Objective
To analyse tratment strategies and to evaluate the relation between different therapies and survival rate of patients of with asynchronous liver metastases after pancreatic cancer surgery(PCLM).
Methods
From January 2006 to January 2012, 48 patients with PCLM were included in this study, and their medical records were retrospectively analyzed.
Results
Among the 48 patients, 27 cases of liver metastases were found within six months after surgery, and the survival rate for 1, 3 and 5 years was 22.2%, 3.7% and 0%, respectively, with the median survival of 6 months, and 21 cases of liver metastases were found after six months, and the survival rate for 1, 3 and 5 years was 85.7%, 30.6% and 9.2%, with the median survival of 15 months, and the difference between the two groups was statistically significant (P<0.01). After pancreatic cancer surgery and adjuvant gemcitabine chemotherapy, the probability of liver metastases was 33.3%(8/24) within six months, the median disease-free survival time was 8 months and the disease-free survival rate for 1, 3 and 5 years was 20.8%, 4.3% and 0%. For patients without adjuvant gemcitabine chemotherapy, the probability of liver metastases was 79.2%(19/24), the median disease-free survival time was 3 months and the disease-free survival rate for 1, 3 and 5 years was 4.2%, 0% and 0%, and the difference between the two groups was statistically significant (P<0.01). The overall survival for patients undergoing resection of liver metastases combined with gemcitabine treatment was better than the other groups (P<0.01). And the overall survival for patients undergoing transhepatic arterial embolization (TACE) combined with gemcitabine treatment was better than TACE group, gemcitabine group or the observation group(P<0.05). There were no difference in overall survival between TACE group, gemcitabine group and observation group.
Conclusions
Pancreatic cancer patients who develop liver metastasis within six months after surgery have poor prognosis, but postoperative chemotherapy can delay the development of liver metastasis. For patients with resectable lesion, resection of asynchronous liver metastasis is the treatment of choice, and TACE combined with gemcitabine has better efficacy than that of single treatment.
Key words:
Pancreatic neoplasms; Liver metastasis; Postoperative period; Prognosis
To observe the cytopathic effect of Staphylococcus aureus L-form on human carcinoma cells of gallbladder (GBC-SD),these cells were infected with S.aureus L-forms. Light and electron microscopy and PCR assay were used to test whether the L-forms could enter into the infected cells and MTT assay was employed to test whether they could promote the proliferation of GBC-SD and production of the proliferating cell nuclear antigens (PCNA) in vivo. In addition,the alteration of cellular genes after action of L-form was determined by means of gene clip. As demonstrated by PCR assay as well as light and electron microscopy,S.aureus L-forms could enter into GBC-SD cells efficiently. Also,they could improve proliferation of these cells as revealed by MTT assay and testing for PCNA. The result in gene clip showed that 15 gene expression alterations could be demonstrated in GBC-SD cells infected with S.aureus L-forms. Meanwhile,the result in up-regulation gene of EMR2 (EGF-like module-containing mucin-like hormone-like 2) and down-regulation gene of ECM2 (extracellular matrix protein-2) were matched with those of the gene clip by RT-PCR. It is evident that S.aueus L-forms can enter into GBC-SD cells to promote cellular proliferation in vivo and induce up-regulation of ERM2 gene and down-regulation of EMC2 gene,suggesting that they may be related to the development and carcinogenesis of gallbladder cancers.
Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems.We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan-Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging.Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696-0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P < .001), and the AJCC 6th edition staging system (0.712, P = .033). Moreover, in the stratified data, the differences between the stages identified using the modified AJCC staging classification were significant, especially among patients over 60 years in age, white patients and patients who underwent surgery.These findings suggest that the modified AJCC staging classification may be applicable to the staging of ICC and can be adopted in clinical practice.
Abstract Intrahepatic cholangiocarcinoma (ICC) is a rare but highly aggressive malignant tumor arising within the liver, with a 5-year survival rate of only 20–40% after surgery. The role of interleukin-8 (IL-8) in ICC progression remains elusive. A transcriptomic approach based on IL-8 stimulation first revealed significant upregulation of the prometastatic gene CD97 and key epithelial–mesenchymal transition (EMT) factors E-cadherin and vimentin. Immunohistochemistry of 125 ICC tissues confirmed the positive correlation between IL-8 and CD97. Multivariable Cox regression indicated that they are both independent predictors of ICC prognosis. Mechanistically, IL-8 treatment induced CD97 expression at 50 and 100 ng/ml in QBC-939 and QBE cells, respectively. Moreover, the induction of cell migration and invasion upon IL-8 treatment was attenuated by CD97 RNA interference, and the expression of EMT-associated genes was dramatically inhibited. To determine whether CXCR1 or CXCR2 are downstream effectors of IL-8, siCXCR2 was applied and shown to significantly attenuate the oncogenic effects of IL-8 by inhibiting the phosphorylation of PI3K/AKT. Finally, the induction of CD97 expression by the PI3K pathway was verified by treatment with the inhibitor LY294002. In vivo, the significant tumor growth and lung metastasis effects induced by intraperitoneal injection of IL-8 were greatly inhibited by silencing CD97 in nude mice. Collectively, the study presents a novel mechanism of the IL-8-CXCR2-PI3K/AKT axis in regulating CD97 expression, which leads to ICC metastasis mainly through EMT. The study may provide alternatives for targeting the tumor microenvironment in metastatic ICC.
Abstract Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study. Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database. The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child–Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child–Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival. Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.
Gallbladder carcinoma (GBC) is the most common cancer of the biliary tract. Lymph node metastasis (LNM) is the major diffusion route of GBC and is a prognosis factor. The aim of study was to assess the potential of the serum VEGF-C and VEGF-D (sVEGF-C/D) levels to predict the presence of LNM and the survival of GBC patients. The preoperative sVEGF-C/D levels of 31 patients with GBC, 10 patients with cholesterol polyps, and 10 healthy volunteers were measured by enzyme-linked immunoadsorbent assay (ELISA). The sVEGF-C/D levels of patients with GBC were significantly higher than those of people with healthy gallbladders (p < 0.001 and p = 0.001, respectively) and cholesterol polyp (p = 0.032 and p = 0.004, respectively). In GBC, the sVEGF-C levels were associated with LNM (p = 0.011), distant metastasis (p = 0.018), and stage (p = 0.045), but the sVEGF-D levels had a significant association with the tumor depth (p = 0.001), LNM (p = 0.001), distant metastasis (p = 0.047), and stage (p = 0.002). The sVEGF-C/D diagnostic values for the presence of GBC were sensitivity of 71.0 and 74.2 % and specificity of 80.0 and 85.0 %, respectively. With respect to the diagnosis of LNM, the diagnostic values of sVEGF-C/D were as follows: sensitivity 81.2 and 87.5 % and specificity 73.3 and 80.0 %, respectively. The mean survival time with high sVEGF-C was significantly shorter than that with low sVEGF-C (p < 0.001), which was also true for low sVEGF-D (p = 0.032). The preoperative sVEGF-C/D levels might be reliable biomarkers for the presence of disease and LNM in patients with GBC. The sVEGF-C/D levels may be prognosis factors that can predict a poor outcome for GBC patients.
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