Effectiveness of fibrin sealant as hemostatic technique in accelerating ESD-induced ulcer healing: a retrospective study.

OBJECTIVES: Healing of gastric endoscopic submucosal dissection (ESD)-induced ulcer is critical for patient recovery. During ESD treatment, submucosal incisions are made with an electrosurgical knife to accomplish en bloc resections of superficial lesions. Nevertheless, excess electrocoagulation may decrease the blood supply of ESD-induced ulcer and delay the ulcer healing. The aim of this retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a wound microvessels-protective hemostatic technique in promoting the healing of ESD-induced ulcer. METHODS: A total of 332 patients with early gastric cancer (EGCs), or gastric precancerous lesion and gastric adenoma were retrospectively analyzed. Propensity score matching was used to compensate for the differences in age, gender, tumor location, resected specimen area, and pathology. One-month ulcer healing rates and delayed bleeding were compared between two matched groups (combined hemostats group and electrocautery group). RESULTS: A total of 115 matched pairs were created after propensity score matching. There was no difference in tumor location, specimen surface area, tumor differentiation and invasion depth between groups. The completed healing rate 1 month after ESD was 44.3% in combined hemostats group and 30.4% in electrocautery group (P = 0.004). There was no difference in delayed massive bleeding rate between two groups (P = 0.300). In addition, based on the multivariate regression analysis for ulcer healing rate, the use of FS (OR, 0.348, 95% CI 0.196 - 0.617, P = 0.000) and larger specimen size (OR, 2.640, 95% CI 2.015-3.458, P = 0.000) were associated with nonhealing ulcer 1 month after ESD. CONCLUSION: Applying conservative electrocoagulation followed by porcine FS as a wound microvessels-protective hemostatic technique can promote ESD-induced ulcer healing without increasing delayed bleeding.

The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results from a Chinese mono-institutional study of 1663 patients.

BACKGROUND: We investigated the superiority of the 8th edition of the tumor-node-metastasis (TNM) system for patients in China with gastric cancer. METHODS: The survival outcomes of 1663 patients with gastric cancer undergoing radical resection were analyzed. RESULTS: In the 8th edition system, homogeneous 5-year survival rates among different pathological TNM (pTNM) categories belonging to the same stage were observed. However, in the 7th edition system, the differences of 5-year survival rate among pTNM categories belonging to the same stage were observed in stages IIB (P = 0.010), IIIB (P = 0.004), and IIIC (P < 0.001). For patients in the pT1-3 (P < 0.001) and pT4a (P < 0.001) categories, there were significant differences in survival between patients in the pN3a and pN3b categories. Furthermore, partial cases (pT4bN0M0/T4aN2M0) of stage IIIB were downstaged to stage IIIA in the 8th edition system, and the 5-year survival rate of these patients was significantly better than that of patients in stage IIIB in the 8th edition system. Similarly, the 5-year survival rate of patients in p4bN2M0/T4aN3aM0 downstaged from stage IIIC to IIIB was significantly better than that of patients in stage IIIC. Compared with the 7th edition system, the 8th edition system had a higher likelihood ratio and linear trend chi-squared score and a smaller Akaike information criteria value. CONCLUSIONS: The 8th edition system is superior to the 7th edition system in terms of homogeneity, discriminatory ability, and monotonicity of gradients for Chinese patients with gastric cancer.

Prognostic significance of the total number of harvested lymph nodes for lymph node-negative gastric cancer patients.

BACKGROUND: The relationship between the number of harvested lymph nodes (HLNs) and prognosis of gastric cancer patients without an involvement of lymph nodes has not been well-evaluated. The objective of this study is to further explore this issue. METHODS: We collected data from 399 gastric cancer patients between November 2006 and October 2011. All of them were without metastatic lymph nodes. RESULTS: Survival analyses showed that statistically significant differences existed in the survival outcomes between the two groups allocated by the total number of HLNs ranging from 16 to 22. Therefore, we adopted 22 as the cut-off value of the total number of HLNs for grouping (group A: HLNs <22; group B: HLNs≥22). The intraoperative and postoperative characteristics, including operative blood loss (P=0.096), operation time (P=0.430), postoperative hospital stay (P=0.142), complications (P=0.552), rate of reoperation (P=0.966) and postoperative mortality (P=1.000), were comparable between the two groups. T-stage-stratified Kaplan-Meier analyses revealed that the 5-year survival rate of patients at the T4 stage was better in group B than in group A (76.9% vs. 58.5%; P=0.004). An analysis of multiple factors elucidated that the total number of HLNs, T stage, operation time and age were independently correlated factors of prognosis. CONCLUSIONS: Regarding gastric cancer patients without the involvement of lymph nodes, an HLN number ≥22 would be helpful in prolonging their overall survival, especially for those at T4 stage. The total number of HLNs was an independent prognostic factor for this population of patients.

The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival.

BACKGROUND: The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer. METHODS: We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study. RESULTS: We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival. CONCLUSIONS: For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.

Comparison of different methods of splenic hilar lymph node dissection for advanced upper- and/or middle-third gastric cancer.

BACKGROUND: Surgery for advanced gastric cancer (AGC) often includes dissection of splenic hilar lymph nodes (SHLNs). This study compared the safety and effectiveness of different approaches to SHLN dissection for upper- and/or middle-third AGC. METHODS: We retrospectively compared and analyzed clinicopathologic and follow-up data from a prospectively collected database at the Peking University Cancer Hospital. Patients were divided into three groups: in situ spleen-preserved, ex situ spleen-preserved and splenectomy. RESULTS: We analyzed 217 patients with upper- and/or middle-third AGC who underwent R0 total or proximal gastrectomy with splenic hilar lymphadenectomy from January 2006 to December 2011, of whom 15.2 % (33/217) had metastatic SHLNs, and from whom 11.4 % (53/466) of the dissected SHLNs were metastatic. The number of harvested SHLNs per patient was higher in the ex situ group than in the in situ group (P = 0.017). Length of postoperative hospital stay was longer in the splenectomy group than in the in situ group (P = 0.002) or the ex situ group (P < 0.001). The splenectomy group also lost more blood volume (P = 0.007) and had a higher postoperative complication rate (P = 0.005) than the ex situ group. Kaplan-Meier (log rank test) analysis showed significant survival differences among the three groups (P = 0.018). Multivariate analysis showed operation duration (P = 0.043), blood loss volume (P = 0.046), neoadjuvant chemotherapy (P = 0.005), and N stage (P < 0.001) were independent prognostic factors for survival. CONCLUSIONS: The ex situ procedure was more effective for SHLN dissection than the in situ procedure without sacrificing safety, whereas splenectomy was not more effective, and was less safe. The SHLN dissection method was not an independent risk factor for survival in this study.

Capecitabine plus paclitaxel induction treatment in gastric cancer patients with liver metastasis: a prospective, uncontrolled, open-label Phase II clinical study.

AIM: To determine the overall survival rate, radical resection rate, objective response rate and safety of capecitabine plus paclitaxel induction chemotherapy in gastric cancer patients with liver metastases. PATIENTS & METHODS: A total of 30 patients (median age: 59.5 years) diagnosed as gastric adenocarcinoma with liver metastasis received ≥3 cycles of capecitabine and paclitaxel therapy followed by radical resection 4-6 weeks after termination of chemotherapy. RESULTS: The median survival time was 11.4 months, and the objective response rate was 53.3%. The radical resection rate was 23.3% (95% CI: 9.9-42.3). Major toxicities included grade 3 neutropenia (10.0%) and grade 3 diarrhea (3.3%). CONCLUSION: Capecitabine plus paclitaxel chemotherapy may be effective and safe to improve overall survival and the resection rate of gastric cancer patients with liver metastases. ClinicalTrials.gov identifier: NCT0116704.

Neoadjuvant chemoradiation therapy for resectable esophago-gastric adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The efficacy and safety of preoperative chemoradiation therapy (CRT) for advanced esophago-gastric adenocarcinoma are still in question, and the prognosis of these patients is poor. METHODS: We systematically searched electronic databases from January 1990 to July 2014. The primary outcome was overall survival. The secondary outcomes were a R0 resection rate, positive rate of lymph node metastasis, postoperative recurrence rate, pathological complete response (pCR) rate and perioperative mortality. Overall survival was measured with a hazard ratio (HR), while other secondary outcomes were measured with an odds ratio (OR). RESULTS: Seven randomized controlled trials (RCTs) including 1085 patients were searched and, of these, 869 had adenocarcinoma. Patients receiving preoperative CRT had a longer overall survival (HR 0.74; 95% confidence interval (CI) 0.63-0.88), higher likelihood of R0 resection and greater chance of pCR, while they had a lower likelihood of lymph node metastasis and postoperative recurrence. The difference of perioperative mortality was non-significant. In addition, the result of the comparison between preoperative CRT and preoperative chemotherapy (CT) in two RCTs was non-significant. CONCLUSION: Patients with resectable esophago-gastric adenocarcinoma can gain a survival advantage from preoperative CRT. However, limited to the number of RCTs, the effect of adding radiotherapy to preoperative CT separately is still uncertain and more high-quality prospective trials are needed.

[Application of endoscopic submucosal dissection in treatment of early gastric cancer].

OBJECTIVE: To evaluate the clinical outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in a single center in China. METHODS: We performed a retrospective analysis of the patients with single EGC lesion who received ESD in Peking University Cancer Hospital from January 2011 to December 2013.Their clinicopathologic data, resectability, curability, complications and follow-up data were assessed. RESULTS: A total of 116 patients were enrolled in the study. The patients included 88 men and 28 women, with a median age of 63 years (range: 25-80 years).The post-operative histology of the lesions included 28 (24.1%) high grade intraepithelial neoplasia, 35 (30.2%) well differentiated adenocarcinoma, 35 (30.2%) moderated differentiated adenocarcinoma and 18 (15.5%) poorly differentiated adenocarcinoma. Of all the lesions, 75.0% (87/116) were confined into mucosa, 15.5% (18/116) invaded SM1 (<500 µm from the muscularis mucosae) and 9.5% (11/116) invaded SM2 (≥ 500 µm from the muscularis mucosae). The mean tumor size was (1.49 ± 0.96) cm, and the rate of ulceration was 14.7% (17/116). The en bloc resection rates were 96.7% (111/116), complete resection rates were 93.1% (108/116) and curative resection rates were 77.6% (90/116). According to the curability, 62 (53.4%) cases were classified into the standard curative resection (sCR) group, 28 (24.2%) into the expanded curative resection (eCR) group and 26 (22.4%) into the non-curative resection (nCR) group. The mean tumor size of the sCR group was smaller than that of the eCR and nCR group (t=-4.121, P<0.001 and t=-3.420, P=0.001). In the nCR group, the portion of type 0-III lesion and ulceration were significantly higher (χ² = 10.287, P=0.006 and χ² = 17.737, P<0.001). In multivariate analysis, EGC with ulceration and submucosal invasion were the risk factors for non-curative resection (OR=6.634, P=0.006 and OR=12.735, P<0.001). The ESD-related complications included 4 (3.4%) post-operative bleeding, 3 (2.6%) intra-operative perforation, 2 (1.7%) cardiac stenosis and 1 (0.9%) heart failure. In the study, 106 of the 116 patients received periodic follow-up, during a median follow-up of 22 months (12-47 months). Local tumor recurrence developed in 1 patient of the eCR group 8 months post the ESD. CONCLUSION: ESD is a safe and feasible option for EGC in China, ulceration and submucosal invasion are associated with non-curative resection, and post-operative bleeding and intra-operative perforation should be concerned as the main complications.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination.

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19-71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS + HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1-18.9 months) but was only 10.4 months (95 % CI 8.5-12.2 months) in the CRS group (P = 0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS + HIPEC was significantly higher than that for the patients treated with CRS alone (P = 0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P = 0.141). A multivariate analysis revealed that CRS + HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.

Imatinib mesylate in clinically suspected gastric stromal tumors.

Gastrointestinal stromal tumors (GISTs) occur most frequently in the stomach. Diagnosis of gastric GIST is not always clear before surgery. Flexible endoscopy may suggest the nature of the lesion (a bulky tumor with preserved mucosa); however, biopsy is rarely diagnostic. Therefore, diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained. Based on the excellent efficacy of imatinib mesylate (IM) in the treatment of GIST, we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors. In conclusion, the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer.

BACKGROUND: Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. METHODS: This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences. RESULTS: There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths. CONCLUSION: Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.

Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer.

BACKGROUND: This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy. METHODS: We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy. RESULTS: There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups. CONCLUSION: The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.

Utility of the gastric window in computed tomography for differentiation of early gastric cancer (T1 stage) from muscularis involvement (T2 stage).

OBJECTIVE: To analyze the diagnostic value of using the gastric window in computed tomography for differentiation of early gastric cancer (T1 stage) from muscularis involvement (T2 stage). MATERIALS AND METHODS: All patients with pathologically confirmed T1 stage and T2 stage gastric cancer and who underwent endoscopic resection or gastrectomy at our institution from January 2011 to November 2018 were examined. Each patient received an enhanced CT scan of the abdomen before the operation. T staging of tumors based on the CT scans was performed independently by two radiologists using the gastric window (width 150-200 HU, level 80-100 HU) and the abdominal window (width 350-400 HU, level 50 HU). RESULTS: Use of the gastric window to diagnose stage T1 EGC led to an accuracy of 88.9% for observer1 and 91.5% for observer2; use of the abdominal window led to an accuracy of 53.6% for observer1 and 51.6% (38/106) for observer2. Use of the gastric window to diagnose stage T2 led to an accuracy of 85.6% for observer1 and 82.4% for observer2; use of the abdominal window led to an accuracy of 52.3% for both observer1 and observer2. For observer1, use of the gastric window had a diagnostic accuracy of 69.2% for stage T1a and 62.5% for stage T1b; for observer2, the diagnostic accuracy was 65.1% for stage T1a and 67.0% for stage T1b. A Kappa test indicated moderate and substantial inter-observer agreement for T staging with gastric window (κ = 0.598, P < 0.001) and abdominal window (κ = 0.745, P < 0.001). CONCLUSION: Use of the gastric window in computed tomography provided more accurate staging for T1 and T2 stages of gastric cancer than the conventional abdominal window.

Preliminary results of simultaneous integrated boost intensity-modulated radiation therapy based neoadjuvant chemoradiotherapy on locally advanced rectal cancer with clinically suspected positive lateral pelvic lymph nodes.

BACKGROUND: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs. METHODS: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated. RESULTS: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence. CONCLUSIONS: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).

[Surgical treatment results and prognostic analysis of 514 cases with gastroesophageal junction carcinoma].

OBJECTIVE: To clarify the important clinicopathological and therapeutical factors affecting the prognosis of patients with gastroesophageal junction carcinoma. METHODS: Data of 514 cases with gastroesophageal junction carcinoma who underwent surgical treatment from September 1995 to January 2007 was retrospectively analyzed. Relevant prognostic factors were studied with univariate and multivariate analysis. RESULTS: For all 514 cases (424 men and 90 women), the median age was 63 years. The 1-, 3- and 5-year survival rates of this group were 74.8%, 42.1% and 29.1%, respectively. Gross type, TNM classification, histological type, vascular invasion and extent of surgical resection affected patients' survival remarkably. There was no significant difference in survival between operative approaches (via laparotomy or left thoracotomy) (P > 0.05). Long-term survival was similar between proximal subtotal gastrectomy and total gastrectomy in advanced cases (P > 0.05). For stage II and III tumors, patients with neoadjuvant chemotherapy had better prognosis than those without (P < 0.05). Cox multivariate regression analysis revealed TNM classification and vascular invasion were independent prognostic factors. CONCLUSIONS: TNM classification and vascular invasion are independent prognostic factors for gastroesophageal junction carcinoma. Neoadjuvant chemotherapy may improve prognosis of the patients with stage II and III tumors. Radical resection should be achieved with rational surgical procedures tailored by tumor position, size, staging and so on.

Endoscopic ultrasonography for pretreatment T-staging of gastric cancer: An in vitro accuracy and discrepancy analysis.

In the current era of multi-disciplinary treatment, precise and detailed diagnosis prior to treatment is crucial for clinical practice. For different lesions that fit different indications, the optimum approach for treatment differs significantly. Thus, the recent 8th American Joint Committee on Cancer classification system has introduced 'clinical stage' as a criterion. Endoscopic ultrasonography (EUS) has been the first-line choice for pretreatment staging; however, there is no standardization of the depth classification nor a standard EUS method. Additionally, the accuracy for this diagnostic test has ranged between <40 and 90% in previous studies. The aim of the present study was to determine the accuracy of EUS, identify the discrepancies between EUS and histological results, and analyze the underlying causes. Between June 2014 and February 2016, EUS was performed on gastric carcinoma specimens from 60 consecutive patients. EUS was performed on the resected specimens following surgery, but prior to fixation in formalin, invasion of the gastric wall was determined and the deepest location was marked with sutures. The ultrasound images were independently interpreted, and the quality of the images was scored by two endoscopists. Subsequently, the ultrasound images were compared with the pathological results of the same section. The overall accuracy of EUS was 75%. For locally advanced gastric cancers, EUS had a relatively high accuracy (33/43, 86%). The EUS results corresponded well with the pathological hematoxylin and eosin staining results, and the deepest points determined by EUS were confirmed by pathology in the majority of cases (85%). In total, 50 and 10 cases were scored as having high/moderate and low quality, associated with accuracies of 86% (43/50) and 20% (2/10), respectively. EUS is valuable for pretreatment T-staging, particularly for advanced cases. Proximal stomach cancer exhibited a tendency for improved accuracy. Overall, the results of the present study suggest that standardized scanning processes, particularly including all-encompassing scanning, proper probe-placement and high image quality, lead to improved accuracy of EUS.

Increased expression of S100A6 promotes cell proliferation in gastric cancer cells.

S100A6 is involved in regulating the progression of cancer. S100A6 can regulate the dynamics of cytoskeletal constituents, cell growth and differentiation by interacting with binding or target proteins. The present study investigated whether S100A6 affects cell proliferation in gastric cancer cells by stimulating several downstream factors. Firstly, the expression and localization of S100A6 were investigated using immunohistochemical staining, an immunoelectron microscopy and laser confocal scanning. A ChIP-Chip assay was performed to determine the downstream factors of S100A6 using promoter Chip analysis, including approximately the -800 to +200 regions around the transcription starting point. Polymerase chain reaction analysis was performed to confirm this. It was found that the intensity of S100A6 staining was markedly higher in the cytoplasm and nucleus, and its expression level correlated with that of the Ki67 protein. The overexpression of S100A6 also promoted cell proliferation in AGS and BGC823 cell lines, detected using a Cell Counting-Kit 8 assay. In cells overexpressing S100A6, the expression levels of interleukin (IL)-8, cyclin-dependent kinase (CDK)5, CDK4, minichromosome maintenance complex component 7 (MCM7) and B-cell lymphoma 2 (Bcl2) were noticeably increased. In conclusion, the increased expression of S100A6 promoted cell proliferation by regulating the expression levels of IL-8, CDK5, CDK4, MCM7 and Bcl2 in gastric cancer cells.

Paclitaxel enhances tumoricidal potential of TRAIL via inhibition of MAPK in resistant gastric cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promise for cancer therapy due to its unique capacity to selectively trigger apoptosis in cancer cells. However, TRAIL therapy is greatly hampered by its resistance. A preclinical successful strategy is to identify combination treatments that sensitize resistant cancers to TRAIL. In the present study, we fully assessed TRAIL sensitivity in 9 gastric cancer cell lines. We found combined administration of paclitaxel (PTX) markedly enhanced TRAIL-induced apoptosis in resistant cancer cells both in vitro and in vivo. The sensitization to TRAIL was accompanied by activation of mitochondrial apoptotic pathway, upregulation of TRAIL receptors and downregulation of anti-apoptotic proteins including C-IAP1, C-IAP2, Livin and Mcl-1. Noticeably, we found PTX could suppress the activation of mitogen-activated protein kinases (MAPKs). Inhibition of MAPKs using specific inhibitors (ERK inhibitor U0126, JNK inhibitor SP600125 and P38 inhibitor SB202190) facilitated TRAIL-mediated apoptosis and cytotoxicity. Additionally, SP600125 upregulated TRAL receptors as well as downregulated C-IAP2 and Mcl-1 suggesting the anti-apoptotic role of JNK. Thus, PTX-induced suppression of MAPKs may contribute to restoring TRAIL senstitivity. Collectively, our comprehensive analyses gave new insight into the role of PTX on enhancing TRAIL sensitivity, and provided theoretical references on the development of combination treatment in TRAIL-resistant gastric cancer.

Prognosis of patients with gastric cancer and solitary lymph node metastasis.

AIM: To investigate the relationship of solitary lymph node metastasis (SLNM) and age with patient survival in gastric cancer (GC). METHODS: The medical records databases of China's Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People's Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012. Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis. In total, 936 patients with GC + SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up (range: 13-2925 d) were collected. The Kaplan-Meier method was used to stratify patients by age (≤ 50 years-old, n = 198; 50-64 years-old, n = 321; ≥ 65 years-old, n = 446) and by metastatic lymph node ratio [MLR < 0.04 (1/25), n = 180; 0.04-0.06 (1/25-1/15), n = 687; ≥ 0.06 (1/15), n = 98] for 5-year survival analysis. The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS: The 5-year survival rate of the entire GC + SLNM patient population was 49.9%. Stratification analysis showed significant differences in survival time (post-operative days) according to age: ≤ 50 years-old: 950.7 ± 79.0 vs 50-64 years-old: 1697.8 ± 65.9 vs ≥ 65 years-old: 1996.2 ± 57.6, all P < 0.05. In addition, younger age (≤ 50 years-old) correlated significantly with mean survival time (r = 0.367, P < 0.001). Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time: < 0.04: 52.8% and 0.04-0.06: 51.1% vs ≥ 0.06: 40.5%, P < 0.05. The patients with the shortest survival times and rates were younger and had a high MLR (≥ 0.06): ≤ 50 years-old: 496.4 ± 133.0 and 0.0% vs 50-65 years-old: 1180.9 ± 201.8 and 21.4% vs ≥ 65 years-old: 1538.4 ± 72.4 and 37.3%, all P < 0.05. The same significant trend in shorter survival times and rates for younger patients was seen with the mid-range MLR group (0.04-0.06), but the difference between the two older groups was not significant. No significant differences were found between the age groups of patients with MLR < 0.04. Assessment of clinicopathological parameters identified age group, Borrmann type, histological type and tumor depth as the most important predictors of the survival rates and times observed for this study population. CONCLUSION: GC patients below 51 years of age with MLR of SLNM above 0.06 have shorter life expectancy than their older counterparts.

[Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer].

OBJECTIVE: To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer. METHODS: Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively. RESULTS: Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05). CONCLUSION: S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.