Effective Treatment of Lung Adenocarcinoma With a Novel SLC44A1-BRAF Fusion Using Pembrolizumab Followed by Trametinib: A Case Report.

The serine-threonine protein kinase B-RAF (BRAF) fusions are rarely observed in non-small cell lung cancer (NSCLC) accounting for less than 1%, and therapeutic evidence for molecular-targeted drugs is lacking, unlike for BRAF V600E mutation by RAF and MEK inhibitors. A 75-year-old female patient with no smoking history and mild renal dysfunction developed recurrent lung adenocarcinoma and was initially treated with pembrolizumab immunotherapy followed by chemotherapy using docetaxel showing a certain efficacy but the disease finally progressed. Comprehensive genome profiling showed a novel SLC44A1-BRAF fusion and the tumor progression was controlled with the MEK inhibitor trametinib. Because of the rarity of NSCLC with BRAF fusion, the description of this case would be helpful for the treatment strategy for such tumors.

Rheumatoid Arthritis Symptoms Diagnosed by Rheumatic Immune-related Adverse Events Caused by Nivolumab in a Patient with Esophageal Cancer.

This report described the case of a 70-year-old man who developed polyarthralgia after nivolumab treatment for recurrent esophageal cancer. Arthritis developed after initiating nivolumab therapy, and the patient tested positive for rheumatoid factor and anti-citrullinated peptide antibodies. The hand and elbow joints were already deformed, suggesting that he had had rheumatoid arthritis for several years and that the symptoms had only become apparent after nivolumab administration. This patient had rheumatoid arthritis, which was diagnosed as a nivolumab-induced rheumatic immune-related adverse event (rh-irAEs). Arthralgia during nivolumab administration can occur in rh-irAE cases. Patients should be assessed for autoimmune diseases before initiating immune checkpoint inhibitors.

New Closure Method Using Loop and Open-Close Clips after Endoscopic Submucosal Dissection of Stomach and Colon Lesions.

Endoscopic submucosal dissection (ESD) and en bloc resection of stomach and colon tumors have become common. However, mucosal defects resulting from ESD may cause delayed bleeding and perforation. To prevent adverse events, we developed a new clip closure technique, namely, the loop and open-close clip closure method (LOCCM), and aimed to examine its efficacy after ESD for stomach and colon tumors. The LOCCM uses loop and open-close clips. Here, the open-close clip was used to grasp the loop to bring it to the edge of the post-ESD mucosal defect. Another clip with a loop was then inserted into the opposite edge and clipped to the contralateral mucosa to pull both edges together. Once apposed, additional clips facilitated complete closure. The LOCCM was performed in 19 patients after ESD at Tottori University between October 2020 and March 2021. The outcomes retrospectively analyzed were the LOCCM success and adverse event rates. The complete closure rate using LOCCM was 89.5% and none of the patients had post-ESD bleeding or perforation. The results show that LOCCM is an effective and safe closure technique for mucosal defects after stomach and colon ESD to prevent bleeding and perforation.

Salvage Photodynamic Therapy Using Talaporfin Sodium for Local Failure of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been reported to be highly effective and less invasive, compared to other treatment modalities. TS-PDT was recently introduced at the Tottori University Hospital, Japan. The aim of this study is to clarify the efficacy and safety of PDT in our hospital. METHODS: This was a single-center observational study. We examined eight cases of TS-PDT performed between January 2016 and December 2019. The main endpoints were local complete remission (L-CR) rate and the adverse events. In addition, age, gender, histology, tumor location, TNM stage, tumor depth, irradiation dose, and overall survival (OS) were examined. RESULTS: The patients included 7 men and a woman, with an average age of 72.1 years (range 63-82 years). The baseline clinical stages before CRT or radiotherapy were stage I in 1, stage II in 3, stage III in 3, and stage IVA in 1 patient. The T stage on endoscopic assessment before TS-PDT was T1 in 6 patients and T2 in 2 patients. Treatment outcomes and adverse events were evaluated. There were no treatment-related deaths, and no significant adverse events occurred intraoperatively or postoperatively. The L-CR rate was 7/8 (87.5%); T1 cases had 100% (6/6) L-CR, while T2 cases had 50% (1/2). The 2-year OS rates were 87%. CONCLUSION: TS-PDT was observed to be safe and effective in the first eight cases of its application following its introduction in our hospital.

Neutrophil-to-Lymphocyte Ratio Is a Useful Marker for Predicting Histological Types of Early Gastric Cancer.

BACKGROUND: The indications for endoscopic submucosal dissection (ESD) for gastric cancer are based on preoperative histological assessment; however, examination of tissue biopsy is not always reliable as only a limited portion of the lesion can be obtained. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammatory response and are potentially associated with the grade of malignancy in gastric cancer. We aimed to investigate the association between NLR and PLR and the histology of gastric cancer. METHODS: This study included 218 patients who underwent ESD for gastric cancer. The relationship between NLR/PLR and histological diagnosis was investigated. RESULTS: Patients with adenocarcinomas showed significantly higher NLR and PLR than those with adenomas (p < 0.001 and p < 0.05, respectively). Further, patients with undifferentiated adenocarcinoma showed a significantly higher NLR (p < 0.05) than those with differentiated adenocarcinoma. CONCLUSION: This study suggests that NLR could be a useful marker for assessing early gastric cancer.

Phase reduction and synchronization of a network of coupled dynamical elements exhibiting collective oscillations.

A general phase reduction method for a network of coupled dynamical elements exhibiting collective oscillations, which is applicable to arbitrary networks of heterogeneous dynamical elements, is developed. A set of coupled adjoint equations for phase sensitivity functions, which characterize the phase response of the collective oscillation to small perturbations applied to individual elements, is derived. Using the phase sensitivity functions, collective oscillation of the network under weak perturbation can be described approximately by a one-dimensional phase equation. As an example, mutual synchronization between a pair of collectively oscillating networks of excitable and oscillatory FitzHugh-Nagumo elements with random coupling is studied.