BRAFV600E mutation does not predict lymph node metastases and recurrence in Chinese papillary thyroid microcarcinoma patients.

OBJECT: Previous studies suggest BRAFV600E mutation is a marker for poor prognosis in papillary thyroid cancer, however, its ability to further risk stratify papillary thyroid microcarcinoma (PTMC) remains controversial. We aimed to explore the association between BRAFV600E mutation and the clinicopathological features and recurrence in Chinese PTMC patients. METHODS: We retrospectively reviewed 2094 PTMC patients who underwent surgery and had a valid BRAFV600E mutation test result. Among them, 1292 patients had complete follow-up data. The mutation incidence was determined. Moreover, the clinicopathological characteristics, disease-free survival (DFS), and response to therapy distribution were compared between the mutation and non-mutation groups. RESULTS: BRAFV600E mutation was observed in 90.6 % of all patients and 89.2 % of patients with complete follow-up data. No significant difference was observed in lymph node metastases (LNM) number categories between the mutation and non-mutation groups among all patients (P = 0.329) and 1292 patients (P = 0.408). Neither the 3-year DFS (97.9 % vs. 98.0 %, P = 0.832) nor the response to therapy distribution (P > 0.05) indicated a significant difference between the mutation and non-mutation groups. The 3-year DFS differs among patients having different LNM number categories (99.8 % vs. 98.5 % vs. 77.3 %, P < 0.001). Multivariate analysis revealed that high-volume (over 5) LNM (Total thyroidectomy (TT): OR = 4.000, 95 % CI 2.390-6.694, P < 0.001; Unilateral thyroidectomy (UT): OR = 4.183, 95 % CI 1.565-11.190, P = 0.004), rather than BRAFV600E mutation (P > 0.05), was an independent risk factor of response to therapy. CONCLUSIONS: Our results suggested that BRAFV600E mutation could not accurately predict LNM or the recurrence of Chinese PTMC patients. Moreover, high-volume LNM is significantly associated with PTMC prognosis.

An immediate postoperative response to therapy assessment can help avoid unnecessary RAI therapy.

Background: Radioiodine (RAI) therapy plays a vital role in the postoperative treatment of differentiated thyroid cancer (DTC) patients underwent total thyroidectomy (TT). However, even in the presence of capsular invasion and lymph node metastasis prognosis can be excellent and a postoperative RAI treatment might not be necessary for all patients. Therefore, this study explored the criteria for avoiding unnecessary RAI therapy in these patients. Method: We applied response to therapy assessment immediately after surgery and prospectively recruited 179 excellent or indeterminate response DTC patients with capsular invasion and/or LNM who underwent TT without RAI therapy. During the follow-up, thyroglobulin (Tg), thyroglobulin antibody (TgAb) levels, and cervical ultrasonography were collected and analyzed. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. In addition, response to therapy assessments was performed on patients during each follow-up. Results: The mean follow-up period was 29.85 ± 17.44 months, and the 3- and 5-year DFS for all the patients was 99.3% in each. At the last follow-up, 165 (92.2%) patients had excellent responses, while 12 (6.7%) had an indeterminate response, and one (0.6%) each had biochemical and incomplete responses. No significant difference was observed in response to therapy between the subgroups of LNM and tumor invasion (P>0.05). For patients with capsular invasion and a number of metastatic lymph nodes ≤5 and >5, the proportions of recorded excellent responses were 95.9%, 91.0%, and 85.7%, respectively. Better responses were observed in females (excellent response: 95.5%, P=0.023), patients with stimulated Tg (s-Tg) ≤1ng/ml (excellent response: 100%, P<0.001), s-Tg ≤ 2ng/ml (excellent response: 98.4%, P<0.001), and excellent response for the immediate postoperative assessment (excellent response: 98.5%, P=0.004). Conclusions: The current study suggested that the response to therapy assessment immediately applied postoperatively could help avoid unnecessary RAI therapy among DTC patients with capsular invasion and/or LNM. Moreover, excellent response patients and patients with indeterminate response and s-Tg ≤ 2ng/ml could be managed without RAI therapy.

Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis.

Background: The prognostic factors for differentiated thyroid cancer (DTC) patients with pulmonary metastases (PM) remain scantly identified and analyzed. Therefore, this systematic review and meta-analysis were performed to identify and summarize the prognostic factors in adult DTC patients with PM to help distinguish patients with different prognoses and inform the rational treatment regimens. Method: We performed a comprehensive search of the relevant studies published in the Cochrane Library, PubMed, Scopus, Embase, Wanfang database, VIP database, China National Knowledge Infrastructure, and Google Scholar from their inception until February 2021. The pooled hazard ratios (HR) for overall survival and/or progression-free survival (PFS) with 95% confidence intervals were applied to evaluate and identify the potential prognostic factors. Pooled OS at different time points were also calculated for the available data. A random-effects model was used in the meta-analysis. Results: The review and meta-analysis included 21 studies comprising 2722 DTC patients with PM. The prognostic factors for poor OS were: age over 40 years (HR=7.21, 95% confidence interval [CI] 1.52-34.10, P=0.01, N=788), age over 45 years (HR=2.18, 95% CI 1.26-3.77, P<0.01, N=601), male gender (HR=1.01, 95% CI 1.01-1.19, P=0.03, N=1396), follicular subtype of thyroid cancer (HR=1.63, 95% CI 1.36-1.96, P<0.01, N=2110), iodine non-avidity (HR=3.10, 95% CI 1.79-5.37, P<0.01, N=646), and metastases to other organs (HR=3.18, 95% CI 2.43-4.16, P<0.01, N=1713). Factors associated with poor PFS included age over 45 years (HR=3.85, 95% CI 1.29-11.47, P<0.01, N=306), male gender (HR=1.36, 95% CI 1.06-1.75, P=0.02, N=546), iodine non-avidity (HR=2.93, 95% CI 2.18-3.95, P<0.01, N=395), pulmonary metastatic nodule size over 10mm (HR=2.56, 95% CI 2.02-3.24, P<0.01, N=513), and extra-thyroidal invasion (HR=2.05, 95% CI 1.15-3.67, P=0.02, N=271). The pooled 1, 3, 5, 10, 15, and 20-years OS were 95.24%, 88.46%, 78.36%, 64.86%, 56.57%, and 51.03%, respectively. Conclusions: This review and meta-analysis identified the prognostic factors of DTC patients with PM. Notably, FTC, metastases to other organs, and iodine non-avidity were particularly associated with poor prognosis. The identified prognostic factors will help guide the clinical management of DTC patients with PM. Systematic review registration: https://inplasy.com/inplasy-2022-2-0026/, identifier (INPLASY202220026).

Risk Factors of Lymphnode Metastasis in Patients with Thyroid Papillary Carcinoma Associated with Graves Disease.

Objective To summarize the characteristics of lymph node metastasis in patients with papillary thyroid carcinoma accompanied with Graves disease,and to provide evidence for clinical treatment. Methods Totally 98 patients with papillary thyroid carcinoma and Graves disease who had been treated in Peking Union Medical College Hospital from January 2004 to December 2013 were divided into the lymph node metastasis positive group (n=34) and lymph node metastasis negative group (n=64). The general information,blood biochemical results,pathological results,and prognoses were compared between these two groups. Results These two groups showed no significant differences in gender (χ2=0.2113,P=0.6458),age (t=1.7000,P=0.0922),tumor diameter (t=1.2559,P=0.2122),and multifocal tumors (χ2=1.9170,P=0.1661). The median level of thyrotropin receptor antibody (TR-Ab) value in the lymph node metastasis positive group was 4.84 U/L,which was significantly higher than that in the negative group which was 2.99 U/L (t=2.0169,P=0.0465). There were no significant differences in serum thyroid stimulating hormone (t=0.0257,P=0.9800),free triiodothyronine (t=1.3610,P=0.1770),free thyroxine (t=0.0082,P=0.9930),thyroid peroxidase antibody (t=0.0177,P=0.9860),and thyroglobulin antibody levels (t=1.1450,P=0.2550) between two groups. The postoperative pathological results showed that tumor capsular invasion rate (26.5% vs. 9.38%;χ2=5.006,P=0.0253) and lymph node recurrence rate (14.7% vs. 1.56%;χ2=4.583,P=0.0323) were significantly higher in the positive group than in the negative group. The distal metastasis rate in the positive group and negative group were 5.88% and 0,respectively. Conclusions There is no definite association between lymph node metastasis and tumor size in patients with thyroid papillary carcinoma associated with Graves disease. The risk factors for lymph node metastasis include TR-Ab and tumor capsular invasion,with a higher incidence of lymph nodes recurrence.

Risk Factors for Nodal Metastasis in cN0 Papillary Thyroid Microcarcinoma.

BACKGROUND: Despite the majority of papillary thyroid microcarcinoma (PTMC) patients having an excellent prognosis, cervical lymph node metastases are common. The purpose of this study was to investigate the incidence and the predictive risk factors for occult central compartment lymph node metastasis (CLNM) in PTMC patients. MATERIALS AND METHODS: 178 patients with clinically node-negative (cN0) PTMC undergoing prophylactic central compartment neck dissection in our hospital from January 2008 to Jun 2010 were enrolled. The relationship between CLNM and the clinical and pathological factors such as gender, age, tumor size, tumor number, tumor location, extracapsular spread (ECS), and coexistance of chronic lymphocytic thyroiditis was analyzed. RESULTS: Occult CLNM was observed in 41% (73/178) of PTMC patients. Multivariate analysis showed that male gender, tumor size (≥6mm) and ECS were independent variables predictive of CLNM in PTMC patients. CONCLUSIONS: Male gender, tumor size (≥6mm) and ECS were risk factors of CLNM. We recommend a prophylactic central lymph node dissection (CLND) should be considered in PTMC patients with such risk factors.

Clinicopathologic features of familial nonmedullary thyroid carcinoma.

BACKGROUND: Familial nonmedullary thyroid carcinoma (FNMTC) is a variant of nonmedullary thyroid carcinoma(NMTC) with particular clinicopathologic features. In recent years, a number of studies have shown that FNMTC is more invasive than sporadic NMTC(SNMTC). The purpose of this study was to explore the differences in clinicopathologic features of FNMTC between different types of families and to determine in which of these families more invasive FNMTC occurred. METHODS: We retrospectively reviewed all patients with thyroid carcinoma admitted to Peking Union Medical College Hospital from January 2009 to July 2013 in the database. Of all 2000 cases, 55 met the inclusive criteria for FNMTC and were studied. There are two different grouping methods. The first is that all samples were allocated to families with three or more first-degree relatives affected (FNMTC-3 group) and families with only two affected first-degree relatives (FNMTC-2 group). The second is that all patients were divided into families with three or more affected first-degree relatives over two generations (FNMTC-3-2 group) and the other families. We compared the clinicopathologic features such as sex, age, tumor size, multifocality, location, complications by thyroiditis, complications by benign thyroid nodules, surgical procedure, capsule invasion, histological type, lymph node metastases, tumor node metastasis stage, and BRAF mutation between FNMTC-2 group and FNMTC-3 group. We also made the same comparison between FNMTC-3-2 group and other families. RESULTS: No pronounced differences in clinicopathological features were present between FNMTC-2 group and FNMTC-3 group. The proportion of FNMTC-3-2 group aged <45 years was significantly higher than that in the other families (58.8% vs. 26.3%, P = 0.021). A similar difference was found in the proportion of lymph node metastasis (64.7% vs. 34.2%, P = 0.035). CONCLUSIONS: FNMTC-3-2 is more invasive than the other families. Early screening and positive treatment for members of these families are recommended.

[Diagnosis and treatment of primary pigmented nodular adrenocortical disease report of 4 cases].

OBJECTIVE: To study the diagnosis and treatment of primary pigmented nodular adrenocortical disease (PPNAD). METHODS: The clinical data including symptom, endocrinal examination, surgical operation and prognosis of 4 cases of PPNAD hospitalized from 2000 to 2007 were analyzed respectively, relative literature were reviewed. RESULTS: 1 case received total adrenalectomy needed adrenocortical hormone postoperatively, 3 cases responded favorably to subtotal adrenalectomy and did not need adrenocortical hormone, however, 1 case was diagnosed of thyroid carcinoma 2 years after subtotal adrenalectomy. CONCLUSIONS: PPNAD is a rare subtype of ACTH-independent Cushing's syndrome, the diagnosis is depend on symptom, endocrinal examination and pathology. Total adrenalectomy is suitable to the patients with obvious symptom; subtotal adrenalectomy to the patients with mild symptom, the lesion of other endocrinal organ must be followed up postoperatively.

[Gastric small cell carcinoma: 6 cases report and review of literature].

OBJECTIVE: To report the management experiences of of gastric small cell carcinoma. METHODS: The clinicopathological data of 6 cases of gastric small cell carcinoma treated from 1997 to 2007 were retrospectively reviewed. And meanwhile review the relevant literature. RESULTS: All the 6 cases were male with an average age of 56.5 years (range, 40-66 years). All the patients received surgery and 4 of them received postoperative adjuvant chemotherapy. Two cases were followed up, one lived without recurrence for 4 years all along, the other one died of recurrence and extensive metastasis 9 months after operation. In the literature, 164 male and 59 female patients have been reported to date, with an average age of 64.2 yrs (range, 42-84 years). Tumor located in the fundus in 97 cases, 55 in gastric body,54 in gastric antrum. In gross, 137 cases were classified as ulcerative type, 47 were protruded type. The average tumor diameter was 6.23 cm (range, 0.8-17.0 cm). Among 223 cases, only 43 survived more than 1 year. CONCLUSIONS: It is difficult to make a definite diagnosis before or during the operation for gastric small cell carcinoma. The radical operation could be done according to other gastric cancer and the lymph node dissection could be simplified. Postoperative chemotherapy with the same scheme as lung small cell carcinoma may help improving the outcome.

[Investigation of selective neck dissection for differentiated thyroid cancer].

OBJECTIVE: To investigate the indication, operative method and results of selective neck dissection (SND) for differentiated thyroid cancer. METHODS: According to the level system and the operative guideline of the American Head and Neck Society, 40 cases of thyroid cancer (phase I: 35 cases, phase II: 2 cases, phase III: 3 cases) were collected prospectively. Thyroidectomy plus SND was performed on all the cases. And the indication, operative methods and results were investigated. RESULTS: Nine of the 40 cases received level VI dissection only. Twenty-four of the 40 cases received SND with levels 0.05). One parathyroid was found in 20% (8/40) of the specimen and 27% (11/40) of the patients had transient hypocalcemia, but no permanent hypocalcemia. Three (7.5%) of the patients had vocal cord paralysis for a short period of time and no permanent case was detected. Nineteen patients were followed up for more than 6 months after the operation and no enlarged neck lymph node was found by ultrasound at the 6th month postoperatively. CONCLUSION: It is reasonable to give SND to the early thyroid cancer patients.

[Coexistent chronic lymphocytic thyroiditis with nodules: diagnosis and treatment].

OBJECTIVE: To discuss the principles of diagnosis and treatment of coexistent chronic lymphocytic thyroiditis (CLT) with nodules. METHODS: Patients who were operated from 1995 to 2005 were divided into two groups according to pathological results. A comparison of the clinical data, including clinicopathologic features, treatment and prognosis was made between these groups by retrospective research. RESULTS: The patients of CLT with carcinoma included 48 women and 3 men, with an average age of 36.8 years and symptoms duration of 24.6 months, and there were 28 cases of solitary nodule and 34 cases of calcification; the patients with benign nodules included 94 women and 2 men, with an average age of 48.0 years and symptoms duration of 59.0 months, and there were 27 cases of solitary nodule and 14 cases of calcification. Age of onset, symptoms duration, nodule numbers and calcification in nodules had significant difference between these groups. CONCLUSION: Coexistent carcinoma was the main reason of operation in cases of CLT with nodules. thyroiditis nodule, coexistent nodular goiter or adenoma were also common reasons. CLT patients with thyroid nodules should be diagnosed and treated carefully. Surgical intervention should also be considered with such conditions, including malignant finding of fine-needle aspiration, rapid enlargement of thyroid nodule, solitary solid nodule, and calcification revealed by ultrasonography.

[Endoscopic thyroid surgery: a comparison of the trans-subclavian and the trans-areolar approach].

OBJECTIVE: To compare the advantages and shortcomings of the endoscopic thyroid surgery by trans-subclavian approach and trans-areolar approach. METHODS: Twelve patients received the trans-areolar approach and 10 patients were given the trans-subclavian approach procedure. RESULTS: With the trans-areolar approach: the mean size of tumor was 1.8 cm, the mean operating time was 115 min, the mean blood loss during operation was 63 ml. Two patients converted to the conventional operation. With the trans-subclavian procedure: the mean size of tumor was 4.2 cm, the mean operating time was 85 min, the mean blood loss during operation was 66 ml. No complications were found in all of the patients and they were satisfied with the cosmetic effects of the procedures. There were significant differences in tumor size and operating time between the two operation types. CONCLUSIONS: Compared with the trans-areolar approach, the trans-subclavian approach comes with less trauma, higher success rate and it fits for bigger tumor.

[Diagnosis and treatment of chronic lymphocytic thyroiditis coexistent with thyroid malignancy].

OBJECTIVE: To explore the principles of diagnosis and treatment of chronic lymphocytic thyroiditis (CLT) coexistent with thyroid malignancy. METHODS: The clinical data of 52 patients with CLT, including clinicopathologic features, treatment, and prognosis were retrospectively analyzed. Among these 52 patients, 40 patients had coexisting thyroid carcinoma (TC group) and 12 had coexisting thyroid lymphoma (TL group). RESULTS: These two thyroid malignancies accounted for 13.87% of all the CLT inpatients during this period, in which 10.67% were CLT with carcinoma and 3.20% were CLT with lymphoma. Significant differences existed between TC group and TL group in sex (P = 0.008) , age (P = 0.000), and B-mode ultrasound findings (P = 0.000). Most patients in TC group received total lobectomy of one lobe and subtotal lobectomy of the other side, of which some received elective lymphadenectomy. The operations varied among patients in TL group, and most of them received chemotherapy after surgery. The median follow-up was (35.51 +/- 39.84) months for 37 patients in TC group, and 36 patients survived with a median period of (34.50 +/- 39.91) months; the median follow-up was (39.50 +/- 29.00) months for 12 patients in TL group, and 10 patients survived with a median period of (44.70 +/- 28.78) months. CONCLUSIONS: CLT with thyroid malignancies are not uncommon in clinical practice. While thyroid carcinoma accounts for majority of these malignancies, its clinicopathologic features, treatment, and prognosis differs with thyroid lymphoma. Surgery may be appropriate for CLT patients with rapid thyroid enlargement or nodule, and for patients with solitary solid nodule or nodules with calcification revealed by B ultrasound.

[Therapeutic effect of excision of hypomere esophagus and proximal stomach on portal hypertension and upper gastrointestinal bleeding].

OBJECTIVE: To analyze the therapeutic effect of excision of hypomere esophagus and proximal stomach (Phemister operation) on portal hypertension and upper gastrointestinal bleeding. METHODS: Retrospectively analyze the clinical data of 136 cases treated with the Phemister operation for portal hypertension and upper gastrointestinal bleeding from August 1999 to May 2005. RESULTS: Varication of the patients improved markedly, 50.8% of the varication disappeared completely, incidence of complications was 5.0%, rebleeding rate was 4.4%, mortality rate was 0.7%. CONCLUSIONS: The Phemister operation could treat the upper gastrointestinal bleeding and prevent rebleeding effectively in portal hypertension, it is a radical, precise and secure disconnection for portal hypertension with varication in fundus of stomach and esophagus.

[The first case of primary epithelial-myoepithelial carcinoma in the liver].

OBJECTIVE: To report the first case of primary epithelial-myoepithelial carcinoma (EMC) in the liver. METHODS: The clinical manifestations, imaging characteristics, and histopathological changes of EMC in this case were described. The patient was a thirty-seven-year old female. A 10 cm lesion was detected in the right liver upon a routine examination. Following that, the CT scan, magnetic resonance imaging (MRI), repeated puncture biopsies, and serum alpha-fetoprotein (AFP) detection were done with no specificity and significance found. RESULTS: Right hemi-hepatectomy was performed. The special double catheterization cannula was found in the histopathological examination, and the final diagnosis of EMC was proven by immuno-histochemical staining. CONCLUSIONS: Primary EMC is difficult to be finally diagnosed prior to the surgery. The diagnosis can be confirmed using pathological examination and immuno-histochemical staining of the specimen.