Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. 166Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. 166Holmium-Chitosan complex, in which chitosan is chelated with 166Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of 166Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. 166Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.
alpha-Fetoproteins/metabolism ; Tomography, X-Ray Computed ; Radiopharmaceuticals/administration & dosage/*therapeutic use ; Pilot Projects ; Middle Aged ; Male ; Liver Neoplasms/pathology/radiography/*radiotherapy ; Injections, Intra-Arterial ; Humans ; Female ; Chitosan/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/pathology/radiography/*radiotherapy ; Aged ; Adult

Type I neurofibromatosis is an autosomal dominant disorder that occurs in 1 of 3, 000 births. It is characterized by multiple cutaneous neurofibromas, cafe-au-lait spots of the skin. Patients with neurofibromatosis are at increased risk of developing malignancies, particularly neural crest and other non-neural crest neoplasms. The term `malignant fibrous histiocytoma' was first introduced in 1963 to refer to a group of soft tissue tumors characterized by a storiform or cartwheel like growth pattern. Malignant fibrous histiocytomas are the most common type of soft tissue sarcoma that occurs in late adult life. Herein, our recent experienced a case of a malignant fibrous histiocytoma in a 28 year-old female with type I neurofibromatosis is reported, with a review of the literature.
Adult ; Cafe-au-Lait Spots ; Female ; Histiocytoma, Malignant Fibrous* ; Humans ; Neural Crest ; Neurofibroma ; Neurofibromatoses* ; Neurofibromatosis 1 ; Parturition ; Sarcoma ; Skin

PURPOSE: For patients with Dukes' stage B and C rectal cancer, surgery followed by adjuvant chemoradiotherapy is considered to be the standard treatment. However, the drugs used in combination with 5-fluorouracil (5-FU), the method of administration, duration of adjuvant therapy and the frequencies of administration presently remain controversial topics. We investigated (1) the efficacy and safety of adjuvant radiotherapy and 5-FU/leucovorin (LV) chemotherapy for patients who had undergone curative resection and (2) the effect of dose related factors of 5-FU on survival. MATERIALS AND METHODS: 130 rectal cancer patients with Dukes' B or C stage disease who were treated with curative resection were evaluated. The adjuvant therapy consisted of two cycles of 5-FU/LV chemotherapy followed by pelvic radiotherapy with chemotherapy, and then 4~10 more cycles of the same chemotherapy regimen were delivered based on the disease stage. The cumulative dose of 5-FU per body square meter (BSA), actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor, and the patients' survival rates were compared. RESULTS: With a median follow-up duration of 52 months, the 5-year disease-free survival and overall survival rates of 130 patients were 57% and 73%, respectively. Loco- regional failure occurred in 17 (13%) of the 130 patients, and the distant failure rate was 27% (35/130). The chemotherapy related morbidity was minimal, and there was no mortality for these patients. The cumulative dose of 5-FU/ BSA had a significant effect on the 5-year overall survival for Dukes' C rectal cancer patients (p=0.03). Multivariate analysis demonstrated that only the performance status affected the 5-year overall survival (p=0.003). CONCLUSION: An adjuvant therapy of radiotherapy and 5-FU/LV chemotherapy is effective and tolerable for Dukes' B and C rectal cancer patients. A rospective, multicenter, randomized study to evaluate the effects of the cumulative dose of 5-FU/BSA on survival is required.
Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Mortality ; Multivariate Analysis ; Radiotherapy ; Radiotherapy, Adjuvant ; Rectal Neoplasms* ; Survival Rate

PURPOSE: A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy.
Breast Neoplasms* ; Breast* ; Cisplatin* ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination* ; Fever ; Humans ; Intention to Treat Analysis ; Leukopenia ; Mucositis ; Paclitaxel* ; Pneumonia ; Radiotherapy ; Thrombocytopenia ; Treatment Refusal

PURPOSE: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy* ; Febrile Neutropenia ; Humans ; Neutropenia ; Platinum ; Small Cell Lung Carcinoma ; Thrombocytopenia

PURPOSE: Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line. MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment. RESULTS: We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration-dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP. CONCLUSION: The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP.
Aging ; Apoptosis ; Blotting, Southern ; Breast Neoplasms ; Cell Aging ; Cell Line ; Cell Proliferation ; Enzyme Assays ; Genetic Phenomena ; Humans* ; RNA-Directed DNA Polymerase* ; Telomerase* ; Telomere ; Transcription Factors ; Zidovudine

Mucoepidermoid carcinoma is a common malignant tumor of the salivary glands, but rare in other sites. Only 10 cases of mucoepidermoid carcinoma of liver have been reported, and there was 1 case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma. The definite diagnosis and pathogenesis are still controversial. However, hepatocellular carcinoma is the second most common cancer in Korea. Its etiology is better known compared to mucoepidermoid carcinoma. We report a rare case of double primary cancer of mucoepidermoid carcinoma and hepatocellular carcinoma in liver.
Carcinoma, Hepatocellular* ; Carcinoma, Mucoepidermoid* ; Diagnosis ; Korea ; Liver* ; Salivary Glands

BACKGROUND: Pleural effusion is one of most common clinical mainifestations associated with a variety of pulmonary disease such as malignancy, tuberculosis, and pneumonia. However, there are no useful laboratory tests to determine the specific cause of pleural effusion. Therefore, an attempt was made to analyze the various types of pleural effusion and search for useful laboratory tests for pleural effusion in order to differentiate between the disease, especially between a malignant pleural effusion and a non-malignant pleural effusion. METHODS: 93 patients with a pleural effusion, who visited the Severance hospital from January 1998 to August 1999, were enrolled in this study. Ultrasound-guided thoracentesis was done and a confirmational diagnosis was made by a gram stain, bacterial culture, Ziehl-Neelsen stain, a mycobacterial culture, a pleural biopsy and cytology. RESULTS: The male to female ratio was 56:37 and the average age was 47.1±21.8 years. There were 16 cases with a malignant effusion, 12 cases with a para-malignant effusion, 36 cases with tuberculosis, 22 cases with a para-pneumonic effusion, and 7 cases with transudate. The LDH2 fraction was significantly higher in the para-malignant effusion group compared to the para-pneumonic effusion group [30.6±64.% and 20.2±7.5%, respectively (p<0.05)] and both the LDH and LDH2 fraction was significantly in the para-malignant effusion group compared to those with tuberculosis [16.4±7.2% vs. 7.6±4.7%, and 30.6±6.4% vs. 17.6±6.3% respectively (p<0.05)]. The pleural effusion/serum LDH4 fraction ratio was significantly lower in the malignant effusion group compared to those with tuberculosis [1.5±0.8 vs. 2.1±0.6, respectively (p<0.05)]. The LDH4 fraction and the pleural effusion/serum LDH4 fraction ratio was significantly lower in the para-malignant effusion group compared to those with tuberculosis [17.0±5.8% vs. 23.5±4.6% and 1.3±0.4 vs. 2.1±0.6, respectively(p<0.05)]. CONCLUSION: These results suggest that the LDH isoenzyme was the only useful biochemical test for a differential diagnosis of the various disease. In particular, the most useful test was the pleural effusion/serum LDH4 fraction ratio to distinguish between a para-malignant effusion and a tuberculous effusion.
Biopsy ; Diagnosis ; Diagnosis, Differential* ; Exudates and Transudates ; Female ; Humans ; Lung Diseases ; Male ; Pleural Effusion* ; Pleural Effusion, Malignant ; Pneumonia ; Tuberculosis

PURPOSE: The purposes of this study were to evaluate the biodistribution and effect of Ho-166 radionuclide by intra-arterial injection of the Ho-166 chitosan complex in dogs and to assess the clinical efficacy and side effects of this complex in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In an experimental study, 20 mCi of Ho-166 chitosan complex was injected into the left hepatic artery of six adult dogs. The distribution of radioactivity in each organ was calculated using a gamma camera scan at regular intervals. A beta ray radioactivity count (cpm) of blood and urine was performed periodically, and hematologic and hepatic function were regularly assessed. At 4, 8 and 12 weeks after intra-arterial injection, bone marrow and liver were pathologically evaluated. Twenty-five patients with a single, nodular HCC mass 3 -9 cm in diameter were treated by intra-arterial injection of Ho-166 chitosan complex, and immediately after the procedure a gamma camera scan was obtained. A beta ray radioactivity count(cpm) of blood was performed periodically, hematologic and hepatic function were regularly evaluated, and CT scans and angiograms were obtained 3 months after the procedure. On the basis of the CT and angiographic findings, the treatment effects were classified as complete (CR), partial (PR) or non-response(NR). RESULTS: In the animal study, blood radioactivity peaked immediately after injection and then declined rapidly. Urinary excretion was 0.17%. The proportion of radioactivity in each organ per whole body was 25% in the left lobe of the liver, 7% in the right lobe, 3% in the lung, 1.4 -3% in the bladder, and 2% in bone. WBC and platelet counts declined maximally at 3 -4 weeks and recovered at 12 weeks. The cellularity of bone marrow was 25% at 4 weeks and 55% at 12 weeks, findings which correlated well with the observed hematologic changes. In the clinical study of 25 HCC patients, CR was achieved in 17 (68%) cases, PR in 5 (20%) and NR in 3 (12%). At gamma camera imaging immediately after treatment, tumor radioactivity was localized in 76% of cases. In six cases (24%) WBC and platelet counts decreased 50% or more compared with their pretreatment level. In 67 -75% of cases, SGOT and SGPT were, within 1 -3 days, 2 -3 times higher than their pre-treatment level, and recovered at post 4 weeks. CONCLUSION: Ho-166 chitosan complex administrated intra-arterially localized the target organ with minimal side effects, and we therefore suggest that it may be used in the treatment of nodular and hypervascular HCC. Further study of its dosimetry and possible hematologic side reactions is needed, however.
Adult ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Beta Particles ; Bone Marrow ; Carcinoma, Hepatocellular* ; Chitosan* ; Dogs ; Gamma Cameras ; Hepatic Artery ; Humans ; Injections, Intra-Arterial* ; Liver ; Lung ; Platelet Count ; Radioactivity ; Radionuclide Imaging ; Tomography, X-Ray Computed ; Urinary Bladder

In this paper, a case of corneal squamous cell carcinoma is reported. Invasive squamous cell carcinoma of the cornea is a rare disorder and has not been previously described in the Korean literature. In this case, the invasive squamous cell carcinoma of the cornea was treated by complete excision and cryotherapy. No evidence of metastasis or recurrence has been found since the procedure. Complete excision and adjunctive cryotherapy has become the treatment of choice because of the higher recurrence rate following a simple excision.
Aged ; Carcinoma, Squamous Cell/*pathology/surgery/therapy ; Case Report ; Corneal Diseases/*pathology/surgery/therapy ; Cryotherapy ; Eye Neoplasms/*pathology/surgery/therapy ; Human ; Male ; Neoplasm Invasiveness