A case of Von Meyenburg Complex associated with calculous cholecystitis, cerebral aneurysm and renal cortical cyst / 대한내과학회지

Von Meyenburg complexes (VMC) have many synonyms such as bile duct hamartomas and biliary hamartoma. These rare benign disorders are considered as congenital diseases caused by malformed differentiation of ductal plate. The diagnosis of VMC by common radiologic modality such as ultrasound and computed tomography was nearly impossible until the emergence of cholangiopancreatography by magnetic resonance imaging (MRCP) and the pathologic examination was the only way to confirm the diagnosis of VMC. But MRCP is now considered as most accurate noninvasive method for diagnosis of VMC. We report a histologically proven case of VMC associated with calculous cholecystitis, cerebral aneurysm and renal cortical cyst. To our knowledge, no comparable case has been reported and this would be the only second reported case of VMC, which was diagnosed by MRCP.

Lipid peroxidation, NF-kappaB activation and cytokine production in neutrophil-stimulated pancreatic acinar cells

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. The present study aims to investigate whether neutrophils primed by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) affect the productions H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by an antioxidant, N-acetylcysteine (NAC) and superoxide dismutase (SOD). H2O2 (ferrithiocyanate method), LPO (as thiobarbiturate reactive substances), and cytokines (IL-1beta, IL-6, TNF-alpha enzyme-linked immunosorbent assay) and NF-kappaB activation (electrophoretic mobility shift assay) were analyzed in acinar cells treated with or without PMA-primed neutrophils in the absence or presence of NAC (10 mM) or SOD (300 U/ml). As a result, the productions of H2O2, LPO and TNF-alpha were increased with the ratio of PMA-primed neutrophils to acinar cells while the productions of LPO, IL-1beta, IL-6 and TNF-alpha were increased with time. PMA-primed neutrophils resulted in the activation of NF-kappaB. Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatary cytokines in acinar cells. Antioxidants might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.

Chromosome Analysis of Korean Adult Patients with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: There has been some reports demonstrating the geographic heterogeneity in frequency of specific cytogenetic aberrations, but little is known about the types, frequency and prognostic value of specific chromosomal abnormalities in Korean adults with acute myelogenous leukemia. To evaluate cytogenetic characteristics of Korean adults with acute myelogenous leukemia, following study was performed. METHODS: Cytogenetic studies using high-resolution banding technique were done on newly diagnosed 38 patients with de nono acute myelogenous leukemia (AML) admitted to Asan medical center from January 1995 to May 1996. RESULTS: 1) Sixteen patients (42.1%) had clonal chromosomal abnormalities. 2) The t (8;21) was detected in 8 patients (21.1%). The t (15;17) was detected in 2 patients. The inv (16), del (11)(q23) and 7q- were detected in 1 patient each. Trisomy 21 as a sole abnormality was detected in 1 patient and complex abnormalities were detected in 2 patients. risomy 8 was not detected. 3) Eight (50%) of the 16 patients with AML-M2 had t (8;21), 2 of the 3 patients with AML-M3 had t (15;17) and 1 patient with AML-M4Eo had inv (16). 4) The median age of patients with chromosomal abnormalities was significantly younger than that of patients with normal karyotype (34 vs. 48 years, P=0.003). Other clinical andlaboratory characteristics were not significantly different between abnormal and normal cytogenetic groups. 5) The complete remission rate of patients with chromosomal abnormalities was lower than that of patients with normal karyotype, but the difference of CR rates was not statistically significant (78.1 vs. 84.2%, P=NS). CONCLUSION: These results suggest that lower incidence of trisomy 8, higher incidence of t (8;21) and stronger association between t (8;21) and AML-M2 than usually described may be the cytogenetic characteristics of acute myelogenous leukemia in Korean adult.

High Dose Cyclophosphamide, Thiotepa, and Carboplatin followed by Autologous Peripheral Stem Cell Rescue in Patients with Responsive Metastatic or High - Risk Primary Breast Cancer / 대한암학회지

PURPOSE: Positive correlation between dosage of antineoplastic agents and tumor response is well demonstrated in advanced breast cancer. But severe bone marrow depression limit the clinical application of high dose chemotherapy. Autologous peripheral blood stem cell transplantation(PBSCT) after high dose chemotherapy(HDC) was introduced to promote rapid bone marrow recovery. This study was designed to establish the feasibility of combining high dose cyclophosphamide, thiotepa, and carboplatin chemotherapy followed by stem cell rescue in patients with responsive metastatic or high risk primary breast cancer. MATERIALS AND METHOD: Eligibility criteria included the presence of high risk primary breast cancer(10 or more involved axillary lymph node, n=4), recurrent disease after curative resection(n=6) or stage IV disease at the time of diagnosis(n=1). The responses of recurrent disease to initial chemotherapy were 4 complete responses and 1 partial responses. One recurrent case with solitary pulmonary metastasis underwent metastasectomy and got chemotherapy after operation. Colony stimulating factor was administered to mobilize stem cells from bone marrow to peripheral blood. The stem cell collection was performed 4~10 times(median 4) and the number of collected stem cell was 1.95~7.34x10(8)kg(median 4.87x10(8)/kg). High dose chemotherapy with CTCb (cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day, carboplatin 200 mg/m2/ day) was performed from day -7 to day -4 and peripheral stem cell infusion was performed on day 0 as planned. RESULT: Eleven patients were enrolled in this study. Their median age was 39 years old. The median time for bone marrow recovery was 11 days for neutrophil(>500/mm2) and 28 days for platelet(>50,000/mm2). Packed red blood cell and platelet transfusion were performed in 11 patients. The group whose infused mononuclear cell count was less than 4.0 x 10(8)/kg(n=9) needed longer time for bone marrow recovery than those(n=2) who had more than 4.0 x 10(8)/kg( 20 vs 13 day, p < 0.05 ). For non-hematologic toxicity, none have experienced toxicity more than grade III. There were 2 recurrences of 4 cases with high risk breast cancer at the 22 th, and 25 th month but they are still alive at the 28 th, and 29 th month each. The other 2 cases are alive without recurrences at the 18 th, and 20 th months each. In the recurrent disease group, one case who showed partial response to initial chemotherapy recurred at the 4 th month and died at the 13 th month after PBSCT. The other 5 cases are alive without recurrence at the 1st, 3 rd, 3 rd, 5 th, and 31 th month each. One case with stage IV disease(bone metastasis) is alive without evidence of progression at the 3 rd month. CONCLUSION: High dose chemotherapy with PBSCT can be performed safely. Long term survival of patients with advanced breast cancer would be possible by PBSCT after HDC. Further clinical trials based on larger patient population is required to evaluate clinical efficacy of PBSCT after HDC in high risk and recurrent breast cancer.

The Effects of Mesima-Ex, the Immunomodulator in Curatively Resected Gastric Cancer / 대한암학회지

PURPOSE: The Mesima-Ex is a kind of biologic response modifier, which is extracted from a mushroom called Phellinus linteus. Mesima-Ex consists of various chemical compounds which include protein bound polysaccharide, mucoprotein, triterpenoid, and quinones. Mesima-Ex exerts its antitumor effects by augmenting host immune response without any toxic side effects. In vitro study, Mesima-Ex seems to potentiates antibody dependent cell mediated cytotoxicity (ADCC) and cell mediated cytotoxicity (CMI) against tumor cells. We initiated this study to verify antitumor effects of Mesima-Ex as an antineoplastic agent. MATERIALS AND METHOD: Gastric cancer patients who underwent curative resection with normal hepatic and renal function were eligible. They were divided into two groups by random number table. One group (N=30: Mesima-Ex group) received postoperative adjuvant chemotherapy with 5-FU (500 mg/m2 weekly), adriamycin (40 mg/m2 every 3 weeks) and Mesima-Ex (6 cap daily per Os). Another group (N=37: control group) received 5-FU and adriamycin only without Mesima-Ex. NK (natural killer cell) activity, ADCC (antibody dependent cell mediated cytotoxicity), CD4 , and CD8 cells were measured and an analysis of disease free survival rate of the two study groups was performed. RESULTS: Sixty seven patients were enrolled in this study. Their median age was 55 years old. NK activity (basal activity: 25%) was enhanced significantly at the 2nd, and 4th months in the Mesima-Ex group (28.9%, 43.4%, p0.05). There were no toxic side effects more than grade III from Mesima-Ex administration. The two year disease free survival rate was higher in the Mesima-Ex group than that of the control group (77% vs 58%, p<0.05). CONCLUSION: Mesima-Ex can be used safely as an immunomodulator with standard chemotherapeutic agents for purpose of adjuvant chemotherapy. Mesima-Ex was effective in augmenting host immune response in vitro. The Mesima-Ex group showed a higher two year disease free survival rate than that of the control group.

The Clinical Outcome of IgA Nephropathy After Renal Transplantation / 대한내과학회지

OBJECTIVES: Primary IgA nephropathy is the most common type of glomerulonephritis, which may progress to end stage renal failure in about 30-35% of the cases. The incidence of recurrence of IgA nephropathy in transplanted kidney is approximately 50-60% but IgA nephropathy which is recurred in graft has relatively benign clinical course so the rate of graft loss due to recurrent IgA nephropathy is about 10%. Overall graft survival rate of IgA nephropathy is higher than other glomerular disorders which cause end stage renal disease according to recent clinical studies. However accurate causative disorders of end stage renal failure had seldom been reported by pathologic examination and accurate graft survival rate and recurrence rate of original disease after renal transplantation couldn't be investigated. We performed analysis of clinical outcome and prognosis for IgA group. METHODS: 1259 cases of kidney transplantation were performed in the Severance hospital between Apr 1979 and Dec.1994. We selected 178 cases of those who got renal biopsy and excluded the cases of cadaveric transplants, hepatitis B antigen carrier, diabetes mellitus and not taking cyclosporine A. 178 cases of those were divided into two groups, IgA and nonIgA group. We performed analysis of 5 year graft and patient survival rate between two groups. The IgA group was divided into two group, recurrent and not-recurrent IgA group. We also performed analysis of recurrence rate and graft survival rate between two groups. RESULTS: 1) 62 cases(35.2M) were IgA group and 116 cases were non-IgA group. 2) Male to female ratio of IgA group was 2.9:1, whose age averaged 35 years old. 3) Among 6 cases of the IgA group, 3 cases lost their graft due to chronic rejection, 2 cases due to recurrence and 1 case due to acute rejection. 4) The 5 year graft survival rate of IgA and nonIgA group were 85%, 90% each without statistical significance(p>0.05). The 5 year patient survival rate of IgA and nonlgA group after renal allograft were 100%, 97% each without statistical significance(p>0.05). 5) 266 cases of posttransplant kidney biopsies were performed and 10 cases were diagnosed as recurrent IgA nephropathy with recurrence rate of 15%. 6) Renal insufficiency was noted in 4 cases of recurrent IgA nephropathy, 2 cases of those were chronic renal failure and the other 2 cases lost their graft. The histologic findings of these cases included mesangial widening and proliferation(4 cases), glomerulosclerosis(2 cases), crescent formation(1 cases). 7) The interval between transplantation and recurrence averaged 41 months. 24hr proteinuria and serum level of creatinine at the time of diagnosis averaged 2.6g and 2.2 mg/dl each. 8) Male to female ratio, age, HLA type and degree of HLA match showed no significant difference between nonrecurrent and recurrent IgA group in graft but 5 year graft survival rate of recurrent IgA group was lower than nonrecurrent group with statistical significance(71% vs 83%, p<0.05). CONCLUSION: Recurrent IgA nephropathy in transplanted kidney might be one of major cause of graft loss with chronic rejection. However precise pathologic examination of before k after transplantation on larger patient population and more long term follow-up are advised.

The effects of adjuvant therapy and prognostic factors in completely resected stage IIIa non-small cell lung cancer / 결핵

BACKGROUND: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long term survival. Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. METHODS: From 1990 to 1995, curative resection was performed in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was performed by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. RESULTS: Squamous cell carcinoma was present in 166 patients (59%) ; adenocarcinoma in 86 patients(30%) ; adenosquamous carcinoma in 11 patients (3.9%) ; and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I ; 58 patients in stage II ; and 131 patients in stage IIIa. There were 139 postoperative recurrences which include 28 local and 111 distant failures (20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p<0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage IIIa. Among 131 patients with stage IIIa, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or chemo-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy (p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p <0.0001) were significant prognostic indicators. CONCLUSION: The age and pathologic stage of the NSCLC patients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

The effects of adjuvant therapy and prognostic factors in completely resected stage IIIa non-small cell lung cancer / 결핵

BACKGROUND: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long term survival. Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. METHODS: From 1990 to 1995, curative resection was performed in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was performed by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. RESULTS: Squamous cell carcinoma was present in 166 patients (59%) ; adenocarcinoma in 86 patients(30%) ; adenosquamous carcinoma in 11 patients (3.9%) ; and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I ; 58 patients in stage II ; and 131 patients in stage IIIa. There were 139 postoperative recurrences which include 28 local and 111 distant failures (20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p<0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage IIIa. Among 131 patients with stage IIIa, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or chemo-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy (p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p <0.0001) were significant prognostic indicators. CONCLUSION: The age and pathologic stage of the NSCLC patients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

A Case of Acute Lung Injury Complicated by Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma / 결핵

Transcatheter arterial chemoembolization(TACE) was performed in a 61 year old male patient with hepatocellular carcinoma with 10 cc of Lipiodol and 50 mg of doxorubicin. Three days later, he complained of dyspnea and dry cough. The arterial blood gas study revealed moderate hypoxemia and hypocarbia. The chest PA showed acute pulmonary edema with bilateral pleural effusion. To rule out the possibilities of acute respiratory failure caused by infection, pulmonary embolism or congestive heart failure, we performed several laboratory studies. The blood and sputum culture studies revealed negative results for bacterial growth. The echocardiogram was normal. The abdominal CT scan and MR imaging revealed no thrombus or mass lesion in the inferior vena cava. So we concluded pulmonary oil embolism induced by lipiodol as the cause of acute lung injury. Four weeks later, clinical symptoms and chest x-ray were markedly improved with conservative care. We report a case of acute lung injury after TACE with lipiodol and doxorubicin, with review of literatures.