BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

BACKGROUND: Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. PATIENTS AND METHODS: We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. RESULTS: A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07) cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. CONCLUSIONS: Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

A Shift in Molecular Drivers of Papillary Thyroid Carcinoma Following the 2017 World Health Organization Classification: Characterization of 554 Consecutive Tumors With Emphasis on BRAF-Negative Cases.

Most studies for comprehensive molecular profiling of papillary thyroid carcinoma (PTC) have been performed before the 2017 World Health Organization (WHO) classification, in which the diagnostic criteria of follicular variants of PTC have been modified and noninvasive follicular thyroid neoplasm with papillary-like nuclear features has been introduced. This study aims to investigate the shift in the incidence of BRAF V600E mutations in PTCs following the 2017 WHO classification and to further characterize the histologic subtypes and molecular drivers in BRAF-negative cases. The study cohort consisted of 554 consecutive PTCs larger than 0.5 cm between January 2019 and May 2022. Immunohistochemistry for BRAF VE1 was performed for all cases. Compared with a historical cohort of 509 PTCs from November 2013 to April 2018, the incidence of BRAF V600E mutations was significantly higher in the study cohort (86.8% vs 78.8%, P = .0006). Targeted RNA-based next-generation sequencing using a FusionPlex Pan Solid Tumor v2 panel (ArcherDX) was performed for BRAF-negative PTCs from the study cohort. Eight cribriform-morular thyroid carcinomas and 3 cases with suboptimal RNA quality were excluded from next-generation sequencing. A total of 62 BRAF-negative PTCs were successfully sequenced, including 19 classic follicular predominant PTCs, 16 classic PTCs, 14 infiltrative follicular PTCs, 7 encapsulated follicular PTCs, 3 diffuse sclerosing PTCs, 1 tall cell PTC, 1 solid PTC, and 1 diffuse follicular PTC. Among them, RET fusions were identified in 25 cases, NTRK3 fusions in 13 cases, BRAF fusions in 5 cases including a novel TNS1::BRAF fusion, NRAS Q61R mutations in 3 cases, KRAS Q61K mutations in 2 cases, NTRK1 fusions in 2 cases, an ALK fusion in 1 case, an FGFR1 fusion in 1 case, and an HRAS Q61R mutation in 1 case. No genetic variants, from our commercially employed assay, were detected in the remaining 9 cases. In summary, the incidence of BRAF V600E mutations in PTCs significantly increased from 78.8% to 86.8% in our post-2017 WHO classification cohort. RAS mutations accounted for only 1.1% of the cases. Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.

Printing a Three-Dimensional Patient-Specific Safety Device for Reducing the Potential Risk of Mental Nerve Injury During Transoral Thyroidectomy.

BACKGROUND: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. METHODS: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. RESULTS: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. CONCLUSIONS: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive.

Hepatoid carcinoma of the pancreas.

BACKGROUND: Hepatoid carcinoma of the pancreas is extremely rare. This article tries to summarize the clinical features and outcomes of pancreatic hepatoid carcinoma. METHODS: The data pool for analysis includes the case we encountered with hepatoid carcinoma of the pancreas and the reported cases in the literature. RESULTS: Twenty-three cases of hepatoid carcinoma of the pancreas were analyzed. This tumor occurred more frequently in male than in female patients (69.6 vs. 30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic head, nausea/vomiting (62.5 %) is more common, followed by jaundice and epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in 60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form or mixed form with other malignancy (40.9 %), with the most common coexisted pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4 % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8 % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1 % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and lymph node metastases are associated with negative impact on survival outcome. CONCLUSIONS: Elevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma. This tumor could be mixed form with other malignancy. Surgical resection should be the treatment of choice whenever possible.

Parathyroidectomy for dialysis patients in the era of calcimimetics: The surgeons' point of view.

Calcimimetics is a new drug for lowering serum parathyroid hormone (PTH), calcium and phosphate in patients with hyperparathyroidism (HPT) on long-term dialysis. It became available on market in 2006. The impact of calcimimetics on the treatment by parathyroidectomy (PTx) was reviewed from the surgeons' point of view. Cure of renal HPT by calcimimetics is not feasible, but calcimimetics can improve preoperative cardiac ventricle ejection fractions by lowering serum PTH. Heart failure is not necessarily a contraindication for PTx. PTx should be done before irreversible organ damage occurs. Limb gangrenes is an ominous sign and should be prevented by frequent checkup for peripheral arterial circulation. The impact of renal osteodystrophy on the quality of life and as indirect cause of mortality deserves more attention in patients with renal HPT. Delayed referral to PTx leads to more complicated patients. A consensus between nephrologists and surgeons about propitious timing for PTx is necessary. Future prospect on the surgical treatment of renal HPT is proposed. Supplemental figure; http://links.lww.com/ASAIO/A782.

Clusterin expression in nontumor tissue in patients with resectable hepatocellular carcinoma related with postresectional survival.

BACKGROUND: Surgical resection offers an effective treatment for patients with hepatocellular carcinoma (HCC); however, it has high tumor recurrence rate. Clusterin is a highly conserved glycoprotein that enhances cell aggregation in vitro. It is upregulated in several types of cancers such as breast, ovarian, colon, prostate and kidney cancers, and HCC. Clusterin overexpression is correlated with tumor metastasis. We evaluated the significance of clusterin expression levels in serum and resected tissues of patients with HCC. METHODS: Serum, resected tumor tissue, and nontumor tissue were collected from 140 patients with HCC undergoing hepatic resection. Serum clusterin levels were determined by enzyme-linked immunosorbent assay. Clusterin expression in resected tissue was evaluated by immunohistochemistry. Median follow-up time was 57.8 months. RESULTS: Mean serum clusterin levels were found to be 130.0 ± 58.7 µg/mL (range, 10.1-366.6 µg/mL). Serum clusterin levels were independent of tumor stage and deterioration of liver function in patients. No significant difference was observed in the survival of patients with high (>130.0 ± 58.7 µg/mL) or low (≤130.0 ± 58.7 µg/mL) serum clusterin level. Clusterin was expressed in HCC tissues of 76 patients (54.3%) and nontumor liver tissues of 53 patients (37.9%). No significant difference was observed in the survival of patients with positive or negative clusterin expression in HCC tissues. In nontumor tissues, patients with positive clusterin expression were observed to have low postoperative disease-free survival rate (p = 0.001) compared to patients with negative clusterin expression. Multivariate analysis showed that tumor with macrovascular/microvascular invasion and clusterin expression in nontumor tissues are independent prognostic factors following hepatic resection. CONCLUSION: In HCC, clusterin expression in nontumor tissue shows worse prognosis after hepatic resection. Clusterin can be a prognostic marker for patients with postresection HCC.