Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. @*Materials and Methods@#This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. @*Results@#A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. @*Conclusion@#NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

Delayed Gastric Emptying after Esophagectomy: Management and Prevention

The quality of life associated with eating is becoming an increasingly significant problemfor patients who undergo esophagectomy as a result of the improved survival rate afteresophageal cancer surgery. Delayed gastric emptying (DGE) is a common complication afteresophagectomy. Although several strategies have been proposed for the managementand prevention of DGE, no clear consensus exists. The purpose of this review is to presenta brief overview of DGE and to help clinicians choose the most appropriate treatmentthrough an analysis of DGE by cause. Furthermore, we would like to suggest some tips toprevent DGE based on our experience.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity / 대한핵의학회잡지

PURPOSE: This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer.METHODS: A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV₁) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT.RESULTS: The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV₁ showed significant correlation with ppoFEV₁ based on lung perfusion SPECT and perfusion scan.CONCLUSIONS: We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity / 대한핵의학회잡지

PURPOSE@#This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer.@*METHODS@#A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV₁) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT.@*RESULTS@#The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV₁ showed significant correlation with ppoFEV₁ based on lung perfusion SPECT and perfusion scan.@*CONCLUSIONS@#We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for the diagnosis and staging of lung cancer. However, evidence of its usefulness for re-biopsy in treated lung cancer, especially according to the previous treatment, is limited. We evaluated the role of EBUS-TBNA for re-biopsy and its diagnostic values in patients with different treatment histories. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent EBUS-TBNA for re-biopsy of suspicious recurrent or progressive lesions between January 2006 and December 2016 at the National Cancer Center in South Korea. Patients were categorized into three groups based on the previous treatment modalities: surgery, radiation, and palliation. RESULTS: Among the 367 patients (surgery, n=192; radiation, n=40; palliation, n=135) who underwent EBUS-TBNA for re-biopsy, the overall sensitivity, negative predictive value (NPV), and diagnostic accuracy of EBUS-TBNA in detecting malignancy were 95.6%, 82.7%, and 96.3%, respectively. The sensitivity was lower in the radiation group (83.3%) when compared with the surgery (95.7%, p=0.042) and palliation (97.7%, p=0.012) groups. The NPV was lower in the palliation group (50.0%) than in the surgery group (88.5%, p=0.042). The sample adequacy of EBUS-TBNA specimens was lower in the radiation group (80.3%) than in the surgery (95.4%, p < 0.001) or palliation (97.8%, p < 0.001) groups. EGFR mutation analysis was feasible in 94.6% of the 92 cases, in which mutation analysis was requested. There were no major complications. Minor complications were reported in 12 patients (3.3%). CONCLUSION: EBUS-TBNA showed high diagnostic values and high suitability for EGFR mutation analysis with regard to re-biopsy in patients with previously treated lung cancer. The sensitivity was lower in the radiation group and NPV was lower in the palliation group. The complication rate was low.

The Korean guideline for lung cancer screening

Lung cancer is the leading cause of cancer death in many countries, including Korea. The majority of patients are inoperable at the time of diagnosis because symptoms are typically manifested at an advanced stage. A recent large clinical trial demonstrated significant reduction in lung cancer mortality by using low dose computed tomography (LDCT) screening. A Korean multisociety collaborative committee systematically reviewed the evidences regarding the benefits and harms of lung cancer screening, and developed an evidence-based clinical guideline. There is high-level evidence that annual screening with LDCT can reduce lung cancer mortality and all-cause mortality of high-risk individuals. The benefits of LDCT screening are modestly higher than the harms. Annual LDCT screening should be recommended to current smokers and ex-smokers (if less than 15 years have elapsed after smoking cessation) who are aged 55 to 74 years with 30 pack-years or more of smoking-history. LDCT can discover non-calcified lung nodules in 20 to 53% of the screened population, depending on the nodule positivity criteria. Individuals may undergo regular LDCT follow-up or invasive diagnostic procedures that lead to complications. Radiation-associated malignancies associated with repetitive LDCT, as well as overdiagnosis, should be considered the harms of screening. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Education and actions to stop smoking must be offered to current smokers. Chest radiograph, sputum cytology at regular intervals, and serum tumor markers should not be used as screening methods. These guidelines may be amended based on several large ongoing clinical trial results.

Clinical Characteristics of Malignant Pericardial Effusion Associated with Recurrence and Survival / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated clinical outcomes after drainage for malignant pericardial effusion with imminent or overt tamponade. MATERIALS AND METHODS: Between August 2001 and June 2007, 100 patients underwent pericardiocentesis for malignant pericardial effusion. Adequate follow-up information on the recurrence of pericardial effusion and survival status was available for 98 patients. RESULTS: Recurrence of effusion occurred in 30 patients (31%), all of whom were diagnosed with adenocarcinoma. Multivariate analysis indicated that adenocarcinoma of the lung (hazard ratio [HR], 6.6; 95% confidence interval [CI], 1.9 to 22.3; p=0.003) and progressive disease despite chemotherapy (HR, 4.3; 95% CI, 1.6 to 12.0; p=0.005) were independent predictors of recurrence. Survival rates three months after pericardiocentesis differed significantly with the type of primary cancer; the rates were 73%, 18%, 90% and 30% in patients with adenocarcinoma of the lung, squamous cell carcinoma of the lung, breast cancer and other cancers, respectively. CONCLUSION: Recurrence and survival of patients with malignant pericardial effusion are dependent on the type of primary cancer and response to chemotherapy. Patients with adenocarcinoma of the lung may be good candidates for surgical drainage to avoid repeated pericardiocentesis, but pericardiocentesis is considered effective as palliative management in patients with other cancers.

Compliance with Adjuvant Chemotherapy for Completely Resected Non-small Cell Lung Cancer

PURPOSE : To evaluate the compliance of patients who underwent complete resection of non-small cell lung cancer (NSCLC) with adjuvant chemotherapy. MATERIALS AND METHODS : Between January 2004 and May 2006, patients who underwent a complete resection for NSCLC were referred to oncologists for adjuvant chemotherapy. Three or 4 cycles of platinum-based adjuvant chemotherapy was then performed according to the protocol or the preference of the oncologists. RESULTS : Two hundred and thirty-two patients were enrolled in this study. The median age of the study group was 60.9 years and 76.7 % of the patients enrolled were male. 34.9%, 28.8% and 36.2% of the patients were in stage IB, II and III respectively. In addition, 142 of the patients (61.2%) completed all planned cycles, whereas 65 patients (28%) received no therapy. The causes of start failure for adjuvant chemotherapy consisted of decreased postoperative performance status (n=39), refusal (n=13) and distant metastasis at the initial follow-up (n=2). The causes of cessation during adjuvant chemotherapy included the occurrence of severe adverse effects (n=12), aggravation of the disease with newly developed metastasis (n=4) and others (n=6). The mortality related to the adjuvant chemotherapy was 1.3 % (n=3), all of the fatalities were due to pneumonia and sepsis. Univariate analysis showed that age, postoperative complications and pathologic staging were the significant factors that determined whether the adjuvant chemotherapy was completed. Multivariate analysis demonstrated statistically significant differences in compliance when age and pathologic staging were considered. CONCLUSION : Adjuvant chemotherapy for completely resected NSCLC was performed with satisfactory compliance in approximately 60% of the patients included in this study, and age plays an important role in the compliance of adjuvant chemotherapy. Elderly subsets will be examined to help determine the effect of age on compliance and outcome. In addition, the medical oncologist tended to complete the adjuvant chemotherapy for more advanced cases of lung cancer than for stage IB lung cancer

Conservative Treatment with Octreotide as an Adjunct for Chylothorax after Lung Cancer Surgery: Two Cases / 대한흉부외과학회지

Postoperative chylothorax is a rare but serious complication of thoracic surgical procedures. We report two cases of chylothorax after lobectomy and mediastinal lymph node dissection for lung cancer. The patients were successfully treated with subcutaneous octreotide injection as an adjunct to conservative treatment.

Effect of Postoperative Pulmonary Morbidities on the Survival in Patients with Non-small Cell Lung Cancer

PURPOSE: The purpose of this study was to identify the effect postoperative pulmonary complications (PPCs) in patients with non-small cell lung cancer undergoing pulmonary resection on survival. MATERIALS AND METHODS: The study involved a retrospective review of 635 patients over a 4-year period who had undergone curative lung resection for non-small cell lung cancer. The patient group included 504 (79.4%) males, and the overall mean age was 61.3 years. Patients were classified as those who had experienced PPCs (PPCs group, n=105, 16.5% of all patients) or those who had not (no PPCs group, n=530 patients). RESULTS: The surgical procedures performed were 101 (15.9%) pneumonectomies, 505 (79.5%) lobectomies and 29 (4.6%) lesser resections. Cancer types comprised 330 (52.0%) squamous cell carcinomas, 255 (40.2%) adenocarcinomas and 50 (7.8%) others. Overall survival 3 years after surgery was 68.2% in the no PPCs group and 38.8% in the PPCs group (p<0.0001). Regardless of tumor staging, overall survival differed significantly between the PPCs and no PPCs groups, while disese-free survival did not. Seventy-six patients (14.9%) in the no PPCs group and 24 patients (27.3%) in the PPCs group died during the follow up period. The primary cause of death was the recurrence of the primary lung cancer in both groups (68 patients in the no PPCs and 14 in the PPCs). The second most frequent cause of deaths was respiratory failure in the PPCs group (9 patients : 10.2%). Respiratory failure was less observed in the no PPCs group. In contrast, the incidence of respiratory failure leading to death constantly increased in the PPCs group. CONCLUSION: Patients who had postoperative pulmonary complications have taken the risk of poor survival. We emphasize on the fact that patients who experienced postoperative pulmonary complications need careful and frequent shortterm follow-up to improve overall survival

Esophagectomy for Esophageal Cancer in Elderly Patients Over 70 Years of Age / 대한흉부외과학회지

BACKGROUND: Advanced age in Esophagectomy increases the risk of postoperative morbidity and mortality. However, the recent development of operative technique and perioperative care might have decreased the postoperative morbidity and mortality after esophagectomy. MATERIAL NAD METHOD: From March 2001 to July 2004, 174 patients underwent esophageal resection for esophageal cancer in the Center for Lung Cancer, National Cancer Center. The patients were divided into two groups : group 1 consisted of 27 patients aged 70 years or more, and group 2 consisted of 147 patients under 70 years of age. The two groups were compared according to preoperative risk factors, postoperative morbidity, operative mortality and survival. RESULT: The mean age was 63.4. There were 159 men. On histopathological examination, 93.1% had squamous cell carcinoma. On the locations, 78.7% were in mid and lower esophagus. Curative resections for esophageal cancer were possible in 162 (93.1%) patients. Mean hospital stay was 19.4 days with out difference between the groups. The overall postoperative morbidity were occurred in 61 patients (35.1%). The most frequent morbidity was pulmonary complication in 30 (17.2%). Preoperative incidence of hypertension, cardiac and pulmonary dysfunction were more common in Group I. However, there was no difference in overall postoperative morbidity, operative mortality and survival rate between the two groups. CONCLUSION: Esophagectomy for esophageal cancer could be carried out safely in patients over 70 years of age with satisfactory short-term results. Advanced age is no longer a risk factor for esophagectomy.

Metastsectomy a Feasible Treatment in Selected Patients with Gynecologic Malignancy / 대한산부인과학회잡지

To report cases of metastasectomy for metastatic gynecologic malignancies, we reviewed the medical records of all patients who have undergone metastasectomy for metastatic gynecologic malignancies in Center for Uterine Cancer from June 2001 to October 2002. Six patients were identified with median age of 55 years (range 52-66 years). The metastatic sites and primary sites were as follows: 3 liver metastasis from ovary; 1 abdominal wall metastasis from uterus (endometrial cancer), 1 brain metastasis from ovary, 1 lung metastasis from uterus (sarcoma). The median disease free interval was 48 months (range 10 months-13 years). There was no perioperative mortality. Postoperative morbidity was tolerable with 1 case of bile leakage. In three patients with hepatectomy, one patient was dead of disease after 15 months, one patient is alive with disease at 20 months of follow up, one patient have no evidence of recurrence at 7 months follow up. The patient with brain metastasis was dead due to lung metastsis after 9 months later postoperatively. Remaining two patients with abdominal wall and lung metastasis have no evidence of tumor recurrence at 4, 7 months follow up respectively. Metastasectomy for metastatic gynecologic malignancies can be performed safely and may help prolong survival in carefully selected patients.

Treatment of Stomach Cancer Involving Esophagogastric Junction / 대한흉부외과학회지

BACKGROUND: The origin site of carcinoma invading esophagogastric junction is variable. It may arise from squamous cell carcinoma of low esophagus, adenocarcinoma arising from Barrett's esophagus, adenocarcinoma of gastric cardia, or extension from proximal stomach cancer. In Korea, the majority of adenocarcinoma invading esophago-gastric junction seems to arise from proximal gastric carcinoma. MATERIAL AND METHOD: We reviewed the data of surgically-resected gastric adenocarcinoma involving esophagogastric junction in KCCH between 1988 and 1999. RESULT: There were 212 cases. Male to female ratio was 156 to 56. Age distribution was between 22 and 78. Variable surgical approaches including median laparotomy, laparotomy with left or right thoracotomy, left thoracotomy, and thoracoabdominal approach were used. Postoperative pathologic stages were : Stage IA-7, IB-11, II-25, IIIA-73, IIIB-34, and IV-57. Curative resection was performed in 199 patients, and total gastrectomy was performed in 200 patients. There were 77.4%(164 cases) with esophageal involvement, 74.1%(157 cases) with tumor involvement in the abdominal LN, and 8%(17 cases) with mediastinal LN metastasis. Operative mortality was 3.3%, and over-all 5 year survival rate was 35%. CONCLUSION: There are various surgical approaches and many things to consider for surgical resection, thoracic and abdominal approach may need for obtain proper resection margin and adequate lymph node dissection in stomach cancer invading esophagogastric junction.

A Case Report of Endobronchial Lipoma / 대한흉부외과학회지

Endobronchial lipomas are rare lesions that usually obstruct a major bronchus and cause irreversible pulmonary damage distally. They are histologically benign tumors. But they can produce pulmonary damage or irreversible bronchiectasis if dignoses or treatments are delayed. Whenever possible, the treatment of choice is resection by means of bronchoscopy. If endoscopic removal is not possible or if the nature of the tumor is unclear, surgery is necessary, with lobectomy or pneumonectomy being required in most cases due to the extensively damaged pulmonary parenchyma. We present a case of endobronchial lipoma causing bronchial obstruction and peripheral organizing pneumonia with its clinical features, diagnosis and treatment methods.