Satoshi Shinya

AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer.

AKT is a protein in the phosphatidylinositol-3 kinase (PI3K) pathway and associated with diverse pro-tumoral responses. Activation of the human telomere reverse transcriptase (hTERT) is one of AKTs tumorigenic effects. In this study, the significance of AKT phosphorylation and hTERT on prognosis of gastric cancer were examined. AKT activation by epidermal growth factor increased hTERT expression and telomerase activity. In contrast, AKT inactivation by inhibitors and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric cancer cells. In 40 gastric cancer tissues, significant correlations were found among the levels of phosphorylated AKT (pAKT), hTERT expression, and telomer length. The pAKT levels or the levels of pAKT/hTERT were not associated with clinicopathological parameters, including stage and nodal metastasis. However, survival rates of the pAKT-high patients or the pAKT-high and hTERT-high patients were significantly poorer than those in other patients. These findings suggest that AKT and hTERT are good molecular targets for the treatment of gastric cancer.

The “right” way is not always popular: comparison of surgeons’ perceptions during laparoscopic cholecystectomy for acute cholecystitis among experts from Japan, Korea and Taiwan

Generally, surgeons’ perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces.

What are the appropriate indicators of surgical difficulty during laparoscopic cholecystectomy? Results from a Japan‐Korea‐Taiwan multinational survey

Serious complications continue to occur in laparoscopic cholecystectomy (LC). The commonly used indicators of surgical difficulty such as the duration of surgery are insufficient because they are surgeon and institution dependent. We aimed to identify appropriate indicators of surgical difficulty during LC.

Procalcitonin as a useful biomarker for determining the need to perform emergency biliary drainage in cases of acute cholangitis

It is important to identify biomarkers for sepsis and organ damage in acute cholangitis patients. We investigated the usefulness of procalcitonin (PCT) as a biomarker of inflammation based on the Tokyo Guidelines 2013 (TG13).

Significance of epithelial growth factor in the epithelial-mesenchymal transition of human gallbladder cancer cells.

Five gallbladder cancer (GBC) cell lines were examined for morphological changes in collagen gel culture. GBh3 and HUCCT‐1 cells formed tubules in response to treatment with epithelial growth factor (EGF) and hepatocyte growth factor (HGF), and showed high levels of expression of E‐cadherin (ECD), and low levels of SNAIL, vimentin, transforming growth factor (TGF)‐β, and nucleostemin (NS). In contrast, the GBd15 and FU‐GBC‐1 cell lines treated with EGF and HGF showed a scattering phenotype, and expressed low levels of ECD and high levels of SNAIL, vimentin, TGF‐β, and NS. All cell lines expressed the EGF receptor, c‐Met, EGF, and TGF‐α, but not HGF. Transforming growth factor‐β was upregulated by EGF. Knockdown of the EGF receptor abrogated both tubule formation and scattering, whereas KD of TGF‐β abrogated only scattering. Knockdown of EGF induced nuclear translocation of β‐catenin and Wnt‐related NS induction in the scattering cell lines, but not in the tubule‐forming cell lines, whereas KD of glycogen synthase kinase‐3β in the tubule‐forming cell lines resulted in the nuclear translocation of β‐catenin and Wnt‐related NS induction in response to EGF treatment. These results suggest that EGF enhances epithelial–mesenchymal transformation and acquisition of stemness in GBC cells with a scattering phenotype through the activity of β‐catenin. Repression of ECD in scattering GBC cells induced the release of β‐catenin from the cell adhesion complexes along the plasma membrane and its translocation to the nucleus to activate Wnt signaling, which upregulated NS. (Cancer Sci 2012; 103: 1165–1171)

An opportunity in difficulty: Japan–Korea–Taiwan expert Delphi consensus on surgical difficulty during laparoscopic cholecystectomy

We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty.

Serum CD10 is associated with liver metastasis in colorectal cancer.

INTRODUCTION Colorectal cancer (CRC) is the third leading cause of cancer death in Japan. CD10 expression is closely associated with liver metastasis. In the present study, we explored the possibility of serum CD10 as a marker of liver metastasis in CRC. METHODOLOGY BALB/c mouse with subcutaneous tumor of syngeneic CT26 CRC cells were examined serum CD10. In 84 CRC patients and patients undergoing hemodialysis, serum CD10 was examined. CD10 concentration was measured by enzyme-linked immunosorbent assay. RESULTS In a mouse subcutaneous tumor model, serum CD10 correlated with the weight of the tumors. Serum CD10 was examined in 84 patients with CRC. The serum levels of CD10 were higher in patients with more advanced cancer stages. Patients with liver metastasis showed the highest levels of serum CD10 among all patients. Importantly, patients with high serum CD10 levels had metachronous liver metastasis. Healthy volunteers showed low levels of CD10; however, serum CD10 levels in patients undergoing hemodialysis showed levels as high as those with stage II and III CRC. A cutoff of serum CD10 set to >1000 pg/mL showed 70% sensitivity and 93% specificity for liver metastasis in CRC. This cutoff included all cases of metachronous liver metastasis. CONCLUSIONS With the exclusion of mimicking factors, serum CD10 levels might serve as a useful marker of synchronous and metachronous liver metastasis in CRC.

Two rare metachronous metastases of hepatocellular carcinoma after liver transplantation.

A 59-year-old male with hepatocellular carcinoma (HCC) due to liver cirrhosis caused by the hepatitis C virus underwent cadaveric whole liver transplantation. Two years later, he had a metastatic HCC in the superior mediastinum. Over the following postoperative year, he underwent transcatheter arterial chemoembolization (TACE) for 4 tumors in the implanted liver. In the third post-TACE month, he was emergently hospitalized due to intracerebral hematoma with a tumor invading the bone in the medial frontal segment. He underwent emergency intracranial tumorectomy and hemorrhage removal. The histopathologic diagnosis was metastatic HCC. He regained consciousness as well as the ability to speak and to feed himself, resulting in an improved quality of life. The incidence of HCC recurrence after liver transplantation is observed in approximately 8% to 11% of selected cases, with frequent relapses observed in the implanted liver, bones, adrenal glands, and lungs. Mediastinal and intracranial metastases from HCC post-liver transplantation are very rare.

Safe approach to the splenic hilum by first mobilizing the pancreatic tail in laparoscopic splenectomy

We employed a safe approach during laparoscopic splenectomy by first mobilizing the pancreatic tail and then dissecting the splenic vessels at the splenic hilum before mobilizing the spleen.

Tu1496 Treatment Strategy for Chronic Pancreatitis: Dissolution Therapy for Pancreatic Stones

(12.2% vs. 3.1%; p<0.05). There was no difference in surgical interventions (12% vs. 14.3%; p<0.05) and exocrine pancreatic insufficiency (17% vs. 16,5%, NS) between both groups. Diabetes was observed more frequent in HP group (14.6% vs. 7.6%, p<0.05). Limitations: Retrospective analysis based on medical history. Conclusions: Hereditary pancreatitis in children has worse clinical course than CP in children without PRSS1 mutations.