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Introduction and importance Mediastinal cystic lesions, such as paratracheal air cyst (PTAC) and bronchogenic cyst (BC), are rare anomaly usually found incidentally in thoracic imaging. Special attention is needed in the case of thoracic surgery. Case presentation All three patients were male, 71, 73, and 76 years old. Preoperative CT showed each had a lobular cystic lesion at the right posterolateral side of trachea in the thoracic outlet 11, 14, and 19 mm in size, respectively, with air density and tracheal communication, leading to a diagnosis of PTACs. An oval cystic lesion, 7 mm in size, was found in one patient at the right lateral side of the upper esophagus with low density and without tracheal communication, leading to a diagnosis of paraesophageal BC. Intraoperative findings of the three PTACs demonstrated a soft bulge from the membranous portion of trachea that was left intact. The BC had an oval elastic structure, mimicking a metastatic lymph node, and was removed with the mediastinal lymph nodes. Histological examination showed ciliated columnar epithelium, confirming a diagnosis of BC. Clinical discussion PTACs are associated with increased intraluminal pressure due to chronic lung disease. BCs are congenital anomalies that originate from abnormal budding of the embryonic foregut. Conclusion PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer. PTACs should be left intact to avoid tracheal injury, while removal of isolated BCs is recommended as a diagnostic and therapeutic measure., Highlights • Paratracheal air cyst (PTAC) and bronchogenic cyst (BC) are rare anomaly. • Three PTACs and a BC were found in patients who received thoracoscopic esophagectomy for esophageal cancer. • PTACs were carefully left intact to avoid tracheal injury. • BC was removed for diagnostic and therapeutic measure. • PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer.

Background Multiple pancreaticoduodenal artery aneurysms in association with median arcuate ligament syndrome (MALS) are relatively rare. A treatment option, such as a median arcuate ligament (MAL) release or embolization of the aneurysms, should be considered in such cases, but the treatment criteria remain unclear. Case report A 75-year-old man was transferred to our hospital because of a ruptured pancreaticoduodenal aneurysm. Emergency angiography showed stenosis of the root of the celiac axis (CA), a ruptured aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA), and an unruptured aneurysm of the anterior inferior pancreaticoduodenal artery (AIPDA). Coil embolization of the PIPDA was performed. Five days after embolization, the gallbladder became necrotic due to decreased blood flow in the CA region, and an emergency operation was performed. We performed a cholecystectomy and released the MAL to normalize the blood flow of the CA region. However, the patient died on postoperative day 8 because of rupture of the untreated aneurysm of the AIPDA. Conclusions This is the first report of metachronous ruptures of multiple pancreaticoduodenal aneurysms due to MALS, even after a MAL release. Although rare, a residual aneurysm in the pancreatic head region may need to be embolized quickly.

658 Background: Early studies raised concerns over whether preoperative treatment led to postoperative complications or even death. In contrast, recent studies have reported that initial treatment (IT) prior to resection of pancreatic ductal adenocarcinoma (PDAC) is safe, with no significant increase in overall morbidity or mortality, despite evidence for more advanced disease. In this study, we analyzed the clinical impact of chemotherapy or chemoradiotherapy as IT, focusing on treatment duration, on morbidity and mortality in patients with resected PDAC. Methods: We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for < 8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien–Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications. Results: The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. The rate of postoperative pancreatic fistula was significantly less in the IT group. Rates of other complications did not significantly differ, except for severe infection and delayed gastric emptying. Initiation of adjuvant chemotherapy was later in the IT group than in the upfront surgery group (43.2 vs 57.8 days, P < 0.001). In contrast, rates of overall complications significantly differed between the < 8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR: 4.508, 95%, P = 0.0156) were independent predictive factors for postoperative complications. Conclusions: The incidence of postoperative complication was similar between the upfront surgery group and the IT group, however, it was significantly higher in the ≥8 months IT group in patients who underwent PDAC resection.

Recently, some gastric schwannomas have been reported to have high uptake of FDG. However, Glut-1 was reported to be negative in gastric schwannomas tested. A 64-year-old female patient received a laparoscopic partial gastrectomy for a FDG PET-positive submucosal tumor (SUVmax 6.61). The resected tumor was diagnosed as a benign gastric schwannoma. Glut family immunohistochemical examination revealed diffuse positive expression of Glut-3 and partial positive expression of Glut-1. On the other hand, Glut-2 and Glut-4 expression in the tumor were negative. This case suggested that Glut-3 and Glut-1 expression were facilitators of high FDG uptake in the benign gastric schwannoma.

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of 18F-FDG PET are not specific for malignancy because 18F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for 18F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on 18F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on 18F-FDG PET.

We previously reported that microRNA-210 regulates cancer cell proliferation by targeting fibroblast growth factor receptor-like 1 (FGFRL1) in esophageal squamous cell carcinoma (ESCC). In order to clarify the role of FGFRL1 in ESCC, we evaluated FGFRL1 expression by tissue microarray and compared it with the clinicopathological factors of patients. Sixty-nine specimens of ESCC were obtained from patients who underwent an operation from 1990 to 2008. The patients consisted of 62 males and 7 females. Average age was 64.1 years old. The TNM stages of the patients were as follows: stage I, 7 patients; stage IIA, 10; stage IIB, 10; stage III, 35; stage IV, 7. After careful examination by two independent researchers, the immunohistochemical results for these patients were scored according to intensity and distribution. Among the 69 patients with ESCC, 56 patients (81 %) were FGFRL1 positive and 13 patients were FGFRL1 negative. FGFRL1 positivity was associated with lymph node metastasis (p = 0.004) and tended to be associated with the depth of the tumor (p = 0.089). As a result, the prognosis of the FGFRL1-positive patients was significantly worse than that of the FGFRL1-negative patients (logrank p = 0.0311). However, FGFRL1 expression was not an independent prognostic factor for the patients. FGFRL1 expression was associated with both lymph node metastasis and tumor growth in the patients with ESCC.

Colorectal cancer is a major cause of cancer-related mortality worldwide, with a high incidence of recurrence following curative resection, particularly among patients with stage II and III disease. There is therefore a need for novel prognostic biomarkers for advanced colon cancer and it was recently reported that aquaporin-1 (AQP1) may be associated with aggressive characteristics of colon cancer cells in experimental data. The association of clinicopathological findings with AQP1 expression was evaluated by tissue microarray (TMA) analysis, to determine whether AQP1 is a prognostic biomarker for colon cancer. A total of 120 consecutive stage II and III colon cancer patients (51 with stage II and 69 with stage III) who underwent curative resection between 1997 and 2008 were analyzed. The TMA was prepared from archival formalin-fixed, paraffin-embedded tissue blocks. Immunostaining was graded semi-quantitatively by considering the staining intensity and the percentage of positive tumor cells. Results showed the AQP1-positive rate to be 35.8%. The expression of AQP1 was associated with lymph node metastasis, lymphovascular and vascular invasion. The 5-year survival rate of the AQP1-positive and -negative groups was 73.7 and 87.9%, respectively. The survival rate of the positive group was significantly lower compared to that of the negative group (P=0.030). Furthermore, the expression of AQP1 was an independent poor prognostic factor according to the multivariate analysis. Therefore, AQP1 may be a promising candidate as a prognostic biomarker for colon cancer.

Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. Gemcitabine is a key drug for pancreatic and biliary tract cancer. However, gemcitabine is not widely used for esophageal squamous cell carcinoma (ESCC). In this study, we analyzed the expression of dCK in ESCC and evaluated the possibility of gemcitabine treatment for ESCC. In total, 76 ESCC patients who underwent esophagectomy between 1990 and 2008 were analyzed. dCK expression was analyzed immunohistochemically using tissue microarray and compared to the clinocopathological characteristics of the patients. Results identified 41 patients positive for dCK and 35 patients negative for dCK. A significant association was observed between dCK expression and gender (P=0.01), whereas the remaining factors were not associated with dCK expression. Prognosis of the patients with a high dCK expression was significantly worse than that of the patients with a low dCK expression (P=0.022). Furthermore, dCK expression was an independent prognostic factor regarding cause-specific prognosis (risk ratio, 2.2; P=0.031). In conclustion, the results of the present study suggested that dCK expression is a prognostic factor of the ESCC patients.

Recently, prone position esophagectomy for esophageal cancer is thought to be an easier and safer procedure. Here, we introduced prone position for enucleation of the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) positive esophageal leiomyoma. The patient was a 47-year-old man with a 4 cm mid-thoracic esophageal submucosal tumor. The tumor was enucleated safely without injury of the esophageal mucosa under the gravity effect of the prone position with use of a sponge spacer and Sengstaken-Blakemore balloon. Postoperative examination revealed that the tumor was a leiomyoma that was positive for smooth muscle actin and negative for CD117. Postoperative course was uneventful and the patient was discharged on day 7 after the operation. The prone position with use of a sponge spacer and Sengstaken-Blakemore balloon was a safer and easier procedure for the enucleation of the esophageal submucosal tumor.

Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients. In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis. Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014). Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.

Objectives: To evaluate the influence of confluence pattern of the right posterior sectional bile duct (RPSBD) on clinocopathological outcome in patients with hilar cholangiocarcinoma who underwent left hemihepatectomy (LH). Summary Background Data: Bliary vascular anatomy may affect the cutting line of proximal bile ducts, especially in case of LH, because of the shorter distance from the sectional ramification to the ductal confluence. However, there were few studies as to the relationship between anatomic variation and clinocopathological outcome. Methods: A total of 209 patients with hilar cholangiocarcinoma underwent surgical resection. We retrospectively investigated confluence patterns of the RPSBD in relation to the right portal vein (RPV) by preoperative imaging studies in 63 patients who underwent LH, and classified them into 3 groups (supraportal type: the RPSBD runs cranially around the RPV; infraportal type: the RPSBD runs caudally to the RPV; combined type: one segmental duct runs infraraportally and the other supraportally to the RPV). Furthermore, the effects of these variations on clinocopathological outcome were evaluated. Results: The supraportal type was observed in 53 cases (84.1%), the infraportal type in 8 cases (12.7%), and the combined type in 2 cases (3.2%). Although most of the clinocopathological features were similar between the groups, positive margin of proximal bile duct was significantly lower in the infraportal group, as compared with the supraportal group. Furthermore, it was noted that there was no incidence of bilioenteric anastomotic leakage in the infraportal group. Conclusions: Negative proximal margin and secure reconstruction were more easily achieved in the infraportal group than in the supraportal group. Preoperative evaluation of confluence pattern of RPSBD may be clinically useful for the management of hilar cholangiocarcinoma when applied to left-sided hepatectomy.

症例は49歳，女性．潰瘍性大腸炎（以下UC）で内科的加療を受けていた．経過中に貧血を認め，上部消化管内視鏡検査で進行胃癌と診断され，当科を紹介された．胃癌は術前検査でリンパ節転移，播種性病変も疑われたため，術前化学療法の導入なども考慮したが，貧血の原因が胃癌であると判断し手術を施行した．UCは全結腸炎型で，活動性は中等症であり，内科的治療で管理可能となり始めていたので，大腸全摘術は施行しなかった．UCと胃癌の合併の報告は稀であるが，昨今のUC患者の増加とともに胃癌との合併症例も今後増加すると予想される．UCと胃癌それぞれの病態に応じて治療方針は異なるが，多くのUC患者はステロイドが長期もしくは大量に投与されており，周術期管理にはステロイド補充，合併症の対策などが重要であると思われる．今回，これらのことを考慮して周術期を安全に加療できたので，若干の文献的考察を加えて報告した．

症例は71歳，男性．夜間に右下腹部痛が出現．発症から12時間後に急激に症状が増悪，右下腹部に圧痛を認めたが，明らかな腹膜刺激症状はなかった．直腸温は39.1℃であり，皮膚温37.1℃に比べ異常に高値であった．腹部CT検査では上行結腸が著明に拡張し，上行結腸狭窄部には腫瘤像を認めた．大腸穿孔を伴う大腸癌イレウスと診断し，同日緊急手術を施行した．開腹所見では，結腸肝彎曲部に径5cm大の腫瘤性病変を認め，その口側結腸は著明に拡張し，全長約10cmにわたる結腸壁損傷を2箇所に認めた．腸管内容物として，スイカの種，トウモロコシなどの食物残渣が大量に排出された．右半結腸切除術，回腸人工肛門，横行結腸粘膜瘻造設術を施行し，術後合併症なく23日目に退院した．今回，われわれは口側結腸壁損傷を示した食餌性イレウスを伴った上行結腸癌の1例を経験した．文献的考察を加えて報告する．

A 6 1-year-old man who was admitted to our hospital because of obstructive jaundice. He was diagnosed with locally advanced cancer of the pancreatic head on computed tomography. Gemcitabine (1,000 mg/m² on days 8 and 15, every 21 days) + S-1 (6 0 mg/m² on day 1-15, every 21 days) chemotherapy was administered because the tumor had invaded the common hepatic artery and portal vein. The tumor was reduced following 9 months of chemotherapy. Thus, subtotal stomach- preserving pancreaticoduodenectomy (SSPPD)was performed. The histopathological findings indicated no invasion of the cancer into the surrounding tissues. No recurrence has occurred 7 months after surgery. Neoadjuvant chemotherapy is important for effective treatment of locally advanced pancreatic cancer.

Humoral mediators are potentially involved in the pathogenesis of postoperative complications following surgery. The aim of the present study is to evaluate the postoperative responses of circulating cytokines, chemokines, and stress hormones following liver resection, and their effects on postoperative infectious complications and organ dysfunction.Perioperative plasma concentrations of interleukin (IL)-6, IL-10, IL-4, IL-8, macrophage chemoattractant protein (MCP)-1, cortisol, macrophage migration inhibitory factor (MIF), and leptin were measured by immunoassays in 128 consecutive patients undergoing liver resection.Forty-three patients had postoperative infection and 11 had infection-related organ dysfunction. Plasma levels of all mediators except for IL-4 increased postoperatively. Postoperative levels of IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin were significantly higher in patients with organ dysfunction than in those without organ dysfunction (P0.05). However, postoperative MIF levels were not affected by postoperative infection or organ dysfunction. Plasma levels of IL-6, IL-10, IL-8, and MCP-1 were positively correlated with operation time (P0.0001) or blood loss (P0.0001), and higher in patients with jaundiced liver (P0.05). In univariate logistic regression analyses, elevated IL-6, IL-10, IL-8, and MCP-1, advanced age, large volume of blood loss, long operation time, long hepatic ischemia time, and major liver resection were significantly correlated with postoperative infection (P0.05). In multivariate analyses, IL-6 and IL-10 were significant predisposing factors for postoperative infection (P0.05), and blood loss and IL-6 for organ dysfunction (P0.01).These results suggest that IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin are released after liver resection in response to surgical stress and correlated with postoperative infection and organ dysfunction, and that of these circulating mediators, IL-6 and IL-10, have a close relationship to the complications.

We report a case of esophageal perforation caused by an explosion, but which was not diagnosed until 3 days after the injury. A 53-year-old worker sustained superficial dermal burns to his trachea, face, neck, and legs during an explosion. The burns were treated conservatively at a local hospital, but he was transferred to our hospital 3 days after the injury, when mediastinal emphysema and bilateral pleural effusion became evident. An esophagogram followed by computed tomography showed an esophageal perforation caused by the blast injury, and we performed an esophagectomy with recontruction of the gastric tube. After the operation, an X-ray showed a foreign body in the lower abdomen, which we found in the upper thoracic esophagus on the day of injury. We surmised that the patient had inadvertently swallowed a foreign body, which had been heated and scattered by the explosion, and it had melted the upper thoracic esophagus.

Cytokines and chemokines potentially modulate postoperative immune response. Association of circulating cytokines and chemokines with postoperative infectious complications after pancreaticoduodenectomy was evaluated.Plasma concentrations of interleukin (IL) 6, IL-10, IL-8, macrophage chemoattractant protein 1, heat shock protein 70, and amylase, as well as amylase levels in peritoneal exudative fluid, were measured perioperatively in 60 consecutive patients who underwent pancreaticoduodenectomy.Of the 60 patients, 27 patients had surgical site infection (SSI), including peritoneal infection in all, intra-abdominal abscess in 14, and radiologically visualized pancreatic leakage in 6. Postoperative plasma levels of IL-6, IL-8, and macrophage chemoattractant protein 1, as well as peritoneal amylase levels, were significantly higher in patients with SSI than in those without SSI (P0.05). Nonpancreatic cancer as a histopathologic diagnosis, high pancreatic juice flow, and increased levels of IL-6 and IL-8 were independently associated with SSI (P0.05) in multiple logistic regression analysis. Plasma levels of IL-6 and IL-10 among patients with SSI were significantly higher in those with pancreatic leakage than in those without leakage.These results suggest that, in addition to pancreatic exocrine function, IL-6 and IL-8 are associated with postoperative SSI, including pancreatic leakage after pancreaticoduodenectomy.

Background Advanced hepatobiliary-pancreatic malignancy occasionally involves major vasculatures, such as the portal vein or the inferior vena cava, and complete removal of the tumor is required for longterm survival. We used a left renal vein graft to reconstruct resected vessels in some patients. In this study, we evaluated early and late renal complications of this procedure. Study design We identified 14 patients undergoing vascular reconstruction with use of a left renal vein graft in hepatobiliary-pancreatic surgery. Renal function and graft patency were assessed by observing serum creatinine levels and radiologic findings during perioperative and followup periods. Results Of these 14 patients, 7 were men and 7 were women. Diseases included hilar cholangiocarcinoma in two, gallbladder carcinoma in two, intrahepatic cholangiocarcinoma in one, pancreas carcinoma in five, hepatic metastasis in three, and mass-forming pancreatitis in one. No significant postoperative renal dysfunction was recognized, and the mean value of the maximal serum creatinine was 1.0 mg/dL during the perioperative period. Renal scintigraphy was performed in six patients postoperatively, and there was no significant left renal dysfunction. Mean followup time was 18months after operation, and no severe renal dysfunction was found. Graft patency, which was assessed with enhanced abdominal CT, was well maintained after operation. Conclusions The left renal vein could be safely obtained and used for vascular reconstruction in resection of hepatobiliary-pancreatic malignancy without adverse effects on early and longterm renal function.

Transmembrane proteins of the tetraspanin superfamily are associated with integrins and are thought to regulate adhesion-dependent signaling. The molecular mechanisms of this regulation remain unknown. We used rat fibroblasts to analyze the contribution of the tetraspanin CD151 in the adhesion-dependent signaling. Expression of CD151 specifically attenuated adhesion-dependent activation of Ras. Furthermore, activation of PKB/c-Akt and ERK1/2, downstream targets in the Ras signaling pathway, was also diminished in cells expressing CD151. In contrast, adhesion-dependent activation of FAK and c-Src were not affected by CD151. The attenuation of Ras signaling did not correlate with phosphorylation of Tyr925-FAK, tyrosine phosphorylation of Shc, or with assembly of the p120RasGAP-p62Dok complex. Using mutants of CD151 we established that the cytoplasmic C-terminal portion is critical for activity of CD151 toward Ras. Taken together these results identify CD151 as a negative regulator of Ras and suggest a novel mechanism of adhesion-dependent regulation of Ras activity.

This study was designed to establish an intrahepatic metastasis model to investigate the biology and therapy of hepatocellular carcinoma (HCC) in mice. A fragment of mouse HCC tumor CBO140C12 was orthotopically implanted into the mouse liver. The number of intrahepatic metastatic colonies and the volume of the implanted tumor increased in a time‐dependent manner. At 28 days after fragment implantation, all mice showed intrahepatic metastasis. Intravenous administrations of cisplatin and doxorubicin at 7 and 21 days after the implantation significantly sup‐ pressed the growth of the primary tumor nodule, but tended to inhibit intrahepatic metastasis. However, a marked decrease of body weight was observed during the experiment. On the other hand, an inhibitor of matrix metalloproteinases (MMPs), ONO–4817, decreased the gelatinase activity of MMP–9 secreted by CBO140C12 cells, and significantly reduced the number of colonies of intrahepatic metastasis when administered orally. Our established model, which is focused on intrahepatic metastasis, is suitable for evaluating the therapeutic effect of HCC and for analyzing intrahepatic metastasis, because this model reflects the clinical features of HCC and all the steps of tumor metastasis.

Intrahepatic metastasis is a major modality in the recurrence of hepatoma. Establishment of the intrahepatic metastasis model would be useful for evaluating new anticancer therapies and analyzing the molecular mechanisms of tumor metastasis. Orthotopic implantation of a fragment of CBO140C12 hepatoma into the liver resulted in the formation of a solitary tumor nodule and its intrahepatic metastasis. In contrast, implantation of ADras3 cancer cells did not show any metastasis on day 21. CBO140C12 cells showed enhancement of the invasive, adhesive and migratory capabilities, as compared with ADras3 cells. Furthermore, mRNA expression and gelatinolytic activity of MMP-9 were detected in CBO140C12 cells, and the expression of mRNA for MT1-MMP in CBO140C12 cells was greater than that in ADras3 cells. Thus, intrahepatic metastasis of CBO140C12 tumor might be involved in the enhancement of the invasiveness of tumor cells via marked expression of MMP-9 and MT1-MMP.

We report the case of an adult male with progressing focal nodular hyperplasia (FNH). Although imaging studies suggested that the tumor was a classical FNH, the tumor biopsy showed glutamine synthetase expression and heat shock protein 70 in part of the tumor. As we could not definitely distinguish this case of FNH from early hepatocellular carcinoma (HCC), we performed laparoscopic partial hepatectomy. The surgical resected specimen showed that the tumor had a central scar with vascular and cholangiolar proliferation, which is compatible with FNH. Immunohistochemical analysis showed that the molecular expression pattern was compatible with FNH in the center of the tumor, whereas it partly resembled early HCC in the periphery of the tumor. FNH progression is occasionally found, and the molecular pattern of the progressing area in FNH might resemble that of early HCC due to morphologic and phenotypic changes induced by the regenerative mechanism and the alteration of blood flow. We should carefully observe progressing FNH.

Room for discretion is allowed in setting the period for amortizing prior service costs due to a reduction in projected benefit obligation (PBO). The aim of this chapter is to clarify the amount of discretion in management’s choice and the factors influencing it. The situation is examined in which the amortization period for prior service costs is set shorter than that for actuarial gains and losses. The results are summarized as follows. (1) The amortization period for prior service costs due to a PBO decrease, in contrast to a PBO increase, tends not to be conservative. (2) Greater discretion is likely exercised in setting the length of the amortization period for prior service costs, compared with that for actuarial gains and losses. (3) These tendencies likely reflect a goal to reach target earnings quickly. (4) It is, however, possible that this behavior can be deterred through monitoring by foreign or institutional investors. The results imply that, with regard to setting the length of the amortization period for prior service costs due to a PBO decrease, there may be a trade-off between the benefit of reaching target earnings and the cost of greater accountability to shareholders.

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET.

The clinical outcome of gastrointestinal stromal tumor (GIST) has been improved by the introduction of molecular-targeting drugs. However, resistance to these drugs appears during the course of treatment. The aim of this study was to establish and characterize a human xenograft model of GIST.GIST tissue from a patient with esophageal GIST was implanted under the skin of a NOD-SCID mouse. The tumor became successfully engrafted and we investigated the effects of imatinib and sunitinib on this model. KIT mutation was investigated by complementary DNA analysis, and c-KIT (CD117) expression was evaluated by immunohistological staining.cDNA analysis of the tumor revealed a KIT mutation in exon 11. c-KIT expression was observed in each passaged tumor. Both imatinib and sunitinib significantly reduced the size of the xenograft tumor.We established a novel xenograft model of human GIST in mice. This xenograft model may be useful for studying GIST.

To understand the role of iPS inductive genes in esophageal cancer, we examined the expression of Sex determining region Y-box 2 (SOX2), Octamer-binding transcription factor 3/4 (OCT3/4), Krueppel-like factor 4 (KLF4), c-Myelocytomatosis viral oncogene (c-MYC) and Tir Na Nog (NANOG) using an esophageal squamous cell carcinoma tissue micrroarray.The immunohistochemical expression levels of the five genes were compared to the clinicopathological data of the 81 patients with esophageal cancer.There was no relationship between the expression of the five genes and TNM factors of the patients. High expression of NANOG was an independent favorable prognostic factor (p=0.041). Among the patients who received postoperative cisplatin-based chemotherapy, patients with NANOG-positive tumor had significantly better prognosis than those whose tumors were NANOG negative (p=0.024). On the other hand, those with c-MYC-positive expression tended to have a worse prognosis and were resistant to cisplatin-based chemotherapy.NANOG expression was found to be an independent prognostic factor for patient with esophageal cancer. Patients with NANOG-positive expression tumor may be good candidates for cisplatin-based treatment.

Prognosis for patients with gallbladder carcinoma (GBC) is poor and the standard treatment for GBC has not yet been established.We established the human GBC cell line TYGBK-1, from a patient with papillary, tubular adenocarcinoma.The doubling time was 48 hours. This cell line has a missense mutation of p53 and no mutation of the K-RAS gene. This cell line was transplantable to nude mice. We characterized the sensitivity of TYGBK-1 to gemcitabine. We also examined the association of two gemcitabine-related genes (deoxycytidine kinase, dCK, and Hu antigen R, HuR). Among four GBC cell lines (TYGBK-1, NOZ, G-415, TGBC2TKB), TYGBK-1 and NOZ exhibited sensitivity to gemcitabine. Furthermore, these cells expressed both dCK and HuR mRNA, rather than gemcitabine-resistant cells.The newly established GBC cell line TYGBK-1, may represent an effective tool for development of chemotherapeutic treatment for GBC.

A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant chemotherapy because the liver metastases were unresectable. However, after 2 cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a partial response after 5 cycles of FOLFIRI. The patient was subjected to curative resection. Sigmoidectomy and liver resection were performed. Histological response was Grade 1b at liver metastasis. The patient was discharged and had an uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal level, and the patient is free of recurrence. Neoadjuvant chemotherapy for metastatic colorectal cancer may render some unresectable patients resectable, affording these patients the possibility of prolonged survival. However, the optimal approach is unknown.

This study set out to evaluate, in patients with gemcitabine-resistant pancreatic cancer, the response rate and toxicity of S-1 plus cisplatin (CDDP).Seventeen patients with histologically diagnosed invasive ductal pancreatic cancer were enrolled in this study. All patients had growing recurrent pancreas cancer despite the administration of gemcitabine. Thirteen patients underwent pancreatectomy, and 2 underwent choledochojejunostomy and gastrojejunostomy without pancreatectomy. S-1 (80 mg/m(2) per day) was orally administered for 21 consecutive days, followed by a 14-day rest period. CDDP (40 mg/m(2)) in 500 ml saline was administered by intravenous drip on day 8. This schedule was repeated every 5 weeks until the occurrence of disease progression, unacceptable toxicities, or the patient's refusal to continue.Five (29.4%) patients achieved a partial response and 2 (11.8%) had stable disease. In 5 of 15 patients (33.3%) who had elevated serum carbohydrate antigen (CA)19-9 levels at the start of treatment the CA19-9 was reduced by more than 50%. The median survival time was 10 months (range, 20 months), with 63.7% and 31.9% of patients alive at 6 and 12 months, respectively. Major adverse reactions in the 15 patients included gastrointestinal toxicities of grade 1 or 2. Only one patient (5.9%) developed grade 3 leucopenia.S-1 with CDDP has a promising effect against gemcitabine-resistant pancreatic cancer, with easily manageable toxicities. Further investigation of this regimen is warranted in patients with pancreatic cancer, especially in comparison with gemcitabine.

The patient was a 73-year-old man diagnosed with bile duct cancer. He underwent hepato-pancreatoduodenectomy and a combined resection of portal vein in July 2002. The post operative course was uneventful. In December 2003 he had a loss of consciousness, and was admitted to our hospital as an emergency patient. Abdominal CT scan and angiography revealed the presence of portal vein stenosis due to local recurrence of bile duct cancer resulting in portal hypertension. Thus, a metallic stent was placed in the portal vein to maintain portal blood flow. A non-covered metallic stent, 10 mm in diameter and 80 mm in length (SMART stent, Cordis Endovascular), was deployed through the stenotic portal vein. Portography after the stent placement showed a relief of the portal vein stenosis. Intravenous heparin administration was performed at a dose of 5,000 IU per day for 5 days after the stent placement, and this was followed by oral warfarin potassium administration. The clinical course was uneventful and the patient was discharged 21 days after portal stent placement. Portal stenting successfully improved portal hypertension due to stenosis of the portal vein without any complication. Our experience suggests that the portal vein stenting using the SMART stent is useful palliative therapy for portal vein stenosis.

Surgical resection has been reported to be only hope for cure for the patients with hilar cholangiocarcinoma. Therefore, first of all, radical surgical resection should be considered to be a therapeutic option for hilar cholangiocarcinoma as much as possible. In preoperative staging for hilar cholangiocarcinoma, various extensive patterns of cancer such as the involvements of bile duct, portal vein, hepatic artery and lymph node etc, should be evaluated in each patient. As most patients are associated with obstructive jaundice at presentation, liver function has to be evaluated by appropriate tests for deciding the suitable surgical procedure. When the future remnant liver volume is less than 40% or severe liver functional damage exists or greater surgical stress is expected, preoperative portal vein embolization might have to be selected. On the other hand, if hilar cholangiocarcinoma involves limited region of the hilar bile duct confluence, parenchyma preserving hepatectomy such as S1 resection and S1 + S4 resection should be selected for avoiding the occurrence of liver failure. Combined portal vein resection should be done for the case of the cancer involvement of the portal vein without hesitation to improve the prognosis. However, hepatic artery resection and reconstruction in the involved case should be carefully performed only in severely selected cases. By using several useful pre-operative and intra-operative therapeutic modalities, hilar cholangiocarcinoma should be surgically resected with curative intent and without increasing surgical morbidity and mortality rates.

When advanced hepatobiliary malignancy involves the major veins that are requisite for draining venous flow from the remnant liver after hepatectomy, it may be unresectable, unless the hepatic vein involved by the tumor can be reconstructed after combined resection with hepatectomy.Seven patients with hepatobiliary malignancy underwent hepatic vein resection and reconstruction using autologous vein grafts in our study. Five patients had patch repairs of the hepatic vein, with the gonadal vein used in 2 cases, the umbilical vein in 2, and the inferior mesenteric vein in 1. Two other patients underwent segmental reconstruction of the hepatic vein, using the inferior mesenteric vein for reconstruction of the middle hepatic vein, and the internal iliac vein for reconstruction of the right hepatic vein. Operative results and postoperative outcome, including liver function, patency, and survival, were evaluated. Literatures reporting hepatic vein reconstruction in hepatic resection, including this study, are also reviewed.In 6 of 7 patients, autologous vein grafts were obtained from the upper abdominal operative field without making an additional skin incision. The right internal iliac vein was used in segmental reconstruction of the right hepatic vein, and the inferior mesenteric vein was used in segmental reconstruction of the middle hepatic vein, based on caliber matching. Patch repairs of the right hepatic vein were successfully performed in 2 cases, the middle hepatic vein in 2, and the left hepatic in 1, using the umbilical vein, the gonadal vein and the inferior mesenteric vein. During hepatic vein reconstruction, total hepatic vascular exclusion was required in 2 cases, and Pringle's inflow clamp with selective clamp of reconstructed hepatic vein in 5, in order to avoid massive bleeding, congestion, and air embolism. Postoperatively, there were no remarkable complications of liver dysfunction or other organ damage encountered in any of the patients. Reconstructed hepatic veins were revealed to be patent postoperatively in all cases. Six patients survived for 60-1035 days after surgery, and 1 patient died of cancer recurrence 550 days after surgery.We conclude that hepatic vein reconstruction using an autologous vein graft can be safely and effectively performed with a suitable vascular control method for appropriately selected patients with advanced hepatobiliary cancer.

Background. Although it is well-known that excessive surgical stress augments the growth of residual cancer and metastasis, whether surgical stress is increased according to the degree of surgical manipulation and can consequently lead to the enhancement of cancer metastasis has not been thoroughly examined. Moreover, the molecules associated with response for stress-enhanced metastasis have not been well-analyzed. The aim of this study was to examine whether cancer metastasis is enhanced with an increase of surgical stress with an experimental lung metastasis model and to analyze the related molecules responsible for stress-enhanced metastasis. Methods. Colon 26-L5 carcinoma cells (1.5 × 104/mouse) were injected intravenously into 6-week-old female BALB/c mice (Japan SLC, Hamamatsu, Japan). Two hours later, the mice were divided into 5 groups: untreated controls (the C group); mice given anesthesia only (the A group); mice given anesthesia and laparotomy (the AL group); mice given anesthesia, laparotomy, and appendectomy (the ALAp group); and mice given anesthesia, laparotomy, appendectomy, and left hepatic lobectomy (the ALApH group). The anesthesia procedures were the same in all groups (intraperitoneal administration of 0.8 mg/mouse sodium pentobarbital). In the AL, ALAp, and ALApH groups, a 3-cm long laparotomy was performed, and the time of the whole operation was just 5 minutes. All mice were killed 14 days after the procedures, and the number of lung metastases on the lung surface was counted manually. At the same time, BALB/c mice without tumor burden were given the same 5 kinds of surgical stress, and the messenger RNA expression of various metastasis-related molecules in the lung was measured with reverse transcriptase-polymerase chain reaction at 6, 24, and 48 hours after surgical stress. We also examined the effect of ONO-4817 (an inhibitor of matrix metalloproteinases ([MPs]) on lung metastasis in the mice with the 5 kinds of surgical stress. Results. The numbers of lung metastases on the lung surface and the messenger RNA expression of MMP-9, membrane type IBMMP, and urokinase-type plasminogen activator at 24 hours after surgery were enhanced in proportion to the degree of surgical stress. Moreover, ONO-4817 significantly inhibited lung metastasis. Conclusion. These results strongly suggest that increased surgical stress augments cancer metastasis via surgical stress-induced expression of proteinases in the target organ of metastasis. (Surgery 2003;133:547-55.)

We have previously reported that the expression of matrix metalloproteinase-9 (MMP-9), membrane type-1 matrix metalloproteinase (MT1-MMP) and beta1 integrins in murine hepatocellular carcinoma (HCC) was associated with the occurrence of intrahepatic metastasis, which is considered to be a major modality in recurrence. Here we show that intravenous administration of synthetic RGD pseudo-peptide (FC-336) inhibited intrahepatic metastasis produced by orthotopic implantation of a fragment of murine HCC (CBO140C12) tumor as compared with control administration of vehicle (p

The liver undergoes pathogenic changes such as hepatitis, fibrosis and cirrhosis under continuous stimulation by hepatitis virus or alcohol intake, leading to the development of hepatocellular carcinoma. The metastatic potential of HCC can be positively or negatively regulated by pathogenic alterations of liver. We investigated whether the metastatic abilities of HCC after orthotopic implantation can be influenced in the fibrotic liver by continuous injection of carbon-tetrachloride (CCl4) for seven weeks. The incidence of lung metastasis after orthotopic implantation of murine HCC (CBO140C12) fragments into CCl4-treated livers was higher than into normal livers. The amount of mRNA for MMP-2 increased in the CCl4-treated livers as compared with normal livers, and CBO140C12 cells constitutively expressed mRNA for MT1-MMP in early amplification cycles by RT-PCR. In addition, we found that the culture of CBO140C12 cells on the substrates pre-coated with ECM components increased the expression of MMP-2 mRNA. Thus, enhanced incidence of lung metastasis in the fibrotic liver might be partly due to: i) over-expression of MMP-2 in the fibrotic liver in cooperation with MT1-MMP on the CBO140C12 cell surface, ii) over-expression of MMP-2 in CBO140C12 cells, possibly mediated by the interaction of tumor cells (surface integrins) with accumulated ECM in the fibrotic liver. This is the first report showing that increase of MMP-2 in the fibrotic liver can influence the metastatic potential of HCC cells.

Although 10 esophageal adenocarcinoma cell lines have been reported, only 5 were Barrett's adenocarcinoma cell lines. Furthermore, there was only one mouse-inoculated esophageal adenocarcinoma cell line. In this paper, we present a newly established Barrett's esophageal adenocarcinoma cell line (TYAE-1). Material and Method: The Barrett's esophageal adenocarcinoma cells were obtained from the resected tumor of a patient (74 years-old male). The resected tumor was confirmed as well-differentiated intraepithelial Barrett's adenocarcinoma without lymphnode metastasis. The tumor was too small (T1a) for a primary culture, so we transplanted the tumor in the back of a nude mouse. Results: One month later, the tumor grew rapidly and was able to be re-transplanted to other mice. Up to the writing of this report, the tumor (TYAE-1m) was able to be re-transplanted 10 times every month. The histology of the transplanted tumor was slightly different from the primary tumor. The majority of the tumor was cribriform type and there were a few tubular-trabecular type cells. The expression of beta-Catenin was cytoplasmic in the cribriform part and membranous in the tubular part. Both cell types did express VEGF slightly however they did not express HER-2. We also started to perform in vitro cultures from the mice transplanted tumor and established TYAE-1c cell. TYAE-1c cells were able to be transplanted in nude mice and transplanted tumor showed the same histological features as TYAE-1m. TYAE-1m and TYAE-1c cells were sensitive to Gemcitabine treatment. On the other hand, both tumors did not show sensitivity for Docetaxel treatment. In conclusion: Although the tumor was small and had no invasive characteristics by clinicopathological examination, this tumor has aggressive behavior. This in vitro and in vivo Barrett's adenocarcinoma model may useful for understanding the behavior of Barrett's adenocarcinoma. Citation Format: Yutaka Shimada, Makoto Moriyama, Tomoyuki Okumura, Shinichi Sekine, Shigeaki Sawada, Koshi Matsui, Shozo Hojo, Kazuto Shibuya, Isaku Yoshioka, Toru Yoshida, Takuya Nagata, Kazuhiro Tsukada. Newly established Barrett's adenocarcinoma cell line (TYAE-1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2013-2720

Background: Recent progress is enabling us to induce iPS cells using somatic differentiated cells. We are now establishing iPS cells from normal gastrointestinal epithelial cells. However, the risks associated with transfection of iPS inductive genes (Sox2, Oct 3/4, klf4 and c-Myc) to somatic differentiated cells has not been well examined. Thus, in order to understand the role of iPS inductive genes in gastrointestinal cancer, we examined the expression of Sox2, Oct3/4, klf4, c-Myc and Nanog by cancer tissue microarray. Methods: We examined gene expression in 86 esophageal cancers, 50 gastric cancers, 80 colorectal cancers, 37 biliary tract cancers and 34 pancreatic cancers. Immunohistochemical expression levels of 5 genes were evaluated by the combination of their intensity and distribution. The expression level was compared to the clinico-pathological data of the patients. Results: Klf4 reduction was associated with lymph node metastasis of colorectal cancer which resulted in a poor prognosis for the patients (p=0.02). Klf4 reduction also tended to indicate a poor prognosis in esophageal cancer (P=0.06). Furthermore, Sox2 reduction was an independent prognostic factor in gastric cancer (p=0.03) and a high expression of OCT3/4 tended to indicate a poor prognosis in esophageal cancer (p=0.07). Nanog reduction was associated with poor prognosis in biliary tract and pancreatic cancer(p=0.02). On the other hand, c-Myc did not have any association with clinico-pathological factors of gastrointestinal cancer. Clustering analysis revealed that prognosis of the subgroup of simultaneous positive expressions of iPS inductive genes was better than that of other subgroups in colon cancer, however there was no difference among subtypes in esophageal cancer. Conclusions: The role of iPS inductive genes may differ in various gastroenterological cancer patients. However, further large-scale analysis is needed to elucidate this issue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4184. doi:10.1158/1538-7445.AM2011-4184

InIntroduction: microRNA (miRNA) are small non-coding RNAs which target specific mRNA. Recent progression of RNA extraction technology from formalin-fixed paraffin-embedded (FFPE) tissues enables us to access miRNA profiling using world wide stored specimens. Here, we present miRNA profiling of gastric cancer patients from FFPE specimens. Method: First, we examined the level of cross-linking caused by formalin and degradation of mRNA and miRNA from day to year levels. Then, we established the criteria of evaluable RNA from FFPE specimens. The miRNA profiling was obtained from 47 gastric cancer patients who received operations from 1997 to 2007 using 3D-Gene human miRNA chip (Toray) which contains 885 miRNA species. Results: Out of 47 paired samples, 37 pairs (78.8%) were determined evaluable with our criteria. As results, we showed that 30 miRNAs were significantly down-regulated and that 15 miRNAs were up-regulated in gastric cancer in comparison to normal gastric tissue. Of these, 18 miRNAs, including mir-21 and mir-34a, were identified as a prognostic factor of gastric cancer patients. Furthermore, we found 25 miRNAs have association with the recurrence of adjuvant oral Tegaful treatment and 5 miRNAs have association with lymph node metastasis. Conclusion: We have discovered miRNAs that are associated with prognosis, chemosensitivity and lymph node metastasis in gastric cancer patients. miRNA profiling using FFPE specimens is a useful and promising method of evaluation of world wide stored specimens that accompany may valuable clinical data. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3039.

AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and α-smooth muscle actin (α-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-β1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-β1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (α-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-β1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-β1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.