Details of a Researcher - Nakamura, Rieko

Papers - Nakamura, Rieko

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Optimal minimally invasive surgical procedure for gastric submucosal tumors

Shoji Yoshiaki, Takeuchi Hiroya, Goto Osamu, Tokizawa Kazunori, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Yahagi Naohisa, Kitagawa Yuko

Gastric Cancer 1 - 8 2017.07

ISSN 1436-3291

Background: Laparoscopic wedge resection (LWR) is widely performed for managing gastric submucosal tumors (SMTs). Despite the development of novel procedures such as laparoscopy–endoscopy cooperative surgery (LECS) and nonexposed endoscopic wall-inversion surgery (NEWS), the most appropriate surgical intervention for gastric SMTs remains unclear. Methods: We retrospectively reviewed patient characteristics, surgical outcomes, postoperative courses, results of histopathological examinations, and surgical costs of 71 consecutive patients who underwent LWR, LECS, or NEWS for gastric SMTs from January 2010 to June 2016 in our institute. Results: LWR, LECS, and NEWS were performed in 31, 14, and 26 cases, respectively. Patient backgrounds were comparable between groups. LWR was not performed for esophagogastric (E–G) junction tumors to avoid postoperative stricture, and LECS was not performed for ulcerated tumors to prevent tumor dissemination. NEWS was considered for tumors smaller than 3 cm for transoral extraction. Resected specimen area of the LWR group was significantly larger than that of the other groups. Further, the LWR group had a significantly higher complication rate. Compared to the LECS group, postoperative serum C-reactive protein level was significantly lower and postoperative hospitalization was significantly shorter in the NEWS group. Also, operation costs were significantly lower in the NEWS group. Conclusions: The surgical procedure for gastric SMTs must be carefully chosen according to tumor size, location, and presence or absence of ulceration. For selected patients, NEWS is suggested to be an appropriate option for the treatment of gastric SMTs.

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Prognostic Impact of Change in the Fibrinogen and Albumin Score During Preoperative Treatment in Esophageal Cancer Patients

Matsuda Satoru, Takeuchi Hiroya, Kawakubo Hirofumi, Fukuda Kazumasa, Nakamura Rieko, Suda Koichi, Wada Norihito, Kitagawa Yuko

World Journal of Surgery 1 - 8 2017.06

ISSN 0364-2313

Background: For resectable advanced esophageal cancer, a transthoracic esophagectomy following preoperative treatment is recognized as one of the standard treatments. Therefore, predictive markers which can be identified before surgery need to be established to identify patients with a poor prognosis. Methods: We retrospectively reviewed 102 consecutive patients who underwent curative transthoracic esophagectomy following preoperative treatment in our institution between 2004 and 2013. Based on plasma fibrinogen and serum albumin levels, the pretreatment and preoperative fibrinogen and albumin score (FA score) were investigated and the prognostic significance of the FA score change was compared with RECIST. Results: The patients were classified according to whether the FA score had remained unchanged or decreased (n = 77) or the FA score increased (n = 25). When the correlation between the response rate and change in the FA score was investigated, the response rate was significantly lower in the group with the increased FA score. In the survival analysis, patients in the increased FA score group exhibited a significantly worse recurrence-free survival (RFS) (P = 0.038). A multivariate analysis using the clinical stage and the change in the FA score as covariates revealed that a change in the FA score (HR 1.802; P = 0.047; 95% CI 1.008–3.221) was shown to be a significant independent predictive factor for RFS. Conclusions: A change in the FA score was shown to be an independent prognostic factor for postoperative recurrence in esophageal cancer patients who have undergone transthoracic esophagectomy following preoperative treatment.

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The alpha-lipoic acid derivative DHLHZn

Shoji Yoshiaki, Takeuchi Hiroya, Fukuda Kazumasa, Fukunaga Koichi, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Miyasho Taku, Hiratsuka Takahiro, Inomata Masafumi, Betsuyaku Tomoko, Kitagawa Yuko

Inflammation Research 1 - 9 2017.06

ISSN 1023-3830

Objective and design: An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action. Material: Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(−) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn). Treatment: Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(−) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration. Methods: Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann–Whitney U test. Results: Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(−) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(−) group (p < 0.001). Conclusions: Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.

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Laparoscopy-assisted distal gastrectomy in a case of gastric cancer with situs inversus totalis

Kigasawa Yu, Takeuchi Hiroya, Kawakubo Hirofumi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kitagawa Yuko

Asian journal of endoscopic surgery 10 ( 1 ) 47 - 50 2017.02

ISSN 1758-5902

Situs inversus totalis (SIT) is a rare congenital condition in which abdominal and thoracic organs are transposed from normal positions. Laparoscopy-assisted distal gastrectomy for situs inversus totalis is technically difficult and has rarely been reported. Here, we report the case of man in his 40s with situs inversus totalis and a preoperative diagnosis of stage IA gastric cancer (cT1b, cN0, cM0). We successfully performed laparoscopy-assisted distal gastrectomy with D1+ lymph node dissection and Billroth I reconstruction. To ensure a safe procedure, we evaluated the vessels preoperatively with 3-D CT angiography. Furthermore, we performed the surgery by reversing our surgical positions, using a two-monitor method, and then reconstructing under direct vision through the incision. The surgery was performed with minimal blood loss, and no severe postoperative complications were observed. Histopathological examination revealed poorly to moderately differentiated stage IA (pT1b, pN0, pM0) adenocarcinoma. No recurrence has been observed as of 2 years postoperatively.

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Evaluation of pharyngo-oesophageal involvement in pemphigus vulgaris and its correlation with disease activity

Okamura A., Nakamura R., Yamagami J., Ishii K., Kawakubo H., Omori T., Takeuchi H., Amagai M., Kitagawa Y.

British Journal of Dermatology 176 ( 1 ) 224 - 226 2017.01

ISSN 0007-0963

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Soft palatal melanosis, a simple predictor for neoplasia in the upper aerodigestive tract in Japanese alcoholic men

Hirata Kenro, Yokoyama Akira, Nakamura Rieko, Omori Tai, Kawakubo Hirofumi, Mizukami Takeshi, Maruyama Katsuya, Kanai Takanori, Yokoyama Tetsuji

Cancer Science 2017

ISSN 1347-9032

Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. The aim of this study was to evaluate the association between squamous cell neoplasia in the upper aerodigestive tract (UAT) and soft palatal melanosis. We reviewed digitized records of high-quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening. Soft palatal melanosis was observed in 381 (21.3%) of the subjects (distinct, 6.3%). Older age, an inactive heterozygous aldehyde dehydrogenase-2 genotype, smoking, and a high mean corpuscular volume were positively associated with the presence of soft palatal melanosis. The age-adjusted odds ratio (95% confidence interval) for UAT neoplasia was 1.92 (1.40-2.64) in the group with melanosis and 2.51 (1.55-4.06) in the group with distinct melanosis, compared with the melanosis-free group. A multivariate analysis showed that the presence of soft palatal melanosis was independently associated with a high risk of UAT neoplasia. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, mean corpuscular volume ≥106 fL, and distinct soft palatal melanosis. Compared with the risk-factor-free condition, the odds ratio (95% confidence interval) values of UAT neoplasia for one, two, three, and four risk factors were 1.49 (0.97-2.30), 3.14 (2.02-4.88), 4.80 (2.71-8.51), and 7.80 (2.17-28.1), respectively. The presence of soft palatal melanosis provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.

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Endoscopic findings of laryngopharyngeal and esophageal involvement in autoimmune bullous disease

Nakamura Rieko, Omori Tai, Suda Koichi, Wada Norihito, Kawakubo Hirofumi, Takeuchi Hiroya, Yamagami Jun, Amagai Masayuki, Kitagawa Yuko

Digestive Endoscopy 2017

ISSN 0915-5635

Background and Aim: Autoimmune bullous disease (ABD) is induced by autoantibodies against cell adhesion molecules, and blistering may occur on the mucous membranes of the eyes, nose, mouth, oral cavity, laryngopharynx, and esophagus. Endoscopic prevalence and features of ABD-associated esophageal lesions are not well known. We conducted the present study to assess the endoscopic prevalence of ABD-associated mucosal lesions. Methods: Endoscopic prevalence of mucosal lesions, particularly laryngopharyngeal and esophageal lesions, was used as the primary endpoint to assess the significance of upper gastrointestinal endoscopy, and clinical and endoscopic features were secondary endpoints. Results: Of 123 ABD patients, 50.4% had apparent oral or laryngopharyngeal lesions and 30.8% had laryngopharyngeal lesions. Esophageal lesions were detected through normal observation in 16.8% of affected patients, whereas 40.6% exhibited epidermolysis or blood blisters by mechanical inducement, regardless of esophageal mucosal lesion detection by normal observation. Additionally, 56.0% exhibited the Nikolsky sign with mechanical inducement. Of the 123 patients, 29.2% did not have exposed skin lesions. Of these patients, 77.7% had oral cavity or laryngopharyngeal lesions, 36.1% had esophageal lesions, and 58.3% exhibited the Nikolsky sign on esophageal mucosa. Conclusion: It is important to determine the endoscopic characteristics and findings of ABD. ABD can be suspected from endoscopic findings.

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Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma

Takesue Tomoko, Kawakubo Hirofumi, Hayashida Tetsu, Tsutsui Mai, Miyao Kazuhiro, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Takeuchi Hiroya, Kitagawa Yuko

Oncology Letters 14 ( 4 ) 4220 - 4224 2017

ISSN 1792-1074

Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

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Two atypical cases of esophagogastric junctional bronchogenic cyst

Kigasawa Yu, Takeuchi Hiroya, Kamiya Satoshi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Tsujikawa Hanako, Kameyama Kaori, Kitagawa Yuko

Esophagus 1 - 4 2016.12

ISSN 1612-9059

Bronchogenic cysts are congenital lesions that are derived from the lung bud and are often found in the thoracic cavity, and intra-abdominal bronchogenic cysts are really rare. They are associated with respiratory symptoms and typically require surgical resection. Herein, we describe two cases with esophagogastric junctional bronchogenic cysts. Our first case was a man in his 30s who had a submucosal tumor at esophagogastric junction, which required laparoscopic enucleation. The second case was a woman in her 50s who underwent laparoscopy-assisted proximal gastrectomy. The resected tumor was diagnosed as a bronchogenic cyst, with squamous cell carcinoma at the mucosal surface. Bronchogenic cysts are occasionally associated with complications and malignancies, and thus, preventive and diagnostic resection is recommended.

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CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis

Uchi Yusuke, Takeuchi Hiroya, Matsuda Sachiko, Saikawa Yoshiro, Kawakubo Hirofumi, Wada Norihito, Takahashi Tsunehiro, Nakamura Rieko, Fukuda Kazumasa, Omori Tai, Kitagawa Yuko

BMC Cancer 16 ( 1 ) 2016.07

ISSN 1471-2407

Background: The chemokine CXCL12 and its corresponding receptor CXCR4 are key players in the development of several cancers. Therefore, we hypothesized that there is a functional causality between CXCL12 expression and tumor progression in patients with esophageal squamous cell carcinoma (ESCC). Methods: We performed an immunohistochemical analysis in 79 consecutive patients with ESCC. We performed in vitro and in vivo cell proliferation assays using ESCC cell lines and a newly established transfectant stably overexpressing CXCL12. Results: Immunohistochemistry revealed positive CXCR4 and CXCL12 expression in 48 (61 %) and 62 (78 %) patients, respectively. Additionally, the expression levels did not significantly correlate with any clinicopathological factors. The MIB-1 proliferation index was markedly higher in ESCC with a positive expression of CXCR4 or CXCL12. Positive CXCL12 expression was significantly correlated with lower recurrence-free survival (RFS, p = 0.02). Cox's hazard models revealed CXCL12 expression as an independent predictive factor for recurrence. In vitro, CXCL12 exposure or overexpression enhanced ESCC proliferation; and AMD3100, a specific inhibitor of CXCR4, equally decreased proliferation irrespective of CXCL12 exposure or overexpression. In the mouse model, AMD3100 significantly decreased ESCC tumor size (p = 0.03). Conclusions: CXCL12 stimulates ESCC proliferation, and its expression levels are related to lower RFS in patients with ESCC. Our findings indicate that positive CXCL12 expression may be a useful marker for predicting the outcome in patients with ESCC and is a potentially new therapeutic target for ESCC.

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Pylorus-Preserving Surgery Based on the Sentinel Node Concept in Early Gastric Cancer

Shimada Ayako, Takeuchi Hiroya, Ono Taiki, Kamiya Satoshi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Nakahara Tadaki, Jinzaki Masahiro, Murakami Koji, Kitagawa Yuko

Annals of Surgical Oncology 1 - 6 2016.06

ISSN 1068-9265

Background: In patients with early stage gastric cancer in the middle third of the stomach, pylorus-preserving gastrectomy (PPG) can be an option as function-preserving surgery, although its oncologic safety is not definitively defined. This issues may be overcome using the sentinel node (SN) concept. The aim of this study was to investigate the effectiveness of the SN concept in early gastric cancer patients who are candidates for PPG. Methods: One hundred fifty-six patients with middle-third location of cT1N0 gastric cancer (single lesion,

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Clinical outcome of transthoracic esophagectomy with thoracic duct resection Number of dissected lymph node and distribution of lymph node metastasis around the thoracic duct

Matsuda Satoru, Takeuchi Hiroya, Kawakubo Hirofumi, Shimada Ayako, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kameyama Kaori, Kitagawa Yuko

Medicine (United States) 95 ( 24 ) 2016.06

ISSN 0025-7974

The number of dissected lymph nodes (LNs), surgical outcomes, and postoperative recurrence-free survival (RFS) were compared between thoracic duct (TD)-preserved and TD-resected groups. The distribution of metastasis in LNs around TD (TDLN) was reviewed. Transthoracic esophagectomy (TTE) with TD resection for esophageal cancer patients has been one of the standard procedures. Because the adipose tissue surrounding the TD contains LNs, TD resection might be necessary for radical LN dissection. However, few studies have investigated the oncological outcome of TTE with TD resection. Two hundred fifty-six consecutive patients who underwent TTE between 2004 and 2015 were retrospectively reviewed and classified into TD-preserved or TD-resected groups. The number of dissected LNs for each LN station and surgical outcomes were compared. RFS was analyzed in 155 patients who underwent TTE before December 2012. Since 2013, the TDLN number was prospectively examined, independent of the regional LNs (n=72). Of these, the TDLN number for each location (TDLN-Ut/Mt/Lt) was investigated and the correlation between TDLN metastasis and clinicopathological factors was analyzed. The TD was preserved in 89 patients and resected in 167 patients. Patients with TD resection showed significant advanced stage. There was no significant difference in the incidence of postoperative complications, including pneumonia, anastomotic leakage, and chylothorax. The number of dissected mediastinal LNs was significantly increased in the TD-resected group. The 5-year RFS rate of cStage I patients was 67.3% in the TD-preserved group against 90.3% in the TD-resected group, showing a tendency towards RFS extension that did not quite reach statistical significance (P=0.055). The mean TDLN-Ut/Mt/Lt numbers were 0.89/0.56/0.44, respectively. Eight of 72 (11%) patients displayed TDLN metastasis. Metastatic TDLNs were observed on the same or cranial level of the primary lesion in 7 of 8 patients. Transthoracic esophagectomy with TD resection could increase the number of dissected mediastinal LNs without increase of postoperative complication. TDLN metastasis was observed in patients with advanced disease. A prospective trial, investigating the survival between TD-preserved and TD-resected groups, should be conducted to clarify if TD should be resected in TTE.

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Salvage endoscopic resection as a treatment for locoregional failure or recurrence following chemoradiotherapy or radiotherapy for esophageal cancer

Nakamura Rieko, Omori Tai, Takeuchi Hiroya, Kawakubo Hirofumi, Takahashi Tsunehiro, Wada Norihito, Saikawa Yoshiro, Kitagawa Yuko

Oncology Letters 11 ( 6 ) 3631 - 3636 2016.06

ISSN 1792-1074

Radiotherapy (RT) or chemoradiotherapy (CRT) is a potentially curative, non-surgical treatment option for esophageal cancer, although the rate of local failure within the esophagus remains relatively high. Salvage esophagectomy is not regarded as a common treatment for esophageal cancer, since it is a high-risk surgery with a relatively high surgical mortality rate. Salvage endoscopic resection (ER) for local failure is used for treatment when esophageal cancer is localized and superficial. To evaluate to usefulness of salvage ER, the present study reviewed the clinicopathological records and follow-up data of 37 patients that underwent salvage ER for esophageal cancer, following initial treatment with RT or CRT. Salvage ER was conducted on a total of 78 lesions observed in the 37 patients. Since a thick epithelium and lack of normal vessels on the surface of the mucosa are characteristics of esophageal mucosa following RT or CRT, almost all the lesions were detected using iodine dyeing, and not by narrow band imaging. The growth rate of the detected lesions was relatively high, and early treatment was required. No particular complications occurred during the endoscopic treatment. A total of 11 patients survived for >5 years subsequent to initial endoscopic treatment. Only 4 patients succumbed to esophageal cancer. In conclusion, the present study demonstrated that salvage ER following CRT or RT for esophageal cancer is a minimally invasive, safe, adaptive and curative method for superficial lesions without distant metastases in patients with esophageal cancer with local failure following CRT or RT.

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Xanthogranulomatous gastritis of the remnant stomach mimicking a malignant tumor

Okamura Akihiko, Takahashi Tsunehiro, Saikawa Yoshiro, Nakadai Jumpei, Ono Taiki, Nakamura Rieko, Wada Norihito, Kawakubo Hirofumi, Takeuchi Hiroya, Emoto Katsura, Sasaki Aya, Kameyama Kaori, Kitagawa Yuko

Oncology Letters 11 ( 2 ) 1453 - 1456 2016.02

ISSN 1792-1074

Xanthogranulomas are known to develop in the gallbladder and kidney. Xanthogranuloma of the stomach is a rare disease, and to the best of our knowledge, only a few cases have been reported to date. The present patient was a 64-year-old man who underwent a wide resection of the stomach following a Billroth-I reconstruction for a gastric ulcer ~40 years prior to the current presentation. Due to tarry stools, a gastrointestinal endoscopy was performed, leading to identification of an ulcerated gastric lesion located at the previous suture line at the lesser curvature of the remnant stomach. This lesion was elevated, appearing to indicate a submucosal tumor. Positron emission tomography revealed uptake of fluorodeoxyglucose radiotracer by the tumor. Although not indicated by the biopsy specimens, a malignant tumor of the remnant stomach was suspected, in the form of a malignant gastrointestinal tumor or remnant gastric cancer. Curative resection of the tumor was successfully performed. Histological examination of the resected specimens revealed xanthogranulomatous inflammation consisting of foamy histiocytes and plasma cells, however, no cancer cells were observed. The tumor was diagnosed as xanthogranulomatous gastritis that mimicked a malignant tumor of the remnant stomach. The present study therefore indicates that inflammatory tumors should be considered in the differential diagnosis of malignant tumors.

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Auxiliary diagnosis of lymph node metastasis in early gastric cancer using quantitative evaluation of sentinel node radioactivity

Kamiya Satoshi, Takeuchi Hiroya, Nakahara Tadaki, Niihara Masahiro, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Murakami Koji, Kitagawa Yuko

Gastric Cancer 1 - 8 2015.11

ISSN 1436-3291

Background: Sentinel node (SN) mapping using dye and radioisotope (RI) tracer has been reported to be feasible in cases of early gastric cancer. Because accurate diagnosis of micrometastasis is sometimes difficult in the limited time available during surgery, a faster and simpler method of improving the intraoperative diagnostic precision of lymph node metastasis is needed. The amount of tracer deposited in an SN can be determined from its radioactivity; however, the significance of the RI count has not been fully discussed. We investigated the clinical impact of the RI count when used as an adjunct to conventional lymph node dissection when diagnosing lymphatic metastasis in cases of early gastric cancer. Methods: From 2008 to 2009, patients with clinically diagnosed T1N0M0 gastric cancers who underwent gastrectomy and SN mapping were enrolled. SNs were examined by intraoperative and postoperative pathology. The RI count was measured for each SN with a handheld gamma probe; the correlation between nodal metastasis and the RI count was assessed. Results: A total of 308 SNs were harvested from 72 patients. Patients with SN metastasis had significantly higher total RI counts than those without SN metastasis (p = 0.007). Among cases with SN metastasis, RI counts were also significantly elevated in metastasis-positive nodes, stations, and basins. In these cases, the most of SNs having the highest RI count in each case had metastasis including isolated tumor cells. Conclusion: In early gastric cancer patients, a high RI count from an SN was correlated with lymph node metastasis. Therefore, RI counting may aid efficient pathological diagnosis and focused lymph node dissection.

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Clinical significance of the anterosuperior lymph nodes along the common hepatic artery identified by sentinel node mapping in patients with gastric cancer

Shimada Ayako, Takeuchi Hiroya, Kamiya Satoshi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Nakahara Tadaki, Jinzaki Masahiro, Murakami Koji, Kitagawa Yuko

Gastric Cancer 2015.11

ISSN 1436-3291

Background: The sentinel node (SN) concept is safely applied and validated in early gastric cancer. Gastric lymph nodes are divided into five basins with the main gastric arteries, and the anterosuperior lymph nodes with the common hepatic artery (No. 8a) are classified in the right gastric artery (r-GA) basin. Although No. 8a are considered to have lymphatic flow from the r-GA basin, there might be additional multiple lymphatic flows into No. 8a. The aim of this study is to analyze the lymphatic flows to No. 8a and to investigate the clinical significance of No. 8a as a sentinel node (SN No. 8a). Methods: Four hundred and twenty-nine patients with cT1N0 or cT2N0 gastric cancer underwent SN mapping. We used technetium-99 tin colloid solution and blue dye as a tracer. Results: We detected SN No. 8a in 35 (8.2 %) patients. In these patients, we detected SN No. 8a with SNs that belonged to the left gastric artery (l-GA) basin (66 %), right gastroepiploic artery (r-GEA) basin (54 %), and right gastric artery (r-GA) basin (46 %). In addition, celiac artery lymph nodes were detected as SNs significantly more frequently. Function-preserving surgery was performed significantly less often in patients with SN No. 8a (p =0.018). Conclusions: We found that SN No. 8a seemed to have lymphatic flow not only from the r-GA basin, but also from the l-GA basin or r-GEA basin. When SN No. 8a are detected, we should be careful to perform function-preserving surgery, even in SN-negative cases.

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Comprehensive screening of genes resistant to an anticancer drug in esophageal squamous cell carcinoma

Tsutsui Mai, Kawakubo Hirofumi, Hayashida Testsu, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Saikawa Yoshiro, Omori Tai, Takeuchi Hiroya, Kitagawa Yuko

International Journal of Oncology 47 ( 3 ) 867 - 874 2015.09

ISSN 1019-6439

Drug resistance to chemotherapy is a major issue in esophageal cancer management. Drug resistance may be mediated by genetic changes in the tumor; therefore, the identification of gene mutations may lead to better therapeutic outcomes. We used a novel method involving transposons to screen and identify drug-resistant genes. Transposons are DNA sequences that move from one location on the gene to another. A modified piggyBac transposon was designed as an insertion mutagen, and a cytomegalovirus (CMV) promoter sequence was added to induce strong transcription. When the transposon is inserted to the upstream of a certain gene, the gene will be overexpressed while when intserted down or intragenically, it will be downregulated. After establishing a transposon-tagged cell library, we treated cell lines derived from esophageal squamous cell carcinomas (ESCC) [Tohoku esophagus (TE)] with cisplatin (CDDP). We performed splinkerette PCR and TOPO cloning on the resistant colonies. Bacterial colonies were sequenced, and next-generation sequencing was used to identify the overexpressed/downregulated sequences as candidate genes for CDDP resistance. We established 4 cell lines of transposon-tagged cells, TE4, 5, 9 and 15. We treated the two relatively viable cell lines, TE4 and TE15, with CDDP. We identified 37 candidate genes from 8 resistant colonies. Eight genes were overexpressed whilst 29 were downregulated. Among these genes was Janus kinase 2 (JAK2) that is implicated in the progression of myeloproliferative neoplasms. We identified 37 candidate genes responsible for CDDP resistance in the two cell lines derived from ESCC cells. The method is inexpensive, relatively simple, and capable of introducing activating and de-activating mutations in the genome, allowing for drug-resistant genes to be identified.

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Clinical Significance of Sentinel Node Positivity in Patients with Superficial Esophageal Cancer

Takeuchi Hiroya, Kawakubo Hirofumi, Nakamura Rieko, Fukuda Kazumasa, Takahashi Tsunehiro, Wada Norihito, Kitagawa Yuko

World Journal of Surgery 2015.08

ISSN 0364-2313

Background: Sentinel node (SN) mapping in esophageal cancer has been reported to be technically feasible with an acceptable detection rate and accuracy. However, the clinical significance and survival analysis findings associated with the metastatic status of SNs in patients with early-stage esophageal cancer have not been clarified. In this study, we investigated the clinical significance and survival impact of SN mapping in early-stage esophageal cancer. Methods: Among patients who were diagnosed preoperatively with clinical T1N0M0 or T2N0M0 esophageal cancer and who underwent SN mapping, 70 consecutive patients who were diagnosed with pathological T1 primary thoracic esophageal cancer were enrolled in this study. Sixty-four (91 %) patients were diagnosed with squamous cell carcinoma while 5 (7 %) patients were with adenocarcinoma. Endoscopic injection of technetium-99m tin colloid was performed before surgery, and radioactive SNs were identified by preoperative lymphoscintigraphy and intraoperative gamma probing. Standard esophagectomy with lymphadenectomy was performed in all patients, and all resected nodes were evaluated by routine pathological examination. Results: SNs were successfully detected in 65 (92.9 %) of 70 patients with pT1 esophageal cancer. The sensitivity to predict lymph node metastasis was 91.7 %, and the diagnostic accuracy based on SN status was 96.9 %. Although there was a wide distribution of SNs from cervical to abdominal areas, 84.5 % of the patients had no lymph node metastasis or had lymph node metastasis only in SN. The disease-specific survival of the patients with metastatic non-SNs was significantly worse relative to that of the patients with no lymph node metastasis or lymph node metastasis only in SN. Conclusions: This study demonstrated that radio-guided SN mapping is useful not only as an accurate diagnostic tool for detecting lymph node metastasis but also as a tool for prognostic stratification in patients with cN0 early esophageal cancer.

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The impact of postoperative complications on survivals after esophagectomy for esophageal cancer

Booka Eisuke, Takeuchi Hiroya, Nishi Tomohiko, Matsuda Satoru, Kaburagi Takuji, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Omori Tai, Kitagawa Yuko

Medicine (United States) 94 ( 33 ) e1369 2015.08

ISSN 0025-7974

The aim of this study was to assess the impact of postoperative complications after esophagectomy on long-term outcome. The treatment of esophageal cancer has recently been improved; however, esophagectomy with thoracotomy and laparotomy carries considerable postoperative morbidity and mortality. The real impact of postoperative complications on overall survival is still under evaluation. A retrospective analysis was performed on patients with esophageal cancer who underwent esophagectomy with thoracotomy and laparotomy, with R0 or R1 resection between January 1997 and December 2012. Of 402 patients, we analyzed the following parameters 284 patients who could be followed up for over 5 years: stage of disease, neoadjuvant therapies, surgical approaches, surgical complications, postoperative medical complications, and overall and relapse-free survivals using medical records. Of the 284 patients, 64 (22.5%) had pneumonia, 55 (19.4%) had anastomotic leakage, and 45 (15.8%) had recurrent laryngeal nerve paralysis (RLNP). Pneumonia had a significant negative impact on overall survival (P=0.035); however, anastomotic leakage and RLNP did not affect overall survival. Multivariate analysis revealed that the presence of pneumonia was predictive of poorer overall survival; the multivariate hazard ratio was 1.456 (95% confidence interval 1.020-2.079, P=0.039). Pneumonia has a negative impact on overall survival after esophagectomy. Strategies to prevent pneumonia after esophagectomy should improve outcomes in this operation.

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CXCR2 expression and postoperative complications affect long-term survival in patients with esophageal cancer

Nishi Tomohiko, Takeuchi Hiroya, Matsuda Sachiko, Ogura Masaharu, Kawakubo Hirofumi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Saikawa Yoshiro, Omori Tai, Kitagawa Yuko

World Journal of Surgical Oncology 13 ( 1 ) 2015.08

Background: Esophagectomy is one of the most invasive surgical treatments for digestive tract cancer, and the blood levels of inflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8 are increased for several hours after surgery or in patients experiencing postoperative complications. CXCR2, an interleukin-8 receptor, is reportedly expressed in several carcinomas, and interleukin-8 signaling promotes cancer cell proliferation. The impact of postoperative complications following esophagectomy on long-term survival is controversial. In this study, we demonstrate the significance of CXCR2 expression and validate the effects of CXCR2 expression and postoperative complications on long-term prognosis of esophageal squamous cell carcinoma using resected specimens. Methods: Eighty-two specimens were sectioned from archived, paraffin-embedded tumor tissues obtained from patients with esophageal squamous cell carcinoma who underwent esophagectomy and extended lymphadenectomy for complete resection of cancer in our institute between 1997 and 2002. Immunohistochemistry was performed using a polyclonal antibody to CXCR2, and the correlation of stainability with clinicopathological factors and long-term survival was examined. Results: CXCR2 was expressed in 33 of 82 (40.2%) specimens. In the CXCR2-positive group, the recurrence-free survival and overall survival rates of patients who developed postoperative complications were both significantly lower than those for patients who did not develop any complications. In contrast, in the CXCR2-negative group, there was no significant difference in long-term prognosis between patients with and without complications. CXCR2 positivity combined with postoperative complications was an independent risk factor for subsequent tumor recurrence, showing the highest hazard ratio. Conclusions: Our results suggest that the patients with CXCR2-positive esophageal cancer who develop postoperative complications have a poor prognosis and should be carefully followed. Trial registration: This study was approved by Keio University School of Medicine Ethics Committee with a trial registration number of 2011-241.

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