Hisafumi Kinoshita

Kurume University, Куруме, Fukuoka, Japan

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Publications (107)81.34 Total impact

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    ABSTRACT: To review the usefulness of endoscopic biliary stenting for obstructive jaundice caused by hepatocellular carcinoma and identify problems that may need to be addressed.
    World journal of gastroenterology : WJG. 06/2014; 20(22):6968-73.
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    ABSTRACT: Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time intensity curve was used to determine the percentage brightness increase in cancerous and normal regions and the patients were divided into two groups, hyperperfusion, with a percentage brightness increase over 80% (n=6) and hypoperfusion, with an increase of less than 80% (n=7) on CE-US. The hyperperfusion group included well-differentiated tubular adenocarcinoma, adenosquamous cell carcinoma and acinar cell carcinoma, while all 7 patients in the hypoperfusion group had moderately differentiated tubular adenocarcinoma. Immunological staining (α-SMA and anti-CD34) of the resected specimens showed significantly higher microartery count (MAC) in the hyperperfusion group (p<0.005) than in the hypoperfusion group or normal pancreas. In the normal pancreas, the mean vessel diameter was significantly higher (over 100 μm) than in the hyperperfusion group (30 μm; p<.005). It was concluded that a muscular arterial vessel density of less than 30 μm is an important factor in determining staining degree and carcinoma progression by CE-US in pancreatic carcinoma.
    The Kurume Medical Journal 02/2014;
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    ABSTRACT: Cancer stem cells (CSCs), a minority population with stem cell-like characteristics, play important roles in cancer development and progression. Putative CSC markers, such as CD13, CD90, CD133, and EpCAM, and side population (SP) technique are generally used in an attempt to isolate CSCs. We aimed to clarify the relationship between CSCs and clonal dedifferentiation in hepatocellular carcinoma (HCC). We used a well-differentiated HCC cell line (HAK-1A) and a poorly differentiated HCC cell line (HAK-1B) established from a single nodule with histological heterogeneity. HAK-1B arose due to clonal dedifferentiation of HAK-1A. The SP cells and non-SP (NSP) cells were isolated from the two cell lines with a FACSAria II and used for the analyses. The SP cell fractions in HAK-1A and HAK-1B were 0.2% and 0.9%, respectively. CD90 or EpCAM was not expressed in either HAK-1A or HAK-1B, while CD13 and CD133 were expressed in HAK-1B alone. Although sphere forming ability, tumorigenicity, growth rate, and CD13 expression were higher in HAK-1B SP cells than HAK-1B NSP cells, there were no differences in drug resistance, colony forming ability, or cell cycle rates between HAK-1B SP and NSP cells, suggesting HAK-1B SP cells do not fulfill CSC criteria. Our findings suggested a possible relationship between the expression of CSC markers and clonal dedifferentiation. However, the complete features of CSC could not be identified in SP cells, and the concept of SP cells as a universal marker for CSC may not apply to HAK-1A and HAK-1B.
    Journal of Gastroenterology and Hepatology 12/2013; · 3.33 Impact Factor
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    ABSTRACT: We measured the slope gradients (SGs) of the vascular time-intensity curves (TICs) of the intrahepatic vessels on contrast-enhanced ultrasonography (CEUS). The aim of this study was to assess the diagnostic accuracy of the SG of each hepatic vessel, particularly the portal vein (PV), for detecting cirrhosis and to compare this method with conventional modalities. Fifty-one preoperative patients underwent CEUS, and the TICs were plotted. The SGs of the hepatic artery, PV and hepatic vein were obtained from the linear functions between the slope of the arrival time of the contrast agent and the peak enhancement time of each vessel. The transit times and levels of biochemical markers were also measured. The patients were divided into three groups according to the Metavir score: F0/1 group (n = 14), F2/3 group (n = 21) and F4 group (n = 16). The PVSG significantly decreased in the F4 group (F0/1: 29.1 ± 2.27, F2/3: 23.1 ± 1.86, F4: 14.7 ± 2.13). The PVSG demonstrated high accuracy for diagnosing cirrhosis and was correlated with the levels of ICG-R15 and hyaluronic acid (Spearman rank correlation; ρ = -0.5691, p < 0.001 and ρ = -0.4652, p = 0.0006). The PVSG has the potential to be a diagnostic marker for identifying patients with well-compensated cirrhosis.
    Surgery Today 10/2013; · 0.96 Impact Factor
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    ABSTRACT: Splenectomy may be a treatment option in hepatocellular carcinoma (HCC) and cirrhosis when there is no potential donor for liver transplantation. We retrospectively investigated the long-term outcome of splenectomy on survival in advanced cirrhotic patients with HCC and thrombocytopenia. Between 1999 and 2009, 46 cirrhotic patients with thrombocytopenia (Child-Pugh class B or C) who underwent splenectomy for the simultaneous or secondary treatment of HCC at our institute were evaluated. The 1-, 3-, and 5-year survival rates were 93.5, 76.0, and 37.9%, respectively. Splenectomy resulted in a significant reduction in mean portal venous pressure from 21.2 to 16.8 mmHg and improvements in liver function tests such as total bilirubin, prothrombin time, platelet count, Child-Pugh score for 3 years, and albumin for 2 years. The mean frequency of treatment for HCC recurrence after surgery was 3.0 times (range: 1-11). Seven patients out of 16 scheduled for Interferon (IFN) therapy after surgery achieved a sustained virological response (SVR). Multivariate analysis identified SVR after IFN therapy as an independent significant prognostic factor (Hazard ratio 0.18, 95%CI 0.03-0.65, P=0.006). Postoperative complications including liver failure (n=1), portal thrombosis (n=7), ascites (n=5), and bacterial infections (n=4) were observed in 14 patients (30%). Splenectomy can be a feasible supportive therapy for the continuation of anticancer therapy and completion of IFN therapy based on improvements in liver function and thrombocytopenia with minimum complications in patients with HCC and advanced cirrhosis with no potential donor.
    The Kurume Medical Journal 09/2013;
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    ABSTRACT: We classified resected intraductal papillary mucinous neoplasms (IPMNs) into four subtypes (gastric, intestinal, pancreatobiliary and oncocytic) according to their morphological features and mucin expression, determined their clinicopathological characteristics and investigated the possibility of preoperatively diagnosing these subtypes. Sixty resected tumors, 4 preoperative tumor biopsies and 10 preoperative pancreatic juice cytology specimens were analyzed. The gastric and intestinal types accounted for the majority of IPMNs. Non-gastric type IPMNs were of high-grade malignancy. Many of the pancreatobiliary-type IPMNs were in an advanced stage and were associated with a poor prognosis. The results of mucin immunohistochemical staining of preoperative biopsy and surgically resected specimens were in agreement with each other, and in close agreement with those for pancreatic juice cytology specimens obtained from 10 patients during endoscopic retrograde cholangiopancreatography (ERCP). The immunostaining of preoperative biopsy specimens and ERCP-obtained pancreatic juice cytology specimens may be useful in the differential diagnosis of gastric and intestinal types of IPMN. If such techniques enable the preoperative diagnosis of IPMN subtypes, their use in combination with conventional preoperative imaging modalities may lead to surgical treatment best suited for the biological characteristics of the four subtypes.
    Oncology Reports 09/2013; · 2.30 Impact Factor
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    ABSTRACT: Splenectomy improves hypersplenic thrombocytopenia in cirrhotic patietnts with hypersplenism. However, the long term influence of splenectomy has not been calrified. We examined whether splenectomy improved liver fibrosis and casused immunological changes. We collected liver and spleen specimens and peripheral blood (PB) from 26 patients with hepatitis C virus (HCV)-related liver cirrhosis. An immunohistochemical examination of CD4, CD8, forkhead box P3 (FOXP3), granzyme B, and transforming growth factor (TGF)-β1, and Masson's Trichrome stain were performed in spleen and liver tissues and in 7 cases of follow-up liver biopsy sections obtained after splenectomy. We obtained PB before and at various intervals after splenectomy. We also examined the ratio of CD4(+) and CD8(+) lymphocytes in PB using flow cytometry. We observed improvements in liver fibrosis in 4 biopsy specimens obtained after splenectomy, in which fibrotic areas significantly decreased from 19.5% to 8.2% (p<0.05). Increases were also observed in the ratio of CD8(+) cells in PB after splenectomy, which resulted in a significant decrease in the CD4(+) /CD8(+) ratio (p<0.001). The carcinogenic rate in patients with a CD4(+) /CD8(+) ratio that decreased by more than 0.5 one month after splenectomy was significantly lower than that in patients with a ratio that decreased by less than 0.5 (p<0.05). Splenectomy may improve liver fibrosis and cause beneficial immunological changes in cirrhotic patients with hepatitis. Improvements in anti-tumor mechanisms can be also expected.
    Hepatology Research 09/2013; · 2.07 Impact Factor
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    ABSTRACT: Intestinal malrotation is caused by a developmental anomaly of the embryonic intestine. Most cases develop in neonates, and development in adulthood is rare and difficult to diagnose before surgery. Pancreaticoduodenectomy was performed for cancer of the ampulla of Vater accompanied by incomplete fixation in a 63-year-old male patient. A branch of the superior mesenteric artery was present on the resection line and was deemed likely to cause circulatory disorder in the small intestine, and the duodenum and jejunum were covered with a membranous structure making dissection, anatomical identification, and jejunectomy difficult. Herein, we report the case with a review of the literature.
    The Kurume Medical Journal 08/2013;
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    ABSTRACT: The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB). We performed a multi-institutional, retrospective study of patients with MCN or M-IPNB pathologically defined by the presence or absence of an ovarian-like stroma. The M-IPNB and MCN were diagnosed in 119 and nine patients, respectively. MCN was observed in female patients, while M-IPNB produced symptoms of cholangitis. M-IPNBs were classed as low or intermediate grade in 53 cases, high grade in 23 and invasive carcinoma in 43. Fifty-one of the M-IPNBs were the pancreatobiliary type (PT), 33 were the intestinal type (IT), 23 were the oncocytic type (OT), and 12 were the gastric type (GT). The 1-, 5- and 10-year survival rates for the 105 patients with M-IPNB were 96%, 84% and 81%, respectively, while the 5-year survival rate for patients with MCN was 100%. OT and GT M-IPNB had better 10-year survival rates than PT and IT M-IPNB. Although MCN has different features from M-IPNB, both diseases have a good prognosis after resection. The cellular type of M-IPNB appears to predict outcome.
    Journal of hepato-biliary-pancreatic sciences. 08/2013;
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    ABSTRACT: 60-year-old woman was referred to us for epigastralagia under the diagnosis of chronic cholecystitis. Cholecystectomy was performed, and gallbladder carcinoma was pinpointed by postoperative pathological diagnosis. Because liver invasion should have been detected by pathological diagnosis, we conducted liver S4a+S5 resection, extrahepatic bile duct resection and D2 lymphadenectomy. The pathological diagnosis was advanced gallbladder carcinoma with liver metastasis. We treated a patient with curative operation and hepatic arterial infusion adjuvant chemotherapy by low-dose FP therapy for advanced gallbladder carcinoma, and she is doing well now without disease recurrence eight years after surgery.
    Gan to kagaku ryoho. Cancer & chemotherapy 08/2013; 40(8):1081-3.
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    ABSTRACT: Little is known about the effects of neoadjuvant therapy on outcomes in patients with pancreatic cancer. This study evaluated the effects of neoadjuvant therapy on resectability and perioperative outcomes. A total of 992 patients were enrolled, with 971 deemed eligible. Of these, 582 had resectable tumors and 389 had borderline resectable tumors, and 388 patients received neoadjuvant therapy. Demographic characteristics and peri- and postoperative parameters were assessed by a questionnaire survey. The R0 rate was significantly higher in patients with resectable tumors who received neoadjuvant therapy than in those who underwent surgery first, but no significant difference was noted in patients with borderline resectable tumors. Operation time was significantly longer and blood loss was significantly greater in patients who received neoadjuvant therapy than in those who underwent surgery first, but there were no significant differences in specific complications and mortality rates. The node positivity rate was significantly lower in the neoadjuvant than in the surgery-first group, indicating that the former had significantly lower stage tumors. Neoadjuvant therapy may not increase the mortality and morbidity rate and may be able to increase the chance for curative resection against resectable tumor.
    Journal of hepato-biliary-pancreatic sciences. 08/2013;
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    ABSTRACT: Detailed endoscopic findings of the bile duct mucosa, even of the non-neoplastic mucosa, have not yet been established. The aim of the present study was to compare a currently used video cholangioscope (CCS) with a magnifying endoscope (ME) that is commonly used for the gastrointestinal tract, for visualization of the bile duct mucosa. Ten freshly resected common bile ducts were used in this study. We observed the non-neoplastic bile duct mucosa with CCS and ME, and carried out both conventional white light imaging and narrow band imaging. After histological diagnosis, the 10 specimens were classified into three categories according to the degree of histological inflammation: normal to mild, moderate, and severe. Then, we examined the relationship between the magnifying endoscopic findings and the histopathological findings. In eight of the 10 cases, the visualization obtained with CCS was inferior to that obtained by ME. Five specimens were classified as normal to mild inflammation, and many oval-shaped, depressed areas and a fine, regular network of the microvessels were observed by ME on the mucosal surfaces of these specimens. The remaining specimens were classified as moderate or severe inflammation, and the aforementioned findings could not be clearly visualized. CCS does not allow visualization of the bile duct mucosa with high sensitivity. Oval-shaped depressed areas and a fine, regular network of microvessels are characteristic endoscopic features of non-neoplastic bile duct mucosa without inflammation.
    Digestive Endoscopy 05/2013; 25(3):322-8. · 1.61 Impact Factor
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    ABSTRACT: PURPOSE: Hepatectomy of segments 4a and 5 (S4a+5) is the recommended treatment for pT2 gallbladder cancer. However, gallbladder bed resection is also occasionally used. Using nationwide data from the Japanese Biliary Tract Cancer Registry and a questionnaire survey, we retrospectively compared these 2 methods of treatment. METHOD: The study involved 85 patients with pT2, pN0 gallbladder cancer (55 treated with gallbladder bed resection, and 30, with S4a+5 hepatectomy). The prognosis and mode of tumor recurrence following treatment were analyzed retrospectively, with overall survival as the endpoint. RESULTS: The 5-year survival rate did not differ significantly between the 2 groups. Univariate analysis showed that bile duct resection and perineural tumor invasion were significant prognostic factors, but the extent of hepatectomy, location of the major intramural tumor, regional lymph node excision, and histological type were not. Multivariate analysis identified perineural tumor invasion as a significant prognostic factor. Recurrence occurred most frequently in both lobes than S4a+5 of the liver following gallbladder bed resection. CONCLUSION: In the present study of cases of Japanese Biliary Tract Cancer Registry, it was not possible to conclude that S4a+5 hepatectomy was superior to gallbladder bed resection.
    Journal of hepato-biliary-pancreatic sciences. 02/2013;
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    ABSTRACT: Cystic lesions of the liver consist of a heterogeneous group of disorders that can present diagnostic and therapeutic challenges. A retrospective review of all medical records of adult patients diagnosed with large (>7 cm) cystic lesions of the liver between January 2000 and December 2011, at Kurume University Hospital. Cases with polycystic disease were excluded. Twenty three patients were identified. The mean size was 13.9 cm (range, 7-22cm). The majority of simple cysts were found in women (females: males, 2: 21). In 19 patients, the cyst was removed surgically by wide deroofing (laparoscopically in 16 cases, combined with ethanol sclerotherapy in 13 cases). Infection of the liver cyst occurred in one patient, who later underwent central bi-segmentectomy. Simple large cysts of the liver can be successfully treated by laparoscopic deroofing and alcohol sclerotherapy. Large hepatic cyst considered to need drainage should be removed surgically to avoid possible infection.
    PLoS ONE 01/2013; 8(10):e76537. · 3.73 Impact Factor
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    ABSTRACT: The success of biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice influences its prognosis greatly. In this study, we report a retrospective evaluation of endoscopic retrograde biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice. Materials and methods: From April 2004 to December 2011, 9 patients with liver metastases from colorectal cancer and obstructive jaundice who underwent endoscopic biliary drainage were evaluated retrospectively. Results: The mean serum levels of total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase improved significantly after biliary drainage. The median survival time after biliary drainage was 133 days. Only 4 cases were able to resume chemotherapy after biliary drainage, and their prognosis was significantly better than patients who were not able to resume chemotherapy(p=0.014). Discussion: Endoscopic biliary drainage in patients with liver metastases from colorectal cancer and obstructive jaundice was effective, led to the resumption of chemotherapy, and improved prognosis. However, sufficient consideration of the patient's prognosis and performance status is required in order to perform biliary drainage.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1860-2.
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    ABSTRACT: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion). Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.
    World Journal of Gastroenterology 07/2012; 18(28):3673-80. · 2.55 Impact Factor
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    ABSTRACT: BACKGROUND/PURPOSE: Mastering the technique of pancreaticoduodenectomy (PD) is a major theme in hepato-biliary-pancreatic surgery, and education for PD has not been established even in each institution. With the progression of disease, the difficulty of PD increases due to cases requiring resection of multiple organs and borderline resectable cases, and complications affecting survival also often occur. To help to improve the education of young surgeons, we clarified the institutions' principles and the status of operations performed by young surgeons. METHODS: We sent questionnaires to institutions as members of the Japanese Society of Pancreatic Surgery about the institutions' educational principles in 2010 and surgeons who performed PD and patients treated by PD between January and December 2007. The PD operators were classified into two groups: postgraduate year ≤10 or ≥11, and each institution's principles, and pre-, intra-, and postoperative factors were evaluated. RESULTS: PD was performed by surgeons at postgraduate year ≤10 in 29 (40.6%) institutions. Education programs were using 29 (41.4%) institutions. High-volume centers, where the surgeons performing PD tend to be at postgraduate year ≤10, can provide more training. Preoperative risks were not included in the criteria for selecting cases for operations by young surgeons, and young surgeons tended to perform PD in patients with less advanced stages. The incidence of pancreatic fistula classified as International Study Group of Pancreatic Surgery Grade B or C was significantly higher (P = 0.010) in the operator group at postgraduate year ≤10 (24.6%, 32 patients) than that at postgraduate year ≥11 (17.6%, 177 patients). Cumulative survival rate of pancreatic cancer or extrahepatic bile duct cancer did not significantly differ between the two operator groups. CONCLUSION: The present questionnaire showed increased opportunities of performing operations by young surgeons. Although the incidence of Grade B/C fistula is higher for postgraduate year ≤10, postoperative outcome is acceptable. It is acceptable for the pancreaticoduodenectomy performed by young surgeons, when young surgeons receive high-level education under the guidance of supervisory doctor. Prognosis did not differ between two operator groups at postgraduate year ≤10 and ≥11 in this study. Based on these findings, operations by surgeons at postgraduate year ≤10 present can be recommended.
    Journal of hepato-biliary-pancreatic sciences. 03/2012;
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    ABSTRACT: Considering that the prognosis of patients with advanced biliary tract cancer (BTC) remains very poor, with a median survival of less than 1 year, new therapeutic approaches need to be developed. In the present study, a phase II clinical trial of personalized peptide vaccination (PPV) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers. A maximum of 4 human leukocyte antigen-matched peptides, which were selected based on the pre-existing host immunity prior to vaccination, were subcutaneously administered (weekly for 6 consecutive weeks and bi-weekly thereafter) to 25 advanced BTC patients without severe adverse events. Humoral and/or T cell responses specific to the vaccine antigens were substantially induced in a subset of the vaccinated patients. As shown by multivariate Cox regression analysis, lower interleukin-6 (IL-6) and higher albumin levels prior to vaccination and greater numbers of selected vaccine peptides were significantly favorable factors for overall survival [hazard ratio (HR)=1.123, 95% confidence interval (CI) 1.008-1.252, P=0.035; HR=0.158, 95% CI 0.029-0.860, P=0.033; HR=0.258, 95% CI 0.098-0.682, P=0.006; respectively]. Based on the safety profile and substantial immune responses to vaccine antigens, PPV could be a promising approach for refractory BTC, although its clinical efficacy remains to be investigated in larger-scale prospective studies. The identified biomarkers are potentially useful for selecting BTC patients who would benefit from PPV.
    Experimental and therapeutic medicine 03/2012; 3(3):463-469. · 0.34 Impact Factor
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    ABSTRACT: The contrast harmonic imaging technique allows visualization of micro bubbles and has facilitated the detection of blood flow on contrast-enhanced ultrasonography (CE-US). In hypovascular tumors such as pancreatic cancer a hypoxic nutrition-deficient environment increases tumor malignancy. In this study, we investigated the relation between CE-US findings, intratumoral microvessel density (MVD), and pathological analysis in pancreatic cancer, and we also investigated the clinicopathological significance of CE-US.The subjects were 16 pancreatic cancer patients who underwent CE-US before surgery. A time-signal intensity curve (TIC) was prepared based on the region of interest (ROI) in the tumor on CE-US, and the signal intensity (SI) was defined as an increase from the value before contrast imaging to the maximum value. Regarding MVD, histological sections were stained with anti-CD34 and α-smooth muscle actin (α-SMA) antibodies, and double stained micro-blood vessels were counted. The correlation between SI and MVD was investigated. In addition, disease-free survival (DFS) was compared between the hypo (≤mean SI) and hyper (>mean SI) SI groups.SI in cancerous lesions was 54.6±42.9 dB (mean±SD), and MVD in cancerous lesions was 12.5±5.02 (mean±SD). A positive correlation was noted between the SI and MVD (r(2)=0.408, p=0.008). The median DFS were 212 and 606 days in the hypo and hyper SI groups, respectively, showing a significantly shorter DFS in the hypo SI group (P=0.003). No patient died of the primary disease during the follow-up period in the hyper SI group, and a maximum 47-month follow-up was possible. A positive correlation was noted between SI and MVD, indicating that MVD of pancreatic cancer could be evaluated using CE-US. We suggested that CE-US is a useful predictor of patient prognosis after pancreatic cancer surgery.
    The Kurume Medical Journal 01/2012; 59(3.4):45-52.
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    ABSTRACT: Our recent study demonstrated that higher expression of N-myc downregulated gene 1 (NDRG1) is closely correlated with poor prognosis in gastric cancer patients. In this study, we asked whether NDRG1 has pivotal roles in malignant progression including metastasis of gastric cancer cells. By gene expression microarray analysis expression of NDRG1 showed the higher increase among a total of 3691 up-regulated genes in a highly metastatic gastric cancer cell line (58As1) than their parental low metastatic counterpart (HSC-58). The highly metastatic cell lines showed decreased expression of E-cadherin, together with enhanced expression of vimentin and Snail. This decreased expression of E-cadherin was restored by Snail knockdown in highly metastatic cell lines. We next established stable NDRG1 knockdown cell lines (As1/Sic50 and As1/Sic54) from the highly metastatic cell line, and both of these cell lines showed enhanced expression of E-cadherin and decreased expression of vimentin and Snail. And also, E-cadherin promoter-driven luciferase activity was found to be increased by NDRG1 knockdown in the highly metastatic cell line. NDRG1 knockdown in gastric cancer cell showed suppressed invasion of cancer cells into surround tissues, suppressed metastasis to the peritoneum and decreased ascites accumulation in mice with significantly improved survival rates. This is the first study to demonstrate that NDRG1 plays its pivotal role in the malignant progression of gastric cancer through epithelial mesenchymal transition.
    PLoS ONE 01/2012; 7(7):e41312. · 3.73 Impact Factor

Publication Stats

456 Citations
81.34 Total Impact Points

Institutions

  • 1992–2014
    • Kurume University
      • • Division of Gastroenterology
      • • Department of Surgery
      • • Department of Pathology
      • • School of Medicine
      Куруме, Fukuoka, Japan
  • 2012
    • National and Kapodistrian University of Athens
      • Department of Surgery
      Athens, Attiki, Greece