Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Calcitriol-Loaded Multifunctional Nanospheres with Superlubricity for Advanced Osteoarthritis Treatment.

Osteoarthritis (OA) is characterized by the lubrication dysfunction of a cartilage sliding interface caused by chronic joint inflammation, and effective nonsurgical therapy for advanced OA remains lacking. Addressing chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation simultaneously may hopefully tackle this challenge. Herein, we developed superlubricative zein@alginate/strontium@calcitriol (ZASC) nanospheres to treat advanced OA. ZASC was confirmed to significantly improve joint lubrication through traditional tribological tests and our proposed tribological experiment to mimic the intra-articular condition based on the human medial tibiofemoral joint tissues. This finding was attributed to the hydration lubrication formed around the alginate-strontium spheres that enabled ball-bearing lubrication and the filling of cartilage defects. Moreover, ZASCs that released calcitriol in a sustained manner showed proliferative, anti-inflammatory, and anti-apoptosis effects in vitro. Further experiments demonstrated that ZASC exerted chondroprotective effects by inhibiting the breakdown of the extracellular matrix in patient-derived OA cartilage explants. In vivo results demonstrated that ZASC can effectively maintain a normal gait to improve joint function, inhibit abnormal bone remodeling and cartilage degradation in early OA and can effectively reverse the advanced OA progression. Therefore, ZASC is a potentially nonsurgical therapeutic strategy for advanced OA treatments.

circDYRK1A tethers biological behaviors of gastric carcinoma using novel bioinformatics analysis and experimental validations.

Gastric cancer has been one of the wide public health burdens with its high morbidity and mortality over several decades. As the unconventional modules among RNA families, circular RNAs present their blazing biological effects during gastric carcinogenesis. Though diverse hypothetical mechanisms were reported, further tests were necessitated for authentication. Herein, this study pinpointed a representative circDYRK1A which screened from vast amounts of public data sets using surprisingly novel bioinformatics approaches together with validations from the in vitro findings and then concluded that circDYRK1A tethered the biological behavior and swayed the clinicopathological features with gastric cancer patients thus providing an in-depth awareness for gastric carcinoma.

Pyroptosis is related to immune infiltration and predictive for survival of colon adenocarcinoma patients.

Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients' prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183-3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061-1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.

Effect of Chemoradiotherapy on the Survival of Resectable Gastric Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) after surgery are necessary to reduce the risk of metastasis and recurrence for resectable gastric cancer (GC) patients. Adjuvant CT and CRT have been proven to significantly improve the prognosis for GC patients, when compared with surgery only. However, it is still unclear whether radiotherapy offers additional survival benefits to advanced gastric cancer (AGC) patients. METHODS: PubMed, Cochrane Library, and Embase databases were systematically searched for eligible studies that compared survival benefits between CRT and CT. The endpoints of this meta-analysis were measured as HR for OS or DFS and 95% CI using fixed- or random-effect models. Additionally, side effects, completed rate, and metastatic risk, were calculated as OR. Subgroup analyses according to clinicopathological factors were presented. RESULTS: A total of 28 eligible studies involving 20,220 patients were included in our study. Of these, 17 studies evaluated the survival benefits of additional radiotherapy on overall survival (OS) of gastric cancer patients, ten reported the impact of CRT on disease-free survival (DFS), and 26 studies showed long-term survival rate. The pooled results were significant (HR for OS 0.84, 95% CI 0.71-0.99; HR for DFS 0.76, 95% CI 0.66-0.89). The subgroup analysis showed that adjuvant CRT increased OS for patients without preoperative treatment; showed similar nausea/vomiting, but an increased risk of neutropenia; reduced the risk of locoregional recurrence; failed to improve OS for lymph node (LN)-positive GC patients; and significantly improved prognosis for R1-treated patients. Of note, DFS was improved in all the subgroups via decreasing the locoregional recurrence. CONCLUSION: Compared with CT, adjuvant CRT can improve survival for advanced gastric cancer patients, with similar nausea/vomiting, but increased risk of neutropenia. Patients without preoperative treatment or with positive surgical margins should be strongly recommended to undergo CRT. Treatment regimens should be carefully decided by doctors based on patients' tolerance, physical status, and reaction to treatment. Moreover, CRT improves the DFS for patients regardless of subgroups, because it significantly reduced the risk of locoregional recurrence.

Differentiated/undifferentiated mixed type is a prognostic factor for T2/T3 gastric cancer patients.

OBJECTIVES: This work aimed to find the association of mixed-type histology and prognosis of T2/T3 GC patients. METHODS: Eligible T2/T3 gastric cancer patients at our institution were identified. The histological types and risk factors affecting OS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 972 T2/T3 gastric cancer patients, including 283 differentiated-type patients, 544 undifferentiated-type patients and 145 mixed type. Mixed-type histology was associated with shorter 5-year OS (DT vs UDT vs MT:57.5% vs 44.9% vs 39.6%, P = 0.002). MT histology can be predictive for prognosis of T2/T3 GC patients (HR for OS: 1.386, 95% CI: 1.028-1.868, P = 0.032), and its malignant potential is not inferior to UDT. In the subgroup analysis, MT can potentially be independent risk factor for non-distal GC patients (P = 0.010). CONCLUSION: This study reported that mixed histology could be regarded as a potential prognostic factor for T2/T3 gastric cancer patients, especially for those with non-distal cancer. MT patients have higher incidence of metastasis and recurrence and had poorer prognosis than those with pure histological type. It is necessary for MT patients to have preoperative pathological examination for accurate histologic classification, so as to make the comprehensive treatment strategies..

Central lymph node metastasis is predictive of survival in advanced gastric cancer patients treated with D2 lymphadenectomy.

BACKGROUND: The number of positive lymph nodes, which was defined as "N stage", is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A "central lymph node" (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. METHODS: Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138-1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). CONCLUSION: Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.

Different clinicopathologic features and prognostic significance of signet ring cell histology in early and locally advanced gastric cancer patients.

BACKGROUND: Although many studies have evaluated the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients, the results were conflicting. The objective of this study was to compare clinicopathologic characteristics between SRC type and other types, and evaluate its impact on survival outcome. METHODS: We retrospectively reviewed clinicopathologic and survival data of 1891 patients who underwent curative resection for GC. All patients were divided into differentiated, undifferentiated and SRC type according to the histological classification. The prognostic differences between different types were compared and clinicopathologic factors were analyzed. RESULTS: SRC histology type had a poorer disease-free survival (DFS) than differentiated type (5-year DFS, 37.7% vs 52.2%, P<0.001), but there was no prognostic difference between SRC type and undifferentiated type (37.7% vs 41.9%, P>0.05). For early GC patients, SRC type was more frequent in younger, female patients and T1a stage tumors; the 5-year DFS of SRC type was similar to that of any other histology type (P>0.05). SRC type showed more aggressive biological features, including extensive stomach involvement, large tumor size, advanced pTstage and pN stage, than other types for locally advanced GC patients; poorer DFS was observed in SRC type compared with differentiated type. Multivariate analysis indicated that SRC type (HR:1.71, 95%CI:1.10-1.68, P<0.01) and undifferentiated type (HR:1.21, 95%CI:1.04-1.40, P<0.05) were independently associated with poor DFS in locally advanced GC patients. CONCLUSION: There was a significant difference between early and locally advanced GC patients with regard to clinicopathologic features and prognostic significance of SRC histology. SRC type was an independent prognostic factor for locally advanced GC patients, but not for early GC patients.

Risk of lymph node metastasis and prognostic outcome in early gastric cancer patients with mixed histologic type.

BACKGROUND: Whether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type. METHODS: We retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated. RESULTS: Histopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P < 0.01). However, there was no significant difference between mixed type and pure undifferentiated type for LNM (32.4% vs 21.1%, P = 0.139). Multivariate analysis revealed that tumor size >2 cm (odds ratio [OR]: 2.153, 95% confidence interval [CI]: 1.113-4.164, P < 0.05), submucosal invasion (OR: 3.881, 95%CI: 1.832-8.222, P < 0.001), lymphovascular invasion (OR: 8.797, 95% CI: 2.643-29.277, P < 0.001), undifferentiated type (OR: 3.146, 95% CI: 1.352-7.320, P < 0.01), and mixed histologic type (OR: 3.635, 95% CI: 1.272-10.390, P < 0.05) were independent risk factors for LNM in early gastric cancer patients. However, mixed histologic type did not affect the survival outcome of these patients (hazard ratio: 0.629, 95% CI: 0.074-5.311, P > 0.05). CONCLUSION: Mixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients. The decisions regarding endoscopic submucosal dissection for mixed histologic type should be carefully considered.

Impact of Lymphovascular Invasion on Survival Outcome in Patients With Gastric Cancer.

OBJECTIVES: To evaluate the prognostic significance of lymphovascular invasion (LVI) for patients with gastric cancer (GC). METHODS: A total of 1,720 consecutive patients who underwent curative gastrectomy were retrospectively identified. The association between LVI and clinicopathologic characteristics was determined and its impact on survival outcome was evaluated. RESULTS: LVI was detected in 21.3% of GC patients, 5.9% of patients with early GC, 24.0% of patients with advanced GC, and 6.7% of node-negative patients using H&E staining. Tumor size (odds ratio [OR], 1.509; 95% confidence interval [CI], 1.159-1.965; P < .01), differentiated type (OR, 1.817; 95% CI, 1.377-2.398; P < .001), and the depth of tumor invasion (OR, 3.011; 95% CI, 2.174-4.171; P < .001) were independent predictive factors for LVI. LVI-positive patients have a poorer prognosis than LVI-negative patients, irrespective of tumor stage or lymph node metastasis. LVI was an independent prognostic factor for patients with GC (hazard ratio, 1.299; 95% CI, 1.112-1.518; P < .001). CONCLUSIONS: LVI provided additional prognostic information for GC patients, and LVI-positive patients should be considered candidates for adjuvant chemotherapy.

Clinicopathological features, risk of lymph node metastasis and survival outcome of synchronous multiple early gastric cancer.

OBJECTIVE: To determine clinicopathological features, risk of lymph node metastasis (LNM) and survival outcome in synchronous multiple early gastric cancer (MEGC) patients. METHODS: A total of 338 solitary early gastric cancer (SEGC) and 26 MEGC patients who underwent surgical resection were retrospectively reviewed. The clinicopathological features and predictive factors for MEGC patients were evaluated. Also, we analyzed risk factors for LNM and compared survival difference between SEGC and MEGC patients. RESULTS: The frequency of multiple synchronous lesions was 7.1% in early gastric cancer (EGC) patients. The main and minor lesions were mostly confined to the same third of the stomach (84.6%, 22/26), and the most common location was the lower third of the stomach. With regard to the number of coexisting lesions, most of the patients had two lesions and more than three lesions were not common. Tumor size≤2cm (OR:2.684, 95%CI:1.131-6.368, P<0.05) and the presence of atrophic gastritis (OR:2.418, 95%CI:1.052-5.555, P<0.05) were independent risk factors for synchronous MEGC. There was no significant statistical difference between SEGC and MEGC for LNM (17.5% vs 23.1%, P=0.311). The number of coexisting lesions was not associated with the risk of LNM in EGC. In addition, the survival outcome of MEGC patients was similar to that of SEGC (5-year RFS rate, 96.0% vs 93.7%, P=0.329;5-year OS rate, 96.0% vs 88.3%, P=0.479). CONCLUSION: Meticulous endoscopic examination at the initial diagnosis of MEGC was very important, especially for those with precancerous lesions such as atrophic gastritis. In terms of treatment methods, endoscopic resection may be equally suitable for synchronous MEGC if the lesions fulfilled its indication criteria.

Clinicopathologic Features, Survival Outcome, and Prognostic Factors in Gastric Cancer Patients 18-40 Years of Age.

Purpose: Whether young patients with gastric cancer (GC) had a distinct prognostic outcome from older patients remains controversial. The objective of this study was to investigate the clinicopathologic characteristics and prognostic factors of young GC patients and evaluate the survival outcome in comparison to their older counterparts. Methods: We retrospectively reviewed clinicopathologic and survival data of 2022 patients who underwent curative resection for GC. All patients were divided into the young patient group (18-40 years) and older patient group (>40 years) according to the patient age. Clinicopathologic characteristics and prognostic factors of young GC patients were analyzed, and the survival difference between the two groups was compared. Results: The incidence of GC in the patients 18-40 years of age was 8.1% (164/2022). The young patient group had different clinicopathologic features from the older group, including a significant female predominance, a larger number of retrieved lymph nodes, a higher proportion of undifferentiated histology type, and middle or lower 1/3 GC. However, the survival outcome of young patients was similar to that of their older counterparts (5-year disease free survival [DFS]: 47.0% vs. 44.0%, p = 0.247), even when comparison based on the TNM stage was made. Deeper tumor invasion (T3-T4 stage, hazard ratios [HR]: 5.791, 95% confidence intervals [CIs]: 2.908-11.533, p < 0.001), lymph node metastasis (HR: 2.500, 95% CIs: 1.308-4.781, p = 0.006), and lymphovascular invasion (HR: 2.191, 95% CIs: 1.306-3.677, p = 0.003) were independent prognostic factors for young GC patients. Conclusions: Young age (18-40 years) was not associated with poorer survival outcome in GC patients. However, early diagnosis and curative resection with adequate lymphadenectomy will still be necessary for improving the survival outcome of young GC patients.

Does delayed initiation of adjuvant chemotherapy following the curative resection affect the survival outcome of gastric cancer patients: A systematic review and meta-analysis.

BACKGROUND: Adjuvant chemotherapy(AC) following the curative resection could improve the survival outcome of advanced gastric cancer(GC) patients. However, there is no specific timing interval from radical surgery to initiation of AC. Whether delayed initiation of AC could affect the survival outcome of these patients remains unclear. In this study, we performed a systematic review and meta-analysis to evaluate the relationship between delaying AC and the survival outcome of GC patients. METHODS: PubMed, Embase and Cochrane Library databases were systematically searched for eligible studies that evaluated the relationship between time to AC and survival outcome. Survival data for HR and 95% CI were extracted and converted to a regression coefficient(ß) corresponding to a continuous representation per 4-week delay of AC. Individual adjusted ß were combined using a fixed-effects or random-effects model. Heterogeneity was assessed by I2 statistic and publication bias was detected using standard error-based funnel plots. RESULTS: A total of 11 eligible studies involving 6,017 patients were included in this meta-analysis. Eight studies evaluated the impact of delaying AC on overall survival(OS) and five evaluated the impact of delaying AC on disease-free survival(DFS). The pooled results demonstrated that the initiation of AC per 4-week delay was associated with a significant decrease in OS(HR:1.05, 95% CI: 1.03-1.08, P < 0.001; I2 = 18.5%) and DFS (HR:1.06, 95% CI: 1.02-1.10, P = 0.001; I2 = 40.6%). CONCLUSION: The initiation of AC per 4-week delay was associated with worse survival outcomes in GC patients. If physical status and postoperative recovery were appropriated, GC patients should be recommended to receive adjuvant chemotherapy timely.

Does Helicobacter pylori Eradication Reduce the Incidence of Metachronous Gastric Cancer After Curative Endoscopic Resection of Early Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Whether Helicobacter pylori eradication could reduce the risk of metachronous gastric cancer remain controversial. In the present study, we performed a systematic review and meta-analysis to evaluate the preventive effect of H. pylori eradication on the occurrence of metachronous gastric cancer after curative endoscopic resection of early gastric cancer. METHODS: The related studies were identified by searching PubMed and Embase databases. According to the H. pylori infection status and subsequent treatment, all patients were classified into H. pylori negative group, H. pylori eradication group and noneradication group. The relevant data were extracted and pooled effect size was assessed using a fixed effect model or a random effect model. RESULTS: A total of 11 retrospective cohort studies and 3 randomized controlled trials were included in this meta-analysis. The results based on the cohort studies indicated that the risk of metachronous gastric cancer was significantly lower in H. pylori eradication group than in noneradication group (hazard ratios: 0.65, 95% confidence interval: 0.50-0.86, P=0.002; I=0%). The pooled result of 2 randomized controlled trials demonstrated that the patients receiving anti-H. pylori treatment had a lower risk of metachronous gastric cancer than those who did not receive H. pylori eradication treatment (hazard ratios: 0.43, 95% confidence interval: 0.26-0.70, P=0.001; I=0%). In addition, the occurrence of metachronous gastric cancer in H. pylori eradication group was not significantly different from that in H. pylori negative group. CONCLUSIONS: Successful H. pylori eradication may be useful for the prevention of metachronous gastric cancer after curative endoscopic resection of early gastric cancer. Thus, anti-H. pylori treatment should be considered for those patients with H. pylori infection after curative endoscopic resection.

Feasibility of laparoscopy gastrectomy for gastric cancer in the patients with high body mass index: A systematic review and meta-analysis.

The aim of this study was to evaluate the impact of high body mass index (BMI) on surgical outcome of laparoscopic gastrectomy for gastric cancer (GC). Systematic literature search was performed using PubMed and Embase databases. The relevant data were extracted, and surgical outcomes and postoperative complications were compared between BMI≥25 kg/m2 and BMI<25 kg/m2 group using a fixed effect model or random effect model. 16 studies, with a total of 9572 GC patients, were included in this meta-analysis. The results indicated that operation time was significantly longer (WMD:16.22, 95% CI: 14.10-18.34, P < 0.001; I2 = 0%) and the number of lymph nodes retrieved was significantly fewer (WMD:-2.11, 95%CI: -3.14, -1.07, P < 0.001; I2 = 64.0%) in high BMI patients than in other patients. In addition, the amount of intraoperative blood loss was significantly larger in high BMI patients (WMD: 23.43, 95%CI: 20.05-26.81, P < 0.001; I2 = 40.3%). Compared with non-high BMI patients, overweight and obese patients had a higher risk of postoperative complications (RR:1.26, 95%CI: 1.11-1.43, P < 0.001; I2 = 39.1%), especially for wound infection (RR:1.62, 95%CI: 1.15-2.29, P < 0.01; I2 = 18.8%) and postoperative ileus (RR:1.80, 95% CI: 1.05-3.09, P < 0.05; I2 = 0%). However, there was no significant difference between two patient groups for postoperative recovery, major surgery-related complications (eg: anastomotic leakage, pancreatic fistula and intra-abdominal bleeding) and postoperative mortality. Despite increased technical challenge and risk of postoperative complications, the majority of these complications may be minor and cured. Laparoscopic gastrectomy for GC was a feasible and safe procedure even for high BMI patients.

Impact of proximal resection margin involvement on survival outcome in patients with proximal gastric cancer.

AIM: The aim of this study was to evaluate the risk factors for proximal resection margin involvement and its impact on survival outcome in patients with proximal gastric cancer. METHODS: A total of 488 patients who underwent potentially curative resection for proximal gastric cancer were retrospectively reviewed. Clinicopathological characteristics and survival differences between patients with positive and negative resection margins were compared and prognostic factors were determined by Cox multivariate analysis. RESULTS: In this study, 7.6% (37/488) of patients with proximal gastric cancer had a positive proximal resection margin after postoperative histopathological examination. Positive resection margins were significantly associated with advanced tumour stage and more aggressive biological features including larger tumour size, serosal invasion and lymphovascular invasion. Serosal invasion (OR 4.543, 95% CI 2.201 to 9.380, p<0.001) and lymphovascular invasion (OR 2.279, 95% CI 1.129 to 4.600, p<0.05) were independent risk factors for positive proximal resection margins. In terms of survival outcome, positive resection margins had an adverse impact on the prognosis of patients with proximal gastric cancer (median DFS: 20.7 vs 30.2 months, p<0.001). The multivariate analysis indicated that positive resection margins (HR 1.494, 95% CI 1.042 to 2.142, p=0.029), T stage (T3-T4, HR 2.264, 95% CI 1.484 to 3.454, p<0.001) and N stage (N1-N2 stage, HR 1.696, 95% CI 1.279 to 2.248, p<0.001; N3 stage, HR 2.691, 95% CI 1.967 to 3.681, p<0.001) were independent prognostic factors for patients with proximal gastric cancer. CONCLUSION: Proximal resection margin involvement was an indicator of more aggressive tumours and an independent prognostic factor for patients with proximal gastric cancer. Aggressive efforts should be made to achieve a negative resection margin if gastric cancer was deemed to be potentially resectable.

Impact of skip lymph node metastasis on the prognosis of gastric cancer patients who underwent curative gastrectomy.

PURPOSE: Skip metastasis (SK) is an exceptional pattern of lymph node metastasis and the incidence of skip metastasis is not infrequent in gastric cancer (GC). In the present study, we evaluated the clinical significance of skip LN metastasis in GC patients. METHODS: According to the anatomical location of positive lymph nodes (LNs), the patients who underwent curative gastrectomy in our institute were classified in three groups: only perigastric involvement (PG group), only extraperigastric involvement (SK group) and both perigastric and extraperigastric involvement (PG+EP group). The clinicopathologic features and prognostic differences between the different groups were compared. RESULTS: The incidence of skip metastasis was 3.9% in all GC patients and the most common location of skip metastasis was No.7 and No.8a node station. The proportion of only one involved station accounted for 83.0% of all cases. In addition, the SK group had fewer numbers of retrieved LNs than the PG and the PG+EP group, especially in the perigastric area. There were significant differences between different groups in the baseline characteristics. After clinicopathologic factors were adjusted and matched, we found that the prognosis of skip metastasis was poorer than that of only perigastric involvement, but was similar to that of both perigastric and extraperigastric involvement. CONCLUSION: The patients with skip metastasis had a poorer prognosis than those with only perigastric involvement. Anatomical location of metastatic LNs may be not ignored, and adequate lymphadenectomy should be indispensable for node-positive patients.

Clinicopathologic factors associated with recurrence and long-term survival in node-negative advanced gastric cancer patients.

BACKGROUND: despite a better prognosis in node-negative advanced gastric cancer (GC), a proportion of patients have a tumor recurrence within five years and eventually die due to cancer-related causes. The present study aimed to evaluate the predictive factors of tumor recurrence and long-term survival in node-negative advanced GC. METHODS: a total of 646 node-negative advanced GC patients who underwent a curative gastrectomy in our institution were included in the study. The impact of different clinicopathologic factors on tumor recurrence and overall survival were analyzed. RESULTS: tumor recurrences were observed in 181 patients and the cumulative recurrence rate at two-years and five-years were 50.8% and 86.2%, respectively. Lymphovascular invasion, advanced T stage (T3-T4) and an inadequate number of retrieved lymph nodes (LNs) were independent predictive factors of tumor recurrence in node-negative advanced GC. Older age, an upper 1/3 tumor, lymphovascular invasion, infiltration growth pattern (INFγ) and the depth of tumor invasion (T4 stage) were independently associated with long-term survival. With regard to node-negative patients with ≥ 15 retrieved LNs, infiltration growth pattern (INFγ) and advanced T stage (T3-T4) were independent risk factors for both tumor recurrence and long-term survival. CONCLUSION: in addition to lymphovascular invasion, inadequate RLNs and advanced T stage, the prognostic significance of infiltration growth pattern in node-negative advanced GC was especially emphasized. These risk factors should be considered when selecting candidates for adjuvant chemotherapy and postoperative surveillance.