Yasumasa Niwa

Publications (109)304.92 Total impact

• Article: The aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism interacts with alcohol drinking in the risk of stomach cancer.

  Keitaro Matsuo, Isao Oze, Satoyo Hosono, Hidemi Ito, Miki Watanabe, Kuka Ishioka, Seiji Ito, Masahiro Tajika, Yasushi Yatabe, Yasumasa Niwa, Kenji Yamao, Shigeo Nakamura, Kazuo Tajima, Hideo Tanaka
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  ABSTRACT: Impact of alcohol on the risk of stomach cancer is controversial. Although ALDH2 Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1,372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.45 (0.82-2.59) for those with ALDH2 Glu/Glu and 2.37 (1.37-4.12) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (p for interaction =0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis.
  Carcinogenesis 03/2013; · 5.70 Impact Factor
• Article: Can mosapride citrate reduce the volume of lavage solution for colonoscopy preparation?

  Masahiro Tajika, Yasumasa Niwa, Vikram Bhatia, Shinya Kondo, Tsutomu Tanaka, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Koji Komori, Kenji Yamao
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  ABSTRACT: To evaluate the possibility of reducing the volume of polyethylene glycol (PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. This was a single-center, prospective, randomized, investigator-blinded, non-inferiority study involving 252 patients of both sexes, aged from 20 to 80 years, scheduled for screening or diagnostic colonoscopy in our department. A total of 126 patients was randomized to receive 1.5 L PEG-electrolyte solution plus 15 mg of mosapride (1.5 L group), and 126 received 2 L PEG-electrolyte solution plus 15 mg of mosapride (2 L group). Patients completed a questionnaire on the acceptability and tolerability of the bowel preparation process. The efficacy of bowel preparation was assessed using a 5-point scale based on the Aronchick scale. The primary end point was adequate bowel preparation rates (score of excellent/good/fair) vs (poor/inadequate). Acceptability and tolerability, as well as disease detection, were secondary end points. A total of 244 patients was included in the analysis. There were no significant differences between the 2 L and 1.5 L groups in age, sex, body mass index, number of previous colonoscopies, and the preparation method used previously. The adequate bowel preparation rates were 88.5% in the 2 L group and 82.8% in the 1.5 L group [95% lower confidence limit (LCL) for the difference = -14.5%, non-inferiority P = 0.019] in the right colon. In the left colon, the adequate bowel preparation rates were 89.3% in the 2 L group and 81.1% in the 1.5 L group (95% LCL = -17.0%, non-inferiority P = 0.066). Compliance, defined as complete (100%) intake of the PEG solution, was significantly higher in the 1.5 L group than in the 2 L group (96.8% vs 85.7%, P = 0.002). The proportion of abdominal distension (none/mild/moderate/severe) was significantly lower in the 1.5 L group than in the 2 L group (36/65/22/3 vs 58/48/18/2, P = 0.040). Within the subgroup who had undergone colonoscopy previously, a significantly higher number of patients in the 1.5 L group than in the 2 L group felt that the current preparation was easier than the previous one (54.1% vs 28.0%, P = 0.001). The disease detection rate was not significantly different between the two groups. Although the 1.5 L group had better acceptability and tolerability, 15 mg of mosapride may be insufficient to compensate for a 0.5-L reduction of PEG solution.
  World Journal of Gastroenterology 02/2013; 19(5):727-35. · 2.47 Impact Factor
• Article: Diagnostic ability and factors affecting accuracy of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions: Japanese large single center experience.

  Shin Haba, Kenji Yamao, Vikram Bhatia, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Yasuhiro Shimizu, Yasushi Yatabe, Waki Hosoda, Hiroshi Kawakami, Naoya Sakamoto
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  ABSTRACT: BACKGROUND: Several studies have investigated the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic lesions, but they have included only limited patient populations. This study aimed to clarify the diagnostic accuracy of EUS-FNA in a large number of pancreatic lesions, and to describe the factors that influence it. METHODS: From March 1997 to May 2010, 944 consecutive patients who had undergone EUS-FNA for pancreatic solid lesions were evaluated retrospectively. Factors affecting EUS-FNA accuracy were then analyzed. RESULTS: A total of 996 solid pancreatic lesions were sampled by EUS-FNA. The overall sampling adequacy and diagnostic accuracy of these lesions were 99.3 % (989/996) and 91.8 % (918/996), respectively. The sensitivity and specificity for differentiating malignant from benign lesions were 91.5 % (793/867) and 97.7 % (126/129), respectively. The diagnostic performance was significantly higher when both cytological and cell-block examinations were carried out than with only cytological examination. In multivariate analysis, final diagnosis, location of lesion, lesion size, availability of on-site cytopathological evaluation, and experience of EUS-FNA procedure were independent factors affecting the accuracy of EUS-FNA. On-site cytopathological evaluation and lesion size were found to be the most weighted factors affecting diagnostic accuracy. CONCLUSIONS: EUS-FNA for pancreatic solid lesions yielded a high accuracy and low complication rate. Both cytological and cell-block preparations and on-site cytopathological evaluation contributed to improve the accuracy. The diagnostic ability of EUS-FNA was less for smaller lesions, and repeated procedures may be needed if malignancy is suspected.
  Journal of Gastroenterology 10/2012; · 4.16 Impact Factor
• Article: Prognostic value of K-ras mutation status and subtypes in endoscopic ultrasound-guided fine-needle aspiration specimens from patients with unresectable pancreatic cancer.

  Takeshi Ogura, Kenji Yamao, Kazuo Hara, Nobumasa Mizuno, Susumu Hijioka, Hiroshi Imaoka, Akira Sawaki, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Yasuhiro Shimizu, Vikram Bhatia, Kazuhide Higuchi, Waki Hosoda, Yasushi Yatabe
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  ABSTRACT: BACKGROUND: Although recent reports indicate that K-ras mutation status is a biomarker that acts as a prognostic factor, only a few analyses of K-ras mutation subtypes have been published. In addition, there are no reports that analyze overall survival and prognostic factors according to K-ras mutation status and subtypes in only unresectable pancreatic cancer (PC) determined from tissues obtained by endoscopic ultrasound-guided fine-needle aspiration. METHODS: We retrospectively analyzed 242 patients who were diagnosed as having unresectable PC with available histological diagnosis. Clinical data collected included sex, age, Eastern Cooperative Oncology Group performance status, carbohydrate antigen (CA) 19-9, primary tumor location, stage (local or metastatic) according to TNM staging, first-line chemotherapy, K-ras mutation status and subtypes (G12D, G12V, and G12R), and overall survival. We analyzed the negative prognostic factors for reduced overall survival in unresectable PC patients using these data. RESULTS: From multivariate analysis, CA19-9 ≥1000 U/ml (hazard ratio [HR] 1.78, 95 % confidence interval [CI] 1.28-2.46, P < 0.01), metastatic stage (HR 2.26, 95 % CI 1.58-3.24, P < 0.01), and mutant-K-ras (HR 1.76, 95 % CI 1.03-3.01, P = 0.04) were negative prognostic factors, indicating a reduced survival. Among the patients who had K-ras mutation subtypes, CA19-9 ≥1000 U/ml (HR 1.65, 95 % CI 1.12-2.37, P < 0.01), metastatic stage (HR 2.12, 95 % CI 1.44-3.14, P < 0.01), and the presence of the G12D or G12R mutations (HR 1.60, 95 % CI 1.11-2.28) were negative prognostic factors for overall survival. CONCLUSIONS: K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients.
  Journal of Gastroenterology 09/2012; · 4.16 Impact Factor
• Article: Efficacy of mosapride citrate with polyethylene glycol solution for colonoscopy preparation.

  Masahiro Tajika, Yasumasa Niwa, Vikram Bhatia, Hiroki Kawai, Shinya Kondo, Akira Sawaki, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Kazuya Matsumoto, Yuji Kobayashi, Akira Saeki, Asana Akabane, Koji Komori, Kenji Yamao
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  ABSTRACT: To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. We conducted a randomized, double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol (PEG)-electrolyte solution. Of 250 patients undergoing colonoscopy, 124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group), and 126 received 2 L PEG plus placebo (placebo group). Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process. The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria. The primary end point was optimal bowel preparation rates (scores of excellent/good/fair vs poor/inadequate). A total of 249 patients were included in the analysis. In the mosapride group, optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group (78.2% vs 65.6%, P < 0.05), but not in the right colon (76.5% vs 66.4%, P = 0.08). After excluding patients with severe constipation, there was a significant difference in bowel preparation in both the left and right colon (82.4% vs 66.7%, 80.8% vs 67.5%, P < 0.05, P < 0.01). The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience, a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group (34/72 patients vs 24/74 patients, P < 0.05). Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation, especially in patients without severe constipation.
  World Journal of Gastroenterology 05/2012; 18(20):2517-25. · 2.47 Impact Factor
• Article: A retrospective comparison of S-1 plus cisplatin and capecitabine plus cisplatin for patients with advanced or recurrent gastric cancer.

  Kohei Shitara, Akira Sawaki, Keitaro Matsuo, Chihiro Kondo, Daisuke Takahari, Takashi Ura, Masahiro Tajika, Yasumasa Niwa, Kei Muro
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  ABSTRACT: BACKGROUND: Based on the results of the SPIRITS trial, combination chemotherapy of S-1 plus cisplatin (SP) is now considered the standard treatment for patients with advanced gastric cancer (AGC) in Japan. On the other hand, several non-Japanese studies have shown the efficacy of capecitabine plus cisplatin (XP), which has been used as the reference arm in recent global studies of AGC. METHODS: We retrospectively compared the efficacy and safety of SP and XP in first-line treatment for patients with AGC. RESULTS: From August 2006 to November 2008, 26 AGC patients received XP in the context of 2 global trials (AVAGAST and ToGA), and 50 patients received SP during the same period. The objective response rate was 43.2 % in the SP group and 50 % in the XP group, with no significant difference (p = 0.62). There were also no significant differences in progression-free survival (median 5.8 vs. 5.2 months; p = 0.91) and overall survival (median 13.8 vs. 13.5 months; p = 0.97) between the SP and XP groups. The frequencies of hematological toxicities of grade 3 or more and non-hematological toxicities were not significantly different between the 2 groups. Although grade 1 or 2 hand-foot syndrome was more common in the XP group, no patients experienced grade 3 or more. CONCLUSIONS: Although the retrospective nature of this study and the small number of patients is a major limitation, SP and XP were associated with similar efficacy and safety in patients with AGC.
  International Journal of Clinical Oncology 05/2012; · 1.41 Impact Factor
• Article: Pre-operative diagnosis of synchronous solid-pseudopapillary neoplasms of the pancreas

  Kazuya Matsumoto, Kazuo Hara, Akira Sawaki, Nobumasa Mizuno, Susumu Hijioka, Shinya Kondo, Yasumasa Niwa, Masahiro Tajika, Hiroki Kawai, Yasuhiro Shimizu, Waki Hosoda, Yasushi Yatabe, Kenji Yamao
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  ABSTRACT: We report the case of a 37-year-old woman with two synchronous solid-pseudopapillary neoplasms (SPNs) of the pancreas. The patient underwent abdominal echography as part of the screening for hepatitis C virus antibody positivity, and a pancreatic tail tumor was detected. She was referred to our hospital for further examination of the pancreatic tail tumor. There were two masses measuring 37 and 20mm, in the pancreatic body and tail, respectively, which were slightly enhanced on abdominal computed tomography. On endoscopic ultrasonography (EUS), their surfaces were smooth, their margins were clear, anechoic spots were seen in the hypoechoic mass, and there were no lateral shadows. Magnetic resonance imaging showed a low- and high-intensity mass of the body and a low- and low-intensity mass of the tail on T1- and T2-weighted images, respectively. EUS-guided fine needle aspiration biopsy (EUS-FNA) suggested SPNs because the tumor cells showed an aberrant nuclear expression of β-catenin and loss of membranous staining of E-cadherin on immunohistochemical analysis. With a diagnosis of SPNs based on the EUS-FNA findings, a distal pancreatectomy was performed. On histopathologic examination of the resected specimen, the SPNs were arising synchronously. KeywordsSolid-pseudopapillary neoplasm (SPN)-Endoscopic ultrasonography (EUS)-Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA)-β-Catenin-E-cadherin
  Clinical Journal of Gastroenterology 04/2012; 3(6):301-306.
• Article: Clinical impact of K-ras mutation analysis in EUS-guided FNA specimens from pancreatic masses.

  Takeshi Ogura, Kenji Yamao, Akira Sawaki, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Yasuhiro Shimizu, Vikram Bhatia, Kazuhide Higuchi, Waki Hosoda, Yasushi Yatabe
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  ABSTRACT: EUS-guided FNA (EUS-FNA) is considered optimal for differentially diagnosing pancreatic masses. However, the sensitivity of EUS-FNA ranges from 65% to 95%, respectively, which requires improvement. To evaluate clinical impact of K-ras mutation analysis in EUS-FNA specimens from pancreatic masses. Prospective registration, single-center study. Tertiary referral center. This study involved 394 consecutive patients with pancreatic masses (307 pancreatic ductal adenocarcinomas [PDACs], 47 pancreatic inflammatory lesions, and 40 other types of tumors) who underwent EUS-FNA and analysis of K-ras mutations. EUS-FNA, Cycleave polymerase chain reaction. Improvement of the diagnostic accuracy by K-ras mutation analysis; absence of K-ras mutations in non-PDAC masses. K-ras mutations were detected in 266 of 307 PDAC aspirates (87%) and in 3 of 87 non-PDAC masses (3%). K-ras mutations were detected in 18 of 39 patients (46%) who remained cytohistopathologically undiagnosed. The sensitivity, specificity, positive and negative predictive values, and accuracy of cytohistopathological and K-ras mutation analyses alone were 87%, 100%, 100%, 54%, and 89%, respectively, and, when combined, were 93%, 100%, 100%, 68%, and 94%, respectively. Adding K-ras mutation analysis to standard cytohistopathological assessment increased the sensitivity and accuracy of EUS-FNA by 6% (P < .001) and 5% (P < .001), respectively. Single-center study. K-ras mutation analysis may be helpful in patients with suspected PDAC yet inconclusive EUS-FNA findings. K-ras mutations were extremely rare in pancreatic inflammation and other pancreatic tumors.
  Gastrointestinal endoscopy 01/2012; 75(4):769-74. · 6.71 Impact Factor
• Article: [Clinicopathological features of 8 patients with metastatic gastric tumors].

  Asana Akabane, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Akira Saeki, Takeshi Ogura, Shin Haba, Yoshikuni Nagashio, Toshiyuki Hasegawa, Tomohiko Oobayashi, Akihide Shinagawa, Kenji Yamao, Yasushi Yatabe, Yasumasa Niwa
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  ABSTRACT: We examined the clinicopathological features of metastatic gastric tumor, using 9 tumors of 8 patients. Histological diagnosis with all biopsy specimens were adenocarcinoma. Most of the metastatic sites were located in the middle or upper gastric corpus. Endoscopic features of the lesion showed a submucosal tumor-like (5 cases) and primary gastric cancer-like (3 cases) appearance. Immunohistochemical staining of cytokeratins, TTF-1, surfactant protein, ER, or MGB1 identified the primary site; 6 in the lung and 2 in the breast. One case was diagnosed based on the EGFR mutation analysis. In conclusion, immunohistochemical staining and molecular method are useful tools to distinguish metastatic gastric tumor from primary gastric cancer.
  Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2012; 109(4):585-92.
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  Article: Diagnostic yield of endoscopic retrograde cholangiography and of EUS-guided fine needle aspiration sampling in gallbladder carcinomas.

  Susumu Hijioka, Kazuo Hara, Nobumasa Mizuno, Hiroshi Imaoka, Takeshi Ogura, Shin Haba, Mohamed A Mekky, Vikram Bhatia, Waki Hosoda, Yasushi Yatabe, Yasuhiro Shimizu, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Kiichi Tamada, Kenji Yamao
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  ABSTRACT: BACKGROUND: Obtaining histological evidence of gallbladder carcinoma (GBC) is difficult due to its extraductal nature, and pathological confirmation remains challenging. We compared the diagnostic value and safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with endoscopic retrograde cholangiography (ERC) in patients with suspected GBC. PATIENTS: Eighty-three patients with GBC were evaluated. Prior to definitive management, pathological evidence of GBC was obtained through either ERC cytopathologic sampling (n = 33), EUS-FNA (n = 24) or both (n = 26). RESULTS: Among the 83 patients, 59 (71.0%) with biliary obstruction were sampled using ERC with 47.4% (28/59) sensitivity. In 19 of the remaining 31 cases, EUS-FNA sampling had 100% diagnostic sensitivity. Likewise, 50 (60.2%) of the 83 patients with suspected GBC underwent EUS-FNA of regional lymph nodes or the gallbladder (GB) mass itself with 94.8% sensitivity. The overall diagnostic sensitivity rates of ERC and EUS-FNA were 47.4 and 96%, respectively (P < 0.001). Post-procedural complications were seen in 6.7% of the ERC group (4/59, all were mild pancreatitis), and in none of the EUS-FNA group (P = 0.10). CONCLUSIONS: Gallbladder carcinoma sampling using ERC and EUS-FNA should be incorporated into the diagnostic workup of GB lesions as complementary tools, and EUS-FNA should be applied in the setting of failed or not indicated ERC.
  Journal of hepato-biliary-pancreatic sciences. 11/2011;
• Article: A case of lymphomatoid gastropathy: An indolent CD56-positive atypical gastric lymphoid proliferation, mimicking aggressive NK/T cell lymphomas.

  Tsutomu Tanaka, Nirmeen Megahed, Katsuyoshi Takata, Naoko Asano, Yasumasa Niwa, Yoshiki Hirooka, Hidemi Goto
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  ABSTRACT: Lymphomatoid gastropathy (LyGa) is a new evolving pathological entity that has been introduced recently. It is designated to describe CD56-positive atypical gastric lymphoid proliferation, mimicking NK/T cell lymphomas, that shows an indolent clinical course with spontaneous regression. We here present our experience with one new case diagnosed and treated in our hospital. An annual upper endoscopic check-up of a 50-year-old male with an unremarkable past history revealed a small reddish lesion on the posterior wall of the gastric angle. Endoscopic biopsy showed atypical cells of NK-cell lineage expressing CD56, CD16, CD3, perforin, and TIA-1, but not CD4, CD5, and CD8. Epstein-Barr virus encoded RNA was negative. The lesion regressed spontaneously after one month without treatment, but recurred two years later in a different site of the stomach with spontaneous regression again one month later. The recurrence of lymphomatoid gastropathy is very rare and should be diagnosed carefully to distinguish it from the aggressive lymphoma.
  Pathology - Research and Practice 11/2011; 207(12):786-9. · 1.21 Impact Factor
• Article: Comparison of endoscopic submucosal dissection and endoscopic mucosal resection for large colorectal tumors.

  Masahiro Tajika, Yasumasa Niwa, Vikram Bhatia, Shinya Kondo, Tsutomu Tanaka, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Takeshi Ogura, Shin Haba, Kenji Yamao
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  ABSTRACT: Endoscopic mucosal resection (EMR) is the standard procedure for treatment of colorectal tumors. Endoscopic submucosal dissection (ESD) can be performed for resection of larger tumors, but has not been studied in the colorectum because of technical difficulties and complications. We compared outcomes and complications after resection of colorectal tumors larger than 20 mm diameter by ESD and EMR. We retrospectively studied 104 colorectal tumors treated with EMR from 1995 to 2004, and 85 colorectal tumors treated with ESD from 2005 to 2009. We compared the tumor location, shape, size, procedure time, en bloc resection rate, recurrence rate, and associated complications between the treatments. Tumors treated with ESD were larger (31.6 ± 9.0 vs. 25.5 ± 6.8 mm, P<0.001), incurred a longer procedure time (87.2 ± 49.7 vs. 29.4 ± 26.1 min, P<0.001), had a higher en bloc resection rate [71 of 85 tumors (83.5%) vs. 50 of 104 tumors (48.1%), P<0.001], and had a lower recurrence rate [one of 84 tumors (1.2%) vs. 16 of 104 tumors (15.4%); P=0.002] compared with EMR. Perforation occurred in five (5.9%) cases after ESD and in none after EMR (P=0.04). Postoperative bleeding occurred in two (2.4%) and three (2.9%) cases after ESD and EMR (P=not significant), respectively. Although 11 of 16 cases with recurrence after EMR were cured by additional endoscopic treatment, three cases required surgery. The only recurrence after ESD was in one patient who developed perforation after snare EMR. Despite its longer procedure time and higher perforation rate, ESD resulted in a higher en bloc resection rate and lower recurrence rate for larger colorectal tumors compared with EMR.
  European journal of gastroenterology & hepatology 08/2011; 23(11):1042-9. · 1.66 Impact Factor
• Article: Retrospective analysis of primary gastric diffuse large B cell lymphoma in the rituximab era: a multicenter study of 95 patients in Japan.

  Tsutomu Tanaka, Kazuyuki Shimada, Kazuhito Yamamoto, Yoshiki Hirooka, Yasumasa Niwa, Isamu Sugiura, Kunio Kitamura, Hiroshi Kosugi, Tomohiro Kinoshita, Hidemi Goto, Shigeo Nakamura
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  ABSTRACT: Primary gastric diffuse large B cell lymphoma (PG-DLBCL) is common subtype of extranodal non-Hodgkin lymphoma. The optimal treatment strategy for PG-DLBCL in the rituximab era still remains unknown. To evaluate clinical outcomes of PG-DLBCL in the rituximab era, we conducted a retrospective, multicenter analysis of 95 patients with PG-DLBCL. In 58 patients with localized disease, 3-year progression-free survival (PFS) and overall survival (OS) were 91% and 91% for patients with six cycles of rituximab plus CHOP (R-CHOP) and 92% and 95% for patients with three to four cycles of R-CHOP plus radiotherapy (Log-rank test, P = 0.595 and P = 0.278, respectively). In 37 patients with advanced disease, 3-year PFS and 3-year OS were 43% and 64% for patients with R-CHOP chemotherapy with or without radiotherapy. On multivariate analysis, advanced stage and elevated serum LDH levels were independent predictors of survival in patients with PG-DLBCL. One patient with localized disease relapsed in lymph node, and eight patients with advanced disease relapsed in lymph node (n = 3), stomach (n = 2), central nervous system (CNS; n = 2), and duodenum (n = 1). Intriguingly, CNS relapse developed within 6 months after initial series of treatment (4.9 and 5.8 months, respectively), and stomach relapse developed in later phase (27.2 and 32.9 months, respectively). Clinical outcomes of PG-DLBCL were extremely favorable for localized-stage patients in the rituximab era, although these might be poor for advanced-stage patients even in the rituximab era. Further prospective analyses are warranted.
  Annals of Hematology 08/2011; 91(3):383-90. · 2.62 Impact Factor
• Article: A first report of tumor cell implantation after EMR in a patient with rectosigmoid cancer.

  Masahiro Tajika, Yasumasa Niwa, Vikram Bhatia, Shinya Kondo, Tsutomu Tanaka, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Shin Haba, Takeshi Ogura, Takashi Hirai, Kenji Yamao, Yasushi Yatabe
  Gastrointestinal endoscopy 07/2011; 75(5):1117-8. · 6.71 Impact Factor
• Article: Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter, retrospective analysis in Japan.

  Katsuyoshi Takata, Hiroyuki Okada, Naoki Ohmiya, Shotaro Nakamura, Yasuhiko Kitadai, Akira Tari, Taiji Akamatsu, Hiroki Kawai, Shu Tanaka, Hiroshi Araki, [......], Yasuharu Sato, Hisataka Moriwaki, Choitsu Sakamoto, Yasumasa Niwa, Hidemi Goto, Tsutomu Chiba, Takayuki Matsumoto, Daisuke Ennishi, Tomohiro Kinoshita, Tadashi Yoshino
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  ABSTRACT: We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.
  Cancer Science 05/2011; 102(8):1532-6. · 3.33 Impact Factor
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  Article: Contrast-enhanced endoscopic ultrasonography (CE-EUS) findings in adrenal metastasis from renal cell carcinoma.

  Susumu Hijioka, Akira Sawaki, Nobumasa Mizuno, Kazuo Hara, Mohamed A Mekky, Hussein El-Amin, Zain El-Abdeen Ahmed Sayed, Mssahiro Tajika, Yasumasa Niwa, Kenji Yamao
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  ABSTRACT: Solitary adrenal metastasis is often difficult to distinguish from benign adrenal tumor using only plain computed tomography (CT) scanning. We describe a solitary left adrenal gland mass in a patient who had undergone simultaneous gastrectomy and right nephrectomy for advanced gastric cancer and renal cell carcinoma (RCC), respectively. Contrast-enhanced endoscopic ultrasonography (CE-EUS) findings indicated a hypervascular adrenal mass, and EUS-guided fine needle aspiration (EUS-FNA) revealed clear cell carcinoma. Adrenalectomy confirmed metastatic clear cell carcinoma of the kidney.
  Journal of Medical Ultrasonics 04/2011; 38(2):89-92. · 0.33 Impact Factor
• Article: Prospective clinical study of EUS-guided choledochoduodenostomy for malignant lower biliary tract obstruction.

  Kazuo Hara, Kenji Yamao, Yasumasa Niwa, Akira Sawaki, Nobumasa Mizuno, Susumu Hijioka, Masahiro Tajika, Hiroki Kawai, Shinya Kondo, Yuji Kobayashi, Kazuya Matumoto, Vikram Bhatia, Yasuhiro Shimizu, Akihiro Ito, Yoshiki Hirooka, Hidemi Goto
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  ABSTRACT: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has recently been reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) in cases of biliary obstruction, when endoscopic biliary drainage (EBD) is unsuccessful. However, prospective studies of EUS-CDS have not yet been performed. We conducted a prospective study to evaluate the safety, feasibility, and efficacy of EUS-CDS in patients with malignant lower biliary tract obstruction. A prospective study to confirm the safety of EUS-CDS was carried out in 6 patients, followed by a trial to evaluate the feasibility and efficacy of EUS-CDS in 12 additional patients. We placed a plastic stent from the duodenal bulb into the extrahepatic bile duct under EUS guidance using an oblique viewing echoendoscope, needle knife, guidewire, and biliary dilators. The site of extrahepatic bile duct puncture was the common hepatic duct in 15 patients and the common bile duct in 3 patients. Mean diameter of the punctured extrahepatic bile ducts was 10 mm (range: 6-20 mm). Technical and functional success rates were 94% (17/18) and 100% (17/17), respectively. Median procedure time was 30 min (range: 10-52 min). Median duration to first oral intake after the procedure was 1 day (range: 1-3 days). Early complications were encountered in three (17%) patients, including focal peritonitis in two patients and hemobilia in one patient. During the follow-up period (median: 163 days; range: 46-484 days), 12 stent occlusion events were observed in nine patients. Re-intervention with exchange of the occluded stent was successful in 8 of 12 (66%) times. Severe early and late complications were not encountered in any patients in this study. Median duration of stent patency by Kaplan-Meier analysis was 272 days. EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD.
  The American Journal of Gastroenterology 03/2011; 106(7):1239-45. · 7.28 Impact Factor
• Article: Interventional endoscopic ultrasonography for pancreatic cancer.

  Kazuo Hara, Kenji Yamao, Nobumasa Mizuno, Susumu Hijioka, Akira Sawaki, Masahiro Tajika, Hiroki Kawai, Shinya Kondo, Yasuhiro Shimizu, Yasumasa Niwa
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  ABSTRACT: Endoscopic ultrasonography (EUS) represents the combination of endoscopy and intraluminal ultrasonography. This allows use of a high-frequency transducer (5-20 MHz) that, due to the short distance to the target lesion, provides ultrasonographic images of higher resolution than those obtained from other imaging modalities, including multiple-detector-row-computed tomography, magnetic resonance imaging, and positron emission tomography. EUS is now a widely accepted modality for diagnosing pancreatic diseases. However, the most important limitation of EUS has been the lack of specificity in differentiating between benign and malignant changes. In 1992, EUS-guided fine needle aspiration (FNA) of lesions in the pancreas head was introduced into clinical practice, using a curved linear-array echoendoscope. Since then, EUS has evolved from EUS imaging to EUS-FNA and wider applications. Interventional EUS for pancreatic cancer includes EUS-FNA, EUS-guided fine needle injection, EUS-guided biliary drainage and anastomosis, EUS-guided celiac neurolysis, radiofrequency ablation, brachytherapy, and delivery of a growing number of anti-tumor agents. This review focuses on interventional EUS, including EUS-FNA and therapeutic EUS for pancreatic cancer.
  World journal of clinical oncology. 02/2011; 2(2):108-14.
• Article: Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by restoration of the SIRP α1/SHP-2 signaling system.

  Kazuo Hara, Takeshi Senga, Md Helal Uddin Biswas, Hitoki Hasegawa, Satoko Ito, Toshinori Hyodo, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto, Michinari Hamaguchi
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  ABSTRACT: Src kinase dysregulation contributes to cancer progression but mechanistic understanding for this contribution remains incomplete. Signal regulatory protein α1 (SIRPα1) is a tumor suppressor that is constitutively suppressed in v-Src-transformed cells, where restoration of SIRPα1 expression inhibits anchorage-independent growth. In this study, we investigated the role of the protein tyrosine phosphatase-2 (SHP-2) in SIRPα1 activity. SHP-2 suppression resulted in a blockade of SIRPα1-mediated inhibition of anchorage-independent growth. Notably, we found that SIRPα1 did not act in v-Src-transformed cells by triggering cell growth arrest but by eliciting a suspension-selective apoptosis (anoikis), and that SHP-2 was required for this effect. Furthermore, we found that SHP-2 was crucial for recovery of stress fiber and focal contact formation by SIRPα1 in v-Src-transformed cells. Finally, we found that SIRPα1/SHP-2 signaling regulates anoikis in human breast carcinoma cells with activated c-Src. Taken together, our findings define SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPα1 in human breast carcinoma cells as well as in v-Src-transformed cells.
  Cancer Research 02/2011; 71(4):1229-34. · 7.86 Impact Factor
• Article: Intraductal Papillary Mucinous Neoplasms of the Pancreas: Differentiation of Malignant and Benign Tumors by Endoscopic Ultrasonography Findings of Mural Nodules.

  Eizaburo Ohno, Yoshiki Hirooka, Akihiro Itoh, Masatoshi Ishigami, Yoshiaki Katano, Naoki Ohmiya, Yasumasa Niwa, Hidemi Goto
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  ABSTRACT: BACKGROUND AND AIM:: Intraductal papillary mucinous neoplasms (IPMNs) have a wide pathological spectrum and it is difficult to differentiate malignant from benign tumors. The aim of this study was to identify predictors of malignancy using contrast-enhanced endoscopic ultrasonography (CE-EUS). SUBJECTS AND METHODS:: In our institute, main duct type and mixed type IPMNs, branch duct type IPMNs with mural nodules, and IPMNs with coexistent invasive ductal cancer were indications for surgery. Eighty-seven IPMNs (14 main duct, 25 mixed, and 48 branch duct type) were resected and CE-EUS findings were compared with pathological findings. Twelve clinicopathologic variables and CE-EUS morphological findings were assessed. Mural nodules defined as blood flow-supplied protrusions were classified into four types: type I: low papillary nodule, type II: polypoid nodule, type III: papillary nodule, and type IV: invasive nodule. RESULTS:: Of these, 42, 26, 16, and 3 were pathologically diagnosed as adenoma, noninvasive carcinoma, invasive IPMNs, and coexistent invasive ductal cancer, respectively. Multivariable logistic regression analysis showed that type III/IV mural nodule (OR, 10.8; 95% CI: 2.75-56.1) and symptomatic IPMNs (OR, 4.31; 95% CI: 1.37-14.7) were significant for malignancy. For mural nodule diameter, invasive IPMNs were significantly larger, but type III and IV mural nodules were more frequently associated with malignancy, particularly invasive cancer, at 88.9% and 91.7%, respectively. The diagnosis of IPMNs with a type III or IV mural nodule as malignant resulted in a sensitivity of 60%, specificity of 92.9%, and accuracy of 75.9%. CONCLUSION:: In conclusion, new morphological criteria were useful to identify the malignant potentials of IPMNs.
  Annals of surgery 01/2011; · 7.90 Impact Factor