A Rare Case of Gastric Schwannoma: A Case Report and Literature Review.

In general, schwannoma is a benign and slow-glowing neoplasm that rarely occurs in the gastrointestinal tract as a submucosal tumor (SMT), with the most common site being the stomach. As gastric schwannoma (GS) is a rare tumor, there is limited data in the literature about its clinical features. The diagnosis of schwannoma can only be made by pathological examination with positive staining for S-100 protein. It is necessary to obtain an accurate diagnosis to introduce optimal treatment options preoperatively. However, a precise diagnosis of GS is difficult, even with modern imaging techniques. On the other hand, a complete resection with a negative surgical margin (R0) of GS is considered the best treatment, with an excellent prognosis. We present a case of a 66-year-old female patient who underwent laparoscopic-assisted wedge gastrectomy for gastric SMT, pathologically diagnosed as GS, with positive staining for S-100 protein and negative for c-kit and CD34. At 12-month follow-up after surgery, there was no recurrence or metastasis of GS. Our treatment is appropriate and effective in case of GS exceeding 50 mm.

Genomic Characterization of Non-Invasive Differentiated-Type Gastric Cancer in the Japanese Population.

BACKGROUND AND AIMS: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. METHODS AND RESULTS: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. CONCLUSION: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer.

Genomic characterization of early-stage esophageal squamous cell carcinoma in a Japanese population.

Major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking, alcohol consumption, and single nucleotide polymorphisms in ADH1B and ALDH2. Several groups have reported large-scale genomic analyses of ESCCs. However, the specific genetic changes that promote the development of ESCC have not been characterized. We performed exome sequencing of 16 fresh esophageal squamous cell neoplasms and targeted sequencing of 128 genes in 52 archival specimens, of which 26 were cancerous, and 26 were adjacent normal tissue, from Japanese ESCC patients. We found significantly more somatic mutations in TP53 and NOTCH1, CDKN2A deletions, and CCND1 amplifications in cancerous areas than in non-cancerous areas, consistent with previous studies that have characterized them as tumor suppressors and oncogenes. These data suggest that mutations, deletions, and amplifications, which alter the function of TP53, NOTCH1, CDKN2A, and CCND1, are the key changes that promote the transformation of esophageal mucosa to ESCC.

Construction of a risk model for the development of metachronous squamous cell carcinoma after endoscopic resection of esopahageal squamous cell carcinoma.

BACKGROUND: Previously, we identified that rs1229984 in ADH1B, rs671 in ALDH2, and smoking status were independently associated with the risk of developing metachronous squamous cell carcinoma (SCC) after endoscopic resection (ER) for esophageal SCC (ESCC). However, this analysis included cases with short-term follow-up. In the present study, we investigated the environmental and genetic factors associated with developing metachronous SCC using long-term follow-up observation after ER for ESCC. METHODS: One hundred and thirty ESCC patients who underwent treatment with ER were followed up using endoscopy for ≥ 30 months. We investigated the incidence of, and genetic/environmental factors associated with, metachronous SCC development after ER for ESCC. We also analyzed the potential risk factors for multiple metachronous SCC development using Cox's proportional hazards model. Moreover, we constructed a risk model for the development of metachronous SCC after ER for ESCC. RESULTS: Male, rs1229984, rs671, alcohol consumption (> 20 g/day), smoking, and multiple Lugol-voiding lesions (LVLs) significantly affected the incidence of multiple metachronous SCCs. Multiple Cox proportional analysis revealed that rs1229984, rs671, alcohol consumption, smoking, and multiple LVLs were independently associated with the risk of developing metachronous SCC. Patients who had ≤ 2 risk factors did not develop metachronous SCC, and the risk of developing metachronous SCC in patients with ≥ 3 risk factors was significantly higher than in patients with ≤ 2 risk factors. CONCLUSION: The risk model using these 5 genetic and environmental factors is useful as an indication for multiple metachronous development in ESCC patients.

ADH1B and ALDH2 are associated with metachronous SCC after endoscopic submucosal dissection of esophageal squamous cell carcinoma.

A previous genome-wide association study identified two novel esophageal squamous cell carcinoma (ESCC) susceptibility genes, ADH1B and ALDH2. We investigated the characteristics of ESCC, and the relationship between metachronous esophageal and/or pharyngeal squamous cell carcinoma (SCC) and the ADH1B & ALDH2 risk alleles. One hundred and seventeen superficial ESCC patients who underwent treatment with endoscopic submucosal dissection (ESD) were followed up using endoscopy for ≥12 months. First, we performed a replication analysis to confirm the relationship between ESCC and the ADH1B & ALDH2 risk alleles using 117 superficial ESCC cases and 1125 healthy controls. Next, we investigated the incidence and genetic/environmental factors associated with metachronous SCC development after ESD. We also analyzed the potential risk factors for metachronous SCC development using Cox's proportional hazards model. rs1229984 GG located on ADH1B and rs671 GA located on ALDH2 were significantly associated with ESCC progression (P = 7.93 × 10(-4) and P = 1.04 × 10(-5) ). Patients with rs1229984 GG, those with rs671 GA, smokers, heavy alcohol drinkers (44 g/day ethanol), and presence of multiple Lugol-voiding lesions (LVLs) developed metachronous SCC more frequently (P = 3.20 × 10(-3) , 7.00 × 10(-4) , 4.00 × 10(-4) , 2.15 × 10(-2) , and 4.41 × 10(-3) , respectively), with hazard ratios were 2.84 (95% confidence interval [CI] = 1.43-5.63), 4.57 (95% CI = 1.80-15.42), 4.84 (95% CI = 1.89-16.41), and 2.34 (95% CI = 1.12-5.31), respectively. Multiple logistic regression analysis revealed that rs1229984 GG, rs671 GA, and smoking status were independently associated with the risk of developing metachronous SCCs after ESD. Moreover, we found cumulative effects of these two genetic factors (rs1229984 GG and rs671 GA) and one environmental factor (tobacco smoking) which appear to increase metachrous SCCs after ESD of ESCC risk approximately nearly 12-fold. Our findings elucidated the crucial role of multiple genetic variations in ADH1B and ALDH2 as biomarkers of metachronous ESCC.

Risk factors for esophageal stenosis after entire circumferential endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) is used to perform en block resection for esophageal squamous cell carcinoma, but it is strongly associated with postoperative stenosis, especially during entire circumferential resection. This study aimed to clarify the risk factors for refractory postoperative stenosis after entire circumferential esophageal ESD. METHODS: Nineteen patients who underwent entire circumferential esophageal ESD from February 2006 to December 2013 at Hiroshima University Hospital were divided into two groups: refractory postoperative stenosis [≥6 endoscopic balloon dilation (EBD) procedures, 12 lesions in 12 patients] and non-refractory postoperative stenosis (≤5 EBD procedures, 7 lesions in 7 patients). We retrospectively examined the patient factors (age, sex, alcohol consumption, smoking index, and chemoradiation therapy history), tumor factors (location, macroscopic type, fibrosis, and depth), and treatment factors (mean procedure time, entire circumferential resection diameter, muscle layer damage, and steroid administration method) between the two groups. RESULTS: Muscle layer damage (p = 0.019) and ≥5 cm of longitudinal mucosal defect length after entire circumferential esophageal ESD (p = 0.010) were significant factors associated with the refractory group. Regarding the patient and tumor factors, there were no significant differences between the two groups. CONCLUSION: Our data suggest that refractory post-ESD stenosis occurs after entire circumferential esophageal ESD with muscle layer damage and ≥5 cm of longitudinal mucosal defect length.

Risk factors and management of positive horizontal margin in early gastric cancer resected by en bloc endoscopic submucosal dissection.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric cancer (EGC), there is no consensus regarding the management of positive horizontal margin (HM) despite en bloc ESD. The aim of the current study was to identify the risk factors and optimal management of positive HM in EGCs resected by en bloc ESD. METHODS: A total of 890 consecutive patients with 1,053 intramucosal EGCs resected by en bloc ESD between April 2005 and June 2011. Clinicopathological data were retrieved retrospectively to assess the positive HM rate, local recurrence rate, risk factors for positive HM, and outcomes of treatment for local recurrent tumor. Positive HM was defined as a margin with direct tumor invasion (type A), the presence of cancerous cells on either end of 2-mm-thick cut sections (type B), or an unclear tumor margin resulting from crush or burn damage (type C). RESULTS: The positive HM rate was 2.0% (21/1,053). The local recurrence rate was 0.3% (3/1,053). All local recurrent tumors were intramucosal carcinomas, and were resected curatively by re-ESD. Multivariate analysis with logistic regression showed tumor location in the upper third of the stomach and lesions not matching the absolute indication to be independent risk factors for positive HM. CONCLUSION: The risk factors for HM positivity in cases of EGC resected by en bloc ESD are tumor location in the upper third of the stomach and dissatisfaction of the absolute indication for curative ESD.

Clinical outcomes of endoscopic submucosal dissection for superficial Barrett's adenocarcinoma.

BACKGROUND: Advances in diagnostic techniques have allowed early stage detection of superficial Barrett's adenocarcinoma (SBA) as well as resection by endoscopic submucosal dissection (ESD). Few reports exist, however, on the safety and efficacy of ESD for SBA. OBJECTIVE: To analyze outcomes of ESD for SBA in relation to clinicopathological features of the lesions. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Twenty-three patients (21 men, 2 women; mean age, 63 years) with 26 SBAs. INTERVENTION ESD MAIN OUTCOME MEASUREMENTS: We examined outcomes of ESD in relation to the clinicopathological features of SBAs. The main outcomes assessed were en bloc resection rate, operation time, adverse event rates, additional resection rate, and time between ESD and any recurrence. RESULTS: Twenty lesions (87%) derived from short-segment Barrett's esophagus, and 3 lesions (13%) derived from long-segment Barrett's esophagus. The majority of SBAs (54%) were located in the 0 to 3 o'clock circumferential quadrant. Median tumor size was 15 mm (range 5-60 mm). Macroscopic types were flat elevated (n = 13, 50%), depressed (n = 12, 46%), and protruded (n = 1, 4%). The SBAs appeared red (n = 23, 88%) or normally pale (n = 3, 12%). Under magnifying narrow-band imaging, all SBAs showed an irregular mucosal pattern and an irregular vascular pattern. The endoscopic en bloc resection rate was 100% (26/26), and the pathological en bloc resection rate was 85% (22/26). The median procedure time was 95 minutes (range, 30-210 minutes). Delayed bleeding occurred in 1 case, but there was no perforation. The SBAs were of the differentiated type (n = 25, 96%) or poorly differentiated type (n = 1, 4%). The tumor had invaded the superficial muscularis mucosa (n = 3, 12%), lamina propria mucosa (n = 5, 19%, deep muscularis mucosa (n = 9, 34%), SM1 (n = 3, 12%), and SM2 (n = 6, 23%). Additional surgical resection after ESD was performed in 9 cases, and there were no residual tumors, but 1 lymph node metastasis was found. There were no recurrent tumors; however, 1 metachronous adenocarcinoma was diagnosed 42 months after ESD. LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: ESD appears to be a safe and effective treatment strategy for early stage SBA.