Geun Dong Lee

Chylothorax Complicating Pulmonary Resection for Lung Cancer: Effective Management and Pleurodesis

BACKGROUND Chylothorax associated with pulmonary resection for lung cancer, although rare, must be considered as a potential complication during thoracic surgery. In the present study, we investigated the effectiveness of a conservative approach (diet or pleurodesis) to the management of chylothorax. METHODS Between January 2000 and December 2010, 3,120 consecutive patients underwent pulmonary resection and mediastinal lymph node dissection at our institution. Among them, 67 patients with confirmed chylothorax were retrospectively reviewed. RESULTS Right-sided chylothorax was more common than left-sided chylothorax (p=0.033). All patients were initially treated with nil per os (NPO; n=46) or a low long-chain triglyceride (LCT) diet (n=21). In the NPO group, 24 patients were successfully treated with diet alone and 20 underwent pleurodesis. In the LCT group, 10 patients were successfully treated with diet alone; of the 11 remaining patients, 4 patients improved after NPO. The 7 patients who did not improve with NPO underwent pleurodesis. No significant differences in chest tube output before and after initial treatment, length of stay, or success rate were observed between patients initially treated with NPO and those receiving low LCT. All 32 pleurodeses performed in 27 patients were successful. Two patients underwent surgery without pleurodesis after dietary treatment failure. Postoperative air leakage or drainage for 5 days greater than 21.6 mL/kg were independent risk factors for dietary treatment failure. CONCLUSIONS Conservative treatment, including pleurodesis, should be the first choice of treatment for chylothorax complicating pulmonary resection.

Video-assisted thoracic surgery for bronchogenic cysts: is this the surgical approach of choice?

OBJECTIVES Although there is no consensus on the management of bronchogenic cyst, most surgeons advocate early removal, even in asymptomatic patients. To evaluate the feasibility and safety of video-assisted thoracic surgery (VATS) in the management of bronchogenic cysts and long-term follow-up, a retrospective analysis was performed. METHODS From January 1995 to April 2013, we retrospectively reviewed the charts of 113 patients who underwent VATS resection of bronchogenic cysts in our institution. Resection of the bronchogenic cysts by VATS was initially performed in patients who had a cyst in the thoracic cavity and no evidence of severely dense adhesion to other organs or tissues on a CT scan. Also, patients with a history of previous thoracic surgeries, in addition to those with concomitant diseases requiring surgical treatment, were enrolled in our series. Operations were carried out using the conventional three-port technique and histological examinations confirmed the diagnosis of benign bronchogenic cyst containing a ciliated columnar epithelial lining. RESULTS The median size of the cysts was 3.7 cm in their greatest diameter (range, 1-10 cm). One hundred and nine patients with bronchogenic cyst were resected completely by VATS. In 4 cases, VATS was converted to open thoracotomy or median sternotomy: major adhesion to the bronchus in 2, left innominate venous injury in 1 and repair of bronchial tear by surgery in 1. We identified 5 intraoperative complications of tracheobronchial tear, vascular injury and oesophageal laceration. The median operation time was 96.8 min (range, 15-320 min). There were no operative mortalities or major postoperative complications. Patients with VATS excision were discharged after a median of 3.7 days postoperatively. The long-term follow-up ranged from 1 to 11 years, with a median follow-up of 4.2 years. There were no late complications or recurrences. CONCLUSIONS Considering the low conversion and complication rate, VATS was safe and effective in the resection of the bronchogenic cysts. The size and the location of cysts were not important considerations in selecting the surgical method. VATS excision should be considered the primary therapeutic option in the management of patients with bronchogenic cysts.

Birt-Hogg-Dube syndrome prospectively detected by review of chest computed tomography scans

Purpose Birt-Hogg-Dube syndrome (BHD) is a rare disorder caused by mutations in the gene that encodes folliculin (FLCN) and is inherited in an autosomal dominant manner. BHD is commonly accompanied by fibrofolliculomas, renal tumors, multiple pulmonary cysts, and spontaneous pneumothorax. The aim of this study was to detect BHD prospectively in patients undergoing chest computed tomography (CT) scans and to evaluate further the characteristics of BHD in Korea. Methods We prospectively checked and reviewed the chest CT scans obtained for 10,883 patients at Gangnam Severance Hospital, Seoul, Korea, from June 1, 2015 to May 31, 2016. Seventeen patients met the study inclusion criteria and underwent screening for FLCN mutation to confirm BHD. We analyzed the characteristics of the patients confirmed to have BHD and those for a further 6 patients who had previously been described in Korea. Results Six (0.06%) of the 10,883 patients reviewed were diagnosed with BHD. There was no difference in demographic or clinical features between the patients with BHD (n = 6) and those without BHD (n = 11). Pneumothorax was present in 50% of the patients with BHD but typical skin and renal lesions were absent. The maximum size of the cysts in the BHD group (median 39.4 mm; interquartile range [IQR] 11.4 mm) was significantly larger than that in the non-BHD group (median 15.8 mm; IQR 7.8 mm; P = 0.001). Variable morphology was seen in 100.0% of the cysts in the BHD group but in only 18.2% of the cysts in the non-BHD group (P = 0.002). Nine (95%) of the total of 12 Korean patients with BHD had experienced pneumothorax. Typical skin and renal lesions were present in 20.0% of patients with BHD. Conclusions Our findings suggest that BHD can be detected if chest CT scans are read in detail.

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values

Introduction Response to mesenchymal‐epithelial transition (MET) inhibitors in NSCLC with mesenchymal‐epithelial transition gene (MET) exon 14 skipping (METex14) has fueled molecular screening efforts and the search for optimal therapies. However, further work is needed to refine the clinicopathologic and prognostic implications of METex14 skipping. Methods Among 795 East Asian patients who underwent a surgical procedure for NSCLC, we screened 45 patients with quintuple‐negative (EGFR‐negative/KRAS‐negative/anaplastic lymphoma kinase gene [ALK]‐negative/ROS1‐negative/ret proto‐oncogene [RET]‐negative) lung adenocarcinomas by using reverse‐transcriptase polymerase chain reaction and found 17 patients (37.8%) with METex14 skipping. We also investigated the effect of small interfering RNA (siRNA) targeting skipping junction in cells with METex14 skipping. Results The median age of the 17 patients was 73 years. The acinar subtype was predominant (52.9%), followed by the solid subtype (35.3%). MET immunohistochemistry demonstrated 100% sensitivity and 70.4% specificity. Multivariate analyses showed that patients with METex14 skipping had a higher recurrence rate than those with ALK fusion (versus METex14 skipping) (hazard ratio = 0.283, 95% confidence interval: 0.119–0.670) in stage I to IIIA disease; however, the differences in overall survival were not significant after adjustment for pathologic stage (p = 0.669). Meanwhile, siRNA decreased MET‐driven signaling pathways in Hs746T cells, and combined treatment with siRNA and crizotinib inhibited cell proliferation in crizotinib‐resistant H596 cells. Conclusions The prevalence of METex14 skipping was quite high in East Asian patients without other driver mutations in lung adenocarcinomas. METex14 skipping was associated with old age, the acinar or solid histologic subtype, and high MET immunohistochemical expression. The prognosis of patients with METex14 skipping was similar to that of patients with major driver mutations. siRNA targeting the junction of METex14 skipping could inhibit MET‐driven signaling pathways in cells with METex14 skipping.

Clinical results of sublobar resection versus lobectomy or more extensive resection for lung cancer patients with idiopathic pulmonary fibrosis

BACKGROUND Lung cancer patients with idiopathic pulmonary fibrosis (IPF) are at a high risk of requiring lung resection. The optimal surgical strategy for these patients remains unclear. This study aimed to compare the clinical results of a sublobar resection versus a lobectomy or more extensive resection for lung cancer in patients with IPF. METHODS From January 1995 to December 2012, 80 patients with simultaneous non-small cell lung cancer and IPF were treated surgically at Asan Medical Center. Predictors of recurrence-free survival and overall survival were evaluated in the series. RESULTS Lobectomy or more extensive resection of the lung (lobar resection group) was performed in 65 patients and sublobar resection (sublobar resection group) was carried out in 15 patients. The sublobar resection group showed fewer in-hospital mortalities than the lobar resection group (6.7% vs. 15.4%; P=0.68). For late mortality after lung resection, cancer-related deaths were not significantly different in incidence between the two groups (55.6% vs. 30.6%; P=0.18). Recurrence-free survival after lung resection was significantly greater in the lobar than in the sublobar resection group (P=0.01). However, overall survival after lung resection was not significantly different between the two groups (P=0.05). Sublobar resection was not a significant predictive factor for overall survival (hazard ratio =0.50; 95% CI: 0.21-1.15; P=0.10). CONCLUSIONS Although not statistically significant, a sublobar resection results in less in-hospital mortality than a lobar resection for lung cancer patients with IPF. There is no significant difference in overall survival compared with lobar resection. A sublobar resection may be another therapeutic option for lung cancer patients with IPF.

Comparisons of the clinical outcomes of thoracoscopic sympathetic surgery for palmar hyperhidrosis: R4 sympathicotomy versus R4 sympathetic clipping versus R3 sympathetic clipping

BACKGROUND Thoracoscopic sympathetic surgery is regarded as a definitive treatment for palmar hyperhidrosis. However, the optimal surgical strategy remains unclear. The aim of this study was to compare outcomes based on the level and type of sympathetic disconnection in patients with palmar hyperhidrosis. METHODS From January 2009 to December 2014, 101 patients with palmar hyperhidrosis underwent thoracoscopic sympathetic surgery at Gangnam Severance Hospital. Complete follow-up information was obtained from 59 patients. We retrospectively analyzed the results of operation, degree of palmar sweating (%), grade of compensatory sweating (none, mild, moderate, severe, very severe), grade of satisfaction (very satisfied, satisfied, moderate, dissatisfied, very dissatisfied), and recurrence/failure. RESULTS R4 sympathicotomy, R4 sympathetic clipping, and R3 sympathetic clipping were performed in 16, 20, and 23 patients, respectively. The mean degree of palmar sweating after sympathetic surgery was not significantly different between these three groups (17.50% vs. 27.00% vs. 29.78%; P=0.38). The rate of life-bothering compensatory sweating was lower in the R4 sympathicotomy group compared with those of other two groups (0% vs. 25%, 47.8%; P=0.09). The rate of very satisfied to moderate grades of satisfaction were lower in the R3 sympathetic clipping group compared with those of other two groups (93.8%, 100% vs. 73.9%; P=0.07). The rate of recurrence/failure rates were lower in the R4 sympathicotomy group compared with those of other two groups (12.50% vs. 35.00%, 34.8%; P=0.25). Sympathetic surgery at the R3 level was the only significant risk factor for patient dissatisfaction (odd ratio =12.353, 95% confidence interval =1.376-110.914; P=0.025). CONCLUSIONS Our data support that R4 sympathicotomy had lower grades of compensatory sweating, higher grades of satisfaction, and lower rates of recurrence/failure. We therefore consider R4 sympathicotomy as an optimal surgical treatment for palmar hyperhidrosis.

Prognostic stratification of thymic epithelial tumors based on both Masaoka-Koga stage and WHO classification systems

BACKGROUND The aims of this study were to stratify the risk of recurrence based on the Masaoka-Koga stage and World Health Organization (WHO) classification systems after R0-resection for thymic epithelial tumors (TETs). METHODS A retrospective analysis was conducted on 479 patients who underwent surgery between Jan 1994 and Feb 2014 for TETs. The study group comprised 251 males and 228 females, with a median age of 52 years (range, 15-84 years). RESULTS Of the 479 patients, 406 (84.8%) patients underwent R0-resection. Recurrence after R0-resection occurred in 32 patients during a median follow-up of 53 months (range, 2-227 months). A multivariate analysis revealed that the preoperative treatment including chemotherapy (P=0.036), Masaoka-Koga stage (P=0.011) and the WHO classification (P=0.001) were predictors for recurrence after R0-resection. Patients were stratified into four risk groups using a potential model incorporating both the Masaoka-Koga stage and WHO classifications. Group 1 comprised WHO types A/AB/B1 in stage I/II; Group 2 comprised WHO type A/AB/B1 in stage III or WHO type B2/B3 in stage I/II or WHO type C in stage I; Group 3 comprised Type B2/B3/C in stage III, or WHO type C in stage II/III; and Group 4 comprised WHO type B2/B3/C in stage IV. The 5-year freedom-from-recurrence (FFR) rates were 99.4% for group 1, 84.7% for group 2, 63.7% for group 3, and less than 44.4% for group 4 (P<0.001). In group 3, the rate of locoregional recurrence of patients treated with postoperative radiation therapy was lower than patients treated without postoperative radiation therapy (P=0.032). CONCLUSIONS A risk model incorporating both Masaoka-Koga stage and WHO classification systems may provide multi-faceted information about recurrence and adjuvant treatment after R0-resection of TETs.

New 3-Tiered Circumferential Resection Margin Criteria in Esophageal Squamous Cell Carcinoma.

Objective: We aimed to investigate the optimal cutoff value of circumferential resection margin (CRM) of esophageal squamous cell carcinoma (ESCC) in patients who underwent radical esophagectomy. Background: Tumor involvement of a CRM in ESCC has not been clearly defined. Methods: We reviewed 479 pT3 ESCC patients to find the optimal cutoff point of distance from CRM in addition to 0 &mgr;m for discriminating survival time. Results: The partitions at and near the 500 &mgr;m distance from CRM generated the largest log-rank statistics (P = 0.0086). Therefore, we added 500 &mgr;m as an additional cutoff value for a positive CRM. Compared to patients with CRM greater than 500 &mgr;m, patients with CRM 0 &mgr;m showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001), followed by patients with 0 to 500 &mgr;m (P = 0.008 and 0.066, respectively). In multivariable analyses, overall survival differences remained significant [0 < CRM ⩽ 500 &mgr;m vs CRM > 500 &mgr;m, hazards ratio (HR) = 1.875, 97.5% CI: 1.243–2.829, P = 0.002; CRM = 0 &mgr;m vs CRM > 500 &mgr;m, HR = 2.666, 97.5% CI: 1.745–4.076, P < 0.001]. In comparison of criteria from the College of American Pathologists, the Royal College of Pathologists, and this study, HRs of positive CRM (95% CI, P-value) were 1.969 (1.501–2.584, P < 0.001), 1.384 (1.039–1.844, P = 0.027), and 1.696 (1.342–2.143, P < 0.001), respectively. Conclusions: In patients with ESCC, we developed new, 3-tiered CRM criteria providing more detailed prognostic information than the 2-tiered criteria.

A comparison of the proposed classifications for the revision of N descriptors for non-small-cell lung cancer.

OBJECTIVES Several new classifications have been proposed for revision of the N descriptors for non-small-cell lung cancer (NSCLC), but external validation is required. The aim of this study was to validate various newly proposed nodal classifications and to compare the discrimination abilities of these classifications. METHODS A retrospective analysis was conducted of 1487 patients who underwent complete resection with systematic lymph node dissection for NSCLC between 2000 and 2008. Four nodal classifications based on the following categories were analysed: zone-based classification (single-zone N1, multiple-zone N1, single-zone N2 and multiple-zone N2), number-based classification (the number of metastatic lymph nodes; 1-2, 3-6 and ≥7), rate-based classification (ratio of the number of metastatic lymph nodes to the total number of resected lymph nodes; ≤15, 15-40 and >40%) and the combination of location- and number-based classification (N1: 1-3, N1: ≥4, N2: 1-3 and N2: ≥4). Concordance (C)-index and net reclassification improvement (NRI) index were used to assess the discrimination abilities of the models. RESULTS In multivariate analysis, all of the newly proposed classifications were independent predictors (P < 0.001) of overall survival (OS) after adjustment for significant variables (age, tumour histology and pathological T status). The C-indices of the classifications based on the nodal zone, nodal number, rate and location alongside the number of metastatic lymph nodes were 0.6179, 0.6280, 0.6203 and 0.6221, respectively; however, the differences in the C-indices were statistically insignificant. Compared with the zone-based classification, the NRI for OS of classifications based on the nodal number, rate and location with number were 0.1101, 0.0972 and 0.0416, respectively. CONCLUSIONS All four proposed classifications based on the nodal zone, nodal number, rate and the combination of location and number are prognostically valid and could serve as future N descriptors after complete resection of NSCLC. The discrimination ability was not significantly different among the four proposed classifications, although the number-based classification tended to have a higher predictive ability compared with the zone-based classification. Future studies with an in-depth discussion are needed to clarify optimal future N descriptors for NSCLC.

Gastric conduit cancer after oesophagectomy for oesophageal cancer: incidence and clinical implications

OBJECTIVES Gastric conduit cancer (GCC), which is a carcinoma that arises in the gastric conduit after oesophagectomy, often negatively affects long-term survivors of oesophageal cancer. The aim of this study was to evaluate the incidence and clinical implications of GCC. METHODS We reviewed data for 863 patients who underwent an oesophagectomy and a reconstruction of the gastric conduit from 1993 to 2011 for oesophageal cancer. RESULTS A total of 18 cases of GCC in 18 patients were identified. Cumulative incidence rates of GCC were 2.4% at 5 years and 5.7% at 10 years. The median interval between oesophagectomy and detection of gastric tube cancer was 5.0 years (range, 1-16 years). Ten patients were incidentally diagnosed with GCC under periodic endoscopy. All cases of gastric tube cancer were adenocarcinoma and 12 cases were located at the antrum of the gastric conduit. For GCC treatment, endoscopic submucosal dissection was performed in 6 patients, total gastric conduit gastrectomy with colon interposition in 3 patients and chemotherapy in 6 patients. Five patients received conservative treatment alone. The 5-year survival rate of all patients was 22.2%. The 3-year survival rates of the patients who underwent endoscopic resection, total gastrectomy with colon interposition or chemotherapy or conservative treatment were 100, 50, and 9.1%, respectively (P = 0.003). CONCLUSIONS Patients had a constant risk of GCC occurrence after oesophagectomy for oesophageal cancer. Endoscopic or surgical resection for early GCC showed favourable outcomes compared with chemotherapy or conservative treatment for advanced GCC. A regular and long-term follow-up, including detailed endoscopy, is essential for the early detection of GCC in patients who underwent oesophagectomy for oesophageal cancer.