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1.
Eur J Surg Oncol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-32044202

RESUMO

BACKGROUND: and purpose: For gastric cancer patients with peritoneal metastasis (GCPM), there is no universally accepted prognostic staging system. This study aimed to validate the predictive ability of the 15th peritoneal metastasis staging system (P1abc) of the Japanese Classification of Gastric Carcinoma (JCGC). METHODS: The data of 309 GCPM patients from July 2007 to July 2017 were retrospectively analyzed. This study compared the prognosis prediction performances of P1abc, the previous JCGC PM staging (P123) and Gilly staging systems. RESULTS: The survival curve revealed a significant difference in overall survival (OS) predicted by P1abc, P123 and Gilly staging (all P < 0.05), and the survival of the two adjacent substages were well distinguished by P1abc but not by P123 and Gilly staging. Both P123 and Gilly staging were substituted with P1abc staging in a 2-step multivariate analysis. The results showed that P1abc staging was superior to both P123 and Gilly staging in its discriminatory ability (C-index), predictive accuracy (AIC) and predictive homogeneity (likelihood ratio chi-square). A stratified analysis by different therapies indicated that for the P1a and P1b patients, OS following palliative resection combined with palliative chemotherapy (PRCPC) was better than that after palliative resection (PR) or palliative chemotherapy (PC) alone (P < 0.05). For the P1c patients, OS after receiving PC was significantly superior to that after receiving PRCPC or PR (P = 0.021). CONCLUSION: P1abc staging is superior to P123 and Gilly staging in predicting the survival of GCPM patients. Surgeons can provide these patients with appropriate treatment options according to the corresponding substages within P1abc.

2.
J Gastrointest Surg ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016671

RESUMO

BACKGROUND: Whether the change of the pre- and postoperative systemic inflammatory response (SIR) levels will affect the prognosis of gastric cancer (GC) is unclear. We aimed to investigate the dynamic changes in the pre- and postoperative SIR and their prognostic value for GC. METHODS: The clinicopathological data from 2257 patients who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were analyzed. Perioperative SIR changes were reported as changes in the lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). RESULTS: The SIR levels showed different trends from postoperative months 1 to 12. Multivariate analysis showed that preoperative (pre)-LMR was an independent predictor for the prognosis (P = 0.024). The postoperative 12-month (post-12-month) LMR predicted the 5-year overall survival (OS) rate with the highest accuracy (areas under the curve [AUC] 0.717). Patients were divided into four groups according to the optimal cutoff of the preoperative and post-12-month LMR: high pre-LMR to high postoperative (post)-LMR group, high pre-LMR to low post-LMR group, low pre-LMR to high post-LMR group, and low pre-LMR to low post-LMR group. The survival analysis showed 5-year OS rate was significantly higher in patients with high post-12-month LMR than in patients with low post-12-month LMR, regardless of pre-LMR levels (81.6% vs. 44.2%, P < 0.001). The prognostic accuracy was significantly improved by incorporating the post-12-month LMR in the tumor-node-metastasis (TNM) staging system (P = 0.003). CONCLUSIONS: The remeasurement of LMR at post-12-month is helpful in predicting the long-term survival of GC.

3.
Surg Endosc ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953725

RESUMO

BACKGROUND: Numerous studies have shown that the short-term efficacy of three-dimensional (3D) laparoscopic radical gastrectomy (LG) is comparable to that of two-dimensional (2D)-LG. Whether 3D-LG affects the recurrence patterns of gastric cancer (GC) patients has not been investigated. METHODS: From January 2015 to April 2016, a total of 419 patients were recruited for a phase III clinical trial (NCT02327481), which compared the short-term outcomes between the 2D and 3D groups. The long-term efficacy including recurrence patterns was compared between the 2D and 3D groups in this retrospective study. Multivariate analyses were performed to determine whether 3D-LG affects the recurrence patterns. RESULTS: Ultimately, 401 patients were analyzed (197 in the 2D-LG group and 204 in the 3D-LG group), and no differences were observed in the clinicopathological data between the two groups. There were no significant differences between the two groups in the recurrence types, first recurrence time or recurrence-free survival (RFS) (all p > 0.05). According to the 7th American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system, both groups were stratified into pathological stages I, II, and III. The stratified analysis showed no significant differences in RFS or overall survival (OS) among patients in each subgroup (all p > 0.05). The multivariate analysis of RFS showed that tumor diameter, pTNM stage, lymphovascular invasion, and adjuvant chemotherapy were independent factors (all p < 0.05). The multivariate analysis of post-recurrence survival (PRS) showed that adjuvant chemotherapy was an independent protective factor (p = 0.043). CONCLUSIONS: 3D-LG for GC did not differ significantly from 2D-LG in the effects on 3-year recurrence patterns, RFS and OS, which provides more tumor-related evidence for 3D technology. And due to the technological similarity, it may have certain reference value for robotic-assisted gastrectomy. Further multicenter, large-scale clinical trials are warranted.

4.
BMC Gastroenterol ; 19(1): 205, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791240

RESUMO

PURPOSE: To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC). METHODS: A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1-2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45). RESULTS: Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%. CONCLUSION: Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

5.
World J Gastroenterol ; 25(43): 6451-6464, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31798281

RESUMO

BACKGROUND: Because of the powerful abilities of self-learning and handling complex biological information, artificial neural network (ANN) models have been widely applied to disease diagnosis, imaging analysis, and prognosis prediction. However, there has been no trained preoperative ANN (preope-ANN) model to preoperatively predict the prognosis of patients with gastric cancer (GC). AIM: To establish a neural network model that can predict long-term survival of GC patients before surgery to evaluate the tumor condition before the operation. METHODS: The clinicopathological data of 1608 GC patients treated from January 2011 to April 2015 at the Department of Gastric Surgery, Fujian Medical University Union Hospital were analyzed retrospectively. The patients were randomly divided into a training set (70%) for establishing a preope-ANN model and a testing set (30%). The prognostic evaluation ability of the preope-ANN model was compared with that of the American Joint Commission on Cancer (8th edition) clinical TNM (cTNM) and pathological TNM (pTNM) staging through the receiver operating characteristic curve, Akaike information criterion index, Harrell's C index, and likelihood ratio chi-square. RESULTS: We used the variables that were statistically significant factors for the 3-year overall survival as input-layer variables to develop a preope-ANN in the training set. The survival curves within each score of the preope-ANN had good discrimination (P < 0.05). Comparing the preope-ANN model, cTNM, and pTNM in both the training and testing sets, the preope-ANN model was superior to cTNM in predictive discrimination (C index), predictive homogeneity (likelihood ratio chi-square), and prediction accuracy (area under the curve). The prediction efficiency of the preope-ANN model is similar to that of pTNM. CONCLUSION: The preope-ANN model can accurately predict the long-term survival of GC patients, and its predictive efficiency is not inferior to that of pTNM stage.

6.
World J Gastroenterol ; 25(41): 6258-6272, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31749596

RESUMO

BACKGROUND: Increasing numbers of laboratory blood parameters (BPM) have been reported to greatly affect the long-term outcomes of gastric cancer (GC) patients. However, the existing prognostic models do not comprehensively analyze these predictors. AIM: To construct a new prognostic tool, based on all the prognostic BPM, to achieve more accurate prognosis prediction for GC. METHODS: We retrospectively assessed 850 consecutive patients who underwent curative resection for stage II-III GC from January 2010 to April 2013. The patients were classified into developing (n = 567) and validation (n = 283) cohorts using computer-generated random numbers. A scoring system, namely BPM score, was then constructed using least absolute shrinkage and selection operator (LASSO) Cox regression model in the developing cohort, and validated in the validation cohort. A nomogram consisting of BPM score and tumor-lymph node-metastasis (TNM) stage was further created. The discrimination and calibration of the nomogram were evaluated via Harrell's C-statistic and the Hosmer-Lemeshow test. RESULTS: Using the LASSO model, we established the BPM score based on five BPM: Albumin, lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 19-9. The BPM scores were divided into high- and low-BPM groups based on a cut-off value of -0.93. High-BPM patients were significantly older and had more advanced, larger tumors. In the developing cohort, significant differences were found in 5-year overall survival (OS) and 5-year disease-specific survival between the high-BPM and low-BPM patients. Similar results were found in the validation group. Multivariable analysis showed that the BPM score was an independent predictor of OS. High-BPM patients had a poorer 5-year OS for each subgroup. Furthermore, a nomogram that combined the BPM score and TNM stage had significantly better prognostic value compared with TNM stage alone. CONCLUSION: The BPM score provides more accurate prognosis prediction in stage II-III GC patients and is an effective complement to the TNM staging system.

7.
World J Clin Cases ; 7(21): 3419-3435, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31750326

RESUMO

BACKGROUND: The incidence of proximal gastric cancer (GC) is increasing, and methods for the prediction of the long-term survival of proximal GC patients have not been well established. AIM: To develop nomograms for the prediction of long-term survival among proximal GC patients. METHODS: Between January 2007 and June 2013, we prospectively collected and retrospectively analyzed the medical records of 746 patients with proximal GC, who were divided into a training set (n = 560, 75%) and a validation set (n = 186, 25%). A Cox regression analysis was used to identify the preoperative and postoperative risk factors for overall survival (OS). RESULTS: Among the 746 patients examined, the 3- and 5-year OS rates were 66.1% and 58.4%, respectively. In the training set, preoperative T stage (cT), N stage (cN), CA19-9, tumor size, ASA core, and 3- to 6-mo weight loss were incorporated into the preoperative nomogram to predict the OS. In addition to these variables, lymphatic vascular infiltration (LVI), postoperative tumor size, T stage, N stage, blood transfusions, and complications were incorporated into the postoperative nomogram. All calibration curves used to determine the OS probability fit well. In the training set, the preoperative nomogram achieved a C-index of 0.751 [95% confidence interval (CI): 0.732-0.770] in predicting OS and accurately stratified the patients into four prognostic subgroups (5-year OS rates: 86.8%, 73.0%, 43.72%, and 20.9%, P < 0.001). The postoperative nomogram had a C-index of 0.758 in predicting OS and accurately stratified the patients into four prognostic subgroups (5-year OS rates: 82.6%, 74.3%, 45.9%, and 18.9%, P < 0.001). CONCLUSION: The nomograms accurately predicted the pre- and postoperative long-term survival of proximal GC patients.

8.
BMC Cancer ; 19(1): 1127, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752770

RESUMO

BACKGROUND: The platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and neutrophil to lymphocyte ratio (NLR) reflect the systematic inflammatory response, with some evidence revealing that they are associated with poorer survival in patients with gastric cancer. However, the effect of the white blood cell to hemoglobin ratio (WHR) on the long-term prognosis of patients with gastric cancer has not been reported. Therefore, we sought to characterize the effect of WHR on long-term survival after radical gastrectomy and compare its value with that of other preoperative inflammation-based prognostic scores (PIPS). METHODS: Data from 924 patients with a diagnosis of nonmetastatic gastric adenocarcinoma who underwent surgical resection between December 2009 and May 2013 were included in this study. RESULTS: The optimal cutoff values for the WHR, PLR, LMR, and NLR were 2.855, 133.03, 3.405, and 2.61, respectively. Patients with an increased WHR (53% vs. 88.1%, p < 0.001), PLR (60.9% vs 75.6%, p < 0.001) and NLR (56.7% vs 72.8%, p < 0.001) and a decreased LMR (54% vs 74.5%, p < 0.001) had a significantly decreased 5-year OS. However, the stratified analysis showed that only the WHR predicted a significant 5-year survival rate difference at each stage as follows: stage I (82.7% vs 94.3%, p = 0.005), stage II (71.3% vs 90.2%, p = 0.001) and stage III (38.2% vs 58.1%, p < 0.001). The time-ROC curve showed that the predictive value of the WHR was superior to that of the PLR, LMR, and NLR during follow-up. The WHR (0.624) C-index was significantly greater than the PLR (0.569), LMR (0.584), and NLR C-indexes (0.56) (all P < 0.001). CONCLUSION: Compared with other PIPS, the WHR had the most powerful predictive ability when used for the prognosis of patients with gastric adenocarcinoma.

9.
Surg Endosc ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720795

RESUMO

BACKGROUND: Well-designed retrospective studies (RSs) and small-sample prospective studies (PSs) evaluating the efficacy of interventions have received much attention. This study was designed to evaluate the differences between well-designed RSs and small-sample randomized controlled trials based on the efficacy of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (GC). METHODS: The clinicopathological data of 1360 patients with GC who underwent DG were analysed. After propensity score matching (1:1), 380 cases (ODG = 190, LDG = 190) were finally selected in a RS. Meanwhile, data from 120 patients (ODG = 60, LDG = 60) who enrolled in a PS were analysed. RESULTS: In the PS, the LDG group had less intraoperative blood loss, shorter time to first flatus, and shorter time to fluid diet than the ODG group. In the RS, the LDG group had less intraoperative blood loss, and a shorter postoperative hospital stay than the ODG group. In the PS, the 3-year overall survival (OS) rate was 83.3% in the LDG group and 83.2% in the ODG group (p = 0.877). In the RS, the 3-year OS rate was 68.7% in the LDG group and 66.6% in the ODG group (p = 0.752). No significant interactions were observed between the two groups and any of the variables examined, either in the PS or RS. The recurrence patterns were similar in the two groups. Furthermore, Cox regression analysis showed that surgical method (LDG/ODG) was not a prognostic factor affecting OS or DFS, either prospectively or retrospectively. CONCLUSIONS: The oncologic efficacy of laparoscopic and open distal gastrectomy for advanced GC is comparable. Well-designed RSs can be similar to small sample of PSs in assessing long-term oncologic outcomes of surgical interventions, but the short-term outcomes obtained should be treated with caution.

10.
Cancer Cell Int ; 19: 282, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728130

RESUMO

Background: Angiogenesis plays critical roles in the progression and metastasis of malignant tumors. Gastric neuroendocrine carcinoma is an uncommon stomach cancer that is rich in blood vessels and exhibits highly malignant biological behavior with a poor prognosis. The role of CDK5RAP3 in GNEC has not been reported to date. Methods: Immunohistochemistry was used to assess the expression of CDK5RAP3 in GNEC tissues and adjacent non-tumor tissues. Cell lines with stable overexpression or knockdown of CDK5RAP3 were constructed using lentiviral transfection. Wound-healing assays, invasion and metastasis assays, tube formation assays, and tumor xenograft transplantation assays were performed to evaluate the effect of CDK5RAP3 on GNEC angiogenesis in vitro and in vivo. Real-time PCR, ELISA, western blot analysis, and confocal-immunofluorescence staining were used to explore the molecular mechanism of CDK5RAP3's effect on angiogenesis. Results: Compared with their respective adjacent non-tumor tissues, protein levels of CDK5RAP3 were significantly decreased in GNEC tissues. Furthermore, low expression of CDK5RAP3 was correlated with more advanced TNM stage, increased tumor microvessel density, and poor prognosis. Functionally, we found that GNEC cells with CDK5RAP3 knockdown promoted human umbilical vein endothelial cells migration and tube formation via activation of AKT/HIF-1α/VEGFA signaling, resulting in increased levels of VEGFA in GNEC cell supernatant. In addition, CDK5RAP3 overexpression in GNEC cells caused the opposing effect. Consistent with these results, nude mouse tumorigenicity assays showed that CDK5RAP3 expression downregulated angiogenesis in vivo. Lastly, patients with low CDK5RAP3 expression and high VEGFA expression exhibited the worst prognosis. Conclusions: This study demonstrated that CDK5RAP3 inhibits angiogenesis by downregulating AKT/HIF-1α/VEGFA signaling in GNEC and improves patient prognosis, suggesting that CDK5RAP3 could be a potential therapeutic target for GNEC.

11.
BMC Cancer ; 19(1): 1048, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694573

RESUMO

BACKGROUND: Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. METHODS: EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set. RESULTS: In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P <  0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P <  0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set. CONCLUSIONS: The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested.

12.
World J Gastroenterol ; 25(37): 5641-5654, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31602164

RESUMO

BACKGROUND: Robotic surgery has been considered to be significantly better than laparoscopic surgery for complicated procedures. AIM: To explore the short-term effect of robotic and laparoscopic spleen-preserving splenic hilar lymphadenectomy (SPSHL) for advanced gastric cancer (GC) by Huang's three-step maneuver. METHODS: A total of 643 patients who underwent SPSHL were recruited from April 2012 to July 2017, including 35 patients who underwent robotic SPSHL (RSPSHL) and 608 who underwent laparoscopic SPSHL (LSPSHL). One-to-four propensity score matching was used to analyze the differences in clinical data between patients who underwent robotic SPSHL and those who underwent laparoscopic SPSHL. RESULTS: In all, 175 patients were matched, including 35 patients who underwent RSPSHL and 140 who underwent LSPSHL. After matching, there were no significant differences detected in the baseline characteristics between the two groups. Significant differences in total operative time, estimated blood loss (EBL), splenic hilar blood loss (SHBL), splenic hilar dissection time (SHDT), and splenic trunk dissection time were evident between these groups (P < 0.05). Furthermore, no significant differences were observed between the two groups in the overall noncompliance rate of lymph node (LN) dissection (62.9% vs 60%, P = 0.757), number of retrieved No. 10 LNs (3.1 ± 1.4 vs 3.3 ± 2.5, P = 0.650), total number of examined LNs (37.8 ± 13.1 vs 40.6 ± 13.6, P = 0.274), and postoperative complications (14.3% vs 17.9%, P = 0.616). A stratified analysis that divided the patients receiving RSPSHL into an early group (EG) and a late group (LG) revealed that the LG experienced obvious improvements in SHDT and length of stay compared with the EG (P < 0.05). Logistic regression showed that robotic surgery was a significantly protective factor against both SHBL and SHDT (P < 0.05). CONCLUSION: RSPSHL is safe and feasible, especially after overcoming the early learning curve, as this procedure results in a radical curative effect equivalent to that of LSPSHL.

13.
J Exp Clin Cancer Res ; 38(1): 410, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533855

RESUMO

BACKGROUND: UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. METHODS: Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. RESULTS: Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. CONCLUSION: UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

14.
J Cancer ; 10(19): 4488-4498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528213

RESUMO

Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) was identified as a tumor suppressor in gastric cancer, while, minichromosome maintenance complex component 6 (MCM6), which is closely related to the initiation of DNA replication, was reported to be upregulated in multiple malignancies. However, the interaction between these two proteins has not been investigated in gastric cancer. Here, we evaluate the connection between CDK5RAP3 and MCM6 using mass spectrometry and immunoprecipitation. In cells, cell growth and invasiveness indicate that CDK5RAP3 acts as a tumor suppressor by preventing the effects of MCM6. The potential mechanism was revealed using immunofluorescence and nuclear protein extraction. In patients, immunohistochemistry and immunofluorescence show that the protein levels of CDK5RAP3 were markedly decreased in most gastric tumor tissues compared with adjacent nontumor tissues, and the expression levels of MCM6 in the nucleus showed the opposite trend. Prognostic analysis showed that the combined expression of CDK5RAP3 and MCM6 was an independent prognostic factor correlating with the overall survival of gastric cancer patients. Cox regression analysis indicated that the expression of CDK5RAP3 and MCM6 corresponded to T, N, and M stages. Our results demonstrate that CDK5RAP3 can interact with MCM6 and prevent MCM6 from translocating into the nucleus, which may be a potential mechanism through which CDK5RAP3 negatively regulates the proliferation of gastric cancer.

15.
J Cancer ; 10(18): 4389-4396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413759

RESUMO

Objective: Whether age affects lymph node metastasis (LNM) in patients with gastric cancer (GC) is currently inconclusive. This study investigates the effect of age on LNM in patients with GC. Methods: From January 1988 to December 2013, 22,808 GC patients underwent gastrectomy at the Surveillance, Epidemiology, and End Results database were included. The relationship between age and LNM was analyzed. Results: The median number of examined lymph nodes (ELNs) was 12 (interquartile range [IQR], 7-20) among the 22,808 patients with GC, and the median numbers of ELNs were 10 (IQR, 5-18), 12 (IQR, 6-19), 13 (IQR, 7-21) and 13 (IQR, 7-21) in patients with T1 to T4 disease, respectively. A total of 13,780 (60.4%) patients presented with LNM. The LNM rates were 69.6%, 66.1%, 64.7%, 61.8%, 57.8% and 55.6% for patients in the 20-39, 40-49, 50-59, 60-69, 70-79 and ≥ 80 age groups, respectively (P < 0.001). The LNM rates and the number of positive lymph nodes were correlated with age among patients whose diseases were of the same T stage (all P < 0.01). Multivariate analysis showed that age was an independent predictor for LNM in patients with early gastric cancer (EGC) (P < 0.05), and linear regression analysis showed that the LNM rate was higher in young patients with EGC (P < 0.05). Conclusions: Age is an independent predictor for LNM in EGC. Moreover, LNM is more common in young patients with EGC than in other age groups, which indicates that limited lymph node dissection may not be appropriate for young patients with EGC.

16.
J Gastrointest Surg ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452078

RESUMO

OBJECTIVE: To evaluate the effects of three nutritional scoring systems: Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), and Naples Prognostic Score (NPS) on the short- or long-term prognosis of gastric cancer (GC) patients who underwent radical gastrectomy. METHODS: The clinicopathological data of 2182 patients who underwent radical gastrectomy at the Fujian Medical University Union Hospital (FMUUH) from 2009 to 2014 were retrospectively analyzed. The effects of the PNI, CONUT, and NPS on the short- or long-term prognosis of GC patients were analyzed. RESULTS: Overall, 359 (16.5%) patients had postoperative complications. There was no significant association between the PNI, CONUT, and NPS and postoperative complications (P > 0.05); however, high CONUT and NPS were significantly associated with severe postoperative complications (P < 0.05). Univariate analysis showed that PNI, CONUT, and NPS were all associated with overall survival (OS) (P < 0.001). However, multivariate analysis showed that only PNI was an independent risk factor for OS (P = 0.004), and the 5-year OS rate in the low PNI group was significantly lower than that in the normal PNI group (55.5% vs 75.4%, P < 0.05). The area under the curve (AUC) and the c-index of PNI were significantly higher than those of CONUT and NPS. The prognostic efficiency of combining PNI and TNM stage was also significantly better than that of TNM staging alone (P < 0.05). CONCLUSION: The current study demonstrated that CONUT and NPS are important for assessing the risk of severe postoperative complications. However, PNI is an independent risk factor for the long-term prognosis of GC patients who underwent radical gastrectomy and can improve the prognostic efficiency of TNM staging.

17.
Eur J Surg Oncol ; 45(12): 2457-2464, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31362841

RESUMO

OBJECTIVE: To investigate the factors related to positive surgical margins of gastric cancer and their correlation with the prognosis of these patients. METHODS: The clinicopathological data of gastric cancer patients undergoing gastrectomy were collected, and the relationship between surgical margins status and patient outcome was analyzed. RESULTS: A total of 10080 patients were included, among which 311 (3.1%) had positive surgical margins. pT3-4, pN+ and M1 were independent risk factors for positive margins, and a tumor in the middle of the stomach was a protective factor (p < 0.05). The 5-year overall survival (OS) rates of the patients with positive and negative margins after propensity score matching (PSM) were 24.2% and 36.8%, respectively (p < 0.001). For M0 patients, the 5-year OS of the margin-positive patients was lower than that of the margin-negative patients, and was higher than that of patients with M1. For the M1 patients, no statistically significant difference in 5-year OS was noted between patients with positive and negative margins. Age, positive margins, tumor location, pN+, and M1 were independent prognostic factors for OS in patients undergoing gastrectomy, and pN2-3 and M1 stages were independent prognostic factors for patients with positive surgical margins. Postoperative chemotherapy could improve the 5-year OS in pN2-3 and M1 margin-positive patients (p < 0.05). CONCLUSION: The prognosis of M0 gastric cancer patients with positive surgical margins is poor, and it is recommended that these patients should undergo routine intraoperative frozen-section pathological examination to reduce the risk of positive surgical margins.

18.
Cancer Med ; 8(6): 2962-2970, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31070023

RESUMO

BACKGROUND: Whether the tumor-node-metastasis (TNM) staging system is appropriate for patients with node-negative gastric cancer (GC) is still inconclusive. The modified staging system developed by recursive partitioning analysis (RPA) showed good prognostic performance in a variety of cancers. The application of RPA has not been reported in the prognostic prediction of GC. METHODS: Node-negative GC patients who underwent radical resection at Fujian Medical University Union Hospital (n = 862) and Sun Yat-sen University Cancer Center (n = 311) with at least 5 years of follow-up were selected as the training set. RPA was used to develop a modified staging system. Patients from the Surveillance, Epidemiology, and End Results database (n = 1415) were selected as the validation set. RESULTS: The 5-year overall survival (OS) rates of patients with 8th AJCC-TNM stage IA-IIIA in the training set were IA 95.2%, IB 87.1%, IIA 78.3%, IIB 75.8%, and IIIA 72.6%. Multivariate analysis (MVA) showed that larger tumor size, elder age, and deeper depth of invasion were independent predictors for OS in patients with node-negative GC (all P < 0.05). Patients were reclassified into RPA I, RPA II, RPA III, and RPA IV stages based on RPA; the 5-year OS rates were 96.1%, 87.2%, 81.0%, and 64.3%, respectively, with significant difference (P < 0.05). Two-step MVA showed that the RPA staging system was an independent predictor of OS (P < 0.05). Compared with the 8th AJCC-TNM staging system, the RPA staging system had a smaller AIC value (2544.9 vs 2576.2), higher χ2 score (104.2 vs 69.6) and higher Harrell's C-index (0.697 vs 0.669, P = 0.007). The similar results were found in the validation set. CONCLUSIONS: A new prognostic predictive system based on RPA was successfully developed and validated, which may be suggested for staging node-negative GC in future.

19.
Gastroenterol Res Pract ; 2019: 6294382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31097961

RESUMO

Objective: To investigate the validity of the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer. Methods: The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed. Results: Stage migration occurred primarily during stage III between the 7th and 8th edition TNM staging systems. Stages IIIB and IIIC in the 7th edition staging system were divided in the 8th edition and had obvious differences in survival rates (both P < 0.001). The 8th edition TNM stages IIIC and IV showed similar survival rates (P = 0.101). The prognosis of patients with T4aN3bM0 was not different from that of patients with TxNxM1 (P = 0.433), while the prognosis of patients with T4bN3bM0 was significantly poorer than that of patients with TxNxM1 (P = 0.008). A revised TNM system with both T4aN3bM0 and T4bN3bM0 incorporated into stage IV was proposed. Multivariable regression analysis showed that the revised TNM system, but not the 7th and 8th editions, was an independent factor for disease-specific survival (DSS) in the third step of the analysis. Further analyses revealed that the revised TNM system had superior discriminatory ability to the 8th edition staging system, which was also an improvement over the 7th edition staging system. Conclusion: The 8th edition of the AJCC TNM staging system is superior to the 7th edition for predicting the DSS rates of gastric cancer patients. However, for better prognostic stratification, it might be more suitable for T4aN3bM0/T4bN3bM0 to be incorporated into stage IV in the 8th edition TNM staging system.

20.
BMC Surg ; 19(1): 53, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133008

RESUMO

INTRODUCTION: To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict survival after radical gastrectomy in patients with gastric cancer (GC). METHOD: Data from patients with GC who underwent radical gastrectomy from January 2008 to December 2012 in Fujian Medical University Union Hospital were retrospectively analyzed. Patients were categorized into either high ACCI group or low ACCI group based on the effect of ACCI on long-term GC prognosis. 1:1 propensity score matching (PSM) was used to reduce confounding bias. To further analyze the impact of ACCI on the long-term prognosis of patients after radical gastrectomy, a nomogram was built based on the Cox proportional hazards regression model. RESULTS: A total of 1476 patients were included in the analysis. After PSM, there was no statistically significant differences in tumor location, tumor size and tumor stage between low ACCI group (429 cases) and high ACCI group (429 cases) (all P > 0.05). Before and after PSM, the incidence of postoperative complications in high ACCI group was significantly higher than that in low ACCI group (P < 0.05). The 5-year overall survival rate (OS) in low ACCI group was significantly higher than that in high ACCI group. Multivariate analysis showed that ACCI was an independent risk factor for OS (P < 0.05). The Harrell's C-statistics (C-index) of TNMA, a prognostic evaluation system combining ACCI and TNM staging system, was significantly higher than that of TNM staging system in both the modeling and validation groups (all P < 0.05). CONCLUSIONS: ACCI was an independent risk factor for the long-term prognosis of GC patients after radical gastrectomy that could effectively improve the predictive efficacy of the TNM staging system for GC.


Assuntos
Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Gastrectomia/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Nomogramas , Complicações Pós-Operatórias/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
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