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.

The emerging role of cell-free DNA as a molecular marker for duodenal adenocarcinoma.

BACKGROUND: Duodenal adenocarcinoma is rare and its prognostic factors remain controversial. In our study, the role of cell-free deoxyribonucleic acid (cfDNA) as prognostic factor in duodenal adenocarcinoma was evaluated. METHODS: From June 2003 to July 2021, plasma samples were collected from 41 patients with duodenal adenocarcinoma. Plasma cfDNA was assessed in combination with clinicopathological and biochemical characteristics. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival with a Cox proportional hazards regression model. RESULTS: The 1- and 5-year survival rates of the patients with high plasma cfDNA level (>9288 copies/mL) group were 58.7% and 17.6%, respectively, which were much lower than patients with low cfDNA level (≤9288 copies/mL), with 95.2% and 64.6%. In univariate analysis, high cfDNA level, lymph node involvement, lymphovascular invasion, and tumor stage were associated with decreased survival. When subjected to multivariate analysis, only high cfDNA level showed significance in influencing the overall survival of duodenal cancer. CONCLUSION: cfDNA analysis is simple and noninvasive. High cfDNA level is a strong independent prognostic factor for decreased overall survival and it should be integrated into clinical care.

Postoperative fever after liver resection: Incidence, risk factors, and characteristics associated with febrile infectious complication.

PURPOSE: To evaluate the incidence and risk factors of postoperative fever (POF) after liver resection. In patients with POF, predictors of febrile infectious complications were determined. METHODS: A total of 797 consecutive patients undergoing liver resection from January 2015 to December 2019 were retrospectively investigated. POF was defined as body temperature ≥ 38.0°C in the postoperative period. POF was characterized by time of first fever, the highest temperature, and frequency of fever. The Institut Mutualiste Montsouris (IMM) classification was used to stratify surgical difficulty, from grade I (low), grade II (intermediate) to grade III (high). Postoperative leukocytosis was defined as a 70% increase of white blood cell count from the preoperative value. Multivariate analysis was performed to identify risk factors for POF and predictors of febrile infectious complications. RESULTS: Overall, 401 patients (50.3%) developed POF. Of these, 10.5% had the time of first fever > postoperative day (POD) 2, 25.9% had fever > 38.6°C, and 60.6% had multiple fever spikes. In multivariate analysis, risk factors for POF were: IMM grade III resection (OR 1.572, p = 0.008), Charlson Comorbidity Index score > 3 (OR 1.872, p < 0.001), and serum albumin < 3.2 g/dL (OR 3.236, p = 0.023). 14.6% patients developed infectious complication, 21.9% of febrile patients and 7.1% of afebrile patients (p < 0.001). Predictors of febrile infectious complications were: fever > 38.6°C (OR 2.242, p = 0.003), time of first fever > POD2 (OR 6.002, p < 0.001), and multiple fever spikes (OR 2.039, p = 0.019). Sensitivity, specificity, positive predictive value and negative predictive value for fever > 38.6°C were 39.8%, 78.0%, 33.7% and 82.2%, respectively. A combination of fever > 38.6°C and leukocytosis provided high specificity of 95.2%. CONCLUSION: In this study, we found that IMM classification, CCI score, and serum albumin level related with POF development in patients undergone liver resection. Time of first fever > POD2, fever > 38.6°C, and multiple fever spikes indicate an increased risk of febrile infectious complication. These findings may aid decision-making in patients with POF who require further diagnostic workup.

Minimally invasive distal pancreatectomy: Laparoscopic versus robotic approach-A cohort study.

Background and Aims: There is no consensus on the superiority of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP). Methods: Data of patients undergoing RDP and LDP were prospectively collected and compared. Results: There were 65 RDP and 112 LDP. RDP took a shorter operation time than LDP. Overall, DP with splenectomy took a longer operation time than that with spleen preservation. This difference was only significant in LDP group. In both RDP and LDP groups, splenectomy was associated with increased blood loss, as compared with spleen preservation. No significant differences were observed in surgical morbidity between RDP and LDP. The hospital cost in RDP was almost double that of LDP, with a median of 13,404 versus 7765 USD. Conclusion: LDP is comparable to RDP in regard to surgical outcomes. LDP with spleen preservation is highly recommended whenever possible and feasible for benign or low malignant lesions in terms of lower costs and less blood loss.