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ABSTRACT: PURPOSE: DNA aneuploidy, which is characterized by cells containing an abnormal number of chromosomes, is closely associated with carcinogenesis and malignant progression. Aneuploidy occurs during cell division when the chromosomes do not separate properly. Aurora kinases (Aurora-A, -B, and -C) contribute to accurate cell division, and are candidate molecular targets for mitosis-specific anticancer drugs. METHODS: We determined the expression of Aurora-A and -B in 110 gastric cancer specimens by performing an immunohistochemical analysis. We also determined the DNA content, TP53 gene mutations, and microsatellite instability in the same samples. RESULTS: We found the nuclear expression of Aurora-A and -B to increase in tumor tissue in comparison to that in normal epithelial tissue. A high Aurora-B expression significantly correlated with aneuploidy and TP53 mutations, but not with microsatellite instability. In contrast, the Aurora-A expression did not correlate with either aneuploidy or microsatellite instability. In addition, the expression of Aurora-A or -B was not significantly associated with the clinical outcomes or prognosis. CONCLUSIONS: Our results suggest that an overexpression of Aurora-B, but not of Aurora-A, might contribute to DNA aneuploidy in gastric cancers by promoting chromosomal instability.
Surgery Today 04/2013; · 1.22 Impact Factor
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Yoshihiro Kakeji, Tomonori Nakanoko,
Rintaro Yoshida,
Kojiro Eto,
Ryuichi Kumashiro,
Keisuke Ikeda,
Akinori Egashira,
Hiroshi Saeki,
Eiji Oki,
Masaru Morita,
Tetsuo Ikeda,
Yoshihiko Maehara
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ABSTRACT: Gastrointestinal stromal tumors (GISTs) should be surgically resected, even those smaller than 5 cm in size, which is the threshold of clinical malignancy for submucosal tumors (SMTs) in the gastrointestinal tract. This study reviewed the use of laparoscopic surgery for gastric partial resection of GISTs or SMTs that were suspected to be GISTs.
Eighteen patients underwent laparoscopic partial resection of the stomach for GISTs or SMTs. The tumor location was confirmed by intraluminal endoscopy. One-half of the circumference around the tumor was dissected, and the tumor was turned toward the abdominal cavity. The nonresected part of the tumor and the edge of the incision line was lifted up using forceps, and the incision line was closed using laparoscopic stapling devices.
Two cases were diagnosed as GIST by endoscopic biopsy. Six patients underwent endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) examinations, which diagnosed five GISTs. There were 18 tumors smaller than 5 cm, including 10 GISTs, 4 leiomyomas, 3 schwannomas, and one heterotopic pancreas.
Endoscopic ultrasound-guided FNAB is recommended for definite preoperative diagnosis of histopathologically unknown SMTs to determine the indications for surgery. The laparoscopic approach with the assistance of endoscopy is useful for improving the curability, with minimal invasiveness for the partial resection of GISTs.
Surgery Today 11/2011; 42(6):554-8. · 1.22 Impact Factor
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Masaru Morita, Tomonori Nakanoko,
Nobuhide Kubo,
Yoshihiko Fujinaka,
Keisuke Ikeda,
Akinori Egashira,
Hiroshi Saeki,
Hideaki Uchiyama,
Takefumi Ohga,
Yoshihiro Kakeji,
Ken Shirabe,
Tetsuo Ikeda,
Shunichi Tsujitani,
Yoshihiko Maehara
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ABSTRACT: An esophagectomy followed by reconstruction for esophageal cancer is a highly aggressive operation. The purpose of this study was to justify a two-stage operation for high-risk patients with esophageal cancer.
The clinical results of 27 patients who underwent two-stage operation were compared with 118 patients who underwent a simultaneous resection and reconstruction (control subjects). The reasons for the selection of the two-stage operation were underlying general disease in 13 patients (liver dysfunction, n = 6; pulmonary disease, n = 3; poor performance status, n = 2; diabetes and renal failure, n = 1 each) and high-risk operation in 14 other patients (colon interposition, n = 7; salvage operation after definitive chemoradiotherapy, n = 4; and intraoperative events, n = 3). The patients initially underwent an esophagectomy and a cervical esophagostomy. Reconstruction was usually performed 2-3 weeks later.
The patients in the two-stage group were older than the control patients (mean 67.8 vs. 61.6 years old). The morbidity rate of the two-stage operation was 29.6%, which was not statistically different than control patients (32.2%). Postoperative complications in the two-stage operation were anastomotic leakage in 5 patients, and pneumonia and wound infection in 1 patient each. No patient experienced in-hospital death. The survival rates were not statistically different between the two groups.
A two-stage operation is a safe operation that prevents the occurrence of critical postoperative complications, and it thus may be considered an important treatment strategy for high-risk patients with esophageal cancer.
Annals of Surgical Oncology 03/2011; 18(9):2613-21. · 4.17 Impact Factor
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ABSTRACT: LOH at the p53 locus has been reported to be associated with esophageal squamous cell carcinogenesis. The aim of this study is to identify potential mechanisms resulting in LOH around the p53 locus in its carcinogenesis.
We investigated 10 esophageal cancer cell lines and 91 surgically resected specimens, examining them for LOH at the p53 locus on chromosome 17. We examined the p53 gene by using microsatellite analysis, comparative genomic hybridization (CGH), FISH, and single-nucleotide polymorphism-CGH (SNP-CGH).
In an analysis of specimens by microsatellite markers, a close positive correlation was found between p53 mutations and LOH at the p53 locus (P < 0.01). Although four cell lines were found to be homozygous for p53 mutations, LOH at the p53 locus was not detected by CGH. Among two p53 mutant cancer cell lines and five p53 mutant/LOH cancer specimens analyzed by FISH, both the cell lines and four of the specimens exhibited no obvious copy number loss at the p53 locus. SNP-CGH analysis, which allows both determination of DNA copy number and detection of copy-neutral LOH, showed that LOHs without copy number change were caused by whole or large chromosomal alteration.
LOH without copy number change at the p53 locus was observed in p53 mutant esophageal squamous cell carcinomas. Our data suggest that copy-neutral LOH occurring as a result of chromosomal instability might be the major mechanism for inactivation of the intact allele in esophageal squamous cell carcinogenesis associated with p53 mutation.
Clinical Cancer Research 02/2011; 17(7):1731-40. · 7.74 Impact Factor
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Masaru Morita, Tomonori Nakanoko,
Yoshihiko Fujinaka,
Nobuhide Kubo,
Natsumi Yamashita,
Keiji Yoshinaga,
Hiroshi Saeki,
Yasunori Emi,
Yoshihiro Kakeji,
Ken Shirabe,
Yoshihiko Maehara
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ABSTRACT: Resections for esophageal cancer are invasive, with high mortality and morbidity rates. The object of this study was to clarify the factors associated with in-hospital death while also evaluating any associated historical changes in the characteristics of such deaths.
The factors associated with mortality were examined by logistic regression analysis in 1106 patients who underwent an esophagectomy for esophageal cancer. The historical changes in the characteristics of in-hospital deaths were also evaluated.
A multivariate analysis revealed that not only undergoing an esophagectomy before 1979, but also a patient's age (odds ratio 1.070 for every increase in age by year) and an incomplete resection (odds ratio 2.265) were independent factors associated with in-hospital death. The in-hospital mortality rates were 16.1%, 5.8%, 2.5%, and 3.1%, while the 30-day mortality rates were 9.2%, 2.2%, 0.8%, and 0.3% during 1964-1979, the 1980s, the 1990s, and the 2000s, respectively. Eight patients had preoperative comorbidities among 11 patients who died in the hospital after 1997. The mortality rate was 5.5% in patients with any comorbidities, while it was 1.3% in patients without any comorbidities (P = 0.026). The most common direct cause of in-hospital death was previous pulmonary complications; however, cancer progression has recently become the most common cause.
To prevent in-hospital mortality after an esophagectomy, strict indications for surgery and careful perioperative management are important, especially in high-risk patients with advanced esophageal cancer.
Annals of Surgical Oncology 01/2011; 18(6):1757-65. · 4.17 Impact Factor
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Masahiko Sugiyama,
Yoshihiro Kakeji,
Nobuhide Kubo, Tomonori Nakanoko,
Yoshihiko Fujinaka,
Kouji Ando,
Takanobu Masuda,
Kenji Yagi,
Keishi Yoshinaga,
Hiroshi Saeki,
Kazuya Endo,
Yasunori Emi,
Masaru Morita,
Yoshihiko Maehara
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ABSTRACT: Nowadays, the advancements of systemic chemotherapy for colorectal carcinoma improve a clinical response rate, and expand the possibility of resection which couldn't operable at the initial visit. In addition, the prognoses of the patients, who had a radical operation for metastasis, are clearly longer than the non-operable patients. Bevacizumab, anti-human VEGF monoclonal antibody, is significantly effective when used in combination with one of the systemic multi-agent chemotherapy such as FOLFOX regimen or FOLFIRI regimen. We report here two cases with colon carcinoma, which had initially unresectable liver metastases, were respond to the treatment of systemic multi-agent chemotherapy with bevacizumab. Then, both cases were able to undergo radical resections of primary tumor and liver metastases safely.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2169-71.
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Hiroyuki Kitao,
Yoshihiko Fujinaka,
Nobuhide Kubo, Tomonori Nakanoko,
Keiji Yoshinaga,
Eriko Tokunaga,
Hiroshi Saeki,
Kazuya Endo,
Masaru Morita,
Yoshihiro Kakeji,
Yoshihiko Maehara
Fukuoka igaku zasshi = Hukuoka acta medica 07/2008; 99(6):115-22.
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洋之 北尾,
良彦 藤中,
信英 久保,
智徳 中ノ子,
敬士 吉永,
えり子 徳永,
浩司 佐伯,
和也 遠藤,
勝 森田,
吉弘 掛地, [......],
ヨシヒコ フジナカ,
ノブヒデ クボ,
トモノリ ナカノコ,
ケイジ ヨシナガ,
エリコ トクナガ,
ヒロシ サエキ,
カズヤ エンドウ,
マサル モリタ,
ヨシヒロ カケジ,
ヨシヒコ マエハラ
