Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Objective:To investigate the expression level of serum vascular endothelial growth factor(VEGF) in patients with unresectable hepatocellular carcinoma(HCC) and its relationship with the clinicopathological characteristics,and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization(TACE) treatments.Methods:Serum VEGF levels were measured using enzyme-linked immunosorbent assay(ELISA) in 60 random patients who underwent TACE or transarterial infusion(TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control.All patients’ clinicopathological features were retrospectively analyzed.Serum VEGF levels were correlated with clinicopathological features of the HCC patients.The patients’ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test.The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results:The median serum VEGF level in the HCC patients was 285 pg/ml(range 14 1,207 pg/ml),significantly higher than that of healthy controls(P=0.021).The serum VEGF levels were significantly correlated with platelet counts(r=0.396,P=0.002) but not other clinicopathological features.Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml(P=0.002).By multivariate analysis,the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.     

Successful surgical resection of large hepatocellular carcinoma with portal vein tumor thrombus after conversion therapy with mFOLFOX-HAIC combined with donafenib and sintilimab: two case reports and a literature review

The aim of our study was to evaluate the clinical efficacy of m FOLFOX-HAIC combined with donafenib and sintilimab conversion therapy followed by surgical resection of large hepatocellular carcinoma with portal vein tumor thrombus(PVTT). The clinical data of two patients with large hepatocellular carcinoma who were admitted to the Second Affiliated Hospital of Kunming Medical University were retrospectively collected. Both patients received m FOLFOX-HAIC combined with donafenib and sintilimab co...     

Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum

Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.
Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits.
Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）.
Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell met     

Relationship of Serum Interleukin-18 and Interleukin-12 Levels with Clinicopathology in Renal Cell Carcinoma

Objective:To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma.Methods:Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery.IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay.Results:Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers(P<0.05)and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed.A positive correlation was observed between serum IL-12 and IL-18 levels(P<0.05).In patients with renal cell carcinoma,increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade.Conclusion:Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.     

Jinlong capsule decreases adverse reactions after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma

Objective The aim of this study was to analyze whether Jinlong capsule could decrease adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma. Methods Eighty-two patients with hepatocellular carcinoma were randomly divided into the control group and experimental group. On the first day after TACE, the experimental group started receiving four Jinlong capsules orally three times daily, whereas the control group did not receive the treatment.Results The incidences of erythropenia and thrombocytopenia in the experimental group was lower than those in the control group(P = 0.040 and 0.033, respectively). The differences in serum levels of aminotransferase, albumin, potassium, and sodium between the two groups were significant(P = 0.034, 0.034, 0.013, and 0.044, respectively). The mean durations of stomachache and abdominal distension in the experimental group was significantly shorter than those in the control group(P = 0.004 and 0.021, respectively). However, there were no significant differences in the incidences of nausea, fever, and vomiting between the two groups(P = 0.490, 0.495, and 0.585, respectively). Conclusion The reduction in the incidence rate and duration of partial adverse reactions after TACE was observed in hepatocellular carcinoma patients treated with Jinlong capsule compared to untreated patients, suggesting possible beneficial effects exerted by Jinlong capsule on the reduction of TACE-induced liver damage, thereby improving liver function and, consequently, the quality of life.     

Long-term survival of patients with hepatocellular carcinoma with inferior vena cava tumor thrombus treated with sorafenib combined with transarterial chemoembolization:report of two cases and literature review

The prognosis of hepatocellular carcinoma （HCC） with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.     

肝癌术后复发

Objective:To analyze pest-surgical recurrence of hepatocellular carcinoma (HHC) according to pathologic findings, primary tumor and angiographic features of the recurrent tumor. Methods:In this series, 100 cases of recurrent HCC were analyzed in following aspects: (1) size, tumor nodular numbers, gross and histologic findings of the primary tumor; (2) post-surgical recurrent time; (3) size, tumor nodular numbers, blood supply, staining property, and accumulation of lipiodol oil in the recurrent tumor. Following angiography, arterial chemoembolization was performed. Results:In the primary tumor, single nodules were seen in 80 cases, multiple nodules in 16 cases and multiple fused nodules in 4 cases. All tumors were classified as: trabecular type, 65 eases; compact type, 12; sclerotic type, 2 cases; mixed type, 15 cases and cholangiocareinoma type, 6 cases. 38 cases had incomplete or no capsule. Satellite tumor nodules were grossly identified during operation in 33 cases, but were proven microscopically in 66 cases. Tumor thrombi of portal vein was noted in 18 cases during oeration, but 85 cases in histopathological sections. The recurrent tumors were diagnosed post surgically within 6 months in 67 cases, 6-12 months in 15 cases and after 12 months in 18 cases respectively. On angiography, 67% recurrent tumors was rich in blood supply and with abundant accumulation of lipiodol after embolization. Conclusion:The post-surgical recurrence rate of the HCC patients with massive size, incomplete or no capsule, satellite tumor nodules and portal vein tumor thrombus was high. The patients shoud receive angiography in 1-2 months after surgery in order to detect early recurrence and, if confirmed, the patients may be treated by transcatheter arterial chemoembolization     

肝癌原位肝移植术后肿瘤复发的多层螺旋CT和MRI影像学诊断

Objective To investigate the manifestation and diagnostic value of multislice spiral CT (MSCT)and MRI imaging in detection of tumor recurrence after liver transplantation for bepatocellular carcinoma(HCC).Methods The clinical data of 161 consecutive HCC patients who underwent orthotopic liver transplantation were retrospectively reviewed.Twenty-nine HCC patients were classified by pTNM according to the "Pittsburgh criteria".MSCT and MRI findings of tumor recurrence after liver transplantation were evaluated retrospectively in 29 stage Ⅱ-Ⅳ b HCC patients.The recurrence site and relapse interval between liver transplantation and recurrence were analyzed.Results Lung tumor recurrence were found in 21 cases,presented as cotton-like lesions in a diameter of 2-3 cm,with a clear margin and homogeneous density.Pleural tumor recurrence was detected in 4 cases.Liver tumor recurrence were found in 9 cases,which can be divided into four subtypes:multinodular in 4 cases,diffuse lesion in 2 cases,huge mass in 2 cases,and uninodular in 1 case.Two cases showed tumor thrombus in the inferior vena cava and portal vein.Lymph node tumor recurrence was found in 9 cases,presented as multiple nodules at hepatic hilum,lesser peritoneal sac,posterior mediastinum,retroperitoneum,or around pancreatic head,and accompanied with merging and necrosis in one case.Bone tumor recurrence were found as osteolytie destruction in 4 cases,and accompanied with adjacent soft-tissue mass in 2 cases.The recurrence sites of the 29 cases were as following:lung(21 cases,72.4%),liver(9 cases,31.0%),lymph nodes(9 cases,31.0%),bone (4 cases,13.8%)and other sites(3 cases,10.3%).Lung tumor recurrence was found in all the 10 stage Ⅳb patients with tumor recurrence after liver transplantation,significantly more frequent than that in stage Ⅳ a patients(P = 0.023).After liver transplantation,all 25 patients with stage Ⅲ～Ⅳ b HCC developed recurrence within one year,but in the 4 cases with stage Ⅱ HCC at one year later(P = 0.009).Conclusion The results of our study show that in hepatoceUular carcinoma patients after liver transplantation,the lung and pleura are the most fequent site of recurrence,followed by liver,lymph node and bone as the second and third sites.The Stage Ⅳ b hapatocellular carcinoma should be regarded as a contradiction for liver transplantation due to rapid recurrence.Tumor recurrence occurs later in stage Ⅱ HCC than in stage Ⅲ～Ⅳb patients.MSCT and MRI are of significant importance in diagnosis and formulating operation plan in HCC patients with recurrence after liver transplantation.     

血管内皮生长因子、环氧合酶-2在甲状腺乳头状癌中的表达及其意义

Objective To study the expression and clinical significance of VEGF and COX-2 in papillary thyroid carcinoma (PTC).Methods The expression of VEGF and COX-2 were investigated by immuonhistochemical S-P method in 78 cases of papillary thyroid carcinoma tissue and adjacent tissue.78 cases of PTC including 42 cases with intrathyroidal invasion, 36 cases with extrathyroidal invasion,and 38 cases with lymph node metastasis and 40 cases without lymph node metastasis.Adjacent tissues including 34 cases of nodular goiter(NG),25 cases of Hashimoto thyroiditis(HT)and 19 cases of normal tissue.Results There was a significant difference between thyroid cancer tissue and the tumor free tissue(P＜0.05)and the expression levels of VEGF and COX-2 increased from the tumor free tissue,adjacent tissue to the thyroid cancer tissue(P＜0.05).The expression of VEGF and COX-2 were not related with site of tumor(P＞0.05),but were correlated to the degree of the infiltration and lymph node metastasis in PTC.Expression of COX-2 was correlated positively with VEGF.Conclusion The high expression of VEGF and COX-2 in PTC relates to the development,progression and metastasis of PTC,which may serve as one of the parameters for diagnosis of PTC and determing biological behavior and prognosis of PTC.     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.