Details of a Researcher - Nakamura, Rieko

Papers - Nakamura, Rieko

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Superior mesenteric artery syndrome caused by massive lumbar osteophytes

Booka Eisuke, Kawakubo Hirofumi, Ishii Ken, Hikata Tomohiro, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Ishii Yoshiyuki, Takeuchi Hiroya, Kitagawa Yuko

Spine 40 ( 15 ) E909 - E912 2015.08

ISSN 0362-2436

Study Design. Case report. Objective. To present a rare case of superior mesenteric artery (SMA) syndrome caused by massive lumbar osteophytes. Summary of Background Data. SMA syndrome is a relatively rare condition thought to be secondary to functional obstruction. Although several risk factors for SMA syndrome have been reported, no other previous reports have suggested that lumbar osteophytes caused SMA syndrome. Methods. A rare case of SMA syndrome caused by massive lumbar osteophytes was treated by resecting the osteophytes. Results. An 82-year-old man, with a history of polysurgery, presented with frequent vomiting. He was diagnosed with SMA syndrome after endoscopic and several radiological examinations, and was successfully treated by the resection of the osteophytes. Conclusion. To the best of our knowledge, a case of SMA syndrome secondary to lumbar osteophytes has not been reported in the literature. The possibility of SMA syndrome caused by massive lumbar osteophytes should be taken into consideration when the cause of SMA syndrome is unknown. In addition, the resection of osteophytes could be a less invasive treatment in such cases.

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A Prospective Randomized Trial of Enteral Nutrition After Thoracoscopic Esophagectomy for Esophageal Cancer

Takesue Tomoko, Takeuchi Hiroya, Ogura Masaharu, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Kitagawa Yuko

Annals of Surgical Oncology 2015.07

ISSN 1068-9265

Background: Several studies have reported that postoperative enteral nutrition (EN) reduced complications and decreased weight loss and hospital stay periods; however, the majority of patients analyzed in these studies underwent open thoracic surgery. No studies have been conducted regarding EN in patients after thoracoscopic esophagectomy as a less invasive surgery. The aim of this study was to investigate the efficacy of EN after thoracoscopic esophagectomy. Methods: Fifty patients who underwent thoracoscopic esophagectomy for esophageal cancer were divided into two groups: parenteral nutrition (PN; n = 25) and EN (n = 25). The rate of weight loss at postoperative day (POD) 14, levels of prealbumin at POD 10, postoperative complications until POD 14, and other perioperative data were collected for each group. Results: This study analyzed data for 47 patients. The rate of weight loss at POD 14 was significantly lower in the EN group (3.0 ± 3.2 %) than in the PN group (4.0 ± 3.6 %; p = 0.020). Prealbumin levels were 21.0 ± 7.5 mg/dL in the PN group and 18.4 ± 5.8 mg/dL in the EN group at POD 10, with no significant differences between the groups. However, the incidence of postoperative pneumonia was higher in the PN group (30.4 %) than in the EN group (12.5 %). Conclusions: EN could suppress weight loss and reduce the incidence of pneumonia after thoracoscopic esophagectomy.

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Surgical Resection of Remnant Gastric Cancer Following Distal Gastrectomy

Takahashi Masashi, Takeuchi Hiroya, Tsuwano Shinichi, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Kitagawa Yuko

Annals of Surgical Oncology 2015.06

ISSN 1068-9265

Background: Remnant gastric cancer (RGC) is one of the less prevalent gastric cancers. The purpose of this study was to explore the clinicopathological characteristics and results of the operation of RGC following distal gastrectomy. In particular, we examined factors related to prognosis. Methods: Between January 1970 and December 2012, 122 patients with RGC following distal gastrectomy underwent further surgery and were analyzed retrospectively. Results: Initial gastric diseases included benign (49 patients, 40.2 %) and malignant diseases (73 patients, 59.8 %). Reconstructions by initial surgery included Billroth I (80 patients, 65.6 %) and Billroth II (42 patients, 34.4 %). Tumors were located at anastomotic (44 patients, 36.1 %) and nonanastomotic sites (78 patients, 63.9 %). There were 59 patients (48.4 %) classified with pathological (p) stage I, 19 as p stage II (15.6 %), 22 as p stage III (18.0 %), and 22 (18.0 %) as p stage IV. A total of 100 patients (82.0 %) underwent curative resection, and 22 underwent noncurative resection. The number of cases of postoperative morbidity, 90-day mortality, and adjuvant chemotherapy were 23 (18.9 %), 3 (2.5 %), and 20 (16.4 %), respectively. Univariate and multivariate analyses were performed to identify the prognostic factors of RGC. Multivariate analysis revealed historical periods, pathological venous invasion, curative resection, and postoperative morbidity to be independent prognostic factors. Conclusions: The prognosis of patients with RGC can be improved by aggressively performing curative resection without causing complications.

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Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade

Ishii Kenjiro, Takeuchi Hiroya, Fukunaga Koichi, Hirano Yuki, Suda Koichi, Hagiwara Tomoko, Miyasho Taku, Yamada Shingo, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Betsuyaku Tomoko, Ichihara Atsuhiro, Kitagawa Yuko

Experimental Lung Research 41 ( 4 ) 199 - 207 2015.05

ISSN 0190-2148

Purpose/Aim: We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. Materials: We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d). Methods: We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung. Results: The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorrhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin. Conclusions: The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.

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Correlation Between Intense Postoperative Inflammatory Response and Survival of Esophageal Cancer Patients Who Underwent Transthoracic Esophagectomy

Matsuda Satoru, Takeuchi Hiroya, Kawakubo Hirofumi, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Saikawa Yoshiro, Kitagawa Yuko

Annals of Surgical Oncology 2015.04

ISSN 1068-9265

Background: The correlation between postoperative systemic inflammation and cancer survival needs to be elucidated. This study evaluated postoperative inflammation using the peak concentration of postoperative serum C-reactive protein (CRP) levels and duration of CRP elevation, then investigated its correlation with prognosis. Methods: The study retrospectively reviewed 216 consecutive patients who underwent curative transthoracic esophagectomy at the authors’ institution between 2004 and 2012. The postoperative serum CRP levels in 215 patients were analyzed during 14 days after esophagectomy. The patients’ characteristics, surgical procedures, postoperative complications, and survival were investigated. To evaluate postoperative inflammatory status objectively using CRP, patients with a delayed CRP level peak and persistent CRP elevation were classified as having an intense postoperative inflammatory response (IIR). Results: The distributions of postoperative pathologic stages 0, 1, 2, 3, and 4 were respectively 5, 70, 58, 66, and 16. Regarding postoperative complications, pneumonia was diagnosed in 42 patients (20 %), anastomotic leakage in 32 patients (15 %), and superficial surgical-site infection in 21 patients (10 %). A delayed CRP level peak was observed in 88 patients (41 %) and persistent CRP elevation in 49 patients (23 %). Overall, 31 patients (14 %) were classified as having IIR. In the survival analysis, the patients with IIR showed a significantly shorter overall survival. In the multivariate analysis, using histology, neoadjuvant treatment, field of lymph node dissection, pathologic stage, and IIR as covariates, IIR was seen as a significantly independent predictive factor for overall survival (hazard ratio 2.019; P = 0.019). Conclusions: In this study, IIR was significantly correlated with postoperative survival. Therefore, the oncologic benefit of reducing postoperative inflammation in esophageal cancer needs to be investigated.

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Gastric tube cancer after radical esophagectomy

Booka Eisuke, Takeuchi Hiroya, Okamoto Nobuhiko, Uchi Yusuke, Fukuda Kazumasa, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Ozawa Soji, Omori Tai, Kitagawa Yuko

Esophagus 2015.03

ISSN 1612-9059

Background: Recent improvements in the survival of patients after esophagectomy have led to an increasing occurrence of gastric cancer in the reconstructed gastric tube (GTC). The aim of this study was to assess generational changes in the clinicopathological characteristics and treatment of GTCs in a single center.Methods: Thirteen GTC lesions in ten patients were diagnosed and treated at Keio University Hospital between 2006 and 2014. In our previous study, we reported eight cases of GTC [1]. We compared clinicopathological characteristics and treatment of GTC, as well as overall survival achieved in this study with those in our previous study [1].Results: In this study, median patient age at the time of GTC detection was 74 years (range 62–81 years) and the median interval between esophagectomy and GTC detection was 95 months (range 21–159 months). Nine (69 %) of 13 lesions satisfied the criteria for endoscopic resection. On comparing this study with our previous study, there were no significant differences in patient age at the time of GTC detection, the interval between esophagectomy and GTC detection, or pathological stage [1]. Compared with our previous study, the use of less invasive treatments, such as endoscopic submucosal dissection and partial gastric tube resection with sentinel lymph node dissection, generationally increased and a significant difference was observed in the type of GTC treatment [1]. However, there was no significant difference in overall survival between the studies.Conclusion: Long-term periodic endoscopy permits less invasive treatments and combinations of various treatments for effective GTC therapy.

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Characteristics and diagnosis of esophageal basaloid squamous cell carcinoma

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

Esophagus 2015.03

ISSN 1612-9059

Background: Basaloid squamous cell carcinoma (BSCC) is a relatively rare, malignant disease of the esophagus. The prognosis of patients with BSCC is thought to be poorer than that of typical squamous cell carcinoma (SCC), but the treatment strategy for BSCC is generally the same as that for typical SCC. This study examined the diagnosis, the clinical and pathological characteristics, and the results of therapy in patients with BSCC.Methods: The medical records for 13 patients with pathologically confirmed esophageal BSCC were extracted. The pretreatment endoscopic diagnosis and the pathological diagnosis after resection were reviewed for each patient, and the histological features and patient outcome were examined. We especially focus on histological difference and endoscopic findings of the 13 patients with BSCC.Results: Macroscopically, BSCC was mainly visualized as an elevated lesion with normal epithelium on the surface layer which indicated the tumor growth into submucosa. Further pathological examination allowed the 13 BSCC patients to be grouped into 2 groups according to differences in the microscopic appearances of the BSCC cancer cells: a typical BSCC pattern and a pattern similar to that of poorly differentiated SCC. Six of the patients who received an esophagectomy as the primary treatment died, and only 1 patient survived. Two patients who received chemoradiotherapy before an esophagectomy did not develop recurrences. Almost all the patients who died as a result of the recurrence of esophageal cancer had a lymph node recurrence. Prognoses of BSCCs with a pattern similar to that of poorly differentiated SCC without preoperative chemotherapy were poorer than BSCCs with a typical BSCC pattern, while BSCC with a pattern similar to poorly differentiated SCC with preoperative chemotherapy showed good prognoses than BSCC without preoperative chemotherapy.Conclusions: BSCC esophageal cancer mainly appears as an elevated lesion with submucosal growth, which can be diagnosed preoperatively by understanding of macroscopic characteristics of esophageal BSCC. The outcome of the BSCC patients in the present study was relatively poor, while pretreatment diagnosis of BSCC influences the strategy of treatment and pathological diagnosis including histological difference of BSCC may lead to appropriate treatment and better prognosis of esophageal BSCC.

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Factors Affecting Cytokine Change After Esophagectomy for Esophageal Cancer

Okamura Akihiko, Takeuchi Hiroya, Matsuda Satoru, Ogura Masaharu, Miyasho Taku, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Kitagawa Yuko

Annals of Surgical Oncology 2015.01

ISSN 1068-9265

Background: Esophagectomy for esophageal cancer is one of the most invasive operative procedures. Surgical stress induces the release of proinflammatory cytokines, and overproduction induces a systemic inflammatory response syndrome, which may lead to acute lung injury and multiple organ dysfunction syndrome. In addition, surgical stress may cause immunosuppression, which may affect not only perioperative mortality but also long-term survival.Methods: Between 2006 and 2013, levels of perioperative serum cytokines were evaluated in 90 patients who underwent esophagectomy for esophageal carcinoma. The serum interleukin (IL)-6, IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assays. We reviewed and assessed medical records, including cytokine profiles, and determined the factors affecting postoperative serum cytokine levels.Results: These cytokine levels peaked on postoperative day 1 and decreased gradually. Of the clinicopathologic factors, a thoracoscopic approach was a significant factor in attenuating IL-6 and IL-8 levels on postoperative day 1 in multivariate analysis, and a longer operative time was a significant factor in increasing these levels. During postoperative days 3–7, the thoracoscopic approach and early enteral nutrition were significant factors in attenuating serum cytokine changes in multivariate analysis, and postoperative infectious complications were significant factors in increasing these levels.Conclusions: The thoracoscopic approach and early enteral nutrition could attenuate the cytokine change after esophagectomy, and a longer operative time and postoperative infectious complication could increase it. We should undertake strategies to minimize the surgical stress to reduce potential short-term and long-term consequences for patients.

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Postoperative Hyperbilirubinemia Suggests the Occurrence of Complications After Esophagectomy for Esophageal Cancer

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

Presentations from the 9th Annual Electric Utilities Environmental Conference 2015.01

ISSN 0364-2313

Background: Serum bilirubin levels frequently increase after esophagectomy for esophageal cancer. Several studies have reported hyperbilirubinemia in patients with postoperative complications. We aimed to perform a detailed large-scale analysis to clarify this association.Methods: We compared postoperative serum bilirubin levels of 200 patients with esophageal cancer who underwent esophagectomy, with and without postoperative complications, from January 2008 to July 2013 at Keio University Hospital, Tokyo, Japan. We also analyzed other risk factors for postoperative hyperbilirubinemia by univariate and multivariate analyses in an attempt to determine the mechanism of postoperative hyperbilirubinemia.Results: Hyperbilirubinemia (total bilirubin >2.0 mg/dL) occurred in 71 patients (35.5 %). The mean total bilirubin peak level was 1.5 mg/dL in patients without complications, 2.0 mg/dL in those with at least one complication, 2.1 mg/dL in those with pneumonia, and 2.3 mg/dL in those with anastomotic leakage. Bilirubin levels were significantly higher in each complication group than in the non-complication group (p < 0.05 for all). Risk factors of postoperative hyperbilirubinemia by univariate analysis were the preoperative bilirubin level, video-assisted thoracoscopic surgery, three-field lymph node dissection, thoracic duct resection, prolonged surgical duration, severe complications (Clavien–Dindo grade ≥3), and severe anastomotic leakage (Clavien–Dindo grade ≥3). In contrast, the pT factor and postoperative enteral nutrition were negatively associated with postoperative hyperbilirubinemia. Risk factors by multivariate analysis were the preoperative bilirubin level, prolonged surgical duration, severe complications, and postoperative enteral nutrition.Conclusions: Although various factors impact postoperative hyperbilirubinemia, postoperative complications were most significantly associated with postoperative hyperbilirubinemia. Patients with postoperative hyperbilirubinemia after esophagectomy must be managed more carefully because unnoticed complications may be associated with hyperbilirubinemia.

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Phase i study of s-1 plus fractional cisplatin as adjuvant chemotherapy for advanced gastric cancer in an outpatient setting (KOGC-03)

Takahashi Tsunehiro, Saikawa Yoshiro, Fukuda Kazumasa, Nakamura Rieko, Wada Norihito, Kawakubo Hirofumi, Takeuchi Hiroya, Takaishi Hiromasa, Kitagawa Yuko

Anticancer Research 35 ( 1 ) 467 - 472 2015.01

ISSN 0250-7005

Aim: The aim of this phase I study was to adjust the dose of cisplatin as adjuvant combination chemotherapy with S-1 in an outpatient setting for gastric cancer.Patients and Methods: The first course was initiated with S-1 monotherapy on days 1-28. From the second to the sixth course, S-1 was administered on days 1-28 and cisplatin was added on days 1, 15, and 29. The dose level of cisplatin was escalated as follows: 20 mg/m² (level 1); 25 mg/m² (level 2); 30 mg/m2 (level 3). Dose-limiting toxicity was a delay factor of the start of the next course due to incomplete recovery.Results: The maximum tolerated and recommended doses were confirmed as level 3 and level 2, respectively.Conclusion: Although further clinical trials are recommended to evaluate efficacy, this combination of S-1 plus cisplatin regimen is expected to become a standard adjuvant treatment for gastric cancer in the outpatient setting.

Prognostic significance of circulating tumor cells in patients with advanced esophageal cancer

Tanaka Motomu, Takeuchi Hiroya, Osaki Yoshiki, Hiraiwa Kunihiko, Nakamura Rieko, Oyama Takashi, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Kitagawa Yuko

Esophagus 2014.12

ISSN 1612-9059

Introduction: The purpose of this study was to establish the clinicopathological significance of circulating tumor cells (CTCs) in patients with advanced or recurrent esophageal cancer who received either chemotherapy or chemoradiotherapy.Methods: CTCs from 38 patients with advanced or recurrent esophageal cancer were quantified using the CellSearch system before and approximately 3–5 weeks after the initiation of a new line of chemotherapy or chemoradiotherapy. The correlation between CTC counts and clinicopathological variables was examined.Results: Of the 38 patients, 15 (39 %) had recurrent esophageal cancer, and 23 patients (61 %) had primary advanced esophageal cancer. The mean age was 63 years (range 43–87 years). One patient (2.6 %) had a complete response to treatment, 16 (42.1 %) had a partial response, 12 (31.6 %) showed stable disease, and nine (23.7 %) showed signs of progressive disease. The overall survival of patients with ≥2 CTCs was significantly shorter than that of patients with <2 CTCs both at baseline and at first follow-up (p = 0.047 and p = 0.011, respectively). Significant correlation was found between the change in CTC counts and the response to treatment (p = 0.036). The overall survival in patients with ≥2 CTCs both at baseline and at first follow-up was significantly shorter than patients with <2 CTCs both at baseline and at first follow-up (p = 0.002). Patients with a reduction rate in the CTC value <80 % experienced significantly shorter survival than patients with a reduction rate of ≥80 % (p = 0.035). The CTC counts at first follow-up served as an independent prognostic factor (p = 0.011).Conclusions: Our results suggest that measuring the number of CTCs in patients with advanced or recurrent esophageal cancer can be useful for predicting the survival of patients and for monitoring the response to cancer treatments.

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Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia

Imaeda Hiroyuki, Hosoe Naoki, Kashiwagi Kazuhiro, Ida Yosuke, Nakamura Rieko, Suzuki Hidekazu, Saito Yoshimasa, Yahagi Naohisa, Iwao Yasushi, Kitagawa Yuko, Hibi Toshifumi, Ogata Haruhiko, Kanai Takanori

World Journal of Gastroenterology 20 ( 43 ) 16311 - 16317 2014.11

ISSN 1007-9327

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN).METHODS: Surveillance esophagogastroduodenoscopy (EGD) using a TME was conducted in 182 patients that had undergone ESD for SGN. Autofluorescence imaging (AFI) was conducted after white-light imaging (WLI). When SGN was suspicious, magnifying endoscopy with narrow-band imaging (ME-NBI) was conducted. Final diagnoses were made by histopathologic findings of biopsy specimens. The detection rates of lesions in WLI, AFI, and NBI, and the characteristics of lesions detected by WLI and ones missed by WLI but detected by AFI were examined. The sensitivity, specificity, and accuracy of endoscopic diagnosis using WLI, AFI and ME-NBI were evaluated.RESULTS: In 242 surveillance EGDs, 27 lesions were determined pathologically to be neoplasias. Sixteen early gastric cancers and 6 gastric adenomas could be detected by WLI. Sixteen lesions were reddish and 6 were whitish. Five gastric neoplasias were missed by WLI but were detected by AFI, and all were whitish and protruded gastric adenomas. There was a significant difference in color and pathology between the two groups (P = 0.006). Sensitivity, specificity and accuracy in MENBI were higher than those in both WLI and AFI. Specificity and accuracy in AFI were lower than those in WLI.CONCLUSION: Surveillance using trimodal imaging endoscopy might be useful for detecting another lesion after endoscopic submucosal dissection for superficial gastric neoplasia.

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A case of late lymph node metastasis after three endoscopic mucosal resections of intramucosal gastric cancers

Booka Eisuke, Takahashi Tsunehiro, Tokizawa Kazunori, Uchi Yusuke, Okamura Akihiko, Fukuda Kazumasa, Nakamura Rieko, Wada Norihito, Kawakubo Hirofumi, Saikawa Yoshiro, Omori Tai, Takeuchi Hiroya, Sasaki Aya, Mikami Shuji, Kumai Koichiro, Kameyama Kaori, Kitagawa Yuko

World Journal of Surgical Oncology 339 2014.11

We describe a patient with solitary lymph node (LN) metastasis after three endoscopic mucosal resections (EMRs) in which a gastrointestinal stromal tumor was difficult to differentiate from the carcinoid and lymphoma tumors. A 77-year-old man underwent three EMRs at 62, 72, and 75 years of age, and all resections were determined to be curative. However, 2 years after the last EMR, screening abdominal ultrasonography detected a 20-mm solitary tumor at the lesser curvature of the upper stomach. Laparoscopic tumor resection confirmed the pathological diagnosis. Intraoperative pathological diagnosis showed that the adenocarcinoma was compatible with recurrence of gastric cancer; thus, total gastrectomy with D1 lymphadenectomy was performed. Metastasis was not recognized by pathological examination but was detected by preoperative radiological examinations of the LN. We report a rare recurrence case after several EMRs of intramucosal gastric cancers.

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Antitumor effect of the tyrosine kinase inhibitor nilotinib on gastrointestinal stromal tumor (GIST) and imatinib-resistant GIST cells

Sako Hiroyuki, Fukuda Kazumasa, Saikawa Yoshiro, Nakamura Rieko, Takahashi Tsunehiro, Wada Norihito, Kawakubo Hirohumi, Takeuchi Hiroya, Ohmori Tai, Kitagawa Yuko

PLoS One 9 ( 9 ) 2014.09

Despite the benefits of imatinib for treating gastrointestinal stromal tumors (GIST), the prognosis for high risk GIST and imatinib-resistant (IR) GIST remains poor. The mechanisms of imatinib resistance have not yet been fully clarified. The aim of the study was to establish imatinib-resistant cell lines and investigate nilotinib, a second generation tyrosine kinase inhibitor (TKI), in preclinical models of GIST and imatinib-resistant GIST. For a model of imatinib-resistant GIST, we generated resistant cells from GK1C and GK3C cell lines by exposing them to imatinib for 6 months. The parent cell lines GK1C and GK3C showed imatinib sensitivity with IC₅₀of 4.59±0.97 μM and 11.15±1.48 μM, respectively. The imatinib-resistant cell lines GK1C-IR and GK3C-IR showed imatinib resistance with IC₅₀values of 11.74±0.17 μM (P<0.001) and 41.37±1.07 μM (P<0.001), respectively. The phosphorylation status of key cell signaling pathways, receptor tyrosine kinase KIT (CD117), platelet-derived growth factor receptor alpha (PDGFRA) and downstream signaling kinases: serine-threonine kinase Akt (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) or the non-receptor tyrosine kinase: proto-oncogene tyrosine-protein kinase Src (SRC), was analyzed in established cell lines and ERK1/2 phosphorylation was found to be increased compared to the parental cells. Nilotinib demonstrated significant antitumor efficacy against GIST xenograft lines and imatinib-resistant GIST cell lines. Thus, nilotinib may have clinical potential for patients with GIST or imatinib-resistant GIST.

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Cumulative Prognostic Scores Based on Plasma Fibrinogen and Serum Albumin Levels in Esophageal Cancer Patients Treated with Transthoracic Esophagectomy

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

Annals of Surgical Oncology 2014.06

ISSN 1068-9265

Purpose The purpose of this study was to establish a prognostic indicator based on preoperative plasma fibrinogen and serum albumin levels (FA score) in esophageal cancer patients and to compare the correlation with survival to that of the Glasgow prognostic score. Methods Patient characteristics, clinicopathological factors, and preoperative biochemical markers (fibrinogen, albumin, and C-reactive protein) were investigated in esophageal cancer patients who underwent transthoracic esophagectomy. Pretreatment fibrinogen and albumin levels were reviewed in patients who received neoadjuvant treatment. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these abnormalities were allocated a score of 1, and those with neither of these abnormalities were allocated a score of 0. The fibrinogen cut-off value was defined as 350 mg/dL according to our previous report, and the albumin cut-off value was defined as the lower quartile. Results Among 199 consecutive patients, the interquartile range of preoperative albumin was 3.8-4.3 g/dL and the cut-off value was 3.8 g/dL. Thus, 108 (54 %), 68 (34 %), and 23 (12 %) patients had an FA score of 0, 1, and 2. The patients with a high preoperative FA score showed considerably shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that pretreatment stage and preoperative FA score were independently associated with postoperative DFS and OS. Conclusions Preoperative FA score was significantly associated with postoperative survival in esophageal cancer patients, and the prognostic value is currently being validated in a prospective multicenter cohort study.

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Intra-abdominal desmoid tumor mimicking gastric cancer recurrence

Okamura Akihiko, Takahashi Tsunehiro, Saikawa Yoshiro, Mayanagi Shuhei, Fukuda Kazumasa, Nakamura Rieko, Wada Norihito, Kawakubo Hirofumi, Omori Tai, Takeuchi Hiroya, Sasaki Aya, Kitagawa Yuko

World Journal of Surgical Oncology 12 ( 1 ) 2014.05

Intra-abdominal desmoid tumors are rare and most often occur in patients with a history of familial adenomatous polyposis, surgery, or pregnancy. We report a case of an intra-abdominal desmoid tumor mimicking the recurrence of gastric cancer. A 57-year-old male had undergone distal gastrectomy for advanced gastric cancer. Serum levels of carcinoembryonic antigen were found to be elevated 27 months after surgery. Computed tomography revealed a 15-mm mass in the mesentery of the transverse colon. In addition, radiotracer fluorodeoxyglucose uptake of the tumor was detected by positron emission tomography. The patient was diagnosed with gastric cancer recurrence, and chemotherapy consisting of cisplatin and S-1 was commenced. After five courses of chemotherapy, although no significant clinical response was seen, no new lesions were seen either. Thus, a curative resection of the recurrent tumor seemed possible, which was successfully performed. Histological examination of the resected specimen revealed spindle-shaped tumor cells with collagen fiber progression; no cancer cells were detected. The tumor was diagnosed as an intra-abdominal desmoid tumor. We report a rare case of an intra-abdominal desmoid tumor that mimicked a recurrent tumor arising from gastric cancer. In patients with history of surgery for intra-abdominal malignancies, it may be difficult to distinguish the recurrence of malignancy from desmoid tumors but the possibility of desmoid tumors must be considered in the differential diagnosis.

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CC-Chemokine receptor CCR7

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

BMC Cancer 14 ( 1 ) 2014.04

Background: CC-chemokine receptor 7 (CCR7), a known lymph node homing receptor for immune cells, has been reported as a key molecule in lymph node metastasis. We hypothesized a clinicopathological correlation and functional causality between CCR7 expression and lymph node metastasis in patients with esophageal squamous cell carcinoma (ESCC).Methods: We performed immunohistochemical analysis of 105 consecutive and 61 exclusive pathological T1 ESCC patients, followed by adhesion assay and in vivo experiment using a newly developed lymph node metastasis mouse model. The adhesive ability in response to CC-chemokine ligand 21/secondary lymphoid-tissue chemokine (CCL21/SLC) was assessed in the presence or absence of lymphatic endothelial cells and anti-CCR7 antibody. We established a heterotopic transplantation mouse model and analyzed lymph node metastasis by quantitative real-time RT-PCR.Results: Positive CCR7 expression in immunohistochemistory was detected in 28 (27%) of 105 consecutive patients and 17 (28%) of 61 T1 patients, which significantly correlated with lymph node metastasis (p = 0.037 and p = 0.040, respectively) and poor five-year survival (p = 0.013 and p = 0.012, respectively). Adhesion assay revealed an enhanced adhesive ability of CCR7-expressing cells in response to CCL21/SLC, in particular, in the presence of lymphatic endothelial cells (p = 0.005). In the mouse model, lymph nodes from mice transplanted with CCR7-expressing cells showed significantly higher DNA levels at 5 weeks (p = 0.019), indicating a high metastatic potential of CCR7-expressing cells.Conclusion: These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients.

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Successful management of anastomotic leakage and lung fistula after esophagectomy

Wada Takeyuki, Takeuchi Hiroya, Yoshikawa Takahisa, Oyama Takashi, Nakamura Rieko, Takahashi Tsunehiro, Kawakubo Hirofumi, Wada Norihito, Saikawa Yoshiro, Omori Tai, Kitagawa Yuko

Annals of Thoracic Surgery 97 ( 3 ) 1071 - 1073 2014.03

ISSN 0003-4975

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Clinical utility of the Revised Cardiac Risk Index in non-cardiac surgery for elderly patients

Hirano Yuki, Takeuchi Hiroya, Suda Koichi, Oyama Takashi, Nakamura Rieko, Takahashi Tsunehiro, Kawakubo Hirofumi, Wada Norihito, Saikawa Yoshiro, Obara Hideaki, Jinno Hiromitsu, Hasegawa Hirotoshi, Tanabe Minoru, Kitagawa Yuko

Surgery Today 44 ( 2 ) 277 - 284 2014.02

ISSN 0941-1291

Purpose: We investigated the association between the Revised Cardiac Risk Index (RCRI) and postoperative outcomes in patients undergoing non-cardiac surgery. Methods: The predictive value of the RCRI for the risk of perioperative complications, length of hospital stay and hospital cost were evaluated from a prospective cohort of 119 patients aged ≥65 years undergoing elective major digestive, breast or vascular surgery. Results: Comparing three groups RCRI 0, 1 and ≥2, the morbidity rates were 0, 30 and 68 %; the median length of hospitalization was 5, 14 and 28 days; and the median cost was 665,000, 1,480,000 and 2,160,000 yen, respectively. The mortality rate was 0 % in all groups. The RCRI 0 group included only non-high-risk (breast and peripheral vascular) surgeries. In addition, comparing the two groups by excluding non-high-risk surgeries (RCRI 1 and ≥2), the median morbidity rates were 31 and 67 %, the median length of hospitalization was 15 and 28 days, and the median cost was 1,550,000 and 2,130,000 yen, respectively. The RCRI score was the only independent predictor of the perioperative complications. Conclusions: In the case of non-cardiac surgery, the RCRI can identify patients at higher risk of perioperative complications, a prolonged hospital stay and higher hospital cost.

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Endoscopic laryngo-pharyngeal surgery (ELPS) for superficial carcinoma of the pharynx and cervical esophagus

Kawakubo Hirofumi, Omori Tai, Nakamura Rieko, Takeuchi Hiroya, Kitagawa Yuko

Gastroenterological Endoscopy 56 ( 1 ) 64 - 70 2014.01

ISSN 0387-1207

Recent advances in endoscopic procedures, such as narrow band imaging systems and magnifying endoscopy, have enabled the precise observation of the hypopharynx and cervical esophagus. We developed endoscopic laryngo-pharyngeal surgery (ELPS) as minimally invasive surgery for superficial carcinoma of the larynx and pharynx. First, we insert the laryngoscope with endoscopic guide and place it at on the upper part of the vocal cord. We lift the larynx by the laryngoscope and fix the laryngoscope. The curved laryngoscope gives us a good visual field and working space between the hypopharynx and the cervical esophagus. After lifting the larynx using the laryngoscope, the endoscopist inserts the endoscope and the operator inserts the forceps and electric device transorally. After iodine staining, we mark the normal mucosa just 1-2 mm away from the cancer margin and inject Epinephrine-added physiological saline solution to the subepithelial layer. After the circumferential cutting, we resect the lesion with the forceps and electric device. ELPS for superficial carcinoma of the hypopharynx and cervical esophagus is a feasible and effective treatment.

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