Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration.

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.

Transcriptomic discovery of a theranostic signature (SERPINE1/MMP3/COL1A1/SPP1) for head and neck squamous cell carcinomas and identification of antrocinol as a candidate drug.

Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC.

Routine Intraoperative Neuromonitoring of the Recurrent Laryngeal Nerve to Facilitate Complete Resection and Ensure Safety in Thyroid Cancer Surgery.

Routine use of intraoperative neuromonitoring (IONM) in thyroid cancer surgery is controversial. We aimed to investigate whether it improves the completeness of thyroidectomy and ensures safety. This retrospective study included 380 thyroid cancer patients who underwent thyroidectomy, by one surgeon, between July 2006 and November 2015. Patients were grouped according to the surgeon's adaptation of IONM, as follows: none (period 1; n = 92), early (period 2; n = 141), and late (period 3; n = 147). The operative time and rates of vocal cord palsy were determined. Surgical completeness was assessed by technetium-99m imaging of the thyroid remnant and serum thyroglobulin measurement before ablation. The rate of recurrent laryngeal nerve (RLN) palsy showed a decreasing trend over time. No permanent RLN palsies occurred in nerves not invaded by tumor after routine IONM was introduced. Technetium-99m uptake (periods 1-3, 0.62 vs 0.32 vs 0.20; P < 0.01) and thyroglobulin levels (periods 1 and 2, 37.93 vs 8.98 ng/mL, respectively; P = 0.034; period 3, 9.10 ng/mL) progressively decreased. The mean thyroglobulin level dropped significantly after introduction of routine IONM. We conclude that routine IONM during thyroid cancer surgery improves surgical completeness and might prevent permanent RLN palsy over time.

The preoperative evaluation prevent the postoperative complications of thyroidectomy.

OBJECTIVE: Thyroid surgery is generally a safe surgery but its complications are still common. We wish to identify preoperative factors that predict postoperative complications. METHODS: A nationwide survey was conducted by senior surgeons from 16 medical centers and 5 regional hospitals in Taiwan to thyroid operations performed over 3 years. 3846 cases were retrospectively examined to identify factors influencing complications: indication for surgery, preoperative evaluation, such as ultrasonography, chest X-ray, computed tomography and magnetic resonance imaging, isotope scanning, fine-needle aspiration cytology (FNAC) and thyroid function test, and patient characteristics. RESULTS: Eighty-four percent of patients were female. Seven percent of the patients had immediate postoperative hypocalcemia (mild and severe) and 2.3%, hoarseness (recurrent laryngeal nerve (RLN) injury, temporary/permanent). Logistic regression analysis identified an association between hypocalcemia and RLN injury with age, hospital category, surgical procedure types (total thyroidectomy, unilateral, bilateral subtotal or total resection). A lower incidence of hypocalcemia was related to preoperative neck ultrasound and FNAC analysis (the odds ratio (OR) = 0.5 and 0.65, [95% confidence interval (CI) 0.331-0.768 and 0.459-0.911], P = 0.0014 and 0.0127, respectively), while RLN injury was not associated with any preoperative evaluation. The ORs of hypocalcemia and RLN injury for patients older than 50 years were 0.55 and 2.15, [0.393-0.763 and 1.356-3.4], P < 0.001 and 0.0012, respectively. CONCLUSIONS: The success of thyroid surgery depends on careful preoperative planning, including a preoperative neck ultrasound to determine the proximity of the nodule to the recurrent laryngeal nerve course, and the consideration of the type of anesthesia, adjuvant devices for intra-op monitoring of the RLN, and surgical modalities. Our results suggest that preoperative evaluation implementations are positively associated with strategy of surgery and postoperative hypocalcemia prevention.

Hyalinizing trabecular tumor of thyroid: does frozen section prevent unnecessarily aggressive operation? Six new cases and a literature review.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is very accurate in detecting papillary thyroid carcinomas (PTCs). According to the Bethesda system for reporting thyroid cytopathology, the risk for malignancy is 97-99% when FNAC is used to diagnose PTC; the malignancy risk is 60-75% when FNAC results in suspected PTCs. The presence of hyalinizing trabecular tumor (HTT) of the thyroid can cause misdiagnosis because its cytological features mimic PTCs. However, the use of frozen section analysis can assist in the recognition of unique architecture features of HTT, and thus may help prevent the undertaking of an unnecessarily aggressive operation. METHODS: We retrospectively reviewed all patients diagnosed with HTT by permanent histopathology from February 2009 to October 2013. After acquired agreement of the patients, we analyzed all data and reviewed another nine cases of HTT reported in the English-language medical literature to examine the efficacy of frozen section. RESULTS: There were six patients included in our research (5 women and 1 man), with an average age of 48.8 years. Using frozen section, four patients were diagnosed with HTT and two patients were misinterpreted as PTC. Consequently, four patients had lobectomy and two patients had total thyroidectomy, with no surgical complications. Of the nine cases of HTT reviewed from the English literature, the use of frozen section showed three HTT cases, three PTC cases, two medullary thyroid carcinoma cases, and one deferral case. Overall, the use of frozen section as a diagnostic method prevented additional surgical resection in eight patients (53%). CONCLUSION: Frozen section can sometimes but not always be used to diagnose HTT. When HTT is diagnosed by its trabecular pattern through the use of frozen section, it may prevent total thyroidectomy.

Persistent renal hyperparathyroidism caused by intrathyroidal parathyroid glands.

Renal hyperparathyroidism usually occurs in chronic renal failure patients on regular dialysis. However, renal hyperparathyroidism resulting from intrathyroidal parathyroid glands is an uncommon condition. We herein present the case of a 35-year-old woman who has been on hemodialysis for 20 years. She had renal hyperparathyroidism with generalized weakness and bone pain for 2 years. The patient initially underwent parathyroidectomy at a local institution, during which two large parathyroid glands were resected from the right side (no parathyroid glands were found on the left side); however, the surgical procedure was unsuccessful, and the patient had persistent renal hyperparathyroidism after the operation. She was then transferred to our hospital and ectopic intrathyroidal parathyroid glands were localized by neck ultrasonography and technetium-99m sestamibi scans with single-photon emission computed tomography imaging preoperatively. A left thyroid lobectomy was performed and two intrathyroidal parathyroid glands were found. The patient recovered uneventfully and her symptoms resolved. Therefore, clinicians should be aware of the possibility of renal hyperparathyroidism resulting from intrathyroidal parathyroid glands in cases where the renal hyperparathyroidism persists after parathyroidectomy.

Application of marionette technique for 3-port laparoscopic liver resection.

BACKGROUND: Laparoscopic liver resection has become a feasible and safe procedure for liver tumor, but it requires experienced surgeons in the case of hepatobiliary and laparoscopic surgeries. More minimally invasive laparoscopic techniques of liver surgery are developed. We here report our experience of using a marionette technique for 3-port laparoscopic liver resection. METHODS: Between June 2009 and December 2010, 7 patients underwent 3-port laparoscopic liver resection with the use of marionette technique. Five patients had hepatocellular carcinoma. Two patients with prior abdominal operations for colon cancer had colorectal liver metastasis. The procedure of marionette technique was performed as below: after insertion of the 3 trocars, a 2-0 nylon straight needle line was inserted through the abdominal wall, and using the needle holder, it was allowed to traverse the liver edge twice. Then, the straight needle line was forced out of the abdominal wall and clamped using mosquito for traction. Another straight needle line was similarly created at the opposite side of the liver edge. RESULTS: None of the patients had to be converted to open surgery. The mean operative time was 96.7 ± 63.2 minutes (range, 45 to 195 min), and the mean volume of blood loss was 45.6 ± 27.9 mL (range, 30 to 100 mL). The mean pain score recorded on the visual analog scale was 2.7 ± 0.8. The mean hospital stay was 5.6 ± 1.7 days (range, 4 to 9 d). Currently, all the 7 patients are alive, and the tumors have not recurred (Supplementary Digital Content video 1 http://links.lww.com/SLE/A67). CONCLUSIONS: Our experience demonstrated that the simple marionette technique procedure could help surgeons ease laparoscopic liver resection and achieve better postoperative results.

Superselective transarterial chemoembolization vs hepatic resection for resectable early-stage hepatocellular carcinoma in patients with Child-Pugh class a liver function.

PURPOSE: In contrast to hepatic resection (HR) for resectable early-stage HCC, the efficacy of transarterial chemoembolization (TACE) is controversial. This study is designed to compare the long-term outcome of TACE using superselective technique with hepatic resection for the treating resectable early-stage HCC and Child-Pugh class A liver function. METHODS: In total, 185 consecutive patients with resectable early-stage HCC and Child-Pugh class A liver function were included: 73 patients received superselective TACE (group I) and 112 patients underwent HR (group II). We evaluated the therapy-related recurrence and long-term outcome and in both groups. The risk factors of recurrence and mortality were assessed by Cox's model. RESULTS: The mean survival time of group 1 patient was similar to that of group 2 patient (40.8±19.8 vs 46.7±24.6 months respectively, p=0.91). The 1-, 3-, and 5-year overall survival rates after TACE (group I)and HR (group II) were 91%, 66%, and 52% and 93%, 71%, and 57%, respectively (p=0.239). The 1-, 3-, and 5-year recurrence-free survival rates in groups 1 and 2 were 68%, 28%, and 17% and 78%, 55%, and 35%, respectively (p<0.0001). Serum albumin, tumour size, tumour number and recurrence interval were independent risk factors for mortality. Serum albumin level, tumour size, tumour number, and treatment modality of TACE or HR could predict HCC recurrence. CONCLUSION: TACE is an efficient and safe treatment for resectable early-stage HCC with overall survival rates similar to that of HR. Thus, TACE is indicated in selected patients with resectable early-stage HCC.

Bilateral superficial cervical plexus block combined with general anesthesia administered in thyroid operations.

BACKGROUND: We investigated the analgesic efficacy of bilateral superficial cervical plexus block in patients undergoing thyroidectomy and to determine whether it reduces the adverse effects of general anesthesia. METHODS: We prospectively recruited 162 patients who underwent elective thyroid operations from March 2006 to October 2007. They were randomly assigned to receive a bilateral superficial cervical block (12 ml per side) with isotonic saline (group A; n = 56), bupivacaine 0.5% (group B; n = 52), or levobupivacaine 0.5% (group C; n = 54) after induction of general anesthesia. The analgesic efficacy of the block was assessed with: intraoperative anesthetics (desflurane), numbers of patients needing postoperative analgesics, the time to the first analgesics required, and pain intensity by visual analog scale (VAS). Postoperative nausea and vomiting (PONV) for 24 h were also assessed by the "PONV grade." We also compared hospital stay, operative time, and discomfort in swallowing. RESULTS: There were no significant differences in patient characteristics. Each average end-tidal desflurane concentration was 5.8, 3.9, and 3.8% in groups A, B, and C, respectively (p < 0.001). Fewer patients in groups B and C required analgesics (A: B: C = 33:8:7; p < 0.001), and it took longer before the first analgesic dose was needed postoperatively (group A: B: C = 82.1:360.8:410.1 min; p < 0.001). Postoperative pain VAS were lower in groups B and C for the first 24 h postoperatively (p < 0.001). Incidences of overall and severe PONV were lower, however, there were not sufficient numbers of patients to detect differences in PONV among the three groups. Hospital stay was shorter in group B and group C (p = 0.011). There was no significant difference in operative time and postoperative swallowing pain among the three groups. CONCLUSIONS: Bilateral superficial cervical plexus block reduces general anesthetics required during thyroidectomy. It also significantly lowers the severity of postoperative pain during the first 24 h and shortens the hospital stay.

Experience with reversed L-shaped incision for right hemicolectomy combined with liver resection.

BACKGROUND: Various types of incisions have been applied in simultaneous resections of colorectal cancer and synchronous liver metastases. We describe our experience with the reversed L-shaped incision for simultaneous right hemicolectomy and liver resection. METHODS: We applied the reversed L-shaped incision in nine patients who underwent simultaneous right hemicolectomy and right liver resection or left hepatectomy. A reversed L-shaped incision of the abdomen was consisted of midline and transverse incisions with the junction of the umbilicus. The operative field was kept open using Kent retractors. First, right colon mobilization was performed easily and right hemicolectomy was performed. Subsequently, liver mobilization with identification of hepatic vessels was achieved and right liver resection or left hepatectomy was performed. RESULTS: The reversed L-shaped incision successfully provided a good and rapid exposure in nine patients. There were no complications, such as wound infection, lung atelectasis/pneumonia, or incisional hernia, in patients with the reversed L-shaped incision. CONCLUSIONS: Our preliminary experience demonstrated that the reversed L-shaped incision might be a good choice in a subset of patients with simultaneous right hemicolectomy and right liver resection or left hepatectomy. However, a large, prospective, controlled study comparing different incision types in the same procedure with variables, such as operating time, postoperative pain scores, patient's satisfaction, and postoperative complication, is needed to support the benefit of the reversed L-shaped incision.

Hürthle cell carcinoma of the thyroid with contralateral malignant pleural effusion.

BACKGROUND: Thyroid cancers with pulmonary metastases have been well documented. However, malignant pleural effusion has rarely been reported. CASE REPORT: We present a 77-year-old patient who had Hürthle cell carcinoma of the thyroid with contralateral malignant pleural effusion. The diagnosis was based on consistency in the histopathological and immunohistochemical features of pleural fluid cytology and the final pathology of the thyroid tumor. RESULTS: The patient was treated with total thyroidectomy and postoperative radioactive-iodine ablation. Unfortunately, he died for recurrent pleural effusion and pulmonary complication 6 months later. CONCLUSION: Identifying the origin of malignant pleural effusion is important to provide treatment guidance. In this report, we review the literature on diagnosis and treatment of thyroid cancer with malignant pleural effusion.

Total parathyroidectomy without autotransplantation for secondary hyperparathyroidism.

BACKGROUND: To treat secondary hyperparathyroidism with subtotal parathyroidectomy or total parathyroidectomy with autotransplantation might cause the disease to recur because of growth of the parathyroid remnant or the autografts. The aim of the present study was to determinate an alternative surgical treatment for secondary hyperparathyroidism. METHODS: Of 94 uremic patients, 44 (median age: 50.5 years; 33 women/11 men) were assigned to group A, patients who were not expected to receive kidney transplantation for various reasons and had total parathyroidectomy without autotransplantation; 50 (median age 46 years; 33 women/17 men) were assigned to group B, patients who had either total parathyroidectomy with autotransplantation or subtotal total parathyroidectomy with preservation of parathyroid tissue in situ. Parameters measured included demographics, perioperative and follow-up biochemistry tests, operative time, postoperative complications, length of hospital stay, patients' compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D supplementation regimen, symptom relief, and presence of recurrence. RESULTS: Mean operative times were 103 and 122 min (P = 0.007); postoperative complication rates were 18.2% and 12.0% (P = 0.563); mean hospital stays were 6 and 9 days (P = 0.259); adequate patient compliance with the postoperative calcium and 1,25 dihydroxy-viatmin D regimens were 84.1% and 78.0%, respectively (P = 0.6); symptom relief rates were 88.6% and 80.0% (P = 0.277). Recurrence rates over 60 months in group A and group B were 4.5% and 18.0%, resectively (P = 0.028 by Kaplan-Meier analysis). CONCLUSIONS: Because of the lower recurrent rate and shorter operative time, total parathyroidectomy without autotransplantation may be an option for treating patients with symptomatic secondary hyperparathyroidism who are not expected to receive kidney transplantation.

Thyroidectomy for Hashimoto's thyroiditis: complications and associated cancers.

BACKGROUND: Hashimoto's thyroiditis is usually treated medically; however, thyroidectomy is sometimes indicated. Thyroiditis can make thyroid dissection more difficult and possibly increase the risk of surgical complications. The aim of this study was to determine the rate of complications and associated cancer in patients with Hashimoto's thyroiditis. METHODS: Retrospective series of 474 patients treated surgically at the University of California, San Francisco, between January 1985 and June 2005 with final pathology demonstrating Hashimoto's thyroiditis, chronic lymphocytic thyroiditis, or chronic thyroiditis. Parameters evaluated included demographics, surgical indications, and postoperative complications. RESULTS: Among the 474 patients, 133 had thyroidectomy because of preoperative diagnosis of thyroid cancers (median age 39 years; 116 females and 17 males), 316 had thyroidectomy because of benign thyroid nodules or goiter (median age 47.5 years; 292 females and 24 males), and 25 had thyroidectomy to relieve local symptoms caused by thyroiditis but did not have thyroid nodules (median age 42 years; 25 females). No death or permanent surgical complications occurred. One hundred and fifty-two patients (32.1%) had transient postoperative hypocalcemia, 2 (0.4%) had transient recurrent nerve palsy, and 4 (0.8%) had a postoperative neck hematoma. Fifty-three percent had thyroid cancer at final histological examination. CONCLUSIONS: Thyroidectomy can be performed in patients with Hashimoto's thyroiditis with a low risk of permanent surgical complications. Cancer is common in patients who have a thyroidectomy for Hashimoto's thyroiditis even when not suspected preoperatively.

Primary malignant fibrous histiocytoma of the thyroid: review of the literature with two new cases.

Primary malignant fibrous histiocytoma of thyroid is extremely rare. Only three cases have been reported. We report two cases of this rare disease. Case 1 was a 70-year-old woman who had Graves' disease and a growing 3.5-cm thyroid nodule with constrictive symptoms. Fine-needle aspiration cytology showed suspicious atypical cells. She had a total thyroidectomy; frozen section showed sarcoma. Final pathology showed malignant fibrous histiocytoma. Case 2 was a 67-year-old woman who had a 5-cm thyroid nodule that rapidly grew, causing tracheal deviation. A diagnostic lobectomy and pathology showed malignant fibrous histiocytoma. She then had a completion total thyroidectomy. Neither patient had metastatic lesions found by whole body gallium scans, computerized tomographic scans, and neck sonography. Both patients had postoperative radiotherapy and were alive and without recurrence at 6 months follow-up.

Accurate diagnosis and successful treatment for massive obscure small intestinal bleeding by means of intra-operative enteroscopy: a case report.

Obscure gastrointestinal bleeding from the jejunum and ileum is always difficult to diagnose. Unstable patients with massive bleeding are not good candidates either for radiological studies or traditional endoscopic techniques. They usually need urgent operations to stop the bleeding. To identify the lesions, intraoperative enteroscopy is crucial for a better curing rate and for preventing massive unnecessary bowel resection. We report a 53-year-old unstable patient with massive obscure small intestinal bleeding. Urgent laparotomy with intraoperative enteroscopy was done. Two bleeding ulcers in the distal ileum were accurately identified and the diseased ileum was resected. Intraoperative enteroscopy may be a choice of diagnostic and therapeutic modality for unstable patients with obscure small intestinal bleeding.