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For the biodiesel-fuel production by methanolysis, the reaction mixture is composed of a methyl-ester phase and a glycerol phase. One of the reactants, triglyceride, is mainly contained in the ester phase. The other reactant, methanol, is easily dissolved in the glycerol phase. Therefore, the methanol in the system is not effectively used for the reaction due to interface mass transfer resistance. An excess amount of methanol is required to increase the conversion in single-step operation. Since the glycerol phase is removed during the operation, a two-step batch operation can effectively intensify the process. In the present study, the optimal operating conditions to increase the conversion are obtained for the methanolysis of rapeseed oil using a KOH catalyst. The distribution ratio of methanol addition in the first step was about 0.8, which is confirmed by a simple reaction model.

Background: Recent studies have suggested that CD44 and/or CD133 expressing pancreatic cancer cells have potential abilities of self-renewal, tumorigenesis and tumor metastasis. The aim of this study was to investigate whether CD44 and CD133 expressions in primary tumor cells correlate to the survival and clinicopathological findings of pancre- atic cancer patients. Methods: Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohisto- chemically assessed for CD44 and CD133 expressions. Results: Of the 80 specimens, 34 (42.5 %) and 48 (60%) specimens were immunohistochemically positive for CD44 and CD133 expression, respectively. CD44 was expressed on the cell surface and CD133 expression was observed in the cy- toplasm of the positive cells, which were located at the peripheral adenocarcinoma glandular structures. There was no sig- nificant difference in the 5-year survival rate of patients based on CD44 expression, but the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P = 0.0002). Multivariate analysis revealed that CD44-positive and CD133-negative expression was a favorable prognostic indicator (P = 0.0424). Conclusions: CD44 and CD133 expressions are association with survival and malignant behavior in pancreatic cancer pa- tients.

粘液産生胆管腫瘍の生物学的特徴に関してはまだ不明な点が多い．今回，我々は粘液産生胆管癌に対して，計5回の治療を施行し，約11年間の長期経過を観察している症例に関して，文献的考察を加えて報告する．症例は67歳の男性で，最初にB4胆管を主座とする粘液産生胆管腫瘍を指摘され，肝内側区切除術＋左尾状葉切除術を施行した．病理組織学的検査では深達度mの粘液産生胆管癌であった．半年後に右尾状葉枝根部の腫瘍に対してYAGレーザー焼灼を施行し，さらにその半年後に総肝管の腫瘍に対して，総肝管切開腫瘍摘出術を施行した．2年4か月後に右肝管の腫瘍を指摘され，肝外胆管切除術＋胆管空腸吻合術を施行し，その2か月後に肝後区域枝の腫瘍に対してYAGレーザー焼灼施行した．最終治療から7年後の現在まで再発を認めておらず，厳重な経過観察と根気強い外科的治療の繰り返しで長期生存を得ることが可能であることが示唆された．

症例は74歳，男性．平成17年8月より全身の皮疹が出現し，近医にて加療されていたが軽快再燃を繰り返すため，原因検索目的に平成19年6月当院皮膚科紹介受診．皮疹は多形紅斑と診断．原因として感染症・薬剤アレルギー等は否定された．更なる精査目的行った腹部CT検査で，脾臓に腫瘍性病変を指摘されたため，当科紹介となった．Gaシンチグラフィー，PETにて同部位に集積を認めた．また，血液生化学検査において，可溶性IL-2レセプター抗体・チミジンキナーゼのいずれも陽性．これらの所見より，脾原発悪性リンパ腫と診断し，同年9月腹腔鏡下脾臓摘出術施行．術後1日目より皮疹の軽快を認め，術後3日目には掻痒感が消失，その後多形紅斑は消失した．脾臓の病理診断はdiffuse large B cell lymphomaであった．術後は補助化学療法を施行し現在術後10カ月無再発生存中である．本症例では多形紅斑と脾原発悪性リンパ腫との因果関係が示唆され，脾摘が多形紅斑の治療に極めて有効であった．

症例は54歳，女性．腹部CTで偶然発見された膵体部の内分泌腫瘍の診断で当科紹介．入院後精査にて，転移性肝腫瘍を伴っていたが，膵体部の腫瘍より尾側の膵に実質組織や主膵管を認めず，膵体尾部欠損合併膵内分泌腫瘍の診断．治療方針として，膵腫瘍は切除を行い，転移性肝腫瘍は肝動注療法を中心とした化学療法を行う方針とした．手術所見では，膵体部に腫瘍を認め，それより尾側は分厚い脂肪組織に置換し，膵実質・主膵管を認めなかった．膵中央切除術を行い，膵の消化管再建は行わなかった．組織学的には，高分化型神経内分泌癌であり，膵腫瘍の尾側は，ほぼ脂肪置換しており，ラ島を散在性に認めたが，膵外分泌細胞は認めなかった．術後の膵内分泌機能は良好で，耐糖能異常を認めなかった．膵体尾部脂肪置換を合併した膵内分泌腫瘍に対して膵中央切除術を行い，尾側膵の消化管への再建を行わなかった極めて稀な症例を経験したので報告する．

Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.

An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer. The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated. Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage-related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery. Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients.

Background Pancreatic hamartoma is an extremely rare benign disease of the pancreas. Only 30 cases have been reported to date. Case presentation A 68-year-old man presented with an asymptomatic solid and multi-cystic lesion in the uncus of the pancreas, incidentally detected on abdominal enhanced computed tomography. The tumor was found to be a well-demarcated solid and multi-cystic lesion without any enhancement, measuring 4 cm in diameter. After 28 months of follow-up, the tumor enlarged. At 31 months after initial diagnosis, the patient underwent surgical resection because it was difficult to clinically determine whether the tumor was malignant or not. Macroscopically, the solid tumor consisted of yellow adipose tissue with a smooth thin capsule confined to the pancreatic uncus. The inner structure of the tumor consisted of multiple cysts with a white nodule between the cysts. Histologically, the solid part and the multi-cystic portion consisted of mature adipose tissue and colonization of dilated pancreatic ducts with mild fibrosis, respectively. Immunohistochemical findings revealed cytokeratin 7 and 19 positive staining in the epithelial cells of the ducts. Adipose tissue showed positive staining for S-100 protein and there were only a few MIB-1 positive cells. The tumor was then diagnosed as a pancreatic hamartoma. Conclusion Beside on the above findings, we suggest that the term “well-demarcated solid and cystic lesion with chronological morphological changes” could be a clinical keyword to describe pancreatic hamartomas. Electronic supplementary material The online version of this article (doi:10.1186/s12876-016-0419-2) contains supplementary material, which is available to authorized users.

The aim of this study was to further examine the utility of mucin (MUC) expression profiles as prognostic factors in pancreatic ductal adenocarcinoma (PDAC).Mucin expression was examined by immunohistochemistry analysis in endoscopic ultrasound-guided fine-needle aspiration specimens obtained from 114 patients with PDAC. The rate of expression of each MUC was compared with clinicopathologic features.The expression rates of MUCs in cancer lesions were MUC1, 87.7%; MUC2, 0.8%; MUC4, 93.0%; MUC5AC, 78.9%; MUC6, 24.6%; and MUC16, 67.5%. MUC1 and MUC4 were positive, and MUC2 was negative in most PDACs. Patients with advanced stage of PDAC with MUC5AC expression had a significantly better outcome than those who were MUC5AC-negative (P = 0.002). With increasing clinical stage, total MUC6 expression decreased (P for trend = 0.001) and MUC16 cytoplasmic expression increased (P for trend = 0.02). The prognosis of patients with MUC16 cytoplasmic expression was significantly poorer than those without this expression. Multivariate survival analysis revealed that MUC16 cytoplasmic expression was a significant independent predictor of a poor prognosis after adjusting for the effects of other prognostic factors (P = 0.002).Mucin expression profiles in ultrasound-guided fine-needle aspiration specimens have excellent diagnostic utility and are useful predictors of outcome in patients with PDAC.

We describe herein the case of a 68-year-old man who experienced leptomeningitis after esophagectomy from an esophageal basaloid carcinoma. Although the patient had a good operative course for the first 10 days after surgery, he suddenly had general convulsions with unconsciousness. He was placed on mechanical ventilation in an intensive care unit. Computed tomography and magnetic imaging resonance did not reveal any abnormal findings. No abnormal data in the cerebrospinal fluid were found by biochemical, virological, and cytological examination. The positive expression of carcinoembryonic antigen messenger ribonucleic acid in cerebrospinal fluid was detected by a quantitative reverse transcription-polymerase chain reaction method. Immunohistochemical staining using an anticytokeratin antibody confirmed the presence of tumor cells in the cerebrospinal fluid. Spontaneous breathing was recovered after treatment with systemic chemotherapy. Six months after surgery, computed tomography revealed multiple brain metastases. This case demonstrates that the quantitative reverse transcription-polymerase chain reaction method of analyzing carcinoembryonic antigen messenger ribonucleic acid may be a sensitive and useful method for determining leptomeningeal metastasis before the detection of tumors by cytological and imaging examinations in patients with cancer.

Purpose: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer. Patients and Methods: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging. Results: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P < 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities. Conclusions: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.

Pancreatic fistula (PF) is a major complication after distal pancreatectomy (DP). Popularization of laparoscopic surgery for DP has promoted the use of stapler for transection and closing of the pancreas.We reviewed the medical records of 50 consecutive patients who underwent DP with stapler. Patients were divided into 2 groups: bare stapler (n=36) and reinforced stapler (n=14). We assessed the incidence of postoperative PF, systemic inflammatory response syndrome (SIRS), and intra-abdominal fluid collection on postoperative day 7.The numbers of patients who developed grade A, grade B, and grade C PF were 17 (34%), 6 (12%), and 0, respectively. The incidence of postoperative PF was significantly lower in the reinforced stapler group (p=0.017). None of the patients in the reinforced stapler group developed grade B PF. Patients in the bare stapler group showed significantly higher incidence of postoperative SIRS (p=0.046), more extensive fluid collection (p=0.020), and longer postoperative hospital stay (p=0.023).Decreased leakage of postoperative pancreatic juice into the abdominal cavity associated with the usage of the reinforced stapler may lead to reduced inflammatory reaction, low incidence of PF, and early hospital discharge.

The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer.Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups.The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months.EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.

Background Sarcoid-like reaction is often seen in various types of carcinoma, not only in the primary tumor, but also in regional lymph nodes, and can occur at any time, not only at the time of diagnosis, but also after treatment. However, few cases of hepatopancreatobiliary carcinoma, and no cases of gallbladder cancer with sarcoid-like reaction involving the lymph nodes have been described. This report is the first report of a sarcoid-like reaction involving the lymph nodes in a case of gallbladder cancer. Case presentation We encountered a rare case of gall bladder cancer with sarcoid-like reaction in the lymph nodes. Since regional lymph node swelling that was difficult to differentiate from metastasis was found preoperatively, swollen nodes were examined histologically using frozen sections. Based on this histology, the swollen nodes were diagnosed as showing sarcoid reaction and therefore extended lymphadenectomy was avoided. The patient did not receive any adjuvant chemotherapy and has shown no recurrence of disease as of 4 years after surgery. Conclusion Distinguishing between metastasis and sarcoid-like reaction in lymph nodes by preoperative imaging is still difficult. The present case shows that it is important to histologically examine swollen nodes by biopsy or by sampling before deciding on the treatment strategy for gall bladder cancer with swollen lymph nodes.

An appropriate timing for surgical resection of branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) to achieve sufficient postoperative survival is still unknown.Of 80 patients with histologically proven IPMNs, 61 patients who had BD-IPMN without pancreatic cancer concomitant with IPMN were enrolled in this study. We divided BD-IPMN into four groups according to disease progression: low to intermediate grade of dysplasia (LGD/IGD-IPMN), high grade of dysplasia (HGD-IPMN), minimally invasive IPMN (MI-IPMN: T1a), and invasive IPMN (IN-IPMN: ≥T1b). Indicators of surgical resection were investigated on the basis of pathological findings and postoperative prognosis.Postoperative survival was distinctly worse for patients with IN-IPMN than for patients with MI-IPMN, HGD-IPMN, and LGD/IGD-IPMN. Postoperative disease-specific 5-year survival rate was 100 % in patients with IN-IPMN, HGD-IPMN, and LGD/IGD-IPMN, by contrast, 40 % in patients with IN-IPMN. The presence of two of the three factors (pancreatitis, serum carbohydrate antigen [CA] 19-9 levels13 U/mL, and mural nodules) could distinguish HGD-IPMN from LGD/IGD-IPMN with a sensitivity of 92.9 %, specificity of 90.2 %, positive predictive value of 76.5 %, negative predictive value of 97.4 %, and accuracy of 90.9 %.To manage patients with BD-IPMN and achieve a good postoperative prognosis, surgical resection should be performed before progression to IN-IPMN.

Introduction: Laparoscopic surgery in distal pancreatectomy (DP) is as an effective approach for patients with pancreatic disease because of the reduction in the blood loss, length of hospital stay, and risks of overall postoperative complications and wound infection, without a substantial increase in the operating time.1 Moreover, single-port laparoscopic surgery has become increasingly popular with a widened indication in more types of surgery. However, compared with the conventional laparoscopy, this approach may take longer to complete and requires advanced skills and dedicated instrumentations to compensate for the lack of triangulation.2 In particular, the Gelport laparoscopic system provides a flexible, airtight fulcrum to facilitate the triangulation of standard instrumentation while maintaining the pneumoperitoneum for a minimally invasive surgery. As it is easy to perform hand-assisted operation at the same time, the surgeon can cope with unexpected bleeding with safe quickly. The devic...

Lymph node micrometastasis (LNM) can now be detected thanks to the development of various biological methods such as immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Although several reports have examined LNM in various carcinomas, including gastrointestinal (GI) cancer, the clinical significance of LNM remains controversial. Clinically, the presence of LNM is particularly important in patients without nodal metastasis on routine histological examination (pN0), because patients with pN0 but with LNM already in fact have metastatic potential. However, at present, several technical obstacles are impeding the detection of LNM using methods such as IHC or RT-PCR. Accurate evaluation should be carried out using the same antibody or primer and the same technique in a large number of patients. The clinical importance of the difference between LNM and isolated tumor cells (≤0.2 mm in diameter) will also be gradually clarified. It is important that the results of basic studies on LNM are prospectively introduced into the clinical field. Rapid diagnosis of LNM using IHC and RT-PCR during surgery would be clinically useful. Currently, minimally invasive treatments such as endoscopic submucosal dissection and laparoscopic surgery with individualized lymphadenectomy are increasingly being performed. Accurate diagnosis of LNM would clarify issues of curability and safety when performing such treatments. In the near future, individualized lymphadenectomy will develop based on the establishment of rapid, accurate diagnosis of LNM.

The percentage of gastroduodenal neuroendocrine tumors (NETs) among all gastroenteropancreatic (GEP) NETs has gradually increased worldwide. Sentinel node navigation surgery (SNNS) has been developed as a personalized approach in the surgical strategy for early gastrointestinal tract cancers. We herein report 2 cases of gastroduodenal NETs treated with SNNS. 99m Technetium-tin colloid including indocyanine green was endoscopically injected into the submucosa around a tumor the day before surgery. Basin dissection including the sentinel nodes (SNs), which were identified by Navigator GPS and near-infrared fluorescence imaging, was performed during laparoscopic surgery. SNs were intraoperatively examined using hematoxylin–eosin (HE) staining. SNs were detected in 2 patients. Lymph node metastasis was intraoperatively identified in 1 of the 2 patients. Consequently, 1 patient with metastatic SNs underwent laparoscopic gastrectomy with lymphadenectomy. Pathological findings identified submucosal NET measuring 6.0 mm × 5.0 mm. Our results suggest that SNNS is a promising surgical tool for detecting subclinical lymph node metastasis in patients with gastroduodenal NETs.

A 5 5-year-old woman was admitted to our hospital for pancreatic cancer with liver metastasis. We performed pancreatoduodenectomy, D2 dissection, and partial liver resection. Tissue from a resected liver metastasis was submitted to a chemosensitivity test. Based on the test results, we performed systemic chemotherapy with paclitaxel and hepatic artery infusion with gemcitabine for lung and liver metastasis after surgery. Furthermore, we added stereotactic body radiation therapy(SBRT)(48 Gy/4 Fr)for 3 liver metastases that showed enlargement after chemotherapy. Effective control of recurrent tumors was possible for 2 years and 5 month, and she maintained normal daily activities. She died of peritoneal dissemination 3 years and one month after surgery. Combined modality therapy with anticancer agents based on a chemosensitivity test and SBRT may be one useful therapy for pancreatic cancer with distant metastases.

To examine the appearance and distribution of folate receptor β-expressing (FRβ+) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients. Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FRβ+ and tumor-infiltrating (CD68+) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FRβ monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FRβ-expressing or CD68+ macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68+ or FRβ+ macrophages, clinicopathologic factors, and overall survival. FRβ+ macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68+ macrophages. A high number of FRβ+ macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients. FRβ+ macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRβ+ macrophages may be promising a targeting therapy for pancreatic cancer.

BACKGROUND AND OBJECTIES: Phenotypic plasticity of cancer cells via epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) is essential for tumor progression and metastasis.Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm.High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases.In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively.

A 68-year-old man admitted for pancreatic tumor detected by US was found by computed tomography(CT)to have locally advanced pancreatic cancer invading the portal vein and neural plexus of the superior mesenteric artery without distant metastasis. We conducted preoperative chemoradiation therapy containing S-1 and hyperfractionated accelerated radiation therapy (50 Gy). Reevaluation of CT after chemoradiation therapy showed that the primary tumor reduced 52% without distant metastasis. Based on these findings, we conducted subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection. Pathological examination revealed moderately-differentiated adenocarcinoma. Extensive fibrosis with a small amount of cancer cells was observed in the marginal area of the tumor. The portal vein was surrounded with extensive fibrosis and free from cancer cells. Extrapancreatic nerve plexus invasion and lymph node metastasis were not observed. There were no residual cancer cells (R0). The postoperative course was uneventful, and adjuvant chemotherapy (S-1) was started. The patient remains well without recurrence 12 months after surgery.

The aim of this study was to investigate the significance of lymphangiogenesis in primary pancreatic tumors and in draining lymph nodes during lymphatic metastasis of pancreatic head cancers.Specimens were obtained from 70 patients. To evaluate lymphangiogenesis, we measured lymphatic vessel density (LVD) using D2-40 antibody in the primary tumors and in the draining lymph nodes. AE1/AE3 antibody was used to detect tiny, histologically negative metastases in lymph nodes.Patients with high LVD of primary tumors had significantly higher incidence of node metastasis (P = 0.0006) and lower postoperative survival rate (P = 0.0066) than those with low LVD. Intranodal LVDs increased with increasing size of the intranodal metastases. The LVDs of non-metastatic nodes in patients with node metastasis were also significantly higher than those of non-metastatic nodes in patients without node metastasis (P 0.0001). The LVDs of peripancreatic nodes in patients with paraaortic node metastases were significantly higher than those in patients without paraaortic metastasis (P 0.0001).Lymphangiogenesis in primary tumors and draining lymph nodes is essential for efficient spread of tumor cells through the lymphatic system. Thus, inhibition of lymphangiogenesis could limit lymphatic dissemination of tumor cells.

Background and Objectives Delayed gastric emptying (DGE) is one of main complications after pylorus-preserving pancreaticoduodenectomy (PPPD) with regional lymph node dissection (RLND). The aim of this study was to retrospectively investigate whether subtotal stomach-preserving PD (SSPPD) decreased incidence of DGE. Methods This study included 112 consecutive patients underwent PPPD (n = 48) or SSPPD (n = 64) with/without RLND. DGE was classified into three categories (grades A, B, and C) according to the guideline proposed by the International Study Group of Pancreatic Surgery. Results The incidence of DGE grade B/C in SSPPD with RLND (13.0%) was lower compared with that (34.8%) in PPPD with RLND (P = 0.0326). Consequently, the mean length of postoperative hospital stay of SSPPD with RLND group was significantly shorter than that of PPPD with RLND (P = 0.0476). Conclusions SSPPD could be substituted for PPPD due to decreased postoperative DGE when RLND is involved. A randomized control trial of SSPPD versus PPPD should be considered. J. Surg. Oncol. 2010;102:615–619. © 2010 Wiley-Liss, Inc.

A 65-year-old woman was admitted with upper abdominal pain and pyrexia. She was given a diagnosis of acute pancreatitis and treated with intravenous infusion. After recovering, abdominal enhanced-CT showed a low density area in the head of the pancreas, measuring 2 cm in maximum dimension. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) revealed acinar cell carcinoma (ACC). She underwent curative subtotal stomach-preserving pancreaticoduodenectomy. The definitive diagnosis, based on the histopathological examinations including immunohistochemical staining, was ACC. ACC of the pancreas is extremely rare, occurring in approximately 1% of all cases of pancreatic neoplasm. We report a rare case diagnosed as ACC by EUS-FNA prior to surgical treatment.

The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in dividing the uptake with and without the main tumor for the treatment of patients with pancreatic cancer.Ninety-eight patients with primary pancreatic cancer were evaluated with 18F-FDG-PET. For the main tumor, the maximum standardized uptake values(SUVmax)were compared with clinicopathological factors and analyzed. We examined the site of accumulation and the rate of malignancy without the main tumor.For the accumulation of FDG in the main tumor, the high SUVmax level was significantly correlated with T-category in TNM classification (p=0. 003), tumor invasive size (3 cm) (p0. 001), CA19-9 levels100 U/mL) (p=0. 002). The overall survival of the group in which SUVmax was less than 7. 5 was better than that of the group in which it was more than 7. 5 (p=0. 03). Meanwhile, 58 patients (59%) showed the accumulation of FDG except for the main tumor. Lymph node uptake was shown in 44% of them. As for visceral accumulation, the liver was 11, lung 10, pancreas except main tumor 9, thyroid 7, peritoneal wall 3, colon 2, gall bladder 2, and bone 1. As for the rate of malignancy among them, the liver was 100%, lung 50%, pancreas except main tumor 0%, thyroid 29%, peritoneal wall 67%, colon 50%, gall bladder 50%, and bone 0%.We conclude that FDG-PET is a useful tool for predicting the prognosis in pancreatic cancer, and for detection of distant metastases and hidden malignant disease. FDG-PET has an important clinical impact on the selection of proper treatment.

As a pleiotropic cytokine, transforming growth factor-beta (TGF-beta) controls the functions of proliferation, adhesion, and differentiation, and contributes to cancer promotion and suppression. Moreover, it is related to the epithelial-mesenchymal transition process and T cell differentiation associated with inflammation. The Smad4 protein is the downstream mediator of TGF-beta. In this study, we examined the relationship between Smad4 expression and clinicopathological features in patients with hepatocellular carcinoma (HCC).Expression of Smad4 was assessed in five HCC cell lines and in paired cancerous and noncancerous tissues in three patients with HCC, using Western blotting analysis. Moreover, Smad4 expression in 121 HCC patients was evaluated by using immunohistochemistry.Only the Li7 and HT17 cell lines expressed the Smad4 protein. All human samples expressed the protein. Immunohistochemistry showed that Smad4 expression tended to be strong in small HCC nodules less than 45 mm in diameter (P=0.06) and in the infiltrated part of the tumor capsule. Postoperative survival analysis indicated that HCC patients with strong Smad4 expression had shorter disease-specific survival than those with weak expression (P=0.04). Multivariate analysis also showed that Smad4 expression could be one predictor of prognosis, but the correlation was not significant (P=0.07).Although TGF-beta/Smad4 signaling may have various biological effects on human malignancies, strong Smad4 expression in HCC is likely to suggest poor prognosis. The information has implications for predicting HCC prognosis and developing targeted therapeutics.

Concurrent chemoradiotherapy with gemcitabine improves median survival for patients with unresectable pancreatic cancer. Recently, hyperfractionated accelerated radiotherapy (HART) has been used to treat these patients; however, the safety and efficacy are not well defined.The standard-fractionated radiotherapy (SFRT) group (n=17) received 50.4 Gy in 28 fractions of 1.8 Gy/day. The HART group (n=18) received 50 Gy in 40 fractions of 1.25 Gy twice/day. Concurrent gemcitabine was administered to both groups.Median survival times were 11.3 months (SFRT) and 12.9 months (HART). One- and two-year survival rates were 37.5% and 18.8% (SFRT) and 47.1% and 17.6% (HART), respectively. The response rates did not differ significantly. The HART regimen required significantly fewer treatment days (35.5) than did the SFRT regimen (41.3). The toxicity profiles were similar.The HART/gemcitabine regimen has equivalent efficacy and a shorter treatment time as compared with the SFRT/gemcitabine regimen for patients with unresectable pancreatic cancer.

A 44-year-old man was attending routine follow-up 5 years after colon cancer resection, when ultrasonography detected a pancreatic tumor with a low echoic area. He had no symptoms. Computed tomography (CT) showed a protruding-type tumor, 4 cm in diameter, in the pancreatic head with central necrosis. Angiography revealed that the tumor was hypervascular. The serum somatostatin level was elevated, at 27 pg/ml (normal range, 1.0-12 pg/ml). As somatostatinoma of the pancreas was suspected, we performed pylorus-preserving pancreaticoduodenectomy. Histological and immunohistochemical staining confirmed somatostatinoma of the pancreas without nodal metastasis. Thus, if an endocrine tumor of the pancreas is suspected in a patient with a hypervascular tumor, the possibility of somatostatinoma should be included in the differential diagnosis.

It has been reported that anatomic resection may be preferable to nonanatomic resection for small hepatocellular carcinomas (HCCs), by reducing so-called "micrometastases" (portal venous tumor extension and intrahepatic metastases). Nonanatomic resection or ablation has also been used as therapy for small HCCs. We studied the effectiveness of anatomic resection for small nodular HCCs, especially from the viewpoints of tumor size and gross classification.A retrospective cohort study was performed in 116 consecutive patients who underwent curative hepatic resection for HCCs 3 cm or smaller and with three or fewer nodules. The outcome of anatomic resection (including segmentectomy, sectoriectomy, and hemihepatectomy) was compared to that of nonanatomic partial hepatectomy.The group that underwent anatomic resection (n = 52) had relatively better overall survival and significantly better recurrence-free survival than those with nonanatomic resection (n = 64). On Cox multivariate analysis, however, liver function was more closely associated with survival. The effect of anatomic resection was more prominent in the subgroup with the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular type, and invasive type) than in the subgroup with the boundary type (vaguely nodular and single nodular type). Micrometastases in the nonboundary type were found further from the main tumor (9.5 +/- 6.2 mm) than those in the boundary type (within 3.1 +-1.4 mm).In patients with HCC nodules equal to or less than 3 cm and with the nonboundary type, anatomic resection should be employed to the extent that liver function allows, because this procedure would be more favorable than nonanatomic resection in eradicating micrometastases that have extended away from the tumor's margin.

Chemoradiation therapy (CRT), a combination of X-ray irradiation and anticancer agents as a radiosensitizer, has been found to be an effective treatment for esophageal cancer and has been linked to p53 genetics. The p53 gene family regulates cell-cycle arrest, apoptosis and DNA damage repair. A recently identified ribonucleotide reductase, p53R2, is directly regulated by p53 in the supply of nucleotides for repairing damaged DNA. In the present study, we investigated the improvement in radiosensitivity of human esophageal squamous cell carcinoma (ESCC) cell lines using p53R2 small interfering RNA (siRNA). p53R2 expression in ESCC cells (TE-8) with or without transfection of p53R2 siRNA was examined by Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). The radiosensitivity of TE-8 cells was also measured by cell survival assay. In addition, we investigated the relationship between the expression of p53R2 mRNA in the biopsy specimens of untreated primary tumors and the efficacy of CRT, using RT-PCR. The expression of p53R2 was amplified after X-ray irradiation (14 Gy) and diminished after X-ray irradiation following the transfection of p53R2 siRNA in TE-8 cells. The radiosensitivity of the TE-8 cells significantly improved following the transfection of p53R2 siRNA. In the clinical study, a significantly lower p53R2 mRNA expression was detected in the effective response cases. We demonstrated that p53R2 is associated with the radiosensitivity of ESCC cell lines, and that p53R2 expression is reduced after X-ray irradiation following the transfection of p53R2 siRNA. This protocol could potentially improve the efficacy of radiation therapy.

We herein present a rare case of a mucinous cystic neoplasm of the pancreas producing CA 19-9 and the clinical implications are discussed.A 35-year-old woman with no history of abdominal surgery presented at Saisei Kai Sendai Hospital with an upper abdominal distention. Abdominal CT showed a large lobulated cystic tumor at the pancreatic tail. No distant metastases were identified. The preoperative serum CA 19-9 level was 6,200 U/mL (reference range: 0-37 U/mL). A mucinous cystic neoplasm of the pancreas was diagnosed and elective surgery was performed. On laparotomy, a round tumor 15 cm in diameter was encountered in the upper left abdomen. No invasion of neighboring organs or the portal vein was apparent. The entire tumor was curatively resected with a distal pancreatectomy. The final histopathological analysis revealed mucinous cystadenocarcinoma with no invasive component. Immunohistochemical staining disclosed CA 19-9 expression within the tumor cells. The CA 19-9 level normalized rapidly postoperatively and, although a minor pancreatic fistula occurred, this was resolved conservatively. She was discharged on the 45th postoperative day with no sign of tumor relapse; her CA 19-9 level was within the normal range 20 months postoperatively.We present this rare case of a mucinous cystic neoplasm producing CA 19-9 and discuss the relevant literature. The CA 19-9 production in this tumor does not appear to be directly correlated to aggressive clinical behavior.

Lymph node metastasis is one of the most important prognostic factors in patients with gastric cancer.1–5 Therefore, D2 lymph node dissection for gastric cancer has become a standard procedure that has increased the long-term survival of patients with lymph node metastasis.6 The 5-year survival rates of patients with mucosal and submucosal gastric cancer are 95% to 100% and 85% to 95%, respectively.7–9 However, the incidence of lymph node metastasis determined by histology in mucosal and submucosal gastric cancer is 2% to 4% and 13% to 20%, respectively.8–12 Thus, standard lymph node dissection may be unnecessary for patients without lymph node metastasis. However, it is difficult to precisely diagnose lymph node metastasis, especially micrometastasis, using preoperative examinations such as endoscopic ultrasonography (EUS) and computed tomography (CT). The sentinel node (SN) concept was first advocated by Morton et al13 in patients with melanoma. Sentinel node navigation surgery (SNNS) for breast cancer and malignant melanoma can accurately asses lymph node dissection areas.14,15 The SN concept has recently been applied to cancers of the gastrointestinal tract.16–20 If SNNS could be applied to such patients, then minimally invasive surgery with personalized lymphadenectomy might be possible. At present, lymph node metastasis, including micrometastasis, must be identified when performing SNNS.21 Some authors have reported the clinical significance of lymph node micrometastasis detected by immunohistochemistry (IHC).21–23 Others have found that real-time reverse transcription-polymerase chain reaction (RT-PCR) can detect lymph node micrometastasis more sensitively than IHC.24,25 A few reports have examined micrometastasis of SN using RT-PCR in gastric cancer. Thus, whether the SN concept is applicable in the presence of lymph node micrometastasis should be investigated. The present study determines the applicability of the SN concept to gastric cancer based on lymph node micrometastasis determined by IHC and RT-PCR.