Conversion Surgery After Chemotherapy Plus Nivolumab as the First-Line Treatment for Unresectable Advanced or Recurrent Gastric Cancer and a Biomarker Study Using the Gustave Roussy Immune Score: A Multicenter Study.

BACKGROUND: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases. RESULTS: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b. CONCLUSIONS: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.

Prognostic Nutrition Index as a Biomarker for Treatment Sensitivity to Chemotherapy and Nivolumab as the First-Line Treatment in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study.

INTRODUCTION: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer (GC) treated using chemotherapy and nivolumab as the first-line treatment. METHODS: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value. RESULTS: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time to treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075). CONCLUSIONS: PNI is a score composed of a patient's albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity.

Identification of Biomarkers for Assessing Treatment Efficacy of Chemotherapy plus Nivolumab as the First Line in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study.

INTRODUCTION: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index, and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment. RESULTS: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease/progressive disease group significantly increased (p = 0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased. CONCLUSION: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy.

Perioperative risk calculator for distal gastrectomy predicts overall survival in patients with gastric cancer.

BACKGROUND: Although some predictive factors of long-term survival after a distal gastrectomy for gastric cancer have been reported, only few studies have predicted long-term outcomes based on preoperative parameters. We aimed to evaluate the reliability of perioperative risk calculator for predicting overall survival (OS) after distal gastrectomy in patients with gastric cancer. METHODS: Overall, 337 patients (225 males, 112 females) who had undergone a distal gastrectomy for gastric cancer at the Keio University Hospital, Tokyo, Japan, between January 2009 and December 2013 were enrolled in this study. We investigated the reliability of a risk calculator for the prediction of OS. RESULTS: In multivariate analysis, the risk models for operative mortality and 30-day mortality were identified as predictors of death. Time-dependent receiver operating characteristics (ROC) curve analysis indicated that the estimated area under the curve (AUC) value of the risk model for operative mortality was > 0.870 during the first postoperative 3 years. We set optimal cutoff values of the risk model operative mortality for OS using the Cutoff Finder online tool. The cutoff values of 4.117% were significant risk factors of death. Similar results were observed in the external validation set. CONCLUSIONS: We elucidated the associations among risk calculator values and OS rates of patients with gastric cancer. Time-dependent ROC curve analysis suggested that the AUC value of the risk model for operative mortality was high, indicating that this risk calculator would be useful for not only short-term outcomes, but also long-term outcomes.

Single-Port Totally Extraperitoneal Preperitoneal Hernia Repair: Procedure, Tips, and Our Experience.

Single-port laparoscopic surgery is gaining increased attention because of its superiority in terms of cosmesis. A 1.5 cm vertical transumbilical incision is used for the single port, which is created by the glove method. We began applying single-port surgery to hernia repair in 2010, at which time we used the transabdominal preperitoneal (TAPP) approach. We began applying the totally extraperitoneal peritoneal (TEP) approach in 2013. Single-port TEP repair is now our standard procedure for inguinal hernia repair, and we consider it to be indicated for all cases of inguinal hernia unless the hernia has occurred during pregnancy, the patient is assigned to American Society of Anesthesiologists (ASA) class 3/4, or ascites due to liver cirrhosis is present. Provided herein is a step-by-step description of our single glove-port TEP hernia repair procedure, tips that facilitate the procedure, and a brief summary of the 102 cases in which we have performed TEP repair.

A slight bending of an α-helix in FliM creates a counterclockwise-locked structure of the flagellar motor in Vibrio.

Many bacteria swim by rotating flagella. The chemotaxis system controls the direction of flagellar rotation. Vibrio alginolyticus, which has a single polar flagellum, swims smoothly by rotating the flagellar motor counterclockwise (CCW) in response to attractants. In response to repellents, the motor frequently switches its rotational direction between CCW and clockwise (CW). We isolated a mutant strain that swims with a CW-locked rotation of the flagellum, which pulls rather than pushes the cell. This CW phenotype arises from a R49P substitution in FliM, which is the component in the C-ring of the motor that binds the chemotaxis signalling protein, phosphorylated CheY. However, this phenotype is independent of CheY, indicating that the mutation produces a CW conformation of the C-ring in the absence of CheY. The crystal structure of FliM with the R49P substitution showed a conformational change in the N-terminal α-helix of the middle domain of FliM (FliMM). This helix should mediates FliM-FliM interaction. The structural models of wild type and mutant C-ring showed that the relatively small conformational change in FliMM induces a drastic rearrangement of the conformation of the FliMM domain that generates a CW conformation of the C-ring.

Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer.

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis-related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation-specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5-fluorouracil-based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer.

[Second-line chemotherapy in gastric cancer following S-1 with CPT-11 chemotherapy performed as clinical trial].

We previously conducted a phase I/II study of irinotecan (CPT-11) combined with S-1 as first-line chemotherapy for metastatic advanced gastric cancer. In the present study,second-line chemotherapy was given to 32 of 44 patients whose disease became refractory to this first-line treatment. Overall survival time of the patients given second-line chemotherapy was significantly longer than that of patients not given such therapy (444 days vs. 230 days, p = 0.013). The response rate to second-line chemotherapy was 13% (4/32). Survival time of patients who responded to second-line chemotherapy was significantly longer than that of non-responders. Second-line chemotherapy may produce a better clinical response in patients who have progressive disease during first-line chemotherapy. Overall survival time and time to progression after second-line chemotherapy did not significantly differ between patients who received second-line chemotherapy regimens including S-1 and those who received regimens not including S-1.

Laparoscopy-assisted resection of gastric remnant cancer.

We report a case of gastric remnant carcinoma (GRC) that was successfully treated by laparoscopy-assisted gastrectomy. A 69-year-old man was referred to our department for management of GRC. Preoperative investigations revealed a slightly elevated tumor, 5.0 cm in maximal diameter, confined to the gastric mucosa. Computed tomography and endoscopic ultrasonography identified no lymph node metastasis. Laparoscopy-assisted gastrectomy was performed including perigastric and mesenteric lymph node dissection. The postoperative course was uneventful. This is the first reported case of laparoscopically treated GRC. In cases with little adhesion from previous surgery, laparoscopic procedure might represent the treatment of choice for early GRC in terms of minimal invasiveness.

[Laparoscopic surgery for gastric cancer].

Recently, the treatment of gastric cancer is becoming diversified. In Japan, gastrectomy with D2 lymphadenectomy has been recognized as a standard operation and has been performed widely for years. However, instead of D2 conventional gastric resection, various treatments using endoscopic or laparoscopic methods have been developed. Their usefulness and safety have been established, and the rate of detection of early gastric cancer has risen with the progress of medical technology and systems. The treatment suitable for the given stage must be chosen. In our department, we introduced laparoscopic operations and considered their usefulness and indication. Now, laparoscopic gastrectomy is recommended for cases in cStage I A and cStage I B of the guideline proposed by the Japanese Gastric Cancer Society. Future randomized controlled trials consisting of open surgery and laparoscopic gastrectomy are warranted.