The reduction of peripheral blood cells is a common and serious complication in hepatic cirrhosis portal hypertension patients with splenomegaly, and severely affects the prognosis.Its reasons include hypersplenism and non-hypersplenism factors.We should correctly understand these two factors.Hypersplenism factors is common, and non-hypersplenism factors, including the toxic effects of virus on the bone marrow, liver cirrhosis, hepatosis, immunodeficiency, the toxic effects of drugs, dystrophia, the destruction of platelets in blood circulation and hemorrhage.Etiological treatment and liver transplantation is the main treatment.Now, treatment of the reduction of peripheral blood cells has become an important topic.In this paper, the causes and treatments of peripheral blood cytopenias, which were caused by non-hypersplenism factors in the patients of liver cirrhosis and portal hypertension, were reviewed.

Objective To investigate the expressions of T helper cell 1 (Th1)-associated chemokine receptors CXCR3, CCR5 and T helper cell 2 (Th2)-associated chemokine receptor CCR3 in the spleen tissues of rats with cirrhosis and hypersplenism and probe into the balance between Th1/Th2 lymphocyte subsets.Methods Experimental study was adopted.Forty-six male SD rats were randomized into the hypersplenic group (n =36) and the control group (n =10).In the hypersplenic group, the rats were fed with 40％ CCl4 peanut oil solution (3.0 mL/kg, twice per week) and 15％ white spirit for 8 weeks to build the hypersplenic model.The rats in the control group received normal feeding.The animal models with cirrhosis and hypersplenism were confirmed by liver function test, routine blood test, HE staining and Masson staining after visual inspection.The expressions of chemokine receptors of CXCR3, CCR5 and CCR3 were detected by immunohistochemical staining and Western blot.Measurement data with normal distribution were presented as x ± s.Comparison between groups was done using the independent sample t test.Results Results of visual inspection: the rats in the hypersplenic group suffered from severe hair-shedding, metal fatigue and inappetence, with hair dimming and inactivity.There were rats dead successively 5 weeks after model establishment and 19 rats finally survived.The rats in the control group had color and gloss hair, with good appetite and spirits.They were active and sensitive to external stimulation.Changes of pathological morphology in liver: in the hypersplenic group, the fibers became denser and disordered, making normal structure of liver tissues destroyed.The hepatic lobules separated by fibrous bundle and proliferative hepatic cell mass were segmented and surrounded by thick fibrous,leading to the formation of pseudolobule.Disorganized hepatocytes suffused adipocytes, the nucleus of heterocysts enlarged or even multinucleated cells appeared.There was no change in the control group.Changes of pathological morphology in spleen: the rats in the hypersplenic group had slightly swelling spleen with the areas of red pulp increased and whit pulp disappeared gradually.Vascular endothelium became thicker and proliferated.Thickened central artery and fibrosis were depicted.Splenic sinusoid extended.There was no change of spleen tissues in the control group.Changes of liver function : the levels of ALT and AST of rats were (264 ± 111) U/L and (687 ± 299) U/L in the hypersplenic group,which were significantly different from (27 ± 8)U/L and (124 ± 20)U/L in the control group (t =5.64, 4.98,P ＜ 0.05).The level of total protein was (54 ± 8)g/L in the hypersplenic group, which was significantly different from (65 ± 3)g/L in the control group (t =-3.35, P ＜ 0.05).Changes of peripheral blood cell count: the white blood cell (WBC) count in the hypersplenic group was (23.9 ± 5.0) × 109/L, which was significantly different from (6.2 ± 2.4) × 109/L in the control group (t =3.50, P ＜ 0.05).The red blood cell count and platelet count in the hypersplenic group were (6.3 ±0.7) × 1012/L and (418 ± 124) × 109/L, which were significantly different from (8.0 ± 0.6) × 1012/L and (1 109 ± 161) × 109/L in the control group (t =-2.28,-4.92, P ＜ 0.05).Results of immunohistochemical staining: the cytomembrane and/or cytoplasm stained yellow, brown or sepia were defined as positive performance of CXCR3, CCR5 and CCR3.The absorbance A values of CXCR3 and CCR5 were (81.7 ±24.4) × 10-3 and (3.6 ± 1.3) × 10-3 in the hypersplenic group, which were significantly different from (19.2 ± 5.8) × 10-3 and (1.2 ± 0.4) × 10-3 in the control group (t =16.22, 9.09, P ＜ 0.05).The absorbance A value of CCR3 was (8.8 ±3.7) × 10-3 in the hypersplenic group and (7.9 ±2.8) × 10-3 in the control group, respectively, showing no significant difference between the 2 groups (t =0.87, P ＞ 0.05).The rates of positive cells of CXCR3 and CCR5 was 52％ ± 9％ and 19％ ± 5％ in the hypersplenic group, which were significantly different from 21％±5％ and 10％±3％ in the control group (t =17.31, 8.21, P ＜0.05).The rates of positive cells of CCR3 in the hypersplenic group and control group were 35％ ± 9％ and 33％ ± 14％, respectively, showing no significant difference between the 2 groups (t =0.43, P ＞ 0.05).Results of Western blot test : the relative expressions of CXCR3 and CCR5 were 2.45 ± 0.85 and 0.94 ± 0.48 in the hypersplenic group, which were significantly different from 1.31 ± 0.95 and 0.32 ± 0.26 in the control group (t =2.62, 2.91, P ＜ 0.05).The relative expression of CCR3 was 0.47 ± 0.27 in the hypersplenic group, which was significantly different from 0.92 ± 0.67 in the control group (t =-2.18, P ＜ 0.05).Conclusion The abnormal expression of chemokine receptors in the spleen tissues of rats with cirrhosis and hypersplenism induced by CCl4 suggests that functional imbalance of Th1/Th2 lymphocyte subsets may play an important role in the regulation of peripheral blood cytopenia.

Objective To investigate the intra-splenic blood cell count of posthepatitic cirrhotic portal hypertension,and compare it with patients' peripheral blood cell count to explore the role the spleen plays in peripheral cytopenia often seen in posthepatitic cirrhotic portal hypertension.Methods A prospective study was made on 15 cases with post hepatitis B cirrhotic portal hypertension undergoing splenectomy.Intrasplenic blood was sampled from upper pole,hilus (central pole),and lower pole of the spleen respectively for blood cell count.Results were compared with that of preoperative peripheral blood.Results There were significant statistical differences in the WBC count between splenic blood and peripheral blood,(11.20 ± 4.73) × 109/L vs.(4.06 ± 1.75) × 109/L,t =5.05,P ＜ 0.05),and in PLT count,(182.45±66.57) × 109/L vs.(63.54 ±28.40) × 109/L,t =7.285,P ＜0.05.There was no differences in the RBC count,(3.55 ± 0.94) × 1012/L vs.(3.01 ± 0.62) × 1012/L,t =1.874,P ＞ 0.05.Positive correlations were found between splenic PLT count and peripheral PLT count (r =0.610,P ＜0.05).Conclusions In posthepatitic B cirrhotic portal hypertension patients the intra-megalosplenic PLT and WBC count are significantly higher than that in peripheral blood.Megalosplenic PLT count correlates positively with peripheral PLT count.

Objective To investigate the causes of peripheral cytopenia in patients with posthepatitic cirrhosis and portal hypertensive splenomegaly.Methods The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia who were operated in our hospital in the past 17 years were retrospectively studied.Results All these patients underwent splenectomy.Before operation,all these patients had one or more types of peripheral cytopenia (cumulative cytopenia:390 patient-times).After splenectomy,blood counts in 79.2％ returned to normal;in 15.9％ increased but failed to reach normal levels;and in 4.9％ became lower than before operation.5 patients died soon after operation.Conclusion Hypersplenism is the main cause for the peripheral cytopenia most cirrhotic portal hypertension patients.Splenectormy is an effective method to treat hypersplenism.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.