Nobuhiko Kanaya

Visualized Evaluation of Blood Flow to the Gastric Conduit and Complications in Esophageal Reconstruction

BACKGROUND Evaluation of the blood supply to gastric conduits is critically important to avoid complications after esophagectomy. We began visual evaluation of blood flow using indocyanine green (ICG) fluorescent imaging in July 2015, to reduce reconstructive complications. In this study, we aimed to statistically verify the efficacy of blood flow evaluation using our simplified ICG method. STUDY DESIGN A total of 285 consecutive patients who underwent esophagectomy and gastric conduit reconstruction were reviewed and divided into 2 groups: before and after introduction of ICG evaluation. The entire cohort and 68 patient pairs after propensity score matching (PS-M) were evaluated for clinical outcomes and the effect of visualized evaluation on reducing the risk of complication. RESULTS The leakage rate in the ICG group was significantly lower than in the non-ICG group for each severity grade, both in the entire cohort (285 subjects) and after PS-M; the rates of other major complications, including recurrent laryngeal nerve palsy and pneumonia, were not different. The duration of postoperative ICU stay was approximately 1 day shorter in the ICG group than in the non-ICG group in the entire cohort, and approximately 2 days shorter after PS-M. Visualized evaluation of blood flow with ICG methods significantly reduced the rate of anastomotic complications of all Clavien-Dindo (CD) grades. Odds ratios for ICG evaluation decreased with CD grade (0.3419 for CD ≥ 1; 0.241 for CD ≥ 2; and 0.2153 for CD ≥ 3). CONCLUSIONS Objective evaluation of blood supply to the reconstructed conduit using ICG fluorescent imaging reduces the risk and degree of anastomotic complication.

HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer

An issue of concern is that no current HER2-targeted therapeutic agent is effective against Trastuzumab (Tmab)-resistant gastric cancer. Gold nanoparticles (AuNPs) are promising drug carriers with unique characteristics of a large surface area available for attachment of materials such as antibodies. Here, we created HER2-targeted AuNPs (T-AuNPs) and examined their therapeutic efficacy and cytotoxic mechanisms using HER2-postive Tmab-resistant (MKN7) or Tmab-sensitive (NCI-N87) gastric cancer cell lines. In vitro, T-AuNPs showed stronger cytotoxic effects than controls against MKN7 and NCI-N87 cells although Tmab had no effect on MKN7 cells. Autophagy played an important role in T-AuNP cytotoxic mechanisms, which was considered to be driven by internalization of T-AuNPs. Finally, T-AuNPs displayed potent antitumor effects against NCI-N87 and MKN7 subcutaneous tumors in in vivo mouse models. In conclusion, HER2-targeted AuNPs with conjugated Tmab is a promising strategy for the development of novel therapeutic agents to overcome Tmab resistance in gastric cancer.

Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus with stealth effect on the immune system

Oncolytic virotherapy has the disadvantage of being unsuitable for systemic delivery due to immune elimination. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream. In the present study, the potential of liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery was investigated. Lipo-pTS, which has a diameter of 40–50 nm, showed potent antitumor effects on HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS reduced production of adenovirus-neutralizing antibodies (AdNAbs) after intravenous administration into immune-competent mice compared to TelomeScan, and even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent suitable for systemic delivery with the characteristics of CAR-independent antitumor activity and a stealth effect on the immune system.

Abstract 4717: Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer

Interaction of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) induces functional impairment of antigen-specific T cells, which leads to immune evasion of tumors. Immune checkpoint therapy including PD-1/PD-L1 blockade is an emerging treatment strategy which brings great improvement in patient’s prognosis. Microsatellite instability (MSI) is a condition of genomic instability caused by the loss of DNA mismatch repair activity, which has recently received a lot of attention from the standpoint of cancer immunotherapy. While the TNM classification system is commonly used on various malignant tumors for prediction of prognosis and planning of treatment strategy, establishment of prognostic factors related to cancer immune system is considered important as cancer immunotherapy has recently become more and more popular. Thus, we investigated the usefulness of PD-L1 expression and MSI status in addition to histological type as prognostic factors in gastric cancer. In this study, 255 gastric cancer cases which had curative surgical resection at Okayama University Hospital between 2002 and 2009 were analyzed retrospectively. PD-L1 expression level was classified into 4 groups according to PD-L1 positive rate on tumors on immunohistochemical staining (0: Citation Format: Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara. Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4717. doi:10.1158/1538-7445.AM2017-4717

Changes over time in milk test results following pancreatectomy

AIM To investigate changes over time in, and effects of sealing technology on, milk test results following pancreatectomy. METHODS From April 2008 to October 2013, 66 pancreatic resections were performed at the Iwakuni Clinical Center. The milk test has been routinely conducted at the institute whenever possible during pancreatectomy. The milk test comprises the following procedure: A nasogastric tube is inserted until the third portion of the duodenum, followed by injection of 100 mL of milk through the tube. If a chyle leak is present, the patient tests positive in this milk test based on the observation of a white milky discharge. Positive milk test rates, leakage sites, and chylous ascites incidence were examined. LigaSure™ (LS; Covidien, Dublin, Ireland), a vessel-sealing device, is routinely used in pancreatectomy. Positive milk test rates before and after use of LS, as well as drain discharge volume at the 2(nd) and 3(rd) postoperative days, were compared retrospectively. Finally, positive milk test rates and chylous ascites incidence were compared with the results of a previous report. RESULTS Fifty-nine milk tests were conducted during pancreatectomy. The positive milk test rate for all pancreatectomy cases was 13.6% (8 of 59 cases). One case developed postoperative chylous ascites (2.1% among the pancreatoduedenectomy cases and 1.7% among all pancreatectomies). Positive rates by procedure were 12.8% for pancreatoduodenectomy and 22.2% for distal pancreatectomy. Positive rates by disease were 17.9% for pancreatic and 5.9% for biliary diseases. When comparing results from before and after use of LS, positive milk test rates in pancreatoduodenectomy were 13.0% before and 12.5% after, while those in distal pancreatectomy were 33.3% and 0%. Drainage volume tended to decrease when LS was used on the 3(rd) postoperative day (volumes were 424 ± 303 mL before LS and 285 ± 185 mL after, P = 0.056). Both chylous ascites incidence and positive milk test rates decreased slightly compared with those rates from the previous study. CONCLUSION Positive milk test rates and chylous ascites incidence decreased over time. Sealing technology may thus play an important role in preventing postoperative chylous ascites.

Surgical resection of splenic metastasis from the adenosquamous gallbladder carcinoma: A case report

Highlights • We report a case of splenic metastasis of adenosquamous carcinoma of gallbladder.• Splenic metastasis of adenosquamous gallbladder carcinoma is a rare.• Resection of splenic metastasis may represent the treatment for prolonging survival.