Differentiated thyroid carcinoma: prognostic factors

Factors influencing prognosis and long term outcome of thyroid cancer have been described by several groups. It is, however, not clear how the moderate iodine deficiency in Hungary can influence the previously described prognostic factors by other means than shifting differentiated cancer incidence toward the follicular type. Data of 423 out of 472 patients who had been operated on for papillary (372) and follicular (100) thyroid cancer between 1971 and 1997 at our institution have been analyzed retrospectively. Histological specimens were re-evaluated and, if needed, revised. Survival curves were compared using the Kaplan-Meier method. The overall 5 and 10 year survival rates were 93% and 89% for papillary, and 92% and 80% for follicular carcinoma. As an independent factor extrathyroidal invasion (papillary p = 0.000, follicular p = 0.000), lymph node involvement (papillary p = 0.000, follicular 0.011), distant metastases (papillary p = 0.000, follicular p = 0.000), and age over 40 years (papillary p = 0.000, follicular p = 0.000) had negative influence on survival. Multifocality, gender, type of surgery (total or near-total thyroidectomy vs. less than near-total thyroidectomy), and lymphocytic infiltration did not influence survival. Iodine intake did not influence survival, however, the incidence of follicular cancer was higher in iodine deficient regions. When analyzing the papillary and follicular groups separately by Cox regression, extrathyroidal invasion (p = 0.008), lymph node metastasis (p = 0.004), distant metastasis (p = 0.000), and age over 40 years (p = 0.000) were significant predictors in the papillary group, while only tumor extrathyroidal invasion (p = 0.019), and distant metastases (p = 0.000) were significant negative factors in the follicular group.     

The influence of pNx/pN0 grouping in a multivariate setting for outcome modeling in patients with clear cell renal cell carcinoma

PURPOSE: Lymphadenectomy, especially extended lymphadenectomy, is not commonly performed in patients undergoing a radical nephrectomy for clear cell renal cell carcinoma. Surgeons may sample suspicious regional lymph nodes, but the lymph node status of many patients with renal cell carcinoma remains unknown, termed stage pNx. Outcome models based on large institutional reviews have been criticized for grouping stages pNx and pN0 cases because of concern that the pNx category may include unrecognized stages pN1/pN2 disease. We evaluated cancer specific survival differences in patients with clear cell renal cell carcinoma and a lymph node stage of pNx, pN0 or pN1/pN2. MATERIALS AND METHODS: We searched the registry at our institution for patients who underwent radical nephrectomy for clear cell histology renal cell carcinoma between 1970 and 1998. Those with distant metastases at surgery were excluded from study. Clinical features obtained from the medical record included age at surgery, history of tobacco use, hypertension and symptomatic disease at presentation. A single urological pathologist reviewed all tumor specimens for nuclear grade, tumor necrosis, surgical margin status, 1997 tumor stage and lymph node status. These features were compared in patients with stages pNx and pN0 tumors. Cox proportional hazards models were used to compare cancer specific survival in univariate fashion, and after adjusting for tumor stage and grade. RESULTS: The study cohort consisted of 1,535 patients with sporadic, unilateral clear cell renal cell carcinoma who underwent radical nephrectomy. There were 600 patients (39%) with stage pNx, 870 (57%) with stage pN0 and 65 (4%) with stages pN1/pN2 tumors. At an average of 4.2 years after surgery 414 patients died of renal cell carcinoma. On univariate analysis patients with stage pN0 tumors were significantly more likely to die of renal cell carcinoma than those with stage pNx tumors (risk ratio 1.40, 95% confidence interval 1.12 to 1.75, p = 0.003). However, after adjusting for tumor stage and nuclear grade the difference in outcome for stages pNx and pN0 tumors was not statistically significant (risk ratio 1.07 95% confidence interval 0.85 to 1.34, p = 0.583). Patients with stage pNx disease were significantly less likely to be symptomatic at presentation (p = 0.002), have tumors that were less than 5 cm. (p <0.001) and of lower stage (p <0.001) and grade (p = 0.005), and to have tumors with necrosis (p = 0.024) than patients with stage pN0 disease. CONCLUSIONS: Combining stages pNx and pN0 cases to create outcome prediction models after radical nephrectomy for clear cell renal cell carcinoma is appropriate in a multivariate setting that includes tumor stage and grade. Clinical features available preoperatively and during surgery can help guide the decision to perform limited lymph node sampling. When the tumor is 5 cm. or greater, shows pathological necrosis or is advanced grade 3 or 4, lymph node sampling adds little prognostic information.     

Evidence-based protocols for the management of well-differentiated carcinomas of the thyroid

OBJECTIVES: In recent years, well-differentiated carcinomas of the thyroid have been stratified into low-risk and high-risk groups. The pattern of thyroid cancer in India is different from that seen in the West. Moreover, patients present with more advanced stages of the disease. Our aim was to develop protocols for the management of well-differentiated thyroid cancer, based on the analysis of our data and our experience. METHODS: Cases of thyroid carcinoma, which were surgically treated at the Tata Memorial Hospital during 1970-5, were studied. The survival curves were plotted according to the Kaplan-Meier method. Univariate analysis was done using the log rank test. The prognostic factors analyzed were age, sex, tumour size, extra-thyroid extension, distant metastases and lymph node metastases. Multivariate analysis using the Cox regression model was performed. Analyses were separate for follicular and papillary carcinomas. RESULTS: Four hundred and seventeen cases were entered in the study, of which 198 were follicular and 219 were papillary. Based on the evidence derived from this study, we stratified our cases into low- and high-risk groups. The low-risk group consisted of patients below 40 years of age, nodules smaller than 5 cm, absence of extra-thyroidal spread and absence of distant metastases. For follicular carcinoma, the low-risk group had 100% survival at 15 years, compared with 40% for the high-risk group. (p < 0.001). For papillary carcinomas, the survival at 15 years was 95% for the low-risk group and 40% for the high-risk group (p < 0.001). CONCLUSIONS: We recommend lobectomy for the low-risk group, and total thyroidectomy for the high-risk group and for cases with lymph node metastases. In the latter, total thyroidectomy facilitates the use of 131I.     

The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer

Though survival for well-differentiated thyroid cancer is very good, specific populations suffer greater recurrence and mortality. Defining these cohorts can significantly influence prognosis and extent of treatment. This study, using a large, multi-institutional database, seeks to determine how the presence of lymph node disease in patients with well-differentiated thyroid cancer affects outcome. The Surveillance, Epidemiology, and End Results (SEER) database is a large-scale sample of 14 per cent of the U.S. population. It was used to identify patients with papillary and follicular thyroid carcinomas and identify the prognostic implications of lymph node metastasis. Additional factors, including presence of metastasis, age, and tumor size, were compared using multivariate and chi2 analyses. Of 19,918 patients identified, lymph node status was known for 9,904 (49.7%). On multivariate analysis, age > 45 years, presence of distant metastasis, large tumor size, and lymph node involvement significantly predicted poor outcome. Overall survival at 14 years was 82 per cent for node negative and 79 per cent for node positive patients (P < 0.05). This study shows that the survival of patients with well-differentiated thyroid cancer is adversely affected by lymph node metastases. The optimum treatment for this cohort needs further delineation, as particular populations are at greater risk of recurrence and death.     

Prognostic factors for well-differentiated thyroid cancer in an endemic area

A retrospective analysis of 215 differentiated thyroid cancers was undertaken to identify the various prognostic variables. There were 132 papillary and 83 follicular cancers; both histologic types occurred at an earlier age, with a male to female ratio of 1: 1.1 (signifies near parity in both sexes, in contrast to marked female preponderance in most of the reports and amongst benign thyroid disorders). There was a significant difference in the size of the primary tumours; 60/132 (45%) of papillary and 30/83 (36%) of follicular cancers were early T0-1 lesions and 20 (15%) papillary and 24 (29%) follicular cancers were advanced T3 lesions. Age did not affect the size of the primary tumour. Regional lymph node and pulmonary metastases were common in both types of cancer while distant metastases occurred more frequently in follicular cancers (p < 0.005). Following surgery, contralateral lobe recurrence in the remaining lobe was more common in the follicular cancer group, while loco-regional recurrence after near-total thyroidectomy was more frequent in the papillary cancer group (p > 0.05). Mortality in 26/132 (20%) papillary and 28/83 (34%) follicular cancer patients was high in both groups, but significantly higher in the follicular cancer group (p < 0.05). Although mortality among patients with papillary cancer was higher in patients older than 40 years of age (p < 0.05), age did not affect survival in patients with follicular cancer. Gender did not affect survival in either group. The extent of the disease at presentation was the most important determinant of survival, with mortality significantly higher among patients with T3N3M1 lesions (p < 0.001).     

Importance of lymph node metastases in follicular thyroid cancer

There are many concepts of risk and prognostic factor analysis for differentiated thyroid cancer. The prognostic role of lymph node metastases in follicular thyroid cancer (FTC), however, is still controversial. We performed a retrospective trial in 186 patients with FTC (124 women, 62 men; mean follow-up 5.5 years) questioning whether lymph node metastases and radical thyroid surgery with neck dissection contribute to the prognosis of FTC. Univariate analysis demonstrated that lymph node metastasesp <0.005), tumor size (p <0.005), tumor stage (p <0.005), distant metastases p = 0.0063), and gender (p = 0.003) are significant prognostic factors for recurrence (Kaplan-Meier). Tumor size (p = 0.004), lymph node metastases p = 0.0478), and distant metastases p = 0.0064) influenced mortality. Age and extent of surgery were not significant for recurrence nor was gender for mortality. Multivariate analysis (Cox regression test) characterized tumor size (p <0.005) and lymph node metastases p = 0.004) as prognostic factors for recurrence of FTC. No significant difference was detected between patients being treated by thyroidectomy when compared to patients treated by thyroidectomy plus neck dissection in relation to recurrence. Our data demonstrate lymph node metastases to be a significant prognostic factor for recurrence of FTC and the patient’s survival. We advocate thyroidectomy plus central lymph node dissection as the basic surgical strategy. For T3 and T4 tumors, unilateral modified neck dissection is an all but optional procedure. Whether radical surgery with thyroidectomy plus neck dissection has an impact on survival remains questionable.     

Prognostic factors in differentiated carcinoma of the thyroid gland.

A retrospective review of a consecutive series of 931 previously untreated patients with differentiated thyroid carcinoma treated over a 50-year period was undertaken to analyze prognostic factors. Data pertaining to demographic status, clinical, operative, and pathologic findings, and survival were analyzed. Univariate statistical analysis was performed based on the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. There were 630 female and 301 male patients, with an average age of 43 years. A total of 532 patients were younger than 45 years. Seven hundred thirty-one patients had either pure or mixed papillary carcinoma, and 200 had follicular carcinoma. In 153 patients, lesions were larger than 4 cm. Extrathyroidal extension was noted in 71 patients. Multifocal lesions were present in 159 patients. Regional lymph node metastasis was present on admission in 451 patients, and distant metastases were noted on presentation in 45 patients. Determinate survival for all patients was 87% at 10 years. Favorable prognostic factors using univariate analysis included female gender, multifocal primary tumors, and regional lymph node metastases. Adverse prognostic factors included age over 45 years, follicular histology, extrathyroidal extension, tumor size exceeding 4 cm, and the presence of distant metastases. On multivariate analysis, the only factors that affected the prognosis were patient age, histology, tumor size, extrathyroidal extension, and distant metastases. These observations support findings of reports from the Mayo Clinic and Lahey Clinic regarding the significance of prognostic factors for differentiated carcinoma of the thyroid gland.     

Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease?

BACKGROUND: The current American Joint Committee on Cancer/International Union Against Cancer classification designates cervical and mediastinal lymph nodes as regional lymph nodes. In a unilateral thyroid neoplasm, however, involvement of the contralateral cervical lymph node compartment or the mediastinal lymph node compartment, both of which have been designated "distant" lymph nodes, may serve as a surrogate parameter of distant metastases. METHODS: This institutional series consisted of 105 consecutive patients with medullary thyroid cancer who underwent systematic dissections of both distant lymph node compartments. RESULTS: Thirty-eight patients had no distant lymph node metastasis, 36 patients had involvement of only 1, and 31 patients of both distant lymph node compartments. Significant associations (P < .001) were seen on univariate analysis between the number of involved "distant" lymph node compartments (none, one, or both) and extrathyroidal extension (3%, 33%, and 58%), the number of positive lymph nodes (means of 3, 13, and 33), and distant metastasis (8%, 36%, and 61%). In a multivariate logistic regression model, only involvement of one or both "distant" lymph node compartments (versus no distant lymph node metastasis) remained significantly related to distant metastasis in a dose-dependent fashion. CONCLUSIONS: "Distant" lymph nodes in medullary thyroid cancer should be regarded as nonregional lymph nodes because their involvement is indicative of distant metastasis.     

Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma

OBJECTIVE: To define the role of BRAF gene mutation in the progression of papillary thyroid carcinoma. SUMMARY BACKGROUND DATA: BRAF gene mutation is frequently detected in papillary thyroid carcinoma. Its role in pathogenesis or progression is under investigation. METHODS: Patients who underwent thyroidectomy and sentinel lymph node biopsy for papillary thyroid cancer were accrued. BRAF mutation was assessed in primary tumors and matched sentinel lymph nodes by a quantitative real-time PCR assay. RESULTS: Tissue specimens from 103 consecutive patients were evaluated. BRAF mutation of the primary tumor was detected in 34 (33%) patients. In 26 of 34 (76%) patients with BRAF mutation, concomitant lymph node metastasis was detected. On the contrary, in 69 patients with BRAF mutation-negative primary tumors, only 12 (17%) patients had lymph node metastasis (chi, P < 0.0001). BRAF mutation was detected in 20 of 26 (77%) lymph node metastases matched to BRAF mutation-positive primary tumors; it was not detected in lymph node metastases matched to BRAF mutation-negative primary tumors. Univariate analysis identified age, stage, tumor size, and BRAF mutation as prognostic factors for lymph node metastasis. In multivariate analysis, only BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5-34.0, P < 0.0001). CONCLUSIONS: BRAF mutation may be a key genetic factor for the metastatic progression of papillary thyroid carcinoma. The study demonstrates that this gene mutation is a significant risk factor for locoregional lymph node metastasis and has potential utility as a surrogate marker.     

Differentiated thyroid cancer in children and adolescents

Introduction: There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. Methods: We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. Results: The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P = 0.009), more lymph-node involvement (P = 0.007) and more distant metastases (P = 0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P = 0.02) associating with distant metastasis. Conclusion: It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type. Received: 31 January 1998     

Prospective management of nodal metastases in differentiated thyroid cancer

Previous studies have concluded that lymph node metastases do not affect survival rates in patients with differentiated thyroid carcinoma and, therefore, nodal metastasis has not been evaluated as a prognostic factor in recent definitions of risk groups. To determine the significance of nodal disease, we reviewed 227 consecutive patients with differentiated thyroid carcinoma (173 with papillary, 37 with follicular, and 17 with Hürthle cell carcinoma). Of 70 (31%) patients with lymph node metastases (14 [20%] palpable preoperatively and 56 [80%] detected by routine sampling of middle and lower cervical nodes), 13 (19%) developed a recurrence compared with only 3 of 157 (2%) without nodal disease (p less than 0.01). Sixty-eight patients were treated with modified neck dissection, 63 of whom received adjuvant radioiodine. There were 10 recurrences in 63 patients (16%) who had been treated with radioiodine, compared with 3 recurrences in 7 (42%) patients who did not receive adjuvant radioiodine. Follow-up ranged from 2 to 28 years, with a mean of 8 years. Involvement of the lymph nodes was a marker for systemic disease occurring synchronously in 4 of 5 patients who presented with distant metastases and preceding systemic recurrence in 9 of 10 patients. Four patients (2%), all with lymph node metastases (three with concomitant extrathyroidal invasion and one with systemic metastases at initial presentation), died of thyroid carcinoma. Cervical lymph node metastases were associated with a higher incidence of recurrence and occurred synchronously or preceded the development of distant metastases in 13 of 15 (87%) patients. Although these findings were not statistically significant for overall survival, they lend support to routine cervical lymph node sampling for detection of and modified neck dissection with adjuvant radioiodine therapy for treatment of lymph node metastases. Such measures should reduce the subsequent recurrence rate and permit early detection and treatment of systemic disease.     

Extranodal extension in regional lymph nodes is associated with outcome in patients with renal cell carcinoma

PURPOSE: The 2002 American Joint Committee on Cancer pN classification for renal cell carcinoma is based on the number of positive regional lymph nodes. We examined the associations of pathological features of lymph node metastases with patient outcome to improve the prognostic accuracy of the current classification. MATERIALS AND METHODS: We studied the records of 2,076 patients treated with radical nephrectomy for unilateral, sporadic pM0 renal cell carcinoma between 1970 and 2000. There were 34 patients with metastasis in a single regional lymph node (pN1) and 35 with metastases in more than 1 lymph node (pN2). Pathological features of lymph node metastases, including the number and percent of positive lymph nodes, total number of lymph nodes removed, grade, necrosis, extranodal extension, and largest dimension and surface area of metastases were determined by 2 urological pathologists (HHD and JCC). RESULTS: There was no statistically significant association between the pN classification and death from renal cell carcinoma (pN2 vs pN1 RR 1.05, 95% CI 0.62 to 1.79, p = 0.846). However, patients with extranodal extension were twice as likely to die of renal cell carcinoma than patients in whom metastases did not extend outside of the lymph node capsule (RR 2.02, 95% CI 1.18 to 3.45, p = 0.010). The 5-year cancer specific survival rate was 18% and 35% in patients with and without extranodal extension, respectively. CONCLUSIONS: We believe that a pN classification based on the presence or absence of lymph node metastases with a notation regarding the presence or absence of extranodal extension represents a significant improvement in the prognostic accuracy of the current pN classification.     

病理N3期胃癌310例预后分析

目的探讨UICC第7版TNM分期标准中病理N3（pN3）期胃癌患者的预后特征及预后影响因素。方法回顾性分析2000年1月至2006年12月间天津医科大学附属肿瘤医院收治的实施胃癌根治术或扩大根治术的310例pN3期胃癌患者的临床病理和随访资料,分别采用Logrank检验和Cox比例风险模型进行单因素和多因素预后分析。结果310例患者均获随访,随访时间为2～103（平均35．7）月,术后5年生存率为14．6％。其中pN3a期201例,pN3b期109例,5年生存率分别为16．8％和10．3％,差异有统计学意义（P=0．013）。单因素预后分析显示,肿瘤部位、Borrmann分型、pT分期、pN分期、淋巴结转移率及手术方式与患者预后有关（均P〈0．05）。多因素分析显示,浸润深度、手术方式及淋巴结转移率是影响预后的独立危险因素（均P〈0．01）,而pN分期并不是独立的预后影响因素（P=0．658）。按浸润深度对患者进行分层分析显示,对于210例pT4a期患者,pN3a和pN3b亚组5年生存率分别为16．1％和12．8％,差异有统计学意义（P=0．001）;但对于88例pT4b期患者,pN3a和pN,b亚组5年生存率的差异则无统计学意义（8．6％比3．1％,P=0．137）。结论pM期胃癌患者预后较差,肿瘤浸润深度和不同手术方式是影响其预后的重要因素,淋巴结转移率对判断pM期胃癌预后有重要意义。第7版TNM分期中pN3分期能较好反映患者的预后情况。     

Central mesenteric lymph node BER-Ep4+ cells in colorectal cancer: challenge to sentinel node concept?

BACKGROUND: The role of sentinel lymph nodes in colorectal cancer remains unclear. METHODS: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. RESULTS: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher's exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). CONCLUSION: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.     

淋巴结转移率对胃癌患者预后的评估价值

目的 探讨淋巴结转移率（rN）对胃癌根治术患者预后的评估价值.方法 回顾性分析1980-2006年间中国医科大学附属第一医院肿瘤外科收治的接受根治性手术的710例胃癌患者的临床资料.按淋巴结捡取数目将710例患者分为少于15枚组（327例）和15枚以上（含15枚）组（383例）.按淋巴结转移率进行rN分期;按淋巴结转移数量进行pN分期.分别采用Logrank检验和Cox比例风险模型来进行单因素和多因素预后分析.结果 少于15枚组和15枚以上组胃癌患者中位生存时间分别为74个月（95％ CI：55.6～92.4个月）和96个月（95％ CI：77.8～119.2个月）,差异无统计学意义（P＞0.05）.多因素预后分析显示,rN分期既是少于15枚组（P＜0.01,RR=1.225,95％ CI：1.102～1.362）,又是15枚以上组（P＜0.01,RR=1.421,95％ CI：1.269～1.592）胃癌患者的独立预后因素;而pN分期仅仅是少于15枚组胃癌患者的独立预后因素（P＜0.01,RR=1.475,95％ CI：1.168～1.863）.采用rN分期系统,相同分期的两组胃癌患者生存时间的差异均无统计学意义（P＞0.05）;而采用pN分期系统,在pN1期患者中少于15枚组患者生存时间明显短于15枚以上组（P＜0.01）.结论 淋巴结转移率是影响胃癌预后的独立因素.在判断胃癌预后中,按淋巴结转移率的rN分期不受检出淋巴结数目的限制,较pN分期系统更为可靠.     

Cyclin D1 expression is predictive of occult metastases in head and neck cancer patients with clinically negative cervical lymph nodes

BACKGROUND: The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control. RESULTS: Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059). CONCLUSIONS: Our study indicates that the expression of cyclin D1 correlates with the presence of occult cervical metastases in head and neck carcinoma patients, thus suggesting that its immunohistochemical evaluation in biopsy samples may be used as an additional tool for identifying patients to be treated with elective neck dissection.     

Papillary Thyroid Carcinoma: Factors Influencing Recurrence and Survival

Background The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. Materials and Methods From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. Results Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2–17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). Conclusion Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.     

Skip metastases in thyroid cancer leaping the central lymph node compartment

HYPOTHESIS: Discontinuous nodal metastasis, or skip metastasis, in thyroid cancer may display clinicopathologic features different from those seen in continuous nodal metastasis and thus may have a different prognosis. DESIGN: Retrospective analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS: Two hundred fifteen consecutive patients who underwent systematic central lymph node dissection for papillary, follicular, or medullary thyroid cancer and who on histopathologic analysis exhibited nodal metastases in at least 1 lateral or mediastinal lymph node compartment. MAIN OUTCOME MEASURES: Various clinicopathologic variables that were stratified for tumor entity and type of nodal metastasis (discontinuous vs continuous). RESULTS: Skip metastases (negative central and positive lateral or mediastinal compartments) were found in 13 (19.7%) of 66 papillary, 0 of 8 follicular, and 30 (21.3%) of 141 medullary thyroid cancers. After adjustment for multiple testing, skip metastasis was only associated with significantly fewer positive lymph nodes: 3.7 vs 12.9 nodes (r = -0.43, P<.001) in papillary thyroid cancer and 6.0 vs 17.1 nodes (r = -0.40, P<.001) in medullary thyroid cancer. No other significant correlation was identified with any other clinicopathologic variable. CONCLUSIONS: Skip metastasis is an epiphenomenon of low-intensity nodal metastasis in thyroid cancer and entails a moderate risk of local recurrence. Consequently, clearing the central lymph node compartment should be considered when lateral or mediastinal lymph node compartments are involved.     

甲状腺微小乳头状癌颈部淋巴结转移的危险因素分析

目的:探讨甲状腺微小乳头状癌(PTMC)颈部淋巴结转移的危险因素。方法:回顾性分析贵州医科大学附属医院甲状腺外科2014年1月—2016年3月收治的169例PTMC患者临床病理资料。结果:169例患者均行预防性中央区淋巴结清扫,其中54例(32.0%)发生中央区淋巴结转移,单因素分析发现中央区淋巴结转移与年龄45岁、多灶性肿瘤、侵出包膜有关(均P0.05),多因素分析显示,年龄、多灶性肿瘤、侵出包膜都是中央区淋巴结转移的独立危险因素(均P0.05)。30例行中央区淋巴结加侧颈区淋巴结清扫,其中18例(10.7%)发生侧颈区淋巴结转移,单因素分析显示,肿瘤最大径、侵出包膜、多灶性肿瘤、中央区淋巴结转移与侧颈区淋巴结转移有关(均P0.05),多因素分析显示,肿瘤侵出包膜为侧颈区淋巴结转移的高危因素(P0.05);11例(6.5%)发生中央区并侧颈区淋巴结转移,侵出包膜、多灶性肿瘤为中央区并侧颈区淋巴结共同发生转移的高危因素(均P0.05)。高分辨率颈部淋巴结B超对中央区淋巴结转移的灵敏度、特异度分别为14.8%、96.5%,其对侧颈区淋巴结转移的灵敏度、特异度分别为94.4%、83.3%。结论:年龄45岁、多灶性肿瘤、侵出包膜是PTMC颈部淋巴结转移的危险因素。高分辨率颈部淋巴结B超可以作为甲状腺癌颈部淋巴结转移术前评估的重要手段。     

Recurrent papillary thyroid cancer: analysis of prognostic factors including the histological variant.

OBJECTIVE: To analyse the factors that influence the development of recurrent papillary thyroid carcinoma, including the histological variant. DESIGN: Retrospective study. SETTING: Teaching hospital, Spain. SUBJECTS: 200 patients who had papillary thyroid cancers resected between 1970 and 1995. MAIN OUTCOME MEASURES: Prognostic factors and disease-free interval assessed by univariate and multivariate analysis. RESULTS: All patients were followed up for a mean of 9 years (range 4-29). 54 patients presented with recurrent disease (27%) of whom 19 (35%) died of their disease. 5-year, 10-year, and 15-year survival for those with recurrent disease were 75%, 68%, and 60%, respectively. The corresponding figures for the whole series were 93%, 90%, and 84%. The significant variables on multivariate analysis were completeness of resection (p = 0.002), extrathyroid involvement (p < 0.002), presence of lymph node metastases (p = 0.002), and histological variant of the carcinoma (P < 0.001). CONCLUSION: Using these risk factors it is possible to draw up a prognostic index and classify patients as being at low, medium, or high risk of recurrence.