Soo Jung Gong

Correlation of tissue and blood plasminogen activation system in breast cancer

The plasminogen activation system plays a crucial role during cancer invasion and metastasis. In the solid tumor, urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and uPA receptor (uPAR) are considered as prognostic factors. In this study, we have investigated whether secretion of the uPA, PAI-1 and uPAR from the primary breast cancer tissue can be detected in the blood of the patients using the ELISA assay. We have found that the plasminogen activation system (uPA, PAI-1, uPAR) of tumor tissue is activated from the early stage of breast cancer. However, only a number of metastatic lymph nodes was a prognostic factor in multivariate analysis for relapse. The blood level of the plasminogen activation system correlated with that of tissue in an order of uPAR (r(2)=0.61; P=0.001), uPA (r(2)=0.35; P=0.001) and PAI-1 (r(2)=0.11; P=0.001). We conclude that the total uPAR level of cancer tissue can be substituted by that which is detected in the blood for further clinical applications.

Adenocarcinoma has an excellent outcome with pemetrexed treatment in Korean patients: a prospective, multicenter trial.

OBJECTIVE This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500 mg/m(2) every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. RESULTS The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4-12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8-57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17-5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19-10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0-1 [hazards ratio (HR)=0.331, 95% CI 0.135-0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283-0.899) were independent factors for prolongation of overall survival. CONCLUSIONS Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.

Systemic chemotherapy after cranial irradiation in patients with brain metastases from non-small cell lung cancer : A retrospective study

BACKGROUND Brain metastases (BMs) are found in about 10% of patients with newly diagnosed non-small cell lung cancer (NSCLC). This retrospective study was conducted to assess the clinical outcomes and prognostic factors of patients who received chemotherapy after cranial irradiation for NSCLC with synchronous BMs. MATERIALS AND METHODS From January 2000 through July 2007, we reviewed the medical records of patients who received systemic chemotherapy following cranial irradiation for BMs from newly diagnosed NSCLC. RESULTS A total of 40 patients were included in this review. As the first-line chemotherapy, a total of 114 cycles were administered, for a median number of 2 cycles per patient (range, 0.5-8 cycles). Thirty-four patients (85%) received platinum-based combination regimen and the remaining 6 received chemotherapy with a single agent. Sixteen (40%) patients, 11 of whom had ECOG of 2, only received 1 cycle or less of chemotherapy due to early death, rapid progression, clinical impairment, or toxicity. For 28 patients who were evaluable for response, the extracranial overall response rate was 43%. The median overall survival for all patients was 7 months (range, 0.9-25.3 months) and an estimated 1-year survival rate was 23%. Multivariate analysis revealed that ECOG status (P=0.018) and number of BM (P=0.038) were independent prognostic factors. CONCLUSION Our results suggest that chemotherapy can be used to increase survival of patients treated with cranial irradiation for newly diagnosed NSCLC with synchronous BM. However, systemic chemotherapy should be carefully considered according to the patients prognostic condition. Especially, patients with good performance status and limited number of BM may be good candidates for systemic chemotherapy after cranial irradiation.

Comparison of the Effectiveness of Monitoring Cisplatin-Induced Ototoxicity with Extended High-Frequency Pure-Tone Audiometry or Distortion-Product Otoacoustic Emission

Background and Objectives To compare the effectiveness of monitoring cisplatin-induced ototoxicity in adult patients using extended high-frequency pure-tone audiometry (EHF-PTA) or distortion-product otoacoustic emission (DP-OAE) and to evaluate the concurrence of ototoxicity and nephrotoxicity in cisplatin-treated patients. Subjects and Methods EHF-PTA was measured at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6, 8, 9, 11.2, 12.5, 14, 16, 18, and 20 kHz and DP-OAE at frequencies of 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, and 8 kHz in cisplatin-treated patients (n=10). Baseline evaluations were made immediately before chemotherapy and additional tests were performed before each of six cycles of cisplatin treatment. Laboratory tests to monitor nephrotoxicity were included before every cycle of chemotherapy. Results Four of 10 patients showed threshold changes on EHF-PTA. Five of 10 patients showed reductions in DP-OAE, but one was a false-positive result. The results of EHF-PTA and DP-OAE were consistent in two patients. Only one patient displayed nephrotoxicity on laboratory tests after the third cycle. Conclusions In our study, the incidence rate of cisplatin-induced ototoxicity was 40% with EHF-PTA or DP-OAE. Although both EHF-PTA and DP-OAE showed the same sensitivity in detecting ototoxicity, they did not produce the same results in all patients. These two hearing tests could be used to complement one another. Clinicians should use both tests simultaneously in every cycle of chemotherapy to ensure the detection of ototoxicity.

Multiple myeloma with biclonal gammopathy accompanied by prostate cancer.

We report a rare case of multiple myeloma with biclonal gammopathy (IgG kappa and IgA lambda type) in a 58-year-old man with prostate cancer who presented with lower back pain. Through computed tomography (CT) imaging, an osteolytic lesion at the L3 vertebra and an enhancing lesion of the prostate gland with multiple lymphadenopathies were found. In the whole body positron emission tomography-computed tomography (PET-CT), an additional osteoblastic bone lesion was found in the left ischial bone. A prostate biopsy was performed, and adenocarcinoma was confirmed. Decompression surgery of the L3 vertebra was conducted, and the pathologic result indicated that the lesion was a plasma cell neoplasm. Immunofixation electrophoresis showed the presence of biclonal gammopathy (IgG kappa and IgA lambda). Bone marrow plasma cells (CD138 positive cells) comprised 7.2% of nucleated cells and showed kappa positivity. We started radiation therapy for the L3 vertebra lesion, with a total dose of 3,940 cGy, and androgen deprivation therapy as treatment for the prostate cancer.

Waldenstrom Macroglobulinemia with CD5+ Expression Presented as Cryoglobulinemic Glomerulonephropathy: A Case Report

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.

A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy

A 50-year-old male patient presented with a right scrotal mass that had been growing rapidly for more than one year. A heterogeneous enhancing right scrotal mass (12×9 cm) with para-aortic and peri-caval lymphadenopathies was found on abdominal computed tomography (CT). Right orchiectomy was performed and the gross finding had shown intact testis with a well-defined, huge, whitish solid mass adjacent to the testis. According to pathology, the mass was characterized as a leiomyosarcoma, grade 3 (by National Cancer Instituted [NCI] system). Therefore, the diagnosis was stage III, grade 3 paratesticular leiomyosarcoma. The patient underwent additional systemic chemotherapy using ifosfamide and adriamycin. After nine cycles of chemotherapy, positron emission tomography-CT was performed and no FDP uptake was observed. The patient has been followed up for 12 months after systemic chemotherapy, and he has maintained a complete response. We report here on a rare case of paratesticular leiomyosarcoma treated successfully with orichiectomy and additional systemic chemotherapy.

[A case of a Korean adult affected by type B Niemann-Pick disease: secondary sea-blue histiocytosis and molecular characterization].

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.

Unicentric Castleman Disease Is Not Clearly Distinguished from Multicentric Type: A Case Report

Castleman disease (CD) was recently classified as a unicentric hyaline vascular variant, unicentric plasma cell variant, and multicentric plasma cell variant. It is rare that unicentric CD is presented as multiple retroperitoneal lymphadenopathy. The clinical manifestations and prognosis depends on histologic type. We report an unusual case of CD with multiple retroperitoneal lymphadenopathy, which had unicentric hyaline vascular variant histologically but was clinically multicentric. The patient experienced anemia, weight loss, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome), and plasmacytosis in bone marrow without human herpesvirus-8 or HIV. After exploratory laparotomy and lymphadenectomy under presumptive diagnosis of CD, the patients symptoms recovered, and CRP and ESR decreased. Therefore, we suggest that unicentric CD is not clearly distinguished from multicentric, the type in this report, focusing on the useful role of CRP, ESR, and positron emission tomography/computed tomography in the disease activity of CD.

Ureteral Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Chronic Inflammation, and Renal Artery Atherosclerosis

Malignant lymphoma of the upper urinary tract including the renal pelvis and ureter is extremely rare. Less than ten cases have been reported in the literature, of which extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the most frequent histologic type [1]. MALT lymphoma arising in the stomach, skin, thyroid, and salivary gland is associated with chronic inflammation caused by pathogenic microorganisms or autoimmune disorder [2]; however, the pathogenesis of MALT lymphoma in the upper urinary tract is unknown. Herein, we report a case of upper ureteral MALT lymphoma with extensive peri-ureteropelvic inflammation and atherosclerosis of the renal artery, and discuss the possible correlation between these lesions.