Wasaburou Koizumi

Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma

BACKGROUND AND STUDY AIMS Narrow band imaging combined with magnifying endoscopy (NBI-ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. The risk of a second primary SCC of the head and neck is very high in patients with esophageal SCC. This prospective study evaluated the detection rate of superficial SCC within the head and neck region (superficial SCCHN) with NBI-ME in patients with esophageal SCC. PATIENTS AND METHODS Between March 2006 and February 2008, 112 patients with a current or previous diagnosis of esophageal SCC were enrolled. All patients underwent endoscopic screening of the head and neck by NBI-ME. The primary end point was the detection rate for superficial SCCHN. Secondary end points were to compare demographic characteristics between patients with and without superficial SCCHN and to assess the clinical course of patients with superficial SCCHN. RESULTS The detection rate for superficial SCCHN was 13 % (15/112). The prevalence of multiple Lugol-voiding lesions, observed endoscopically throughout the esophageal mucosa after application of Lugol dye solution, was significantly higher in patients with superficial SCCHN than in those without (100 % vs. 24 %, P < 0.0001). Minimally invasive curative treatment with organ preservation was feasible without severe complications in patients with superficial SCCHN after curative treatment of esophageal SCC. CONCLUSIONS In patients with esophageal SCC, NBI-ME is useful for detecting superficial SCCHN, thereby facilitating minimally invasive treatment.

Submucosal Fibrosis and Basic-Fibroblast Growth Factor-Positive Neutrophils Correlate with Colonic Stenosis in Cases of Ulcerative Colitis

Background and Aims: The frequency of benign stenosis in ulcerative colitis (UC) is low, reported as being 3.2–11.2%, with fibrosis in the submucosa or deeper pointed out as one of the causes. The aim of the present study was to assess stenosis in UC cases using immunostaining and to analyze differences between stenotic and nonstenotic cases, focusing on basic-fibroblast growth factor (b-FGF) expression and myofibroblasts. Methods: Totals of 9 stenotic and 17 nonstenotic UC cases were histopathologically examined and immunohistochemically stained for b-FGF, α-smooth muscle actin (α-SMA), CD34, CD68 and IL-6. To identify b-FGF-positive cells, double immunostaining for b-FGF and myeloperoxidase or CD68 was performed. Results: In addition to submucosal fibrosis, a significant increase of b-FGF-positive inflammatory cells and myofibroblasts was observed in stenotic portions. Most b-FGF-positive cells were also positive for myeloperoxidase, and a correlation between b-FGF-positive and total neutrophil counts was found. Conclusions: One of the major causes of stenosis in long-standing UC is fibrosis in the bowel wall, possibly induced by infiltrating inflammatory neutrophils producing b-FGF.

Propofol sedation with bispectral index monitoring is useful for endoscopic submucosal dissection: a randomized prospective phase II clinical trial.

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) has become a standard treatment. However, the treatment time tends to be relatively long and insufflation and manipulation of the endoscope can increase pain and discomfort. We aimed to find an optimal method for sedation during ESD. PATIENTS AND METHODS Patients scheduled to undergo ESD for early gastric cancer or adenoma were randomly assigned to sedation with midazolam or propofol, and consciousness level was evaluated by bispectral index (BIS) monitoring. Primary end points of effectiveness (three parameters) and secondary end points of safety during ESD and after return to the ward were compared between the groups. Study registration was in the UMIN Clinical Trial Registry (UMIN 000001497), and the institutional trial number was KDOG 0801. RESULTS From June 2008 through June 2009, we enrolled 178 patients (90 midazolam, 88 propofol). Regarding safety after ESD, recovery was significantly better in the propofol group immediately after and at 1 hour and 2 hours after return to the ward (P < 0.001). The number of patients who required a continuous supply of oxygen 2 hours after returning to the ward was significantly lower in the propofol group (midazolam 18; propofol 6; P = 0.010). Though propofol seemed to be better for effectiveness and safety, there were no statistically significant differences for all three primary end points and the safety parameters (hypotension, hypoxia, bradycardia). CONCLUSIONS Propofol with BIS monitoring improved recovery of patients after ESD, though this study was underpowered to prove the effectiveness and safety of propofol.

Fine needle aspiration using forward-viewing endoscopic ultrasonography.

BACKGROUND AND STUDY AIM A prototype forward-viewing instrument has been developed for therapeutic endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA). We had the opportunity to use this forward-viewing echo endoscope and to study its clinical usefulness, mainly for diagnostic EUS-FNA. PATIENTS AND METHODS The prototype forward-viewing echo endoscope was used for 15 months between November 2006 and March 2010, in a study group comprising 47 consecutive patients. Diagnostic EUS-FNA was done in 38 patients and the diagnostic accuracy of the forward-viewing device was compared with that from an oblique-viewing echo endoscope in reference patients who were matched by disease and puncture route. Therapeutic EUS was done in nine patients (pseudocyst drainage in six; celiac ganglia neurolysis, biliary drainage, and pancreatic duct drainage in one each). RESULTS Diagnostic EUS-FNA provided a correct diagnosis in 97.4 % (37/38 patients), which was not significantly different from the 94.7 % (36/38) in the reference patients. Lesions considered difficult to access with an oblique-viewing scope, such as those located at the fornix, or the head of the pancreas, or associated with strictures, were easily punctured, as were those located at the body or tail of the pancreas or at the porta hepatis. Treatment was successful in all nine patients who underwent therapeutic EUS procedures. None of the 47 patients had any complications. CONCLUSIONS A forward-viewing echo endoscope that allows target sites to be punctured more perpendicularly with minimal effort, can be used for diagnostic EUS-FNA and this may be advantageous, depending on the site of target lesions.

Endoscopic management of malignant biliary obstruction by means of covered metallic stents: primary stent placement vs. re-intervention

BACKGROUND AND STUDY AIMS Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Occlusion of covered metallic stents now occurs in about half of all patients with malignant biliary strictures. The removal of metallic stents followed by placement of a second stent has been attempted, but outcomes remain controversial. The aim of the current study was to evaluate the effectiveness and safety of the primary placement and secondary placement (re-intervention) of covered metallic stents and to assess the feasibility and safety of stent removal. PATIENTS AND METHODS The study included 186 patients with unresectable malignant biliary strictures who underwent primary stent placement between October 2001 and March 2010.  Covered biliary self-expandable metal stents (SEMSs) were removed in 39 of these patients, and 36 underwent re-intervention. The patency times, occlusion rates of the first stent and re-intervention, success rates of stent removal, and complications were investigated. RESULTS Covered SEMSs were placed in 186 patients. The median patency time of the first stent was 352 days. Stent occlusion occurred in 48.9 % of the patients and was mainly caused by debris or food residue (37 %), dislocation (19 %), and migration with hyperplasia (19 %). Stent removal was attempted in 50 patients and was successful without complication in 39 (78 %). Most of the patients in whom stent removal was unsuccessful had migration with hyperplasia. The median patency time of the second stent was 263 days. The stent patency time did not significantly differ between the first and the second stent. CONCLUSIONS Covered SEMSs could be safely removed at the time of stent occlusion. Patency rates were similar for initial stent placement and re-intervention.

Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer

BACKGROUND Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups. PATIENTS AND METHODS This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing. RESULTS The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001). CONCLUSIONS Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.

Quadruple therapy with ecabet sodium, omeprazole, amoxicillin and metronidazole is effective for eradication of Helicobacter pylori after failure of first-line therapy (KDOG0201 Study).

Background and object:  An antiulcer agent, ecabet sodium, is active against Helicobacter pylori. The aim of the present study was to clinically examine whether eradication therapy, which includes ecabet sodium, is effective in eradication of H. pylori after failure of first‐line therapy.

Endoscopic mucosal resection (EMR) for the management of poorly differentiated adenocarcinoma of the stomach: a patient who had recurrence and died 4 years after EMR.

Recent studies have explored the possibility of using endoscopic mucosal resection (EMR) to treat lesions with a relative indication for endoscopic therapy. We used EMR to manage poorly differentiated adenocarcinoma, a relative indication for endoscopic treatment, in a patient who requested such treatment and refused surgical intervention. We describe our experience with this patient, who died of tumor recurrence 4 years after the EMR. This case describes the problems of using EMR for the treatment of poorly differentiated adenocarcinoma.

1490PAPREPITANT, GRANISETRON AND DEXAMETHASONE VERSUS PALONOSETRON AND DEXAMETHASONE FOR CISPLATIN-INDUCED NAUSEA AND VOMITING IN PATIENTS WITH UPPER GASTROINTESTINAL CANCER: A RANDOMIZED CROSSOVER PHASE II TRIAL (KDOG 1002)

ABSTRACT Aim: Large-scale clinical studies on chemotherapy-induced nausea and vomiting (CINV) induced by highly emetogenic chemotherapy (HEC) showed that antiemetic therapy with a 3-drug combination of aprepitant, granisetron and dexamethasone (AGD) or a 2-drug combination of palonosetron and dexamethasone (PD) were superior to conventional antiemetic therapy a 5HT3 receptor antagonist and dexamethasone. But the AGD and PD regimens have not been compared. We performed a randomized crossover trial to compare the efficacy of AGD and PD in HEC. Methods: The subjects were patients with esophageal or gastric cancer who underwent HEC including ≥60 mg/m2 cisplatin as first-line treatment. Patients were randomly assigned into groups treated with AGD (oral aprepitant 125 mg on day 1, 80 mg on days 2–3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone (D) 6.6 mg on day 1 and oral D 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous D 13.2 mg on day 1 and oral D 8 mg on days 2-3). The antiemetic therapies were crossed-over in the second course. The primary endpoint was a complete response (CR: defined as no emetic episodes and no requirement for rescue medication) in the overall phase (0-120 h) during the first course. The planned sample size of 80 patients provided 80% power to detect a 30% improvement in CR with a two-sided alpha of 0.05. Results: Eighty-fifth patients were enrolled in the study and 84 were evaluable. Baseline factors were well-balanced between the two groups. The CR rate did not differ significantly between the two groups, but the frequency of no vomiting was significantly higher in the AGD group (Table 1). Regarding patients preference after the second course, 41.0% of patients preferred AGD, 19.7% preferred PD, and 39.3% indicated no preference. Based on a QOL survey, the frequency of no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1% vs. 53.7%; p = 0.014). Persentages of patients reaching efficacy endpoints AGD, N=43 PD, N=41 p value Complete response 67.4% 58.5% 0.399 No vomiting 81.4% 58.5% 0.025 No nausea 39.5% 39.0% 0.962 No rescue 674% 75.6% 0.409 Conclusions: The primary endpoint of CR was not achieved, but AGD combination therapy seems to more effective than PD therapy for prevention of HEC-induced CINV. Disclosure: All authors have declared no conflicts of interest.

Experimental and clinical studies on heater probe hemostasis for upper gastrointestinal bleeding with special reference to comparison with ethanol injection.

SummaryThe hemostatic effects in patients with upper gastrointestinal bleeding was evaluated using an endoscopic heater probe method and ethanol injection method. The heater probe method was effective in 94.4% of patients with few complications. The ethanl injection method was effective in 86.5% of patients. The heater probe method is considered to be an effective and safe technique in the treatment of upper gastrointestinal bleeding.