Deog Gon Cho

Immunohistochemical Analysis of Non-Small Cell Lung Cancer: Correlation with Clinical Parameters and Prognosis

Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC.

E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model

It remains unclear whether patients with non-small-cell lung cancer (NSCLC) develop brain metastasis during or after standard therapy. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate expression of such markers. A case–control study of patients who were newly diagnosed with NSCLC and who had developed brain metastasis during follow-up was conducted between 2004 and 2009. These patients were compared with a control group of patients who had NSCLC but no evidence of brain metastasis. Immunohistochemical analysis of expression of Ki-67, p53, Bcl-2, Bax, vascular endothelial growth factor, epidermal growth factor receptor, caspase-3, and E-cadherin was conducted. The methylation status of the genes for O6-methylguanine-DNA-methyltransferase, tissue inhibitor of matrix metalloproteinase (TIMP)-2, TIMP-3, and death-associated protein-kinase was also determined, by use of a methylation-specific polymerase chain reaction. A significantly increased risk of developing brain metastasis was associated with the presence of primary tumors with low E-cadherin expression in patients with NSCLC. We also investigated the effects of pioglitazone, a peroxisome proliferator-activated receptor γ-activating drug, in tumor-bearing mouse models. We found that E-cadherin expression was proportional to pioglitazone exposure time. Interestingly, pioglitazone pretreatment before cancer cell inoculation prevented loss of E-cadherin expression and reduced expression of MMP9 and fibronectin, compared with the control group. E-cadherin expression could be a predictor of brain metastasis in patients with NSCLC. Preventive treatment with pioglitazone may be useful for modulating E-cadherin expression.

Short-term and intermediate-term results after unclipping: what happened to primary hyperhidrosis and truncal reflex sweating after unclipping in patients who underwent endoscopic thoracic sympathetic clamping?

Endoscopic thoracic sympathetic clamping (ETC) is used to treat patients with primary hyperhidrosis because it offers the potential of a reversal operation (unclipping) when severe reflex sweating (RS) occurs. Although unclipping has been reported to be effective, the short-term or intermediate-term results after unclipping are unclear. From March 2002 to October 2006, 15 (12.9%) out of 116 patients with primary hyperhidrosis, who underwent ETC, had the endoclip(s) removed as a result of RS. Fourteen patients could be followed up for more than 6 months. The patients answered a telephone interview on the severity of RS, the recurrence of the primary site, and their level of satisfaction. There was no mortality or significant morbidity encountered. On the follow-up, 9 (64%) of the 14 patients who underwent unclipping reported symptomatic recovery from RS. Of these 9 patients with early unclipping (within 4 wk after ETC), only 7 (78%) were satisfied with the outcomes. This suggests that early unclipping does not always guarantee satisfactory recovery from RS. Because early unclipping does not guarantee a full recovery in all patients, special consideration in ETC is needed to determine when to remove the clamp and how strongly to apply the clamp to achieve better results.

Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in various skin tumours.

Background  Various types of external stress cause the skin and central neuroendocrine system to express corticotropin‐releasing hormone (CRH)–proopiomelanocortin (POMC) axis‐related hormones. However, the precise role of the CRH–POMC axis‐related hormones in various skin tumours is unclear.

Thoracoscopic stapled resection of multiple esophageal duplication cysts with different pathological findings

Esophageal duplication cyst is a rare congenital esophageal anomaly of the foregut. This cyst usually occurs in isolation, and thus far, was treated by enucleation through thoracoscopic or thoracotomic surgery. Here we report a case of multiple esophageal duplication cysts that showed different pathological findings, i.e., the cysts were lined with pseudostratified ciliated columnar and stratified squamous epithelium. Esophageal cysts were incidentally detected in a 53-year-old man during the treatment of pneumonia. In chest-computed tomography, the cysts showed a thin wall and homogeneous inner density, while in endoscopy, no communication with esophageal mucosa was observed. We resected the esophageal cysts with endo-staplers under thoracoscopic surgery. No postoperative complications, including esophageal mucosal injury, occurred. A follow-up chest computed tomography revealed the complete resection of the cysts.

Primary Polymorphous Low-Grade Adenocarcinoma of Lung Treated by Sleeve Bronchial Resection : A Case Report

We report a surgical case of primary polymorphous low-grade adenocarcinoma (PLGA) of the minor salivary gland-type of the lung. A PLGA originating from the right upper lobar bronchial inlet was successfully treated by sleeve right upper lobectomy. PLGAs are thought to be indolent tumors that are preferentially localized to the palate, and they affect the minor salivary glands almost exclusively. Until now, two cases of distant metastases to the lung have been reported in the English literature. To the best of our knowledge, only one case of PLGA of minor salivary gland-type of the lung without evidence of a previous oropharyngeal primary tumor has been reported in the English literature. But the case was not a single lesion; it was bilateral tumors accompanied by tumors of the cervical lymph nodes. We report here the first case of a single primary PLGA of the minor salivary gland-type of the lung, which was successfully treated by sleeve bronchial resection of right upper lobe.

New protocol for a reversal operation in endoscopic thoracic sympathetic clamping: pulling back the suture sling linked to the clip under local anesthesia.

Endoscopic thoracic sympathetic clamping (ETC) has widely been used for treating the patients with primary hyperhidrosis, as it offers the potential of reversal operation (unclipping) under general anesthesia (GA) when severe reflex sweating would occur. However, we modified ETC to unclip under local anesthesia. From March 2002 to January 2005, we performed ETC in 87 patients with primary hyperhidrosis. From September 2002 on, the suture sling which was made with a 3-0 propylphylene suture was additionally placed between the endoclip and the subcutaneous tissue of the thoracoport. When unclipping was needed, the endoclip was removed by being pulled back under portable fluoroscopy. Four of 53 patients (7.5%) who underwent ETC alone underwent unclipping under GA. By contrast, unclipping was successfully performed under local anesthesia in 5 of 34 patients (14.7%) who underwent the modified ETC. ETC will be more effective operation if it is modified concomitantly with the suture sling; otherwise the reversal operation will need GA for the unclipping.

Expression of caspase-3 and c-myc in non-small cell lung cancer.

PURPOSE Caspase-3 is a cysteine protease that plays an important role in the process of apoptotic cell death, but little has been studied clinically on caspase-3 in lung cancer. Increased c-myc expression can result in mitosis or apoptosis, and its contribution to the pathogenesis and prognosis of lung cancer has gained interest. In the present study, the expressions of caspase-3 and c-myc, along with their possible correlations with prognostic variables, were analyzed in resected non-small cell lung carcinomas (NSCLC). MATERIALS AND METHODS Archival tumor tissues from 147 previously untreated NSCLC patients were examined by immunohistochemistry for the expressions of caspase-3 and c-myc proteins. Clinical information was obtained through the computerized retrospective database from the tumor registry. RESULTS The expressions of caspase-3 and c-myc were detected in 60 (88/147) and 16% (24/147) of tumors, respectively. No association was found between caspase-3 and c-myc expressions. A multivariate analysis demonstrated the N status and pathologic stage to be significantly correlated with poor survival (p-value=.018 and .002, respectively), but positive expression of caspase-3 was associated with a good prognosis (p=.03). CONCLUSION Our data suggest the involvement of caspase-3 in the tumorigenesis of NSCLC. It is also noteworthy that caspase-3 expression might be a favorable prognostic indicator in these tumors.

Fluoroscopy-assisted thoracoscopic resection for small intrapulmonary lesions after preoperative computed tomography-guided localization using fragmented platinum microcoils.

BACKGROUND Preoperative localization is frequently necessary to perform thoracoscopic resection of a small and/or deeply located intrapulmonary lesion. We developed a new method that uses a fragmented platinum microcoil, and retrospectively evaluated the efficacy of our technique. METHODS Between January 2006 and May 2010, self-made microcoils (Easimarker) were used to localize total 32 lesions (21 solid nodules, and 11 ground glass opacities) in 30 patients. Computed tomography-guided localization was performed into, or just around the lesions. Localized lesions were resected using fluoroscopy-assisted thoracoscopic surgery (FATS), and the histopathologic diagnosis was confirmed. The accuracy and complications of the localization procedure, and operative results of FATS were observed. RESULTS Mean size and depth of all lesions were 11.8 ± 5.1 mm (range: 3 to 22) and 12.2 ± 7.1 mm (range: 2 to 30). CT-guided localizations were successfully performed in all lesions. Four minimal pneumothorax and one parenchymal hematoma related with localization procedure occurred. There were three repeated procedures, which resulted from pleural rebounding of the microcoils. There were two microcoil detecting failures due to intrathoracic displacement during FATS. All 32 resected lesions were histopathologically diagnosed. CONCLUSION CT-guided localization using the fragmented microcoil combined with FATS of small intrapulmonary lesions is a safe, effective, and a diagnostically accurate procedure.

The value of F-18 FDG-PET/CT in diagnosis of chronic empyema-associated malignancy

A 61-year-old man presented with right flank pain.He was a 30 pack-year heavy smoker, and had beendiagnosed as having chronic empyema 9 yearspreviously, without definite evidence of tuberculo-sis. Posteroanterior chest radiograph (Fig. 1)onadmission showed a large, curved tubular opacityalong the right lower lateral portion of the pleurawith partial rim-like calcification. Unenhancedand contrast-enhanced (Fig. 2) chest CT revealeda chronic empyemic lesion containing thick fluidof non-enhancing soft-tissue attenuation, withmultifocal calcifications at the wall of the empy-ema. Posterior to the empyema, a flat, ovoidheterogeneously enhancing mass was noted, whichabutted the posterior wall of the empyema andextended into the extrapleural fat layer. Nodefinite evidence of adjacent rib destruction wasdemonstrated. FDG-PET/CT imaging (Fig. 3)wascarried out using a combined PET/CT system(Reveal-CT, Molecular Imaging, Knoxville, TN,USA). Intense FDG uptake [maximum SUV (stan-dardized uptake value), 6.4] was only observed atthe flat ovoid mass posterior to the empyema; thechronic empyema itself showed little FDG uptake.CT-guided core-needle biopsy of the mass witha 20 G needle revealed chronic inflammatory cellinfiltration and fibrosis without evidence of malig-nancy. Because PET/CT findings indicated a strongpossibility of the malignancy, the patient under-went complete mass excision combined withresection of the right 6e11th ribs and right lowerlobectomy due to severe inflammatory adhesionbetween the mass and the surrounding structures.The tumour was a tan egrey, rubbery, firm, plaque-likemass that measured 5 4 2cm