BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gas...BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gastric cancer,detect core genes,develop a prognostic model,and provide treatment options.METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed.Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis.Then,patients from The Cancer Genome Atlas were assigned to high-and low-risk cohorts according to the mean value of the risk score as the threshold,which was verified in the Gene Expression Omnibus database.Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.RESULTS An integrated evaluation was performed in this study.Fatty acid metabolismrelated genes were used to construct the risk model.Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the“pRRophetic”R package.Patients in the high-risk cohort were associated with type Ⅰ/Ⅱ interferon activation,increased inflammation level,immune cell infiltration,and tumor immune dysfunction based on the exclusion algorithm,indicating the potential benefit of immunotherapy in these patients.CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis,chemotherapy sensitivity,and immunotherapy.展开更多
AIM To investigate the influence of L-methioninedeprived total parentaral nutrition with 5-FU on gastric cancer and host metabolism.``METHODS N-methyI-N-nitro-nitrosoguanidine ( MNNG )induced gastric cancer rats were ...AIM To investigate the influence of L-methioninedeprived total parentaral nutrition with 5-FU on gastric cancer and host metabolism.``METHODS N-methyI-N-nitro-nitrosoguanidine ( MNNG )induced gastric cancer rats were randomly divided into four groups: Met-containing TPN group (n= 11 ), Metdeprived TPN group (n = 12), Met-containing TPN + 5-FU group (n = 11) and Met-deprived TPN + 5-FU group (n-12). Five rats in each group were sacrificed after 7days of treatment and the samples were taken for examination. The remaining rats in each group were then fed separately with normal diet after the treatment until death, the life span was noted.``RESULTS The tumors were enlarged in Met-containing group and shrank in Met-deprived group markedly after the treatment. The DNA index (DI) of tumor cells and the body weight (BW) of rats had no significant change in the two groups, however, the ratio of tumor cells' S phase was increased The ratio of G2M phase went up in Metcontaining group, but down in Met-deprived group. In the other two groups that 5-FU was added, the BW of rats,and the diameter of tumors, the DI of tumor cells, the S and G2M phase ratio of tumor cells were all decreased,particularly in Met-deprived plus 5-FU group. Pathological examination revealed that the necrotic foci of the tumor tissue increased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In -MetTPN + 5-FUgroup, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased markedly (P<0.001), while other amino acids, such as serum free serine and glutamine increased significantly ( P< 0.005).All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18.6 days in Met-containing TPN group. 31 days in Met-deprived TPN group, 27.5 days in Met-containing TPN + 5-FU group, and 43 days in Met-deprived TPN+ 5-FU group (P<0.05).``CONCLUSION Met-deprived TPN causes methionine starvation of tumor cells, and can enhance the anti-tumor effect of 5-FU and prolong the life span of gastric cancerbearing rats.展开更多
INTRODUCTIONGastric cancer is one of the most common fatal malignancies in the world. The prognosis is generally poor in advanced gastric cancer .The low survival is related to delayed diagnosis, metastasis and recurr...INTRODUCTIONGastric cancer is one of the most common fatal malignancies in the world. The prognosis is generally poor in advanced gastric cancer .The low survival is related to delayed diagnosis, metastasis and recurrence after operation .The aim of this paper was to find correlation between clinical factors was to find correlation between clinical factors and biologic behavior of gastric cancer in a series of 1200 patients undergoing surgical resection.展开更多
BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among patholog...BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.展开更多
Studies on morbid obesity have shown remarkable improvement of diabetes in patients who have undergone bariatric operations.It was subsequently shown that these operations induce diabetes remission independent of the ...Studies on morbid obesity have shown remarkable improvement of diabetes in patients who have undergone bariatric operations.It was subsequently shown that these operations induce diabetes remission independent of the resultant weight loss;as a result,surgeons began to investigate whether operations for gastric cancer(GC)could have the same beneficial effect on diabetes as bariatric operations.It was then shown in multiple reports that followed that certain operations for GC were able to improve or even cure type 2 diabetes mellitus(T2 DM)in GC patients.This finding gave rise to the concept of"oncometabolic surgery",in which a patient diagnosed with both GC and T2 DM undergo a single operation with the purpose of treating both diseases.With the increasing incidence of T2 DM,oncometabolic surgery has the potential to improve the quality of life and even extend survival of many GC patients.However,because the GC patient population and the bariatric patient population are wildly different and because different GC operations have different properties,the effect of oncometabolic surgery must be carefully assessed and engineered in order to maximize benefit and avoid harm.This manuscript aims to summarize the findings made so far in the field of oncometabolic surgery and to provide an outlook regarding the possibility of oncometabolic surgery being incorporated into standard clinical practice.展开更多
BACKGROUND pT2+prostate cancer(PCa),a term first used in 2004,refers to organ-confined PCa characterized by a positive surgical margin(PSM)without extracapsular extension.Patients with a PSM are vulnerable to biochemi...BACKGROUND pT2+prostate cancer(PCa),a term first used in 2004,refers to organ-confined PCa characterized by a positive surgical margin(PSM)without extracapsular extension.Patients with a PSM are vulnerable to biochemical recurrence(BCR)following radical prostatectomy(RP);however,whether adjuvant radiotherapy(aRT)is imperative to PSM after RP remains controversial.This study had the longest follow-up on pT2+PCa after robotic-assisted RP since 2004.Moreover,we discussed our viewpoints on pT2+PCa based on real-world experiences.AIM To conclude a 10-year surveillance on pT2+PCa and compare our results with those of the published literature.METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled.Two serial tests of prostate specific antigen(PSA)≥0.2 ng/mL were defined as BCR.Various designed factors were analyzed using statistical tools for BCR risk.SAS 9.4 was applied and significance was defined as P<0.05.Univariate,multivariate,linear regression,and receiver operating characteristic(ROC)curve analyses were performed for statistical analyses.RESULTS With a median follow-up period of 9 years,25(52%)patients had BCR(BCR group),and the remaining 23(48%)patients did not(non-BCR group).The median time for BCR test was 4 years from the first postoperative PSA nadir.Preoperative PSA was significantly different between the BCR and non-BCR groups(P<0.001),and ROC curve analysis of preoperative PSA suggested a cutoff value of 19.09 ng/mL(sensitivity,0.600;specificity:0.739).The linear regression analysis showed no correlation between time to BCR and preoperative PSA(Pearson’s correlation,0.13;adjusted R2=0.026).CONCLUSION Robotic-assisted RP in pT2+PCa of worse conditions can provide better BCR-free survival.A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+PCa BCR rate.Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR.Based on our experiences and review of the literature,we do not recommend routine aRT for pT2+PCa.展开更多
文摘BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gastric cancer,detect core genes,develop a prognostic model,and provide treatment options.METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed.Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis.Then,patients from The Cancer Genome Atlas were assigned to high-and low-risk cohorts according to the mean value of the risk score as the threshold,which was verified in the Gene Expression Omnibus database.Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.RESULTS An integrated evaluation was performed in this study.Fatty acid metabolismrelated genes were used to construct the risk model.Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the“pRRophetic”R package.Patients in the high-risk cohort were associated with type Ⅰ/Ⅱ interferon activation,increased inflammation level,immune cell infiltration,and tumor immune dysfunction based on the exclusion algorithm,indicating the potential benefit of immunotherapy in these patients.CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis,chemotherapy sensitivity,and immunotherapy.
基金Supported by the National Natural Science Foundation of China,No.39370780.
文摘AIM To investigate the influence of L-methioninedeprived total parentaral nutrition with 5-FU on gastric cancer and host metabolism.``METHODS N-methyI-N-nitro-nitrosoguanidine ( MNNG )induced gastric cancer rats were randomly divided into four groups: Met-containing TPN group (n= 11 ), Metdeprived TPN group (n = 12), Met-containing TPN + 5-FU group (n = 11) and Met-deprived TPN + 5-FU group (n-12). Five rats in each group were sacrificed after 7days of treatment and the samples were taken for examination. The remaining rats in each group were then fed separately with normal diet after the treatment until death, the life span was noted.``RESULTS The tumors were enlarged in Met-containing group and shrank in Met-deprived group markedly after the treatment. The DNA index (DI) of tumor cells and the body weight (BW) of rats had no significant change in the two groups, however, the ratio of tumor cells' S phase was increased The ratio of G2M phase went up in Metcontaining group, but down in Met-deprived group. In the other two groups that 5-FU was added, the BW of rats,and the diameter of tumors, the DI of tumor cells, the S and G2M phase ratio of tumor cells were all decreased,particularly in Met-deprived plus 5-FU group. Pathological examination revealed that the necrotic foci of the tumor tissue increased after Met-deprived TPN treatment, and the nucleoli of tumor cells enlarged. In -MetTPN + 5-FUgroup, severe nuclear damage was also found by karyopyknosis and karyorrhexis, meanwhile there was slight degeneration in some liver and kidney cells. The serum free Met and Cysteine decreased markedly (P<0.001), while other amino acids, such as serum free serine and glutamine increased significantly ( P< 0.005).All the rats died of multiple organ failure caused by cancer metastasis. The average survival time was 18.6 days in Met-containing TPN group. 31 days in Met-deprived TPN group, 27.5 days in Met-containing TPN + 5-FU group, and 43 days in Met-deprived TPN+ 5-FU group (P<0.05).``CONCLUSION Met-deprived TPN causes methionine starvation of tumor cells, and can enhance the anti-tumor effect of 5-FU and prolong the life span of gastric cancerbearing rats.
文摘INTRODUCTIONGastric cancer is one of the most common fatal malignancies in the world. The prognosis is generally poor in advanced gastric cancer .The low survival is related to delayed diagnosis, metastasis and recurrence after operation .The aim of this paper was to find correlation between clinical factors was to find correlation between clinical factors and biologic behavior of gastric cancer in a series of 1200 patients undergoing surgical resection.
文摘BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.
文摘Studies on morbid obesity have shown remarkable improvement of diabetes in patients who have undergone bariatric operations.It was subsequently shown that these operations induce diabetes remission independent of the resultant weight loss;as a result,surgeons began to investigate whether operations for gastric cancer(GC)could have the same beneficial effect on diabetes as bariatric operations.It was then shown in multiple reports that followed that certain operations for GC were able to improve or even cure type 2 diabetes mellitus(T2 DM)in GC patients.This finding gave rise to the concept of"oncometabolic surgery",in which a patient diagnosed with both GC and T2 DM undergo a single operation with the purpose of treating both diseases.With the increasing incidence of T2 DM,oncometabolic surgery has the potential to improve the quality of life and even extend survival of many GC patients.However,because the GC patient population and the bariatric patient population are wildly different and because different GC operations have different properties,the effect of oncometabolic surgery must be carefully assessed and engineered in order to maximize benefit and avoid harm.This manuscript aims to summarize the findings made so far in the field of oncometabolic surgery and to provide an outlook regarding the possibility of oncometabolic surgery being incorporated into standard clinical practice.
文摘BACKGROUND pT2+prostate cancer(PCa),a term first used in 2004,refers to organ-confined PCa characterized by a positive surgical margin(PSM)without extracapsular extension.Patients with a PSM are vulnerable to biochemical recurrence(BCR)following radical prostatectomy(RP);however,whether adjuvant radiotherapy(aRT)is imperative to PSM after RP remains controversial.This study had the longest follow-up on pT2+PCa after robotic-assisted RP since 2004.Moreover,we discussed our viewpoints on pT2+PCa based on real-world experiences.AIM To conclude a 10-year surveillance on pT2+PCa and compare our results with those of the published literature.METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled.Two serial tests of prostate specific antigen(PSA)≥0.2 ng/mL were defined as BCR.Various designed factors were analyzed using statistical tools for BCR risk.SAS 9.4 was applied and significance was defined as P<0.05.Univariate,multivariate,linear regression,and receiver operating characteristic(ROC)curve analyses were performed for statistical analyses.RESULTS With a median follow-up period of 9 years,25(52%)patients had BCR(BCR group),and the remaining 23(48%)patients did not(non-BCR group).The median time for BCR test was 4 years from the first postoperative PSA nadir.Preoperative PSA was significantly different between the BCR and non-BCR groups(P<0.001),and ROC curve analysis of preoperative PSA suggested a cutoff value of 19.09 ng/mL(sensitivity,0.600;specificity:0.739).The linear regression analysis showed no correlation between time to BCR and preoperative PSA(Pearson’s correlation,0.13;adjusted R2=0.026).CONCLUSION Robotic-assisted RP in pT2+PCa of worse conditions can provide better BCR-free survival.A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+PCa BCR rate.Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR.Based on our experiences and review of the literature,we do not recommend routine aRT for pT2+PCa.
