Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort.

BACKGROUND: We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). METHODS: A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). RESULTS: Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. CONCLUSION: AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

[Huikangling Tablet Intervened Peripheral Blood Micrometastasis of Differentiated Thyroid Carcinoma].

OBJECTIVE: To observe the clinical effect of Huikangling Tablet (HT, extracted from Scabrous Patrinia root) on peripheral blood micrometastasis of differentiated thyroid carcinoma (DTC) patients. METHODS: Totally 87 DTC patients with positive micrometastasis were randomly assigned to the treatment group (45 cases) and the control group (42 cases). DTC endocrine inhibition treatment standards were executed in all patients. They all took levothyroxine sodium (50 microg/tablet, from low dose, 25 microg each time, once per day, 0.5 h before breakfast), and its dosage was gradually added one week later. The dosage was adjusted according to tested results of TSH combined recurrence risk stratification and endocrine suppression induced adverse reactions risk stratification. Patients in the treatment group took HT (0.4 g per tablet, 3 tablets each time, three times per day for a total of 12 weeks) combined TSH suppression therapy, while those in the control group only received TSH suppression therapy. Peripheral micrometastatic cytokeratin 19 (CK19) and polymorphic epithelial mucin1 (MUC1) were detected by FCM at week 4 and 12. Meanwhile, distant metastasis and adverse reactions were observed. RESULTS: After 4-week treatment positive micrometastasis was shown in 18 cases (40%) of the treatment group and 29 cases (69%) in the control group with statistical difference (chi2 = 5.68, P < 0.05). After 12-week treatment positive micrometastasis was shown in 7 cases (15.6%) of the treatment group and 17 cases (44.7%) in the control group with statistical difference (chi2 = 8.49, P < 0.01). Pulmonary metastasis occurred in 2 cases and bone metastasis in 1 case of the control group at follow-ups. Cervical lymph node metastasis without accompanied recurrence of thyroid cancer occurred in one case of the treatment group. No obvious liver or renal abnormalities occurred. CONCLUSION: HT inhibited peripheral blood micrometastasis of DTC patients and its mechanism needed to be further studied.

Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.

Expression and correlation of sodium/iodide symporter and thyroid stimulating hormone receptor in human thyroid carcinoma.

AIMS: To investigate the expression of sodium/iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHR) in human thyroid cancer. PATIENTS AND METHODS: NIS and TSHR mRNA levels quantified by real-time PCR as well as NIS and TSHR proteins evaluated by immunohistochemistry were examined in surgical specimens including 38 benign nodules, 32 thyroid carcinomas and 36 normal thyroid samples. RESULTS: NIS and TSHR mRNA levels in thyroid carcinomas were significantly lower than in benign nodules and normal thyroid samples (P <0.001). Interestingly, we found that NIS and TSHR mRNA expression in benign nodules had similar levels to those in normal thyroid tissues. However, NIS and TSHR protein expression in benign nodules and thyroid carcinomas was stronger than in normal thyroid samples (P <0.05) but mainly located in cytoplasm. In addition, there was a significant positive correlation between NIS and TSHR in benign nodules and normal thyroid samples (r = 0.551 and 0.667, respectively, P = 0.001 and 0.000, respectively) but there was no such correlation in thyroid carcinomas (r = 0.222, P = 0.376). CONCLUSIONS: In thyroid carcinomas, NIS and TSHR mRNA levels were lower but the proteins were overexpressed. The NIS protein mainly locates in the cytoplasm, which therefore lacks the ability of transporting and absorbing iodine in patients with thyroid carcinoma. In addition, there was no correlation between NIS and TSHR in thyroid cancer, which may explain why, even after TSH stimulation, 10-20% of these malignant tumors are unable to concentrate enough radioiodine for effective therapy.

[Diagnosis and surgical treatment of Castleman's disease].

OBJECTIVE: To explore the clinical features and surgical treatment of tumors associated with Castleman's disease (CD). METHODS: The clinical profiles of 19 patients with neck giant lymph node hyperplasia were analyzed retrospectively. There were 8 males and 11 females with a median age of 40 years old (range: 7 - 74). The tumor locations were neck (n = 12), neck & mediastinal cavity (n = 2), axillary fossa (n = 2), retroperitoneal area (n = 2) and abdominal cavity (n = 1). RESULTS: Eighteen of them underwent surgical resection of tumor or lymph nodes. All were diagnosed as CD by pathological examinations. There were 16 localized CD (LCD) including hyaline vascular type (HV type, n = 11), mixed type (mix type, n = 4) and plasma cell type-Hodgkin's disease (n = 1). Among 3 multicentric CD (MCD), there were 2 case of plasma cell type (PC type) and 1 case of mixed type (mix type). Long-term survival was achieved in 19 cases among which 1 case of plasma cell type MCD survived for 5 years and underwent a second operation and postoperative chemotherapy of CVP (cyclophosphamide, vincristine & prednisone) regimen for 3 cycles due to recurrence in 2 years and 1 case of plasma cell type LCD-Hodgkin's disease survived for 15 months and underwent a second operation and postoperative chemotherapy of ABVD (adriamycin, bleomycin, vinblastine & dacarbazine)regimen for 6 cycles due to recurrence in 6 months. One case of plasma cell type MCD in abdominal cavity on chemotherapy of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine & prednisone) regimen for 6 cycles was discharged after a successful management of intestinal obstruction. CONCLUSIONS: The major clinical symptom of CD is a gradually enlarging painless mass. Surgical resection of tumor remains the first-line treatment for localized CD and the prognosis is excellent. Multicentric and plasma cell type CDs are prone to recurrence and transformation to lymphoma. And their first-line therapeutic should encompass multi-modality regimens of surgery and adjuvant chemotherapy. However, the clinical prognosis is still poor.

Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up.

The extent of surgical resection in patients with sporadic medullary thyroid carcinoma (SMTC) remains controversial. The aim of the present study was to discuss the prognosis of sporadic medullary thyroid carcinoma with different surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0). Having given their informed consent, 12 patients underwent total thyroidectomy with bilateral central neck dissection (group A), 40 underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with ipsilateral modified radical neck dissection (group B), and 18 patients underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with bilateral modified radical neck dissection (group C). The diagnosis was confirmed by a pathology examination. The incidences of hypoparathyroidism and recurrent laryngeal nerve injury, the cancer recurrence rates and survival time were investigated post-operatively. Significant differences were found between groups A, B and C in the incidence of hypoparathyroidism (χ(2)=40.9, P<0.01), as well as that of recurrent laryngeal nerve injury (χ(2)=32.9, P<0.01). The cancer recurrence rates in groups A, B and C were 75.0% (9/12), 2.5% (1/40) and 44.4% (8/18) respectively, (χ(2)=31.1, P<0.01) and the cure rates were 25, 97.5 and 55.6% respectively (χ(2)=31.1, P<0.01). The mean survival times in groups A, B and C were 77.8, 106.1 and 111.0 months respectively, but significant difference was noted (χ(2)=3.2, P>0.05). In conclusion, compared to total thyroidectomy with bilateral central neck dissection, subtotal thyroidectomy with ipsilateral/bilateral modified radical neck dissection showed a lower incidence of hypoparathyroidism, recurrent laryngeal nerve injury and lower rates of recurrence, along with a similar cumulative survival.

[Clinical analysis on giant lymph node hyperplasia on neck].

OBJECTIVE: To improve the diagnosis and management level of giant lymph node hyperplasia (Castleman's disease). METHODS: To retrospective analyze 10 misdiagnosed cases with Castleman's disease in order to give some suggestions for clinical diagnosis and differential diagnosis. RESULTS: Ten patients with neck giant lymph node hyperplasia underwent surgical treatment after misdiagnosis. There were 8 localized Castleman's disease constituted of 6 cases with hyaline vascular type and 2 cases with mixture type and 2 multicentric Castleman's disease constituted of 1 cases with plasma cell type and 1 cases with mixture type were classified according to the criteria described by Frizzera. Ten cases were diagnosed by secondary operation after misdiagnosis and were clinically characterized by painless neck lymphadenectasis, 2 cases with multicentric Castleman's disease accompanied with aspecific systemic symptom and (or) multi-system damage. Ten cases survived for 4 - 17 years during follow-up periods in which 1 case with plasma cell type, multicentric Castleman's disease was recurrent 2 years later and underwent lymphadenectomy and chemotherapy and have no local recurrence so far. CONCLUSIONS: Castleman's disease on neck is seldom seen and liable to misdiagnose. The diagnosis of Castleman's disease is based on its histopathological characteristics by lymph node resection biopsy. It should be considered in the differential diagnosis with lymph node tuberculosis, lymphadenitis, sarcoidosis and granuloma. Operation is the first choice for patient with localized type and multicentric type without serious involvement of multiple system functions.