Needle tract implantation of hepatocellular carcinoma and pancreatic carcinoma after ultrasound-guided percutaneous puncture: clinical and pathologic characteristics and the treatment of needle tract implantation.

Tumor implantation along the needle tract following percutaneous procedures under ultrasonographic guidance for hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC) has been well documented. The purpose of the present study was to investigate the correlation between the procedure, the pathologic differentiation of the primary tumor, and the treatment after implantation. Between July 1992 and March 2000, HCC patients (n=372) who underwent biopsy, percutaneous ethanol injection (PEI) therapy and percutaneous microwave coagulation therapy (PMCT) and PC (n=73) patients who underwent biopsy were retrospectively studied. Needle tract implantation was found in six of the HCC patients (1.6%) and one of the PC patients (1.4%). The interval to diagnosis ranged from 5 to 25 months (mean +/- SD 11.2 +/- 7.6 months) in the HCC patients. The needle tract implantation was evident for all procedure types in these patients (two after PEI alone, two after both biopsy and PEI, and one after PMCT) and for each degree of pathologic differentiation of the primary tumors (well differentiated in one, moderately differentiated in two, and poorly differentiated in one). Each implanted tumor was surgically resected, with no recurrence at the focal lesion. These results suggest that needle tract implantation develops regardless of the procedure or the pathologic differentiation of the primary tumor, and that surgical resection might be effective for controlling these implanted lesions.

Analysis of T cell receptor variable regions and complementarity determining region 3 of infiltrating T lymphocytes in the liver of patients with chronic type B hepatitis.

OBJECTIVES: T cell receptor (TCR) variable regions and complementarity determining regions 3 (CDR3) of infiltrating T cells in the livers of patients with chronic hepatitis B were examined in detail. METHODS: TCR usage was examined by the inverse polymerase chain reaction in 2 hepatitis B e antigen-positive patients, one at an early stage and the other at an advanced stage. RESULTS: In 61 productively rearranged clones bearing TCRalpha genes in the liver of the patient with early stage chronic hepatitis B, the Valpha 7.2 gene segment was most frequently used (16.4%), while the other Valpha gene segments were used less frequently. All but one of the clones with the Valpha7.2 gene were joined with the Jalpha33 gene, and the CDR3 regions of these clones were the same length and similar in amino acid sequence. In contrast, in 68 productively rearranged clones from the liver of the patient with advanced stage disease, all Valpha gene segments were used less frequently, and combinations of the Valpha and Jalpha gene segments varied. CONCLUSIONS: Our data suggest a relatively restricted usage of TCR in the liver in early stage chronic hepatitis B.

Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma.

We prospectively evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) with microembolization material, degradable starch microspheres (DSMs), and epirubicin, for treatment of multifocal hepatocellular carcinoma (HCC). Seventeen patients with multifocal HCC were treated. At the first treatment, DSMs were injected alone to determine the dose for embolization of the hepatic artery in each patient. After 4 weeks, TACE was performed every 4 to 6 weeks with a mixture of DSMs and epirubicin at a dose of 40 mg/m2. A necrotic area of more than 50% was produced in 6 patients by DSMs alone, and in 11 patients by TACE. The overall response rate was 52.9% (2 complete and 7 partial responses). The duration of the responses ranged from 4 to 21 months (median: 9 months). Common toxicities were transient abdominal pain, nausea/vomiting, fever, and leukopenia. In four patients, grade III or IV toxicity was observed as gamma-glutamyl transpeptidase elevation. TACE with DSMs had tumor necrosis efficacy with acceptable toxicity. The median survival time was 21.7 months, and the 2-year survival rate was 45.3%. Further investigation of the effects of DSM treatment on survival should be carried out.

Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma.

BACKGROUND: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU). METHODS: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method. RESULTS: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months. CONCLUSIONS: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma.

A phase I study of hepatic arterial infusion chemotherapy with zinostatin stimalamer alone for hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion of zinostatin stimalamer and lipiodol emulsion shows a moderate activity against hepatocellular carcinoma. However, the anti-tumor activity of zinostatin stimalamer alone is uncertain. METHODS: The primary endpoint was to evaluate the frequency of dose-limiting toxicity and determine the maximum-tolerated dose of zinostatin stimalamer when used by intra-arterial infusion. The candidates for this study were patients with hepatocellular carcinoma no longer amenable to established forms of treatment. Hepatic arterial infusion chemotherapy was performed by selectively introducing a catheter into the hepatic artery with zinostatin stimalamer alone. Treatment was repeated at 4-8-week intervals until disease progression or the appearance of unacceptable toxicity. The starting dose of zinostatin stimalamer was 3 mg/m(2), and doses were increased in 1 mg/m(2) increments in successive cohorts. At least three patients were treated at each dose level and three additional patients were treated in the presence of dose-limiting toxicity. RESULTS: Twelve patients were entered into this trial. Dose-limiting toxicity was observed in one of six patients at 3 mg/m(2), and in two of six patients at 4 mg/m(2). The maximum-tolerated dose was judged to be 3 mg/m(2) with liver dysfunction and serum creatinine increase as the dose-limiting toxicity. There was one early death suggested to be related to the protocol treatment. None of the 12 patients achieved an objective tumor response. CONCLUSION: Hepatic arterial infusion with a zinostatin stimalamer of 3 mg/m(2) may be tolerated, but not active, in patients with far advanced hepatocellular carcinoma.

Intrahepatic pseudoaneurysm: a complication following radio-frequency ablation therapy for hepatocellular carcinoma.

A 70-year-old male was admitted to hospital for a liver tumor. We diagnosed that hepatocellular carcinoma (HCC), 1.5 cm in diameter, by several examinations. We performed ultrasonically guided radio-frequency ablation (RFA). Ultrasonography (US) 9 days post-therapy revealed a cystic lesion 1.5 cm in diameter. Color Doppler US revealed color imaging throughout the lesion and dynamic computed tomography (CT) demonstrated an area of hyperattenuation. Intrahepatic pseudoaneurysm was diagnosed. On 14 days post-therapy, no color signals on color Doppler US or enhanced areas on CT were seen. We submit that pseudoaneurysm should be recognized as a complication of radio-frequency ablation.

Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus.

Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% CI 28-72%). The 1-year overall survival rate was 25% (95% CI 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT. The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.