Comprehensive bioinformatics analysis unveils THEMIS2 as a carcinogenic indicator related to immune infiltration and prognosis of thyroid cancer.

The aim of this study was to identify biomarkers associated with the initiation and prognosis of thyroid cancer and elucidate the underlying pathogenic mechanisms. We obtained expression profiles and clinical information from the Cancer Genome Atlas (TCGA)-THCA and three datasets (GSE53157, GSE82208, and GSE76039). The three microarray datasets were combined using Perl and the sva package in R and termed 'merged dataset'. Weighted gene co-expression network analysis (WGCNA) identified 15 gene co-expression modules in the merged dataset and 235 hub genes. Venn diagram analysis revealed 232 overlapping genes between the merged and THCA datasets. Overlapping genes were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The least absolute shrinkage and selection operator (LASSO) regression identified THEMIS2 as a candidate hub gene. Cox, Kaplan-Meier (K-M) survival and gene set enrichment analysis (GSEA) confirmed the correlation of THEMIS2 with overall survival, its enrichment in immunologic processes, and its association with the p53 and JAK-STAT signaling pathways. Its expression was positively correlated with those of immune checkpoints and the infiltration level of immune cells. Receiver operating characteristic curve (ROC) analysis confirmed that THEMIS2, a diagnostic biomarker, could distinguish between tumor and normal specimens. The nomogram (ROC or DCA) model containing THEMIS2, age, and stage predicted favourable prognoses. Thus, THEMIS2 was a biomarker of immune infiltration and prognosis in thyroid cancer.

Sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than moderate.

We collected thyroid-related hormone index levels, sleep duration, and other basic characteristics of the population with depression from the NHANES 2009-2012 cycles and evaluated the association of Thyroid-Stimulating Hormone Index (TSHI) with sleep duration in the euthyroid population with depression via different analysis methods. We found that the association between TSHI and sleep duration was only found in patients with depression degree < Moderate (score: 1-14) rather than > Moderate group. Among the populations with degree < Moderate (N = 1918), only 4 indexes (parametric Thyroid Feedback Quantile Index, PTFQI, Thyrotroph Thyroxine Resistance Index, TT4RI, Thyroid-Stimulating Hormone TSH, and TSHI) reflecting the sensitivity to thyroid hormones were related to the sleep duration, with a significant non-linear relationship after adjusting for potential confounders (all P < 0.05). Trend analysis indicated that with the level increase of these 4 indexes, the sleep duration increased (all P for trend < 0.001). Further, we found that TSHI was relatively more important among the 4 indexes. Sum up, sensitivity to thyroid hormones is associated with sleep duration in the euthyroid population with depression degree lower than Moderate. Poor sensitivity referred to a longer sleep duration.

Aberrant Expression of BUB1B Contributes to the Progression of Thyroid Carcinoma and Predicts Poor Outcomes for Patients.

Objective: This study aimed to clarify the function and potential mechanism of BUB1B in THCA. Methods: Expression of BUB1B in THCA was firstly determined, and its important prognostic value was then demonstrated. The potential mechanism was initially predicted by KEGG analysis. To explore the specific function of BUB1B in THCA, we used lentivirus infection to knock down the BUB1B, and then performed flow cytometry, colony formation, transwell, and wound-healing assays. Related protein expression was detected through western blotting. Additionally, we predicted the BUB1B-regulated pathways involved in THCA by GSEA analysis. Results: BUB1B expression was highly increased in THCA tissues relative to normal controls. We further found that BUB1B was essential for tumor cell proliferation, and BUB1B high expression predicted a shorter PFS time of THCA patients. More importantly, Cox regression determined the BUB1B as an independent prognostic factor for PFS in THCA. BUB1B was initially found to participate in the cell cycle pathway from KEGG analysis. Unexpectedly, we did not detect the disturbing effect on the cell cycle distribution of THCA cells with BUB1B knockdown. But, BUB1B knockdown inhibited the proliferation, invasion, and migration of THCA cells, as well as increased apoptotic cells, and the results were further confirmed by western blotting. Through GSEA analysis, we predicted a positive correlation between BUB1B and metastasis-related pathways such as mTOR and NF-kappa B signaling pathways. Conclusions: Present study identified BUB1B as a promising clinical prognostic factor in THCA, as well as a potential novel therapeutic target for cancer treatment.

Ubiquitin conjugating enzyme E2 C (UBE2C) may play a dual role involved in the progression of thyroid carcinoma.

The present study aimed to explore the role of ubiquitin-conjugating enzyme E2 C (UBE2C) in the progress of thyroid carcinoma (THCA). We firstly explored the prognostic impact and expression level of UBE2C in THCA. Then, we performed the UBE2C knockdown and evaluated the effects on the proliferation, cell cycle distribution, apoptosis, migration, and invasion of THCA cells, as well as resistance to sorafenib. Finally, we predicted the possible pathways and explored the correlation between UBE2C with immune infiltrates. The results showed that high expression of UBE2C independently predicted a shorter disease-free survival time of THCA patients. And UBE2C also presented a better prognostic performance on the survival probability of patients. Expression analysis showed that UBE2C was statistically upregulated in THCA tissue compared with normal tissue. After UBE2C knockdown, the proliferation of THCA cells was inhibited and apoptosis was increased. These results indicated that UBE2C acted as an oncogene in THCA. However, the migration and invasion of THCA cells with UBE2C knockdown were enhanced, and the expressions of migration-related proteins were upregulated. In addition, UBE2C knockdown increased the resistance of THCA cells to sorafenib. These results implied the potential of UBE2C as a suppressor gene in THCA. The pathway analysis further predicted that metabolism-related pathways were activated in the UBE2C low expression class, and cell growth and immune-related pathways were focused on the UBE2C high expression class. Finally, we observed a significant positive relationship between UBE2C and several immune infiltrates in THCA. It followed that UBE2C high expression might play a vital role in THCA to some extent. This study revealed that UBE2C participated in the progression of THCA and may play the dual role of both oncogene and tumor suppressor gene. The detailed mechanism needed to be further investigated.

Scarless endoscopic thyroidectomy (SET) lateral neck dissection for papillary thyroid carcinoma through breast approach: 10 years of experience.

BACKGROUND: Breast approach endoscopic thyroidectomy with lateral neck lymph node metastases dissection has been described. However, in this article, we report on 10 years' experience with the breast approach to patients with endoscopic thyroidectomy with level II, III, and IV lateral neck dissection (LND). Patients with papillary thyroid carcinoma (PTC) who received scarless endoscopic thyroidectomy (SET) were included to evaluate its therapeutic effect. METHODS: Between June 2009 and June 2019, we selected 155 patients with PTC with level II, III, or IV level lymph node metastasis suspected. Ipsilateral level II, III, and IV dissection was performed, accompanied by thyroidectomy and central compartment dissection. In addition, 102 patients received conventional open LND during the same period and were included. Clinicopathological characteristics, outcomes, and tumor prognosis were retrospectively compared in the two groups. RESULTS: During the 10 years, the submitted patients' clinicopathological characteristics including tumor size, tumor stage, retrieved lymph nodes number, complication rates, postoperative PTH, and mean postoperative hospital stay were similar between the SET and open group. The mean operating time in the SET group (278.2 ± 38.6 min) was longer than in the open group (179.3 ± 25.4 min). The recurrent rate was not significantly different (2/155, 2/106) in the SET and conventional open group. CONCLUSION: The safety and oncological completeness dissection of SET was similar to that of open procedures. SET is an effective treatment approach for patients with PTC having cosmetic results' demand of lateral neck lymph node metastases.

The patterns and treatment of postoperative hemorrhage and hematoma in total endoscopic thyroidectomy via breast approach: experience of 1932 cases.

PURPOSE: Postoperative hemorrhage and hematoma formation is a potentially lethal complication in thyroid surgery, although the patterns and treatment of hemorrhage after total endoscopic thyroidectomy (TET) via breast approach has not been reported previously. We aim to share our experience about postoperative bleeding. METHODS: A retrospective analysis of 1932 patients who underwent TET from April 2008 to May 2018 in our institution was carried out. The patterns of postoperative hemorrhage and hematoma formation that need surgical treatment were summarized and focused on the relation to the source of bleeding and the time interval between first surgery and hemorrhage. Related risk factors were analyzed by univariate or multivariate analysis processes. RESULTS: The overall rate of hemorrhage and hematoma occurrence was only 0.724% (14 in 1932 patients). Of them, 12 occurred in the first 24 h after surgery, and the other two occurred after withdrawal of the drainage tube. The principle independent risk factors for postoperative hemorrhage and hematoma were age (older than 35 years old) and lateral compartment dissection (LCD) revealed by multivariate regression. During re-exploration, obvious bleeding points were detected in 13 patients. Among them, 12 bled from the vessels in the main trocar cavity and another 1 bled from a broken vein located between the two heads of the sternocleidomastoid (SCM) muscle with LCD. CONCLUSIONS: Hemorrhage after TET usually occurs within 24 h, and the main video trocar cavity was the area most likely to bleed. Age and LCD may increase the bleeding risk. Appropriate dissection level is the main solution to prevent postoperative hemorrhage.

LncRNA-SLC6A9-5:2: A potent sensitizer in 131I-resistant papillary thyroid carcinoma with PARP-1 induction.

Recent studies have indicated that long non-coding RNAs play crucial roles in numerous cancers, including thyroid cancer, while their function in the mechanism of thyroid cancer 131I resistance has not been elucidated to date. The present study identified a functional long non-coding RNA, SLC6A9-5:2, which was involved in the radioactive therapy resistance of thyroid cancer. We demonstrated that SLC6A9-5:2 was remarkably downregulated in 131I-resistant thyroid cancer cell lines and 131I-insensitive patients and was positively correlated with Poly (ADP-ribose) polymerase 1 (PARP-1) expression and its activation. After downregulating SLC6A9 or blocking PARP-1 artificially, the sensitive thyroid cancer cells mostly displayed a tolerant phenotype under 131I exposure. Furthermore, SLC6A9-5:2 overexpression was positively correlated with PARP-1 mRNA and protein levels, which restored the sensitivity of resistant thyroid cancer cells. The present study further revealed that cancer cell death was primarily caused by ATP exhaustion in excessive DNA repair with high PARP-1 activity. In patients with thyroid cancer, a positive correlation between SLC6A9-5:2 and PARP-1 was identified, and low SLC6A9-5:2 expression was associated with a worse prognosis of papillary thyroid carcinoma. Hence, our data provide a new lncRNA-mediated regulatory mechanism implying that SLC6A9-5:2 can be used as a novel therapeutic target for 131I-resistant thyroid cancer.

Intrahepatic biliary cystadenoma presenting with pleural effusion.

Hepatobiliary cystadenomas are rare cystic neoplasms that often occur in middle aged women. The exact etiology of these tumors is unknown. Diagnosis is often delayed in these cases. However, misdiagnosis and inappropriate treatment may result in unfavorable outcome. We report a case of hepatobiliary cystadenoma with pleural effusion. We also review the literature and discuss the current diagnostic and treatment modalities.

Extended Appleby's operation for pancreatic cancer involving celiac axis.

BACKGROUND: In Appleby's operation, the adequate flow of proper hepatic artery (PHA) from pancreaticoduodenal arcades was considered to be important in the previous reported pancreatic cancer cases. Insufficient blood flow of PHA was considered as the contraindication for Appleby's operation. METHODS: We herein reported a 20 cm in diameter pancreatic sarcomatoid carcinoma involving celiac axis (CA), which was treated by extended Appleby's operation without proper hepatic arterial flow. The extended Appleby's operation for pancreatic cancer involving CA and/or common hepatic artery (CHA) was firstly applied to the current case according to the 43 previous reported cases in English literature from a Medline search. In the extended Appleby's operation, the resection scope included total pancreas, total stomach, spleen, and CA; the anterior and posterior pancreaticoduodenal arcades were removed in whipple's procedure, which was previously thought to be the contraindication for Applyby's operation. RESULTS: Proper hepatic arterial flow from superior mesenteric artery (SMA) was totally lost; No liver failure happened postoperatively. CONCLUSIONS: The extended Appleby's procedure without blood flow of PHA might be feasible and offered a new approach to resection of pancreatic cancer involving CA and/or CHA; the involvement of pancreatic head might not be the contraindication for Appleby's operation.

Risk factors for infectious morbidity in gallbladder cancer patients treated surgically.

BACKGROUND/AIMS: To explore risk factors associated with postoperative infectious morbidity in gallbladder cancer patients. METHODOLOGY: We investigated 58 consecutive patients undergoing surgery for primary gallbladder cancer between January 2000 and June 2005 in our hospital. Records of all patients were retrospectively reviewed. Twenty-two independent tumor-, patient-, and treatment-related variables were analyzed. The dependent variable was clinical infectious complications. A binary logistic regression analysis was used to assess the independent association of variables with the dependent variable. RESULTS: Overall surgical morbidity was 33% (19/58), and 14 (24%) of the 58 patients developed infectious complications postoperatively. On univariate analysis, presence of jaundice, hypoalbuminemia and intraoperative blood transfusion were found to be significantly associated with infectious morbidity. The multivariate analysis of logistic regression disclosed that presence of jaundice and intraoperative blood transfusion of 4 units or more only showed marginally significant impacts on infectious complications (odds ratio, 8.004, 7.782; 95% confidence interval, 0.886-72.278, 0.914-66.283, respectively), while weight loss and hypoalbuminemia were significantly associated with infectious complications postoperatively (odds ratio, 9.609, 40.257; 95% confidence interval, 1.269-72.253, 3.901-415.438, respectively). CONCLUSIONS: Hypoalbuminemia and weight loss are significantly associated with postoperative infectious morbidity independently. While presence of jaundice and intraoperative blood transfusion of 4 units or more appear to be marginally significant factors, modality of operation or liver resection, blood loss, and additional gastrointestinal operation are not risk factors.

Resection of non-cystic adenocarcinoma in pancreatic body and tail.

AIM: To report the outcome of Chinese patents with non-cystic adenocarcinoma in pancreatic body and tail (NCAPBT) after resection and to discuss its surgical strategy. METHODS: Resection of NCAPBT was performed in eight Chinese patients with complete clinical-pathological data in our hospital from January 2000 to May 2004. The surgical strategy was explored by analyzing the results of these patients. RESULTS: The resection rate of NCAPBT in patients without back pain was higher than that in patients with back pain (66.67% vs 20%, 2/3 vs 1/5). The prognosis in the group receiving palliative resection was poorer than that in the group receiving curative resection. The median survival time was 12 mo in the curative resection group and 6 mo in the palliative resection group, respectively. CONCLUSION: The overall survival time of the Chinese patients with NCAPBT is dismal. The Chinese patients after curative resection of NCAPBT have a longer survival time. The Chinese NCAPBT patients with back pain trend to have a lower curative resection rate, but back pain should not be considered a contraindication for curative resection.

Pancreatic benign schwannoma treated by simple enucleation: case report and review of literature.

Benign schwannoma in the pancreatic head is very rare, with only 11 patients being reported in the English literature from a Medline search. Furthermore, only 1 of them was treated by simple enucleation. Herein, we present another enucleation case: a 71-year-old male patient with a 1.5 x 1.2-cm low-density mass, mimicking a cystic lesion located at the head of pancreas, which was detected by computed tomography. This tumor failed to be discovered by abdominal ultrasound. At laparotomy, a solid mass 1 cm in diameter was identified; it was the smallest one in the pancreatic head according to the 11 previous reported cases. No complications were found after the operation. At 10-month follow-up, the patient remains asymptomatic and has no signs of recurrence. The data of the 12 patients indicated that simple minimal invasive enucleation for small benign schwannoma in the pancreatic head was feasible and safe; early detection and early treatment of the tumor were helpful in increasing the ratio of enucleation and avoiding a very invasive Whipple operation.

[Distribution of sentinel lymph nodes in gastric cancer and factors correlated with its metastasis].

OBJECTIVE: To investigate the distribution of sentinel lymph nodes in gastric cancer, and evaluate clinicopathologic characteristics leading its metastasis. METHODS: The location of metastatic lymph nodes was analyzed retrospectively in 27 patients of gastric carcinoma with solitary lymph node metastases, and in 80 cases metastasis was limited to only 1 station in Japanese nodal classification. The clinicopathologic characteristics of the patients with solitary lymph node metastases and 111 cases without lymph node metastases were compared. RESULTS: Twenty-five in 27 cases with solitary lymph node metastases were limited in level I. Skip metastasis occurred in 2 cases. Sentinel lymph nodes of 16 cases in 21 patients with the tumors in the lower and middle third stomach were located in less curvature (No. 3) and in greater curvature (No. 4). Sentinel lymph nodes of 3 cases in 6 patients in the upper third stomach were located in right cardia (No. 1). Multivariate analysis showed that the frequency of sentinel lymph node metastasis of pT(3) lesion was significantly higher than that of pT(1) lesion with an odds ratio of 4.926 (P < 0.01). The frequency of sentinel lymph node metastasis in the tumor located in the upper third stomach was significantly higher than that in lower third stomach, with an odds ratio of 4.381 (P < 0.05). Early gastric cancer had lower risk for sentinel lymph node metastasis than that in Borrmann type I cancer, with an odds ratio of 0.082 (P < 0.05). CONCLUSIONS: Majority of sentinel lymph nodes are located in the regional perigastric lymph node groups close to the tumor. Skip metastasis is rare. Depth of invasion and location of tumor are correlated with sentinel lymph node metastasis. Sentinel lymph node assessment can instruct to determine extent of lymph node dissection for gastric cancer.