Timing to Surgery and Lymph Node Upstaging in Gastric Cancer: An NCDB Analysis.

BACKGROUND: Prior studies have shown tumor specificity on the impact of longer time interval from diagnosis to surgery, however in gastric cancer (GC) this remains unclear. We aimed to determine if a longer time interval from diagnosis to surgery had an impact on lymph node (LN) upstaging and overall survival (OS) outcomes among patients with clinically node negative (cN0) GC. PATIENTS AND METHODS: Patients diagnosed with cN0 GC undergoing surgery between 2004-2018 were identified in the National Cancer Database (NCDB) and divided into intervals between time of diagnosis and surgery [short interval (SI): ≥ 4 days to < 8 weeks and long interval (LI): ≥ 8 weeks]. Multivariable regression analysis evaluated the independent impact of surgical timing on LN upstaging and a Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes. RESULTS: Of 1824 patients with cN0 GC, 71.8% had a SI to surgery and 28.1% had a LI to surgery. LN upstaging was seen more often in the SI group when compared to LI group (82% versus 76%, p = 0.004). LI to surgery showed to be an independent factor protective against LN upstaging [adjusted odds ratio = 0.62, 95% CI: (0.39-0.99)]. Multivariate Cox regression analysis indicated that time to surgery was not associated with a difference in overall survival [hazard ratio (HR) = 0.91, 95% CI: (0.71-1.17)], however uncontrolled Kaplan-Meier curves showed OS difference between the SI and LI to surgery groups (p = 0.037). CONCLUSION: Timing to surgery was not a predictor of LN upstaging or overall survival, suggesting that additional medical optimization in preparation for surgery and careful preoperative staging may be appropriate in patients with node negative early stage GC without affecting outcomes.

Comparative anatomic and symptomatic recurrence outcomes of diaphragmatic suture cruroplasty versus biosynthetic mesh reinforcement in robotic hiatal and paraesophageal hernia repair.

BACKGROUND: Hiatal and paraesophageal hernia (HH/PEH) recurrence is the most common cause of failure after gastroesophageal anti-reflux surgery. Crural reinforcement with mesh has been suggested to address this issue, but its efficacy remains debated. In this study, we aimed to determine the impact of biosynthetic mesh reinforcement compared to suture cruroplasty on anatomic and symptomatic hernia recurrence. METHOD: Data of patients who underwent robotic HH/PEH repair with suture cruroplasty with or without biosynthetic mesh reinforcement between January 2012 and April 2024 were retrospectively reviewed. Gastroesophageal reflux disease symptoms and anatomic hernia recurrence were assessed at short-term (3 months to 1 year) and longer-term (≥ 1 year) follow-up. Symptomatic hernia recurrence was defined as having both anatomic recurrence and symptoms. RESULTS: Out of the 503 patients in the study, 308 had undergone biosynthetic mesh repair, while 195 had suture-only repair. After the surgery, both groups demonstrated comparable improvements in symptoms. Short-term anatomic hernia recurrence rates were 11.8% and 15.6% for mesh and suture groups, respectively (p = 0.609), while longer-term rates were 24.7% and 44.9% (p = 0.015). The rates of symptomatic hernia recurrence in the same group were 8.8% and 14.6% in the short-term (p = 0.256), and 17.2% and 42.2% in longer-term follow-ups (p = 0.003). In the repair of medium and large-size hernias, mesh reinforcement resulted in a 50.0% relative risk reduction in anatomic hernia recurrences and a 59.2% reduction in symptomatic hernia recurrences at ≥ 1-year follow-up. CONCLUSION: After more than a year of follow-up, it has been found that using biosynthetic mesh for medium and large hiatal or paraesophageal hernia repair significantly reduces the likelihood of both anatomic and symptomatic recurrence compared to using only suture cruroplasty. These findings strongly support the use of biosynthetic mesh to manage larger hernias. However, further long-term multicenter randomized studies are needed to provide more conclusive evidence.

Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. IMPLICATIONS: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.