Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

BACKGROUND: The aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study. METHODS: Ten rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting. RESULTS: The HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged. CONCLUSIONS: We concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite cylinder showed better results for the sustained morphology.

Gemcitabine versus Gemcitabine Combined with Cisplatin Treatment Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gemcitabine is the most active agent to treat unresectable pancreatic cancer. The superiority of combining other drugs with cisplatin is still controversial; therefore, we performed a retrospective analysis of gemcitabine versus gemcitabine combined with cisplatin to determine the treatment outcomes for patients with locally advanced or metastatic pancreatic cancer. MATERIALS AND METHODS: From 2001 to 2007, we enrolled 60 patients who were treated with gemcitabine or gemcitabine combined with cisplatin for locally advanced or metastatic pancreatic cancer. Gemcitabine 1, 000 mg/m2 (G) was administrated at day 1 and day 8 every 3 weeks. Cisplatin 60 mg/m2 was added at day 1 every 3 weeks to the gemcitabine schedule (GP). RESULTS: Number of G: GP was 34: 26, locally advanced to metastatic ratio was 35% to 65% in group G and 46% to 54% in group GP. Median follow up duration was 29 months. The median number of chemotherapy cycles was 4 (range: 2~11) for the G group, and 4 (range: 1~11) for the GP group. The response rate of the G and GP groups was 17% and 11%, respectively. The progression free survival (PFS) was 4.5 months and 2.8 months, respectively, for the G and GP groups. The overall survival (OS) was 10.7 and 8.7 months respectively, for the G and GP groups, but there is no statistically significant difference of the PFS (p=0.2396) and OS (p=0.4643) between the 2 groups. The hematological toxicity profile was similar (the grade III neutropenia and thrombocytopenia was 4.4% and 3.1%, respectively, in G group, and 7.5% and 2.8%, respectively, in the GP group). But non-hematological toxicities such as skin rash, abnormal liver function and nausea/vomiting were observed in 3 patients of the GP group. On the prognostic factor analysis, no factors predicted a longer PFS and OS for both the G and GP groups. CONCLUSIONS: Gemcitabine single treatment might be more tolerable and it had the same efficacy compared to cisplatin combination treatment in this retrospective study.

The Clinical Characteristics and Treatment Results of Ocular Adnexal Lymphoma

PURPOSE: To assess the clinical pattern, the histopathological findings, the response to treatments, the recurrence pattern and the prognosis of malignant lymphoma in the ocular adnexa. METHODS: This study was performed on 22 total eyes from 17 patients who were diagnosed with ocular adnexal malignant lymphoma. We retrospectively analyzed the medical records for patient information including the histological classification based on age, the gender of each patient, the symptoms and signs at the initial diagnosis, the presence of binocular invasion, the findings of the surgical biopsy, the clinical stage of each patient's tumor, and the treatment methods used and their effectiveness. The mean follow-up period was 24.8 months. RESULTS: The mean age of patients studied was 46.8 years old. Six females and 11 males were included in the study. Fifteen cases consisting of 20 total eyes represented extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT). Five of seven patients (71.4%) whose lymphoma occurred within the conjunctiva relapsed after irradiation or chemotherapy, and four of the relapsed patients were salvaged with further therapy. CONCLUSIONS: Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) constituted 88.2% of all lymphomas involving the ocular adnexa. Lymphoma in the ocular adnexa responded well to conventional treatment, but the recurrence rate of lymphoma in the conjunctiva was significantly high.

Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea-induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line

Hydroxyurea is commonly used to treat hematologic disorders and some type of solid tumors, but the mechanism for its therapeutic effect is not clearly known. In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21Waf1, p27Kip1 and p53. Rat hepatoma McA-RH7777 cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth in a dose-dependent manner. But, this growth inhibition was not caused by necrosis or apoptosis but instead was associated with cell senescence-like change as evidenced by senescence associated-beta-galactosidase staining, and cells arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cells with hydroxyurea. But, the expression of p21Waf1 was increased, while p27Kip1 and p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA-RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21Waf1 over-expression.

Primary Liposarcoma of the Mediastinum: Computed Tomographic (CT) Findings

PURPOSE: To describe the CT findings of primary liposarcoma of the mediastinum, and to correlate these with the pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed the medical records, chest radiographs and CT scans of four male patients with histopathologically proven primary liposarcoma of the mediastinum treated between September 1996 and April 2002. The CT scans were analyzed by two radiologists, and final decisions were reached by consensus. They were analysed in terms of tumor size and location, enhancement pattern, the pattern of the fat component, calcification, mass effect, pleural effusion, lymph node enlargement, pericardial effusion, tumor extension to the costophrenic junction, and adjacent organ invasion. RESULTS: All patients presented with dyspnea and chest pain. Pathologic subtypes, which were well-differentiated and pleomorphic, were myxoid (n=2) and mixed (n=2). The transverse diameter of the mass ranged from 10.5 to 21 cm. All tumors were located in the anterior mediastinum, and all had lobulated margins. Soft-tissue attenuation predominance (n=2) occurred in the myxoid type, and roughly equal amounts of fat and soft-tissue attenuation (n=2) were present in the mixed type. A small area at calcification was seen in the mixed type (n=1). Mass effect on mediastinal structures was demonstrated in all patients. In three patients, the tumor draped around and conformed to the shape of the costophrenic junction. Chest wall invasion occurred in one patient. CONCLUSION: Findings of an anterior mediastinal location, fat attenuation, mass effect, the invasion of adjacent organs, and a lobulated margin strongly suggested mediastinal liposarcoma. CT attenuation of the lesions correlated closely with the degree of histologic differentiation.

A case of mantle cell lymphoma associated with tuberculous pleurisy / 대한내과학회지

Mantle cell lymphoma is relatively rare and generally difficult to differentiate from other types of lymphoma. The clinical course is very aggressive. We recently experienced a very rare patient with pleural mantle cell lymphoma associated with pleural tuberculosis. A 60-year-old female patient was admitted because of dyspnea. Chest films revealed pleural effusion. Analysis of pleural effusion was not diagnostic, but we started therapeutic trial for tuberculosis. After 2 months of anti-tuberculosis medication, the pleural effusion was not improved. We repeated pleural biopsy. Histologic finding was chronic inflammation but AFB culture was positive. After another 3 months of medications for tuberculosis, there was no improvement. We repeated pleural biopsy and thoracentesis. Repeated biopsy and the result of flow cytometry of pleural effusion were consistent with mantle cell lymphoma. We started chemotherapy for lymphoma. After three cycles of chemotherapy, pleural effusion was decreased, but she worsened and died of hepatic failure probably due to viral hepatitis.

Prevalence of Drug-resistances in Patients with Pulmonary tuberculosis and Its Association with Clinical characteristics at One Tertiary Rcferral Hospital in Pusan, Korea / 결핵

BACKGROUND: The incidence of drug-resistant tuberculosis has recently decreased in Korea. However, it is still one of the major obstacles in treating pulmonary tuberculosis. This study was performed to determine the prevalence and clinical characteristics associated with drug-resistance in pulmonary tuberculosis at the tertiary referral hospital in Pusan, Korea. METHODS: The medical records of 138 patients, who had been diagnosed as active pulmonary tuberculosis were retrospectively reviewed, and results of drug susceptibility from May 1997 to June 2000. The relationships among those with a history of previous tuberculosis treatment, the extent of lung involvement, the presence of cavities on the initial chest X-ray films and patterns of drug resistance were analyzed. RESULTS: The total number of patients who had drug resistance to at least one drug was 55(39.9%). Among them 34(24.6%) had resistance to isoniazid(INH) and rifampin(RFP). There was drug resistance in 20(22%) of 91 patients without previous tuberculosis therapy, and among them 9(9.9%) were multi-drug resistant. Thirty-two(74.5%) out of 47 patients with previous therapy were drug-resistant and 25(53.2%) were multidrug resistant. For all 138 patients, resistance to INH was the was the most common(34.1%), followed by RFP(26.1%) and ethambutol(EMB)(14.5%). Drug resistance to INH, RFP, PZA and streptomycin(SM) were independently assiciated with a history of previous treatment(odds ratio;9.43, 0.09, 8.93 and 21.6 respectively, p<0.01). The extent of lung involvement on the chest films was significantly associated with the drug resistance to INH and RFP(odds ratio;2.12 and 2.40 respectively, p<0.01). The prevalence of drug resistance to RFP, INH and RFP was significantly more common in patients with a cavitary lesion on the chest films by multivariate analysis(odds ratio;4.17 and 4.81 respectively, p<0.05). CONCLUSION: This study revealed that patients with a prior treatment history for pumonary tuberculosis, and the presence of a cavitary lesion on chest films had a higher prevalence of anti-tuberculosis drug resistance. A very careful clinical and microbiological examination is needed for patients with such characteristics.

Peripheral Lung Mass Attached to The Pleural Diagnostic Effectiveness of Ultrasonically Guided Biopsy

PURPOSE: To evaluate the usefulness of real-time ultrasound-guided biopsy as an aid in diagnosing pleural attached lung lesions. MATERIALS AND METHODS: Over a 2-year period (March 1992 through February 1994), 52 US-guided diagnostic biopsies were performed in 50 patients with peripheral lung lesions in contact with chest wall. 15 cases were performed with gun biospy and 37 cases with fine needles. Final diagnosis was confirmed by surgery and clinical follow-up. RESULTS: In 44 of 52 cases(84.6%), we obtained histologic or cytologic material by US-guided biopsy. Diagnostic accuracy and tissue type specific accuracy for malignancy were 83.9%(26/31) and 67.7% (21/31), respectively. Eighteen case% were reported to be benign and one of them was proven to be metastatic lesion. We could not find any complications such as hemoptysis or pneumothorax. CONCLUSION: Ultrasound-guided biopsy is a simple, safe and accurate diagnostic procedure for evaluation of peripheral lung lesion attached to the pleura.

Congenital Esophageal Stenosis due to Tracheobronchial Remnants: A case report

Congenital esophageal stenosis due to tracheobronchial remnants is one of main forms of congenital esophageal stenosis, and it was first described by Frey and Duschel in l936. An 18-month-old male presented with underdevelopment and dehydration state due to persistent vomiting several times per day since 3 months after his birth. Esophagogram revealed an elongated and diiated esophagus with marked stenosis at distal portion. Partial distal esophagectomy was performed. Histologically, the thickened esophageal wall is composed of tracheobronchial remnants including hyaline cartilages, mucous glands, and ductal structures lined by ciliated respiratory epithelium under stratified squamous mucosa.

Congenital Esophageal Stenosis due to Tracheobronchial Remnants: A case report

Congenital esophageal stenosis due to tracheobronchial remnants is one of main forms of congenital esophageal stenosis, and it was first described by Frey and Duschel in l936. An 18-month-old male presented with underdevelopment and dehydration state due to persistent vomiting several times per day since 3 months after his birth. Esophagogram revealed an elongated and diiated esophagus with marked stenosis at distal portion. Partial distal esophagectomy was performed. Histologically, the thickened esophageal wall is composed of tracheobronchial remnants including hyaline cartilages, mucous glands, and ductal structures lined by ciliated respiratory epithelium under stratified squamous mucosa.