A case of colon metastasis to the lung treated successfully with combined chemotherapy of CPT-11 and 5'-DFUR

We administered pharmacokinetic modulating chemotherapy (PMC, oral tegafur/uracil [UFT] plus fluorouracil infusion) together with irinotecan hydrochloride (CPT-11) in a patient with rectal cancer, who had multiple lung metastases at 2 years and 7 months after surgery. However, because the patient showed resistance, we attempted combination therapy with CPT-11 and doxifluridine (5'-DFUR) on an outpatient basis, which resulted in NC after 9 months. During this period, the therapy was performed safely without any observable adverse reactions such as diarrhea or myelosuppression. This case suggests the efficacy of combination therapy with CPT-11 and 5'-DFUR, which was expected since this is an established treatment for progressive recurrent colon cancer.     

Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression

Neurotrophins enhance the survival of cells in the nervous system under both physiological and pathological conditions, such as those caused by disease or trauma. We recently demonstrated that expression of brain-derived neurotrophic factor (BDNF) was up-regulated in neurons and glia after compression-induced spinal cord injury (SCI). We show here the effects of BDNF on the oligodendrocyte survival and functional recovery after SCI. The effects of intrathecally administered BDNF on both Cu/Zn superoxide dismutase (CuZnSOD) and myelin basic protein (MBP) expression were examined using rats that had received compression-induced spinal cord injury. CuZnSOD expression in the spinal cord was down-regulated within 24 h of compression-induced injury and then recovered. Continuous infusion of BDNF inhibited the acute down-regulation of CuZnSOD expression. In situ hybridization showed that CuZnSOD was expressed in both neurons and glia. Although MBP expression was greatly reduced after injury, BDNF administration promoted the recovery of MBP expression nearly to a control level after 2 wk. Furthermore, BDNF administration also prompted behavioral recovery. These results suggest BDNF's usefulness in human clinical applications. The attenuation of CuZnSOD down-regulation may be related to a protective effect of BDNF and the promotion of MBP up-regulation may be related to a long-lasting restorative effect.     

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease with only minimal non-specific neuropathological findings

An autopsy case with clinically and molecular genetically diagnosed Huntington's disease (HD) accompanied with minimal non-specific neuropathological features was reported. When the patient was 45 years old, he had faulty memory, mood swing, personality change and agitation. Neurological and psychiatric examinations revealed choreoathetoid movements in limbs and trunk, generalized hyperreflexia and mental deterioration. However, cerebellar ataxia and muscle rigidity were not disclosed. Neuroimaging study did not show a definite atrophy of heads of caudate nuclei. Neuroacanthocytosis and Wilson's disease were ruled out by the peripheral blood examination and serum Cu and ceruloplasmin examination. At the age of 55 he died of pneumonia. Post-mortem examination revealed minimal non-specific neuropathological features for HD (Vonsattel's grade 0), that is, no visible fibrillary gliosis in the striatum, and few neuronal loss and only proliferation of astrocytes (astrocytosis) in the striatum. Molecular-genetic study the patient's brain tissues and his youngest son's blood was performed. These studies revealed 40 CAG repeats in the patient, 56 CAG repeats in his youngest son. These results suggest they may be HD. Vonsattel et al. [ 1998] insist that grade 0 comprises 1% of all HD brains, and grade 1 comprises 4% of all HD brains. But we could not find any reports in which the clinical and neuropathological features were described in detail on the cases with clinically and molecular genetically diagnosed HD without specific pathological findings. Therefore, we present in detail the clinical and neuropathological features of such case.     

Enhancement of O2- production from resident peritoneal macrophages by low-dose in vivo gamma-irradiation

Superoxide anion (O2-) production after very low-dose in vivo irradiation (4 cGy) was examined in resident peritoneal macrophages. The level of production rapidly increased following treatment with the PKC activator, phorbol 12-myristate 13-acetate (PMA), but no further enhancement by low-dose in vivo irradiation was observed. On the other hand, treatment with zymosan A gradually induced O2- production, which was further increased in low-dose in vivo irradiated macrophages. The amounts of phagocytosis of zymosan A were not changed by in vivo irradiation. This indicated that the enhancement of O2- production was not due to an increase in phagocytotic activity by low-dose in vivo irradiation. Our results show that low-dose in vivo irradiation induces production of reactive oxygen species by macrophages, not only nitric oxide as reported in our previous paper but also O2-. This may contribute to the increase of cytolytic activity of macrophages after low-dose in vivo irradiation.     

ADULT T CELL LEUKEMIA HISTOLOGICAL CLASSIFICATION AND CHARACTERISTICS

Adult T cell leukemia was classified into two distinct types, monomorphic and pleomorphic, according to their histological and cytological features. The former type is composed of uniform neoplastic cells with round or slightly indented nuclei without any marked deformation. The latter type, on the other hand, occupies a unique position in lymphocytic leukemias with the following characteristics: a) onset in adulthood, b) an acute and subacute course, c) well-differentiated T cell origin of the neoplastic cells, d) pleomor-phism of the neoplstic cells with markedly deformed nuclei, e) difkuse proliferation of the neoplastic cells without nodular pattern, f) histologically heterogeneous features of lymph nodes frequently admixing a cluster of normal lymphocytes, proliferation of macrophages and dendritic cells, and well-developed high endothelium venules, g) high incidence of skin lesions due to the infiltration of neoplastic cells, and h) exclusively limited localization of patients' birth places.     

Improved survival using multi-modality therapy in patients with lung metastases from colorectal cancer: a preliminary study

This retrospective study was conducted to assess the safety, efficacy, and long-term results of multi-modality therapy including radio-frequency thermal ablation (RFA) and radiotherapy as an additional cytoreductive method for eliciting the marked effects of chemotherapy in treating unresectable lung metastases from colorectal cancer. Total of 21 patients with lung metastasis from colorectal cancer were included. They were treated with modified pharmacokinetic modulating chemotherapy (PMC). Eleven were also treated with RFA and/or radiotherapy (multi-modality group), and 10 were treated with chemotherapy alone (chemotherapy group). Characteristics and survival of patients in the multi-modality group were compared with those of the chemotherapy group. The median survival of all patients was 38.6 months after the initial PMC. The cumulative 3-year survival rate of patients in the multi-modality group was 87.5% compared with 33.3% in the chemotherapy group (p=0.0041). The course of multi-modality therapy was uneventful except for pneumothorax in those who received RFA. Although pneumothorax developed in 4 of 11 patients (36.4%) treated with RFA, all were able to receive chemotherapy within 2 weeks after RFA. In conclusion, multi-modality therapy combined with modified PMC, radiation and RFA is a feasible choice of treatment associated with reasonable morbidity and mortality in patients with inoperable lung metastases from colorectal cancer.     

Bioresorbable Hyaluronate-Carboxymethylcellulose Membrane (Seprafilm) in Surgery for Rectal Carcinoma: A Prospective Randomized Clinical Trial

Purpose To evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy. Methods A total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA−). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome. Results Seprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates. Conclusion Seprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery.