Wataru Wada

E/N-cadherin switch mediates cancer progression via TGF- β -induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma

Background:Epithelial-to-mesenchymal transition (EMT) is a fundamental process governing not only morphogenesis in multicellular organisms, but also cancer progression. During EMT, epithelial cadherin (E-cadherin) is downregulated while neural cadherin (N-cadherin) is upregulated, referred to as ‘cadherin switch’. This study aimed to investigate whether cadherin switch promotes cancer progression in cholangiocarcinoma (CC).Methods:CC cell lines were examined for migration, invasion, and morphological changes with typical EMT-induced model using recombinant TGF-β1. The changes in E-cadherin and N-cadherin expression were investigated during EMT. We also examined E-cadherin and N-cadherin expression in resected specimens from extrahepatic CC patients (n=38), and the associations with clinicopathological factors and survival rates.Results:TGF-β1 treatment activated cell migration, invasion, and fibroblastic morphological changes, especially in extrahepatic CC HuCCT-1 cells. These changes occurred with E-cadherin downregulation and N-cadherin upregulation, that is, cadherin switch. Patients with low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression (P=0.0059). Patients with decreasing E-cadherin and increasing N-cadherin expression had a significantly lower survival rate than patients with increasing E-cadherin and decreasing N-cadherin expression (P=0.017).Conclusion:Cadherin switch promotes cancer progression via TGF-β-induced EMT in extrahepatic CC, suggesting a target for elucidating the mechanisms of invasion and metastasis in extrahepatic CC.

Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells

Pancreatic cancer demonstrates a strong resistance to anticancer drugs, presumably due to its resistance to drug induced apoptosis. Although gemcitabine (GEM) might be partially effective for treating advanced pancreatic cancer, its efficacy is still less than satisfactory. Galectin-3 (gal-3), a member of the β-galactoside-binding protein family, is a multifunctional protein with roles in tumor cell adhesion, proliferation, differentiation, angiogenesis, metastasis, and apoptosis. We have utilized gal-3 small interfering RNA (siRNA) to probe whether gal-3 regulates anticancer drug-induced apoptosis in pancreatic cancer cells. We found that Gal-3 siRNA augmented GEM- and cisplatin-induced apoptosis in pancreatic cancer cell lines in vitro. Mitochondrial depolarization induction was increased in gal-3-silenced cells after GEM treatment, resulting in activation of caspase-9, but not caspase-8. Akt phosphorylation was significantly downregulated in gal-3- silenced cells in association with apoptosis. Moreover, intratumoral administration of gal-3 siRNA increased the GEM sensitivity of tumor xenografts produced by subcutaneous inoculation of pancreatic cancer cells into nude mice. These results suggest that gal-3 might provide a novel therapeutic target in pancreatic cancer.

Laparoscopy-Assisted Resection of Ileocecal Intussusception Caused by Ileal Pedunculated Lipoma

We report on a case of ileal lipoma that prolapsed into the ascending colon and was resected by laparoscopy-assisted surgery. A 31-year-old male Japanese patient was admitted to our hospital because of hematochezia and anemia. Colonoscopy revealed a pedunculated polyp arising from the ileum. The surface was covered with slightly edematous mucosa. Abdominal computed tomography showed a low-density mass in the ascending colon. A diagnosis of pedunculated ileal lipoma with intussusception was made, and laparoscopy-assisted surgery was performed. The intussusception was reducted by resection of the lipoma. The surgical specimen was a 40 × 30 × 25 mm round tumor with a long stalk 11 cm in length. Microscopic examination of the specimen revealed ileal lipoma. Laparoscopic surgery is recommended for benign tumors of the small intestine because it is minimally invasive.

An oncocytic variant of intraductal papillary neoplasm of the bile duct that formed a giant hepatic cyst

Intraductal papillary neoplasms of the bile duct (IPNB) is the collective term used to refer to papillary bile duct tumors, mucin producing bile duct tumors, and cystic bile duct tumors. Pathologically, these tumors may be considered a highly differentiated adenocarcinoma or a tumor of borderline malignant potential. IPNB is classified into one of four variants based on cell differentiation. The rarest, oncocytic, is characterized by oxyphilic granular cytoplasm and no mucous cell differentiation. The patient, a 59-year old man, was admitted with a complaint of abdominal fullness and a 30×25 cm cystic mass in the right hepatic lobe demonstrated on computed tomography (CT). The mass had no malignant features on CT or magnetic resonance imaging; however, a portion was FDG avid on 18F-fluorodeoxyglucose positron emission tomography scan (FDG-PET). A fenestration operation was performed for the presumed diagnosis of a hepatic cyst. Pathological examination of the cyst contents demonstrated some atypical cells suspicious for malignancy. After eight months of observation, abnormal FDG uptake was again observed at the residual cyst. A partial hepatectomy was performed to excise the cyst. Pathological examination demonstrated adenocarcinoma in situ derived from an oncocytic IPNB variant. Following the resection, the patient remained disease free for 40 months. This is an extremely rare case of an oncocytic variant of IPNB that was difficult to distinguish clinically from a solitary hepatic cyst.

Mixed ductal-endocrine carcinoma of the pancreas occurring as a double cancer: report of a case.

We present a successfully treated case of mixed ductal-endocrine carcinoma of the pancreas complicated by right renal cell carcinoma. The patient had no symptoms, and laboratory data were close to the normal range. Enhanced computed tomography demonstrated a marked enhanced tumor, which appeared to be an endocrine tumor, at the pancreas uncus. We performed pyrolus-preserving pancreaticoduodenectomy, regional lymph node resection, and right nephrectomy. Histologically and immunohistochemically, the pancreas tumor had both a ductal (exocrine) and an endocrine component. The renal tumor was a typical clear cell carcinoma. A diagnosis of synchronous double cancer was made. As demonstrated in previously published reports, this type of mixed tumor has malignant potential for invasive ductal carcinoma. We propose that mixed ductal-endocrine carcinoma of the pancreas should be treated by surgical resection with a sufficient surgical margin and regional lymph node resection to improve the patients prognosis.

Single-incision laparoscopic surgery for a small-intestinal gastrointestinal stromal tumor: report of a case.

Our report concerns a 64-year-old man with a small-intestinal gastrointestinal stromal tumor (GIST), which was successfully treated with single-incision laparoscopic surgery (SILS). Small-bowel endoscopy detected a submucosal tumor located approximately 10 cm from the ligament of Treitz in the wall of the proximal jejunum. Contrast-enhanced computed tomography revealed a tumor (diameter, 4 cm) containing high- and low-density areas in the proximal jejunum. On 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET), the tumor demonstrated intense FDG uptake (maximum standard uptake value, 3.82), whereas it displayed high signal intensity on diffusion-weighted magnetic resonance images. No metastatic lesions were observed. The patient was diagnosed with a jejunal GIST. Wedge resection of the jejunum was performed using the SILS procedure. The tumor was histopathologically diagnosed as a low-grade malignant GIST. SILS is a useful resection technique for small-intestinal GIST.

A Resected Case of Mucinous Adenocarcinoma of the Duodenum, Mimicking Intraductal Papillary Neoplasm of the Bile Duct

Duodenum mucinous carcinoma is very rare, and the prognosis of the patient is very bad, especially when the tumor is invasive to other organs. In this case, duodenum carcinoma was invasive to commo...

A case of hepatocellular carcinoma with portal vein tumor thrombosis successfully treated by a combination of intra-arterial infusion 5-fluorouracil, cisplatin, and systemic interferon-α therapies.

A 58-year-old female with hepatitis C was referred to our hospital after computed tomography (CT) revealed a tumor in the right lobe of her liver. After thorough examination, tumor thrombosis was detected on the main trunk of the portal vein, and we decided to administer a combination of subcutaneous interferon-alfa and intra-arterial 5-fluorouracil. However, after 2 cycles of treatment, this regimen was ineffective, and thus cisplatin (CDDP) was added for the third cycle. On completion of 5 treatment cycles, the tumor and portal vein tumor thrombosis were not detected by CT or (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography. Hence, chemotherapy was considered effective and stopped. Two years after chemotherapy, Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) levels were within normal limits. Combination therapies have been recognized recently, and judging from the above case, the addition of CDDP to the combination regimen can prove beneficial.