Suitable Patient Selection and Optimal Timing of Treatment for Persistent Air Leak after Lung Resection.

OBJECTIVES: The choice of therapeutic intervention for postoperative air leak varies between institutions. We aimed to identify the optimal timing and patient criteria for therapeutic intervention in cases of postoperative air leaks after lung resection. METHODS: This study utilized data from a prospective multicenter observational study conducted in 2019. Among the 2187 cases in the database, 420 cases with air leaks on postoperative day 1 were identified. The intervention group underwent therapeutic interventions, such as pleurodesis or surgery, while the observation group was monitored without intervention. A comparison between the intervention group and the observation group were analyzed using the cumulative distribution and hazard functions. RESULTS: Forty-six patients (11.0%) were included in the intervention group. The multivariate analysis revealed that low body mass index (p = 0.019), partial resection (p = 0.010), intraoperative use of fibrin glue (p = 0.008), severe air leak on postoperative day 1 (p < 0.001), and high forced expiratory volume in 1 s (p = 0.021) were significant predictors of the requirement for intervention. The proportion of patients with persistent air leak in the observation group was 20% on postoperative day 5 and 94% on postoperative day 7. The hazard of air leak cessation peaked from postoperative day 3 to postoperative day 7. CONCLUSIONS: This research contributes valuable insights into predicting therapeutic interventions for postoperative air leaks and identifies scenarios where spontaneous cessation is probable. A validation through prospective studies is warranted to affirm these findings.

Optimal Chest Drainage Method After Anatomic Lung Resection: A Prospective Observational Study.

BACKGROUND: Several methods for chest drainage after pulmonary resection of malignant lung tumors exist, but consensus on the ideal method has not been reached. METHODS: We conducted a multicenter prospective observational study. We enrolled 2200 patients who underwent lung resection for lung tumors. Of the 1470 patients who underwent anatomic resection, 347 showed air leak on the morning of postoperative day 1. They were assigned to 3 groups according to the chest drainage method on postoperative day 1. RESULTS: Of 347 patients with postoperative air leaks, 107 (30.8%), 179 (51.6%), and 61 (17.6%) were assigned to water seal, continuous suction, and digital drainage, respectively. The median postoperative air leak duration was significantly longer with digital drainage (4.0 days) than with either water seal (2.5 days) or continuous suction (3.0 days; P = .009). Chest tubes were required for significantly more days on average with digital drainage (6.0 days) than with water seal (4.0 days) or continuous suction (4.0 days; P = .003). Prolongation of air leak duration was significantly more likely to occur in patients with body mass index <18.5 kg/m2 (hazard ratio [HR], 1.6; 95% CI, 1.1-2.3), moderate or severe air leak on postoperative day 1 (HR, 2.0; 95% CI, 1.5-2.6), or digital drainage (HR, 1.4; 95% CI, 1.01-1.9). CONCLUSIONS: Water seal was associated with significantly shorter duration of postoperative air leak and chest drainage compared with continuous suction and digital drainage.

SCLC-J1, a novel small cell lung cancer cell line.

Small cell lung cancer (SCLC) is a type of high-grade neuroendocrine carcinoma. It initially responds to chemotherapy but rapidly becomes chemoresistant and it is highly proliferative. The prognosis in SCLC is poor. We have established a novel SCLC cell line, SCLC-J1, from a malignant pleural effusion in a patient with advanced SCLC. SCLC-J1 cells express ganglioside GD2, CD276, and Delta-like protein 3. RB1 is lost. These features of the new SCLC cell line may be useful in understanding the cellular and molecular biology of SCLC and in designing better treatment.

A prophylaxis study of acute exacerbation of interstitial pneumonia after lung cancer surgery.

INTRODUCTION: Acute exacerbation of interstitial pneumonia (AE-IP) is a lethal complication after lung surgery. We conducted a prospective, multi-institutional phase II trial to assess the efficacy and safety of prophylactic measures. METHOD: Patients with lung cancer with dorsal subpleural fibrotic changes occupying three or more segments of both lower lobes and planned anatomical lung resection were enrolled. Prior to surgery, patients received a 125-mg bolus injection of methylprednisolone and continuous intravenous infusion of sivelestat sodium hydrate (sivelestat) for 2 days. RESULTS: Sixty-nine patients were analysed. Preoperative high-resolution computed tomography (HRCT) showed 37 (53.6%) cases presented with usual interstitial pneumonia (UIP) and possible UIP pattern. There were 60 lobectomies and 9 segmentectomies. Thirty-eight cases were in clinical stage I. No adverse events associated with prophylaxis were observed. There were four cases of AE-IP (5.8%), higher than the expected 2.0%. Three of the four cases showed inconsistencies with the UIP pattern in preoperative HRCT and were pathologically diagnosed as UIP. All patients died of respiratory failure. Overall, 89.9% were diagnosed as idiopathic interstitial pneumonias; UIP was found in 48 patients (69.6%). Severe post-operative complications occurred in 11.6% of the cases. There were 35 deaths, 17 cases of lung cancer and 11 cases related to interstitial pneumonias. The overall survival rate at 3 years was 41.8% of the total and 47.2% of cases with clinical stage I. CONCLUSIONS: Perioperative use of sivelestat and low-dose methylprednisolone in patients with anatomical lung resection was safe but did not prove to be a prophylactic effect for AE-IP.

Retrospective study of efficacy of adjuvant chemotherapy using tegafur-uracil in patients with non-small cell lung cancer with primary tumor size of 4.1-5.0 cm.

BACKGROUND: The staging of patients with a tumor of diameter 4.1-5.0 cm and no lymphatic/distant metastases have been up-graded to stage IIA in the latest 8th edition of the TNM staging system. However, the efficacy of adjuvant tegafur-uracil (UFT) therapy in these patients, which has been recommended in the guideline issued by The Japan Lung Cancer Society, remains unclear. We evaluated the efficacy of adjuvant UFT therapy among a cohort by retrospective analyses of multicentric database. METHODS: In 2005-2007, 130 patients with p-stage IB non-small cell lung cancer (NSCLC) (diagnosed according to the 7th edition of the TNM staging system) and tumor size of ≥3.1 cm underwent anatomic complete resection at nine of our affiliated hospitals. We retrospectively reviewed the clinicopathological characteristics and the outcomes among these patients. RESULTS: Ninety-eight patients had tumor size of 3.1-4.0 cm (T2a group), whereas 32 patients had tumor size >4.0 cm (T2b group). Overall, patients who received adjuvant UFT showed a tendency of better outcomes than patients who did not [hazard ratio (HR) 0.564; 95% confidence interval (CI), 0.257-1.238, P=0.147]. In subgroup analyses, patients who received adjuvant UFT also tended to show better outcomes than those who did not in both T2a group and T2b group (HR 0.504; 95% CI, 0.202-1.255, P=0.132 in T2a group and HR 0.855; 95% CI, 0.181-4.033, P=0.843 in T2b group, respectively). CONCLUSIONS: Our results suggest that adjuvant UFT therapy have the potential to improve postoperative outcomes even in patients with p-stage IIA disease, as classified according to the 8th edition of the TNM staging system.

Gender Differences in the Recurrence Timing of Patients Undergoing Resection for Non-Small Cell Lung Cancer

Objective: This study was designed to visually represent postoperative recurrence patterns using event dynamics and to assess sex-based differences in the timing of recurrence for non-small cell lung cancer. Methods: We studied 829 patients (538 men, 291 women) with NSCLC who underwent complete pulmonary resection in 9 hospitals. Event dynamics with the use of life-table methods were evaluated, and only first events (distant metastases or local recurrence) were considered. The effects of sex, histological type, pathological stage, and smoking history were studied. Result: The resulting smoothed hazard rate curves indicated that the recurrence risk pattern definitely correlated with sex, with a sharp peak in the first year in men and a broad peak during the first 2 to 3 years in women. These findings were also confirmed by analyses according to pathological stage, histological type, and smoking history. Conclusion: The peak times of recurrence differed considerably between men and women. The delayed time of peak recurrence in women, associated with a longer disease-free interval within subsets of patients with similar disease stage, histological type, and smoking status, might account for the better survival in women.

Lobe-Specific Lymph Node Dissection as a Standard Procedure in Surgery for Non-Small Cell Lung Cancer: A Propensity Score Matching Study.

INTRODUCTION: Systematic lymph node dissection (SND) is the standard procedure in surgical treatment for NSCLC, but the value of this approach for survival and nodal staging is still uncertain. In this study, we evaluated the potential of lobe-specific lymph node dissection (L-SND) in surgery for NSCLC by using a propensity score matching method. METHODS: From 2005 to 2007, 565 patients with cT1a-2b N0-1 M0 NSCLC underwent lobectomy with lymph node dissection at our 10 affiliated hospitals. Patients were classified into groups that underwent nodal sampling, L-SND, and systematic dissection SND on the basis of pathological data for the number and extent of nodal resection. A total of 77 patients with insufficient pathological data were excluded from the study. RESULTS: Overall, survival did not differ significantly among the groups (p = 0.552), but the rate of detection of pN2 in the SND group (13.1%) was significantly higher than in the nodal sampling (3.3%) and L-SND (9.0%) groups (p = 0.010). However, given the many confounding factors in the patient characteristics in each group, outcomes were reevaluated using a propensity score matching method for the L-SND and SND groups. After matching, the two groups had no significant differences in 5-year overall survival (73.5% for L-SND versus 75.3% for SND, p = 0.977) and pN2 detection (8.2% in both groups, p = 0.779). CONCLUSIONS: These results suggest that lobe-specific lymph node dissection has the potential to be a standard procedure in surgical treatment for NSCLC.

Postoperative follow-up strategy based on recurrence dynamics for non-small-cell lung cancer.

OBJECTIVES: Our study was designed to visually represent recurrence patterns after surgery for non-small-cell lung cancer (NSCLC) with the use of event dynamics and to clarify postoperative follow-up methods based on the times of recurrence. METHODS: A total of 829 patients with NSCLC who underwent complete pulmonary resection from 2005 to 2007 in 9 hospitals affiliated with the Yokohama Consortium of Thoracic Surgeons were studied. Event dynamics, based on the hazard rate, were evaluated. Only first events involving the development of distant metastases, local recurrence or both were considered. The effects of sex, histological type, pathological stage and age were studied. RESULTS: The hazard rate curve displayed an initial surge that peaked about 6-8 months after surgery. The next distinct peak was noted at the end of the second year of follow-up. On non-parametric kernel smoothing, the maximum peak was found 6-8 months after surgery in men. In women, the highest peak occurred 22-24 months after surgery, which was about 16 months later than the peak in men. The peak timing of the hazard curve was not affected by histological type, pathological stage or age in either sex. CONCLUSIONS: Our results suggest that the timing of recurrence after surgery for lung cancer is characterized by a bimodal pattern, and the times with the highest risk of recurrence were suggested to differ between men and women. Postoperative follow-up strategies should be based on currently recommended follow-up programmes, take into account the recurrence patterns of lung cancer, and be modified as required to meet the needs of individual patients.

Therapeutic outcome after resection of pulmonary metastases from oral and/or head and neck cancers: complete republication of the article published in Jpn J Chest Surg.

OBJECTIVE: Thus far, very few studies have assessed the efficacy and outcome of resection of pulmonary metastases originating from primary oral cancer and/or head and neck cancer. METHODS: We retrospectively reviewed 13 cases that had metastases from primary oral cancers and/or head and neck cancers, and had undergone metastasectomy in our hospital from January 2000 through March 2011. RESULTS: Twelve patients were male and one was female. The median disease-free interval from the time of treatment of their primary cancer was 12 (range 1-73) months. Eleven cases underwent partial resection, one underwent segmentectomy, and one underwent lobectomy. The overall 5-year survival rate after last pulmonary metastasectomy was 45.7 %, and the median survival time was 23 months. Factors predicting a poor prognosis according to univariate analysis were a disease-free interval of <12 months and a diagnosis of stage IV primary cancer, but multivariate analysis revealed no significant prognostic factors. CONCLUSIONS: Pulmonary metastasectomy would give a chance for long-term survival in patients with oral and/or head and neck cancers.

Influence of visceral pleural invasion on survival in completely resected non-small-cell lung cancer.

OBJECTIVES: Although the prognostic implications of visceral pleural invasion (VPI) are well established, it remains controversial whether the extent of VPI affects survival in patients with completely resected non-small-cell lung cancer (NSCLC). In addition, the impact of VPI according to nodal status is unclear. We evaluated the influence of the extent of pleural invasion on survival by analysing a multicentre retrospective database of patients who had undergone surgery for NSCLC. METHODS: We retrospectively reviewed the clinicopathological characteristics and outcomes of 639 patients with NSCLC who underwent anatomic complete resection from 2005 to 2007 at nine hospitals affiliated with the Yokohama Consortium of Thoracic Surgeons. RESULTS: The median follow-up was 65.0 months. The extent of pleural invasion was PL0 in 462 patients, PL1 in 135 and PL2 in 42. The 5-year overall survival rate was significantly higher in patients with PL0 tumours (75.9%) than in those with PL1 (63.6%) or PL2 tumours (54.1%). On subgroup analysis according to nodal status, PL0 was associated with a higher survival rate than that of PL1 or PL2 tumours in patients with N0 or N1 metastasis, but not in those with N2 metastasis. There was no difference between PL1 and PL2 in any subgroup. CONCLUSIONS: Our results suggest that the presence of VPI, rather than the extent, has an impact on postoperative survival in patients with NSCLC who have N0 or N1 metastasis. Because very few previous studies have addressed the effects of VPI in patients with N1 disease, further re-evaluation of the prognostic impact of VPI is necessary in this subgroup of patients.

Assessment of spontaneous hemopneumothorax: Indications for surgery.

BACKGROUND: Although spontaneous hemopneumothorax is rare, emergency surgery may be necessary if massive bleeding is present. METHODS: We examined therapeutic strategies and outcomes as well as background factors in 16 patients with spontaneous hemopneumothorax treated at our hospital between April 2002 and August 2013. RESULTS: Emergency surgery was performed in 3 patients, all of whom were hemodynamically unstable. Elective surgery was performed in 7 patients, all of whom showed continuous bleeding from a pleural cavity drain. The surgery consisted of intrapleural hematoma removal, hemostasis, and bullectomy; 3-port thoracoscopy was used in all of the surgical cases. Six patients, none of whom showed continuous bleeding, recovered with conservative therapy. Comparing the conservative therapy and surgery groups revealed the mean continuous bleeding volume and total blood loss to be significantly greater in the latter, but no significant difference was noted between the two groups in terms of the initial bleeding volume following tube thoracostomy. None of the cases required a blood transfusion. CONCLUSIONS: Spontaneous hemopneumothorax is not necessarily an indication for surgery, and even when the initial volume of blood drained through the chest tube is large, some patients can still be treated conservatively with careful monitoring of vital signs and continuous bleeding volumes. However, it is important not to miss the optimal timing of surgery in order to avoid administering unnecessary blood transfusions to young patients.

Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases.

A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One-hundred-and-seventy-nine cases with pathological stage I ADC were classified according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One-hundred-and-thirty-seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5-year disease-free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high-histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post-operative recurrence (HR 3.661, 95% CI 1.421-9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.

Clinical significance of immunohistochemical expression of insulin-like growth factor-1 receptor and matrix metalloproteinase-7 in resected non-small cell lung cancer.

Insulin-like growth factor-1 receptor (IGF-1R) and matrix metalloproteinase-7 (MMP-7) have been reported to be related to tumor invasion and metastasis in various malignancies. The aim of this study was to evaluate the expression levels of IGF-1R and MMP-7 in resected non-small cell lung cancer (NSCLC) and to examine the relationship of such levels to clinical characteristics and survival. Expression was measured immunohistochemically. The percentage of stained cells was multiplied by the staining intensity. The sample was classified as high when the score was equal or higher than the median value or was otherwise considered to be low. High IGF-1R expression was associated with nodal metastasis and recurrence (P=0.034 and 0.006, respectively). High IGF-1R expression was associated with significantly poorer overall survival than low IGF-1R expression (P=0.011). MMP-7 expression did not significantly correlate with any clinicopathological factor. There was a trend toward slightly, but not significantly poorer survival in patients with MMP-7-high tumors than in those with MMP-7-low tumors (P=0.220). There was no significant correlation between IGF-1R expression and MMP-7 expression (P=0.184). Upon multivariate analysis, IGF-1R expression was independently related to the outcomes of patients with NSCLC. Overexpression of IGF-1R may be a useful predictor of lymph node metastasis, recurrence and post-surgical outcomes in patients with NSCLC.

Pneumothorax derived from bronchiolitis obliterans after marrow transplantation.

Long-term survival has become achievable after bone-marrow transplantation, but various pulmonary diseases due to chronic graft-vs.-host disease have been recognized. Particularly, bronchiolitis obliterans is a life-threatening complication with no effective remedy. Bilateral pneumothorax associated with bronchiolitis obliterans is rare, but it requires careful attention. In a 42-year old man with intractable pneumothorax after bone marrow transplantation and surgical procedures, extensive thoracolysis was effective as an acute treatment for this disease.

Prognostic value of CD133 expression in stage I lung adenocarcinomas.

CD133 is one of the most representative cancer stem cell markers. This study evaluated the potential prognostic value of CD133 expression in stage I lung adenocarcinomas (ADC). Tumors from 177 patients were immunohistochemically examined for CD133 expression, and their associations with disease recurrence were analyzed. Also, the potential prognostic value of combining CD133 expression with proliferating activity measured by immunohistochemical expression of Ki-67 and vessel involvement was evaluated. CD133 high expressers showed a significantly higher risk of recurrence than CD133 low expressers: 5-year disease-free survival (DFS) rate 77.2% vs. 95.1% (p=0.004), adjusted Hazard ratio (HR) 4.37, 95% Confidence Interval (CI) 1.30-14.71 (p=0.017). CD133 high expressers having strong proliferating activity and/or with vessel invasion showed a higher risk of recurrence: 5-year DFS rate 66.5% in CD133 high/Ki-67 high expressers vs. 93.2% in the other types (p<0.001), adjusted HR 8.39, 95% CI 2.65-26.54 (p<0.001): 5-year DFS rate 51.0% in CD133 high expressers with vessel invasion vs. 92.9% in the other types (p<0.001), adjusted HR 4.50, 95% CI 1.51-13.34 (p=0.007): 5-year DFS rate 53.9% in CD133 high/Ki-67 high expressers with vessel invasion vs. 91.2% in the other types (p<0.001), adjusted HR 9.32, 95% CI 3.42-25.39 (p<0.001). In conclusion, the level of CD133 expression is an independent prognostic marker and its combination with proliferating activity and/or vessel invasion could have excellent prognostic value to predict postoperative recurrence in patients with stage I lung ADC.

Reduced expression of claudin-7 is associated with poor outcome in non-small cell lung cancer.

Claudin-7 is a tight junction protein that plays an important role in tumorigenesis, tumor invasion and metastasis. We examined the clinical significance of claudin-7 expression in 75 postsurgical non-small cell lung cancer (NSCLC) patients. Claudin-7 expression was measured immunohistochemically and was found to be high in 25 patients (33.3%) and low in 50 (66.7%). Survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high NSCLCs (P=0.024). In particular, survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high squamous cell carcinomas (P=0.011). A reduced expression of claudin-7 was associated with poor outcome in NSCLCs. Claudin-7 may thus be a useful biomarker and a potential therapeutic target in patients with NSCLC.