Purpose: To evaluate the feasibility of radioimmunotherapy (RIT) with radiolabeled antiĉ arcinoembryonic antigen antibodies after complete resection of liver metastases (LM) from colorectal cancer. Patients and Methods: Twenty-two patients planned for surgery of one to four LM received a preoperative diagnostic dose of a 131 I-F(ab ¶) 2^l abeled anti-carcinoembryonic antigen monoclonal antibody F6 (8-10 mCi/5 mg). 131I-F(ab ¶) 2 uptake was analyzed using direct radioactivity counting, and tumor-to-normal liver ratios were recorded. Ten patients with tumor-to-normal liver ratios of >5 and three others were treated with a therapeutic injection I/50 mg F(ab ¶) 2 ] 30 to 64 days after surgery. Results: Median 131 I-F(ab ¶) 2 immunoreactivity in patient serum remained at 91% of initial values for up to 96 hours after injection. The main and dose-limiting-toxicity was hematologic, with 92 % and 85 % grades 3 to 4 neutropenia and thrombocytopenia, respectively. Complete spontaneous recovery occurred in all patients. No human anti-mouse antibody response was observed after the diagnosis dose; however, 10 of the 13 treated patients developed human anti-mouse antibody f3 months later. Two treated patients presented extrahepatic metastases at the time of RIT (one bone and one abdominal node) and two relapsed within 3 months of RIT (one in the lung and the other in the liver). Two patients are still alive, and one of these is diseasefree at 93 months after resection. At a median follow-up of 127 months, the median disease-free survival is 12 months and the median overall survival is 50 months. Conclusion: RIT is feasible in an adjuvant setting after complete resection of LM from colorectal cancer and should be considered for future trials, possibly in combination with chemotherapy, because of the generally poor prognosis of these patients.Surgical resection is the most effective therapy for isolated liver metastases (LM) from colorectal cancer (CRC; refs. 1 -4) and offers the only possibility of cure in these patients. When complete resection is achieved, 5-year survival rates ranging from 25% to 41% have been reported (2, 3, 5 -7). However, approximately two-thirds of patients relapse, often in the first 2 years, demonstrating the need for efficient postoperative therapies capable of sterilizing microscopic disease. Although chemotherapy in this setting has enhanced disease-free survival (DFS), it has not clearly shown a survival advantage. Efforts have thus been focused on immunotherapy and radioimmunotherapy (RIT) with native or radiolabeled monoclonal antibodies (mAb) based on impressive results in the treatment of non -Hodgkin lymphoma (8 -10). Studies of radiolabeled mAb in the adjuvant setting of CRC or with small volume disease have been reported (11,12), although success with bulky, metastatic tumors from CRC has been limited (13 -15). At our institution, an initial phase I study involving patients with nonresectable and chemorefractory LM from CRC showed that the maximal tolerated dose of 131

Iodine-131 metaiodobenzylguanidine ([131I]MIBG), a radiopharmaceutical agent, is used for treating malignant phaeochromocytoma. [131I]MIBG therapy results in a hormone response rate of approximately 50%, but generally it yields only a partial or no tumour response. We present a case of a 46-year-old woman with a familial history of von Hippel-Lindau disease, who was treated with [131I]MIBG for a metastatic phaeochromocytoma involving the lungs, liver and bones. The patient received a cumulative dose of 33.3 GBq (900 mCi) and a complete hormone response was observed, as evaluated on the basis of catecholamine and metanephrine levels. Conventional radiography, computerized tomography and [131I]MIBG scintigraphy indicated that a near-complete tumour regression was achieved, with no evidence of relapse during a 4-year follow-up period. This case thus demonstrates that treatment with [131I]MIBG may lead to a dramatic tumour response in malignant phaeochromocytoma presenting both soft tissue and bone metastases.

BackgroundThere is evidence showing that the hypothyroid state results in increased serum creatinine levels. However, whether this is only due to the peripheral thyroid hormones or if thyroid-stimulating hormone (TSH) is also involved is not known.MethodsSerum creatinine levels and estimated glomerular filtration rate (eGFR) were assessed in thyroidectomized patients with varying thyroid hormones and TSH levels. Blood samples from Group 1 (21 patients) were obtained 1 month after complete thyroidectomy, while under a hypothyroid state (t1) and a sufficient time after thyroid hormones initiation (euthyroid state, t2). Group 2 (20 euthyroid patients) were sampled after recombinant human thyrotropin injections (rhTSH, t1) and later after rhTSH extinction (t2).ResultsIn Group 1, serum creatinine levels decreased after correction of hypothyroidism (85.3 ± 4.3 versus 78.0 ± 3.9 µmol/L; P = 0.04). In Group 2, serum creatinine levels increased after rhTSH withdrawal (70.6 ± 5.7 µmol/L versus 76.5 ± 5.8 µmol/L; P = 0.007). Between t1 and t2, eGFR varied accordingly [Group 1, 71.7 ± 3.5 versus 81.2 ± 4.5 mL/min/1.73 m² (P = 0.02); Group 2, 97.7 ± 7.4 versus 87.5 ± 5.9 (P = 0.007)]. The changes in TSH and eGFR following supplementation with thyroxine were significantly correlated (r = −0.6, P = 0.0041).ConclusionsIatrogenic hypothyroidism significantly increases serum creatinine and reversibly impairs eGFR, while treatment with rhTSH enhances renal function in euthyroid patients, supporting the existence of an influence of TSH level on renal function. The mechanisms by which peripheral thyroid hormones and TSH influence GFR need to be identified in physiology-orientated studies.

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