[A Case of Locally Advanced Unresectable Esophageal Cancer Treated with Nivolumab and Ipilimumab Therapy Followed by Surgery].

In cases of unresectable, locally advanced esophageal cancer, conversion surgery may be considered if chemotherapy produces favorable results and surgical resection is indicated. The use of immune checkpoint inhibitors in chemotherapy for esophageal cancer has expanded, and has increased the number of cases in which conversion surgery becomes possible. The patient in the present report had received a diagnosis of Stage Ⅳa esophageal carcinoma, and a prior nephroureterectomy discouraged the administration of platinum-based agents. Nivolumab and ipilimumab were administered as induction chemotherapy. Despite the achievement of stable disease, the patient's esophageal stricture deteriorated, necessitating surgical intervention. The resected specimen revealed that fewer than 50% of malignant cells remained viable and residual cancer cells were noticeably absent, particularly in the enlarged lymph nodes. We herein present the details of this case and discuss the literature concerning surgery following immune checkpoint inhibitor therapy.

[A Case of Ramucirumab-Related Small Intestinal Perforation in Gastric Cancer].

A 54-year-old man underwent laparoscopic distal gastrectomy with D2 lymph node dissection and ante-colic Roux-en-Y reconstruction for gastric cancer. The histopathological diagnosis was pT2N3aM0, pStage ⅢA, HER2 negative. After 8 courses of S-1 plus oxaliplatin as adjuvant chemotherapy, he was diagnosed as peritoneal dissemination and treated with ramucirumab(RAM)plus paclitaxel(PTX). On the 12th day of course 10, he visited to our hospital with abdominal pain. CT showed free air and massive ascites. Emergent surgery was performed under the diagnosis of gastrointestinal perforation. A small intestinal perforation in front of the jejunal limb near gastric-jejunal anastomosis was identified and there was no peritoneal dissemination. We performed partial resection of remnant stomach and jejunal limb by linear stapler and reconstruction by end to side gastric-jejunal anastomosis. Because the gastric and intestinal wall were quite fragile and RAM impaired wound healing as adverse event, we feared about leakage, but he had no major postoperative complications and discharged on the 33th day after surgery. After 24 courses of nivolumab as third-line chemotherapy, the peritoneal dissemination disappeared. He has been alive without recurrence for about 1 year since then.

[A Case of Metastatic Colorectal Cancer with Hyperammonemic Encephalopathy Induced by mFOLFOX6 and SOX Therapy].

A 77-year-old man was given a diagnosis of pT4aN0M1a(PUL2), stage Ⅳ, RAS mutant type, after the operation for advanced ascending colon cancer. He was administered mFOLFOX6 plus Bmab as first-line chemotherapy. He showed consciousness disturbance on the 2nd day during the 6 cycles. Because of head computed tomography and magnetic resonance imaging showing no abnormal findings, we diagnosed convulsive seizure. His consciousness level gradually improved after intravenous infusion. He showed consciousness disturbance on the 2nd day during the 7 cycles again. Because blood ammonia level were high at 400µg/dL, he was diagnosed as hyperammonemic encephalopathy. His consciousness level rapidly recovered after branched chain amino acid(BCAA)infusion. SOX plus Bmab therapy was started as a post-treatment, he developed hyperammonemia(NH3 288µg/dL)again, on the 4th day during the 3 cycles. After taking of oral administration of BCAA and lactulose, the recurrence of hyperammonemic encephalopathy was not found. Therefore, 3 cycles of SOX plus Bmab therapy and 12 cycles of IRIS plus Bmab therapy were administered.

[A Case of Pneumocystin a Patient with Pneumonia That Developed during Chemotherapy for Sigmoid Cancer].

A 63-year-old man was diagnosed with advanced sigmoid cancer of pT3, pN0, sM1c, sP3, fStage Ⅳ post-operation. After CAPOX plus Bmab as the first-line chemotherapy, he underwent IRIS plus Bmab as the second-line chemotherapy. After 1 course of IRIS plus Bmab, he was admitted to the hospital for fever, dyspnea, and general fatigue. The white blood cell count was 6.2×10 3/mL, and the C-reactive protein was elevated to 12.9 mg/dL. The PaO2 of the artery blood gas analysis in room air was 46.3 mmHg, suggesting respiratory failure. He was diagnosed with PCP based on the bilateral diffused ground-glass opacities on chest CT along with an elevated serum b-D-glucan. The treatment of trimethoprim-sulfamethoxazole and steroid was then initiated. After the patient's clinical condition improved, he was discharged on day 27 post-admission.

[A Case of Nephrotic Syndrome Due to SOX plus Bmab Therapy for Liver Metastasis of Rectal Cancer].

A 66-year-old man was postoperatively diagnosed with pT4a, pN2, cM1a(H2), cP0, fStage Ⅳ, RAS wild type rectal cancer. He underwent SOX plus Bmab chemotherapy 4 weeks later. After 9 courses of SOX plus Bmab, he was admitted to the hospital for leg edema and proteinuria(4+). Because of severe proteinuria(14.7 g/day)and low protein(Alb 2.0 g/dL, TP 4.9 g/dL), he was diagnosed with nephrotic syndrome. His general condition improved on stopping chemotherapy and administration of conservative treatment, and he was discharged on day 20 after admission. The proteinuria improved 3 months later. He had been undergoing SOX chemotherapy for 4 months.

Double-tract reconstruction after laparoscopic proximal gastrectomy using detachable ENDO-PSD.

BACKGROUND: Proximal gastrectomy (PG) is widely performed in Japan as a function-preserving surgical approach. Since esophagogastrostomy (EG) was associated with increased reflux symptoms and anastomotic strictures, we have chosen double-tract reconstruction (DTR) as the standard reconstruction method since March 2013. In this study, we described a novel method of laparoscopic DTR using detachable ENDO-PSD and compared its 1-year outcome with EG performed formerly in our institution. METHODS: Patients who underwent laparoscopic PG between May 2005 and July 2014 were retrospectively divided into two groups based on the type of reconstruction and were subsequently analyzed (19 patients in the DTR group and 22 in the EG group). All of them underwent a laparoscopic PG with regional lymph node dissection. In the DTR group, the lower left port site was extended to 4 cm, and an intracorporeal purse-string suture was performed using the detachable ENDO-PSD. The jejunogastrostomy was fashioned on the anterior side of the remnant stomach parallel to the transection line, 2 cm from the cut end. The EG group used the conventional purse-string suture instrument through the 6 cm upper midline mini-laparotomy incision. Patient characteristics, operative data, early operative complications and 1-year postoperative follow-up findings were compared between the two groups. RESULTS: The frequencies of reflux symptoms (10.5 vs. 54.5%, P = 0.003), usage of proton pump inhibitors (31.6 vs. 72.7%, P = 0.008), and anastomotic strictures (0 vs. 27%, P = 0.014) were significantly lower in the DTR group as compared to the EG group. There were no significant differences between the two groups with regard to operation time, blood loss, postoperative hospital stay, postoperative complications, average postoperative/preoperative weight loss ratio, and postoperative/preoperative ratio of biochemical markers (hemoglobin, total protein, albumin, cholesterol). CONCLUSION: Our results indicate that DTR is a useful reconstruction method after PG, especially in terms of preventing reflux esophagitis and anastomotic strictures.

Different clinical significance of FGFR1-4 expression between diffuse-type and intestinal-type gastric cancer.

BACKGROUND: Receptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1-4 expression separately in DGC and IGC. METHODS: Tumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution. The expression levels of FGFR1, 2, 3, and 4 were measured in the tumors by immunohistochemical analysis. RESULTS: In DGC, high expression of FGFR1, FGFR2, or FGFR4 was significantly associated with the depth of invasion, lymph-node metastasis, pathological stage, and distant metastasis or recurrent disease. Patients with high expression of FGFR1, FGFR2, or FGFR4 had significantly poorer disease-specific survival (DSS) (p = 0.009, p = 0.001, and p = 0.023, respectively). In IGC, only FGFR4 expression was significantly associated with factors relative to tumor progression and with shorter DSS (p = 0.012). CONCLUSION: In conclusion, high FGFR4 expression correlated with tumor progression and survival in both DGC and IGC, whereas high expression of FGFR1 and 2 correlated with tumor progression and survival in only DGC.

[A Case of a-Fetoprotein Producing Gastric Cancer with Lymph Node Recurrence after Endoscopic Submucosal Dissection].

A 70-year-old man underwent endoscopic submucosal dissection(ESD)for 2 early-stage gastric cancers in 2009 and 2014, respectively. Both were pathologically diagnosed after curative resection. In 2015, we detected swollen lymph nodes in the lesser curvature of the stomach on computed tomography(CT). PET-CT revealed that the swollen lymph nodes showed an abnormal uptake of fluorodeoxyglucose; therefore, we considered the possibility of metastatic recurrence of the gastric can- cer. The patient's serum a-fetoprotein(AFP)level was elevated to 30.6 ng/mL. The intraoperative pathological diagnosis of the swollen lymph node was tub2. We diagnosed this case as metastatic recurrence of gastric cancer and performed distal gastrectomy with lymph node dissection. Metastases were found in 3 of the resected lymph nodes. Immunohistochemical staining for AFP was positive in the specimens obtained via ESD in 2014 and in the metastatic lymph nodes. We diagnosed the patient with AFP-producing gastric cancer. On additional trimming of the specimen obtained via ESD in 2014, we found slight lymphatic invasion.

[A case of advanced gastric cancer treated with curative resection after preoperative combined chemotherapy with docetaxel, cisplatin, and S-1].

A 67-year-old woman with epigastralgia was admitted to our hospital and was diagnosed with type 3 advanced gastric cancer with lymph node metastases.The clinical diagnosis was Stage III A(cT3, N2, M0).Since curative surgery was not feasible, we administered preoperative combination chemotherapy with docetaxel, cisplatin(CDDP), and S-1.After 3 courses of chemotherapy, the lymph nodes became undetectable on computed tomography(CT).Distal gastrectomy was performed with curative intent, and the final diagnosis was Stage IIA(ypT3, N0, M0).There has been no recurrence for 1 year and 4 months after the operation.

Capacitance Determination for the Evaluation of Electrochemically Active Surface Area in a Catalyst Layer of NiFe-Layered Double Hydroxides for Anion Exchange Membrane Water Electrolyser.

The determination of the electrochemically active surface area (ECSA) of a catalyst layer (CL) of a non-precious metal catalyst is of fundamental importance in optimizing the design of a durable CL for anion exchange membrane (AEM) water electrolysis, but has yet to be developed. Traditional double layer capacitance (Cdl), measured by cyclic voltammetry (CV), is not suitable for the estimation of the ECSA due to the nonconductive nature of Ni-based oxides and hydroxides in the non-Faradaic region. This paper analyses the applicability of electrochemical impedance spectroscopy (EIS) compared to CV in determining capacitances for the estimation of the ECSA of AEM-based CLs in an aqueous KOH electrolyte solution. A porous electrode transmission line (TML) model was employed to obtain the capacitance-voltage dependence from 1.0 V to 1.5 V at 20 mV intervals, covering both non-Faradic and Faradic regions. This allows for the identification of the contribution of a NiFe-layered double hydroxide (LDH) catalyst and supports in a CL, to capacitances in both non-Faradic and Faradic regions. A nearly constant double layer capacitance (Qdl) observed in the non-Faradic region represents the interfaces between catalyst supports and electrolytes. The capacitance determined in the Faradic region by EIS experiences a peak capacitance (QF), which represents the maximum achievable ECSA in an AEMCL during reactions. The EIS method was additionally validated in durability testing. An approximate 30% loss of QF was noted while Qdl remained unchanged following an eight-week test at 1 A/cm2 constant current density, implying that QF, determined by EIS, is sensitive to and therefore suitable for assessing the loss of ECSA. This universal method can provide a reasonable estimate of catalyst utilization and enable the monitoring of catalyst degradation in CLs, in particular in liquid alkaline electrolyte water electrolysis systems.

[A case of pathologically complete response of local recurrence in the mesorectum after multidisciplinary therapy].

The patient was a 68-year-old man who had undergone sigmoidectomy 1 year previously. Adjuvant therapy with tegafur- uraci(l UFT) and Leucovorin( UZEL) was administered. Seven months later, the carcinoembryonic antigen( CEA) level increased to 7.5 ng/mL. Enhanced computed tomography (CT) revealed a 4-cm mass in the mesorectum, and the patient was diagnosed as having local recurrence. Chemotherapy with oxaliplatin, 5-fluorouracil, and Leucovorin( mFOLFOX6) and radiation therapy( 60 Gy) were administered. As the tumor could not be detected after chemoradiotherapy, abdominoperineal resection was performed. Pathological examination showed no cancer and indicated a complete response. The patients CEA level has not increased and no recurrence has been detected on enhanced CT for 3.5 years. The tumor could be decreased in size by chemoradiotherapy and the operation could be safely performed without resecting other organs. Although surgery is generally performed for local recurrence, multidisciplinary therapy could be useful in performing such surgery safely.

Spatiotemporal observation of quantum crystallization of electrons.

Liquids crystallize as they cool; however, when crystallization is avoided in some way, they supercool, maintaining their liquidity, and freezing into glass at low temperatures, as ubiquitously observed. These metastable states crystallize over time through the classical dynamics of nucleation and growth. However, it was recently found that Coulomb interacting electrons on charge-frustrated triangular lattices exhibit supercooled liquid and glass with quantum nature and they crystallize, raising fundamental issues: what features are universal to crystallization at large and specific to that of quantum systems? Here, we report our experimental challenges that address this issue through the spatiotemporal observation of electronic crystallization in an organic material. With Raman microspectroscopy, we have successfully performed real-space and real-time imaging of electronic crystallization. The results directly capture strongly temperature-dependent crystallization profiles indicating that nucleation and growth proceed at distinctive temperature-dependent rates, which is common to conventional crystallization. However, the growth rate is many orders of magnitude larger than that in the conventional case. The temperature characteristics of nucleation and growth are universal, whereas unusually fast growth kinetics features quantum crystallization where a quantum-to-classical catastrophe occurs in interacting electrons.

High expression of P21-activated kinase 5 protein is associated with poor survival in gastric cancer.

P21-activated kinase 5 (PAK5), also termed PAK7, is one of the six members of the PAK family of serine/threonine kinases, which are downstream effectors in several cancer signaling pathways. PAK5 promotes neural outgrowth, contributes to microtubule stability and induces resistance to apoptosis. However, the clinical importance of PAK5 in gastric cancer has not been comprehensively investigated. In the present study, PAK5 expression was evaluated in gastric cancer tissue samples. Furthermore, the associations between high expression of PAK5, and clinicopathological features and prognosis were examined. PAK5 expression in primary gastric cancer specimens resected from 279 patients who underwent gastrectomy at the Tokyo Medical and Dental University Hospital was evaluated using immunohistochemistry. Of the 279 patients, 44 (15.8%) exhibited high PAK5 expression, which was significantly associated with the differentiated pathological type (differentiated vs. undifferentiated; P<0.001), depth of tumor invasion (T1 vs. T2-T4; P<0.001), lymph node metastasis (N0 vs. N1-N3; P<0.001), presence of distant metastasis or recurrence (present vs. absent; P=0.038), advanced tumor stage (I vs. II-IV; P=0.001) and worse disease-specific survival (P=0.013). In stage I-III disease, 38/254 (15.0%) patients exhibited high PAK5 expression, and high expression of PAK5 was significantly associated with relapse-free interval (P=0.044). PAK5 may serve an important role in tumor progression and influence the outcome of patients with gastric cancer.

Feasibility of laparoscopy-assisted gastrectomy for patients with poor physical status: A propensity-score matching study.

BACKGROUND: Laparoscopically-assisted gastrectomy (LAG) has been established to be a minimally invasive treatment for early gastric cancer. However, few studies have shown the feasibility of LAG in patients with risky comorbidities according to the American Society of Anesthesiologists physical status (ASA-PS) classification. We performed this retrospective cohort study to assess the feasibility of LG in patients with an ASA-PS class of 3 or higher. METHODS: We retrospectively identified 214 patients with an ASA-PS class of 3 or 4 among 1192 patients who underwent radical gastrectomy with lymph-node dissection between 1999 and 2014 in our hospital. Finally, 106 patients were generated by propensity-score matching between LAG and open gastrectomy (OG). Postoperative complications were compared between LAG and OG. RESULT: The overall incidence of complications was the same in LAG (30%) and OG (30%). Surgical complications were similar in LAG and OG (19% and 17%, p = 0.80). Medical complications also did not differ significantly between LAG and OG (21% and 15%, p = 0.45). CONCLUSION: LAG was a feasible procedure for patients with gastric cancer who had an ASA-PS class of 3 or 4 and could undergo general anesthesia. LAG can become an optional treatment for such risky patients.

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer.

The overexpression of fibroblast growth factor receptor (FGFR) 2 is an established prognostic factor and treatment target in gastric cancer. However, the roles of other FGFRs have not been fully elucidated. In this study, we investigated the correlations of the expression of FGFR1-4 with clinicopathological characteristics and outcomes in gastric cancer. Tumor samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy between 2003 and 2007. The expression of each FGFR was measured in the tumors by immunohistochemical analysis. The overexpression of FGFR1, FGFR2 or FGFR4 was found to be significantly associated with tumor progression, including depth of invasion, lymph node metastasis, pathological stage and distant metastasis or recurrent disease. Patients exhibiting overexpression of FGFR1, FGFR2 or FGFR4 had a significantly poorer disease-specific survival (DSS; P<0.001, P=0.008 and P<0.001, respectively). Moreover, the co-overexpression of all three FGFRs was significantly associated with a poorer DSS compared to the expression of none or only one of the FGFRs (P<0.001 and P=0.001, respectively) and it was found to be an independent prognostic factor (HR=1.71, 95% CI: 1.02-2.85, P=0.041). In conclusion, high expression of FGFR1, FGFR2 or FGFR4 was associated with tumor progression and poor survival in patients with gastric cancer. Similar to FGFR2, FGFR1 and FGFR4 may be considered as prognostic factors and treatment targets in gastric cancer.