Young-Pil Wang

Fluoroscopy-aided thoracoscopic resection of pulmonary nodule localized with contrast media

BACKGROUND The pulmonary nodules have become the major indication of video-assisted thoracic surgery (VATS). Recently, several preoperative or intraoperative techniques for identifying small or deeply seated pulmonary nodules have facilitated thoracoscopic resection. We describe the new technique for detecting difficult lesions. METHODS Preoperatively, we marked the visceral pleura near the pulmonary nodules with dye, simultaneously injected contrast media (1 water-soluble Optiray [Mallinckrodt Medical Inc, Quebec, Canada], 18 barium sulfate, 11 Lipiodol [Laboratoire Guerbet, Aulnay-sous-Bois, France]) into or around the nodule under computed tomography (CT) guidance. During VATS, we were able to easily and accurately detect and resect all the nodules localized with contrast media, of which the radiopacity was visualized on the portable fluoroscopic monitor. RESULTS Between February 1996 and December 1998, we thoracoscopically resected 30 nodules in 28 patients (13 were women; age, 53 +/- 14 years). The resected nodules were 17 +/- 7.6 mm (range; 4 to 32 mm) in size, and 8.9 +/- 8 mm (range, 2 to 34 mm) in depth. The pathologic diagnosis of the nodules was benign in 20 and malignant in 10 (six primary cancers of lung and four metastatic cancers). There were only minor complications related CT localization. CONCLUSIONS This new technique can help the surgeons detect and resect the difficult lesions with safety and rapidity by VATS without thoracotomy.

Thoracoscopic plication of diaphragmatic eventration using endostaplers

Unilateral diaphragmatic eventration and paralysis require plication in cases of progressive dyspnea on exertion and recurrent respiratory infection. The patient, a 40-year-old woman, who had complained of worsening dyspnea on exertion and elevation of the left diaphragm on chest radiographs for 4 years, underwent plication by thoracoscopy with knifeless endostaplers. Improvements in pulmonary functions and dyspnea on exertion have been maintained for 14 months.

Merlin Neutralizes the Inhibitory Effect of Mdm2 on p53

The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function. The results showed that merlin increased the p53 stability by inhibiting the Mdm2-mediated degradation of p53, which accompanied the increase in the p53-dependent transcriptional activity. The stabilization of p53 by merlin appeared to be accomplished through Mdm2 degradation, and the N-terminal region of merlin was responsible for this novel activity. This study also showed that overexpression of merlin-induced apoptosis of cells depending preferentially on p53 in response to the serum starvation or a chemotherapeutic agent. These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.

The TGF-β1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients

BackgroudThe underlying molecular and cellular mechanisms of radiation pneumonitis (RP) are very complex. Several biological factors need to be considered together with the well known dosimetric parameters for understanding the molecular events in developing RP in lung cancer patients. The aim of this study was to correlate the variations of the cytokine levels in lung cancer patients during radiation therapy (RT) with the occurrence of symptomatic RP.MethodsThirty-four lung cancer patients who received three-dimensional conformal radiation therapy were evaluated prospectively. Serial blood samples before, at the beginning, in the middle of, at the end of RT and 2 and 4 weeks after RT were analyzed for IL-1α, IL-6, IL-10, TNF-α and TGF-β1 by performing enzyme-linked immunosorbent assay. The predictive values of dosimetric factors for RP were evaluated, too.ResultsOverall, 8 patients (23.5%) had grade ≥ 2 RP. By serial measurement of cytokines level, only the TGF-β1 level showed a correlation to the symptomatic RP. None of the other cytokines, IL-1α, IL-6, IL-10 and TNF-α level was correlated with the risk of RP. The mean pretreatment TGF-β1 level did not differ between RP and non-RP groups. However, during the period of radiation treatment, the TGF-β1 level began to increase at the end of RT in the RP group and became significantly higher 4 weeks after RT (p = 0.007). Using an ANOVA model for repeated-measures, we found significant associations between the changes of TGF-β1 during the time course of the RT and the risk of developing RP (p < 0.001). Most of the dosimetric factors showed a significant association with RP.ConclusionOur results show that the changes of TGF-β1 could be correlated with RP and the incorporation of the biological parameters into the dosimetric data could be useful for predicting symptomatic RP.

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients.

Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P=0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (P<0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R2=0.3499; P<0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

Inhibition of NF-κB activation by merlin☆

Abstract The neurofibromatosis type 2 (NF2) gene encodes an ezrin–radixin–moesin (ERM) related protein, referred to as either merlin or schwannomin, that is known to be a tumor suppressor. NF-κB signaling is known to be important for controlling cellular proliferation and protecting against apoptosis. In this report, merlin was demonstrated to be effective in suppressing the NF-κB signaling pathway in NIH3T3 and C6 cells. In addition, merlin blocked the tumor necrosis factor-α (TNF-α)-induced NF-κB–DNA binding mediated via the inhibition of degradation of IκBα and blocked the activation of NF-κB-dependent transcription. A reporter gene assay using deletion mutants of NF2 showed that the N-terminus (amino acids 1–130) of merlin may be important for its inhibition of NF-κB activation. These results show that merlin acts as a negative regulator of the NF-κB signaling pathway.

Prognostic value of SUVmax and metabolic tumor volume on 18F-FDG PET/CT in early stage non-small cell lung cancer patients without LN metastasis

This paper aimed to evaluate the prognostic value of maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the primary tumor on (18)F-FDG PET/CT scan in early stage non-small cell cancer (NSCLC) patients without lymph node (LN) metastasis. In the experiment, eighty NSCLC patients pathologically staged as T1N0 or T2N0 were included (M:F=50:30; mean age, 64.8 years). All patients had preoperative (18)F-FDG PET/CT scan and curative surgery. FDG uptake in the primary tumor was measured by SUVmax and MTV with various SUV threshold values. SUVmax, MTV of the primary tumor, age, tumor size, histology and differentiation grade were analyzed for association with disease-free survival (DFS). The experimental results showed that the histology types included adenocarcinoma (n=58), squamous cell carcinoma (n=20), and others (n=2); Twenty-two (27.5%) of the 80 patients had a recurrence during follow-up at a median time of 29.1 months; The median SUVmax was 5.26, and the median MTV2.5 was 2.2 cm(3). Univariate analysis showed higher SUVmax (>4), greater MTV (MTV2.5 >4 cm(3)), and non-squamous histology were significantly associated with shorter period DFS (p=0.001, p=0.030 and p<0.001). In multivariate analysis, higher SUVmax (p=0.004) and adenocarcinoma histology (p=0.005) were associated with shorter DFS. Therefore, high SUVmax (>4) of the primary tumor on preoperative (18)F-FDG PET/CT scan is an independent prognostic factor of shorter DFS in early stage of NSCLC.

Surgical Resection of Pulmonary Metastasis from Renal Cell Carcinoma

Background Renal cell carcinoma has shown less response to systemic therapies including chemotherapy, radiation, and immunotherapy than other cancers. Surgery has therefore become an important treatment tool. The protocol for treatment is the same for pulmonary metastasis of renal cell carcinoma. We performed surgery for pulmonary metastatic renal cell carcinomas and analyzed the results. Materials and Methods We retrospectively analyzed 15 patients who had undergone pulmonary metastasectomy from renal cell carcinoma at our hospital from January 2005 to December 2009. Results No patients had extrathoracic metastatsis. The mean age was 60.2 years (range 35~73). There were 12 male and 3 female patients. The number of synchronous and metachronous patients were 8 and 7, respectively. The mean survival times of synchronous and metachronous patients were 32.6 and 42.9 months, respectively. 6 patients had single lesions and 9 patients had multiple (more than 3) lesions. The surgical procedures included wedge resection (10), lobectomy (2), wedge resection with segmentectomy (2), and segmentectomy (1). Median observation and survival time were 54.1 and 34.9 months. The 1-year and 3-year survival rates were 80% and 50%, respectively. Conclusion Pulmonary resection for pulmonary metastatic renal cell carcinoma was found to be a safe and effective treatment modality when complete resection was performed.

Lung Cancer Associated with Sarcoidosis - A case report -

Sarcoidosis is a somewhat common pulmonary disease, but the concurrence of lung cancer and sarcoidosis in the same patient is very rare. Because sarcoidosis usually presents as mediastinal lymphadenopathies, this concurrence in a lung cancer patient detected radiologically is apt to be misunderstood to be mediastinal metastases, and it is thus considered to be an unresectable disease. We report a case of lung cancer associated with sarcoidosis that developed in a 65-year-old woman who underwent surgery. Radiological studies revealed a 1.9×1.7 cm mass in the left upper lobe with multiple enlarged bilateral mediastinal lymph nodes (2R, 3a, 4R, 4L, 5, 6, 7, 8R). Pathologic findings showed that the mass was a well-differentiated adenocarcinoma and all of the enlarged mediastinal lymph nodes were granulomas without cancer metastasis. We report this case with a review of the literature.

Diffuse Alveolar Hemorrhage in a 39-year-old Woman: Unusual Initial Presentation of Microscopic Polyangiitis

Microscopic polyangiitis (MPA) is a necrotizing vasculitis involving the small vessels without granulomatous inflammation. Most MPA initially presents with renal involvement without pulmonary involvement. Isolated and initially presenting alveolar hemorrhage is very rare. The patient was a 39-year-old female with a progressive cough, dyspnea, and blood-tinged sputum for the previous 5 days. We determined that her condition was MPA though VATS lung biopsy and renal biopsy. After 2 months of steroid therapy, the chest lesions had improved. We report here a rare case of MPA with isolated and initial involvement of the lung with a review of the literature.