International Journal of Clinical Oncology (Int J Clin Oncol)

Publications in this journal

• Article: Where will the concept of lymph node micrometastasis advance?

  Shoji Natsugoe
  International Journal of Clinical Oncology 06/2013;
• Article: Intraoperative diagnosis of lymph node metastasis by transcription-reverse transcription concerted reaction assay in gastric cancer.

  Ryouichi Hirayama, Akiyoshi Seshimo, Kunitomo Miyake, Masako Nishizawa, Shingo Kameoka
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  ABSTRACT: BACKGROUND: Increasing evidence has been accumulated to substantiate the clinical usefulness of quantitative evaluation of gene expression. This study was undertaken to assess diagnosis of metastasis in dissected lymph nodes through quantitative evaluation of the expression of carcinoembryonic antigen mRNA (CEA mRNA) by a rapid, simple transcription-reverse transcription concerted reaction (TRC) assay using dissected lymph node washings. METHODS: A total of 110 dissected lymph nodes from 40 patients undergoing surgery for gastric cancer were studied. Each dissected lymph node was cut crosswise and washed with physiological saline. The washings were assayed for CEA mRNA and the assay results were assessed in comparison with the pathological diagnosis [hematoxylin and eosin (H&E) staining]. All lymph nodes were also subjected to immunostaining for cytokeratin (CK staining) and assessed comparatively. RESULTS: By H&E staining, 29 lymph nodes were found to be positive and 81 to be negative for metastasis. By TRC assay, 38 lymph nodes were found to be positive and 72 to be negative. According to the results of CK staining, there were 37 metastasis-positive lymph nodes and 73 negative nodes. The sensitivity and specificity of H&E staining relative to those of CK staining were 78.4 and 100 %, respectively, while the sensitivity and specificity of TRC assay relative to those of CK staining were 91.9 and 94.5 %, respectively. CONCLUSIONS: The TRC assay method using lymph node washings is a rapid, simple genetic diagnosis with greater sensitivity than conventional diagnosis by H&E staining of permanent specimens, and enables conservation of lymph nodes in toto as permanent specimens. This TRC method would enable rapid diagnosis even in town hospitals where no pathologist is ordinarily stationed, and is considered to contribute to the clinical application of the sentinel node theory of gastric cancer treatment.
  International Journal of Clinical Oncology 06/2013;
• Article: A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer.

  Kenya Yamanaka, Etsuro Hatano, Masashi Kanai, Shiro Tanaka, Keiichi Yamamoto, Masato Narita, Hiromitsu Nagata, Takamichi Ishii, Takahumi Machimoto, Kojiro Taura, Shinji Uemoto
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  ABSTRACT: BACKGROUND: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. METHODS: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. RESULTS: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). CONCLUSIONS: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.
  International Journal of Clinical Oncology 06/2013;
• Article: Gemcitabine and docetaxel, an effective second-line chemotherapy for lung metastasis of urothelial carcinoma.

  Taku Naiki, Noriyasu Kawai, Yoshihiro Hashimoto, Takehiko Okamura, Ryosuke Ando, Takahiro Yasui, Atsushi Okada, Toshiki Etani, Keiichi Tozawa, Kenjiro Kohri
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  ABSTRACT: BACKGROUND: The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy. METHODS: From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m(2) and docetaxel 40 mg/m(2) on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study. RESULTS: The median number of GD treatment cycles was 4 (range 2-9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %). CONCLUSIONS: The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.
  International Journal of Clinical Oncology 06/2013;
• Article: Development of a novel interferon-α2b gene construct with a repetitive hypoxia-inducible factor binding site and its suppressive effects on human renal cell carcinoma cell lines in vitro.

  Naotaka Fukui, Yukio Kageyama, Yotsuo Higashi, Kazunori Kihara, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Toshiaki Shinojima, Kenjiro Suzuki, Mototsugu Oya
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  ABSTRACT: BACKGROUND: Despite the advent of targeted therapies, interferon-alpha (IFN-α) remains a therapeutic option for advanced renal cell carcinoma (RCC), especially in Japan, with a treatment response rate of 15-20 %. To improve the efficacy of IFN-α-based therapies, we evaluated a novel treatment strategy for RCC using an IFN-α2b gene construct with a repetitive hypoxia-inducible factor binding site. METHODS: We constructed an expression plasmid designated 5HREp-IFN-α2b containing the coding region of the IFN-α2b gene. Five copies of the hypoxia-response element (HRE) sequences were inserted upstream of the IFN-α2b gene, and the construct was transfected into human RCC cell lines ACHN, 786-O and KU19-20. The concentrations of IFN-α2b in the conditioned media were measured by enzyme-linked immunosorbent assay. Cell viabilities were determined by MTS assays. RESULTS: Construct-induced IFN-α secretion was confirmed in all three cell lines. IFN-α production was significantly enhanced by the hypoxia-mimicking agent deferoxamine mesylate in cell lines expressing the wild-type von Hippel-Lindau (VHL) gene (KU19-20 and ACHN) compared with cells expressing the mutant VHL gene (786-O). The construct exerted significant suppressive effects on the viabilities of all RCC cell lines. CONCLUSION: This is the first study to report on the construction of a cytokine gene with a repetitive hypoxia-inducible factor binding site and its application in the suppression of human cancer cells. Gene therapy using this IFN-α2b gene construct with HREs may represent a novel treatment modality for advanced RCC.
  International Journal of Clinical Oncology 06/2013;
• Article: NRAS mutations in primary and metastatic melanomas of Japanese patients.

  Hisashi Uhara, Atsuko Ashida, Hiroshi Koga, Eisaku Ogawa, Aya Uchiyama, Ryuhei Uchiyama, Koichi Hayashi, Yukiko Kiniwa, Ryuhei Okuyama
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  ABSTRACT: BACKGROUND: Characterization of the MAPK signaling pathway in melanoma has led to the development of MEK inhibitors for the treatment of NRAS-mutated melanoma. The success of molecular-targeted therapies underscores the need to identify mutations in target genes. Most of the current data on genetic mutations have been obtained from Caucasian melanoma patients, and screenings of Asian populations are limited. OBJECTIVE: The aim of the present study was to examine NRAS mutations in primary and metastatic lesions of Japanese melanoma patients. METHODS: Clinical melanoma specimens were collected from 127 Japanese patients, including primary (n = 67), metastatic (n = 25) and paired primary and metastatic lesions (n = 35). NRAS mutations in exons 1 and 2 were assessed by polymerase chain reaction and Sanger sequencing. RESULTS: The incidence of NRAS mutations was 7.1 %. NRAS (Q61) was the predominant genetic alteration (77.8 %). NRAS mutations were most frequently detected in acral melanomas (9.3 %), followed by melanomas without chronic sun-induced damage (7.0 %) and mucosal melanomas (4.8 %), and were not detected in melanomas with chronic sun-induced damage. In addition, NRAS mutations were more prevalent in the extremities than in other sites. The NRAS sequence in metastatic lesions did not match that of the primary tumor in one case. CONCLUSION: The frequency of NRAS mutations is lower in the Asian population than in Caucasian patients. The observed heterogeneity of melanoma suggests that genotyping of both primary and metastatic lesions is important to identify candidate patients for molecular-targeted therapies.
  International Journal of Clinical Oncology 06/2013;
• Article: High incidence of regional and in-transit lymph node metastasis in patients with alveolar rhabdomyosarcoma.

  Yoshihiro Nishida, Satoshi Tsukushi, Hiroshi Urakawa, Hideshi Sugiura, Hiroatsu Nakashima, Yoshihisa Yamada, Naoki Ishiguro
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  ABSTRACT: BACKGROUND: Rhabdomyosarcoma has different extension patterns, including a higher propensity for lymph nodes metastasis, compared with other types of soft tissue sarcoma. The aims of this study were to investigate the patterns of regional and distant metastasis in patients with rhabdomyosarcomas, particularly lymphatic route metastasis, and clarify the clinical factors that affect the pattern of metastasis. METHODS: Forty-four patients with rhabdomyosarcomas were enrolled in this study. The mean age of the patients was 26 (range 1-69) years, and 18 were males. The histological subtypes included alveolar (17 patients), embryonal (10 patients), pleomorphic (7 patients), and unknown (10 patients). Based on location, the sarcomas were divided into three groups: extremity (17 cases), favorable prognosis (10 cases), and unfavorable prognosis (15 cases). There were three cases (7 %) of local relapse, ten cases of regional lymph node relapse, and three cases of in-transit metastasis (total 30 %). Twenty-one patients (48 %) developed distant metastases. Initial sites of metastases were bone (9 patients, 20 %), lung (5 patients), and bone marrow dissemination (5 patients). Clinico-pathological variables affecting relapse patterns were analyzed. RESULTS: Of the three cases of local relapse, two were alveolar type and one was unknown. The three cases of in-transit metastasis were all alveolar type. Patients with alveolar type had a significantly high propensity for lymph node metastasis (P = 0.027). Excluding the pleomorphic type, alveolar type was still a significant factor for lymph node metastasis (P = 0.017). CONCLUSION: Physicians should be aware of in-transit spread, particularly in patients with alveolar-type rhabdomyosarcoma. Novel treatment modalities are required to detect and treat in-transit metastasis.
  International Journal of Clinical Oncology 06/2013;
• Article: Possible peripheral mechanism for taste disorder in rats administered S-1.

  Kumiko Aoki, Koji Obata, Miyako Kurihara, Hiroki Kuniyasu, Tadaaki Kirita, Miyako Takaki
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  ABSTRACT: BACKGROUND: Taste disorders are frequently observed in cancer patients undergoing chemotherapy and are serious adverse events which impair the quality of life (QoL) of the cancer patient. Nevertheless, taste disorder mechanisms in cancer patients undergoing chemotherapy have not yet been fully elucidated. The aim of this study was to reveal taste disorder-related peripheral mechanisms using the two-bottle preference test (TBPT) and histological examination of tongues by hematoxylin-eosin staining and immunohistochemistry with protein-gene product 9.5. METHODS: In the TBPT, one bottle was filled with the 0.01 mM quinine hydrochloride (quinine), as a bitter compound, and the other was filled with water. Doses of 50 and 100 mg kg(-1) day(-1) S-1 (tegafur/gimeracil/oteracil potassium) are lethal to Wistar rats. Therefore, doses ranging from 2-20 mg kg(-1) day(-1) were administered to the rats for 3 weeks. The S-1 dose of 2 mg kg(-1) day(-1) corresponds to the clinical dose administered to cancer patients. The part of the tongue containing the circumvallate papillae was excised the following TBPT. RESULTS: The rate of increase in terms of the average preference rate for the quinine vs. all intake (quinine plus water) was significant from the initial S-1 period to the final one, compared with that in control rats, suggesting the possibility of a worsening sensation for the bitter taste. In S-1 rats, the area of taste nerve fibers were significantly decreased and the rate of degeneration of intra-tongue ganglionic nerve cells was significantly increased. These changes were significantly correlated with the rate of increase in average preference rate of the quinine. CONCLUSION: Neuropathy of the gustatory nerve at the periphery may be involved in taste disorders induced by an anticancer drug.
  International Journal of Clinical Oncology 06/2013;
• Article: Do hormone treatments for prostate cancer cause anxiety and depression?

  Christopher F Sharpley, David R H Christie, Vicki Bitsika
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  ABSTRACT: BACKGROUND: To investigate the relationship between hormone therapy (HT) and incidence of anxiety and depression among prostate cancer patients (PCa). METHODS: 526 PCa patients completed a survey about their cancer status, treatment received, anxiety, and depression status. Total scores on anxiety and depression inventories, plus symptom profiles that discriminated between patients with current HT, past HT, and never having received HT, were compiled for analysis. RESULTS: Patients who were currently receiving HT had significantly higher total anxiety and depression scores than patients who had previously received HT or who had never received HT. Analysis of the symptoms of anxiety and depression which distinguished between these groups of patients suggested that patients who had never received HT had significantly lower scores than current or past HT patients. Although several symptoms could be directly allocated to PCa and/or HT, symptom profiles were indicative of clinically significant anxiety and/or depression in patients who were currently receiving, or who had previously received, HT. CONCLUSION: Current HT may lead to symptoms of anxiety and/or depression which require clinical attention. These effects seem to decrease after completion of HT.
  International Journal of Clinical Oncology 06/2013;
• Article: Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer: long-term follow-up results.

  Masahiro Morimoto, Fumiaki Isohashi, Yasuo Yoshioka, Osamu Suzuki, Yuji Seo, Toshiyuki Ogata, Yuichi Akino, Masahiko Koizumi, Kazuhiko Ogawa
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  ABSTRACT: BACKGROUND: We retrospectively examined outcomes of salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) for locally recurrent rectal cancer (LRRC). METHODS: Nine patients with LRRC were treated with salvage HDR-ISBT. Their median age was 63 years. The median maximum diameter of LRRC was 40 mm (range 20-80 mm). Adenocarcinomas were histologically confirmed in all cases. The prescribed dose was 30 Gy/5 fractions/3 days to 50 Gy/10 fractions/6 days in the combined external-beam radiotherapy group (four patients) and 54 Gy/9 fractions/5 days to 60 Gy/10 fractions/6 days in the monotherapeutic group (five patients). Median follow-up time was 90 months (range 6-221 months). RESULTS: Local control at final follow-up was achieved in five of nine patients. Of these five patients, one experienced a locally re-recurrent tumor in the vaginal wall 33 months after treatment and received re-HDR-ISBT as re-salvage treatment. The 8-year overall survival, local control, and progression-free survival rates were 56, 44, and 33 %, respectively. Based on the Common Terminology Criteria for Adverse Events ver. 4.03, the following Grade 3 adverse events were observed in three patients (≥3 months): Grade 3 skin ulceration in one patient who showed tumor invasion of the skin and whose V100 was 400 cc; Grade 3 vaginal perforation in one patient whose tumor had invaded the vaginal wall; and Grade 3 vagina-to-bladder fistula in one patient whose tumor received re-irradiation. Late adverse events above Grade 3 were not observed. CONCLUSIONS: Long-term follow-up results revealed that salvage HDR-ISBT is a promising treatment for LRRC with tolerable toxicity.
  International Journal of Clinical Oncology 06/2013;
• Article: Amino acid profile index for early detection of endometrial cancer: verification as a novel diagnostic marker.

  Yutaka Ihata, Etsuko Miyagi, Reiko Numazaki, Takahiko Muramatsu, Akira Imaizumi, Hiroshi Yamamoto, Minoru Yamakado, Naoyuki Okamoto, Fumiki Hirahara
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  ABSTRACT: BACKGROUND: Plasma amino acid profiles (PAAPs) vary in individual cancer patients, and it has been suggested that they may be useful for early detection of several types of cancer. We evaluated the diagnostic performance of a profile index for endometrial cancer composed of multiple plasma amino acids as a novel biomarker and compared its diagnostic performance with that of CA125. METHODS: Plasma amino acid levels of 80 patients with endometrial cancer, 122 with benign gynecological diseases, and 240 age- and body mass index-matched control subjects were measured using liquid chromatography and mass spectrometry. After univariate analysis, we applied a multiplex model based on the PAAP multivariate analysis to distinguish patients with endometrial cancer from control subjects. We compared the diagnostic performance of the multiple PAAP index (API) with that of CA125. RESULTS: The levels of several plasma amino acids were significantly different in patients with endometrial cancer. The area under the receiver operating characteristic curves (AUC) used to distinguish endometrial cancer patients from control subjects was 0.94. The AUC for API was significantly larger than that for CA125 (P = 0.0068). For the same specificity of 98.3 %, API showed a significantly higher sensitivity (60.0 %, 95 % CI, 43.3-75.1) than that of CA125 (22.5 %, 95 % CI, 10.1-38.5). In stage I cases, API showed significantly higher positivity than that of CA125 (P = 0.0002). CONCLUSIONS: The sensitivity and disease specificity of API for early-stage detection of endometrial cancer was superior to CA125. This novel plasma biomarker has the potential to become a diagnostic and screening marker for endometrial cancer.
  International Journal of Clinical Oncology 05/2013;
• Article: Safety and efficacy of nimotuzumab in combination with radiotherapy for patients with squamous cell carcinoma of the esophagus.

  Ning-Yi Ma, Xu-Wei Cai, Xiao-Long Fu, Yuan Li, Xiao-Yan Zhou, Xiang-Hua Wu, Xi-Chun Hu, Min Fan, Jia-Qing Xiang, Ya-Wei Zhang, Hai-Quan Chen, Song-Tao Lai, Guo-Liang Jiang, Kuai-Le Zhao
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  ABSTRACT: BACKGROUND: We investigated nimotuzumab (h-R3), a humanized monoclonal antibody against epidermal growth factor receptor, when combined with irradiation or chemoradiation for squamous cell carcinoma (SCC) of the esophagus. The aim of this study was to evaluate its safety and efficacy. METHODS: We retrospectively analyzed 66 patients with esophageal SCC treated with a combination of h-R3 and radiation or chemoradiation between December 2008 and September 2011 at Fudan University Shanghai Cancer Center. Fifty-two of the 66 patients received h-R3 combined with chemoradiation and 14 received h-R3 plus radiation. The median total irradiation dose was 61 Gy given by conventional fractionation. The h-R3 weekly dosage was 100 mg (6/66), 200 mg (54/66), or 400 mg (6/66) given concurrently during the irradiation period. RESULTS: Patients tolerated the treatment well. Grade 3-4 adverse events and toxicities occurred in 50 % of the patients. h-R3-related toxicities manifested as Grade 1 skin rash in 1 case and Grade 2 infusion-related reaction in 2 cases. The median overall survival (OS) and progression-free survival (PFS) were 26.0 months and 16.7 months, respectively. OS, PFS and locoregional control (LC) at 2 years were 54, 37 and 80 %, respectively. CONCLUSIONS: h-R3 in combination with irradiation or chemoradiation was safe and tolerable, and yielded encouraging OS, PFS and LC.
  International Journal of Clinical Oncology 05/2013;
• Article: Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression.

  Tze Fang Wong, Takashi Takeda, Bin Li, Kenji Tsuiji, Akiko Kondo, Mari Tadakawa, Satoru Nagase, Nobuo Yaegashi
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  ABSTRACT: BACKGROUND: Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma. METHODS: Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2-3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors. RESULTS: Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups. CONCLUSION: Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.
  International Journal of Clinical Oncology 05/2013;
• Article: Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer.

  Yiting Geng, Xiaofeng Chen, Jinrong Qiu, Yue Zhou, Jian Wang, Lingxiang Liu, Yongfeng Shao, Yongmei Yin
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  ABSTRACT: BACKGROUND: Amplification and overexpression of human epidermal growth factor receptor-2 (HER-2) has been shown in subgroups of gastric cancer, correlated to more aggressive disease and predictive for the treatment with HER-2 antibodies. In this study, we examined the prognostic value of HER-2 expression in primary gastric cancer and in associated lymph node metastases and confirmed the role of HER-2 in tumor angiogenesis by examining vascular endothelial growth factor (VEGF) expression. METHODS: Immunohistochemistry was used to detect HER-2 and VEGF expression in 110 gastric cancer specimens and associated lymph node metastases and in 96 specimens of normal gastric mucosa. RESULTS: The expression level of HER-2 in gastric tissues was significantly higher than in normal tissues (19.1 % vs. 8.3 %; P < 0.05). HER-2 overexpression was homogeneous in primary gastric cancer and metastatic lymph nodes (P = 0.607). There was a significant positive correlation of HER-2 expression and VEGF expression (P = 0.007). HER-2 overexpression in primary tumor correlated with lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Cox regression multivariate analyses confirmed that tumor size, histological grade, lymph node ratio, AJCC stage, chemotherapy, and HER-2 expression were all prognostic factors. Patients with HER-2 positivity in both primary and metastatic tissues (+/+) had the poorest survival (OS, 12.5 months; DFS, 11.0 months) (P < 0.01). CONCLUSIONS: HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.
  International Journal of Clinical Oncology 05/2013;
• Article: Idiopathic pulmonary fibrosis as a prognostic factor in non-small cell lung cancer.

  Taichiro Goto, Arafumi Maeshima, Yoshitaka Oyamada, Ryoichi Kato
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  ABSTRACT: BACKGROUND: We investigated the postoperative mortality and long-term survival of lung cancer patients with underlying idiopathic pulmonary fibrosis (IPF). METHODS: The data of 387 primary lung cancer patients treated by surgical resection at our hospital between 1995 and 2008 were retrospectively reviewed. Clinicopathological characteristics such as age, gender, survival, presence/absence of underlying IPF, atypical adenomatous hyperplasia (AAH), and the associations among these factors were examined. RESULTS: Among the 387 patients, 65 (16.8 %) had underlying IPF as detected by histopathology of the resected specimen (IPF group). The percentages of men and squamous cell carcinomas were significantly higher in the IPF group. None of our patients showed concomitant presence of AAH and IPF. Four of the 65 patients showed acute exacerbation of the IPF postoperatively, and all 4 of these patients died in hospital. In patients with non-small cell lung carcinoma, the postoperative survival tended to be lower in the IPF group than in the non-IPF group. Analysis using a Cox proportional hazards model by disease stage revealed that presence of underlying IPF was a risk factor for postoperative mortality in patients with pathological stage I/II but not for stage III/IV. Respiratory failure was the second main cause of death in the stage I/II lung cancer patients of the IPF group. CONCLUSION: Histopathological evidence of IPF was a risk factor for postoperative mortality and poor long-term survival, especially in patients with stage I/II non-small cell lung cancer, with postoperative respiratory failure representing the major cause of death.
  International Journal of Clinical Oncology 05/2013;
• Article: Clinicopathologic characteristics and survival of male breast cancer.

  Dongying Liu, Guangru Xie, Ming Chen
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  ABSTRACT: BACKGROUNDS: Male breast cancer (MBC) is a rare disease and accounts for <1 % of all breast cancers. METHODS: We retrospectively analyzed clinicopathologic characteristics and prognosis of MBC patients who were diagnosed in our hospital between March 2002 and March 2012. RESULTS: The median age of diagnosis of MBC was 62 years, which was 9 years older than female breast cancer (FBC) patients. The highest proportion of MBC patients was in the 50-59-year age group. The percentage of invasive ductal carcinoma in MBC was much higher than in FBC (P = 0.000). The positive rate of estrogen receptors in MBC patients (87.9 %) was significantly higher than in FBC patients (P = 0.048), whereas HER-2 was positive in 17.2 % of MBC patients, which was significantly lower than in FBC patients (P = 0.001). There was a consistent significant difference in luminal subtypes of FBC and MBC patients (P = 0.000). The overall survival rates of MBC were significantly higher than FBC (P = 0.004). HER-2-positive patients had a statistically worse prognosis than HER-2-negative patients (P = 0.040). Lymph node metastasis and larger tumor size were also associated with poorer prognosis (P = 0.056 and P = 0.088). The level of hormones was examined in 7 patients, and abnormal hormone levels were detected in 4. CONCLUSION: The FBC patients were significantly different from the MBC in clinicopathologic and prognostic characteristics. HER-2 positivity was an important factor for prognosis.
  International Journal of Clinical Oncology 05/2013;
• Article: Old but new methods in radiation oncology.

  Keisuke Sasai
  International Journal of Clinical Oncology 04/2013;
• Article: Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia.

  Takashi Shibata, Yosuke Minami, Ayako Mitsuma, Sachi Morita, Megumi Inada-Inoue, Tomoyo Oguri, Tomoya Shimokata, Mihoko Sugishita, Tomoki Naoe, Yuichi Ando
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  ABSTRACT: BACKGROUND: Nilotinib is a BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism UGT1A1*28 (*28)/*28 has been linked to an increased risk of hyperbilirubinemia in patients with CML who receive nilotinib. Beside *28, UGT1A1*6 (*6) is another important variant allele in Japanese patients because it is associated with adverse events of irinotecan, metabolized by UGT1A1. We retrospectively investigated the association between severe toxicity of nilotinib and UGT1A1 polymorphisms (*6 and*28) in Japanese patients with CML. PATIENTS AND METHODS: Eight patients with cytogenetically confirmed CML who were receiving nilotinib were studied to explore the association of UGT1A1 polymorphisms with severe nilotinib-related toxicity. Genotyping analyses were determined for *6 and *28. RESULTS: All 3 patients with the *6/*6 or *6/*28 genotype had severe toxicity, including QT interval prolongation (grade 3), elevated lipase levels (grade 3) plus hyperbilirubinemia (grade 2), and anemia (grade 3) plus hepatic cyst hemorrhage (grade 2) in 1 patient each. Among the 5 patients with the *6/*1 or *1/*1 genotype, 1 had elevated lipase levels (grade 3) and another had severe pain in the lower extremities (grade 3). CONCLUSION: These findings suggest that UGT1A1 polymorphisms are important determinants of severe toxicity of nilotinib in Japanese patients.
  International Journal of Clinical Oncology 04/2013;
• Article: Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials.

  Wei-Xiang Qi, Li-Na Tang, Ai-Na He, Yang Yao, Zan Shen
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  ABSTRACT: AIMS: The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab. METHODS: We performed a meta-analysis of relevant randomized controlled trials identified in Pubmed, Embase, and Cochrane databases. Abstracts presented at the conferences were also searched. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: A total of 8963 patients with a variety of solid tumors from 7 randomized controlled trials (RCTs) were included for the meta-analysis. The overall incidence of ONJ in cancer patients receiving denosumab was 1.7 % [95 % CI: 0.9-3.1 %]. Also, the use of denosumab was associated with significantly increased risk of ONJ in comparison with bisphosphonates (BPs)/placebo treatment (RR 1.61, 95 % CI: 1.05-2.48, P = 0.029). Subgroup analysis based on controlled therapies demonstrated an increased risk of ONJ in denosumab therapy, when compared with BPs (RR 1.48, 95 % CI: 0.96-2.29, P = 0.078) or placebo (RR 16.28, 95 % CI: 1.68-158.05, P = 0.017). Similar results were observed in prostate cancer (RR 3.358, 95 % CI: 1.573-7.166, P = 0.002) while there was a non-significantly increased risk of denosumab-related osteonecrosis of the jaw (DONJ) in non-prostate cancers (RR 1.142, 95 % CI: 0.678-1.921, P = 0.618). CONCLUSIONS: The use of denosumab is associated with an increased risk of developing ONJ when compared with BP treatment or placebo, although the increased risk was not statistically significant between denosumab and BP treatment. Further studies are still needed to establish guidelines for the prevention and effective treatment of ONJ.
  International Journal of Clinical Oncology 04/2013;