Transarterial infusion with gemcitabine and oxaliplatin for the treatment of unresectable pancreatic cancer.

The aim of this study was to evaluate the therapeutic efficacy and the safety of transarterial infusion (TAI) with gemcitabine and oxaliplatin in patients with unresectable pancreatic cancer (PC). After celiac arteriogram and super-mesenteric arteriography, 1000 mg/m gemcitabine and 100 mg/m oxaliplatin were infused through 4- or 5-Fr catheters in arteries supplying blood to the tumor. In cases in which the blood-supplying artery could be selectively catheterized, the infusion was performed through a 3-Fr catheter placed in the tumor-supplying artery. Therapeutic courses were repeated every 4 weeks. The tumor response, the overall survival, and adverse effects were monitored. Thirty-two patients with unresectable PC were enrolled in this study, including 20 male and 12 female patients. A total of 105 cycles of TAI (mean=3.3 cycles/patient) were performed. Of 32 patients, partial remission was achieved in eight (25.0%), stable disease in 13 (40.6%), and progressive disease in 11 (34.4%). The overall response rate was 25.0%. The median survival time was 10.0 months (range=4-21 months). Grade III-IV toxicity, vomiting, occurred with a rate of 21.9%. Grade I-II neutropenia, thrombocytopenia, peripheral nerve toxicity, elevated serum transaminases levels, and serum total bilirubin were observed. TAI with gemcitabine and oxaliplatin is well tolerated and highly effective in patients with unresectable PC.

Fine needle aspirating and cutting is superior to Tru-cut core needle in liver biopsy.

BACKGROUND: Liver biopsy is the "gold standard" for evaluating liver disorders, but controversies over the potential risk of complications and patient discomfort still exist. Using a 21G fine needle, we developed a new biopsy procedure, fine needle aspirating and cutting (FNAC). Our procedure obtains enough tissue for pathological examination and meanwhile, reduces the risk of biopsy complications. The present study was to determine the safety and efficiency of 21G FNAC compared with 18G Tru-cut core needle (TCN) in liver tumor biopsies. METHODS: Ninety-four patients with unresectable malignant tumors were included in this study. Patients were divided into 2 groups: 18G TCN and 21G FNAC. The total positive rate (TPR) and safety of both groups were compared. RESULTS: TPR was not different between the two groups. Liver puncture track subcapsular hemorrhage and arteriovenous shunt were reported with 18G TCN but not with 21G FNAC. The incidence of pain caused by biopsy was higher for the 18G TCN group compared to the 21G FNAC group (P<0.05). About 82.6% of the patients in the 18G TCN group had a sample length >0.5 cm, but 52.1% in the 21G FNAC group (P<0.05). More than 50% of patients in both groups had sufficient tissue for immunohistochemical examination. CONCLUSIONS: TPR is not different between the 21G FNAC and 18G TCN biopsy procedures, but the safety of 21G FNAC is superior to that of 18G TCN. Tissues obtained by either of these two procedures are sufficient for a pathological diagnosis.

Damage to pig bile duct caused by intraluminal brachytherapy using a (125)I ribbon.

BACKGROUND: Stent occlusion by tumor ingrowth or overgrowth is the main cause of jaundice recurrence after metal stent insertion in patients with malignant obstructive jaundice (MOJ). The application of intraluminal brachytherapy (ILBT) in patients with MOJ results in local control of malignant tumors, which prolong stent patency. PURPOSE: To evaluate the safety of ILBT in pig bile ducts using ribbons of iodine-125 ((125)I) seeds. MATERIAL AND METHODS: Sixteen healthy pigs were randomly assigned to four groups of four pigs each. A (125)I seed ribbon was implanted into the common bile duct of each animal through an incision in the duct wall, and was fixed by suturing. The four groups of animals were sacrificed at 15, 30, 60, and 120 days after ribbon implantation, respectively. Serum bilirubin concentrations, alanine aminotransferase concentrations, and white blood cell counts before and after implantation were compared within each group. Pathological changes to the bile duct wall were observed using a light microscope. Morphological changes in biliary epithelial cells and organelles were observed with electron microscopy. RESULTS: (125)I ribbons were successfully implanted in all animals without surgery-related death. We found no significant difference in pre- and post-implant serum bilirubin, alanine aminotransferase, or white blood cell counts. Light and electron microscopy showed that the most severe bile duct damage occurred in the 15-day group, which exhibited necrosis and detachment of numerous epithelial cells, and infiltration of inflammatory cells. Repair and proliferation of the bile duct epithelium began 30 days after implantation and was nearly complete at 60 days. CONCLUSION: This study demonstrated the safety of ILBT using a (125)I ribbon in the pig bile duct. (125)I seed ribbons may be used in the treatment of MOJ in humans.

The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma.

BACKGROUND: The 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. METHODS: Between 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. RESULTS: The 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. CONCLUSION: TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

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.

Identifying serum biomarkers for TACE therapy efficiency of hepatocellular carcinoma.

Transcatheter Arterial Chemoembolization (TACE) is the first line of treatment in inoperable hepatocellular carcinoma. Magnetic affinity beads can be used to extract peptides from un-fractionated serum samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can detect the presence and the molecular mass of peptides. In this study, we used a highly optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight mass spectrometer (MALDI-TOF-MS) to screen hepatocellular carcinoma markers for TACE. 40 sera from 20 patients, including before and after TACE to explore those biomarkers, might be related with therapy efficiency, and some of the patients who received another therapy were analyzed as well. The spectra were analyzed statistically using FlexAnalysis™ and Clin-Prot™ bioinformatic software. The seven most significant differential peaks (p < 0.0.5) were selected out by ClinProTool software to identify hepatocellular carcinoma markers for TACE therapy. Furthermore, the differential peptide of 3883Da was identified as plasma serine protease inhibitor precursor (Protein C inhibitor). This study provides a direct link between peptide marker profiles and TACE therapy, and the markers may have clinical utility for monitoring efficiency of therapy.

[Features of blood supply and results of transarterial infusion and embolization in spinal metastases].

OBJECTIVE: To study the features of blood supply and results of transarterial infusion and embolization in spinal metastases. METHODS: Forty-one patients with spinal metastasis received transarterial infusion and embolization between March 2001 and June 2008. The inclusion criteria were: The metastatic lesion caused back pain; The metastatic lesion involved vertebra at or below T3 level. There were 29 males and 12 females with a mean age of 56.0 (33 - 71) years. Epirubicin was used as the chemotherapeutic agent. Lipoid Ultra-Fluid, Contour SE or gelfoam particles were used as embolitic material. RESULTS: The technical success of therapy was achieved in 52 vertebrae (100%) including 14 thoracic, 35 lumbar and 3 sacral vertebrae. 105 arteries were used for infusion and embolization (16 intercostal arteries, 78 lumbar arteries, 4 iliolumbar arteries, 4 branches of iliac arteries, and 3 median sacral arteries). Lipoid Ultra-Fluid (2 - 8 ml) was used in 15, Contour SE (300 approximately 500 microm, 20 - 100 mg) in 20, and gelfoam particles in 33 arteries. Three days after treatment, complete pain relief (CR) was achieved in 17 patients, partial pain relief (PR) in 20, and moderate pain relief (MR) in 4, with an effective rate of 90.2%. Two weeks after treatment, CR was achieved in 17 patients, PR in 21, and MR in 3, with an effective rate of 92.7%. No adverse nervous system effect occurred. 16 patients developed swelling and pain of normal tissues which were alleviated after symptomatic treatment. CONCLUSION: Transarterial infusion and embolization is an effective therapy in relieving pain resulting from spinal metastases.

[The preliminary study of metallic stent implantation in combination with three-dimensional conformal radiation therapy in the treatment of hepatocellular carcinoma patients with portal vein tumor thrombus].

OBJECTIVE: To study the clinical efficiency of metallic stent implantation in combination with three-dimensional conformal radiation therapy in the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus. METHODS: 22 cases of HCC patients with portal vein tumor thrombus were devided into 2 groups: 10 patients (group A) recieved stent implantation in combination with conformal radiation therapy, 12 patients (group B) recieved stent implantation and transcatheter arterial chemoembolization. The adverse reactions, and liver function before and after treatment were compared between the two groups. The stent patency rate at 4, 6 and 12 months and the survival rate at 3, 6 and 12 months were followed up. Comparison of liver function was analyzed by Wilcoxon signed rank test. Comparison of stent patency rate curves and survival curves was analyzed by Log rank test. RESULTS: The portal vein catheterization was successful in all the patients. The stents were successfully implanted by transhepatic portal vein approach, and portal vein stenosis was re-opened. There was no abdominal hemorrhage in all the patients, but there were symptoms of abdominalgia, fever, nausea, vomiting and flatulence of varying degrees after interventional operation, and these symptoms were relieved by symptomatic treatment in one week. All patients in group A completed the treatment. I-II degree gastrointestinal tract reactions occurred in 3 cases, I-II degree myelosuppression occurred in 2 cases, and they were all completely relieved after treatment. The stent patency rate at 4, 6 and 12 months was 90%, 70%, 30% in group A; and 50%, 25% , 16.7% in group B (P < 0.05). The survival rate at 3, 6 and 12 months was 100%, 80% , 30% in group A and 91.7%, 41.7%, 16.7% in group B (P < 0.05). CONCLUSION: Stent implantation combined with three-dimensional conformal radiation therapy is a good treatment for hepatocellular carcinoma with portal vein tumor thrombus and causes less damage to liver.

[Epirubicin in the treatment of malignant obstructive jaundice].

OBJECTIVE: To evaluate the safety and efficiency of epirubicin in the treatment of malignant obstructive jaundice (MOJ). METHODS: Thirty-nine patients with diagnosis of MOJ, whose serum total bilirubin (TB) had not dropped to normal level after stent placement or percutaneous transhepatic biliary drainage, received trans-arterial chemoembolization (TACE). During TACE, epirubicin emulsion containing pharmorubicin at dose of 30 mg/m(2) was used. The toxicity and hepatic injury was observed according to WHO anticancer drug toxicity criterion and Child-Pugh classification criterion, respectively. The time of jaundice recurrence and survival were also observed during follow-up. RESULTS: Median total serum bilirubin in 39 patients was 72.7 micromol/L (range: 52.1 - 91.4 micromol/L) before TACE. The dose of pharmorubicin was 40 - 60 mg with a median of 55.0 mg and the amount of lipiodol was 2 - 25 ml. Decrease in white blood cell count was observed: grade I in 41.0% of patients, grade II in 35.9% and grade III - IV in 15.4%. Grade III - IV nausea and vomiting developed in 100% of the patients. Hepatic injury became aggravated in 8 from A to B class patients, in one from A to C class, and in 3 from B to C class according to Child-Pugh classification criterion. No cardiac toxicity was observed in this series. The median survival time was 6.0 months with a range of 2 to 72 months. Jaundice recurred in 19 patients (48.7%) with a medium jaundice recurrence time of 9.0 months (range: 2 - 20 months). CONCLUSION: Epirubicin-lipiodol emulsion at a dose of 30 mg/m(2) is safe and efficient in the management of patients with malignant obstructive jaundice with total serum bilirubin between 51 and 100 micromol/L after biliary drainage.

HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice.

AIM: To determine the feasibility and safety of intraluminal brachytherapy in treatment of malignant obstructive jaundice (MOJ) and to evaluate the clinical effect of intraluminal brachytherapy on stent patency and patient survival. METHODS: Thirty-four patients with MOJ were included in this study. Having biliary stent placed, all patients were classified into intraluminal brachytherapy group (group A, n = 14) and control group (group B, n = 20) according to their own choice. Intraluminal brachytherapy regimen included: HDR-192Ir was used in the therapy, fractional doses of 4-7 Gy were given every 3-6 d for 3-4 times, and standard points were established at 0.5-1.0 cm. Some patients of both groups received transcatheter arterial chemoembolization (TACE) after stent placement. RESULTS: In group A, the success rate of intraluminal brachytherapy was 98.0%, RTOG grade 1 acute radiation morbidity occurred in 3 patients, RTOG/EORTC grade 1 late radiation morbidity occurred in 1 patient. Mean stent patency of group A (12.6 mo) was significantly longer than that of group B (8.3 mo) (P<0.05). There was no significant difference in the mean survival (9.4 mo vs 6.0 mo) between the two groups. CONCLUSION: HDR-192Ir intraluminal brachytherapy is a safe palliative therapy in treating MOJ, and it may prolong stent patency and has the potentiality of extending survival of patients with MOJ.