Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin

The selective delivery of a high dose of radiation to malignant hepatic tumours by infusion of non-biodegradable yttrium-90 (90Y) microspheres via the hepatic artery while sparing the non-tumorous liver parenchyma depends on the tumour-to-normal uptake ratio (T/N) of the therapeutic radiopharmaceutical. Using intrahepatic arterial technetium-99m macroaggregated albumin (99Tcm-MAA), the effect of tumour type, tumour vascularity assessed by hepatic angiography (HAG), tumour size and the degree of extrahepatic shunting on the T/N was investigated in 377 patients with hepatocellular carcinoma (HCC) and 25 patients with colorectal liver metastases. HCC was shown to have a wider range of T/N (0.2-26.5) compared with liver metastases (2.3-7.2). HCC with vascularity grade 1 on HAG had significantly lower T/N but there was no significant difference in HCC with higher vascularity grades. This confirmed that vascularity on HAG does not predict T/N. Overall there was no correlation between T/N and tumour size. Large tumours (> 20 cm) had a significantly lower T/N, probably due to necrosis in the tumour centres. A decrease in mean T/N with increasing percentages of lung shunting was observed in HCC. Determination of T/N by simulation with 99Tcm-MAA is recommended before internal radiation therapy with 90Y microspheres.     

Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver

PURPOSE: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control. METHODS: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. RESULTS: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. CONCLUSION: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.     

A pilot study of cryochemotherapy for hepatic metastases from colorectal cancer

Cryosurgery of hepatic metastases from colorectal carcinoma is a form of local therapy for unresectable disease. After curative resection, failures occur in the liver, and at extrahepatic sites. This pilot study evaluated the toxicity and tolerance to cryotherapy and intraoperative chemotherapy for unresectable hepatic metastases from colorectal cancer. If after exploratory celiotomy for potential curative resection of hepatic metastases the patient was deemed unresectable because of location and/or number of lesions, cryosurgery and intraoperative chemotherapy with systemic 5-fluorouracil 600 mg/m2 and leucovorin 500 mg/m2 was performed. Four patients were treated with cryochemotherapy. All patients developed toxicity. Two patients developed grade II leukopenia on Postoperative Days 2 and 12, and grades II and III diarrhea on Postoperative Days 5 and 7, respectively. Grade III hyperbilirubinemia and thrombocytopenia occurred in one patient on Postoperative Days 3 and 7. Acute respiratory distress syndrome, postoperative ileus, and grade II mucositis occurred in one patient each. All patients had delays and dose reductions on their subsequent chemotherapy treatments secondary to toxicity. Two patients had disease progression, one had stable disease. and one is "disease free." Combining the tumoricidal effects of chemotherapy and cryosurgery is in theory a good concept. However, the toxicity of 5-FU and leucovorin is enhanced by this approach.     

Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.     

Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation

BACKGROUND: Neuroendocrine tumors commonly metastasize to the liver. Although surgical resection is considered a treatment option for patients with localized metastases confined to the liver, the longterm survival benefit of liver resection has not been clearly demonstrated. We examined the survival of patients undergoing liver resection for this disease. STUDY DESIGN: Between 1984 and 1995, we evaluated 38 patients with liver-only metastases from neuroendocrine tumors, including 21 carcinoid, 13 islet cell, and 4 atypical neuroendocrine neoplasms. Data from a combined prospective and retrospective database and a tumor registry were analyzed. Of these patients, 15 underwent complete resection of all known disease. The remaining 23 patients, who also had disease confined to the liver, had comparable tumor burden but were believed to be unresectable. The longterm survival rates of these two groups were compared. RESULTS: Patients who underwent liver resection did not differ from those who were unresectable with regard to age, pathology, primary tumor site, serum alkaline phosphatase levels, or percentage of the liver involved. All resections were complete, leaving no residual disease, and consisted of lobectomy (n = 3), segmentectomy (n = 1), and wedge resections (n = 11). There were no operative deaths. Patients who underwent hepatic resection had a significantly longer survival than unresected patients. Although median survival had not been reached in resected patients, the median survival in the unresectable group was 27 months. Patients who underwent liver resection had a higher 5-year actuarial survival (73% versus 29%). CONCLUSIONS: Hepatic resection in selected patients with isolated liver metastases from neuroendocrine tumors may prolong survival. This conclusion was reached by comparing our resected group with an unresectable group with similar tumor burden.     

The approach to the patient with single and multiple liver metastases, pulmonary metastases, and intra-abdominal metastases from colorectal carcinoma

Recurrent colorectal carcinoma constitutes a major health care problem, with 90,000 patients diagnosed annually with metastatic disease. Recent advances have offered treatment to selected patients with liver, lung, and intra-abdominal metastases. Resection of liver secondary tumors improves 5-year survival from 0% to approximately 30% and offers the only possibility for cure. As experience mounts, hepatic surgery can be performed with quite acceptable morbidity and mortality. Adjuvant therapies are being developed that may improve results with surgery alone. Cryoablation is a new technique that appears to effectively eradicate liver tumors, but its role remains to be defined. In patients with unresectable disease, the benefit of hepatic artery infusion of chemotherapy is unproven. Resection of pulmonary metastases significantly improves survival in patients with solitary nodules. Consistent data regarding the benefit of pulmonary metastatectomy in patients with multiple nodules are not available. Combined cytoreductive surgery and intraperitoneal hyperthermic chemotherapy is being investigated as a treatment for peritoneal carcinomatosis from colorectal cancer. Although selected patients may benefit, this combined treatment modality appears to be less effective in patients with colorectal cancer than with other types of cancer.     

Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer

BACKGROUND/AIMS: Since 1989, thirty-two patients with advanced, intra-abdominal pancreatic cancer were treated with regional chemotherapy in combination with extracorporeal hemofiltration. PATIENTS and METHODS: Eleven patients had locally advanced, unresectable cancer, and ten had advanced disease with liver metastases. Three patients had developed liver metastases following a radical resection. One patient had an incomplete resection with local residual disease, and a second had developed a local recurrence after a radical resection. One patient had an unresectable cystadenocarcinoma. Five patients had failed prior systemic therapies for unresectable pancreatic cancer. The patients underwent 85 treatments with regional chemotherapy plus hemofiltration, an average of 2.7 treatments per patient. RESULTS: Of 21 patients treated primarily with regional chemotherapy plus hemofiltration, there were two complete responses (9%) and eight partial responses (38%), an overall total response rate of 47%. The average survival for patients with Stage II/III localized, unresectable disease is 13 months and that for Stage IV unresectable disease with liver metastases is 9 months. CONCLUSIONS: Patients with recurrent disease following a radical resection or having failed prior systemic therapies generally had no benefit from regional chemotherapy plus hemofiltration.     

Radioembolization with 32P-labelled glass microspheres for advanced hepatocellular carcinoma

We evaluated the efficacy and side effect of 32P-Labelled glass microspheres (32P-GMS) as a radioembolizer for patients with advanced hepatocellular carcinoma (HCC). 24 patients with unresectable HCC received internal radiation treatment of 32P-GMS. The tumor size varied from 3.6 to 18 cm. Hepatic arterial embolization was carried out through intraoperative or Seldinger's method. The mean absorbed radiation dose of the liver was 3250 rad (range from 1200 rad to 8000 rad). The radiation intensity within the tumor was 3.3 times stronger than in liver tissue. Not significant bone marrow renal toxicity was noted within 1 to 3 months. > 50% of tumor shrinkage was found in 17 cases, and < 50% of tumor reduction in 5 cases. The cumulative survival rate of 3, 6, 12, 18, 24 months was 92%, 75%, 54%, 33% and 29%. Hepatic arterial instillation of 32P-GMS appears to be safe and effective for unresectable HCC even with portal vein thrombosis.     

Intratumoral injection of rhenium-188 microspheres into an animal model of hepatoma

Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.     

Microwave coagulation therapy for hepatocellular carcinoma

BACKGROUND & AIMS: Surgical resection is not always feasible in patients with hepatocellular carcinoma. Microwave coagulation therapy has been used as an alternative to resection, and its efficacy has been evaluated. METHODS: Nineteen patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy through laparotomy (n = 12), laparoscopy (n = 5), or thoracotomy (n = 2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 13 patients, tumor size ranged from 5 to 90 mm. Patient outcomes were studied. RESULTS: Microwave coagulation therapy created a reproducible regional necrosis. Fourteen patients underwent potentially curative treatment; the remaining 5 patients underwent palliative treatment (n = 4) or incomplete tumor coagulation (n = 1). Of the 31 nodules treated, 28 underwent complete tumor ablation. Only 2 patients undergoing laparoscopic microwave coagulation therapy developed local recurrence. The coagulated area subsequently shrank. Patients showed rapid recovery without hepatic dysfunction. Thirteen patients, including 2 long-term survivors, are alive either without tumor (n = 10; 14-64 months) or with tumor (n = 3; 17-22 months). Six patients died of hepatocellular carcinoma (n = 4) or liver insufficiency (n = 2). CONCLUSIONS: This preliminary study suggests the efficacy of microwave coagulation therapy, including safety and potential curability, in patients with hepatocellular carcinoma with advanced liver cirrhosis and multifocal or central tumors.     

Prognosis of hepatocellular carcinoma patients with extrahepatic metastases

BACKGROUND/AIMS: There is no effective treatment for hepatocellular carcinoma (HCC) with extrahepatic metastases. This study investigated the survival and causes of death in HCC patients with extrahepatic metastases. MATERIALS AND METHODS: We retrospectively analyzed 34 HCC patients with extrahepatic metastases who received systemic chemotherapy without other anticancer treatment except prior hepatectomy. We classified causes of death as cancer death and death from other causes, and subclassified cancer deaths into hepatic cause, extrahepatic cause and cachectic cause. Each cause of death was analyzed in the two subgroups comprised of 10 patients with bone metastases alone and 22 patients with metastatic lesions in sites other than bone. RESULTS: Thirty-two of the 34 patients had died at the time of analysis. The median survival time and the 1-year survival rate were 4.6 mo and 20.3%, respectively. Incidence of hepatic cause, extrahepatic cause, cachectic cause and death from other causes were 21 (66%), 7 (22%), 2 (6%) and 2 (6%), respectively. In the subgroup of 10 patients with bone metastases alone, nine (90%) died from hepatic causes, but none died from extrahepatic causes. In the group of 22 patients with metastatic lesions in sites other than bone, 7 (32%) patients died from extrahepatic causes. CONCLUSION: The causes of death in HCC patients with extrahepatic metastases depended on metastatic site at the time of diagnosis. The results of this study may be useful in the design and analysis of future clinical trials of the HCC therapy.     

Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy

PURPOSE: Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS: Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS: Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION: The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.     

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.     

Iodine-131-MIBG therapy of a patient with carcinoid liver metastases

Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.     

Multidisciplinary treatment of hepatocarcinoma]

Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical removal; it may be done by resection or total hepatectomy. Although multicentric carcinogenesis predicts that liver transplantation is likely adequate to treat both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the advanced stages or in absence of end-stage liver disease and therefore liver resection remains the treatment of choice for radical cure of HCC. However, low resectability and high recurrence rate make surgery alone ineffective. Unresectable HCC may be converted to resectable by multimodality radiation/chemotherapy, and embolization of portal branch feeding tumour, improving the function of the nonembolized liver, can extend the surgical indications for HCC. Adjuvant chemoembolization has already shown to reduce recurrence rate after radical resection and it should be widely applied. In unresectable or not converted HCCs as well as in postoperative recurrence, alternative therapies, particularly as multimodality treatment, can improve survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma, waiting for further studies on newer modalities (prevention and gene therapy, especially), represents the best way to improve long-term results.     

Locoregional injection of OK-432/fibrinogen/thrombin for unresectable metastatic liver tumors

We performed the locoregional injection of OK-432/fibrinogen/thrombin to unresectable hepatic tumors metastasized from colorectal cancers, which were hardly controlled by arterial infusion chemotherapy. CEA was markedly decreased following this treatment, although abdominal CT did not show a significant reduction of tumor mass. This immuno-injection therapy may be a choice of treatment for metastatic liver tumors, refractory to treatment by conventional chemotherapy.     

Interventional radiology in the treatment of primary and metastatic liver cancer

The data available in the literature and the authors' own treatment outcomes in 600 patients with primary and metastatic carcinoma of the liver (in 1983-1996) were analyzed. Systemic or intravascular therapy as regional drug infusion, embolization, chemoembolization of the hepatic artery (CEHA) and portal vein (CEPV) was performed in unresectable cases. Whether pre- and postoperative chemoembolization was evaluated in resectable tumors. It is concluded that X-ray endovascular interventions play an important role in the treatment of malignant hepatic tumors. Transcatheter CEHA alone and in combination with CEPV is the most effective current treatments of unresectable carcinoma of the liver. In some patients, preoperative CEHA makes it possible to remove the tumor previously considered to be unresectable. Resection in combination with adjuvant CEHA and CEPV reduces the incidence of postoperative recurrences. The combined approach to treating malignant hepatic neoplasms expands the possibilities of delivering care to patients and improving late outcomes.     

Radioiodine I-31 therapy in the management of thyroid cancer. A prospective study

The therapeutic value of I-131 ablation therapy following thyroidectomy for thyroid cancer was evaluated in 54 patients in a prospective study of 25 years. Thirteen (24%) patients had follicular, 24 (44%) papillary, 13 (24%) mixed papillary-follicular, two (4%) Hurthle cell and two (4%) had undifferentiated cell type tumor. Twenty-four (44.5%) patients had metastases at the time of I-131 therapy mainly to cervical and mediastinal lymph nodes, and less frequently to bone, brain, lung, and liver. After surgical thyroidectomy, the mean cumulative dose of I-131 required to achieve therapeutic ablation of functioning post-surgical remnants or tumor metastases was 163.4 mCi. The recurrence rate for patients with metastases was 56% and those without metastases was 25%. Ten patients showed recurrence of I-131 accumulating tissue five to 10 years after initial total ablation. The total mean cumulative dose of I-131 administered for both followup diagnostic studies, and initial and follow-up therapy was 245.3 mCi. Seven deaths were attributable to thyroid cancer, five with differentiated and two with anaplastic cell type tumors. Three of the four patients with differentiated cell type tumors had metastases to brain or bone. Their response to therapy was similar to those patients with anaplastic cell type tumors. In contrast, there were no deaths due to thyroid cancer when total ablation was achieved and maintained. After ablation, all patients were maintained on maximum tolerated doses of thyroid extract or thyroxin. No significant complications attributable to the therapeutic doses of I-131 employed in this series were noted.     

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.     

America: where kids are getting killed

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.