Significance of Size of Persistent/Recurrent Central Nodal Disease on Surgical Morbidity and Response to Therapy in Reoperative Neck Dissection for Papillary Thyroid Carcinoma.

BACKGROUND: To balance the risk of disease progression, morbidity, and efficacy of reoperative central neck dissection (RCND) in papillary thyroid carcinoma, the latest clinical guidelines recommend early surgery over surveillance when the largest diseased node is >8 mm in its smallest dimension. However, the evidence remains scarce. To determine an appropriate size for first-time RCND, the relationship between size of largest diseased central node, morbidity, and response-to-therapy following RCND was examined. METHODS: A total of 130 patients who underwent RCND following initial surgery for persistent/recurrent nodal disease were reviewed. Patients with largest diseased central node measured preoperatively by ultrasonography were included. Eligible patients were categorized into three groups: largest central node <10 mm (group I), 10-15 mm (group II), and >15 mm (group III). Surgical morbidity and response to therapy at one year after RCND were compared between groups. To evaluate biochemical response, patients with structural incompleteness were excluded. RESULTS: Group III not only had significantly more high-risk tumors (by American Thyroid Association risk stratification) at initial therapy (64.5% vs. 44.4%, respectively; p = 0.038), but this group also a higher risk of extranodal extension (35.5% vs. 16.0%; p = 0.055), recurrent laryngeal nerve involvement (19.4% vs. 0.0%; p < 0.001), incomplete surgical resection (48.4% vs. 7.4%; p < 0.001), new-onset vocal cord paresis (16.7% vs. 2.5%; p = 0.017), overall surgical morbidity (22.6% vs. 7.4%; p = 0.021), and biochemical incompleteness (80.6% vs. 67.9%; p = 0.004) than groups I and II combined did. However, overall morbidity did not differ between groups I and II (5.7% vs. 8.7%; p = 0.694). After adjusting for American Thyroid Association risk stratification, only the size of the largest diseased central node ≥15 mm (odds ratio = 7.256 [confidence interval 1.302-40.434], p = 0.001) was an independent risk factor for biochemical incompleteness following RCND. CONCLUSIONS: Patients with larger diseased central node(s) had a significantly higher risk of local invasion, surgical morbidity, and biochemical incompleteness. Relative to nodal size <10 mm, size >15 mm in the largest disease central node was an independent risk factor for incomplete biochemical response, while nodal size 10-15 mm was not. These findings imply that the recommended threshold of 8 mm might be too stringent and could be raised to 15 mm without increasing the surgical morbidity from RCND.

The total number of tissue blocks per centimetre of tumor significantly correlated with the risk of distant metastasis in patients with minimally invasive follicular thyroid carcinoma.

BACKGROUND: Given that careful histological examination plays a pivotal role in follicular thyroid carcinoma categorization, we hypothesize that the number of blocks taken at initial specimen review may be associated with survival outcomes of patients initially diagnosed with minimally invasive follicular thyroid carcinoma. METHODS: A total of 162 patients with confirmed minimally invasive follicular thyroid carcinoma were analyzed. The number of tissue blocks taken from each patient was recorded and the number of blocks per each centimeter of tumor was calculated. A multivariate analysis was conducted to identify independent factors for distant metastasis-free survival. RESULTS: After a mean follow-up of 197.88 ± 155.39 months, 7 (4.3%) patients developed distant metastasis during follow-up (group II). Relative to those who remained disease-free (group I), group II were significantly older at initial operation (p = 0.022), had larger tumors (p = 0.002) and fewer number of blocks taken/cm of tumor (p = 0.001). However, after adjusting for age at initial operation and tumor size, total number of tissue blocks taken/cm of tumor was the only independent determinant for distant metastasis-free survival (p = 0.049). The 10-year distant metastasis-free survival was significantly better in those who had ≥ 4 blocks/cm of tumor (n = 82) than those with ≤ 3 block/cm of tumor (n = 80) (100 vs. 84.7%, p = 0.005, by log rank). CONCLUSIONS: Although our study was not able to identify the precise cause for the association between the total number of tissue blocks taken/cm of tumor and distant metastasis-free survival, our data support a more liberal approach in taking tissue blocks on thyroid nodules especially those showing well-differentiated follicular cell differentiation.

Does microscopically involved margin increase disease recurrence after curative surgery in papillary thyroid carcinoma?

BACKGROUND: The prognostic significance of microscopically involved margin in papillary thyroid carcinoma (PTC) following curative surgery remains unclear. We aimed to evaluate the impact of an involved margin and its location (anterior vs. posterior) on disease recurrence. METHODS: Of the 638 eligible patients, 538 (85.9%) did not have an involved margin (group I) while 100 (14.1%) did (group II). The latter group was further classified according to its location relative to the surface of the thyroid gland (anterior or posterior). A multivariate analysis was conducted to identify independent factors for recurrence risk. RESULTS: After a mean of 130.1 ± 93.5 months, 22 patients had disease recurrence. The 10-year disease-free survival (DFS) was significantly worse in group II (95.0% vs. 97.0%, P = 0.011). After adjusting other significant factors, involved margin was not an independent risk factor for disease recurrence (P = 0.358). Compared to a negative margin, an anterior involved margin did not pose increased recurrence risk (HR = 1.21, 95%CI = 0.93-500.00, P = 0.368), whereas a posterior involved margin had almost 23 times higher recurrence risk (HR = 22.95; 95%CI = 4.33-121.70, P < 0.001). CONCLUSIONS: Overall, a microscopically involved margin was not an independent factor for DFS. However, although an anterior involved margin itself did not increase disease recurrence, a posterior involved margin did. J. Surg. Oncol. 2016;113:635-639. © 2016 Wiley Periodicals, Inc.

Impact of microscopic extra-nodal extension (ENE) on locoregional recurrence following curative surgery for papillary thyroid carcinoma.

BACKGROUND: The presence of microscopic extra-nodal extension (ENE) may increase locoregional recurrence (LRR) in papillary thyroid carcinoma (PTC). We aimed to evaluate the association between microscopic ENE, response to initial therapy and LRR risk following total thyroidectomy, therapeutic neck dissection, and radioactive iodine (RAI) ablation in PTC. METHODS: Of the 369 eligible PTC patients, 264 (71.5%) did not have microscopic ENE (group I) while 105 (28.5%) did (group II). All presented with clinical nodal metastasis (cN1) and underwent therapeutic neck dissection and RAI ablation. Biochemical incompleteness meant post-ablation stimulated thyroglobulin (sTg) >10 ng/ml. Multivariate analyses were conducted to identify independent factors for LRR. RESULTS: Biochemical incompleteness was significantly more common group II (43.8% vs. 17.4%, P < 0.05). The 10-year locoregional free-survival was significantly worse in group II than I (52.0% vs. 86.2%, P = 0.005). After adjusting for other significant factors, age <45 (P < 0.05), multifocality (P < 0.05), presence of ENE (P = 0.027) were independent risk factors of LRR. The number and size of positive lymph nodes were not independent factors. CONCLUSIONS: Patients with microscopic ENE were significantly more likely to have biochemical incompleteness after initial therapy. After adjusting for other significant primary and nodal characteristics, microscopic ENE was an independent factor for LRR in patients with cN1. J. Surg. Oncol. 2016;113:526-531. © 2016 Wiley Periodicals, Inc.

High False Positivity in Positron Emission Tomography is a Potential Diagnostic Pitfall in Patients with Suspected Adrenal Metastasis.

BACKGROUND: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) is a potentially powerful, non-invasive imaging tool in differentiating adrenal metastasis from benign disease, some adenomas also exhibit high FDG uptake, therefore mimicking metastasis (i.e., false positives). We aimed to evaluate the accuracy of FDG-PET/CT based exclusively on histology and to identify risk factors for adrenal metastasis. METHODS: Among the 289 consecutive patients who underwent adrenalectomy, 39 (78.0%) patients had suspected solitary adrenal metastasis and had a positive preoperative FDG-PET/CT. The FDG-PET/CT findings were correlated with the histology of the excised adrenal gland. To identify risk factors for adrenal metastasis, characteristics were compared between patients with histologically proven adrenal metastasis and those without. Youden's index was used to calculate the optimal cut-off value for predicting adrenal metastasis. RESULTS: Histology of the excised adrenal tumor confirmed adrenal metastasis in 28/39 (71.8%) patients while non-metastatic lesions comprised mostly benign adrenal cortical adenoma (n=10) and one non-functional pheochromocytoma. Therefore, the overall false-positive rate of FDG-PET/CT was 28.2%. History of primary lung malignancy [odds ratio (OR) (95% CI) 20.00 (1.01-333.3), p=0.049] and SUVmax>2.65 [OR (95% CI) 31.606 (2.46-405.71), p=0.008] were independent risk factors for adrenal metastasis. CONCLUSIONS: Single adrenal uptake on FDG-PET/CT in suspected solitary adrenal metastasis was associated with a high false-positive rate (28.2%). Risk factors associated with adrenal metastasis included a history of known primary lung malignancy and a SUVmax>2.65 at the adrenal lesion of interest on FDG-PET/CT. Based on these findings, a new algorithm was constructed.

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.

Predictive factors and pattern of locoregional recurrence after prophylactic central neck dissection in papillary thyroid carcinoma.

BACKGROUND: Prophylactic central neck dissection (pCND) at the time of the total thyroidectomy (TT) remains controversial in clinically nodal-negative (cN0) papillary thyroid carcinoma. Our study was designed to examine the predictive factors and pattern of locoregional recurrence (LRR) after pCND in the context of the postoperative stimulated Tg (sTg) level. METHODS: A total of 341 patients who underwent TT and unilateral pCND were analyzed. Patients with an identifiable lesion on ultrasonography or whole-body scan within 6 months of surgery were excluded. LRR was defined as an identifiable lesion on USG, which was later confirmed by cytology/histology. Preablation sTg level was taken 2 months after surgery, whereas postablation sTg level was taken 8 months after surgery. Cox regression was used in the univariate and multivariate analyses to identify significant independent factors for LRR. RESULTS: After a follow-up of 66.6 ± 38.6 months, 14 (4.1 %) suffered from LRR. The duration to first LRR was 36.4 ± 21.7 months. The estimated 5- and 10-year LRR rates were 5.1 and 6.1 %, respectively. Of these 14 LRR, 3 (21.4 %) involved the central compartment alone, 9 (64.3 %) involved the lateral compartment alone, and 2 (14.3 %) involved both central and lateral compartments. After adjusting for other clinicopathological factors, postablation sTg level ≥ 1 µg/L (hazard ratio 265.109, 95 % confidence interval 1.132-62075.644, p = 0.045) was the only independent predictor of LRR. CONCLUSIONS: Annualized risk of LRR after pCND was approximately 1 % in the first 5 years and 0.2 % in the subsequent 5 years. Most (78.6 %) LRRs involved the lateral compartment. Postablation sTg ≥ 1 µg/L significantly predicted risk of LRR.

Does preoperative neutrophil lymphocyte ratio predict risk of recurrence and occult central nodal metastasis in papillary thyroid carcinoma?

BACKGROUND: Preoperative neutrophil to lymphocyte ratio (NLR) might be prognostic in papillary thyroid carcinoma (PTC). Given the controversy of prophylactic central neck dissection (pCND) in clinically nodal-negative (cN0) PTC, our study evaluated whether preoperative NLR predicted disease-free survival (DFS) and occult central nodal metastasis (CNM) in cN0 PTC. METHODS: A total of 191 patients who underwent pCND were analyzed. Complete blood counts with differential counts were taken before operation. NLR was calculated by dividing preoperative neutrophil count with lymphocyte count. Patients were categorized into NLR tertiles: first (NLR < 1.93; n = 63), second (NLR = 1.93-2.79; n = 64), and third tertile (NLR > 2.79; n = 64). Four other patient types, namely, benign nodular goiter, clinically nodal-positive (cN1) PTC, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma (ATC), were used as references. RESULTS: Age at operation (p < 0.001) and tumor size (p = 0.037) significantly increased with higher NLR. First tertile had significantly more TNM stage I tumors (p = 0.01) and lowest MACIS score (p = 0.002). Tumor size [hazard ratio (HR) 1.422, 95% confidence interval (CI) 1.119-1.809, p = 0.004] and multicentricity (HR = 2.545, 95% CI 1.073-6.024, p = 0.034) independently predicted DFS, whereas old age [odds ratio (OR) 1.026, 95% CI 1.006-1.046, p = 0.009), male (OR 2.882, 95% CI 1.348-6.172, p = 0.006), and large tumor (OR 1.567, 95% CI 1.209-2.032, p = 0.001) independently predicted occult CNM. NLR was not significantly associated with DFS or occult CNM. ATC had significantly higher NLR than cN1 PTC (7.28 vs. 2.74, p < 0.001). CONCLUSIONS: Although a higher NLR may imply a poorer tumor profile, it was not significantly associated with a worse DFS or higher risk of occult CNM in cN0 PTC. Perhaps, future research should focus on the prognostic value in other thyroid cancer types with a poorer prognosis.

A systematic review and meta-analysis comparing surgically-related complications between robotic-assisted thyroidectomy and conventional open thyroidectomy.

BACKGROUND: Despite gaining popularity, robotic-assisted thyroidectomy (RT) remains controversial. This systematic review and meta-analysis is aimed at comparing surgically-related complications between RT and conventional open thyroidectomy (OT). METHODS: A systematic review of the literature was performed to identify studies comparing surgically-related outcomes between RT and OT. Studies that compared ≥ 1 surgically-related outcomes between RT and OT were included. Outcomes included operating time, blood loss, complications, and hospital stay. Meta-analysis was performed using a fixed-effects model. RESULTS: Eleven studies were eligible but none were randomized controlled trials. Of the 2,375 patients, 839 (35.3 %) underwent RT, while 1,536 (64.7 %) underwent OT. RT was significantly associated with longer operating time (p < 0.001), hospital stay (p = 0.023) and higher temporary recurrent laryngeal nerve (RLN) injury (p = 0.016). Although there was no correlation between the number of RTs reported in the study and the rate of temporary RLN injury (p = -0.486, p = 0.328, respectively), routine perioperative laryngoscopy was performed in only 2 of 11 studies. Blood loss (p = 0.485), temporary (p = 0.333) and permanent (p = 0.599) hypocalcemia, hematoma (p = 0.602), and overall morbidity (p = 0.880) appeared comparable. Two (0.2 %) brachial plexus injuries in RT were reported in one study. CONCLUSIONS: Relative to OT, RT was associated with significantly longer operating time, longer hospital stay, and higher temporary RLN injury rate but comparable permanent complications and overall morbidity. Given some of the limitations with the literature and the potential added surgical risks and morbidity in RT, application of the robot in thyroid surgery should be carefully and thoroughly discussed before one decides on the procedure.

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.

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.

A systematic review and meta-analysis of prophylactic central neck dissection on short-term locoregional recurrence in papillary thyroid carcinoma after total thyroidectomy.

BACKGROUND: Prophylactic central neck dissection (pCND) at the time of total thyroidectomy (TT) remains controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). Despite occult central lymph node metastases being common, it is unclear if removing these metastases initially would reduce future locoregional recurrence (LRR). This systematic review and meta-analysis aimed at comparing the short-term LRR between patients who underwent TT with pCND and those who underwent TT alone. METHODS: A systematic review of the literature was performed to identify studies comparing LRR between patients with PTC who underwent TT + pCND (group A) and those who underwent TT alone (group B). Inclusion criteria were cN0 patients, with each comparative group containing > 10 patients, and with the number of LRR and mean follow-up duration available. The pooled incidence rate ratio (IRR) was used for calculating the LRR rate between the two groups. Other parameters evaluated included postoperative radioiodine (RAI) ablation, surgically related complications, and overall morbidity. Meta-analysis was performed using a fixed-effects model. RESULTS: Fourteen studies matched the selection criteria. Of the 3331 patients, 1592 (47.8%) belonged to group A, while 1739 (52.2%) belonged to group B. Relative to group B, group A was significantly more likely to have postoperative RAI ablation (71.7% vs. 53.1%; odds ratio [OR] = 2.60 [95% confidence interval (CI) = 2.12-3.18]), temporary hypocalcemia (26.0% vs. 10.8%; OR = 2.56 [CI = 2.04-3.21]), and overall morbidity (33.2% vs. 17.7%; OR = 2.12 [CI = 1.75-2.57]). When temporary hypocalcemia was excluded, overall morbidity was similar between the two groups (7.3% vs. 6.8%; OR = 1.07 [CI = 0.78-1.47]). Group A had a significantly lower risk of LRR than group B (4.7% vs. 8.6%; IRR = 0.65 [CI = 0.48-0.86]). CONCLUSIONS: Group A was more likely to have postoperative RAI ablation, temporary hypocalcemia, and overall morbidity than group B. Temporary hypocalcemia was the major surgical morbidity in pCND and, when excluded, the overall morbidity appeared similar between the two groups. Although our meta-analysis would suggest that those who undergo TT + pCND may have a 35% reduction in risk of LRR than those who undergo TT alone in the short term (< 5 years), it remains unclear how much of this risk reduction is related to increased use of RAI ablation and potential selection bias in some of the studies examined.

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.

Postablation stimulated thyroglobulin level is an important predictor of biochemical complete remission after reoperative cervical neck dissection in persistent/recurrent papillary thyroid carcinoma.

BACKGROUND: The efficacy of reoperative cervical neck dissection (RND) in achieving biochemical complete remission (BCR) (or postreoperation stimulated thyroglobulin [sTg] of <0.5 ng/mL) remains unclear in persistent/recurrent papillary thyroid carcinoma (PTC). We hypothesized that lower postablation sTg levels would indicate a higher rate of BCR after RND. Our study examined the association between postablation sTg and BCR after one or more RNDs. METHODS: Of 199 patients who underwent RND, 81 patients were eligible. The postablation sTg levels (≤2 and >2 ng/mL) were correlated with the postreoperation sTg levels after RNDs. Patients' clinicopathological characteristics, operative findings, and subsequent RNDs were compared between those with BCR after RNDs and those without. RESULTS: Those with postablation sTg levels of ≤2 ng/mL had significantly higher BCR rate after the first RND (77.8 vs. 5.6 %, p < 0.001), overall BCR after one or more RNDs (77.8 vs. 9.3 %, p < 0.001), and better 5-year recurrence-free survival after the first RND (80.0 vs. 60.1 %, p = 0.049) than those with postablation sTg levels of >2 ng/mL. Overall BCR gradually decreased after each subsequent RND. Postablation sTg significantly correlated with postreoperation sTg (ρ = 0.509, p < 0.001). After adjusting for the number of metastatic lymph nodes excised at first RND and presence of extranodal extension, postablation sTg of ≤ 0.2 ng/mL was the only independent factor for BCR after one or more RNDs (odds ratio 37.0, 95 % confidence interval 5.68-250.0, p = 0.001). CONCLUSIONS: Only a third of patients who underwent one or more RNDs for persistent/recurrent PTC had BCR afterward. Postablation sTg level was an independent factor for BCR. Completeness of the initial operation is important for the subsequent success of RND.

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.

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.

Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy.

BACKGROUND: Differentiated thyroid cancer survivors are at increased risk of nonsynchronous second primary malignancy, but the cause remains unclear. This study aimed to evaluate the association between radioiodine therapy and risk of nonsynchronous second primary malignancy and to examine whether the risk of nonsynchronous second primary malignancy in differentiated thyroid cancer survivors treated with radioiodine therapy is increased relative to the general population. METHODS: Among 895 radiation-naïve patients with differentiated thyroid cancer, 643 (71.8%) received ≥1 course of radioiodine therapy (radioiodine therapy-positive group) and 252 (28.2%) received no radioiodine therapy (radioiodine therapy-negative group). After a median follow-up of 93.5 months (range, 23.4-570.8), 64 (7.2%) patients developed ≥1 nonsynchronous second primary malignancy. Potential risk factors for nonsynchronous second primary malignancy were entered into a multivariable regression model and cancer incidence in the radioiodine therapy-positive and -negative groups were compared to that of the general population by estimating the standardized incidence ratios. RESULTS: The 20-year cumulative nonsynchronous second primary malignancy risk in radioiodine therapy-positive group was significantly higher than radioiodine therapy-negative group (13.5% vs 3.1%; P = .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95% CI, 1.079-7.154; P = .034) was the only independent risk factor for nonsynchronous second primary malignancy after adjusting for age, sex, period of differentiated thyroid cancer diagnosis, and stage of differentiated thyroid cancer. For females, the standardized incidence ratio in the radioiodine therapy-positive group was 1.54 (95% CI, 1.11-2.08) and in the radioiodine therapy-negative group it was 0.92 (95% CI, 0.37-1.90). CONCLUSION: Differentiated thyroid cancer female survivors treated by radioiodine therapy appeared to be at elevated risk of nonsynchronous second primary malignancy when compared to the general population and this risk was not apparent in those not previously treated by radioiodine therapy.

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.

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.

Staging systems for papillary thyroid carcinoma: a review and comparison.

OBJECTIVE: To find out the most predictive staging system for papillary thyroid carcinoma (PTC) currently available in the literature. BACKGROUND: Various staging systems or risk group stratifications have been used extensively in the clinical management of patients with PTC, but the most predictive system for cancer-specific survival (CSS) based on distinct histologic types remains unclear. METHODS: Through a comprehensive MEDLINE search from 1965 to 2005, a total of 17 staging systems were found in the literature and 14 systems were applied to the 589 PTC patients managed at our institution from 1961 to 2001. 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 (PVE). RESULTS: All 14 staging systems significantly predicted CSS (P < 0.001). The 3 highest ranked staging systems by PVE were the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS) (18.7) followed by the new AJCC/UICC 6th edition tumor, node, metastases (TNM) (17.9), and the European Organization for Research and Treatment of Cancer (EORTC) (16.6). CONCLUSIONS: All of the currently available staging systems predicted CSS well in patients with PTC regardless of which histologic type from which they were derived. When predictability was measured by PVE, the MACIS system was the most predictive staging system and so should be the staging system of choice for PTC in the future.