Zhiping Yan

Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies

Background: To provide a quantitative assessment of the association between body mass index (BMI) and the risk of gastric cancer, we summarized the evidence from prospective studies. Methods: Eligible studies published up to November 30, 2012, were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Summary relative risks (SRR) with their corresponding 95% confidence intervals (CI) were calculated using a random-effects model. Results: A total of 24 prospective studies of BMI and gastric cancer risk with 41,791 cases were included in our analysis. Overall, both overweight (BMI, 25–30 kg/m2) and obesity (BMI, ≥30 kg/m2) were not associated with risk of total gastric cancer (overweight: SRR, 1.01; 95% CI, 0.96–1.07; obesity: SRR, 1.06; 95% CI, 0.99–1.12). Furthermore, we found increased BMI was positively associated with the risk of gastric cardia cancer (GCC; SRR = 1.21 for overweight and 1.82 for obesity), but not with gastric non-cardia cancer (GNCC; SRR = 0.93 for overweight and SRR = 1.00 for obesity). Similar results were observed in a linear dose–response analysis. Conclusion: On the basis of meta-analysis of prospective studies, we find high BMI is positively associated with the risk of GCCs but not with GNCCs. Impact: (i) On the basis of more definite and quantitative evidence than previously available, we found that increasing BMI was not a clear risk factor for total gastric cancer. (ii) Increased BMI was positively associated with risk of GCC but not with GNCCs. Cancer Epidemiol Biomarkers Prev; 22(8); 1395–408. ©2013 AACR.

The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma

BackgroundThe long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.MethodsBetween June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.ResultsThe median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.ConclusionTACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers.

Although the American College of Gastroenterology colorectal cancer screening guidelines highlight cigarette smoking as a risk factor, cigarette smoking is still an arguably underappreciated risk factor for this disease, especially for its subsites: colon cancer (CC) and rectal cancer (RC). A literature search of MEDLINE and EMBASE was performed up to 30 April 2013 for prospective cohort studies. A random-effects meta-analysis was carried out to estimate the summary relative risks (SRRs) and 95% confidence intervals (CIs) for the associations. A total of 24 prospective studies, which reported data for cigarette smoking and incidence of CC and RC separately, were included. Our analysis showed that, compared with never-smokers, current smokers had a higher risk of RC than CC (CC: SRR=1.09, 95% CI, 1.01–1.18; RC: SRR=1.24, 95% CI, 1.16–1.39; PRC vs. CC=0.034), whereas former smokers had a similar risk of CC and RC. Current smokers had a significantly higher risk of proximal CC than distal CC (P=0.035). This meta-analysis suggests that cigarette smoking is associated with an increased risk of both CC and RC, and that the magnitude of the association is stronger for RC than that for CC.

The Use of 125I Seed Strands for Intraluminal Brachytherapy of Malignant Obstructive Jaundice

This study is sought to evaluate the feasibility and safety of using ¹²⁵I seed strands for intraluminal brachytherapy (ILBT) in the treatment of malignant obstructive jaundice (MOJ), and its clinical effect on stent patency. A total of 34 patients found to have MOJ were randomly assigned to an ILBT treatment group or a control group before biliary stent insertion. For the ILBT group, ¹²⁵I seed strands were implanted into the obstructive segment of the bile duct after stent insertion. For the control group, only the biliary stent was inserted. Alimentary and hematologic complications were examined for patients in the ILBT group. The stent patency of the two groups were compared. In the ILBT group, the number of ¹²⁵I seeds per strand varied from 6 to 16 (mean, 10.9), and were successfully implanted in 17 patients. Serum levels of bilirubin, alanine aminotransferase, granulocytes, and platelets assayed 2 and 4 weeks following the procedure demonstrated no significant difference between the ILBT group and the control group. The mean stent patency for ILBT group (10.2 months) was significantly longer than that of the control group (7.2 months, p=0.032). ¹²⁵I seed strands for ILBT is a feasible and safe palliative therapy for the treatment of MOJ, and may prolong stent patency.

Liver Cancer: Effects, Safety, and Cost-effectiveness of Controlled-Release Oxycodone for Pain Control after TACE

PURPOSE To evaluate the analgesic effect, safety, and cost-effectiveness of controlled-release oxycodone (CRO) to control postoperative pain in patients with liver cancer who are undergoing transarterial chemoembolization. MATERIALS AND METHODS This randomized, double-blind, placebo-controlled, prospective clinical study received institutional review board approval. After written informed consent was obtained, 210 patients with liver cancer were randomized into three groups of 70 patients. Group 1 received 20 mg of CRO, group 2 received 10 mg of CRO, and group 3 received a placebo at 1 hour before transarterial chemoembolization (T(0)) and 12 (T(12)) and 24 (T(24)) hours after T(0). Pain intensity on a numeric rating scale, percentage of patients with each degree of pain, quality of life, adverse reactions, analgesic costs, and hospital stays were evaluated and compared among the three groups. RESULTS Numeric rating scale scores for pain intensity in group 1 and group 2 were significantly lower than those in group 3 at T(0-12) (P < .001); T(12-24) (P < .001); and T(24-48) (P < .001). When group 1 with group 2 were compared, numeric rating scale scores were significantly lower in group 1 than in group 2 during the period of T(0-12) (P < .001) but were not significantly different at T(12-24) (P = .68) and T(24-48) (P = .10). Analgesic cost and hospital stay were significantly lower in treated groups than in the placebo group. No significant difference was observed in quality of life and adverse events between the treated groups and the placebo group. CONCLUSION CRO is effective, safe, and cost-effective in the control of postoperative pain after transarterial chemoembolization for patients with inoperable liver cancer.

Ginsenoside Rg3 attenuates hepatoma VEGF overexpression after hepatic artery embolization in an orthotopic transplantation hepatocellular carcinoma rat model

Background Hypoxia-induced vascular endothelial growth factor (VEGF) upregulation and angiogenesis following treatment of hepatocellular carcinoma (HCC) with transarterial embolization (TAE) or transarterial chemoembolization (TACE) may be mediated by ginsenoside Rg3, an anti-angiogenic saponin extracted from ginseng. Objective To access the synergistic action of Rg3 and TAE treatment on HCC by VEGF and it’s receptor expressions decreasing in a rat model of HCC. Methods An orthotopic transplantation HCC model was established in Buffalo rats. HCC rats were treated with hepatic artery infusions of normal saline or iodized oil (0.1 mL) with or without Rg3 (1 mg/kg) (each n=15 in control, Rg3, TAE, and TAE + Rg3 groups). At 1, 2, 4, and 8 weeks, performance status (body weight), tumor progression (longest tumor diameter), metastasis rate, microvessel density (MVD), and overall survival rate were assessed. Additionally, cluster of differentiation 31 (CD31), VEGF, VEGF receptor 2 (VEGF-R2) and VEGF-R2 phosphorylation levels were assessed by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot. Results Combined Rg3 and TAE treatment reduced tumor progression, body weight loss, angiogenesis, and metastasis rate, and led to better overall survival in the HCC rat model. ELISA results showing VEGF expression in the control, Rg3, TAE, and TAE + Rg3 groups at 4 weeks following treatment were 132.6±2.38, 37.9±0.8, 87.4±0.7, and 45.3±0.4 pg/mL, respectively. Combined Rg3 and TAE reduced the protein expression of CD31 and VEGF-R2 phosphorylation, compared with those in the TAE group at 4 weeks of treatment. Conclusion Combined Rg3 and TAE treatment limited metastasis and promoted survival by downregulating VEGF overexpression in HCC tumors. Thus, this treatment may have potential clinical implications for HCC patients undergoing TAE or TACE.

Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma.

Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. (©) RSNA, 2016.

Combination Therapies in the Management of Large (≥ 5 cm) Hepatocellular Carcinoma: Microwave Ablation Immediately Followed by Transarterial Chemoembolization

PURPOSE To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC). MATERIALS AND METHODS From March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications. CONCLUSIONS MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.

Percutaneous microwave ablation combined with simultaneous transarterial chemoembolization for the treatment of advanced intrahepatic cholangiocarcinoma.

Aim To retrospectively evaluate the safety and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) combined with simultaneous transarterial chemoembolization (TACE) in the treatment of patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods All patients treated with ultrasound-guided percutaneous MWA combined with simultaneous TACE for advanced ICC at our institution were included. Posttreatment contrast-enhanced computed tomography and/or magnetic resonance imaging were retrieved and reviewed for tumor response to the treatment. Routine laboratory studies, including hematology and liver function tests were collected and analyzed. Procedure-related complications were reviewed and survival rates were analyzed. Results From January 2011 to December 2014, a total of 26 advanced ICC patients were treated at our single institute with ultrasound-guided percutaneous MWA combined with simultaneous TACE. There were 15 males and eleven females with an average age of 57.9±10.4 years (range, 43–75 years). Of 26 patients, 20 (76.9%) patients were newly diagnosed advanced ICC without any treatment, and six (23.1%) were recurrent and treated with surgical resection of the original tumor. The complete ablation rate was 92.3% (36/39 lesions) for advanced ICC. There were no major complications observed. There was no death directly from the treatment. Median progression-free survival and overall survival were 6.2 and 19.5 months, respectively. The 6-, 12-, and 24-month survival rates were 88.5%, 69.2%, and 61.5%, respectively. Conclusion The study suggests that ultrasound-guided percutaneous MWA combined with simultaneous TACE therapy can be performed safely in all patients with advanced ICC. The complete ablation rate was high and there was no major complication. The overall 24-month survival was 61.5%.

Rational Classification of Portal Vein Thrombosis and Its Clinical Significance

Portal vein thrombosis (PVT) is commonly classified into acute (symptom duration <60 days and absence of portal carvernoma and portal hypertension) and chronic types. However, the rationality of this classification has received little attention. In this study, 60 patients (40 men and 20 women) with PVT were examined using contrast-enhanced computed tomography (CT). The percentage of vein occlusion, including portal vein (PV) and superior mesenteric vein (SMV), was measured on CT image. Of 60 patients, 17 (28.3%) met the criterion of acute PVT. Symptoms occurred more frequently in patients with superior mesenteric vein thrombosis (SMVT) compared to those without SMVT (p<0.001). However, there was no significant difference in PV occlusion between patients with and without symptoms. The frequency of cavernous transformation was significantly higher in patients with complete PVT than those with partial PVT (p<0.001). Complications of portal hypertension were significantly associated with cirrhosis (p<0.001) rather than with the severity of PVT and presence of cavernoma. These results suggest that the severity of PVT is only associated with the formation of portal cavernoma but unrelated to the onset of symptoms and the development of portal hypertension. We classified PVT into complete and partial types, and each was subclassified into with and without portal cavernoma. In conclusion, neither symptom duration nor cavernous transformation can clearly distinguish between acute and chronic PVT. The new classification system can determine the pathological alterations of PVT, patency of portal vein and outcome of treatment in a longitudinal study.