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Objective To investigate the expressions and correlations of Kiss-1 and matrix metalloproteinases-9 (MMP9) proteins in the colorectal cancer (CRC) tissues of patients with synchronous colorectal liver metastasis (SCRLM),and the association with the clinicopathologic factors and prognosis of patients.Methods The retrospective case-control study was adopted.The clinicopathological data of 96 patients with SCRLM and 69 patients with CRC and no metastasis who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2000 to May 2013 were collected.The 96 CRC tissues and 50 adjacent normal tissues (distance from resection margin ≥ 5 cm) were collected from 96 patients with SCRLM,and 69 CRC tissues were collected from 69 patients with CRC and no metastasis.Expressions of Kiss-1 and MMP9 protein were detected by immunohistochemistry (IHC).The follow-up of outpatient examination and telephone interview was performed to detect survival of patients till August 2014.Comparison of count data and correlation between expressions of Kiss-1 or MMP9 protein and clinicopathological factors were analyzed by the chi-square test and Fisher exact probability.Survival curve was drawn using the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Correlation analysis was done by the Pearson correlation.Results Expression of Kiss-1 protein was located in the cytoplasm of tissue cells.The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 24.0％ (23/96),43.5％ (30/69) and 52.0％ (26/50),respectively,with a significant difference among the 3 tissues (x2 =14.307,P ＜ 0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2 =0.845,P ＞ 0.05).The positive expression rate of Kiss-1 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =0.702,11.594,P ＜ 0.05).Expression of MMP9 protein was located in the cytoplasm of tissue cells.The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 67.7 ％ (65/96),62.3 ％ (43/69) and 36.0％ (18/50),respectively,with a significant difference among the 3 tissues (x2=14.203,P ＜0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2=8.038,P ＞ 0.05).The positive expression rate of MMP9 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =13.475,13.475,P ＜ 0.05).The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM were 66.7％,21.9％ and 17.6％ in the high-,mederate-and low-differentiated tumor,50.0％,28.6％ and 17.5％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 16.9％ in patients with and without lymph node metastasis,respectively,showing significant differences among the tumor differentiation degree,depth of tumor invasion and lymph node metastasis (x2=6.546,6.172,7.453,P ＜0.05).The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM were 25.0％,66.7％ and 76.2％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 76.1％ in patients with and without lymph node metastasis,respectively,showing significant differences between the depth of tumor invasion and lymph node metastasis (x2 =12.094,8.690,P ＜ 0.05).All the 96 patients with SCRLM were followed up for a median time of 68 months (range,12-176 months).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,26 months,69.6％ and 26.1％ in patients with SCRLM and positive expression of Kiss-1 protein and 26 months,19 months,24.7％ and 12.3％ in patients with SCRLM and negative expression of Kiss-1 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=16.578,14.436,P ＜ 0.05).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,19 months,24.6％ and 12.3％ in patients with SCRLM and positive expression of MMP9 protein and 28 months,16 months,58.1％ and 22.6％ in patients with SCRLM and negative expression of MMP9 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=14.073,8.532,P ＜0.05).Of 96 patients with SCRLM,there were 23 patients with positive expression of Kiss-1 protein (10 with positive expression of MMP9 protein and 13 with negative expression of MMP9 protein) and 73 with negative expression of Kiss-1 protein (55 with positive expression of MMP9 protein and 18 with negative expression of MMP9 protein),with a negative correlation between expressions of Kiss-1 protein and MMP9 protein (r =-0.291,P ＜ 0.05).Conclusions The reduced expression of Kiss-1 protein and elevated expression of MMP9 protein are closely associated with invasion and metastasis of CRC and prognosis of patients.A combination detection of Kiss-1 and MMP9 proteins is expected to become a marker for predicting the prognosis of patients with SCRLM based on the negative correlation between them.
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The liver is a primary target organ of colorectal cancer metastases. Surgical resection is pres-ently the only approach that offers patients a substantial chance of cure. Five-year survival ranges 25% -39%. But by the time of diagnosis, only 10% -25% of patients were considered eligible for surgical directed thera-pies. New therapeutic modalities such as ablation, hepatic arterial infusion chemotherapy, neoadjuvant chem-otherapy and targeted therapy present promise for the future treatment of unresectable liver metastases. These treatments and progress in surgical therapy are reviewed in this article.
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Objective To summarize and analyze the surgical therapies for liver and gastric multiple primary cancers. Methods The clinical data of 14 patients with liver and gastric carcinomas surgically treated in our hospital from January 2004 to January 2008 were retrospectively analyzed.Results Of the 14 patients, 12 underwent simultaneous resection of liver and gastric carcinomas,1 resection of the gastric carcinoma 2 months after the liver surgery and 1 removal of liver cancer found 2 years after the surgery for antral adenocarcinoma. The median survival time of these patients was 23 months. The 1-and 3-year survival rate was 78.6% and 35.7%, respectively. Conclusion Due to different pathological characteristics, the therapies of liver and gastric multiple primary cancers are completely different from that of the recurring and metastatic carcinoma. Both tumors can be treated by radical resection and the effect is similar to single cancer. Positive treatment is crucial for long-term survival of the patients.
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Objective To determine the characteristic features of solitary necrotic nodule(SNN)of the liver on precontrast and dynamic contrast enhanced magnetic resonance(MR)imaging.Methods We retrospectively reviewed 15 patients with histopathologically proved SNN.All of the images were evaluated for lesion features including the number,shape,size,location,border,signal intensity and pattern of enhancement.Results Sixteen lesions were found in 15 patients.Nonenhaneed T1-and T2 weighted images depicted 15 lesions in 14 patients and 14 lesions in 13 patients respectively.Maximum diameter of 14 lesions was less than 3 cm.On unenhanced T1-weighted images,5 lesions were hypointense,9 lesions were slishtly hypointense,and 1 was isointense with hypointense capsule and central punctate hypointense foci.Among14 lesions demonstrated on T2-weighted images,5 were hyperintense,4 were slightly hyperintense,3 were slightly hypointense,and 2 were hypointense.Punctate or linear high signal intensities were found in2 lesions.All lesions were not enhanced after contrast injection.On portal venous and delayed phase.all lesions appeared significantly hypointense with well-defined border.The shape was irregular in 12 lesions and was round or oval in 4 lesions.No enhancement was found in the lesion except thin delayed enhancement in capsules of 3 lesions after contrast agent administration.Conclusion Characteristic MRI features of SNN are helpful for distinguishing SNN from other hepatic lesions.
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Objective To evaluate the efficacy of percutaneous laser ablation in the management of portal vein tumor thrombus(PVTT)of hepatocellular carcinoma(HCC).Methods Under ultrasound guidance,a needle was percutaneously punctured into the portal vein,through the axial of the tumor thrombus,and until the proximal end.An optic fiber was inserted through the needle and repeated pulse laser ablation was given.Results Complications included 102 cases(94.4%)of pyrexia 1～3 d after treatment(37.5～39.5 ℃),84 cases(77.8%)of incisional pain,and 3 cases(2.8%)of upper gastrointestinal bleeding.There were three types of findings of PVTT in 53 cases surviving over 1 year:①the tumor thrombus was atrophied and disappeared in 20 cases;②the thrombus was atrophied and the portal vein exhibited a honeycomb-like appearance in 18 cases;③the thrombus kept on growing and the portal vein was enlarged in diameter in 15 cases.Among 95 cases of totally occluded portal vein,color blood flow signals appeared in all of them on the first postoperative day.The signals could still be seen in 76 cases at 1 month after treatment,in 64 cases(out of 91 cases)at 3 months,in 52 cases(out of 71 cases)at 6 months,in 36 cases(out of 42 cases)at 1 year,in 10 cases(out of 14 cases)at 2 years,and in 2 cases(out of 2 cases)at 3 years.The 1-,2-,and 3-year survival rates were 55.56%,35.20%,and 20.30%,respectively.Conclusions Percutaneous laser ablation is a feasible novel option for the treatment of portal vein tumor thrombus of hepatocellular carcinoma.
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Objective To investigate the inhibitory effects of IL-18 gene on HCC growth in vivo. MethodsThe recombinant adenovirus vector containing IL-18 gene was constructed and cotransfected into 293 cells together with EcoT22 I-digested Ad5 DNA-TPC, the recombinant adenoviruses were generated, and injected into a rat model bearing HCC. Results The recombinant adenovirus vector containing IL-18 gene inhibited the proliferation of HCC cell line CBRH 3. The rats receiving IL-18 gene injection within 3 days after inoculation of CBRH 3 all had long term survival, while those injected at day 5 or 7 survived a limited longer period than control groups (P
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Objective To construct a new replicating adenovirus vector CNHK600-p53 carrying anti-tumor gene p53 and investigate its effect on hepatocarcinoma cell line PLC/PRF5. Methods The methylthiazolyl tetrazolium assay (MTT) was used to observe the killing effect of Fluorouracil, Mitomycin and Epirubicin alone or in combination with adenovirus CNHK600-p53 on PLC/PRF5. Results When 5-Fu at concentration of 400?g/ml, the inhibition rate was (65?4. 2) % ; with MMC at 1?g/ml, the rate was (41?1.9)%; and it was (65?1.8)% when EPI at concentration of 10?g/ml. With PLC/PRF5 infected by adenovirus CNHK600-p53 ( MOI = 0. 625) , the inhibition rate was significantly increased to (89?5. 3)%,(60?2.3)% and (75?1.5)% respectively; When MOI was 0.3125, 0.625, 1.25, the inhibition rate in CNHK600-p53 group and Ad-p53 group was (27?2. 5)% , (30?3. 7)% , (61?4. 3)% and(4?2.7)%, (5?3.5)%, (16?4.5)% respectively. Conclusion For hepatocarcinoma cell line PLC/PRF5 the effect of CNHK600-p53 is stronger than Ad-p53.
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Objective To study on imagination features of tumor thrombi in the portal vein of primary liver cancer (PLC). Methods We established a new type system of tumor thrombi, with Ⅰ 0 to Ⅳ, a total of 5 types and 8 sub-types in the portal vein of PLC based on normal intrahepatic portal vein anatomy and growing features of the tumor thrombi. The relationship between the types and the imaging diagnosis of 130 PLC cases with tumor thrombi in the portal vein was studied. Results 85%(110/130) cases of PLC with tumor thrombi in the portal vein belongs to type Ⅱ or Ⅲ when being first diagnosed in the hospital. The resectability rates for type Ⅰ, Ⅱ, Ⅲ, Ⅳ were 62%(5/8), 16%(10/62), 10%(5/48), 0 (0/12), respectively, and chemoembolization therapy (TACE) was given in 38%(3/8), 40%(25/62), 27%(13/48), 16%(2/12), respectively. Conclusions The new types of tumor thrombi are helpful for diagnosis and treatment of PLC with tumor thrombi in the portal vein.
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Objective To study the relationship between gastroesophageal varices and bleeding and portal venous tumor thrombi in patients with hepatocellular carcinoma(HCC). Methods From Jan. 2000 to Jan. 2003, 84 HCC patients with portal vein tumor thrombi were divided into Ⅰ～Ⅳ groups according to Ⅰ～Ⅳ types of tumor thrombi. The grade of gastroesophageal varices, the median survival time and the death cause for group Ⅰ～Ⅳ were retrospectively analyzed. Results Mild grade of gastroesophageal varices accounted for 64.7%, 6.0%, 85.7%,100%, respectively in group Ⅰ(n=17), Ⅱ(n=26),Ⅲ( n=35) and group Ⅳ(n=6),respectively. Severe varices were found in less than 5% in all four groups. The median survival periods were 10.1, 7.2, 5.7 and 3.0 months, respectively (P=0.0001). Most cases died from esophageal and gastric variceal bleeding and hepatic failure, with each accounting for about 50% of the mortality in all the 4 groups. Conclusions Portal venous tumor thrombi of HCC patients was not the major cause leading to esophageal and gastric varices and bleeding.
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This is a retrospective study of 103 cases of early gastric cancer undergoing surgery during the years of 1974-1988 with a special discussion on surgical treatment.The lesions were localized to the mu-cosal layer in 54.3%,to submucosal layer in 45.7%,In 10% of patients there was lymphnode metastasis,all of them were in the first station.Operation consisted of radical subtotal gastrectomy in 94.2%.and total gastrectomy in 5.8%.The extent of lymphatic excision was:Ro in 12.6%,R1 in 61.2% and R2 in 26.2% Postoperative chemotherapy was given in 61.2%.However no statistical difference of 5 years survival rate was found in respect to the extent of lymphatic excision as well as postoperative chemotherapy.Since 60.2% of EGC lesions were of minute,multiple and plane type,preoperattve en-doscopy and intraoperative biopsy of gastric mucosa,if necessary,should be carefully done to ascertain that no lesion was overlooked in the remnant of the stomach.Follow-up rate was 96%,and the survival rates of 3 and 5 years were 97% and 93.7%.This makes the authors believe that a radical operation of R1 is justified and routine postoperative chemotherapy is unnecessary.
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Objective To study the inhibitory effect of intrasplenic injection of retroviral packaging cells encoding human interleukin-2 (hIL-2) and mouse interleukin-12 (mIL-12) fusion gene on the growth of chemically induced hepatocellular carcinoma in rats. Methods The retroviral vector GCIL12EIL2PN encoding hIL-2 and mIL-12 fusion gene was constructed. The retroviral packaging cell line PA317 transfected with the vector was injected into the spleens of rats with established chemically induced hepatoma on on the 90th day (early-stage treatment) or the 105th day (late-stage treatment). The survival time and toxic effect were observed. The serum mIL-12 and hIL-2 levels were assayed with ELISA, and the cytotoxicity of the natural killer (NK) cells was measured by means of a 51Cr-release assay using YAC-1 tumor cells as the target. Results The average survival time (after chemical induction) in the early-stage treatment rats and the late-stage treatment rats were 188.1?14.2 days and 168.5?13.6 days, respectively, in IL-12+IL-2 combination gene treatment group, and it was longer than that of IL-12 gene treatment group (168.2?13.4 days and 149.1?13.8 days, respectively, P