Digital image analysis-based scoring system for endoscopic ultrasonography is useful in predicting gastrointestinal stromal tumors.

BACKGROUND: When gastric mesenchymal tumors (GMTs) measuring 2-5 cm in size are found, whether to undergo further treatment or not is controversial. Endoscopic ultrasonography (EUS) is useful for the evaluation of malignant potential of GMTs, but has limitations, such as subjective interpretation of EUS images. Therefore, we aimed to develop a scoring system based on the digital image analysis of EUS images to predict gastrointestinal stromal tumors (GISTs). METHODS: We included 103 patients with histopathologically proven GIST, leiomyoma or schwannoma on surgically resected specimen who underwent EUS examination between January 2007 and June 2018. After standardization of the EUS images, brightness values, including the mean (Tmean), indicative of echogenicity, and the standard deviation (TSD), indicative of heterogeneity, in the tumors were analyzed. RESULTS: Age, Tmean, and TSD were significantly higher in GISTs than in non-GISTs. The sensitivity and specificity were almost optimized for differentiating GISTs from non-GISTs when the critical values of age, Tmean, and TSD were 57.5 years, 67.0, and 25.6, respectively. A GIST-predicting scoring system was created by assigning 3 points for Tmean ≥ 67, 2 points for age ≥ 58 years, and 1 point for TSD ≥ 26. When GMTs with 3 points or more were diagnosed as GISTs, the sensitivity, specificity, and accuracy of the scoring system were 86.5%, 75.9%, and 83.5%, respectively. CONCLUSIONS: The scoring system based on the information of digital image analysis is useful in predicting GISTs in case of GMTs that are 2-5 cm in size.

Tumor localization using radio-frequency identification clip marker: experimental results of an ex vivo porcine model.

PURPOSE: With the widespread use of minimally invasive surgery, tumor detection is becoming more difficult. We present the experimental results of a radio-frequency identification (RFID) lesion detection system in an ex vivo porcine model. METHODS: The efficacy and feasibility of a newly developed RFID lesion detection system were examined. It was applied to the stomach and colon of pigs weighing 40 kg. The RFID clip was attached to the upper and lower mucosal sides of the stomach. Colon specimens with thin and thick walls were used. The clipped sites were marked on the serosa by a pin. The longest distance from the pin the RFID tag could be detected was measured 25 times in each direction. RESULTS: In the upper gastric wall, the RFID tag detection distance was 4.5 ± 0.9 mm, 5.6 ± 0.7 mm, 12.5 ± 0.7 mm, and 5.3 ± 0.5 mm in the four directions, respectively (right, left, upper, and lower). In the antrum, the RFID tag detection distance was 5.8 ± 0.7 mm, 6.9 ± 0.5 mm, 5.6 ± 0.5 mm, and 3.7 ± 0.5 mm in the four directions. In the thin colon, the RFID tag detection distance was 6.3 ± 0.5 mm, 5.0 ± 0.5 mm, 9.7 ± 0.7 mm, and 6.4 ± 0.4 mm in the four directions. In the thick colon, the RFID tag detection distance was 3.5 ± 0.8 mm, 6.6 ± 0.5 mm, 8.4 ± 0.6 mm, and 9.8 ± 0.5 mm in the four directions. The area of detection was smallest for the antrum (83.7 mm2) and similar for the other sites (150.6, 154.7 and 157.7 mm2 for the upper body, thin colon, and thick colon, respectively). CONCLUSIONS: The distance at which the RFID tag was detected was usually within 10 mm. These results indicate the feasibility of the clinical application of the add-on clip and RFID tag as a marker for identifying the location of various gastrointestinal tumors.

Long-term outcome of endoscopic submucosal dissection is comparable to that of surgery for early gastric cancer: a propensity-matched analysis.

BACKGROUND: Data concerning the long-term outcomes of endoscopic submucosal dissection (ESD) versus surgery for early gastric cancer (EGC) are limited. We aimed to compare the long-term outcomes of ESD and surgery for patients with EGC. METHODS: Data were reviewed from patients treated by ESD or surgery for EGC in 2005-2010. The primary outcome was overall survival (OS). Secondary outcomes were disease-specific survival (DSS), disease-free survival (DFS), recurrence-free survival (RFS), treatment-related complications, and hospital stay duration. RESULTS: Among 617 patients, 342 underwent ESD and 275 underwent surgery. The 5-year OS rates were similar between the ESD group and the surgery group (96.9% vs 98.1%, P = 0.581). In a propensity-score-matched analysis of 117 pairs, there were no significant differences in the OS rates (96.5% vs 99.1%, P = 0.125) and DSS rates (100% vs 99.1%, P = 0.317) between the ESD group and the surgery group. The ESD group had a significantly lower DFS rate (90.3% vs 98.0%, P = 0.002), a significantly lower RFS rate (95.1% vs 98.0%, P = 0.033), a significantly higher early complication rate (6.7% vs 1.5%, P < 0.001), a significantly lower late complication rate (0% vs 9.1%, P < 0.001), and a significantly shorter median hospital stay (3 days vs 10 days, P < 0.001) than the surgery group. CONCLUSIONS: ESD and surgery have comparable OS rates in patients with EGC. ESD has benefits, including a lower late complication rate and shorter hospital stay. However, RFS and DFS rates might be lower after ESD than after surgery.

Two staging systems for gastrointestinal stromal tumors in the stomach: which is better?

BACKGROUND: The prognosis of a gastrointestinal stromal tumor (GIST) is influenced by its anatomic site; however, few studies on the prognosis of gastric GISTs have been reported. The aims of this study were to evaluate long-term prognoses of patients who underwent surgical resection for gastric GISTs and to compare the clinical efficacy of two staging systems: the National Institutes of Health (NIH) consensus criteria and the 7th Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) tumor-node-metastasis (TNM) staging system. METHODS: We conducted a retrospective observational study of 145 patients who underwent surgical resection for gastric GISTs between February 2001 and June 2012 at Pusan National University Hospital (Busan, Korea). Recurrence and 5-year recurrence-free survival (RFS) rates were analyzed. RESULTS: During a median follow-up period of 44 months (range, 6-144 months), 11 recurrent lesions were detected in 9 patients (6.4%). On multivariate analysis, tumor size (>5 cm), mitotic count (>5/50 high-power fields), and epithelioid and mixed pathological type were significantly associated with recurrence. The overall 5-year RFS rate was 93.4%. Although no statistically significant differences were detected (C-statistic difference P = 0.886), all metrics showed lower values for the UICC/AJCC TNM staging system than for the NIH consensus criteria, suggesting that the UICC/AJCC TNM staging system may be a better model. CONCLUSIONS: The 5-year RFS rate in patients who underwent curative resection for gastric GISTs was excellent. The UICC/AJCC TNM staging system may be more useful than the NIH consensus criteria for risk categorization of patients with gastric GISTs.

Prognostic Value of Computed Tomography-Detected Extramural Venous Invasion to Predict Disease-Free Survival in Patients With Gastric Cancer.

OBJECTIVE: This study aimed to investigate whether there is a correlation between the computed tomography-detected extramural venous invasion (ctEMVI) and disease-free survival (DFS) in patients with gastric cancer using pathologic lymphovascular invasion as a reference standard. METHODS: We retrospectively reviewed 153 patients with gastric cancer who underwent computed tomography during 1 year. Differences in pathological findings between the ctEMVI-positive and ctEMVI-negative groups were analyzed. Disease-free survival was estimated using the Kaplan-Meier method. Factors affecting DFS were analyzed with the Cox proportional hazard model. RESULTS: The ctEMVI-positive group was correlated more with lymphovascular invasion (P = 0.008). The 1- and 2-year DFS rates were 92% and 80%, respectively, in the ctEMVI-negative group, but 77% and 54%, respectively, in the ctEMVI-positive group. A multivariate analysis revealed that tumor size, ctEMVI, and pathological stage remained associated with DFS (Ps = 0.037, 0.015, and 0.002, respectively). CONCLUSIONS: The ctEMVI was an independent prognostic factor for worse DFS in patients with gastric cancer.

Various features of laparoscopic tailored resection for gastric submucosal tumors: a single institution's results for 168 patients.

BACKGROUND: Laparoscopic resection is a standard procedure for gastric submucosal tumors. Herein, we analyzed the features of various laparoscopic approaches. METHODS: Between January 2007 and November 2013, 168 consecutive patients who underwent laparoscopic resection for gastric submucosal tumors were enrolled. Patients' demographics and clinicopathologic and perioperative data were reviewed retrospectively. RESULTS: Among the 168 patients, exogastric wedge resection was performed in 99 cases (58.9%), single-port intragastric resection was performed in 30 cases (17.9%), eversion technique was used in 17 cases (10.1%), transgastric resection was performed in 8 cases (4.8%), and single-port wedge resection was performed in 6 cases (3.6%). The remaining cases underwent single-port exogastric wedge resection, laparoscopic and endoscopic cooperative surgery, or major resection. Mean age was 56.8 ± 13.3 years, and body mass index was 24.0 ± 3.2 kg/m(2). Mean operation time was 96.1 ± 58.9 min; laparoscopic proximal gastrectomy had the longest operation time (3 cases, 291.7 ± 129.0 min). In contrast, the laparoscopic eversion technique had the shortest operation time (82.6 ± 32.8 min). Pathologic data revealed a mean tumor size of 2.9 ± 1.2 cm (with a range of 0.8-8.0 cm). Tumors were most common on the body (98 cases, 58.3%), followed by the fundus (44 cases, 26.2%). Exophytic growth occurred in 39 cases (23.2%), endophytic growth occurred in 89 cases (53.0%), and dumbbell-type growth occurred in 40 cases (23.8%). Gastrointestinal stromal tumors occurred in 130 cases (77.4%), and schwannomas occurred in 23 (13.7%). Thirteen patients had postoperative complications (delayed gastric emptying in 5, stricture in 3, bleeding in 3, others in 2). The mean follow-up period was 28.8 ± 20.8 months, and there were three recurrences (1.8%) at 6, 19 and 31 months after the initial surgery. CONCLUSIONS: For gastric submucosal tumors with appropriate locations and growth types, laparoscopic tailored resection which facilitates safer and more precise resection can be good alternative treatment option.

Risk factors for local recurrence in patients with positive lateral resection margins after endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: With the widespread use of endoscopic submucosal dissection (ESD) in patients with early gastric cancer (EGC), the number of cases with incomplete resection due to positive lateral resection margins (LM+) is increasing. Local recurrence, which occurs frequently in LM+ cases, is an important issue. This study aimed to clarify the clinicopathological factors related to tumor recurrence in LM+ cases after ESD for EGC. METHODS: From January 2005 to December 2012, a total of 1,083 patients with EGC underwent ESD at our hospital. Of these, cases with a pathological diagnosis of LM+ were included in this study. Patients with positive vertical resection margins, those who underwent surgical resection immediately or were followed up for less than 6 months after ESD, were excluded. RESULTS: A total of 55 LM+ cases after ESD for EGC were enrolled. Incorrect delineation of a lesion that extended pathologically beyond the ESD marking dots was the main cause of LM+. Local recurrence was found in 20 (36.4 %) patients (median follow-up period, 23 months). Local recurrence rates related to LM+ length were as follows: 7/29 (24.1 %) in 2 mm, 6/16 (37.5 %) in 4 mm, 1/3 (33.3 %) in 6 mm, 4/5 (80 %) in 8 mm, and 2/2 (100 %) in ≥ 10 mm. In multivariate analysis, tumor size > 2 cm (OR 4.48, 95 % CI 1.18-16.99, p = 0.027), and LM+ length > 6 mm (OR 7.65, 95 % CI 1.15-50.70, p = 0.035) were independent risk factors for tumor recurrence. CONCLUSION: To decrease the risk of LM+, it is highly important to accurately delineate the lateral margins during ESD; when the final histopathological result is LM+, cases with LM+ length >6 mm or tumor size > 2 cm should be considered for additional surgical resection or re-ESD because of a high risk of tumor recurrence.

Decreased Muc5AC expression is associated with poor prognosis in gastric cancer.

Mucins reportedly play numerous key roles in carcinogenesis, including in tumor invasion, regulation of differentiation and tumor cell proliferation. We investigated the effect of Muc5AC, a secreted mucin, on the invasiveness/migratory capability of gastric cancer cells and the prognostic significance of Muc5AC in gastric cancer patients. The clinicopathological and prognostic significance of Muc5AC expression was validated using immunohistochemical analysis in 412 gastric cancer patients. Differential gene expression was investigated using complementary DNA microarray analysis of 48 fresh tumor tissue samples. Silencing of Muc5AC by using a small hairpin RNA-containing lentivirus increased the invasion and migration of SNU216 and AGS cells as well as Akt phosphorylation and the expression of vascular endothelial growth factor and matrix metalloproteinase-7, which were blocked by inhibitors of the phosphatidylinositol 3-kinase/Akt pathway. Loss of Muc5AC expression was significantly associated with tumor progression (advanced T stage; p = 0.004), lymph node metastases (p = 0.001), lymphovascular invasion (p < 0.0001), and increased tumor size (p = 0.027). Lower MUC5AC expression was identified as an independent poor prognostic factor in diffuse-type gastric cancer by using the Cox regression proportional hazard model (hazard ratio, 2.39; p = 0.043). Complementary DNA microarray analysis revealed 86 differentially expressed genes, including genes related to metastasis and invasion, in gastric cancer tissues with high (≥25%) and low (<25%) Muc5AC expression levels. Low Muc5AC expression increased the invasion and migration of gastric cancer cells and could be a useful biomarker of poor prognosis in gastric cancer.

Does clear cell carcinoma of stomach exist? Clinicopathological and prognostic significance of clear cell changes in gastric adenocarcinomas.

AIMS: In contrast to clear cell carcinomas developing in other organs (e.g. ovary and uterus), gastric adenocarcinomas with clear cell features are not well characterized. METHODS AND RESULTS: We evaluated a series of 762 gastric adenocarcinomas for the presence of clear cell changes; and investigated the nature of the changes using several histochemical and immunohistochemical markers, their association with various clinicopathological features, and their prognostic significance. Clear cell changes were observed in 8.5% (n = 65) of gastric cancers. Cases with clear cell changes (GCC) were associated significantly with older age, intestinal type histology, body/fundic location, greater depth of invasion, lymph node metastases and lymphovascular invasion. An increasing proportion of clear cell changes indicated a worsening prognosis, and was identified as an independent marker of poor prognosis using the Cox proportional hazard model (hazard ratio, 0.462; P = 0.003). Of 62 GCCs subjected to special staining, 35 cases (55.6%) displayed cytoplasmic accumulation of glycogen, while 21 (33.3%) contained mucin. GCCs showing glycogen accumulation expressed AFP, glypican-3 and CD10 more commonly than those with mucin, which commonly expressed Muc5AC and Muc6. CONCLUSION: Clear cell gastric adenocarcinoma is a unique subgroup of gastric cancer which, although heterogeneous, has a poor prognosis.

Digital image analysis of endoscopic ultrasonography is helpful in diagnosing gastric mesenchymal tumors.

BACKGROUND: Endoscopic ultrasonography (EUS) is a valuable imaging tool for evaluating subepithelial lesions in the stomach. However, there are few studies on differentiation between gastrointestinal stromal tumors (GISTs) and benign mesenchymal tumors, such as leiomyoma or schwannoma, with the use of EUS. In addition, there are limitations in the analysis of the characteristic features of such tumors due to poor interobserver agreement as a result of subjective interpretation of EUS images. Therefore, the aim of this study was to evaluate the role of digital image analysis in distinguishing the features of GISTs from those of benign mesenchymal tumors on EUS. METHODS: We enrolled 65 patients with histopathologically proven gastric GIST, leiomyoma or schwannoma on surgically resected specimens who underwent EUS examination at our endoscopic unit from January 2007 to September 2010. After standardization of the EUS images, brightness values including the mean (Tmean), indicative of echogenicity, and the standard deviation (TSD), indicative of heterogeneity, in the tumors were analyzed. RESULTS: The Tmean and TSD were significantly higher in GIST than in leiomyoma and schwannoma (p < 0.001). However, there was no significant difference in the Tmean or TSD between benign and malignant GISTs. The sensitivity and specificity were almost optimized for differentiating GIST from leiomyoma or schwannoma when the critical values of Tmean and TSD were 65 and 75, respectively. The presence of at least 1 of these 2 findings in a given tumor resulted in a sensitivity of 94%, specificity of 80%, positive predictive value of 94%, negative predictive value of 80%, and accuracy of 90.8% for predicting GIST. CONCLUSIONS: Digital image analysis provides objective information on EUS images; thus, it can be useful in diagnosing gastric mesenchymal tumors.

Risk factors for delayed gastric emptying caused by anastomosis edema after subtotal gastrectomy for gastric cancer.

BACKGROUND/AIMS: Delayed gastric emptying (DGE) is one of the most troublesome complications after subtotal gastrectomy for gastric cancer. We evaluated operative and perioperative variables to assess for independent risk factors of DGE caused by anastomosis edema. METHODOLOGY: The study retrospectively reviewed clinical data of 382 consecutive patients who underwent subtotal gastrectomy for gastric cancer between 2009 and 2011 at a single institution. RESULTS: Delayed gastric emptying had occurred in twelve patients (3.1%). Univariate analysis revealed high body mass index (>25kg/m2), open gastrectomy, and Billroth II or Roux-en Y reconstructions to be significant factors for delayed gastric emptying. Multivariate analysis identified high body mass index and open gastrectomy as predictors of delayed gastric emptying. CONCLUSIONS: To avoid delayed gastric emptying, surgeons should take care in creating the gastrointestinal anastomosis, particularly in patients with high BMI or in cases of open gastrectomy.

The application of enhanced recovery after surgery protocol after distal gastrectomy for patients with gastric cancer: a prospective randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC). METHODS: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed. RESULTS: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22. CONCLUSION: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups.

Learning curve analysis for hand-assisted laparoscopic living donor nephrectomy: an analysis of 96 consecutive cases performed by a trained gastrointestinal surgeon.

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m2. The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases; grade II, 9 cases), with no significant differences across phases. Conclusion: HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Diagnostic performance of F-18 FDG PET or PET/CT for detection of recurrent gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigated the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for the detection of disease recurrence after curative resection of gastric cancer. METHODS: The PubMed and Embase databases, from the earliest available date of indexing through November 30, 2019, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT to detect recurrent disease after gastric cancer surgery. RESULTS: Across 17 studies (1,732 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.82 (95% confidence interval [CI], 0.74-0.88) with heterogeneity of I2=76.5 (p<0.001), and the specificity was 0.86 (95% CI, 0.78-0.91) with heterogeneity of I2=94.2 (p<0.001). Likelihood ratio (LR) tests gave an overall positive LR of 6.0 (95% CI, 3.6-9.7) and negative LR of 0.2 (95% CI, 0.14-0.31). The pooled diagnostic odds ratio was 29 (95% CI, 13-63). The summary receiver operating characteristic curve indicates that the area under the curve was 0.91 (95% CI, 0.88-0.93). CONCLUSION: The current meta-analysis showed good sensitivity and specificity of F-18 FDG PET or PET/CT for detecting recurrent disease after curative resection of gastric cancer despite heterogeneity in ethnicity, recurrence rate, histology, and interpretation method.

Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer. METHODS: We examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail's clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis. RESULTS: Silencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion. CONCLUSION: Snail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.

Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research.

Cancer stem cells have been hypothesized to drive the growth and metastasis of tumors. Because they need to be targeted for cancer treatment, they have been isolated from many solid cancers. However, cancer stem cells from primary human gastric cancer tissues have not been isolated as yet. For the isolation, we used two cell surface markers: the epithelial cell adhesion molecule (EpCAM) and CD44. When analyzed by flow cytometry, the EpCAM(+)/CD44(+) population accounts for 4.5% of tumor cells. EpCAM(+)/CD44(+) gastric cancer cells formed tumors in immunocompromised mice; however, EpCAM(-)/CD44(-), EpCAM(+)/CD44(-) and EpCAM(-)/CD44(+) cells failed to do so. Xenografts of EpCAM(+)/CD44(+) gastric cancer cells maintained a differentiated phenotype and reproduced the morphological and phenotypical heterogeneity of the original gastric tumor tissues. The tumorigenic subpopulation was serially passaged for several generations without significant phenotypic alterations. Moreover, EpCAM(+)/CD44(+), but not EpCAM(-)/CD44(-), EpCAM(+)/CD44(-) or EpCAM(-)/CD44(+) cells grew exponentially in vitro as cancer spheres in serum-free medium, maintaining the tumorigenicity. Interestingly, a single cancer stem cell generated a cancer sphere that contained various differentiated cells, supporting multi-potency and self-renewal of a cancer stem cell. EpCAM(+)/CD44(+) cells had greater resistance to anti-cancer drugs than other subpopulation cells. The above in vivo and in vitro results suggest that cancer stem cells, which are enriched in the EpCAM(+)/CD44(+) subpopulation of gastric cancer cells, provide an ideal model system for cancer stem cell research.

Differential expression of ghrelin mRNA according to anatomical portions of human stomach.

BACKGROUND/AIMS: The detailed ghrelin distribution on mRNA level in different anatomical portions of adult stomach and its association with plasma ghrelin levels are not yet well established. We investigated the ghrelin mRNA and peptide expression in different anatomical portions of stomach in human adults. METHODOLOGY: Stomach tissue samples were obtained from 16 patients with gastric cancer who underwent total gastrectomy. The normal stomach tissues were taken from the upper (gastric fundus and upper body), middle (gastric middle and lower body) and lower (gastric antrum and pylorus) portions of stomach, respectively. The expression of ghrelin mRNA and peptide in stomach tissue samples were measured using RT-PCR and immunohistochemistry. RESULTS: The ghrelin/actin ratio was 0.78 (range 0-3.38; n=16) at the upper portion, 0.20 (range 0-1.28; n=16) at the middle portion and 0.07 (range 0-0.67; n=16) at the lower portion of the stomach (p=0.001). Ghrelin-positive cells were seen in all parts of the gastric mucosa and were most numerous in the glandular compartment compared to foveolar compartment. Gastric body or fundic mucosa showed ghrelin-positive cells most abundantly as compared to other portions of the gastric mucosa (p<0.001). CONCLUSIONS: Ghrelin mRNA expression and immunoreactivity is highest at the upper portion of the human stomach.

Actual 3-Year Survival After Reduced-Port Laparoscopic Distal Gastrectomy for Gastric Cancer (RpLDG): a Propensity Score Matching Analysis.

BACKGROUND: Total laparoscopic distal gastrectomy for early gastric cancer has been widely accepted; however, reduced-port laparoscopic distal gastrectomy has not gained the same popularity because of technical difficulties and oncologic safety issues. This study aimed to analyze the oncologic safety and short-term surgical outcomes of patients who underwent reduced-port laparoscopic distal gastrectomy (RpLDG) for gastric cancer. METHODS: Consecutive patients who underwent surgical treatment between January 2016 and May 2018 were included in this study. Of the 833 patients enrolled, 158 underwent RpLDG and were propensity-matched with 158 patients who underwent conventional port laparoscopic distal gastrectomy (CpLDG). The groups were compared in terms of short-term outcomes and disease-free and overall survival rates. RESULTS: The RpLDG group had shorter operation times (161.8 min vs. 189.0 min, p < 0.00) and shorter postoperative hospital stays (7.6 days vs. 9.1 days, p = 0.04) compared to the CpLDG group. Estimated blood loss was lower in the RpLDG group than in the CpLDG group (52.6 mL vs. 73.7 mL, p < 0.00), while hospital costs incurred by the RpLDG group were lower than those of the CpLDG group (10,033.7 vs. 11,016.8 USD, p < 0.00). No statistical differences were found regarding overall morbidity and occurrence of surgical complications of grade III or higher, as defined by the Clavien-Dindo classification. Furthermore, no significant differences between RpLDG and CpLDG were found in 3-year disease-free (99.4% vs. 98.1%; p = 0.42) and 3-year overall survival rates (98.7% vs. 96.8%; p = 0.25). CONCLUSION: Patients who underwent RpLDG had better short-term surgical outcomes than those who underwent CpLDG in terms of operation time, estimated blood loss, duration of hospital stay, and hospital costs. The oncologic safety of RpLDG was satisfactory.

Endosonographic findings of gastric ectopic pancreas: a single center experience.

BACKGROUND AND AIM: Ectopic pancreas is a common submucosal lesion in the stomach, but its histological diagnosis is usually difficult when tissue samples are obtained with a conventional biopsy forceps. The aim of this study was to describe the endosonographic features of gastric ectopic pancreas. METHODS: We retrospectively analyzed a database of all patients who underwent endoscopic ultrasonography (EUS) at Pusan National University Hospital from July 2006 to August 2010. A total of 26 patients with histologically confirmed ectopic pancreas were included in the study. The EUS features of their lesions were analyzed. RESULTS: Ten lesions were located in the antrum, and 16 lesions were located in the body. Nine lesions (34.6%) showed an umbilication or central dimpling on the surface, and a mural growth pattern was most commonly observed (61.5%). Twenty-four lesions (92.3%) showed hypoechoic echogenicity, and 13 lesions (50.0%) were heterogeneous. The borders were indistinct in 16 lesions (61.5%) and lobulated margins were observed in 16 lesions (61.5%). Anechoic cystic or tubular structures appeared in 17 lesions (65.4%), and 20 lesions (76.9%) involved two or more sonographic layers. CONCLUSIONS: The characteristic EUS features of ectopic pancreas are indistinct borders, lobulated margins, presence of anechoic duct-like structures, a mural growth pattern, and localization within two or more layers. These EUS features are potentially useful for differentiating ectopic pancreas from other mesenchymal tumors in the stomach.