Entrectinib Response to ROS1-Fusion-Positive Non-Small-Cell Lung Cancer That Progressed on Crizotinib with Leptomeningeal Metastasis: A Case Report.

Introduction: C-ros oncogene 1 (ROS1) translocation is an oncogenic driver-mutation identified in 1-2% of non-small-cell lung cancer (NSCLC) cases. Although crizotinib, a tyrosine kinase inhibitor (TKI) against ALK/ROS1, is known to be effective against ROS1-fusion-positive NSCLC, such cases sometimes progress with brain metastases. The most frequently reported crizotinib-resistance mutation is ROS1 G2032R, and some studies have found that even newly developed ROS1 TKIs, such as entrectinib and lorlatinib, show a decreased efficacy against it. The optimal therapies for ROS1-fusion-positive NSCLC and how such cases can be sequenced have not yet been established. Case Presentation: We herein report a patient with ROS1-fusion-positive NSCLC diagnosed at 34 years old. Crizotinib was started at the diagnosis and switched after 25 months to cisplatin/pemetrexed/bevacizumab once the disease progressed with multiple brain metastases that were resistant to stereotactic radiation therapy. The cytotoxic chemotherapy stabilized the patient's condition for 17 months until he developed leptomeningeal metastasis (LM). He underwent lumboperitoneal shunting and whole-brain radiotherapy, followed by crizotinib re-administration. Despite crizotinib treatment, his neurological symptoms, such as double vision, headache, weakness in the legs, and walking difficulties, progressed. Eventually, subsequent entrectinib treatment was initiated, which resolved all of the symptoms mentioned above. Regrettably, liquid next-generation sequencing had failed to detect the resistance mechanism due to minimal ctDNA in this case. Conclusion: These findings imply that sequential entrectinib administration may be effective in patients with disease progression limited to central nervous system metastases during crizotinib administration.

Trans-anal reinforcing sutures after double stapling for lower rectal cancer: report of two cases.

To safely avoid the construction of a covering stoma in patients with advanced lower rectal cancer undergoing laparoscopy assisted colorectal surgery (LACS), we added circumferential manual reinforcing sutures via the transanal approach at the site of mechanical anastomosis. In June 2008, LACS was performed for a tumor of 6 cm in longer diameter in the Rb region of the lower rectum approximately 5 cm from the anal verge. After intraperitoneal coloproctal anastomosis was performed in the pelvis by the double stapling technique (DST), reinforcement was provided by manual trans-anal suturing (trans-anal reinforcing sutures: TARS). A covering stoma was constructed because this was a high-risk case. Complications such as mild wound infection and stoma trouble occurred, and the patient was discharged after conservative therapy. In June 2008, LACS was performed for a tumor of 5 cm in longer diameter in the Ra region of the lower rectum approximately 7 cm from the anal verge. After intraperitoneal colorectal anastomosis was performed in the pelvis by DST, TARS were added to avoid a covering stoma. Minor leakage occurred postoperatively, but this was controlled conservatively and the patient was discharged. In patients having surgical treatment of advanced lower rectal cancer, good results were obtained by adding circumferential reinforcing sutures via the trans-anal approach at the site of ultra-low anastomosis after DST.

Hybrid 2-port hand-assisted laparoscopic surgery for the 2-stage treatment of a complete bowel obstruction by distal sigmoid colon cancer: a case report.

In July 2008, a 40-year-old man presented to his local physician with diffuse abdominal pain and severe abdominal distension. Impending bowel rupture due to colonic obstruction was strongly suspected. Complete obstruction of the distal sigmoid colon by a tumor was diagnosed, and emergency surgery was performed. A sigmoid colon loop colostomy was created within the range of subsequent resection to relieve the obstruction. After his general condition had improved and the risks were assessed, curative resection including removal of the stoma was performed by hybrid 2-port hand-assisted laparoscopic surgery. The tumor showed invasion of the serosa without lymph node metastasis, and its pathological diagnosis was stage II. Postoperatively, mild wound infection occurred at the hand access site (stoma), but it resolved with conservative treatment, and the patient was discharged on postoperative day 13. This case is reported here because of the good results.

Curative resection by hybrid 2-port HALS in a patient with advanced cecal cancer invading the urinary bladder: a case report.

A 67-year-old woman was referred to our department for assessment of a tumor in the right lower abdomen. Advanced cecal cancer invading the urinary bladder was diagnosed, and laparoscopy assisted colorectal surgery (LACS)-hybrid 2-port hand-assisted laparoscopic surgery (HALS) was performed in February 2008. Intraoperative laparoscopic observation revealed direct invasion of the urinary bladder by the primary tumor, so an approximately 6-cm transverse suprapubic incision was made. Under direct vision through this incision, full-thickness partial cystectomy was performed to remove the tumor invading the bladder. Then D3 right hemicolectomy was performed under pneumoperitoneum. In this patient with advanced cecal cancer invading the bladder, we performed radical curative surgery by hybrid 2-port HALS, a minimally invasive procedure in which a 6-cm incision was made in addition to the hand access site and favorable results were obtained.

Synthesis and characterization of mononuclear ruthenium(III) pyridylamine complexes and mechanistic insights into their catalytic alkane functionalization with m-chloroperbenzoic acid.

A series of mononuclear RuIII complexes [RuCl2(L)]+, where L is tris(2-pyridylmethyl)amine (TPA) or one of four TPA derivatives as tetradentate ligand, were prepared and characterized by spectroscopic methods, X-ray crystallography, and electrochemical measurements. The geometry of a RuIII complex having a non-threefold-symmetric TPA ligand bearing one dimethylnicotinamide moiety was determined to show that the nicotine moiety resides trans to a pyridine group, but not to the chlorido ligand. The substituents of the TPA ligands were shown to regulate the redox potential of the ruthenium center, as indicated by a linear Hammett plot in the range of 200 mV for RuIII/RuIV couples with a relatively large rho value (+0.150). These complexes act as effective catalysts for alkane functionalization in acetonitrile with m-chloroperbenzoic acid (mCPBA) as terminal oxidant at room temperature. They exhibited fairly good reactivity for oxidation of cyclohexane (C--H bond energy 94 kcal mol(-1)), and the reactivity can be altered significantly by the electronic effects of substituents on TPA ligands in terms of initial rates and turnover numbers. Catalytic oxygenation of cyclohexane by a RuIII complex with 16O-mCPBA in the presence of H2 18O gave 18O-labeled cyclohexanol with 100% inclusion of the 18O atom from the water molecule. Resonance Raman spectra under catalytic conditions without the substrate indicate formation of a RuIV==O intermediate with lower bonding energy. Kinetic isotope effects (KIEs) in the oxidation of cyclohexane suggest that hydrogen abstraction is the rate-determining step and the KIE values depend on the substituents of the TPA ligands. Thus, the reaction mechanism of catalytic cyclohexane oxygenation depends on the electronic effects of the ligands.

Development of steel damper for menshin bridges

A steel damper was developed for energy dissipation for higway bridges. The steel damper is circular and made of stainless steel. Characteristic tests perfomed on thesteel damper showed that it absorbs large deformation and has hysteresis damping capacity. The perfomance of the steel damper does not vary according to the velocity, frequency and temperature.(AU)