Hiroyuki Kuwano

Gunma University, Maebashi, Gunma Prefecture, Japan

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Publications (898)2182.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA 7 (miR-7) has been reported to be a tumor suppressor in all malignancies including CRC. However, its significance for CRC clinical outcomes has not yet been explored. The potential for miR-7 to act as a tumor suppressor by coordinately regulating the EGFR signaling pathway at several levels was examined. We investigated the tumor inhibitory effect of miR-7 in colorectal cancer, with particular focus on the relationship between miR-7 and the EGFR pathway. Quantitative RT-PCR was used to evaluate miR-7 expression in 105 colorectal cancer cases to determine the clinicopathologic significance of this miRNA. The regulation of EGFR by miR-7 was examined with miR-7 precursor-transfected cells. Furthermore, we investigated whether miR-7 suppresses proliferation of colorectal cancer cells in combination with cetuximab, a monoclonal antibody against EGFR. Multivariate analysis indicated that low miR-7 expression was an independent prognostic factor for poor survival (P=0.0430). In vitro assays showed that EGFR and RAF-1 are direct targets of miR-7, which potently suppressed the proliferation of colorectal cancer cells, and, interestingly, that the growth inhibitory effect of each of these was enhanced by cetuximab. miR-7 is a meaningful prognostic marker. Furthermore, these data indicate that miR-7 precursor, alone or in combination with cetuximab, may be useful in therapy against colorectal cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 12/2014; · 5.64 Impact Factor
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    ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. To improve prognoses in patients with ESCC, we evaluated the potential of transforming growth factor-beta-induced protein (TGFBI), which is overexpressed in ESCC, as a therapeutic candidate. We examined the clinical significance of TBFBI in 102 ESCC samples using real-time RT-PCR. Immunohistochemical studies were conducted to examine the localization of TGFBI. Knockdown of TGFBI in cocultured fibroblasts was performed to determine the roles of TGFBI in migration and invasion. The level of TGFBI in ESCC tissues was higher than that in normal tissues. The high TGFBI expression group (n = 16) had higher TGFB1 expression and more frequent hematogenous recurrence than the low-expression group (n = 86). High TGFBI expression was an independent prognostic factor in patients with ESCC. TGFBI was mainly localized in stromal cells of ESCC. Moreover, suppression of TGFBI in fibroblasts inhibited the migration and invasion capacity of TE8 ESCC cells. High TGFBI expression in ESCC tissues could be a powerful biomarker of poor prognosis and hematogenous recurrence. TGFBI in stromal cells might be a promising molecular target for ESCC treatment.
    Annals of Surgical Oncology 12/2014; · 4.12 Impact Factor
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    ABSTRACT: The amino acid positron emission tomography (PET) tracer [(18)F]-3-fluoro-alpha-methyltyrosine ((18)F-FAMT) is known to be highly specific for malignancies. We evaluated the accumulation of (18)F-FDG or (18)F-FAMT in lymph nodes (LN) prior to definitive chemoradiotherapy (CRT) for esophageal cancer. We retrospectively reviewed 30 patients with esophageal squamous cell carcinoma. All patients received definitive CRT. The relationship between the accumulation of (18)F-FDG PET or (18)F-FAMT PET in LNs prior to CRT and clinical outcomes was assessed. A correlation was observed between LNs in which most of (18)F-FAMT was accumulated and complete response (CR) rate, but was not for (18)F-FDG. Additionally, for (18)F-FAMT, the CR rate was significantly higher in the LN accumulated lesion ≤1 group than in the LN accumulated lesion >2 group. To predict the outcome of definitive CRT in patients with esophageal cancer, it is important to evaluate the LN status. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 12/2014; 34(12):7473-7. · 1.71 Impact Factor
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    ABSTRACT: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration.
    World journal of gastroenterology : WJG. 11/2014; 20(42):15691-702.
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    ABSTRACT: Background/Aims: The purpose of this study was to investigate the effectiveness of sternocleidomastoid (SCM) flap repair for anastomotic leakage after esophagectomy. Methods: A refractory cutaneous fistula from the gastric stump developed in 8 patients with esophageal cancer who underwent esophagogastric anastomosis after esophagectomy. All patients underwent SCM flap repair. The cutaneous fistula was removed and resutured. The sternal head of the left SCM was dissected from the manubrium of the sternum and sutured onto the repaired gastric stump. Results: The operative duration was 80-220 min (median, 120 min). The amount of intraoperative bleeding ranged from 5 to 182 g (median, 15 g). The absence of recurrent anastomotic leakage was confirmed after the SCM flap repair in every patient. Oral intake was initiated 7-15 days (median, 10 days) after the repair operation without discomfort. Conclusions: SCM flap repair is an effective and minimally invasive treatment method for cervical anastomotic leakage after esophageal reconstruction. This method may be considered in patients with refractory leakage of the gastric stump after staple anastomosis. © 2014 S. Karger AG, Basel.
    Digestive surgery. 11/2014; 31(4-5):306-311.
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    ABSTRACT: Abstract A 52-year-old man was admitted to our hospital with a spontaneous esophageal rupture (Boerhaave syndrome) and was successfully treated. Eight years after the first incident, he was readmitted with a recurrent rupture. Recurrence of Boerhaave syndrome is extremely rare, with only 7 cases reported in the English literature. During treatment, the patient was also diagnosed with antiphospholipid syndrome (APS). Although APS is known to cause a variety of symptoms due to vascular thrombosis, recurrence of Boerhaave syndrome, coincident with APS, has never been reported. The pathogenesis of Boerhaave syndrome has not been clearly determined. This report serves to increase awareness of the risk of APS, which results in an increased risk of spontaneous rupture of the esophagus.
    International surgery. 11/2014; 99(6):842-5.
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    ABSTRACT: Abstract Biliary obstruction caused by small simple cysts is very rare. We present a case of biliary dilatation caused by a simple cyst with a 4-cm diameter. The patient was a 75-year-old woman referred to our hospital for evaluation of a cystic tumor associated with peripheral biliary duct dilatation in the left segment of the liver. Computed tomography and magnetic resonance imaging showed that the cyst probably communicated with the intrahepatic bile duct. Malignant tumors, including intrahepatic papillary neoplasms of the bile duct, could not be ruled out; therefore, we performed surgery with the patient's consent. Histopathologic examination of the resected liver showed that the cystic lesion was a simple cyst. The finding that even small simple cysts can obstruct the biliary tract is important for the management of cystic lesions of the liver.
    International surgery. 11/2014; 99(6):753-6.
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    ABSTRACT: Schwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, axillar and supraclavicular lesions are unusual for schwannoma. We report two cases of schwannoma arising in the brachial plexus, which were detected by 18 F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT).Case 1: A 75-year-old Japanese woman showed high FDG accumulation in a subclavicular or axillary lesion found by FDG-PET/CT. Axillar-subclavicular lymph node metastasis was suspected and surgical excision was performed. Histological evaluation revealed schwannoma.Case 2: A 75-year-old Japanese woman was diagnosed with suspected primary lung cancer with brain metastases. She showed high FDG uptake at a subclavicular or axillary lesion found by FDG-PET/CT. Surgical excision was performed to arrive at a definitive diagnosis. The mass was located at the trunk of the brachial plexus and was identified as a schwannoma.
    World Journal of Surgical Oncology 10/2014; 12(1):309. · 1.09 Impact Factor
  • Shinsuke Kiriyama, Hiroshi Naitoh, Hiroyuki Kuwano
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    ABSTRACT: Endoscopic submucosal dissection (ESD) has been proposed as the gold standard in the treatment of early gastric cancer because it facilitates a more accurate histological assessment and reduces the risk of tumor recurrence. However, the time course of ESD for large gastric tumors is frequently prolonged because of the tumor size and technical difficulties and typically requires higher doses of sedative and pain-controlling drugs. Sedative or anesthetic drugs such as midazolam or propofol are used during the procedure. Therapeutic endoscopy of early gastric cancers can often be performed with only moderate sedation. Compared with midazolam, propofol has a very fast onset of action, short plasma half-life and time to achieve sedation, faster time to recovery and discharge, and results in higher patient satisfaction. For overall success, maintaining safety and stability not only during the procedure but also subsequently in the recovery room and ward is necessary. In obese patients, it is recommended that the injected dose be based on a calculated standard weight. Cooperation between gastroenterologists, surgeons, and anesthesiologists is imperative for a successful ESD procedure.
    World journal of gastroenterology : WJG. 09/2014; 20(34):11985-11990.
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    ABSTRACT: Abstract Hematogenous metastasis of esophageal adenocarcinoma to the skeletal muscle is uncommon. We report a rare case of esophageal adenocarcinoma with metastasis to the skeletal muscle. During pretherapeutic examination, a painful mass was detected in the left thigh of a 49-year-old man. Endoscopic biopsy identified poorly differentiated, advanced esophageal adenocarcinoma. Computed tomography (CT) revealed wall thickening in the distal esophagus. Two enlarged lymph nodes were detected-the middle thoracic paraesophageal lymph node in the mediastinum and the right cardiac lymph node. (18)F-fluorodeoxyglucose (FDG) positron emission tomography demonstrated left thigh metastasis, which had not been detected by CT 3 weeks previously, with increased accumulation of FDG. Therefore, ultrasound-guided core-needle biopsy was performed. Histologic and immunohistochemical findings supported a diagnosis of poorly differentiated adenocarcinoma. The final diagnosis was primary esophageal adenocarcinoma with distant metastasis to the skeletal (left thigh) muscle. The rate of disease progression in this case emphasizes the malignant potential of esophageal adenocarcinoma. A few cases of skeletal metastasis from advanced esophageal adenocarcinoma have been previously reported. However, rapid metastasis to a distant skeletal muscle with no other hematogenous metastasis is quite rare. Early detection and rapid treatment are especially important in cases of esophageal adenocarcinoma.
    International surgery. 09/2014; 99(5):650-655.
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    ABSTRACT: The aim of the present study was to clarify the anatomy between the left triangular ligament (LTL) and the appendix fibrosa hepatis (AFH) in order not to sever the AFH when dissecting the LTL.
    Journal of Hepato-Biliary-Pancreatic Sciences 08/2014;
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    ABSTRACT: The FIRIS study previously demonstrated non-inferiority of IRIS (irinotecan plus S-1) to FOLFIRI (5-fluorouracil/leucovorin with irinotecan) for progression-free survival as the second-line chemotherapy for metastatic colorectal cancer (mCRC) as the primary endpoint. The overall survival (OS) data were immature at the time of the primary analysis.
    Journal of Cancer Research and Clinical Oncology 08/2014; · 2.91 Impact Factor
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    ABSTRACT: Arsenic-induced toxicity appears to be dependent on the tissue- or cell-specific accumulation of this metalloid. An early study showed that arsenic was retained in the esophagus as well as the liver, kidney cortex and skin of marmosets after intraperitoneal administration of (74)As-arsenite. However, there is little available information regarding the distribution of arsenic in the esophagus. Here, we compared the retention of arsenic in the esophagus, liver, lung, kidney and heart in mice intraperitoneally administered 1 or 5 mg/kg sodium arsenite (As(III)) daily for 3 or 7 days. The results showed that the arsenic concentration was highest in the esophagus. We compared the mRNA levels of aquaglyceroporin (AQP) 3, AQP7 and AQP9, which are responsible for arsenic influx, and those of multidrug-resistance protein (MRP) 1 and MRP2, which are responsible for arsenic efflux. The levels of AQP3 mRNA in the esophagus were much higher than those in liver, lung and heart, while the mRNA levels of MRP2 were very low in the esophagus. In addition, we found extremely low expression of Nrf2 in the esophagus at the basal and under the activated conditions, which might have resulted in low levels of glutamyl-cysteine ligase catalytic and modulatory subunits, and subsequently in the low levels of glutathione. Thus, the highest retention of arsenic was detected in the esophagus after intraperitoneal administration of As(III) to mice, and this appeared to result from multiple factors, including high expression of AQP3, low expression of MRP2, low capacity of glutathione synthesis and low activation of Nrf2.
    Archive für Toxikologie 08/2014; · 5.22 Impact Factor
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    ABSTRACT: The primary aim of this study was to examine the motor activity (motility) of a gastric tube after laparoscopic-assisted proximal gastrectomy (LPG). A secondary objective was to ascertain whether a correlation exists between gastric tube motor activity and reflux esophagitis.
    Anticancer research 08/2014; 34(8):4293-8. · 1.71 Impact Factor
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    ABSTRACT: Background and Objectives This multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent gastrointestinal stromal tumors (GIST).Methods The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001–2011 were retrospectively reviewed. Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The median follow-up period was 4.0 years.ResultsAfter a median follow-up period of 4.0 years, the patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3%, 74.9%, and 53.8%, respectively. In univariate and multivariate analyses, imatinib dose reduction and achieving a complete or partial response were found to be associated with increased OS.Conclusions Long-term imatinib treatment is recommended for patients with non-progressive disease. If patients experience significant toxicities, temporary dose reduction might be useful. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 08/2014; · 2.64 Impact Factor
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    ABSTRACT: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence.
    Annals of Surgical Oncology 07/2014; · 4.12 Impact Factor
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    ABSTRACT: Abstract The purpose of this study was to evaluate the presence of extracapsular invasion (ECI) in positive sentinel lymph nodes (SLNs) as a predictor of disease recurrence in breast cancer. SLN biopsy was performed on 318 breasts of 316 breast cancer patients, of which 50 (15.7%) had positive SLNs. Six (12.0%) of these 50 cases had disease recurrence. The clinicopathologic features of these cases were reviewed. The ECI at SLNs was not significantly associated with disease recurrence. The recurrence-free interval by Kaplan-Meier curves did not differ significantly among patients with and without ECI at SLNs. On the other hand, metastasis at non-SLNs was observed in 12 cases (24.0%) among the 50 cases with positive SLNs, and in the non-SLN metastasis group there were 7 patients with ECI at non-SLNs. Three of 7 cases with ECI at non-SLNs had disease recurrence and none of those 5 without ECI at non-SLNs had disease recurrence. Our current study suggests that the presence of ECI at metastatic SLNs is not associated with recurrent disease in breast cancer. Our results also imply that patients with ECI at positive non-SLNs have a high risk of disease recurrence.
    International surgery. 07/2014; 99(4):305-308.
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    ABSTRACT: Abstract Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation.
    International surgery. 07/2014; 99(4):479-84.
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    ABSTRACT: In recent years, the number of facilities performing thoracoscopic surgery of the esophagus has increased. Thoracoscopic surgery has many advantages, such as a magnification effect, good lighting, and a wide field of view. Esophagectomy requires fine manipulation within a deep and narrow space. Thus, thoracoscopic surgery is suitable for the performance of esophagectomy. The body position during this procedure may be either prone or left lateral decubitus. Because there are advantages in both cases, the relative merits are controversial. The operation time is longer than that of open thoracotomy, but the amount of bleeding is small in most cases of thoracoscopic esophagectomy. There are also some reports that thoracoscopic esophagectomy is comparable with open esophagectomy in terms of radicality and quality of lymph node dissection, and the intensive care unit and hospital stay durations are shortened. Robot-assisted esophagectomy is a promising technology for the fine manipulations and highquality 3-dimensional visualization required in the performance of esophageal thoracoscopic surgery. Thoracoscopic esophagectomy will become more widespread and undergo further development in the future with the spread of robotic surgery and 3-dimensional endoscopic surgery.
    Kyobu geka. The Japanese journal of thoracic surgery 07/2014; 67(8):773-7.
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    ABSTRACT: Background: We have previously reported that prealbumin and albumin may be sensitive indicators of the risk of recurrent disease in colorectal cancer; however, the relationship between preoperative prealbumin and cancer survival has not been fully-elucidated. The purpose of this study was to examine the relationship between preoperative nutritional conditions, including prealbumin and albumin concentrations, and the risk of recurrence in cases with breast cancer. Patients and Methods: One hundred and fifty-seven patients who underwent breast surgery were analyzed in this study. The detection limit of the prealbumin assay was 22 mg/dl; patients were divided in analytical groups of <22 mg/dl and ≥22 mg/dl. The detection limit of the albumin assay was 4.0 g/dl; patients were divided in analytical groups of <4.0 g/dl and ≥4.0 g/dl. The clinical features of these cases were reviewed according to prealbumin and albumin levels, and statistical analysis was performed. Results: Among 157 cases in this study, five (3.2%) had disease recurrence. Out of the eligible cases, 38 (24.2%) had decreased serum prealbumin and 19 (12.1%) had decreased serum albumin preoperatively. No statistically significant association of the preoperative prealbumin level was found with the clinicopathological variables. The only statistically significant association found for preoperative albumin level was age; age was higher in patients with low albumin levels. In short, we were unable to establish a connection between preoperative prealbumin or albumin and various clinical features, including recurrence, lymph node metastasis and tumor size. Conclusion: Prealbumin and albumin may be sensitive indicators of disturbances in protein metabolism, and reflect inflammation activity and malnutrition. However, our results suggest that evaluation of serum prealbumin and albumin are not useful for predicting disease aggressiveness or recurrence in breast cancer.
    Anticancer research 07/2014; 34(7):3775-9. · 1.71 Impact Factor

Publication Stats

10k Citations
2,182.45 Total Impact Points


  • 1999–2014
    • Gunma University
      • • Department of General Surgical Science
      • • Graduate School of Medicine
      • • Department of Surgery
      Maebashi, Gunma Prefecture, Japan
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 2011–2013
    • Dokkyo Medical University
      • • Division of Surgical Oncology
      • • Department of Surgery I
      Tochigi, Tochigi-ken, Japan
  • 2010–2013
    • National Cancer Center
      • Endoscopy Division
      Tokyo, Tokyo-to, Japan
    • National and Kapodistrian University of Athens
      • Division of Surgery V
      Athens, Attiki, Greece
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka-shi, Osaka-fu, Japan
  • 2001–2013
    • Gunma Prefectural Cancer Center
      Maebashi, Gunma Prefecture, Japan
  • 1981–2012
    • Kyushu University
      • • Medical Institute of Bioregulation - MIB Hospital
      • • Division of Surgery
      • • Division of Pathobiology
      • • Department of Surgery and Science
      • • Faculty of Medical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2003–2011
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2009–2010
    • Gunma Children's Medical Center
      Shibukawa, Gunma Prefecture, Japan
  • 2006–2008
    • Saiseikai Maebashi Hospital
      Edo, Tōkyō, Japan
  • 2005
    • Niigata University
      • Division of Molecular and Diagnostic Pathology
      Niahi-niigata, Niigata, Japan
  • 2003–2005
    • Karmanos Cancer Institute
      Detroit, Michigan, United States
  • 2000
    • The University of Tokyo
      Tōkyō, Japan
    • Fukuoka Dental College
      • Department of Surgery
      Sawara, Chiba, Japan
  • 1988
    • Philadelphia University
      Philadelphia, Pennsylvania, United States