1.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.
2.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
3.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.
4.Prognostic analysis of continuous lumbar cistern external drainage after aneurysmal subarachnoid hemorrhage
Shukai LIN ; Gang LI ; Fen ZHOU ; Hui WANG ; Jianfeng ZENG ; Shihe XIAO
International Journal of Surgery 2022;49(6):421-427,F5
Objective:To analyze the influencing factors, prevention and treatment strategy of short-term poor prognosis of continuous lumbar cistern external drainage after aneurysms subarachnoid hemorrhage (aSAH).Methods:Used retrospective research method, the clinical data of 300 patients with aSAH combined with continuous lumbar cistern external drainage treated in Sanya Central Hospital (Hainan Third People′s Hospital) from March 2019 to March 2021 were selected as the training set. In addition, the clinical data of 144 patients with aSAH with continuous lumbar cistern external drainage treated in Sanya Central Hospital (Hainan Third People′s Hospital) from March 2017 to May 2019 were selected as the verification set. According to the results of postoperative follow-up, the patients in the training set were divided into two groups: good prognosis group ( n=208) and poor prognosis group ( n=92). The demographic characteristics, past history, Hunt-Hess grade, modified Fisher grade, location of responsible aneurysm, postoperative complications, bone flap decompression and lumbar cistern drainage were compared between the two groups. The independent risk factors for prognosis of aSAH patients undergoing continuous lumbar cistern external drainage were screened by Cox proportional hazard regression model, and these factors were included and XGboost model was established. The prediction model was validated internally and externally in the training set and verification set: AUROC(C-index) was used to verify the model differentiation; GiViTI calibration band and Hosmer-Lemeshow test were used to verify the model calibration; DCA curve was used to verify the clinical validity of the model. Results:Hunt-Hess grade, modified Fisher grade, drainage duration, average daily drainage volume, shunt-dependent hydrocephalus, aneurysm rebleeding, cerebral vasospasm and delayed cerebral ischemia were independent risk factors for poor prognosis in patients with aSAH who underwent continuous lumbar cistern external drainage( P<0.05). The XGboost model was successfully established by incorporating the above independent risk factors, and the internal and external verification of the XGboost model was carried out in the training set and verification set, respectively, the area under the curve of receiver operating characteristic was 0.882(95% CI: 0.820-0.955) and 0.878(95% CI: 0.774-0.928) respectively, and the model differentiation was good; the 80%-90% confidence interval of the GiViTI calibration curve did not cross the 45° angle bisector ( P>0.05). In the Hosmer-Lemeshow goodness-of-fit test, the P value were 0.581 and 0.716, respectively. The threshold probability value in the DCA curve was 30.4%. The clinical net benefit rate of the training set and verification set were 31% and 34%, respectively, indicating that the prediction model was clinically effective. Conclusions:The independent risk factors for poor prognosis of aSAH patients undergoing continuous lumbar cistern drainage are Hunt-Hess grade, modified Fisher grade, cerebral vasospasm, delayed cerebral ischemia and shunt-dependent hydrocephalus. The XGboost model constructed in this study can effectively predict the prognosis of patients with aSAH undergoing continuous lumbar cistern drainage, and provide reference for the formulation of follow-up treatment plans.
5.Effect of GREM[STHZ]1 on the proliferation and metastasis of gastric cancer cells
Yajing LIN ; Tianjie LI ; Hua WANG ; Shihe SHAO
Chinese Journal of Clinical Laboratory Science 2019;37(6):418-422
Objective:
To detect the expression of GREM1 gene in gastric cancer cells, investigate its effects on the biological characteristics of gastric cancer cells and evaluate its application value in the diagnosis and prognosis of gastric cancer.
Methods:
The expression difference of GREM1 in gastric cancer tissues and adjacent normal tissues was analyzed by the database, and the correlation of GREM1 expression levels with the prognosis of gastric cancer patients was evaluated. The expression levels of GREM1 protein in gastric cancer cell lines were detected by western blot. After GREM1 gene in AGS cells was silenced, its effects on the proliferation, migration, epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway of AGS cells were detected by the colony formation assay, Transwell and Western blot, respectively.
Results:
Kaplan-Meier analysis showed that the patients with high expression of GREM1 gene had low overall survival (OS) and progression-free survival (PFS). The expression level of GREM1 protein in AGS cells was the highest in all gastric cancer cell lines (1.967 ± 0.056). The analysis of colony formation assay, Transwell and Western blot showed that the silencing of GREM1 gene could decrease the proliferation and migration of gastric cancer cells (t=22.00; t=29.60; P<0.01), increase the expression of E-cadherin (t=10.65, P<0.01), and decrease the expressions of ZEB1 and MMP2 (t=10.74; t=13.67; P<0.01) and the expressions of β-catenin, Cyclin D1, c-myc, p-GSK3β and PCNA in the Wnt/β-catenin pathway (t=12.65; t=16.21; t=8.74; t=7.75; t=8.42; P<0.01).
Conclusion
GREM1 may induce EMT by activating the Wnt/β-catenin pathway, [JP2]and promote the metastasis and growth of tumors, which may be used as a new molecular diagnostic and prognostic marker for gastric cancer.
6.Simultaneous Determination of Stilbene Glycosides, Ferulic Acid and Paeonol in Qubai Granules by a Dual-wavelength HPLC Method
Aixia YANG ; Kai YI ; Shihe LIN
China Pharmacist 2018;21(6):1093-1095
Objective: To establish an HPLC determination method for the quantitative indicators in Qubai granules( stilbene gly-cosides, ferulic acid and paeonol). Methods: A dual-wavelength HPLC assay was used with the following conditions: a chromatogra-phy column ODS (150 mm×4. 6 mm, 5 μm) was used, the mobile phase was methanol: 0. 1% phosphoric acid with gradient elution, the column temperature was 35℃, and the injection volume was 10 μl. Results: The linear ranges of the three active constituents were 1.56-156.00 μg·ml-1(r stilbeneglycoside=0.999 8)、1.00~100.00 μg·ml-1(rferulicacid=0.999 8),1.61~161.00 μg·ml-1(rpaeonol=0. 999 7), respectively, and the average recoveries of the three constituents were between 100. 33% and 100. 76% with the RSDS less than 2% (n=6). Conclusion: The method is simple, stable and reliable, which can be used for the quality control of Qubai granules.
7.Anti-inflammatory Activity of Total Alkaloids from Solanum Lyratum
Shihe LIN ; Yandong YI ; Nancai YU
China Pharmacist 2016;19(7):1263-1266
Objective:To study the anti-inflammatory activity of total alkaloids from Solanum lyratum.Methods:Human umbili-cal vein endothelial cells ( HUVECs) were cultured and induced by H 2 O2 (200 μmol· L-1 ) , and RAW 264.7 cells were cultured and induced by lipopolysaccharide ( LPS ) .The two inflammatory cell models were randomly divided into the normal group , model group, positive control group, and total alkaloids group respectively at low , medium and high dose.After the treatment, the cells were continued to be cultured , and CCK-8 method was applied to observe the cell survival rate .SD rats were randomly divided into the nor-mal group, model group, positive control group, total alkaloid group respectively at low, medium and high dose,and then the rats re-ceived subplantar injection of carrageenan in the paw .After the treatment , inflammation was analyzed by the swelling degree of acute ankle joint injury, and the contents of prostaglandin E2 (PGE2) and cyclooxygenase-2 (cox2-) were detected.Results:The effect of total alkaloids from Solanum lyratum at medium dose on H 2O 2-induced HUVECs and that of total alkaloids from Sola num lyratum at high dose on LPS-stimulated macrophages were similar to that of the positive control group without statistical significance (P>0.05), and the total alkaloids from Solanum lyratum at medium and high dose could significantly reduce the swelling degree of the acute ankle model in rats (P<0.01), and decrease the content of PGE2 in the toe exudate of rats and that of COX-2 in serum (P<0.01) with statistical significance when compared with that in the model group (P<0.01).Conclusion:The total alkaloids from Solanum lyra-tum have significant anti-inflammatory activity , and it is necessary to further study the efficacy and action mechanisms .
8.Study on Water Extraction Process of Traditional Chinese Medicine Qubai Granule by Orthogonal Test
Aixia YANG ; Kai YI ; Yandong YI ; Shihe LIN
China Pharmacist 2016;19(10):1849-1851,1852
Objective:To optimize the water extraction process of traditional Chinese medicine ( TMC) Qubai granule. Methods:The orthogonal test was used to study four influencing factors including water amount, soaking time, extraction time and extraction times with dry extract yielding rate and the content of ferulic acid as the evaluation indices. Results:The optimum extraction process was as follows:A2 B1 C2 D2 , namely adding 10-fold amount of water, without soaking in advance, extracting twice with 2 h for each time. Con-clusion:The process is simple, stable and reproducible, which provides basis for the industrial production.
9.Optimization of Alcohol Precipitation Technology for Qingmai Granules by Orthogonal Test
Yandong YI ; Wei MA ; Shihe LIN ; Nancai YU
China Pharmacist 2014;(4):571-573
Objective:To optimize the alcohol precipitation technology of Qingmai granules. Methods:The relative density of liq-uor,the concentration and time of alcohol precipitation were chosen as the factors,the yield of dry extract and content of diosgenin as the indices,the alcohol precipitation technology was optimized by orthogonal test. Results:The optimal alcohol precipitation technology was as follows:the extraction liquid was concentrated till the relative density was 1. 13-1. 18 g·ml-1 ,ethanol was added until the concen-tration was up to 60% with the alcohol precipitation time of 24h. Conclusion:The optimized technology is stable,reasonable and feasi-ble,which can provide experimental basis for the clinical application of Qingmai granules.
10.Comparative study on mammography between triple negative and triple positive breast cancer
Chunxiao CUI ; Qing LIN ; Qing YANG ; Chuanyu ZHANG ; Shaohua WANG ; Hualong YU ; Feng DUAN ; Shihe LIU
Chinese Journal of Radiology 2012;46(5):420-424
Objective To analyze the mammographic findings of triple-negative breast cancer [TNBC,which is estrogen receptor (ER) negative,progesterone receptor (PR) negative,and human epidermal growth factor receptor 2 ( HER2 ) negative ] and triple-positive breast cancer ( TPBC,which is ER positive,PR positive,and HER2 positive ),and to evaluate the relationship of immunohistochemologic receptor status and mammographic findings.MethodsThe immunohistochemistry results of 631 cases with breast cancers were reviewed,including 117 cases of TNBC and 44 cases of TPBC.All of the patients took mammography at initial diagnosis.We retrospectively evaluated the visibility,morphology,distribution and size of the lesion (masses and calcifications) and breast density on mammography of TNBC,and compared them with those of TPBC.The age onset and tumor sizes of TNBC and TPBC were compared by using Chi-square test and t test.ResultsThe visibility rate of TNBC and TPBC on mammography were 88.0%(103/117) and 90.9% (40/44),and the difference between them was insignificant ( x2 =0.055,P >0.05).TNBC was more frequently associated with merely a mass (56/103) than TPBC (12/40) (x2 =6.860,P<0.01 ),and the mean diameter of the mass of TNBC [ ( 2.6 ± 1.4 ) cm ] was larger than that of TPBC [(2.0 ± 0.6) cm](t =2.087,P < 0.05). TNBC were less frequently associated with microcalcifications (37/103) than TPBC ( 24/40 ) ( x2 =7.423,P < 0.01 ).Mammographic density and lesion visibility were similar between the two different immunophenotypes of breast cancers.The mean age of TNBC (52±9) was more than that of TPBC (48 ±8) (t =2.759,P <0.01).Infiltrating ductal carcinoma was the main pathologic type of both groups.Basal-like breast cancer accounted for 49% (57/117 ) of TNBC while none happened in TPBC.ConclusionsTNBC shows merely a mass with indistinct margins,lager size and is less associated with microcalcifications.These mammographic features might be useful in diagnosing triple negative breast cancer.

Result Analysis
Print
Save
E-mail