Distribution of 5-FU in rat hepatoma, liver tissue and plasma after locoregional infusion / 中国癌症杂志

Background and purpose: Locoregional infusion chemotherapy such as hepatic artery, or hepaticportal vein infusion is one of the most important treatments for hepatocelluar carcinoma. This study was aimed to investigate the distribution of fluorouracil(5-FU) in rat hepatoma, liver tissue and plasma after administrated by caudal vein or locoregional routes of hepatic artery, hepaticportal vein, and hepaticportal vein with ligated hepatic artery. Methods:Twenty-four tumor-bearing rats were divided into 4 groups randomly, and they were infused with 5-FU through peripheral vein(caudal vein), hepatic artery, hepaticportal vein or hepaticportal vein with ligated hepatic artery, which dose was 20 mg/kg. High performance liquid chromatography was adopted to measure the content of 5-FU in hepatoma, liver tissue and plasma, and the drug penetration rate among them were calculated. Results:The group of hepaticportal vein with ligated hepatic artery reached the highest concentrations of 5-FU in live tissue and hepatoma, which concentrations were (22.1±9.5)μg/g and (16.4±7.2)μg/g. Then was the hepatic artery group, and the concentration of the hepaticportal vein group in the hepatoma focus was much smaller than the former 2 groups, which was (8.9±3.7)μg/g. The peripheral vein group got the lowest concentrations both in the liver tissue and hepatoma, which were (9.4±3.7) and (4.3±2.2)μg/g. The concentrations of 5-FU in the plasma in the peripheral vein group, the hepatic artery group, the group of hepaticportal vein with ligated hepatic artery and the hepaticportal vein group were (26.8±12.5), (16.4±9.7), (15.9±10.1) and (14.9±8.5)μg/mL, which indicated that the drug concentrations of the latter 3 groups were much lower than the former group. The hepatoma/plasma penetration rate of 5-FU in the group of hepaticportal vein with ligated hepatic artery, the hepatic artery group, the hepaticportal vein group and the peripheral vein group were 103.47%, 92.94%, 59.58% and 16.08%. Conclusion: Compared to the peripheral venous bolus injection, locoregional infusion could significantly increase the concentrations of chemotherapy agent in hepatoma focus and liver tissue, and decrease the drug distributions in peripheral blood. And the infusion through hepaticportal vein with ligated hepatic artery and through hepatic artery reaches higher concentrations in the hepatoma focuses, which indicate that they are 2 practical and promising routes for the locoregional chemotherapy of hepatoma.

A dosimetric comparison of three-dimensional conformal and intensity-modulated radiotherapy in locally advanced pancreatic cancer and a study of the clinical efficacy / 中华放射医学与防护杂志

Objective To compare the dose distribution between three-dimensional conformal radiotherapy(3D-CRT) and intensity-modulated radiotherapy (IMRT) in treating locally advanced pancreatic cancer,and report the efficacy of IMRT combined with regional chemotherapy using gemcitabine (GEM).Methods Ten patients with locally advanced pancreatic cancer were enrolled in this study.3D-CRT and IMRT plans were designed for each patient.The dose distributions of target volume and normal tissues were analyzed using the dose volume histogram (DVH).Twenty-five locally advanced pancreatic cancers patients who were treated by IMRT combined with regional chemotherapy using gemcitabine (combined group) were retrospective analyzed,as well as 25 hospitalized patients of the same period who were treated by regional chemotherapy using gemcitabine alone (chemotherapy alone group).The therapeutic efficacy and adverse events were compared between two groups.Results IMRT plans decrease the mean dose and volume of duodenum,liver,stomach,both kidney and small bowel that received highdose irradiation.The 1-,2-year survival rate of the combined group and chemotherapy alone group was 60％,28％ and 36％,12％.The median survival time of two groups was 15 and 10 months,respectively (x2 =4.16,P ＜0.05).The total response rate of the combined group and the chemotherapy alone group was 64％ and 32％,respectively (x2 =5.13,P ＜ 0.05).The upper gastrointestinal side-effect rate of the combined group was higher than that of the chemotherapy alone group(Z =-2.354,P ＜ 0.05).There was no statistic significance in hematologic toxicity,liver and renal functional damage between the two groups.Conclusions Compared with 3D-CRT plan,IMRT plan could reduce the dose of organ at risks.IMRT combined with regional chemotherapy using gemcitabine could significantly improve the survival rate of patients with locally advanced pancreatic cancer with mild adverse events.

The effect of intraarterial high-dose cisplatin on lymph nodes in oral and oropharyngeal cancer.

Aim of Study: To assess the effect of strictly local treatment [intraarterial chemotherapy (iaCHT) with high-dose cisplatin and parallel neutralization] in the primary oral and oropharyngeal cancer (OOSCC) on the dependent cervical lymph nodes. Patients and Methods: Seventeen consecutive patients with OOSCC and clinically positive necks underwent a prospective blinded comparison of two pre-surgical fluor18-deoxyglucose (FDG)-positron emission tomography (PET) examinations: baseline examination 1 week before and follow-up examination 3 weeks after iaCHT. Maximal standardized uptake (SUVmax) values of lymph nodes were measured and compared with each other and histopathology. Results: The SUVmax value of the primary and all neck lymph nodes with uptake decreased significantly. Twelve/17 patients having metastases revealed significant decrease (P = 0.03), and benign lymph nodes showed non-significant decrease of the SUVmax. All neck lymph nodes with uptake and nodal metastases showed a significant reduction (P = 0.004) of standard uptake values (SUV). Conclusion: A regional effect of intraarterial cisplatin is proven. To date, it is not clear whether this is due to decreasing inflammatory reaction or a translymphatic anti-neoplastic effect.

Isolated limb perfusion with hyperthermia and chemotherapy: predictive factors for regional toxicity

OBJECTIVE: Isolated limb perfusion combined with melphalan is an accepted treatment for obtaining locoregional control in advanced melanoma of the extremities and other malignant neoplasias restricted to the limb. This study aims to examine the factors associated with toxicity caused by the regional method. We considered the technical aspects of severe complications associated with the procedure in an attempt to diminish the patient morbidity that occurs during the learning curve. METHODS: We conducted a retrospective analysis of the records of patients who underwent perfusion at the AC Camargo Hospital in São Paulo, Brazil between January 2000 and January 2009. The Wieberdink scale was applied to classify local toxicity and its relation to clinical and laboratory variables. RESULTS: Fifty-eight perfusions were performed in 55 patients. Most patients (86.2%) presented a toxicity level between I and III. Grade V toxicity was seen in five cases (8.6%), four of which occurred in the first 2 years. Creatine phosphokinase, an important predictive factor for toxicity, had an average value of 231.8 for toxicity grades I-III and 1286.2 for toxicity grades IV-V (p = 0.001). There was a relationship between the melphalan dose and toxicity, which was 77 mg (25 to 130 mg) for toxicity grades I-II and 93.5 mg (45 to 120 mg) for toxicity grades IV-V (p = 0.0204). CONCLUSION: It is possible to prevent the toxicity associated with melphalan by adjusting the dose according to the patient's body weight (especially for women and obese patients) and the creatine phosphokinase values in the postoperative period.

Effects of perioperative intraperitoneal chemotherapy with 5-fluorouracil sustained release agent on advanced gastric cancer / 中华消化外科杂志

Objective To investigate the effects of perioperative intraperitoneal chemotherapy with 5-fluorouracil (5-FU) sustained release agent on the local recurrence and survival rates of patients with advanced gastric cancer. Methods The clinical data of 100 patients with advanced gastric cancer who had been admitted to our hospital from January 2002 to December 2004 were retrospectively analyzed. All patients were divided into treatment group and control group. Only patients in the treatment group were implanted with 5-FU sustained release agent (800 mg) in abdominal cavity after D2 gastrectomy. All patients accepted chemotherapy according to the FOLFOX regimen. Results The 3-year survival rate and 3-year disease free survival rate were 45% and 28% for treatment group, which were significantly higher than 32% and 16% for control group. Conclusions Intraperi-toneal implantation of 5-FU sustained release agent during operation can decrease local recurrence rate and improve the 3-year survival rate of patients with advanced gastric cancer after radical gastrectomy.

Determination of 5-FU in Serum,Peritoneal Fluid and Tissue by HPLC in Patients Undergoing Rectal Cancer Operation and Receiving Regional Chemotherapy / 中国药房

OBJECTIVE:To determine 5-Fu concentration in serum,peritoneal fluid and tissue by HPLC in patients undergoing rectal cancer operation and receiving regional chemotherapy.METHODS:20 patients who undergoing rectal cancer operation and receiving regional chemotherapy were administered with drugs,whose blood samples were taken from portal veins,peripheral veins,peritoneal fluid and tissues around tumor at 2,5,10,20,30 and 60min,respectively after administration for the determination of 5-FU by HPLC.RESULTS:Peak concentrations in all samples appeared 2 minutes after administration,but lowered gradually thereafter.The drug level in peritoneal fluid was the highest,but was the lowest in the tissue,and that in the portal vein was higher than in peripheral veins.CONCLUSION:For patients who undergoing rectal cancer operation,regional chemotherapy could maintain 5-FU concentration at a higher level in portal vein,peritoneal fluid and tissue around cancer,which has significance in the prevention of metastasis to the local sites and liver after rectal cancer operation.

Research Status on Intraoperative Regional Chemotherapy of Advanced Gastric Cancer / 中国普外基础与临床杂志

Objective To explore the feasibility,safety,efficacy and mechanism of intraoperative regional chemotherapy of advanced gastric cancer. Methods The related literatures were reviewed and analyzed. Results Compared with systemic chemotherapy,intraoperative regional chemotherapy of advanced gastric cancer could increase blood drug concentration of cancerous tissue,reduce the systemic toxic side effects,increase survival rate and improve the quality of life. Conclusion Intraoperative regional chemotherapy,as an adjuvant treatment of advanced gastric cancer,has been gradually applied to clinic because of the definite curative effect,which is worth popularizing. However,it needs systemic researches and accumulation of cases.

Preoperative regional chemotherapy in advanced gastric carcinoma / 中国癌症杂志

Purpose:To study the efficacy of preoperative selective intra arterial chemotherapy in advanced gastric carcinoma. Methods:Between August 1999 and November 2001, a total of 98 hospitalized patients with advanced gastric carcinoma who underwent selective intra arterial regional chemotherapy prior to surgery were recruited in this study. 60 patients with advanced gastric carcinoma on whom surgery were performed did not receive any preoperative regional anti cancer drugs between 1997 and 1998 and served as controls. The surgical resection rate and histologic investigations were compared. Results:The resection rate was 78% in regional chemotherapy group and 68% in control group. Tumor cell necrosis was investigated by postoperative pathological study and revealed that the response rate in regional chemotherapy group was 67%. Only 8 cases in control group showed mild focal necrosis. Conclusions:Preoperative regional chemotherapy in patients with advanced gastric carcinoma may enhance resection rate and destroy large numbers of tumor cells vigorously. The preliminary results are satisfying.

Animal study on the feasibility of regional gastroduodenal artery or splenic artery ligation followed by regional intraarterial perfusion of pancreas with 5-FU / 中国癌症杂志

Background and Purpose:Pancreatic cancer is malignant tumor of the digestive tract with poor prognosis and is not sensitive to conventional chemotherapy.This study investigates the safety and feasibility of regional arterial ligation followed by intra-arterial perfusion chemotherapy in 14 pigs divided into groups A,B and C.Methods:14 pigs were divided into 3 groups.Group A(n=5) underwent gastroduodenal artery ligation and catheterization through the right gastroepiploic artery.Group B(n=5) underwent splenic artery ligation and catheterization.Group C(n=4) underwent left periotic vein puncture.5-FU(20mg/kg) was perfused into these catheters in 60 min.Blood samples and pancreatic tissue were obtained for the purposes of the determination of drug concentration and pathological diagnosis.Results:At 80 min and 100 min the drug concentration in portal vein of group A and group B were higher than those of group C(P

Hepatic Intraarterial Chemotherapy in Unresectable Hepatic Metastases of Colorectal Cancer / 대한암학회지

PURPOSE: Unresectable hepatic metastases of colorectal cancer does not seem to be amenable to the various treatment modalities. We modified hepatic intraarterial chemotherapy by different installation of port and regimen. MATERIALS AND METHODS: Between July 1989 to December 1995, 27 patients of colorectal cancer with unresectable liver metastases were randomly allocated into either hepatic intraarterial (HA, 11 patients) or systemic intravenous (IV, 16 patients) chemotherapy after primary tumor resection. Chemo-port was installed with preservation of hepatic arterial flow. One cycle of HA regimen included 5-fluorouracil (5-FU) and mitomycin-C (MMC) with or without leucovorin (LV) for 14 days every month. The IV regimen included 5-FU and LV for 5 days every month. Both HA and IV chemotherapy were continued from 6 to 12 cycles. RESULTS: The response exceeding partial remission was experienced in six patients (55%) among 11 patients in the HA group, while only two (13%) patients showed response among sixteen patients in the IV group. One year survival was not different between two groups. Although lethal toxicity was not found, patients showed marked increase of the performance scale (ECOG) in both groups. CONCLUSION: Although survival benefit was not prominent, higher response rate with tolerable complication was found in the HA group. Prudent selection of effective drugs and combination of systemic chemotherapy are needed to improve the survival with minimal complication.