Keizo Misumi

Difference in Prognostic Significance of Maximum Standardized Uptake Value on [18F]-Fluoro-2-Deoxyglucose Positron Emission Tomography Between Adenocarcinoma and Squamous Cell Carcinoma of the Lung

OBJECTIVE This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. METHODS We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n = 132) or squamous cell carcinoma (n = 44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. RESULTS The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P< 0.001). Analyses of receiver operating characteristic curves identified an optimal maximum standardized uptake value cutoff value to predict recurrence of 3.7 for adenocarcinoma, whereas such an indicator could not be identified for squamous cell carcinoma. Although 2-year disease-free survival rates were 70.2% for maximum standardized uptake value ≤6.95 and 59.3% for maximum standardized uptake value >6.95 (P = 0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P < 0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P < 0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P = 0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P = 0.001). CONCLUSIONS Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung.

Radical hybrid video-assisted thoracic segmentectomy: long-term results of minimally invasive anatomical sublobar resection for treating lung cancer

We analysed the results of radical segmentectomy achieved through a hybrid video-assisted thoracic surgery (VATS) approach that used both direct vision and television monitor visualization at a median follow-up of over 5 years. Between April 2004 and October 2010, 102 consecutive patients able to tolerate lobectomy to treat clinical T1N0M0 non-small cell lung cancer (NSCLC) underwent hybrid VATS segmentectomy in which we used electrocautery without a stapler to divide the intersegmental plane detected by selective jet ventilation in addition to the path of the intersegmental veins. Curative resection was achieved in all patients. The median surgical duration and blood loss during the surgery were 129 min (range, 60-275 min) and 50 ml (range, 10-350 ml), respectively. The complication rate was 9.8% (10/102) with the most frequent being prolonged air leak, and there was no case of in-hospital death or 30-day mortality post procedure. Five and seven patients developed locoregional and distant recurrences, respectively. The overall and disease-free 5-year survival rates were 89.8% and 84.7%, respectively. Radical hybrid VATS segmentectomy including atypical resection of (sub)segments is a useful option for clinical stage-I NSCLC. The exact identification of anatomical intersegmental plane followed by dissection using electrocautery is critical from oncological and functional perspectives.

Multidisciplinary Team-Based Approach for Comprehensive Preoperative Pulmonary Rehabilitation Including Intensive Nutritional Support for Lung Cancer Patients

Background To decrease the risk of postoperative complication, improving general and pulmonary conditioning preoperatively should be considered essential for patients scheduled to undergo lung surgery. Objective The aim of this study is to develop a short-term beneficial program of preoperative pulmonary rehabilitation for lung cancer patients. Methods From June 2009, comprehensive preoperative pulmonary rehabilitation (CHPR) including intensive nutritional support was performed prospectively using a multidisciplinary team-based approach. Postoperative complication rate and the transitions of pulmonary function in CHPR were compared with historical data of conventional preoperative pulmonary rehabilitation (CVPR) conducted since June 2006. The study population was limited to patients who underwent standard lobectomy. Results Postoperative complication rate in the CVPR (n = 29) and CHPR (n = 21) were 48.3% and 28.6% (p = 0.2428), respectively. Those in patients with Charlson Comorbidity Index scores ≥2 were 68.8% (n = 16) and 27.3% (n = 11), respectively (p = 0.0341) and those in patients with preoperative risk score in Estimation of Physiologic Ability and Surgical Stress scores >0.3 were 57.9% (n = 19) and 21.4% (n = 14), respectively (p = 0.0362). Vital capacities of pre- and post intervention before surgery in the CHPR group were 2.63±0.65 L and 2.75±0.63 L (p = 0.0043), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6815). Forced expiratory volumes in one second of pre- and post intervention before surgery in the CHPR group were 1.73±0.46 L and 1.87±0.46 L (p = 0.0012), respectively; however, their transition in the CVPR group was not statistically significant (p = 0.6424). Conclusions CHPR appeared to be a beneficial and effective short-term preoperative rehabilitation protocol, especially in patients with poor preoperative conditions.

Prediction for prognosis of resected pT1a-1bN0M0 adenocarcinoma based on tumor size and histological status: relationship of TNM and IASLC/ATS/ERS classifications.

OBJECTIVES This study aimed to estimate the relationship between 7th TNM classification and IASLC/ATS/ERS classification with regard to tumor size and pathological status and to determine the utility of these classifications for predicting prognosis in resected node-negative adenocarcinoma with tumor size ≤2.0 cm and >2.0-3.0 cm. MATERIALS AND METHODS We reviewed 321 pN0M0 lung adenocarcinoma cases resected at Hiroshima University Hospital from January 1991 to December 2010. Histological differences between T1a and T1b based on the IASLC/ATS/ERS classification were estimated and followed by evaluation of overall survival (OS) and recurrence-free interval (RFI) based on differences in tumor size and histological features. RESULTS We found 188 cases of pT1a-1bN0M0 (135 T1a, 53 T1b). Pathological T1a tumors included significantly more adenocarcinoma in situ (AIS) cases and minimally invasive adenocarcinoma (MIA) cases than T1b tumors (60.7% vs 18.8%, respectively; p<0.0001), while more invasive adenocarcinoma cases were included in pT1b. By considering the two classifications simultaneously, the 5-year OS rates of T1a AIS/MIA, T1b AIS/MIA, T1a invasive adenocarcinoma, and T1b invasive adenocarcinoma were 97.5%, 87.5%, 95.8%, and 86.8%, respectively. The 5-year RFIs of T1a AIS/MIA, T1b AIS/MIA, T1a invasive adenocarcinoma, and T1b invasive adenocarcinoma were 100%, 100%, 91.3%, and 72.5%, respectively. T1a AIS/MIA and T1b AIS/MIA could be separated as good prognostic cases with a 100% RFI. Multivariate analysis indicated that only T1b invasive adenocarcinoma was an independent factor for predicting recurrence (p=0.001). CONCLUSION Compared to a single classification, combining TNM and IASLC/ATS/ERS classifications could provide more detail information concerning disease recurrence. AIS and MIA should be handled equally, regardless of tumor size, because their non-/less invasive status is more useful for predicting prognosis than their tumor size classification. In contrast, the T descriptors based on TNM classification are important for predicting prognosis in invasive adenocarcinoma.

Classifications of N2 Non–Small-Cell Lung Cancer Based on the Number and Rate of Metastatic Mediastinal Lymph Nodes

BACKGROUND Subdivisions of N2 non-small-cell lung cancer (NSCLC) cases based on metastatic status of mediastinal and non-mediastinal lymph nodes have been proposed. This study aimed to evaluate N2 disease classification by mediastinal lymph nodes alone. PATIENTS AND METHODS We reviewed 187 patients with NSCLC pN1-N2 who were surgically treated to evaluate the proposed classifications: number, rate, nodal zone of metastatic lymph nodes. We evaluated N2 disease classification based on mediastinal lymph nodes alone in 136 pN2 cases. RESULTS The number (1-2, 3-5, and 6 ≤) or rate (15%≥, 15%< to 40%>, and 40%≤) classification based on all metastatic lymph nodes was validated by the log-rank test and Cox proportional hazards model. After reclassification by number or rate of metastatic mediastinal lymph nodes alone, a significant difference was maintained among all groups except between the 3-5 and 6 ≤ groups. The 5-year survival rates of the 1-2, 3-5, and 6 ≤ groups were 63.4%, 32.4%, and 18.2%, respectively (1-2 vs. 3-5, P = .015; 3-5 vs. 6 ≤, P = .134). With rate classification, the 5-year survival rates of the 15%≥, 15%-40% (15%< to 40%>), and 40%≤ groups were 56.0%, 27.3%, and 5.04%, respectively (15%≥ vs. 15%-40%, P = .011; 15-40% vs. 40%≤, P = .011). The Spearmans rank correlation coefficient showed a highly significant correlation of metastatic status between mediastinal lymph nodes and all lymph nodes (both P < .001). CONCLUSION Classification by number and rate of mediastinal lymph nodes alone enabled subdivision of N2 NSCLC cases. Metastatic status of mediastinal lymph nodes reflects that of all lymph nodes and is prognostic indicators.

Outcomes after lobar versus sublobar resection for clinical stage I non−small cell lung cancer in patients with interstitial lung disease

Objective: Since the prognosis after standard lobectomy for non−small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD) is poor, we investigated the possibility of sublobar resection for the improvement of the surgical results in such patients. Methods: Of 796 consecutive patients with clinical stage I NSCLC who underwent pulmonary resection, 107 were diagnosed with ILD using high‐resolution computed tomography (HRCT). Overall survivals (OS) were compared between patients with non‐ILD and those with ILD or between patients with ILD who underwent lobectomy and those who underwent sublobar resection. ILD patterns consisted of usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. The log‐rank statistics and Cox proportional hazard models were used to test for survival differences. Results: OS was significantly lower in patients with “ILD inconsistent with UIP” pattern (hazard ratio [HR], 2.66; 95% confidence interval [CI], 1.19‐5.97; P = .014), or “ILD with possible UIP or UIP” patterns (HR, 2.38; 95% CI, 1.76‐3.21; P < .001) compared with patients with non‐ILD. No significant difference in OS was observed between patients with ILD who underwent either lobectomy or sublobar resection (HR, 1.82; 95% CI, 0.81‐4.06; P = .19). Multivariable Cox analysis demonstrated diffusing capacity of the lung for carbon monoxide (HR, 0.95; 95% CI, 0.91‐0.99; P = .009) and not surgical procedure (HR, 2.76; 95% CI, 0.83‐9.16; P = .099), as an independent prognostic factor for OS. Conclusions: Sublobar resection may be a potential alternative choice for clinical stage I NSCLC with ILD on HRCT.

Prognostic impact of the primary tumor location based on the hilar structures in non-small cell lung cancer with mediastinal lymph node metastasis

The status of mediastinal lymph node metastasis is one of the main factors determining the treatment strategy for non-small cell lung cancer (NSCLC), but the primary tumor location is not considered crucial in the tumor-node-metastasis (TMN) classification at present. The aim of this study was to estimate the prognostic value of the primary tumor location on the basis of the hilar structures in NSCLC with mediastinal lymph node metastasis. We retrospectively reviewed the cases of 337 consecutive patients who underwent surgical resection for NSCLC between 1995 and 2004, divided the pN2 NSCLC cases (n=40) into central- and peripheral-type tumors according to the distance of the primary tumor from the first branch of the extrapulmonary bronchus, and compared the surgical outcomes between these tumor groups. Eighteen and twenty-two cases were classified as central- and peripheral-type tumors, respectively. The 5-year survival rate was significantly better for patients with central-type tumors than peripheral-type tumors (51.5% vs. 21.2%, P=0.034). The location-specific prognostic tendency was noted irrespective of the presence (n=13) or absence of skip metastasis. In a multivariate Cox analysis of the N2 NSCLC cases, the primary tumor location was a significant (P=0.026) prognostic factor for overall survival. In conclusion, evaluation of the primary tumor location based on the hilar structures is useful to predict the prognosis in N2 NSCLC.

Fibrinogen/thrombin-based collagen fleece (TachoComb®) promotes regeneration in pulmonary arterial injury

OBJECTIVES To repair unexpected damage of the pulmonary artery (PA) during thoracic surgery, fibrinogen/thrombin-based collagen fleece (TachoComb(®) [TC]) can be applied as a haemostatic material. The progression of vessel restoration with TC has not been elucidated. In this study, we investigate details of the healing process with TC after PA injury using a canine model. METHODS Left thoracotomy was performed on female beagles under general anaesthesia. PA injury was induced and repaired using TC. Repair sites were histologically evaluated 2, 4 and 8 weeks after surgery (n = 3 in each group). RESULTS Haemostasis of PA injury was achieved promptly after TC application. After surgery, no bleeding was found in the thoracic cavity, and no repair sites revealed stenosis, thrombi or false aneurism formation. Two weeks after surgery, inflammatory cells had infiltrated around the vascular defect, and vascular endothelium had regenerated on the innermost surface of TC applied to the defect. At Week 4, elastic and smooth muscle fibres had begun to extend into the defect between the endothelial layer and collagen fleece. By Week 8, elastic fibres and smooth muscle had completely regenerated in the medial layer. The adventitial layer had also fully regenerated. CONCLUSIONS Haemostasis of injured PA using TC was safe and reliable. TC provided a mechanical scaffold on which vascular regeneration occurred. Three layers reconstructed in the PA defect were identical to those in normal structures.

Video-assisted thoracic surgery lobectomy for lung cancer: the point at issue.

Among the four subjects addressed in this article, the definition of video-assisted thoracic surgery (VATS) lobectomy is fundamentally the point at issue, which leads to various obstacles for upcoming clinical trials. It is strongly expected that VATS lobectomy will be identified as a standard operation for primary lung cancer with confirmed clinical evidence. Standard surgical procedure with a certain oncological validity for lung cancer should be minimally invasive, safe, and technically simple for general thoracic surgeons. In conclusion, most patients with resectable lung cancer will be able to benefit from a validated painless VATS lobectomy in the near future.

Comparison of Postoperative Pain after Different Thoracic Surgery Approaches as Measured by Electrical Stimulation

BACKGROUND Postoperative pain is commonly evaluated using the numerous rating scale (NRS), visual analogue scale, or pain scale; however, these assessments are easily affected by various subjective factors. We measured the degree of postoperative chest pain among different thoracic surgery approaches using NRS and electrical stimulation measurements. METHODS Seventy patients who underwent lobectomy or segmentectomy were enrolled. Concomitant with NRS, pain scores were quantitatively measured on postoperative day 2 using an electrical neurostimulator to compare the degree of pain among three different surgical approaches: pure video-assisted thoracic surgery (VATS), hybrid VATS, and conventional thoracotomy. The risk factors associated with postoperative pain were also analyzed. RESULTS Thirty patients underwent lung resection with pure VATS, while 30 had hybrid VATS, and 10 had conventional thoracotomy. Among the three surgical approaches, analyzing the pain score indicated statistically significant differences (pure, 159.50 ± 26.22; hybrid, 269.36 ± 30.49; thoracotomy, 589.40 ± 141.11; p = 0.003); however, NRS did not obtain a statistically significant difference between the three approaches (pure, 4.26 ± 0.27; hybrid, 4.96 ± 0.30; thoracotomy, 5.50 ± 0.68; p = 0.105). A multivariate analysis showed that the surgical approach was an independent risk factor for postoperative pain as determined by the pain score (pure vs. hybrid, p = 0.076; pure vs. thoracotomy, p < 0.001). CONCLUSION For lung surgery, the differences in surgical approach were an independent risk factor for postoperative pain. In the early postoperative period, pure VATS was shown to be the least painful of the three surgical approaches.