: A higher CLNR was associated with a higher rate of postablative DsTg; this may imply higher future recurrence rate.

Significance of size of lymph node metastasis on postsurgical stimulated thyroglobulin levels after prophylactic unilateral central neck dissection in papillary thyroid carcinoma.

BACKGROUND: The prognostic significance of size of central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) remains unknown. Because postsurgical detectable stimulated thyroglobulin (DsTg) after radioiodine ablation may imply persistent or recurrent disease, we evaluated the association between size of CLNM and rate of DsTg in patients with PTC who underwent unilateral prophylactic central neck dissection. METHODS: To be eligible for analysis, the prophylactic central neck dissection specimen with <3 central lymph nodes (CLNs) or size of CLNM ≥1 cm as measured under the microscope was excluded. Of 132 specimens, 89 (67.4%) were eligible. Forty patients (44.9%) had no metastasis or pN0, 20 (22.5%) had micrometastasis (<2 mm) or pN1mic and 29 (32.6%) had macrometastasis (≥2 mm) or pN1mac. Postablation sTg level was measured 9 months after surgery. A multivariable analysis was conducted to identify independent factors for postablation DsTg. RESULTS: Larger-sized CLNM correlated significantly with younger age (p = 0.028), greater number of CLN retrieved (p = 0.016), greater number of metastatic CLN excised (p < 0.001), higher metastatic CLN ratio (p = 0.006) and postablation sTg level (p = 0.012). In the multivariable analysis, after adjusting for tumor size and metastatic CLN ratio, size of CLNM was an independent predictor of postablation DsTg (odds ratio 1.56, 95% confidence interval 1.09-2.24, p = 0.015). Relative to pN0, the odds ratios for postablation DsTg in pN1mic and pN1mac were 2.53 (95% confidence interval 0.35-19.00, p = 0.351) and 5.81 (95% confidence interval 1.22-27.70, p = 0.027), respectively. CONCLUSIONS: Size of CLNM was an independent factor for DsTg 9 months after surgery. Patients with pN1mac were almost 6 times more likely to have postablation DsTg than those with pN0 or pN1mic.

Factors affecting the adequacy of lymph node yield in prophylactic unilateral central neck dissection for papillary thyroid carcinoma.

BACKGROUND: Determinants for adequate lymph node yield (LNY) in prophylactic central neck dissection (pCND) for papillary thyroid carcinoma (PTC) remain unclear. We aimed to determine factors affecting LNY in pCND. METHODS: Of 230 patients, 109 (47.4%) had total thyroidectomy and unilateral pCND. A specimen of ≥ 6 central lymph nodes (CLNs) was considered adequate. Factors such as patient clinicopathologic features, specimen dimensions, and pathologists' experience were compared between those with LNY < 6 (n = 52) and LNY ≥ 6 (n = 57). A multivariate analysis was conducted to identify independent factors for LNY ≥ 6. RESULTS: Age, sex, presentation, body mass index, tumor characteristics, TNM stages, MACIS score, and pathologist's experience were not significant determinants for LNY ≥ 6. In the univariate analysis, the length (P = 0.021), width (P = 0.047), thickness (P = 0.024), and pN1a (P = 0.042) were significant determinants but in the multivariate analysis, the length (OR = 1.486 (95% CI: 1.053-2.097), P = 0.024) was the only independent factor for LNY ≥ 6. Postoperative vocal cord palsy, hypoparathyroidism, stimulated thyroglobulin and recurrences were similar between LNY <6 and ≥ 6. CONCLUSIONS: Length (or the longest measured dimension) of the fresh CLN specimen was the only factor assuring LNY ≥ 6. Surgical complications and short-term outcomes appeared similar between LNY <6 or ≥ 6.

A review of risk factors and timing for postoperative hematoma after thyroidectomy: is outpatient thyroidectomy really safe?

BACKGROUND: Although postoperative hematoma after thyroidectomy is uncommon, patients traditionally have been advised to stay overnight in the hospital for monitoring. With the growing demand for outpatient thyroidectomy, we assessed its safety and feasibility by evaluating the potential risk factors and timing of postoperative hematoma after thyroidectomy. METHODS: From 1995-2011, 3,086 consecutive patients underwent thyroidectomy at our institution; of these, 22 (0.7 %) developed a postoperative hematoma that required surgical reexploration (group I). Potential risk factors were compared between group I and those without hematoma (n = 3,045) or with hematoma but not requiring reexploration (n = 19; group II). Variables that were significant in the univariate analysis were entered into multivariate analysis by binary logistic regression analysis. RESULTS: Group I was significantly more likely to have undergone previous thyroid operation than group II (27.3 vs. 8.2 %, p = 0.007). The median weight of excised thyroid gland (71.8 vs. 40 g, p = 0.018) and the median size of the dominant nodule (4.1 vs. 3 cm, p = 0.004) were significantly greater in group I than group II. Previous thyroid operation (odds ratio (OR) = 4.084; 95 % confidence interval (CI), 1.105-15.098; p = 0.035) and size of dominant nodule (OR = 1.315; 95 % CI, 1.024-1.687; p = 0.032) were independent factors for hematoma. Sixteen (72.7 %) had hematoma within 6 h, whereas the other 6 (27.3 %) had hematoma at 6-24 h. CONCLUSIONS: Previous thyroid operation and large dominant nodule were independent risk factors for hematoma requiring surgical reexploration. Given that a quarter of hematoma occurred between 6 to 24 h after surgery, routine outpatient thyroidectomy could not be recommended.

Thyroidectomy for Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma is the most common endocrine malignancy and accounts for the overwhelming majority of thyroid carcinoma. This recent dramatic increase in incidence is almost exclusively attributed to the incidental detection of small papillary thyroid carcinoma or microcarcinoma. Surgical management of thyroid carcinoma has been evolving to avoid overtreating patients by adopting the appropriate risk-based approach including the recommendation of hemithyroidectomy for low-risk carcinoma, the avoidance of routine prophylactic central nodal dissections, a higher threshold in using postoperative radioiodine ablation after total thyroidectomy, and the active observation or surveillance of papillary microcarcinoma as a viable alternative option instead of immediate surgical treatment.

Lymph Node Dissection for Papillary Thyroid Carcinoma.

Cervical lymph node metastasis is frequent in patients with papillary thyroid carcinoma. In addition to the extent of thyroidectomy, the need as well as the extent of concomitant lymphadenectomy has been a subject of controversy and debate. The central compartment is the most frequent site of metastasis followed by the lateral compartment although skip metastasis in the lateral compartment can occur. Papillary thyroid carcinoma can also present with cervical lymph node metastasis, while the primary tumor remains clinically undetectable. Surgical removal of clinically involved nodal metastasis should be mandatory to prevent recurrence and improve disease prognosis. However, despite a low accuracy of preoperative imaging for microscopic disease and the frequent microscopic metastasis to the central compartment, routine prophylactic neck dissection has not been shown to have any relevance to prevent recurrence or improve disease cure. Routine or prophylactic central compartment dissection is generally not recommended unless in the presence of high-risk tumors. The potential benefit of reducing central compartment recurrence or avoiding high-risk reoperation probably outweighs the risk of inducing surgical complication including hypoparathyroidism during routine central neck dissection. Therapeutic lateral neck dissection is performed for clinically involved nodes detected by preoperative imaging confirmed by needle biopsy, while prophylactic lateral neck dissection is contraindicated. The extent of neck dissection has been de-escalated, and compartmental nodal dissection aiming at preservation of function is performed to achieve a complete surgical resection. Postoperative adjuvant radioiodine is frequently administered for patients with positive nodal metastasis (intermediate-risk group) to avoid future recurrence. Routine central neck dissection may also upstage patients with microscopic nodal metastases and increase the use of postoperative adjuvant radioiodine.

VEGF-A/VEGF-B/VEGF-C expressions in non-hereditary, non-metastatic phaeochromocytoma.

Vascular endothelial growth factor (VEGF) is important in pathogenesis of different cancers. The aim of this study is to investigate the relationships between different VEGFs and clinicopathological factors in patients with phaeochromocytomas. Twenty patients (10 men; 10 women) with non-hereditary, non-metastatic phaeochromocytomas were examined for VEGF mRNA expressions by polymerase chain reaction. The expressions were correlated with the clinical and pathological factors of the patients. In addition, mouse double minute 2 (MDM2) expression in these tumours were studied by immunohistochemistry. High expressions of VEGF-A, VEGF-B, and VEGF-C mRNA were detected in 11 (55%), 9 (45%), and 9 (45%) of the tumours respectively. High expression of VEGF-A in phaeochromocytomas was significantly correlated with the tumour size (p=0.025) but did not correlate with patients' age, gender, and tumour laterality. Besides, there was a trend of VEGF-A expression correlated with MDM2 expression (p=0.064). On the other hand, expressions of VEGF-B and VEGF-C were not significantly correlated with tumour size, patients' age, gender, tumour laterality, and MDM2 expression. In addition, high expressions of VEGF-B and VEGF-A were associated with increase of tumour size (p=0.042). Co-expression of different VEGFs did not correlate with MDM2 expression. To conclude, there is a role for VEGF-A/VEGF-B/VEGF-C in the pathogenesis of non-hereditary, non-metastatic phaeochromocytomas.

Vitamin D3 deficiency is associated with late-onset hypocalcemia after minimally invasive parathyroidectomy in a vitamin D borderline area.

BACKGROUND: Concurrent vitamin D(3) deficiency is common in primary hyperparathyroidism (pHPT). We aimed to examine the clinicopathologic features and short-term outcomes of vitamin D(3)-deficient patients after minimally invasive parathyroidectomy (MIP). METHODS: Over 2-year period, 80 consecutive MIP patients had preoperative-fasting 25-hydroxyvitamin D(3) (25OHD(3)) checked. Forty-five patients had a 25OHD(3) level <20 ng/ml and were defined as deficient. Intraoperative parathyroid hormone (IOPTH) assay was used for all MIP. Postoperative adjusted calcium (Ca) was checked at 6, 16 (with intact PTH), and 24 h. Oral calcium and vitamin D supplements were given if hypocalcemic symptoms developed or Ca < 2.00 mmol/l. Late-onset hypocalcemia (LOH) was defined as symptoms developed after 24 h. RESULTS: Both deficient and nondeficient groups had similar demographic data and bone density scores. The deficient group had significantly higher PTH (190 vs. 121 pg/ml, p = 0.015). Although IOPTH in the deficient group were higher at induction and 0 min after excision, the percentage drop from induction to 10 min after excision was similar. Ca was similar at 6 and 16 h in the two groups but was significantly lower in the deficient group at 24 h (2.10 vs. 2.45 mmol/l, p = 0.033). At 1 week, the proportion of LOH was significantly higher in the deficient group (12/42 vs. 3/34, p = 0.043) and in those with preoperative PTH > 100 pg/ml (15/57 vs. 0/19, p = 0.013). CONCLUSIONS: Vitamin D(3) deficiency was associated with a higher preoperative PTH level and a greater risk of LOH after MIP. However, the likely cause of LOH remains unclear as both low preoperative vitamin D(3) and high PTH levels could be responsible.

Factors affecting the approaches and complications of surgery in childhood papillary thyroid carcinomas.

BACKGROUND: The aim of the study is to analyse the factors related to permanent surgical complications in children and adolescents with papillary thyroid carcinoma treated by total thyroidectomy with central and bilateral neck dissections. METHODS: Children and adolescents aged ≤18-year-old at presentation with papillary thyroid carcinoma during the years 1988-2010 underwent thyroid and lymph-node surgeries (with a median follow-up of 19.6 years) were analysed for post-surgical complications. RESULTS: Permanent surgical morbidity occurred in 14% (n = 70) of patients who underwent total thyroidectomy as well as bilateral central and lateral neck dissections (n = 509). Factors associated with permanent complications included pN1 with extra-nodal extension, > 4 metastatic lymph nodes in the central neck compartment, presence of distant metastases and younger age of patients at surgery. Patients who received extensive surgery had better relapse-free survival rates (p < 0.001). CONCLUSION: Total thyroidectomy and bilateral central as well as lateral neck dissections for children and adolescents with papillary thyroid carcinoma was associated with substantial postoperative complications. Nevertheless, it is associated with better prognosis for young patients with thyroid cancer. Prophylactic compartment-oriented lymph node dissections to these patients could be the management protocol in experienced hands.

Surgical approach and perioperative complications determine short-term outcomes in patients with insulinoma: results of a bi-institutional study.

BACKGROUND: Despite advancements in radiologic imaging and minimally invasive surgery, the evaluation and management of insulinomas is institution and surgeon dependent. Therefore, the reported surgical outcomes are highly variable. We compared the surgical management and outcomes of insulinomas between two international tertiary-care surgical units to better identify the best management as determined by short-term outcomes. METHODS: We performed a retrospective review of patients who underwent surgery for insulinomas over a 117-month period at UT Southwestern Medical Center in Dallas (UTSW) and Queen Mary Hospital in Hong Kong (QMHK). Data collected included imaging studies, operative procedure, complications, and outcomes. RESULTS: Thirty-seven patients were identified. Preoperative localization by computed tomography (CT) scan was successful in 21 patients (63.9%). In Hong Kong, 16 patients underwent selective arterial cannulation and calcium stimulation (SACST) with a success rate of 87.5%. Surgical management consisted of enucleation in 24 patients and distal pancreatectomy in 13 patients. Thirty patients underwent a concurrent intraoperative ultrasound, with localization in 96.7%. Laparoscopic procedures were accomplished in 20 patients. Nine postoperative complications were identified, four occurring in the laparoscopic group. Patients undergoing laparoscopic procedures had a decreased length-of-stay (LOS) compared with patients undergoing an open procedure and patients who had uncomplicated surgery had a trend toward decreased LOS. CONCLUSION: Though the accuracy of CT scans for localizing insulinomas is only 64%, the addition of SACST or intraoperative ultrasound and pancreatic palpation increases accuracy to 97.1%. Compared with open procedures, laparoscopic resection is associated with comparable complication rates and shorter hospital length of stay.

Staging systems for follicular thyroid carcinoma: application to 171 consecutive patients treated in a tertiary referral centre.

A number of risk-group stratification or staging systems have been found useful at stratifying patients with differentiated thyroid carcinoma into risk groups. Those identified as high risk could be subjected to more aggressive treatment, while those at low risk could be spared of such treatment. However, the best stratification system in patients with follicular thyroid carcinoma (FTC) remains unclear. Through a comprehensive MEDLINE search from 1965 to 2005, a total of 18 different staging systems were identified in the literature and 14 of them were applicable to 171 patients, with FTC managed at our institution from 1961 to 2001. Cancer-specific survivals (CSS) were calculated by Kaplan-Meier method and were compared by log-rank test. Using Cox proportional hazards analysis, the relative importance of each staging system in determining CSS was calculated by the proportion of variation in survival time explained (PVE). CSS were predicted by 13 out of the 14 staging systems significantly (P < 0.001). The three highest ranked staging systems by PVE were the new American Joint Committee on Cancer/Union Internationale Centre le Cancer 6th edition, tumour, node, metastases (TNM; 22.4), followed by the Clinical Class (21.2) and the metastases, age, completeness of resection, invasion, size (MACIS; 20.4). In conclusion, 13 out of the 14 presently available staging systems predicted CSS significantly in FTC. When predictability was measured by PVE, the TNM system was found to have the best predictability and thus, should be the stratification system of choice for FTC in the future.

Benign nodular goitre presenting as acute airway obstruction.

BACKGROUND: Although rare in non-endemic areas, benign nodular goitre may cause acute airway obstruction and the clinical management of this condition remains a challenge. METHODS: From 1996 to 2005, a total of 1115 patients underwent thyroid surgery at our institution and of these, 7 patients were identified to have a benign nodular goitre leading to acute airway obstruction. They were retrospectively reviewed with reference to the aetiology, presentation, perioperative management and postoperative outcome. RESULTS: All seven patients were elderly women with a history of symptomatic goitre and concomitant medical problems. Five patients required emergency tracheal intubation, whereas two patients underwent urgent tracheostomy. Total thyroidectomy was successfully carried out for all patients and there was no hospital death. Perioperative complications included three patients with pneumonia, two with renal failure and one with perforated duodenal ulcer. Surgically related complications included transient recurrent nerve palsy in one patient and transient hypocalcaemia in four. After a median follow up of 22 months (range, 4-53 months), two patients died of cerebrovascular accident. CONCLUSION: Prompt airway protection followed by total thyroidectomy within the same hospital admission should be recommended and can be associated with favourable outcome.