Akira Naruke

Narrow band imaging for detecting superficial oral squamous cell carcinoma: a report of two cases.

We present two cases of superficial squamous cell carcinoma of the floor of the mouth, which were coincidentally detected by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) during gastrointestinal evaluation. We successfully removed the lesions using laser assisted with NBI combined with magnifying GIE. Because NBI combined with magnifying GIE shows a well‐demarcated brownish area and scattered foci of microvascular proliferation, it may play an important role in the management of superficial squamous cell carcinoma in the oral cavity.

A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901)

BACKGROUND Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant. OBJECTIVE To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms. DESIGN Phase II study. SETTING University hospital. PATIENTS Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011. INTERVENTION ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors. MAIN OUTCOME MEASUREMENTS The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination. RESULTS The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%. LIMITATIONS Single-center, nonrandomized study. CONCLUSION Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000002047.).

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.

Double-endoscope endoscopic submucosal dissection for the treatment of early gastric cancer accompanied by an ulcer scar (with video)

BACKGROUND Endoscopic submucosal dissection (ESD) for early gastric cancer accompanied by an ulcer scar remains challenging. Several counter-traction techniques have been attempted to facilitate ESD, but a standard procedure remains to be established. OBJECTIVE To evaluate the efficacy and safety of double-endoscope ESD by using a single light source in patients with early gastric cancer accompanied by an ulcer scar. DESIGN Single center, retrospective study. SETTING Kitasato University East Hospital. PATIENTS A total of 30 early gastric cancers with ulcer scars were treated by double-endoscope ESD in 30 patients from October 2008 through May 2012. INTERVENTION Double-endoscope ESD. MAIN OUTCOME MEASUREMENTS En bloc resection rate, complete resection rate, treatment time, and adverse events. RESULTS The use of two endoscopes for ESD provided a good field of vision and allowed counter-traction to be applied to the lesion, clearly facilitating submucosal dissection. Because only a single light source was used, the working space of the endoscope room was not compromised. Moreover, it was unnecessary to prepare another light source or to coordinate image filing. The en bloc resection rate and complete resection rate were 100% and 90%, respectively, and the median treatment time was 80 minutes. As compared with historical control data obtained before the introduction of double-endoscope ESD, the rate of cutting into the specimen was significantly lower (7% vs 35%; P = .01). No serious adverse events occurred during the procedure. Postoperatively, however, 3 patients (10%) had delayed hemorrhage, and 1 (3.3%) had a delayed perforation. LIMITATIONS Single-center, nonrandomized study. CONCLUSION Our experience indicates that our procedure for double-endoscope ESD is useful and feasible in patients with early gastric cancer accompanied by an ulcer scar.

Argon plasma coagulation for superficial esophageal squamous-cell carcinoma in high-risk patients.

AIM To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients. METHODS We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence. RESULTS The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-IIc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation. CONCLUSION APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy.

DOG1 is useful for diagnosis of KIT-negative gastrointestinal stromal tumor of stomach.

Approximately 80%-95% of gastrointestinal stromal tumors (GISTs) show positive staining for KIT, while the other 5%-20% show negative staining. If the tumor is negative for KIT, but is positive for CD34, a histological diagnosis is possible. However, if the tumor is negative for KIT, CD34, S-100, and SMA, a definitive diagnosis is often challenging. Recently, Discovered on GIST-1 (DOG1) has received considerable attention as a useful molecule for the diagnosis of GIST. DOG1, a membrane channel protein, is known to be overexpressed in GIST. Because the sensitivity and specificity of DOG1 are higher than those of KIT, positive staining for DOG1 has been reported, even in KIT-negative GISTs. KIT-negative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically. We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia. Our findings suggest that immunohistochemical staining for DOG1, in addition to gene analysis, is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.

Comparison of site-specific gene expression levels in primary tumors and synchronous lymph node metastases in advanced gastric cancer

BackgroundMany malignant tumors consist of heterogeneous subpopulations of cells. This heterogeneity is associated with genetic characteristics. However, it remains unclear whether gene expression levels differ among specific sites of tumors in gastric cancer.MethodsWe studied differences in gene expression levels among specific sites of primary tumors and synchronous lymph node metastases, using formalin-fixed, paraffin-embedded specimens resected surgically from 48 patients with previously untreated advanced gastric cancer. Specimens were obtained by laser-captured microdissection from five regions: (1) nonneoplastic mucosa, (2) surface layer (mucosa) of the primary tumor (surface sections), (3) middle layer (submucosa) of the primary tumor (middle sections), (4) the deepest layer of the primary tumor (muscularis propria or deeper) at the site of deepest invasion (deep sections), and (5) level 1 synchronous lymph node metastasis (lymph node metastases). Expression levels of the following target genes were determined by quantitative real-time polymerase chain reaction: thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF1α).ResultsTP, DPD, EGFR, and HIF1α gene expression levels were significantly higher in deep sections than in surface sections. TP, EGFR, VEGF, and HIF1α gene expression levels were significantly higher in lymph node metastases than in surface sections. TP, DPD, EGFR, VEGF, and HIF1α gene expression levels were positively correlated with the specific samples harvested from the tumors.ConclusionsOur results show that the expression levels of some genes in tumor cells can change in specific sites of tumors and can become higher in association with tumor progression.

Intratumoral gene expression profile of genes involved in 5-FU metabolism and angiogenesis, comparison with tumor invasion depth in patients with advanced gastric cancer.

56 Background: The biopsy specimen by endoscopy can only show the surface of its gene profiles. We hypothesis whether the biopsy specimen can reflect all part of gene profile or not. We tested how 5-FU related genes and angiogenesis gene expressed in the invasion depth in the primary tumor of the Stage II or III advanced gastric cancer. Methods: Twenty-five patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed.Formalin-fixed, paraffin-embedded tumor tissues were dissected from the surface section (mainly mucosa), the middle section (mainly submucossa) and the deep section (the part invaded most deeply) of the primary tumor and the normal gastric mucosa tissue by the laser-captured microdissection technique and were analyzed for target gene expressions using a quantitative real-time polymerase chain reaction.We analyzed for target genes as TS, TP, DPD, ERCC1, EGFR, VEGF and HIF1α. Results: In the primary tumor, TP and HIF1α gene expression in the surface section was ...