Volume-Based Parameters of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Outcome Prediction in Early-Stage Non–Small Cell Lung Cancer After Surgical Resection

Hyun, Seung Hyup,Choi, Joon Young,Kim, Kwhanmien,Kim, Jhingook,Shim, Young Mog,Um, Sang-Won,Kim, Hojoong,Lee, Kyung-Han,Kim, Byung-Tae Lippincott Williams Wilkins, Inc. 2013 Annals of surgery Vol.257 No.2

OBJECTIVE:: To evaluate the prognostic significance and predictive performance of volume-based parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in early-stage non–small cell lung cancer (NSCLC). BACKGROUND:: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies. METHODS:: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. RESULTS:: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001). CONCLUSIONS:: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.

Effect of Adjuvant Chemotherapy after Complete Resection for Pathologic Stage IB Lung Adenocarcinoma in High-Risk Patients as Defined by a New Recurrence Risk Scoring Model

Jang, Hyo Joon,Cho, Sukki,Kim, Kwhanmien,Jheon, Sanghoon,Yang, Hee Chul,Kim, Dong Kwan Korean Cancer Association 2017 Cancer Research and Treatment Vol.49 No.4

<P><B>Purpose</B></P><P>We conducted a retrospective analysis to determine if adjuvant chemotherapy prolongs overall survival in patients with pathologic stage IB lung adenocarcinoma who had undergone complete resection and were defined as high-risk by a newly developed recurrence risk scoring model.</P><P><B>Materials and Methods</B></P><P>Patients who underwent curative resection for stage IB lung adenocarcinoma were analyzed with a newly developed recurrence risk scoring model and divided into a low-risk group and a high-risk group. The patients in the high-risk group were retrospectively divided into two groups based on whether they underwent adjuvant chemotherapy or observation. Recurrence-free survival and overall survival were compared between these two groups.</P><P><B>Results</B></P><P>A total of 328 patients who underwent curative resection between 2000 and 2009 were included in this study, of whom 110 (34%) received adjuvant chemotherapy and 218 (67%) underwent observation without additional treatment. According to our risk model, 167 patients (51%) were high-risk and 161 (49%) were low-risk. The 5-year recurrence-free survival rates and overall survival were 84.4% and 91.5% in low-risk patients and 53.9% and 74.7% in high-risk patients (p < 0.001). In high-risk patients, the 5-year overall survival rates were 77% among patients who underwent observation and 87% among those who underwent adjuvant chemotherapy (p=0.019).</P><P><B>Conclusion</B></P><P>Adjuvant chemotherapy prolonged overall survival among high-risk patients who had undergone complete resection for stage IB lung adenocarcinoma.</P>

Long-term results of surgical treatment in benign bronchoesophageal fistula

Kim, Hong Kwan,Choi, Yong Soo,Kim, Kwhanmien,Kim, Jhingook,Shim, Young Mog Elsevier 2007 Journal of thoracic and cardiovascular surgery Vol.134 No.2

<P><B>Objectives</B></P><P>Benign bronchoesophageal fistula is a rare complication resulting from various diseases. The objectives of the study are to report our surgical experience in patients with benign bronchoesophageal fistulas and to evaluate the long-term results of surgical management.</P><P><B>Methods</B></P><P>Between 1995 and 2005, a total of 14 patients (mean age, 52.5 years; male/female = 6:8) underwent operations for benign bronchoesophageal fistulas. The etiology of the fistulas included traction esophageal diverticula in 7 patients and tuberculous lymphadenopathy in 6. Primary repair of the fistula was performed in all patients and a concomitant lobectomy in 6.</P><P><B>Results</B></P><P>There was no in-hospital mortality. Postoperative complications occurred in 1 patient (empyema resulting from a leakage at the repair site). Postoperative esophagography revealed a leakage at the repair site in 1 patient. There was 1 late death with a mean follow-up of 43.9 months. The cause of death was aspiration pneumonia resulting from recurrent fistula. Two of 8 patients who did not undergo a lobectomy had persistent bronchiectasis, whereas none of those who underwent a concomitant lobectomy had any recurrent pneumonia or bronchiectasis. The overall survival was 100% at 5 years and the mean survival time was 124 months (95% confidence interval, 106.5-142.2 months).</P><P><B>Conclusions</B></P><P>We conclude from these data that early detection and definitive surgical repair of benign bronchoesophageal fistulas can yield high success rates with excellent early outcomes and good long-term results.</P>

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

배선현,안용찬,남희림,박희철,표홍렬,심영목,김진국,Kwhanmien Kim,안진석,안명주,박근칠 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.6

Purpose: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. Materials and Methods: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. Results: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. Conclusion: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

Acellular dermal matrix and bone cement sandwich technique for chest wall reconstruction

Chan Yeong Heo,Byungkwon Kang,정재훈,Kwhanmien Kim,명유진 대한성형외과학회 2022 Archives of Plastic Surgery Vol.49 No.1

The authors performed rigid reconstruction using the sandwich technique for full-thickness chest wall defects by using two layers of acellular dermal matrix and bone cement. We assessed six patients who underwent chest wall reconstruction. Reconstruction was performed by sandwiching bone cement between two layers of acellular dermal matrix. In all patients, there was no defect of the overlying soft tissue, and primary closure was performed for external wounds. The average follow-up period was 4 years (range, 2–8 years). No major complications were noted. The sandwich technique can serve as an efficient and safe option for chest wall reconstruction.

Surgical Resection of Recurrent Lung Cancer in Patients Following Curative Resection

Kim, Hyoung Soo,I, Hoseok,Choi, Yong Soo,Kim, Kwhanmien,Shim, Young Mog,Kim, Jhingook The Korean Academy of Medical Sciences 2006 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.21 No.2

<P>We reviewed our experience with resection of recurrent lung cancer to evaluate the benefit and risk of the procedure. From December 1994 to December 2003, 29 consecutive patients underwent pulmonary resections for recurrent lung cancer. The mean duration from the first resection to second surgery was 25.4±15.1 months for the definite 2nd primary lung cancer (n=20) and 8.9±5.7 months for metastatic lung cancer (n=9). The procedures at the second operations were completion-pneumonectomy in 11 patients, lobectomy in 5 patients, wedge resection in 12 patients and resection and anastomosis of trachea in 1 patient. Morbidity was observed in 6 (21%) of the patients and the in-hospital mortality was two patients (7%) after the repeated lung resection. Tumor recurrence after reoperation was observed in 14 patients (48%). The actuarial 5-yr survival rate was 69% and the 5-yr disease free rate following reoperation was 44%. No significant difference was found in overall survival and disease free survival between the 2nd primary lung cancer group and the metastatic lung cancer group. The recurrence rate following reoperation was significantly different between the wedge resection group and lobectomy/completion pneumonectomy group (<I>p</I>=0.008), but the survival rate was not significantly different (<I>p</I>=0.41). Surgical intervention for recurrent lung cancers can be performed with acceptable mortality and morbidity. If tolerable, completion pneumonectomy or lobectomy is recommended for resection of recurrent lung cancer.</P>

Neurologic outcomes of thymectomy in myasthenia gravis: Comparative analysis of the effect of thymoma

Kim, Hong Kwan,Park, Min Soo,Choi, Yong Soo,Kim, Kwhanmien,Shim, Young Mog,Han, Joungho,Kim, Byoung Joon,Kim, Jhingook Elsevier 2007 Journal of thoracic and cardiovascular surgery Vol.134 No.3

<P><B>Objectives</B></P><P>The objectives of this study were to compare the clinical features and the outcomes after thymectomy between patients with and without thymoma and to evaluate the influence of thymectomy on the subsequent clinical course of myasthenia gravis.</P><P><B>Methods</B></P><P>Between 1995 and 2003, 64 consecutive patients underwent thymectomy, and of these, 60 patients were followed up for at least 12 months postoperatively. The study population was divided into 2 groups based on the presence of thymoma. We performed a retrospective analysis to compare the neurologic outcomes of thymectomy between patients with thymomatous myasthenia gravis and those with nonthymomatous myasthenia gravis.</P><P><B>Results</B></P><P>Twenty-four patients had a thymoma. No significant differences were observed between the 2 groups regarding the preoperative severity of myasthenia gravis. There was no significant difference in the follow-up duration between the 2 groups. There was no significant difference in the overall remission rate between the 2 groups (<I>P</I> = .064). The mean time required to reach a remission was 10.6 months and 23.5 months in the thymoma and nonthymoma groups, respectively. The mean duration of remission was 43.1 months and 30.8 months in the thymoma and nonthymoma groups, respectively. In the early phase of follow-up, more patients reached remission in the thymoma group than those in the nonthymoma group (<I>P</I> = .040).</P><P><B>Conclusions</B></P><P>Neurologic outcomes of the thymoma group were no worse than those of the nonthymoma group. It is expected that earlier thymectomy is likely to result in a better prognosis by shortening the disease period, even for patients with nonthymomatous myasthenia gravis.</P>

Tumor Size-Dependent Anticancer Efficacy of Chlorin Derivatives for Photodynamic Therapy

Chang, Ji-Eun,Liu, Yang,Lee, Tae Heon,Lee, Woo Kyoung,Yoon, Il,Kim, Kwhanmien MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>Photodynamic therapy (PDT) with a suitable photosensitizer molecule is a promising anticancer treatment. We evaluated two chlorin molecules as potential photosensitizers, methyl pyropheophorbide a (MPPa) and <I>N</I>-methoxyl purpurinimide (NMPi), against A549 human lung adenocarcinoma cells in vitro as well as in A549 tumor-bearing mice in vivo. Cell viability, microscopy, and fluorescence-activated cell sorting (FACS) analyses were performed for the in vitro studies. MPPa and NMPi showed high phototoxicity in vitro, which was dependent on the concentration of the photosensitizers as well as the light irradiation time. In the animal study, tumor volume change, tumor surface alterations, and hematoxylin & eosin (H&E) and terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL) staining analyses were performed and compared between small (tumor volume of <50 mm<SUP>3</SUP>) and large (tumor volume of >50 mm<SUP>3</SUP>) size of initial tumors. MPPa and NMPi showed high anticancer efficacy against small-size tumors, indicating that early treatment with PDT is effective. Especially, repeated two times PDT with NMPi allowed almost complete eradication against small-size tumors. However, MPPa and NMPi were not effective against large-size tumors. In conclusion, the two chlorin derivatives, MPPa and NMPi, show good anticancer efficacy as promising photosensitizers for PDT in vitro and in vivo. Moreover, their activity in vivo was significantly dependent on the initial tumor size in mice, which confirms the importance of early cancer treatment.</P>

Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor ( <i>EGFR</i> )-Mutant Lung Adenocarcinoma

Park, Eunhyang,Park, Soo Young,Kim, Hyojin,Sun, Ping-Li,Jin, Yan,Cho, Suk Ki,Kim, Kwhanmien,Lee, Choon-Taek,Chung, Jin-Haeng The Korean Society of Pathologists and the Korean 2015 Journal of Pathology and Translational Medicine Vol.49 No.5

<P><B>Background:</B></P><P>Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC.</P><P><B>Methods:</B></P><P>IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance.</P><P><B>Results:</B></P><P>Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (<I>EGFR</I>)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009).</P><P><B>Conclusions:</B></P><P>Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in <I>EGFR</I>-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.</P>

Association of Global Levels of Histone Modifications with Recurrence-Free Survival in Stage IIB and III Esophageal Squamous Cell Carcinomas.

I, Hoseok,Ko, Eunkyung,Kim, Yujin,Cho, Eun Yoon,Han, Joungho,Park, Joobae,Kim, Kwhanmien,Kim, Duk-Hwan,Shim, Young Mog American Association for Cancer Research 2010 Cancer Epidemiology, Biomarkers & Prevention Vol.19 No.2

<P>This study was aimed at understanding the effects of histone modifications on recurrence-free survival (RFS) after esophagectomy in esophageal squamous cell carcinoma (ESCC). The acetylation of histone H3 lysine (H3K9Ac), histone H3 lysine 18 (H3K18Ac), and histone H4 lysine 12 (H4K12Ac), and the dimethylation of histone H3 lysine 9 (H3K9diMe) and histone H4 arginine 3 (H4R3diMe) were analyzed by immunohistochemistry in 237 ESCCs. The K-means clustering algorithm was used to identify unique patterns of histone modifications. At a median follow-up of 5.1 years, 109 (46%) of 237 patients had developed recurrence of disease. Mean global levels of H3K9Ac, H3K18Ac, H3K9diMe, H4K12Ac, and H4R3diMe were 81.5%, 65.1%, 80.3%, 45.9%, and 27.4%, respectively. In the analysis of individual histones, a 1% increase in the global level of H3K18Ac in pathologic stage III worsened RFS at 1.009 times [95% confidence interval (CI), 1.001-1.016; P = 0.03], after adjusting for age, sex, and operative method. Cluster analysis also showed significant effects of histone modifications on RFS. For stage IIB cancers, Cox proportional hazards analysis showed that RFS of cluster 1, with high global levels of H3K18Ac and H4R3diMe, was 2.79 times poorer (95% CI, 1.14-6.27; P = 0.008) than that of cluster 2, with low levels. RFS for stage III cancers was also poorer in cluster 1 than cluster 2 (adjusted hazard ratio, 2.42; 95% CI, 1.10-5.34; P = 0.02). In conclusion, the present study suggests that global levels of histone modifications in ESCC may be an independent prognostic factor of RFS. Cancer Epidemiol Biomarkers Prev; 19(2); 566-73.</P>