Double primary lung adenocarcinoma diagnosed by epidermal growth factor receptor mutation status / 영남의대학술지

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.

Simultaneous chylothorax and chylous ascites / 영남의대학술지

Chylothorax or chylous ascites are rare manifestations of liver cirrhosis. We report a rare case of simultaneous chylothorax and chylous ascites in a patient with hepatitis B virus-related liver cirrhosis. A 76-year-old woman was referred to our hospital with a pleural effusion on her right side. She had no history of recent medical procedures, trauma or tumor. There was no evidence of mass or thoracic duct obstruction in a computed tomography scan. Pleural fluid and ascites were confirmed as chylothorax and chylous ascites by chemistry analysis. Despite thorough conservative care, there was no improvement. Pleurodesis was planned, but hepatic encephalopathy developed suddenly and she did not recover.

Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

Hippo/YAP signaling is implicated in tumorigenesis and progression of various cancers. By inhibiting a plethora signaling cascades, resveratrol has strong anti-tumorigenic and anti-metastatic activity. In the present study, we demonstrate that resveratrol decreases the expression of YAP target genes. In addition, our data showed that resveratrol attenuates breast cancer cell invasion through the activation of Lats1 and consequent inactivation of YAP. Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation. Further, resveratrol in combination with other agents that inactivate RhoA or YAP showed more marked suppression of breast cancer cell invasion compared with single treatment. Collectively, these findings indicate the beneficial effects of resveratrol on breast cancer patients by suppressing the RhoA/Lats1/YAP signaling axis and subsequently inhibiting breast cancer cell invasion.

Double primary lung adenocarcinoma diagnosed by epidermal growth factor receptor mutation status / 영남의대학술지

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.

Simultaneous chylothorax and chylous ascites / 영남의대학술지

Chylothorax or chylous ascites are rare manifestations of liver cirrhosis. We report a rare case of simultaneous chylothorax and chylous ascites in a patient with hepatitis B virus-related liver cirrhosis. A 76-year-old woman was referred to our hospital with a pleural effusion on her right side. She had no history of recent medical procedures, trauma or tumor. There was no evidence of mass or thoracic duct obstruction in a computed tomography scan. Pleural fluid and ascites were confirmed as chylothorax and chylous ascites by chemistry analysis. Despite thorough conservative care, there was no improvement. Pleurodesis was planned, but hepatic encephalopathy developed suddenly and she did not recover.

Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.

Retroperitoneal Hemorrhage after Bone Marrow Aspiration and Biopsy in an Essential Thrombocythemia Patient / 대한내과학회지

Bone marrow examination is useful in the diagnosis and staging of hematologic disease. This procedure is generally considered safe; however, there are several adverse events associated with bone marrow biopsy. The most frequent and serious adverse event is hemorrhage. Risk factors include coagulopathy, myeloproliferative disorders, and anticoagulant or antiplatelet medications. Most hemorrhage is local hematoma; however, infrequently retroperitoneal hemorrhage occurs. In the case of massive hemorrhage, operation or angiographic embolization may be required. We report on a case of retroperitoneal hemorrhage after bone marrow aspiration and biopsy in an essential thrombocythemia patient.

Ovarian Metastasis from Non-Small Cell Lung Cancer Responding to Erlotinib / 이화의대지

Ovarian cancer is generally primary cancer and less frequently originates from metastasis from non-gynecological cancer. Ovarian metastasis from lung cancer represents only 2~4% of all ovarian metastatic cancers. We report a case of ovarian metastasis of non-small cell lung cancer with epidermal growth factor receptor mutation. The patient underwent cytoreductive surgery for the ovarian mass and erlotinib therapy for the metastatic lung cancer. Erlotinib therapy markedly decreased the size of lung mass.

A Multicenter Retrospective Analysis of the Clinical Features of Pernicious Anemia in a Korean Population

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B12 deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

A case of radiation-induced sternal osteosarcoma after treatment of breast cancer / 대한내과학회지

Radiation-induced osteosarcoma is a very rare complication of radiation therapy, with a poor prognosis. We experienced a case of radiation-induced osteosarcoma of the sternum, in a patient who had had breast cancer treated with surgery, adjuvant chemotherapy, and adjuvant radiation therapy 6 years earlier. A 53-year-old woman complained of a painful anterior chest wall mass. The mass was diagnosed as osteosarcoma on biopsy. The radiation-induced osteosarcoma had an aggressive nature.

A case of advanced thymic carcinoma that was resected after concurrent chemoradiotherapy / 대한내과학회지

Thymic carcinoma is a rare, but aggressive, tumor that often metastasizes to regional lymph nodes and distant sites and often has a poor prognosis. Although the efficacy of induction therapy in thymic carcinoma is unclear, we report the clinical course of a patient who underwent complete surgical resection after effective induction chemoradiotherapy. A 66-year-old man was diagnosed with a poorly differentiated thymic carcinoma (Masaoka stage III). The tumor was considered unresectable due to sternal invasion and surrounding fat infiltration. Two cycles of chemotherapy, consisting of paclitaxel (180 mg/m2 on D1) and cisplatin (80 mg/m2 on D1) combined with mediastinal radiotherapy (total 50 Gy) were performed concurrently; the mass decreased to a resectable size. Subsequently, he received adjuvant chemotherapy and adjuvant radiation therapy. He is currently alive and ambulatory and has remained disease-free for 19 months. This case demonstrates that induction chemoradiotherapy with paclitaxel and cisplatin may be tolerated and useful for patients with locally advanced thymic carcinoma.

A Case of Graves' Disease associated with Idiopathic Thrombocytopenic Purpura / 대한내분비학회지

The association of Graves' disease and idiopathic thrombocytopenic purpura(ITP) is a rather rare, but well documented condition, and has also been reported a few times in Korea. At present, two main hypothetical mechanisms are used to explain the association of the two diseases; the presence of autoimmunity, which leads to both diseases, and activation of the reticuloendothelial system by thyroid hormone. A 33 year old female patient visited our hospital with mucosal bleeding and purpura over her entire body of 3 days duration. Her initial platelet count was 2x109/L, and the thyroid function tests showed a suppressed TSH level of 0.09 mU/L(0.4~3.1) and elevated levels of triiodothyronine and free thyroxine. The levels of anti-thyroglobulin Ab anti-TPO Ab, and anti-TSH receptor Ab were also elevated. The clinical, laboratory and bone marrow findings were compatible with Graves' disease associated with ITP. She was treated with methylprednisolone and propylthiouracil, after which her platelet count increased and thyroid function normalized. We report a case of Graves' disease associated with ITP, which was treated well by glucocorticoid and antithyroid medications

A Case of Adrenocortical Carcinoma with Concurrent Cushing's Syndrome and Primary Aldosteronism / 대한내분비학회지

An adrenocortical carcinoma is a rare malignancy, which is associated with a poor prognosis. Eighty percent of adrenal tumors are functional, and commonly secrete glucocorticoids alone (45%), glucocorticoids and androgens (45%) or androgen alone (10%). Less than 1% of all cases secrete aldosterone. A case of a 75 year old female patient was experienced, presenting with anadrenocortical carcinoma and associated concurrent Cushing's syndrome and primary aldosteronism. She had complained of left flank pain for 5 months, and also showed clinical features of Cushing's syndrome, hypertension, hypokalemia and a left abdominal mass. An abdominal CT* demonstrated a large left adrenal mass, with necrosis, and a hemorrhage in the left upper abdomen. The plasma renin activity was 0.51 ng/ml/hr, and the serum aldosterone level was increased by 46.4 ng/dL. A low and high dose dexamethasone suppression test revealed no suppression. Histologically, the tumor was diagnosed as a adrenocortical carcinoma. After complete removal of the mass, she received mitotan and prednisolone as adjuvant therapies. Liver and bone metastasis occurred after 6 months of treatment, so was treated with palliative radiotherapy for the bone metastasis

A Case of Adrenocortical Carcinoma with Concurrent Cushing's Syndrome and Primary Aldosteronism / 대한내분비학회지

An adrenocortical carcinoma is a rare malignancy, which is associated with a poor prognosis. Eighty percent of adrenal tumors are functional, and commonly secrete glucocorticoids alone (45%), glucocorticoids and androgens (45%) or androgen alone (10%). Less than 1% of all cases secrete aldosterone. A case of a 75 year old female patient was experienced, presenting with anadrenocortical carcinoma and associated concurrent Cushing's syndrome and primary aldosteronism. She had complained of left flank pain for 5 months, and also showed clinical features of Cushing's syndrome, hypertension, hypokalemia and a left abdominal mass. An abdominal CT* demonstrated a large left adrenal mass, with necrosis, and a hemorrhage in the left upper abdomen. The plasma renin activity was 0.51 ng/ml/hr, and the serum aldosterone level was increased by 46.4 ng/dL. A low and high dose dexamethasone suppression test revealed no suppression. Histologically, the tumor was diagnosed as a adrenocortical carcinoma. After complete removal of the mass, she received mitotan and prednisolone as adjuvant therapies. Liver and bone metastasis occurred after 6 months of treatment, so was treated with palliative radiotherapy for the bone metastasis

Intracavitary 166 Holmium - chitosan Complex Therapy in Patients with Malignant Peritoneal or Pleural Effusions / 대한암학회지

PURPOSE: Most malignant peritoneal or pleural effusions caused by advanced malignancy are unresponsive to systemic chemotherapy except for chemotherapy sensitive tumors, and they are equally ineffective to regional therapy or radiotherapy. Thus, for the purpose of palliating the symptoms related to malignant effusion and to reduce fluid reaccumulations, we evaluated the therapeutic feasibility and efficacy of intracavitary ' Ho-CHICO (chito- san complex) instillation for intractable malignant effusions. MATERIALS AND METHODS: Thirty one patients with cytologically or pathologically proven malignant effusions underwent intracavitary 166Ho-CHICO therapy from May 1996 to March 1998 at Ajou University Hospital. The subjective and objective responses were evaluated 4 weeks after the treatment, including the changes of symptoms, weight, abdominal girth, doses of diuretics, frequencies and amounts of repeat aspirations for fluid reaccumulations, and imaging studies of chest radiograph and ultrasounds. RESULTS: The response rates treated with Ho-CHICO were 50% in patients with peritoneal effusion and 46% in patients with pleural effusion (overall 49%). The response rates between 166Ho-CHICO doses of 50-80 mCi and 90-100 mCi were similar (50% vs 47%). Response rate of 70% was noted in patients with even distribution of radioisotope on the post-therapy scan, but, the response rate was lower in cases with focal (44%) and uneven (29%) distribution pattern. There was no difference in response by the effusion sites. All patients tolerated intracavitary 166Ho-CHICO instillation well, although the majority of patients experienced Grade I/II side effects such as pain, fever, weakness and dyspnea. But, no serious complications of Grade lII or IV degree were observed with 166Ho-CHICO therapy. CONCLUSION: Intracavitary 166Ho-CHICO instillation was clinically efficacious in controlling malignant effusions without a significant toxicity seen with conventional sclerotic therapy. The therapeutic modality appeared to offer similar benefits obtained with the conventional intracavitary therapy.

A Case of Non-Immune Mediated Marrow Suppression Associated with Phenytoin Therapy / 대한혈액학회지

Diphenylhydantoin (DPH) is one of the most widely used anticonvulsants for treatment and prevention of seizures. However it is frequently associated with drug-induced leukopenia. Hypersensitivity reactions to phenytoin are well recognized and can be severe. Phenytoin is associated with serious hematologic side effects such as agranulocytosis, thrombocytopenia, red cell aplasia and hemolytic anemia, either through humoral or cell-mediated immunemechanism. We describe a 57-year-old male patient who developed a severe granulocytopenia while taking phenytoin for 66 days in the total amount of 21.6 gram. Bone marrow examination showed isolated depletion of myeloid elements. After 10 days of phenytoin withdrawal and G-CSF treatment, the patient recovered from granulocytic suppression. Using in vitro culture, marrow suppression associated with phenytoin therapy was felt to be non-immune mediated marrow suppression.

A Case of Copper Intoxication / 대한신장학회잡지

Copper is an essential trace element for numerous vital enzymes. Recently, copper can be used clinically as assessing the disease activity, prognosis, therapeutic effect and early prediction of recurrence in patient with neoplasia. But overloading of copper can cause fatal outcome. Copper intoxication is usually encountered following accidental ingestion or suicidal intoxication. A 43-year old male was admitted because of epigastric pain and hematuria after ingestion of the copper hydroxide and organophosphate for suicidal purpose. The laboratory findings showed that the serum and urinary copper concentration are elevated, then the acute renal failure, hemolytic anemia and liver injury progressed. With conservative management, the hemolytic anemia was improved, but disseminated intravascular coagulation with sepsis and respiratory failure by pneumonia were developed, and then finally expired on the eighth hospital days. We experienced a case of a patient who presented with acute renal failure, hemolytic anemia and liver injury after ingestion of copper, and we reported with review of literature.

Endoscopic Mucosal Resection for Premalignant Lesions and Early Gastric Cancer / 대한내과학회지

OBJECTIVES: Gastrectomy with lymph node dissec tion is the standard treatment for early gastric can cer(EGC). However, patients who have high risks demand modifications in surgical treatment for EGC. Recently, endoscopic mucosal resection(EMR) has become accepted in many institutions as a treatment for cancerous mucosal lesions of the stomach. Thus we investigated the efficacy and safety of EMR prospectively in the patients with EGC who have high risks in surgery and those with premalignant lesions. METHOD: Twenty-five patients were treated with EMR, thirteen were EGC and twelve were premalignant lesions such as tubular adenoma, severe dysplasia. We used standard snare method and endoscopic mucosal resection using a band ligation kits(EMRL). RESULTS: The complete resection rate at the first step of EMR was 100%(12/12) in premalignant lesions, 76.9%(10/13) in EGC. Of three EGC resected incomple tely at the first step, one patient was treated by surgery and two patients underwent the third step of EMR. The final complete resection rate was 92%(23/25) and it was 100%(12/12) in the premalignant lesions, 84.6%(11/13) in EGC. The final complete resection rate in according to the methods was 100%(5/5) by standard snare method, 75%(6/8) by EMRL. As pathologic results, all cases of EGC were limited to the mucosa. No serious complications such as perforation, major bleeding were encountered. CONCLUSION: We consider that EMR is effective and safe in treatment of the patients with EGC who have high risks in surgery and those with premalignant lesions.

Unexposed Ampullary Cancer / 대한소화기내시경학회지

BACKGROUND: Ampullary cancer is a malignant lesion in the pancreatobiliary system with a relatively good prognosis because of its slow growth, early appearance of symptoms and high resectability. Hndoscopic retrograde cholangiopancreaticography(ERCP) is an important and useful method in the diagnosis of ampullary cancer because it identifies the location of lesions endoseopically and by opacification of the bilio-pancreatic ducts and allows confirmation by biopsy, But the diagnostic accuracy of endoscopic forcep biopsy was variable according to the macroscopic appearance of ampullary cancer. In unexposed type ampullary cancer, biopsy after endoscopic sphincterotomy or intraluminal cannulatian biopsy has been recommended because the cancer tissue was either not visible at all or barely visible from the lumen of the duodenum. The purpose of this study was to evaluate the contribution of endoscopic sphincterotomy to the diagnosis of ampullary cancer and to compare the clinical eharasteristics of unexposed type ampullary cancer with those of exposed type ampullary cancer. METHOD: Thirty-one cases of the ampullary cancers over the past 5 years were reviewed. Macroscopically, thirty one ampullary cancers were classified into two types. The unexposed type ampullary cancer was defined normal ampullary mucosa with or without protruding. The exposed type ampullary cancer was defined abnormal ampullary mucosa including nodular, ulcerative, nodulo-ulcerative and polypoid appearance. Ampullary cancers were diagnosed preoperatively by forcep biopsy, biopsy after endoscopic sphincterotomy, or brushing cytology. RESULT: The proportion of unexposed type in ampullary cancer was 29%(9 cases). There were no differences of age, sex, diagnostic clue, distal common bile duct(CBD) shape and CBD dilatation by ERCP between unexposed and exposed type ampullary cancers. The serum bilirubin, alkaline phosphatase and GGT were lower in unexposed type comparting with exposed type. The unexposed ampullary cancers could be diagnosed with biopsy after endoscopic sphincterotomy except one case. Biopsy samples were successfully obtained immediately after sphincterotomy in 3 patients and a few days (3 days later-1 month later) after sphincterotomy in 5 patients. CONCLUSION: Weconsider the possibility of unexposed ampullary cancer in cases of jaundice or duct dilatation with normal ampullary cancer in cases of jaundice or duct dilatation with normal ampulla mucosa and should perform biopsy after endoscopic sphincterotomy.

The Effect of Vitamin E on the Composition of inflammatory Cells in Alveoli after Paraquat Intoxication in Rats / 결핵

BACKGROUND: Acute pulmonary injury by paraquat are caused by multiple mechanisms including direct injury with oxygen free radicals and several mediators released from inflammatory cells. In order to clarify whether vitamin E could reduce tissue damages induced by intraperitoneal administaration of paraquat and to investigate the pathogenetic mechanisms of paraquat-induced pulmonary injury, vitamin E as a free radical scavenger was administered. METHODS: Rats were divided into three groups (group 1: control, group 2 : paraquat treated group, group 3 : paraquat and vitamin E treated group). Animals were sacrificed on day 1, day 2, day 3, and day 8 after the administration of saline, paraquat, or paraquat/vitamin E. RESULTS: Treatment with vitamin E decreased the death rate of rats treated with paraquat. Comparing with control group (1.37 x 106/ml), mean total cell counts recovered from the lavage fluid from animals treated with paraquat (1.65 x 106/ml) were increased(p=0.06). Magnitudes of increament of the total cell counts on the Day 8 in the vitamin E treated group were smaller than those of the animals treated with paraquat alone. The neutrophils began to appear in significant amounts in the lavage fluid on Day 8 after the administration of paraquat(37.0 + 12.7%). A significant decreasing neutrophil concentration at Day 8 was observed in the paraquat/vitamin E treated group(20.6 + 13.4 %). Histologically the degree of pulmonary fibrosis was most prominent in the paraquat treated group while diffuse alveolar damage was continuously observed in the paraquat/vitamin E treated group and extensive interstitial lymphocytic infiltration was seen in the paraquat/vitamin E treated group. The paraquat/vitamin E treated group showed the less histologic changes. CONCLUISON: In this study vitamin E acting as a scavenger of neutrophil-derived free radicals and suppressant of lipid peroxidation, seemed to be the effective antioxidant in the inhibition of paraquat-induced pulmonary injury.