Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Multicenter pilot study of 5-fluorouracil, folinic acid, interferon alpha-2b and degradable starch microspheres via hepatic arterial infusion in patients with nonresectable colorectal liver metastases.

BACKGROUND: It is necessary to establish therapeutic regimens for patients with nonresectable hepatic metastases of colorectal carcinoma. A new regional chemotherapy regimen was tested in a prospective study in three centers. PATIENTS AND METHODS: An arterial port system was implanted in 95 patients. From January 1994 to March 1999, intra-arterial treatment was applied via the hepatic artery using 450 mg starch microspheres with 5 million IU recombinant interferon-alpha 2B, 500 mg/m2 folinic acid and 600 mg/m2 5-FU body surface for 5 days with a 14-day interval. RESULTS: The tumor response rate was 70%. Median disease progression was 17 months, median survival 24 months. The subgroup analysis shows a significant advantage (p<0.00001) for patients with a liver tumor involvement of <25% and a median survival of 39 months compared to a tumor involvement of 25-50% (24 months) and >50% (14 months). Major toxicity problems were observed in 11%. However, there was no termination of therapy on account of these problems. CONCLUSION: Intra-arterial chemotherapy with our new regimen was useful in patients with colorectal liver metastases who had only an intrahepatic tumor burden of <50%.

Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer.

OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer. METHODS: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1-8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20 vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.

[Portal contrast medium-enhanced spiral computed tomography of the liver--the correlation of radiological and intraoperative findings and the evaluation of resectability]. / Portal kontrastverstärkte Spiral-Computertomographie der Leber--Korrelation radiologischer und intraoperativer Befunde und Beurteilung der Resektabilität.

PURPOSE: To evaluate the accuracy of spiral computed tomography during arterial portography (SCTAP) in the detection, localization, and resectability of liver tumors in a correlative study between radiology and intraoperative findings. METHOD AND MATERIALS: Retrospectively, SCTAP images of 168 consecutive patients before liver tumor resection were analyzed. The SCTAP studies (100 ml lopromid 300 by automated injector with a flow of 3 ml/s; slice thickness, table feed and reconstruction index 5 mm each; scan-delay 30 s; 120 kV; 250 mAs) were evaluated for the detection, localization, and resectability of focal liver lesions by three experienced radiologists in consensus and were correlated with histopathological and intraoperative findings where available (59/168). RESULTS: The sensitivity of SCTAP for the detection of liver tumors was 91% for all lesions and 84% for lesions < 1 cm. The specificity was only 19% due to a high rate of false-positive lesions (30%) and preselection effects. Typical pitfalls in false positive lesions were inhomogeneous liver perfusion near the portal vein, the falciform ligament, and the gallbladder (19/42). In 30% of the patients SCTAP correctly diagnosed inoperability, in 23% the intraoperative tumor expansion was larger than expected from SCTAP images, which would have changed operability. CONCLUSION: The SCTAP has a high sensitivity in the detection and localization of liver tumors and is a valuable method in the preoperative diagnostic procedure. The method is limited by many false-positive lesions often due to inhomogeneous liver perfusion and the insufficient evaluation of local tumor spread. Therefore, SCTAP should be replaced by MRI in the near future.

[Symptoms, tumor stage and primary treatment in patients with colorectal carcinoma]. / Symptomatik, Tumorstadium und primäre Therapie bei Patienten mit kolorektalem Karzinom.

OBJECTIVE: To obtain population-related data, previously not available for Germany, regarding primary symptoms, diagnosis and treatment of patients with colorectal carcinoma. PATIENTS AND METHODS: During 1994, in the catchment area of Bonn (town of Bonn, districts of Euskirchen and Rhein-Sieg), there were 354 cases of newly diagnosed colorectal carcinoma. For all of them initial symptoms, primary diagnosis, cancer stage at time of diagnosis as well as surgical and conservative treatment were prospectively documented. By comparing entries from all relevant hospitals and doctors with those of the pathology institutes of the region, data of about 98% of all these patients were recorded. RESULTS: The average age of the patients was older (median of 69 for men, 72 for women) with more far metastases than in comparable groups reported by German university surgical departments. Only 4.6% of the group had occult blood in the stool as the only symptom. Most of the patients had local or regional metastases (T3-4: 63.9%; N1-3: 41%, respectively). Operations intended to be curative were possible in only 65.9% of the cohort. Adjuvant radiotherapy and/or chemotherapy was given to 11.7%, using current consensus recommendations.

Liver tumors: follow-up with P-31 MR spectroscopy after local chemotherapy and chemoembolization.

The authors examined and quantified the changes observed in the phosphorus-31 magnetic resonance (MR) spectra of liver tumors after chemotherapy and chemoembolization to investigate the suitability of P-31 MR spectroscopy for follow-up. A 1.5-T unit was used before and at specific times during therapy to obtain spectra of liver tumors in 10 patients with liver metastases from colorectal carcinoma and two patients with hepatocellular carcinoma. A marked increase in inorganic phosphate and a decrease in the alpha- and beta-nucleotide phosphate portions of the spectra were observed during the first few hours after local chemotherapy or chemoembolization. Later, the phosphomonoester signals increased markedly and the phosphodiester signals decreased slightly. The effects of successful chemoembolization or local chemotherapy become apparent in the P-31 MR spectrum during the first few hours after the start of therapy. The results demonstrate that P-31 MR spectroscopy is a suitable method for follow-up. However, long-term studies are needed to determine whether it also yields prognostic information.

Combined haemoperfusion, haemofiltration and haemodialysis for systemic detoxification in locoregional 5-fluorouracil therapy.

Combined haemoperfusion, haemofiltration and haemodialysis (HPFD) was examined for its systemic effect on 5-fluorouracil (5-FU) kinetics after locoregional application to one female patient with liver metastases of a colon carcinoma. During each HPFD treatment, which lasted 4 h, 5-FU was given via a port-a-cath system into the hepatic artery on 4 separate days. The HPFD extraction rate was 99%. Extracorporal 5-FU clearance (89 ml/min) was 9% of total body clearance (1094 ml/min). The fraction eliminated within 4 h was only 6% of the applied dose (3500-4000 mg 5-FU). Sufficient extracorporal detoxification during combined HPFD can thus not be guaranteed in locoregional chemotherapy with a high dose of 5-FU.

[Therapeutic protocols in the treatment of liver metastases]. / Therapiestrategien zur Behandlung von Lebermetastasen.

The liver is the main site for metastatic spread from many cancer, particularly those of the colorectum. Surgical treatment of liver metastases is nowadays a safety therapeutical approach, which has been improved by the development of modern imaging procedures, clear indications and standardized surgical techniques. In carefully selected patients the 5-year survival ranges between 30-40%. Unfortunately only 20% of the patients with liver metastases are candidates for this potentially curative therapy. Palliative modalities remain for the majority of patients with unresectable metastases limited to the liver. Although various types of intrahepatic arterial chemotherapy, sometimes in combination with whole liver irradiation or embolization shows a higher response rate than systemic chemotherapy no significant impact on survival time has been proven. One of the main unsolved problem is the extrahepatic spread. For getting better results--median survival of responders ranges between 18 to 24 months versus 8 months of non-responders--a more exact selection is needed.