[Laparoscopic Splenectomy for Metachronous Splenic Metastasis of Fallopian Tube Cancer with Synchronous Rectal Metastasis-A Case Report].

A 59-year-old woman underwent simple abdominal total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and extirpation of intrapelvic disseminated nodules for right fallopian tube cancer with rectal metastasis and peritoneal dissemination as primary debulking surgery(PDS). The histopathological diagnosis was high grade serous carcinoma( HGSC)of the right fallopian tube. After adjuvant chemotherapy with 4 courses of paclitaxel-carboplatin(TC), low anterior resection of the rectum for rectal metastasis and pelvic and para-aortic lymph node dissection were performed as interval debulking surgery(IDS). Histopathologically, lymph node metastasis was detected only in the right obturator lymph node. After adjuvant chemotherapy with 4 courses of TC, bevacizumab maintenance monotherapy was administered. Three years after PDS, laparoscopic splenectomy for splenic metastasis and extirpation of the solitary peritoneal metastases were performed as secondary debulking surgery(SDS). After adjuvant chemotherapy with 4 courses of TC, olaparib maintenance monotherapy was administered. The patient has remained alive without recurrence for 4 years after SDS and for 7 years after PDS. No case of metachronous splenic metastasis from fallopian tube cancer with synchronous rectal metastasis has been reported; however, long-term prognosis may be expected with PDS, IDS and SDS for platinum-sensitive HGSC.

[Neuroendocrine Carcinoma of the Non-Ampullary Duodenum-A Case Report].

A 69-year-old woman was admitted to a territory hospital because of severe right hypochondoralgia after 2 weeks of internal medicine for persistent epigastralgia. Gastroduodenal endoscopy revealed a large tumor with a fistula in the duodenal bulb that expanded to the stomach. Histopathologically, the biopsy specimen indicated a poorly differentiated adenocarcinoma and HER2 negative. Computed tomography revealed that the tumor invaded the left lobe of the liver. The patient was referred to our hospital for cancer treatment. After 1 course of chemotherapy with S-1 and CDDP, laparoscopic gastroenterostomy bypass was performed because of tumor hemorrhage and poor food intake. However, the tumor hemorrhage and poor food intake continued, and the tumor enlarged. Therefore, left hemihepatectomy and distal gastrectomy with resection of the duodenal bulb were performed 1 month after bypass surgery. Histological testing confirmed the diagnosis of duodenal large-cell neuroendocrine carcinoma invading the liver without lymph node metastasis. Adjuvant chemotherapy was not administered, and the patient has been alive without recurrence for 7 years and 3 months. Neuroendocrine carcinoma of the non-ampullary duodenum is very rare; however, a large cell type without lymph node metastasis may be a factor in the long-term prognosis.

[Synchronous Double Primary Non-B, and Non-C Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma-A Case Report].

A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT); therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.

Laparoscopic lithotripsy and lithotomy of impacted stone at the terminal end of the common bile duct using a laparotomy biliary lithotomy spoon: A case report.

INTRODUCTION AND IMPORTANCE: Endoscopic intervention is considered first-line therapy for common bile duct (CBD) stones, in recent times. However, surgically altered anatomy and consequent inaccessibility of the duodenal papilla necessitate surgery in some patients. CASE PRESENTATION: A 61-year-old woman presented with fever and right subcostal pain. She underwent total gastrectomy and Roux-en-Y reconstruction for gastric ulcer, 4 years prior to presentation. Based on the clinical findings, she was diagnosed with acute obstructive cholangitis secondary to a CBD stone. Endoscopic retrograde biliary drainage was attempted; however, the duodenal papilla was endoscopically inaccessible owing to the previous Roux-en-Y reconstruction, and we performed percutaneous transhepatic gallbladder drainage (PTGBD). She underwent laparoscopic cholecystectomy and choledocholithotomy, 6 days after the PTGBD. Choledocholithotomy was attempted using basket forceps under choledochoscopic guidance; however, this procedure was unsuccessful, and we performed laparoscopic choledocholithotomy using a laparotomy biliary lithotomy spoon. CLINICAL DISCUSSION: Usually, laparoscopic cholecystectomy concomitant with CBD exploration is performed in patients with an endoscopically inaccessible duodenal papilla. However, an inadequately opened basket may not capture large impacted stones at the duodenal end of the CBD. Intraductal shock wave lithotripsy (electrohydraulic or laser lithotripsy) is considered in such cases; however, the specialized instruments required for this procedure are unavailable at all centers. Laparoscopic choledocholithotomy using a laparotomy biliary lithotomy spoon may be useful to overcome this surgically challenging situation. CONCLUSION: A laparotomy biliary lithotomy spoon is a simple, user-friendly, and economical device that may be useful for laparoscopic lithotripsy and lithotomy of impacted stones.

[Surgical Resection of Pulmonary Oligometastases of Ampullary Cancer-A Case Report and Review of Seven Cases].

A 62-year-old woman underwent a subtotal stomach-preserving pancreatoduodenectomy for ampullary carcinoma (T3bN0M0, Stage Ⅱb). Histopathologically, the tumor was a tubular adenocarcinoma with mixed features, predominantly the intestinal type, following which adjuvant chemotherapy was not performed. Computed tomography performed 32 months after surgery showed a tumor measuring 6.7 mm in diameter at the apex of the right lung. The tumor had gradually increased in size and measured 10 mm in diameter, 47 months postoperatively. Since other metastatic lesions were absent, partial resection of the right lung under video-assisted thoracic surgery was performed 48 months postoperatively. Histopathological testing confirmed a diagnosis of lung metastasis from the resected specimen of ampullary carcinoma without mediastinal lymph node metastasis. Adjuvant chemotherapy was not performed, and recurrence was not observed even after 53 months following the partial lung resection. Previously, 7 resected cases of solitary lung metastasis from ampullary cancer have been reported. The histopathological sub-type of these 7 cases were intestinal type in 5 and pancreatobiliary type in 2 cases, respectively. No mortality or recurrence was observed for 8-119 months in any of the 7 cases(median, 19 months). In conclusion, owing to the good prognosis, solitary lung metastasis from an ampullary cancer can be classified as an oligometastatic disease, based on the concept proposed by Hellman and Weichselbaum.

[Descending Colon Cancer with Synchronous Solitary Small Intestinal Metastasis-A Case Report].

A 77-year-old man presented with biliary colic and was diagnosed with descending colon cancer and cholelithiasis.During the surgery, a mass was detected in the upper jejunum, located 5 cm from the Treitz ligament on the anal side.Open left hemicolectomy with partial jejunal resection was performed.The mass in the small intestine was diagnosed as solitary small intestinal metastasis of colon cancer through immunohistopathological examination.Isolated intestinal metastases of colorectal cancers are rare.Furthermore, synchronous metastases are rare among these cases.A previous study reported poor prognosis in patients with small intestinal metastasis; therefore, more studies on the small intestinal metastasis of colorectal cancer are necessary.

[A Case of Disturbance of Consciousness Due to Hyperammonemia during Chemotherapy for Metastasis of Sigmoid Colon Cancer].

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

[Laparoscopic Liver Resection for Liver Metastasis from Unresectable Pancreatic Ductal Adenocarcinoma Well-Controlled by Chemotherapy-A Case Report].

A 45-year-old man with unresectable locally advanced pancreas head cancer with multiple synchronous liver metastases was treated with gemcitabine plus nab-paclitaxel therapy as a first-line chemotherapy. During 24 months of 30 courses of this therapy, the primary lesion remained stable and liver metastases were completely disappeared on CT. Three months later, however, solitary relapse of liver metastasis occurred in segment 2. Therefore, we changed the chemotherapy regimen to the second-line treatment, FOLFIRINOX. After 3 courses of FOLFIRINOX, the primary lesion was kept well-controlled, but the solitary metastatic liver lesion was enlarged. An interdisciplinary team suggested surgical resection of the liver metastasis to control disease progress. We performed laparoscopic lateral segmentectomy of the liver. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The patient underwent another round of gemcitabine therapy owing to the good response of the primary pancreatic lesion to this drug. Three years after starting the first-line chemotherapy, the patient is still alive with well-controlled PDAC without distant metastasis. Surgical intervention for liver metastases may be a promising treatment option when unresectable primary PDAC is well controlled by chemotherapy.

[Laparoscopic Resection of Solitary Lymph Node Metastasis of Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization and Percutaneous Locoregional Therapies].

A 75-year-old woman underwent transcatheter chemoembolization(TACE)for 2 small hepatocellular carcinoma(HCC) lesions associated with severe alcoholic liver cirrhosis that necessitated management for ascites. Over 5 years after the initial TACE, she received multidisciplinary therapies with TACE, transcatheter arterial infusion of anticancer agents, percutaneous ethanol injections, or percutaneous radiofrequency ablation performed on 5 occasions for small recurrent HCC lesions. Computed tomography performed after the last therapy for HCC revealed a solitary lymph node swelling(39 mm in diameter) around the common hepatic artery. Magnetic resonance imaging performed 3 months later revealed that the lymph node had enlarged to 45 mm, without recurrence of the primary HCC, and after 4 months, to 60 mm; she then underwent laparoscopic lymph node resection. Histopathological examination of the resected specimen showed HCC metastasis. A recurrent metastatic lymph node(30 mm in diameter)was detected around the common hepatic artery and was resected laparoscopically 17 months postoperatively. Pancreatic head cancer was diagnosed 22 months after the second surgery; however, the patient refused cancer therapy and died 16 months after this diagnosis. No recurrence of the primary HCC or lymph node metastasis was observed over the 38 months after the second surgery.

Stent-graft placement for delayed extrahepatic portal hemorrhage after surgical treatment for perihilar cholangiocarcinoma: A case report.

INTRODUCTION: Potential curative therapy for perihilar cholangiocarcinoma requires extensive surgical treatment, which can still be associated with significant morbidity and mortality. Postoperative hemorrhage from the portal vein is a rare but life-threatening complication. We herein report postoperative hemorrhage from an extrahepatic portal vein pseudoaneurysm successfully treated by stent graft placement late after surgical treatment for perihilar cholangiocarcinoma. PRESENTATION OF CASE: An 83-year-old man was referred to our hospital with a chief complaint of jaundice. Based on radiological findings, we diagnosed the patient with hilar cholangiocarcinoma. After endoscopic retrograde biliary drainage, resection of the extrahepatic bile duct combined with extended left hemi-hepatectomy, including the caudate lobe, lymphadenectomy of the hepatoduodenal ligament, partial resection and reconstruction of the portal vein, and right hepaticojejunostomy was performed. Fourteen days postoperatively, bleeding through the abdominal drain around the portal vein was observed. Twenty days postoperatively, abdominal computed tomography revealed a portal vein pseudoaneurysm that had formed at the portion of reconstruction. Therefore, 24 days postoperatively, a stent graft placement of the pseudoaneurysm through the ileocolic vein was performed. Subsequently, the portal vein hemorrhage ceased. DISCUSSION: Our present postoperative extrahepatic portal vein hemorrhage case was caused by an extrahepatic portal vein pseudoaneurysm that had formed at the reconstructed portion by erosion due to the chemical effect of the leaking bile and mechanical irritation of the surgical drain adjacent to the portal vein. CONCLUSION: Stent-graft placement is a minimally-invasive, safe, and effective treatment option for hemorrhage from postoperative portal vein pseudoaneurysm.

[A Case of Gastric Neuroendocrine Carcinoma with Bulky Lymph Node Metastases, Solitary Liver Metastasis, and Left Adrenal Metastasis Curatively Resected after Chemotherapy].

A 68-year-old man presented with generalfatigue due to anemia. Gastrointestinalendoscopy showed a tumor approximately 60mm in diameter in the lesser curvature of the angle of the stomach. Large cell neuroendocrine carcinoma was diagnosed by biopsy of a tumor specimen. Computed tomography revealed bulky regional lymph node metastases, solitary liver metastasis, and left adrenal metastasis. After three courses of combined chemotherapy with S-1 and CDDP, the gastric lesion and lymph node metastases shrunk, but the liver metastasis and left adrenal metastasis enlarged. After three courses of combined chemotherapy with ramucirumab and paclitaxel, the liver metastasis and left adrenal metastasis also shrunk, and no other new metastatic lesions appeared. Accordingly, total gastrectomy with lymph nodes dissection, partial resection of the liver and left adrenalectomy were performed for a curative resection. The histological findings revealed neuroendocrine carcinoma and adenocarcinoma of the stomach. The lesions of the liver and lymph nodes were all burned out, and a tiny metastatic lesion of neuroendocrine carcinoma was left in the left adrenal gland. S-1 was administrated for 3 months after surgery. The patient has been alive for 16months without recurrence after surgery.

[A Resected Case of Retroperitoneal Metastasis and Small Bowel Metastasis from HCC].

A 71-year-old man underwent right hemi-hepatectomyfor a hepatocellular carcinoma(HCC)measuring 18 cm in diameter. The pathological diagnosis was poorlydifferentiated HCC. Ten months after the surgery, computed tomographyrevealed a nodule 12mm in diameter in the right lung as well as 2 nodules measuring 19 and 11mm in diameter in the retroperitoneum at the cranial aspect of the left kidney. Four months later, the nodule in the right lung had enlarged to 44 mm, while the 2 nodules in the retroperitoneum had enlarged to 68mm and 34 mm. These nodules were resected and histopathologicallydiagnosed as metastasis from HCC. Twenty-one months after liver resection, computed tomographyrevealed nodules 16 and 25mm in diameter in the retroperitoneum around the urinarybladder and jejunum, respectively. One month later, intussusception resulted from the jejunal tumor. Laparoscopic surgerywas performed for both tumors, which were diagnosed as metastases from HCC. Twenty-five months after liver resection, metastasis from the HCC appeared in the left adrenal grand, at the site of the jejunal anastomosis, and in the fattytissue around the right scapula. Twenty-nine months after liver resection, the patient died of respiratoryfailure from multiple metastases in the left lung.

[A Case of Rupture of Esophageal Varices during a Course of CAPOX with Bevacizumab Therapy for Sigmoid Colon Cancer with Multiple Liver Metastases].

The patient was a 67-year-old man with multiple liver metastases from sigmoid colon cancer and had received capecitabine, oxaliplatin, and bevacizumab(CAPOX plus Bev)combination chemotherapy. After 11 courses of this therapy, he had a rupture of esophageal varices and was treated with endoscopic variceal ligation(EVL). Esophageal varices are rare during the course of oxaliplatin-based chemotherapy. More studies are necessary for early detection of esophageal varices during this therapy.

[Long-Term Survival after Multidisciplinary Treatment for Resected Pancreatic Adenocarcinoma with Recurrence of Pulmonary Metastases - A Case Report].

Recent studies indicated that isolated pulmonary metastases could define a favorable subgroup in metastatic pancreatic cancer. We report a case of isolated pulmonary metastases after curative resection of pancreas head cancer treated with chemotherapy and pulmonary metastasectomy survived for 79 months after recurrence. A 72-year-old male underwent pancreatoduodenectomy for pancreas head cancer. Adjuvant chemotherapy was done with gemcitabine hydrochloride (GEM)for 6 months and then S-1 for 2 months. Twenty-seven months after surgery, 2 small metastatic nodules in the left lung was detected. Chemotherapy with GEM was performed but the lesions grew larger very slowly. A new metastatic nodule was detected in the right lung 40 months after surgery and pleural effusion was detected 52 months after surgery. Then combination chemotherapy with GEM and S-1 was performed for 3 months followed chemotherapy with S-1 alone. Seventytwo months after surgery, chemotherapy with GEM was performed again because of patient's intolerance to S-1. Ninety months after initial surgery, pulmonary metastasectomy of the right lung was performed because of its resistance to chemotherapy. Chemotherapy with GEM was started again 4 months after pulmonary metastasectomy but serum levels of tumor markers remained increase. Combination chemotherapy with GEM and nab-paclitaxel was started 8 months after pulmonary metastasectomy but the patient died 16 months after pulmonary metastasectomy.

[A case report of metastatic anal fistula cancer treated with neoadjuvant chemotherapy].

A 69-year-old man with perianal pain was diagnosed with an anal fistula and a rectal tumor by magnetic resonance imaging and pulmonary tuberculosis by computed tomography. A colonoscopy confirmed the presence of a circular mass in the rectum 6 cm from the anal verge. Histological examination revealed a moderately differentiated adenocarcinoma. Initially, seton drainage was used to improve the perianal pain. After 2 months of anti-tuberculosis therapy, the patient underwent low anterior resection for the rectal cancer. Six months after surgery, a perianal tumor was detected at the postoperative site of the anal fistula. Biopsy of the tumor revealed adenocarcinoma. Because the histological appearance of the second tumor was identical to the rectal cancer, it was diagnosed as a metastatic anal fistula cancer. The tumor shrunk after 3 courses of neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) plus bevacizumab and there was no evidence of distant metastasis. Local resection of the anal fistula cancer was performed. Six months postoperatively, the patient is doing well and shows no sign of recurrence.

Postoperative outcomes of primary hepatic neuroendocrine carcinomas: review article.

BACKGROUND: We examined the course of a primary hepatic neuroendocrine carcinoma (PHNEC) patient and analyzed the postoperative outcome of all reported PHNEC cases. METHODS: A literature search for PHNEC cases was performed using PubMed. All reported cases and our present patient were analyzed in this study. Survival analysis was performed using the Kaplan-Meier method. Risk factors for the recurrence of PHNEC following hepatic resection were investigated. RESULTS: A total of 43 patients were analyzed in this study. The 3-, 5-, and 7-year overall survival rates were 55%, 48%, and 48%, respectively. The 3-, 5-, and 7-year overall survival rates in surgery patients were 78% each, and 25%, 17%, and 17%, respectively in nonsurgery patients. Lymph node metastasis posed a significant risk factor for postoperative recurrence. CONCLUSIONS: Hepatic surgery is an appropriate therapeutic treatment for PHNEC without distant metastasis nor lymph node metastasis. Adjuvant chemotherapy might be necessary for PHNEC patients with lymph node metastases.

Granulocyte colony-stimulating factor-producing ascending colon cancer as indicated by histopathological findings: report of a case.

Various types of granulocyte colony-stimulating factor (G-CSF)-producing malignant tumors have been reported. However, a G-CSF-producing colorectal cancer is rare. We present a case of G-CSF-producing ascending colon cancer. An 81-year-old man was referred to our hospital with right lower abdominal pain. A colon fiberscopy revealed an ascending colon tumor, and histological examination revealed tubular adenocarcinoma. He was admitted due to worsening abdominal pain. Although laboratory data showed an elevated white blood cell (WBC) count of 17000/mm3 with 77.8% neutrophils, elevated C-reaction protein (CRP) was insignificant (1.06 mg/dL), and he was afebrile. Because computed tomography indicated that the tumor penetrated into surrounding tissue, a semi-urgent ileocecal resection was performed. An abscess was not located. The tumor was staged as T3N2aM0 and as stage IIB according to the TNM classification. Microscopically, significant neutrophil infiltration between cancer cells was observed, suggesting the presence of a G-CSF-producing tumor. Immunohistochemical staining using a G-CSF antibody revealed cytoplasmic staining in cancer cells. The serum concentration of G-CSF upon admission was 334 pg/mL. After surgical resection, the WBC count decreased to within a normal range. These findings confirmed the diagnosis of G-CSF-producing ascending colon cancer. The prognosis of G-CSF-producing tumors is considered to be poor. Early diagnosis and surgical treatment are needed for patients with G-CSF-producing tumors, and continuous careful follow-up is required.

Phosphorylated smad2 in advanced stage gastric carcinoma.

BACKGROUND: Transforming growth factor ß (TGFß) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFß receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages. METHODS: Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas. RESULTS: The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor. CONCLUSION: The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma.

Synergistic antitumor effects of FGFR2 inhibitor with 5-fluorouracil on scirrhous gastric carcinoma.

Scirrhous gastric carcinoma (SGC) carries the highest mortality because of a frequent metastasis to lymph node (LN). S1, a 5-fluorouracil (5-FU) analog, is clinically available for gastric cancer at an advanced stage. Fibroblast growth factor receptor 2 (FGFR2) is required for the proliferation of SGC. The objective of this study is to clarify the benefit of a combination of S1 and kinase inhibitors including FGFR2 inhibitor Ki23057 in gastric cancer. OCUM-2MLN and KATO-III were derived from SGC. MKN-7 and MKN-74 were derived from non-SGC. MTT assay was used to examine the growth-inhibitory activity of 5 small-synthetic molecules including Ki23057, Sunitinib, Glivec, Lapatinib or SU11274, in cells cultured with 5-FU. Combination effects of 5-FU with Ki23057 on proliferation, apoptosis and mRNA expression were examined. S1 and/or Ki23057 were administered to murine models of SGC created by the orthotopic inoculation of OCUM-2MLN cells. Ki23057 at 100 nM significantly (p < 0.01) inhibited the proliferation and decreased the phosphorylation of FGFR2 in SGC cells, but not in non-SGC. Ki23057 showed synergistic antitumor effects for SGC cells in combination with 5-FU using CalcuSyn analysis, but Sunitinib, Glivec, Lapatinib and SU11274 did not. The combination of Ki23057 and 5-FU decreased DPD expression and increased apoptosis rates and p21 expression level of SGC cells. The combined administration of S1 and Ki23057 significantly (p < 0.05) decreased orthotopic tumors as well as LN metastasis more effectively than S1 alone. These findings suggested that the combined treatment with 5-FU and Ki23057 produced synergistic antitumor effects and is therapeutically promising for SGC treatment.

Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells.

ERas is a recently identified oncogene that supports the tumorigenic growth of embryonic stem cells, it is constitutively active in the absence of mutation. ERas oncogene is expressed only in viviparity phase cells, but not in somatic cells because of epigenetic transcriptional silencing in the somatic phase. The aim of this study was to clarify the ERas expression and its epigenetic regulation in gastric cancer of somatic phase. Fifteen gastric cancer cell lines were used. ERas mRNA expression and its epigenetic regulation were examined by reverse transcription-polymerase chain reaction and bisulfite sequencing analysis. To identify a subset of cancer stem cells, termed 'side population' (SP) cells, flow cytometry analysis was performed. ERas is expressed in 8 of the 15 gastric cancer cell lines, but is silenced in the remaining 7 cancer cell lines and normal cell lines. Six of 7 cancer cell lines without ERas expression had promoter methylation, which correlated with silencing of ERas expression. ERas expression is re-activated following treatment with the DNA methyltransferase inhibitor 5-aza-CdR. The percentage of SP fraction of ERas-positive gastric cancer cells was significantly (p=0.024) higher (3.4+/-1.8%), in comparison to that of ERas-negative cells (1.6+/-0.4%). These findings suggested that the activating ERas oncogene might be associated with tumorigenic growth of somatic cells, and might be a putative molecule responsible for cancer stem cell-like characteristics in gastric cancer. Loss of methylation in the promoter of ERas might be one of mechanisms responsible for the re-expression of an embryonic oncogene in gastric cancer.