Liver Perfusion Chemotherapy Research Articles

3:39 PM, Abstract No. 287 - Efficacy of postoperative adjuvant liver-perfusion chemotherapy for resectable pancreatic cancer: result from 121 patients

3:39 PM, Abstract No. 287 - Efficacy of postoperative adjuvant liver-perfusion chemotherapy for resectable pancreatic cancer: result from 121 patients

Preoperative Chemoradiation with Full-dose Gemcitabine for Locally-advanced Pancreatic Adenocarcinoma

In order to increase the long-term survival after resection of pancreatic adenocarcinoma, it is essential to eradicate both locoregional recurrence and hepatic metastasis. We performed a combination of preoperative chemoradiation (CRT) with full-dose gemcitabine (GEM) and postoperative liver perfusion chemotherapy (LPC) for Stage II (cT3N0-1) pancreatic adenocarcinoma.

Feasibility and Efficacy of Combination Therapy With Preoperative Full-Dose Gemcitabine, Concurrent Three-Dimensional Conformal Radiation, Surgery, and Postoperative Liver Perfusion Chemotherapy for T3-Pancreatic Cancer

To evaluate both the feasibility and efficacy of our combined therapy, which consisted of preoperative chemoradiation, surgery, and postoperative liver perfusion chemotherapy (LPC) for patients with T3 (extended beyond the pancreatic confines) cancer of the pancreas. Because of the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of T3-pancreatic cancer are extremely poor. During the period from 2002 to 2007, 38 patients with T3-pancreatic cancers consented to receive a combination of preoperative chemoradiation, surgery, and postoperative LPC. With the aid of 3D radiation planning, irradiation fields were constructed that included both the primary pancreatic tumor and retropancreatic tissues while taking care to exclude any section of the gastrointestinal tract. The total dose of radiation was 50 Gy (2 Gy x 25 fractions/5 weeks) and was administered in combination with gemcitabine treatments (1000 mg/m/week x 9/3 months). Preoperative restaging via computerized tomography and intraoperative inspection were used to determine if pancreatectomy was indicated. For respected cases, one catheter was placed into the gastroduodenal artery and another one into the superior mesenteric vein. Postoperatively, 5-FU (125 mg/day x 28 days) was infused via each of these 2 routes. Preoperative chemoradiation was completed for all 38 patients, including 3 patients who required gemcitabine-dose reduction. Seven patients (18%) did not undergo surgical resection because either distant metastases or progressive local tumors had been detected after chemoradiation. The remaining 31 patients (82%) underwent pancreatectomy plus postoperative LPC, without postoperative or in-hospital mortality. The 5-year survival rate after pancreatectomy was 53%, with low incidences of both local recurrence (9%) and liver metastasis (7%). Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) for 30 patients (96%) and negative nodal involvement for 28 patients (90%). Results of this trial suggest that a combination of preoperative full-dose gemcitabine, concurrent 3D-conformal radiation, surgery, and postoperative LPC is feasible for the treatment of T3-pancreatic cancer. Using the method described in this article, we were able to effectively reduce the incidence of both local and liver recurrence. Therefore, this type of combination therapy seems promising for improving long-term outcomes for patients with T3-cancers of the pancreas. This study is registered with University hospital Medical information Network clinical trials Registry number, UMIN000001804.

Liver Perfusion Chemotherapy With 5-Fluorouracil Followed by Systemic Gemcitabine Administration for Resected Pancreatic Cancer

Liver perfusion chemotherapy (LPC) for pancreatic cancer has been rarely undertaken in a postoperative adjuvant setting. We evaluated the feasibility and antitumor efficacy of LPC with 5-fluorouracil (5-FU) followed by gemcitabine treatment. This prospective study enrolled 27 patients who underwent pancreatic resection and subsequent LPC + gemcitabine treatment during a 3-year period. The liver was infused with 5-FU (125 mg/body per day per route) via both routes of hepatic artery and portal vein for more than 21 days. After that, gemcitabine (1000 mg/m) was administered biweekly. Portal vein thrombosis developed in 1 patient, but 89% patients tolerated LPC for more than 21 days with no life-threatening complication. Systemic administration of gemcitabine was accomplished in 93%; however, 1 patient died of serious capillary leak syndrome. No grade 4 toxicity was recorded, except for that patient. Median survival time and disease-free survival were 27.5 and 24.5 months, respectively. Hepatic relapse was observed in 25.9% (n = 7). Survival was in favor of paraaortic node-negative cases (n = 20) with a 2-year survival of 68.7%. Liver perfusion chemotherapy was feasible with acceptable toxicity. Systemic use of gemcitabine also seems to be safe for the most part. This adjuvant chemotherapy shows promising survival benefit and seems to be indicative to paraaortic node-negative tumors.

5FU肝動注·門注+gemcitabineによる膵癌術後補助化学療法：第2相試験の中間解析結果

5FU肝動注·門注+gemcitabineによる膵癌術後補助化学療法：第2相試験の中間解析結果

Liver Perfusion Chemotherapy for Selected Patients at a High-Risk of Liver Metastasis After Resection of Duodenal and Ampullary Cancers

To evaluate the prognostic benefit of postoperative liver perfusion chemotherapy (LPC) in patients who undergo curative resection of duodenal and ampullary cancers. Both nodal involvement and pancreatic invasion are poor prognostic indicators after curative resection of ampullary or duodenal cancers due to high incidences of liver metastasis. Therefore, we have performed postoperative LPC on a number of such "high-risk" patients. During the period of 1990 to 2005, 72 consecutive patients successfully underwent curative (R0) resection of duodenal or ampullary carcinomas at our institution, The Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these 72 patients, 38 were found to have positive nodal involvement and/or pancreatic invasion based on an intraoperative inspection, and of these, 28 were deemed to be suitable candidates for intraoperative catheterization: 1 catheter was placed into the gastroduodenal artery; another into the portal vein (group A). Postoperatively, they received an infusion of 5-fluorouracil (5-FU: 125 mg/d) via each of the 2 catheters for a period of 28 continuous days. The remaining 44 patients (group B) did not receive any other adjuvant therapy. The survival rates and patterns of disease failure were compared between these 2 groups and their subgroups. All 72 patients survived the operation, and all 28 patients in group A completed their courses of LPC without showing any significant adverse signs. Postoperative histopathology was later performed to get a more accurate picture regarding the degree of nodal involvement and/or pancreatic invasion: In group A, 21 patients (group A1) proved positive for nodal and/or pancreatic invasion whereas 7 patients (group A2) proved negative; and in group B, 16 patients proved positive (group B1) whereas 28 proved negative (group B2). Although group A displayed higher incidences of nodal involvement and pancreatic invasion, the 5-year survival rates for the 2 groups varied only slightly. The 5-year survival rate was 70% in group A1, 85% in group A2, 35% in group B1, and 92% in group B2, respectively. The difference between B1 and B2 and the difference between A1 and B1 were statistically significant, and these differences were conclusively found to be attributable to the different incidences of liver metastasis. Through this research, both nodal involvement and pancreatic invasion were confirmed to be reliable predictors of liver metastasis after curative resection of ampullary and duodenal cancers. Since LPC was proven to be effective in preventing the postoperative development of liver metastasis, it should be more actively performed for patients with a high-risk of liver metastasis.

Feasibility and Efficacy of Combination Therapy With Preoperative and Postoperative Chemoradiation, Extended Pancreatectomy, and Postoperative Liver Perfusion Chemotherapy for Locally Advanced Cancers of the Pancreatic Head

Feasibility and Efficacy of Combination Therapy With Preoperative and Postoperative Chemoradiation, Extended Pancreatectomy, and Postoperative Liver Perfusion Chemotherapy for Locally Advanced Cancers of the Pancreatic Head

Feasibility and Efficacy of Combination Therapy With Preoperative and Postoperative Chemoradiation, Extended Pancreatectomy, and Postoperative Liver Perfusion Chemotherapy for Locally Advanced Cancers of the Pancreatic Head

The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy. Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days x 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed. After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04). A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.

Clinical Significance of Dihydropyrimidine Dehydrogenase in Adjuvant 5-Fluorouracil Liver Perfusion Chemotherapy for Pancreatic Cancer

To clarify the relationship between intratumoral dihydropyrimidine dehydrogenase (DPD) expression and response to 5-fluorouracil (5-FU) liver perfusion chemotherapy (LPC) in pancreatic cancer patients, we evaluated DPD expression immunohistochemically in resected pancreatic cancer tissues. Pancreatic cancer is considered a disease with a poor prognosis even if aggressive resection is performed. One of the main causes of death is hepatic metastasis soon after surgery. As a treatment, we have assessed adjuvant LPC via the portal vein using 5-FU just after pancreatectomy for advanced pancreatic cancer since 1994. However, the results remain unsatisfying. Sixty-eight resected specimens were obtained from patients with pancreatic cancer from 1988 to 2000. Formalin-fixed paraffin-embedded tissues were immunostained with polyclonal anti-DPD antibody. The relation between intratumoral DPD expression and the prognoses of pancreatic cancer patients was investigated statistically. Of the 68 tumors studied, 27 carcinomas (39.7%) were DPD(+), and 41 (60.3%) were DPD(-). In the DPD(+) group, there was no significant difference between the LPC(+) and LPC(-) subgroups, whereas in the DPD(-) group the LPC(+) subgroup showed a significantly higher survival rate than the LPC(-) subgroup. Moreover, in the LPC(+) group, overall survival in the DPD(-) subgroup was significantly better than in the DPD(+) subgroup. An immunohistochemical evaluation of intratumoral DPD expression might be useful in predicting responsiveness to 5-FU-based chemotherapy in pancreatic cancer patients. In the DPD(-) group, liver perfusion chemotherapy using 5-FU via the portal vein is effective adjuvant therapy for pancreatic cancer once pancreatectomy has been performed.

Liver perfusion chemotherapy via both the hepatic artery and portal vein to prevent hepatic metastasis after extended pancreatectomy for adenocarcinoma of the pancreas

Since hepatic metastasis is a common cause of treatment failure after curative pancreatectomy for adenocarcinoma of the pancreas, we developed a new method of postoperative hepatic perfusion chemotherapy via both the hepatic artery and portal vein. The present study was conducted to determine if this method decreases the hepatic recurrence and improves the survival rate. Following extended pancreatectomy with wide lymphatic and connective tissue clearance for pancreatic cancer, one catheter was placed in the hepatic artery and one in the portal vein. Immediately after surgery, 5-fluorouracil (125 mg/d) was continuously infused via these two routes simultaneously for 28 to 35 days. There were no treatment-related complications in the 20 patients who survived surgery. The 3-year survival rate was 54%, and the cumulative rate of death from hepatic metastasis was 8%. These figures were significantly better than those of our historical control groups. We conclude that this method should be evaluated in a prospective, randomized controlled study.

Histamine metabolism in patients with foregut carcinoid tumours

The urinary excretion of the histamine metabolite, tele-methylimidazoleacetic acid (MemAA), was measured in 15 patients with foregut carcinoid tumours (5 ECLomas, 4 gastric carcinoids of the mixed type and 6 bronchial carcinoids), High levels were related to tumour burden and presence of the foregut carcinoid syndrome. Control of symptoms was either achieved by octreotide in combination with blockade of histamine receptors or by hyperthermic liver perfusion chemotherapy. MemAA served as an exellent tumour marker for diagnosis and guidance of therapy.