Manabu Nakagawa

Hokkaido University, Sapporo-shi, Hokkaido, Japan

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Publications (30)111.32 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal endoscopic submucosal dissection (ESD) is a widely accepted treatment for colorectal tumors, but is technically more difficult and has a higher risk of complications such as perforation than gastric ESD. Few studies have investigated the factors associated with technical difficulty and perforation in colorectal ESD. This study aimed to evaluate the technical difficulty according to location, and the risk factors for perforation, in colorectal ESD. This retrospective study included 134 consecutive colorectal tumors treated by ESD in 122 patients at the Division of Endoscopy of Hokkaido University Hospital and the Department of Gastroenterology of Kitami Red Cross Hospital from November 2011 to February 2013. To evaluate the technical difficulty of performing ESD for colorectal tumors at specific locations, the en bloc R0 resection rate, specimen diameter, procedure speed, and procedure time were compared among tumor locations using the chi (2) test or analysis of variance. Risk factors for perforation were identified by multiple logistic regression analysis. The en bloc R0 resection rate was 86.6 % (116/134), the mean tumor diameter was 27.1 mm, and the mean procedure time was 63.5 min. The mean speed of procedures was significantly slower in the sigmoid colon (24.7 min/cm(2)) than in other areas. Perforation occurred in nine cases (6.7 %). Submucosal fibrosis was the only factor independently associated with perforation (odds ratio 5.684, 95 % confidence interval 1.307-24.727). ESD was slower for sigmoid colon tumors than for tumors in other areas, suggesting that ESD was technically more difficult in the sigmoid colon than in other colorectal areas. Submucosal fibrosis was independently associated with perforation during colorectal ESD.
    Surgical Endoscopy 07/2014; 29(1). DOI:10.1007/s00464-014-3665-9 · 3.31 Impact Factor
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    ABSTRACT: BACKGROUND: Endoscopic submucosal dissection (ESD) has become the standard endoscopic treatment for gastric neoplasms because of its safety and high rate of curability; however, it is not easy for novice operators to learn the technique of ESD. In this study, predictive factors of gastric neoplasms in which novices could not finish ESD by self-completion were evaluated. METHODS: Eighty consecutive ESD procedures performed by four novice operators were retrospectively analyzed. Standard ESD procedures were performed using an insulation-tipped (IT) knife under supervision. Self-completion rates, procedure time, and complete resection rates were evaluated, and predictive factors for "not self-completion" were assessed. RESULTS: The overall self-completion rate and en bloc plus R0 resection rate were 87.5% (70/80) and 95.7 % (67/70), respectively. In "not self-completion" cases (n = 10), the procedure time was longer and resected specimens were larger than those in self-completion cases (83.7 ± 47.3 min vs. 189.5 ± 106.8 min, p < 0.05; 641.2 ± 487.8 vs. 1,116 ± 480.4 mm(2), p < 0.01). Predictive factors of "not self-completion" were tumor location in the middle or upper third of the stomach or in the greater curvature and size of resected specimens larger than 900 mm(2). The self-completion rate of ESD was decreased in cases with more than two predictive factors. CONCLUSIONS: For novice operators, tumor location and resected areas are predictive factors for failure to finish gastric ESD by self-completion. Selection of cancer lesions could be a key factor for effectiveness of ESD training.
    Surgical Endoscopy 04/2013; 27(10). DOI:10.1007/s00464-013-2929-0 · 3.31 Impact Factor
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    ABSTRACT: Background: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD includes impaired fundic accommodation, delayed gastric emptying and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. Method: Subjects were 20 healthy volunteers and 26 successive FD patients according to the Rome III criteria. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. Results: The mean cross-sectional area of the fornix after 800 ml of water intake was significantly lower in the FD group compared with the control group. In the FD group, marked abdominal symptoms developed immediately after initiation of water intake, and VAS score differed significantly (p <0.01) between the control and FD groups at each time point. Conclusion: We developed the novel drinking-ultrasonography test which revealed abnormalities in gastric accommodation and sensation in patients with FD compared with healthy controls. This approach can be readily performed and allows the simultaneous evaluation of gastric accommodation, emptying and sensation.
    Digestion 01/2013; 87(1):34-9. DOI:10.1159/000343935 · 2.03 Impact Factor
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    ABSTRACT: BACKGROUND: Pepsinogen (PG) method is widely used to identify high risk group of gastric cancer.It is very useful before Helicobacter pylori (H. pylori) eradication, but after eradication the method becomes useless because PGI, PGII, PGI/II ratio change. Therefore, we aimed to identify for high risk group of gastric cancer using serum pepsinogen after successful eradication of H. pylori. METHODS: 261 Participants after successful eradication H. pylori in Hokkaido University Hospital from 1995 to 2010 were enrolled. Participants with renal failure, taking Proton Pomp Inhibitor, advanced gastric cancer were excluded. Serum levels of PGI and II were measured using Chemiluminescent Immuno Assey (CLIA) method. RESULTS: ROC curve using cancerous and non-cancerous data in post-eradication determined the optimal cut-off value of PGI/II was 4.5. The sensitivity and the specificity were 65.9% and 79.3%. Usual PG method includes 48.9% of cancer cases, and the PGI/II≦4.5 in post-eradication includes 65.9% of them, and it includes approximately half of the high risk group of diffuse type cancer. PGI/II≦4.5 in post-eradication included many gastric cancer cases detected after eradication (12/16=75%). CONCLUSION: As the identification for high risk group of gastric cancer, we suggest that the opotimal cut-off value of PGI/II after successful eradication of H. pylori is 4.5. PGI/II≦4.5 in post-eradication includes more gastric cancer cases comparing with traditional PG method, and 75% of gastric cancer cases detected after eradication.
    Journal of Gastroenterology and Hepatology 10/2012; 28(1). DOI:10.1111/j.1440-1746.2012.07285.x · 3.63 Impact Factor
  • Gastrointestinal endoscopy 02/2012; 76(6). DOI:10.1016/j.gie.2012.01.006 · 4.90 Impact Factor
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    ABSTRACT: The results of a randomized controlled study and meta-analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. The subjects were 18 early-stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. The average diameter of gastric cancer was smaller and Ki-67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer.
    Helicobacter 06/2011; 16(3):210-6. DOI:10.1111/j.1523-5378.2011.00833.x · 2.99 Impact Factor
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    ABSTRACT: The concomitant use of non-steroidal anti-inflammatory drugs is a risk factor for low-dose aspirin (LDA)-associated upper gastrointestinal toxicity. Lafutidine is an H2-receptor antagonist with gastroprotective activity, produced by acting on capsaicin-sensitive afferent neurons. To evaluate the preventive effect of lafutidine on gastric damage caused by LDA alone and by the combination of both LDA and loxoprofen, we conducted a clinical study using healthy volunteers. A randomized, double-blinded, placebo-controlled, crossover study was carried out. Sixteen healthy volunteers without Helicobacter pylori infection were randomly assigned to two groups. Both groups received 81 mg of aspirin once daily for 14 days (on days 1 to 14) and 60 mg of loxoprofen three times daily for the last 7 days (on days 8 to 14). Placebo or 10 mg of lafutidine was administered twice daily for 14 days in each group. After a 2-week washout period, placebo and lafutidine were crossed over. Endoscopic findings of gastric mucosal damage were evaluated according to the modified Lanza score. The mean modified Lanza score was 2.19 ± 1.06 (SD) for aspirin plus placebo as compared with 0.50 ± 0.77 for aspirin plus lafutidine (P < 0.001), and 3.00 ± 1.56 for aspirin plus loxoprofen and placebo as compared with 1.25 ± 1.37 for aspirin plus loxoprofen and lafutidine (P < 0.01). The addition of loxoprofen to LDA increases gastric mucosal damage. Standard-dose lafutidine significantly prevents gastric mucosal damage induced by LDA alone or LDA plus loxoprofen in H. pylori-negative volunteers. Larger controlled studies are needed to strengthen these findings.
    Journal of Gastroenterology and Hepatology 10/2010; 25(10):1631-5. DOI:10.1111/j.1440-1746.2010.06375.x · 3.63 Impact Factor
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    ABSTRACT: It has not been determined whether low-grade squamous dysplasia (LGD) of the esophagus is a precancerous lesion or not. If LGD progresses to squamous cell carcinoma, early carcinoma lesions that have such a natural history might contain a remaining LGD component. The lesions in the 68 patients with early invasive squamous cell carcinoma who underwent endoscopic mucosal resection were examined for the presence of an LGD component. If LGD components were observed, the degrees of architectural and cytological abnormalities of LGD components and those of tumor invasive fronts in the same lesions were studied. The degrees of abnormalities of 28 small LGD lesions were also studied. Histological examination of resected specimens confirmed LGD components in 43% of the squamous cell carcinoma lesions. The lesions of lamina propria mucosae (m2) cancer contained a significantly broader area of LGD component than did the lesions of muscularis mucosae (m3) and submucosal layer (sm) cancer (P = 0.037). Mean score for the degrees of cytological abnormalities of LGD component was similar to that of tumor invasive front (P = 0.457) and significantly higher than that of small LGD lesions (P < 0.001). Our results indicate the possibility that the lesion was formed by a combination of small lesions that arose as a multicentric occurrence of squamous cell carcinoma and dysplasia. Our results also suggest that an LGD component would transform to carcinoma along with tumor progression. However, the concept of 'basal cell layer type carcinoma in situ' may be suitable for squamous cell lesions with a high degree of cytological abnormalities confined to the lower half of the epithelium.
    Journal of Gastroenterology and Hepatology 11/2009; 25(2):314-8. DOI:10.1111/j.1440-1746.2009.06032.x · 3.63 Impact Factor
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    ABSTRACT: Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum.
    Journal of Clinical Biochemistry and Nutrition 09/2009; 45(2):248-53. DOI:10.3164/jcbn.09-24 · 2.29 Impact Factor
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    ABSTRACT: The utility of magnifying endoscopy for diagnosis of epithelial tumors has been reported, but there are few reports for nonepithelial tumors. To determine the characteristics of magnified images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) before and after treatment. This was a retrospective study. Endoscopy Unit, Hokkaido University Hospital. Eleven patients diagnosed with MALT lymphoma were enrolled. The microstructural pattern, collecting venules, and abnormal vessels in gastric MALT lymphoma were assessed before treatment and at 4 to 7 months after treatment by using magnifying endoscopy. MAIN OUTCOME MEASUREMENT AND RESULTS: The characteristics of magnified endoscopic images before treatment were the disappearance of gastric pits and the appearance of abnormal vessels. Ten cases of Helicobacter pylori-infected MALT lymphoma were treated by H. pylori eradication, and 1 H. pylori-negative case was treated by radiation therapy after eradication therapy. Ten patients achieved complete disease remission. After the treatment, recovery of gastric pits and subepithelial capillary network, and the disappearance of abnormal vessels were revealed by magnifying endoscopy. This was a small pilot study. Magnified findings of gastric MALT lymphoma before and after therapy seem to correlate with complete response and no response.
    Gastrointestinal endoscopy 07/2008; 68(4):624-31. DOI:10.1016/j.gie.2008.02.066 · 4.90 Impact Factor
  • Journal of clinical gastroenterology 05/2008; 42(8):960. DOI:10.1097/MCG.0b013e3180500336 · 3.19 Impact Factor
  • Gastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)61590-5 · 13.93 Impact Factor
  • Gastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)63440-X · 13.93 Impact Factor
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    ABSTRACT: The cause of peptic ulcer is classified into five categories; infectious, drug-induced, hyperacidic, secondary, and idiopathic. Among these factors, H. pylori infection and non-steroidal anti-inflammatory drugs including aspirin (NSAIDs) are most important for development of gastroduodenal ulcer. More than 95 percent of gastroduodenal ulcers are associated with H. pylori or NSAIDs. Therefore, the frequency of non-H. pylori non-NSAIDs ulcer is very low. NSAIDs have the effect to inhibit synthesis of cyclooxygenase-1 (COX 1) and COX-2. This inhibitory action induces analgesic and anti-inflammatory effects. On the other hand, inhibitory action for COX-1 reduces the production of prostaglandin that is related to protective effect for gastrointestinal mucosa. Its mechanism is able to induce gastroduodenal ulcer. Since the elderly population in Japan is rising, the number of patients who need NSAIDs treatment is expected to increase in near future.
    Nippon rinsho. Japanese journal of clinical medicine 11/2007; 65(10):1760-7.
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    ABSTRACT: To investigate the therapeutic effects of triple therapy combining lafutidine with clarithromycin and amoxicillin on H pylori infection and the resolution of gastroesophageal symptoms after eradication. We conducted a randomized, multicenter, open-label controlled trial to compare the effectiveness of a triple therapy of lafutidine, clarithromycin, and amoxicillin (lafutidine group) with that of a triple therapy of lansoprazole, clarithromycin, and amoxicillin (lansoprazole group) in patients with H pylori infection. The study group comprised 22 patients with gastric ulcers and 18 patients with duodenal ulcers who had H pylori infection. H pylori eradication rates were similar in the lafutidine group (14/20, 70%) and the lansoprazole group (14/20, 70%). Gastroesophageal reflux and abdominal symptoms improved after eradication therapy in both groups, whereas abdominal discomfort, diarrhea, and constipation were unchanged. H pylori status had no apparent effect on improvement of gastroesophageal reflux or abdominal symptoms after treatment. Adverse events were similar in both groups. The triple therapy including lafutidine is equivalent to triple therapy including lansoprazole in terms of H pylori eradication rates and improvement in gastroesophageal reflux and abdominal symptoms. These results are attributed to the fact that lafutidine has strong, continuous antisecretory activity, unaffected by CYP2C19 polymorphisms.
    World Journal of Gastroenterology 08/2007; 13(28):3836-40. · 2.43 Impact Factor
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    ABSTRACT: Symptoms of heartburn and regurgitation are the most important for diagnosis of gastroesophageal reflux disease (GERD) in the clinical field. Endoscopic examination is also widely used modality for Los Angeles classification of GERD according to endoscopic severity of esophageal mucosal breaks. However, about half of GERD patients reveal no abnormality under conventional endoscopy. These endoscopic negative GERD is called as non-erosive reflux disease (NERD). There is the possibility to underestimate a minute mucosal change of GERD by conventional endoscopy that has the limitation of visual ability. Magnifying endoscopic examination is able to get clear visualization of intrapapillary capillary loops(IPCL), which are usually shown as dot-like structures in esophageal mucosa by a conventional endoscopy. The changing of IPCLs is associated with inflammation and neoplasia of esophagus. Minute change of IPCLs such as a dilation and elongation with regular intervals were reported to be suggestive of inflammatory change in esophagus. Magnifying endoscopic observation of IPCLs is useful for diagnosis of NERD which cannot be visualized by conventional endoscopy.
    Nippon rinsho. Japanese journal of clinical medicine 06/2007; 65(5):865-71.
  • Gastrointestinal Endoscopy 04/2007; 65(5). DOI:10.1016/j.gie.2007.03.323 · 4.90 Impact Factor
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    ABSTRACT: Because most gastric cancers develop from a background of Helicobacter pylori-infected gastric mucosa, H. pylori plays an important role in gastric carcinogenesis. Therefore, eradication of H. pylori may inhibit the incidence of gastric cancers. In experimental studies, H. pylori eradication has proved to act as a prophylaxis against gastric cancer. However, the results of recent randomized controlled studies are absolutely contradictory. In Japan, mucosal gastric cancer is usually resected by endoscopic treatment. As only a small part of the gastric mucosa is resected, secondary gastric cancer after endoscopic resection of the primary gastric cancer often develops at another site in the stomach. A nonrandomized Japanese study involving 132 early gastric cancer patients reported that eradication of H. pylori after endoscopic resection tended to reduce the development of secondary gastric cancer. Also, a retrospective multicenter survey indicated that the incidence rate of secondary gastric cancer in H. pylori-eradicated patients was about one-third that among patients in the noneradication group. We conducted a large-scale multicenter randomized trial to confirm the effect of H. pylori eradication on secondary and residual gastric cancer after endoscopic resection. This study was begun in 2003 and is ongoing at present. Diagnosis of a new carcinoma at another site of the stomach is defined as the primary end point, and recurrence of tumors at the resection site as a secondary end point. A total of 542 subjects have been enrolled in the study. This study will have the statistical power to demonstrate whether H. pylori eradication decreases the incidence and recurrence of gastric cancer.
    Journal of Gastroenterology 02/2007; 42(S17). DOI:10.1007/s00535-006-1928-5 · 4.02 Impact Factor
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    ABSTRACT: Early detection of hypopharyngeal carcinoma is increasingly possible and patients with such early lesions can be treated with endoscopic resection. To identify the optimal relationship between the mucosal defect of the hypopharynx and malfunction of the hypopharynx after endoscopic resection of early hypopharyngeal carcinoma. Case series. Referral center in Japan. Four patients with early-stage squamous cell carcinoma of the hypopharynx underwent endoscopic submucosal dissection (ESD). By using ESD, an accurate incision line close to the tumor margin could be confirmed while performing treatment. ESD was performed with a small-caliber-tip transparent hood (ST-hood) to open the incision line for better visualization of the submucosa. Feasibility of en bloc resection, complications, and recurrence after ESD. No early or late complications due to treatment occurred in the patients. Histological examination of resected specimens revealed that 2 patients had carcinoma in situ and 2 patients had tumor invasion of the subepithelium. There was no local recurrence or distant metastasis in any of the patients during the follow-up period (3-14 months). We consider that ESD is the optimal method for endoscopic resection not only because it enables an en bloc resected specimen to be obtained but also because it can prevent removal of excess mucosa of the hypopharynx, which is a very narrow and important organ related to swallowing and speech.
    Gastrointestinal Endoscopy 09/2006; 64(2):255-9; discussion 260-2. DOI:10.1016/j.gie.2006.01.049 · 4.90 Impact Factor
  • Gastrointestinal Endoscopy 04/2006; 63(5). DOI:10.1016/j.gie.2006.03.337 · 4.90 Impact Factor

Publication Stats

165 Citations
111.32 Total Impact Points


  • 2003–2013
    • Hokkaido University
      • Department of Gastroenterology and Hepatology
      Sapporo-shi, Hokkaido, Japan
  • 2006–2012
    • Hokkaido University Hospital
      • • Division of Internal Medicine II
      • • Division of Gastroenterology and Hepatology
      Sapporo-shi, Hokkaido, Japan
  • 2007
    • Sapporo Kosei General Hospital
      Sapporo, Hokkaidō, Japan