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Background: Previous studies have reported an association between four or more foci of vascular invasion (VI) and thyroid cancer prognosis, while the current study aimed to investigate the association between extent of VI and outcome of encapsulated angioinvasive follicular thyroid carcinoma (FTC)., Methods: The records of 303 patients with encapsulated angioinvasive FTC confirmed by surgical specimens at Ito Hospital from January 2005 to December 2014 were retrospectively reviewed. Thirteen patients had distant metastasis at diagnosis and were classified as M1., Results: Among the 290 patients with M0 encapsulated angioinvasive FTC, the 10-year disease-free survival (DFS) rate was 85.6%. Those with a VI of 1 (n = 131) or ≥ 2 (n = 159) had a 10-year DFS rate of 94.9% and 77.9% (p < 0.001), respectively, and those with a VI of 1-3 (n = 211) or ≥ 4 (n = 79) had a 10-year DFS rate of 86.3% and 83.3% (p = 0.311), respectively. Multivariate analysis identified age ≥ 55 years (p = 0.031) and VI ≥ 2 (p = 0.002) as independent negative prognostic factors for DFS. Patients with M0 encapsulated angioinvasive FTC aged ≥ 55 years and VI ≥ 2 had significantly poorer prognosis and a 10-year DFS rate of 66.4% (p < 0.001)., Conclusions: Patients with encapsulated angioinvasive FTC who had two or more foci of VI, especially patients aged ≥ 55 years, should be carefully followed-up., (© 2022. Society of Surgical Oncology.)

Background: The lymph node (LN) ratio (LNR) has been proposed as a sensitive prognosticator in patients with esophageal squamous cell carcinoma (ESCC), especially when the number of LNs harvested is insufficient. We investigated the association between the LNR and survival in patients with locally advanced ESCC who received neoadjuvant chemotherapy (NAC) and explored whether the LNR is a prognosticator in these patients when stratified by their response to NAC., Methods: We retrospectively reviewed 199 locally advanced ESCC patients who received curative resection after NAC between January 2011 and December 2019. The predictive accuracy of the adjusted X-tile cut-off values for LNR of 0 and 0.13 was compared with that in the Union for International Cancer Control pathological N (UICC pN) categories. The association between survival rate and clinicopathological features was examined., Results: Multivariate analysis identified that the LNR was an independent risk factor for recurrence-free survival [RFS; hazard ratio (HR) 6.917, p < 0.001] and overall survival (OS) (HR 4.998, p < 0.001). Moreover, even when stratified by response to NAC, the LNR was a significant independent risk factor for RFS and OS (p < 0.001). The receiver operating characteristic curves identified that the prognostic accuracy of the LNR tended to be better than that of the UICC pN factor in all cases and responders., Conclusion: The LNR had a significant prognostic value in patients with locally advanced ESCC, including in those who received NAC., (© 2021. Society of Surgical Oncology.)

Background: Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index., Methods: We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1-2; Group 2: NPS = 3-4). We compared the clinicopathological characteristics and survival rates among the groups., Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P < 0.001). The NPS was superior to other systemic inflammatory and nutritional index for predicting prognoses, as determined using area under the curves (P < 0.05). Multivariate analysis demonstrated that the NPS was a significant predictor of poor RFS (Group 1: hazard ratio [HR] 1.897, P = 0.049; Group 2: HR 3.979, P < 0.001) and OS (Group 1: HR 2.152, P = 0.033; Group 2: HR 3.239, P = 0.006)., Conclusions: The present study demonstrated that NPS was an independent prognostic factor in patients with locally advanced ESCC and more reliable and accurate than the other systemic inflammatory and nutritional index.

Background: The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs., Methods: The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor., Results: Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05)., Conclusion: LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.

Background: Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition)., Patients and Methods: We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared., Results: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (P < 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS [M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254-4.342, P < 0.001; H-LNR: HR 5.148, 95% CI 3.546-7.474, P < 0.001] and OS (M-LNR: HR 2.749, 95% CI 2.038-3.708, P < 0.001; H-LNR: HR 4.654, 95% CI 3.288-6.588, P < 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (P < 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (P = 0.001 and < 0.001, respectively)., Conclusions: High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage.

Background: This study was designed to investigate whether postoperative infectious complications (ICs) are a risk factor for the prognosis in esophageal cancer patients who receive neoadjuvant chemotherapy by stratifying the response to neoadjuvant chemotherapy., Methods: The present study retrospectively examined patients who received neoadjuvant chemotherapy followed by esophagectomy between January 2011 and September 2015. Risk factors for overall survival (OS) were examined by Cox proportional hazard analyses. Pathological responders to neoadjuvant chemotherapy were defined as those with a tumor disappearance of more than one-third of the initial tumor. Postoperative ICs were defined using the Clavien-Dindo classification., Results: Of the 111 patients examined, 45 (40.5%) developed postoperative ICs. A pathological response to neoadjuvant chemotherapy was observed in 54 (48.6%) patients. The multivariate analysis demonstrated that postoperative ICs were a significant independent risk factor for the OS (hazard ratio [HR] 2.359; 95% confidence interval [CI] 1.057-5.263, p = 0.036). In the subset analysis, postoperative ICs were a marginally significant independent risk factor for OS in the nonresponders (HR 2.862; 95% CI 0.942-8.696, p = 0.063) but not in the responders (HR 0.867; 95% CI 0.122-6.153, p = 0.886)., Conclusions: These results suggested that the negative survival impact of postoperative ICs can be canceled out in esophageal cancer patients who respond to neoadjuvant chemotherapy.

Background: Complete surgical resection is essential for a cure for most gastric cancer. Recently it was reported that surgical Apgar score (SAS) can predict postoperative complication and that postoperative complication is associated with poor long-term survival. The aim of this study is to assess whether SAS can predict overall survival (OS) after surgery for gastric cancer., Methods: We retrospectively compared clinicopathological characteristics and survival between high and low SAS score groups in patients who underwent gastrectomy for gastric cancer., Results: Low-scored SAS group (group L) was significantly more common among ASA-PS 2, open approach, total gastrectomy, D2 lymph node dissection, postoperative complication grade 2-4, deep tumor invasion, lymph node metastases, and advanced pathological TNM stage than high-scored SAS group (group H). The 5-year OS of group H and group L were 81.6 and 55.9 %, respectively (p < .001); OS of group L tended to be poorer than that of group H in stage III patients (p = .060) and in stage IV patients (p < .001). In multivariate analysis, pathological stage and SAS were identified as independent predictors for OS., Conclusions: SAS is useful for predicting survival after surgery for gastric cancer.

Background: Lean body mass loss after surgery, which decreases the compliance of adjuvant chemotherapy, is frequently observed in gastric cancer patients who undergo gastrectomy for gastric cancer. However, the risk factors for loss of lean body mass remain unclear., Methods: The current study retrospectively examined the patients who underwent curative gastrectomy for gastric cancer between June 2010 and March 2014 at Kanagawa Cancer Center. All the patients received perioperative care for enhanced recovery after surgery. The percentage of lean body mass loss was calculated by the percentile of lean body mass 1 month after surgery to preoperative lean body mass. Severe lean body mass loss was defined as a lean body mass loss greater than 5 %. Risk factors for severe lean body mass loss were determined by both uni- and multivariate logistic regression analyses., Results: This study examined 485 patients. The median loss of lean body mass was 4.7 %. A lean body mass loss of 5 % or more occurred for 225 patients (46.4 %). Both uni- and multivariate logistic analyses demonstrated that the significant independent risk factors for severe lean body mass loss were surgical complications with infection or fasting (odds ratio [OR] 3.576; p = 0.001), total gastrectomy (OR 2.522; p = 0.0001), and gender (OR 1.928; p = 0.001)., Conclusions: Nutritional intervention or control of surgical invasion should be tested in future clinical trials for gastric cancer patients with these risk factors to maintain lean body mass after gastrectomy.

Background and Aims: Compliance with S-1 adjuvant chemotherapy is not satisfactory, and the aim of the present study was to clarify risk factors for the continuation of S-1 after gastrectomy., Methods: This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage II/III disease, had a creatinine clearance >60 ml/min, and received adjuvant S-1 at our institution between June 2010 and March 2014. The time to S-1 treatment failure (TTF) was calculated., Results: Fifty-eight patients were selected for the present study. When the TTF curves stratified by each clinical factor were compared using the log-rank test, lean body-mass loss (LBL) of 5 % was regarded as a critical cutoff point. Univariate Cox's proportional hazard analyses demonstrated that LBL was a significant independent risk factor for continuation. The 6-month continuation rate was 91.7 % in patients with an LBL < 5 %, and 66.3 % for patients with an LBL > 5 % (p = 0.031)., Conclusions: The present study demonstrated that LBL might be an important risk factor for a decrease in compliance to adjuvant chemotherapy with S-1 in patients with stage II/III gastric cancer who underwent D2 gastrectomy. A multicenter, double-blinded, prospective cohort study is necessary to confirm whether LBL would affect adjuvant S-1 continuation.

Background: Clinical T1 gastric cancer has low metastatic potential to lymph nodes and is generally curable by local treatment. Endoscopic resection can preserve the whole stomach and does not impair the patient's quality of life; however, its indication is strictly limited to the subset of patients without nodal metastasis. The study was designed to predict reliably the patients without nodal metastasis based only on the clinical information., Methods: We examined patients with clinical T1 disease who were treated with surgery. The clinically available information was evaluated for its ability to predict nodal metastasis by logistic regression model. Then, the predictive ability of the logistic regression model using the risk factors for nodal metastasis was evaluated by a receiver operating characteristic curve., Results: A total of 511 patients were entered into this study. The clinical depth (cT1a or cT1b), maximal tumor diameter, and pathological type were confirmed to be significantly different between patients with and without nodal metastasis. The cutoff value of the tumor diameter differed depending on the histology and clinical depth: 79 mm for differentiated type and 48 mm for undifferentiated type in cT1a tumors, and 43 mm for differentiated type and 11 mm for undifferentiated type in cT1b tumors. According to these criteria, 348 of the 511 patients (68.1 %) were classified to have predictive N0 status. The negative predictive value was 95.7 % (95 % confidence interval 94.0-97.5 %)., Conclusions: The predictive criteria based on the multivariate logistic model identified that almost two-thirds of the patients with clinical T1 gastric cancer were possible candidates for endoscopic treatment.

Background: T1 gastric cancer can be diagnosed only by endoscopy and is almost curable by local treatment. It has been unclear how a multidetector-row computed tomography (CT) evaluation is valuable for clinical T1 patients., Methods: Patients with clinical T1 disease, as diagnosed by endoscopy and treated with endoscopic submucosal dissection (ESD) or surgery between October 2000 and October 2007, were examined. The efficacy of CT was evaluated by the reversal rate of endoscopic T1 by CT, the incidence of clinical M1 disease, and the accuracy of diagnosing pathological N+ disease in patients who received surgery. To confirm metachronous distant and nodal metastases, the disease-free survival (DFS) also was evaluated., Results: A total of 761 patients, 236 treated by ESD and 525 treated with surgery, were examined. None of the patients had an endoscopic diagnosis of clinical T1 reversed by CT. No clinical M1 disease was found. Among the 525 patients who underwent surgery, 8 showed clinical N+ disease (1.5 %), while 47 demonstrated pathological N+ disease (8.9 %). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were 90.3, 4.3, 98.7, 25, and 91.3 %, respectively. The 5-year DFS rate was 93.6 % (95 % confidence interval 91.4-95.8 %)., Conclusions: The present study suggests that diagnostic value of CT is limited for staging of clinical T1 gastric cancer patients, because the reversal rate of endoscopic T1 by CT was very low, clinical M1 disease was rare, the diagnosis of N+ status was unreliable, and metachronous M1 and N+ findings were rare.

Background: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer may prevent the development of an impaired nutritional status due to reduced surgical stress compared with open distal gastrectomy (ODG)., Methods: This study was performed as an exploratory analysis of a phase III trial comparing LADG and ODG for stage I gastric cancer during the period between May and December of 2011. All patients received the same perioperative care via fast-track surgery. The level of surgical stress was evaluated based on the white blood cell count and the interleukin-6 (IL-6) level. The nutritional status was measured according to the total body weight, amount of lean body mass, lymphocyte count, and prealbumin level., Results: Twenty-six patients were randomized to receive ODG (13 patients) or LADG (13 patients). The baseline characteristics and surgical outcomes were similar between the two groups. The median IL-6 level increased from 0.8 to 36.3 pg/dl in the ODG group and from 1.5 to 53.3 pg/dl in the LADG group. The median amount of lean body mass decreased from 48.3 to 46.8 kg in the ODG group and from 46.6 to 46.0 kg in the LADG group. There are no significant differences between two groups., Conclusions: The level of surgical stress and the nutritional status were found to be similar between the ODG and LADG groups in a randomized comparison using the same perioperative care of fast-track surgery.

Objective: The purpose of this study was to clarify the priority of nodal dissection in Siewert types II and III adenocarcinoma of the esophagogastric junction (AEG)., Methods: The priority of nodal dissection was evaluated based on the therapeutic value index calculated by multiplying of the frequency of metastasis to each station and the 5-year survival rate of patients with metastasis to that station., Results: A total of 176 patients (95 type II and 81 type III) were examined. Among the lymph nodes that had a metastatic incidence exceeding 10 %, the stations showing the first to fourth highest index were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the node at the root of the left gastric artery (No. 7) in the total cohort, as well as in each type. The next station was the lower thoracic paraesophageal lymph node (No. 110), followed by the nodes along the proximal splenic artery (No. 11p) in type II, whereas it was the nodes along the proximal splenic artery (No. 11p) followed by the para-aortic nodes (No. 16a2), the nodes at the celiac artery (No. 9), and the nodes around the splenic hilum (No. 10) in type III., Conclusions: These results suggest that the highest priority nodal stations to be dissected were the paracardial and lesser curvature nodes (Nos. 1, 2, and 3) and the nodes at the root of the left gastric artery (No. 7), regardless of the Siewert subtype, but the subsequent priority was different depending on the subtype.

Background: Multidetector-row CT (MDCT) may provide accurate preoperative staging of resectable gastric cancer. However, the standard methods and criteria to diagnose the T and N stages to select the patients who are good candidates for neoadjuvant chemotherapy have not been established yet., Methods: The aim of this prospective study was to evaluate the accuracy of MDCT to diagnose the serosal invasion and nodal metastases of gastric cancer. Patients who had gastric adenocarcinoma underwent MDCT scanning using a standardized method. The T and N stage were diagnosed by prespecified criteria. The analyses were performed in the patients who had cN0-2 and M0 tumors and underwent curative gastrectomy as a primary treatment. The accuracy was calculated by comparing the results of MDCT with the histopathological findings., Results: A total of 315 patients were analyzed. The overall diagnostic accuracy (95 % confidence interval) of T staging was 71.4 % (225 of 315, 66.2-76.1). The accuracy, sensitivity, and specificity for serosal invasion were 85.7 % (81.4-89.1), 54.5 % (42.6-66.0), and 94.0 % (90.3-96.3), respectively. The false-positive rate for serosal invasion was 6.0 % (2.9-7.7). The overall diagnostic accuracy of N staging was 75.9 % (239 of 315, 70.9-80.3). The accuracy, sensitivity, and specificity for nodal metastases were 81.3 % (76.6-85.2), 46.4 % (36.8-56.3), and 96.8 % (93.5-98.4), respectively. The false-positive rate for nodal metastases was 3.2 % (1.6-6.5 %)., Conclusions: These results suggest that MDCT provides an accurate diagnosis with high specificity and a low false-positive rate and can be used to select the patients who are candidates for preoperative chemotherapy.

Background: Compliance of S-1 adjuvant chemotherapy is not high. The aim of the present study is to clarify risk factors for continuation of S-1 after gastrectomy., Methods: This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2/3 disease, creatinine clearance more than 60 ml/min, and received adjuvant S-1 at our institution between June of 2002 and December of 2011. Time to S-1 treatment failure (TTF) was calculated., Results: A total of 103 patients were selected for the present study. When TTF curve stratified by each clinical factor was compared by the log-rank test, body weight loss (BWL) of 15 % was regarded as a critical point. Both univariate and multivariate Cox proportional hazard analyses demonstrated that BWL was the significant independent risk factor. Moreover, BWL remained a significant factor in both the univariate and multivariate analyses in the subset excluding 8 patients who discontinued S-1 because of recurrence. The 6-month continuation rate was 66.4 % in the patients with BWL < 15 and 36.4 % in patients with BWL ≥ 15 % (P = .017)., Conclusions: BWL was the most important risk factor for the compliance of adjuvant chemotherapy with S-1 in the patients with stage 2/3 gastric cancer who underwent D2 gastrectomy. To improve drug compliance that leads to survival, it is a key to maintain body weight before starting S-1 adjuvant. Our study emphasizes the requirement for adequate studies of perioperative nutritional intervention in patients who receive gastrectomy for advanced gastric cancer.

Background: The aim of this study is to clarify whether TNM-EC or TNM-GC is better for classifying patients with AEG types II/III., Methods: The patients who had AEG types II/III and received D1 or more radical lymphadenectomy were selected. The patients were staged both by seventh edition of TNM-EC and TNM-GC. The distribution of the patients, the hazard ratio (HR) of each stage, and the separation of the survival were compared., Results: A total of 163 patients were enrolled in this study. TNM-EC and TNM-GC classified 25 (20 and 5) and 32 (20 and 12) patients to stage I (IA and IB), 15 (4 and 11), and 33 (11 and 22) to stage II (IIA and IIB), 88 (24, 3, and 61) and 63 (14, 26, and 23) to stage III (IIIA, IIIB, and IIIC), and 35 and 35 to stage IV, respectively. The distribution of the patients was substantially deviated to stage IIIC in TNM-EC but was almost even in TNM-GC. A stepwise increase of HR was observed in TNM-GC, but not in TNM-EC. The survival curves between stages II and III were significantly separated in TNM-GC (P = 0.019), but not in TNM-EC (P = 0.204). The 5-year survival rates of stages IIIA, IIIB, and IIIC were 69.0, 100, and 38.9% in TNM-EC and were 52.0, 43.4, and 33.9% in TNM-GC, respectively., Conclusions: TNM-GC is better for classifying patients with AEG types II/III than TNM-EC is. These results could impact the next TNM revision for AEG.

Background: Risk factors and treatment strategy in younger patients with papillary thyroid carcinoma are still controversial., Methods: We reviewed 120 consecutive papillary thyroid carcinoma patients younger than 20 years who underwent initial surgery between 1977 and 2004 (14 male and 106 female subjects; mean age, 16.3 years; mean follow-up, 11.6 years). Outcomes were evaluated initially, and risk factors for disease-free survival (DFS) were analyzed statistically. Cox proportional multivariate analysis revealed that initial nodal manifestation (P < .001, hazard ratio 2.97) was the most statistically significant risk factor for DFS. The outcomes were then compared between four subgroups on the basis of the initial nodal manifestation and node dissection: 17 patients in group A (no lymphadenopathy, no or only prophylactic central dissection), 30 patients in group B (no lymphadenopathy, prophylactic modified neck dissection, MND), 46 patients in group C (nonpalpable lymphadenopathy detected by radiological or operative findings, therapeutic MND), and 27 patients in group D (palpable lymphadenopathy, therapeutic MND)., Results: Subtotal/total thyroidectomy and radioactive iodine therapy were performed for 47.1 and 0% in group A, 33.3 and 0% in group B, 43.4 and 10.9% in group C, and 85.1 and 48.1% in group D, respectively. In groups A, B, C, and D, 0%, 3.3%, 28.3%, and 48.1% developed recurrence, respectively (P < .001). DFS Kaplan-Meier curves differed significantly among the four subgroups (P < .0005)., Conclusions: Initial nodal manifestation is useful to predict DFS in younger papillary thyroid carcinoma patients. Our findings will be beneficial to determine the treatment strategy. Conservative therapy is considered acceptable for patients without risk factors.

Background: Although all tumor, node, metastasis system (TNM) stage IVA papillary thyroid carcinomas (PTCs) do not seem to behave equivalently as a result of various tumor and node stages, to our knowledge, subclass evaluation has never been attempted., Methods: We reviewed 119 stage IVA PTC patients who underwent initial thyroidectomy with modified neck dissection as curative surgery at our institution (33 male patients, 86 female patients; age 61.6 years; follow-up 87.7 months). These patients were divided into groups A (T1-3N1b; n = 79), B (T4aN0-1a; n = 9), and C (T4aN1b; n = 31). Outcomes were compared between the groups., Results: The rates of recurrence (P < .05) and disease mortality (P < .001) were 13.9% and 1.3%, 0% and 0%, and 35.5% and 19.4% in groups A, B, and C, respectively. The 10-year disease-free survival (DFS) and disease-specific survival (DSS) were 73.4% and 97.9%, 100% and 100%, and 54.9% and 69.7% in groups A, B, and C, respectively. DFS and DSS curves differed significantly between group A + B and group C (P < .005 and P < .0005, respectively). The relative risks of DFS and DSS in group C were 2.8-fold and 14.9-fold, respectively, compared with group A (P < .05), and 3.2-fold and 17.5-fold compared with group A + B (P < .01). Thus, outcomes were worse in group C. In multivariate analysis, esophageal invasion and lymphadenopathy were independent risk factors for both DFS and DSS in stage IVA PTC patients., Conclusions: Outcomes in stage IVA are not equivalent, and patients with T4aN1b are at greater risk for worse prognosis. Therefore, we recommend subclass evaluation for TNM stage IVA PTCs.