Takuya Nagashima

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.

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.

Relationship between phosphorylation of sperm-specific antigen and prognosis of lung adenocarcinoma.

UNLABELLED Lung cancer is generally considered as a highly malignant cancer. A major challenge for the management of lung adenocarcinoma patients is to predict the clinical course of the disease after resection. We analyzed the different levels of phosphorylation of proteins in lung adenocarcinoma tissues between a poor prognosis (PP) group, in which six patients exhibited recurrence within five years after surgery, and a good prognosis (GP) group, in which seven patients did not exhibit recurrence within five years after surgery. We found that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2) [phospho-SSFA2(pS92)] was stimulated in the PP group. Using samples from a total of 46 patients, we investigated the utility of phospho-SSFA2(pS92) to discriminate patients of GP and PP groups, with multiple reaction monitoring (MRM) mass spectrometry. Consequently, we confirmed that the PP group had significantly elevated phospho-SSFA2(pS92) levels. Additionally, no expression of SSFA2 recognized in the normal lung tissues. From these results, we demonstrate that phospho-SSFA2 (pS92) is related to the prognosis of early resected lung adenocarcinomas. Therefore, we suggest that phosphorylation of this protein indicates its role as a potential biomarker and new therapeutic target. BIOLOGICAL SIGNIFICANCE Lung adenocarcinoma patients often experience a high rate of recurrence after surgery. It is important to discover biomarkers for prognostic prediction and therapeutic targets for treatment of early-stage lung adenocarcinoma. In this study, using tissue samples obtained from patients with lung adenocarcinoma that had been stored for five years at -80°C, we identified 13 unique phosphorylated peptides, which were differentially expressed between poor and good prognosis groups. We confirmed that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2)[phospho-SSFA2 (pS92)], was related to poor prognosis. Our study demonstrates that prognostic prediction of early-stage lung adenocarcinoma is possible, and suggests new therapeutic targets for its treatment.

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.

Thoracoscopic right S6 sleeve segmentectomy for squamous-cell carcinoma arising from the B6 central bronchus

We describe a patient with low respiratory function who underwent thoracoscopic sleeve segmentectomy to preserve lung function as much as possible. The patient had already used home oxygen therapy because of chronic obstructive lung disease. There was a squamous-cell carcinoma at inlet of right B6 bronchus, and cT1aN0M0 disease was diagnosed. Because respiratory function was poor, right S6 segmentectomy was scheduled. Moreover, to preserve the respiratory muscles as much as possible, a thoracoscopic approach was selected. We performed S6 sleeve segmentectomy, and sutured the lower bronchus and basal bronchus. There were some limitations in handling needles during thoracoscopy. To resolve these difficulties, we devised two techniques. One was to suture the bronchus with continuous sutures on the mediastinal side and simple interrupted sutures on the other side. The other was to create a working space for handling the needles to avoid entanglement of the sutures. These techniques allowed us to suture the bronchi relatively easily.

Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal and lung malignancy patients

The present study evaluated the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies. Patients ≥70 years of age who underwent surgery for gastrointestinal or lung malignancy were eligible for participation in the study. The 186 eligible patients were randomly assigned at a 1:1 ratio to receive TJ-54 or control during their peri-operative care (between 7 days prior to surgery and 4 days following surgery, except for the operation day). The signs and symptoms of delirium were assessed using the Diagnostic and Statistical Manual of Mental Disorders-IV by the investigator during the peri-operative period. A total of 186 eligible gastrointestinal or lung malignancy patients were analyzed (93, TJ-54; 93, control). There were no marked differences between the two randomized groups. The incidence of delirium was 6.5% (6 patients) in the TJ-54 group and 9.7% (9 patients) in the control group, with no significant difference (P=0.419). However, of the patients categorized with a mini-mental state examination (MMSE) score of ≤26, the incidence of postoperative delirium was 9.1% in the TJ-54 group and 26.9% in the control group [risk ratio, 0.338; 95% confidence interval (0.078–1.462), P=0.115]. Treatment with TJ-54 reduced the incidence of postoperative delirium compared with the control group. Although TJ-54 did not demonstrate any contribution to preventing or treating postoperative delirium in patients following surgery for gastrointestinal or lung malignancy, TJ-54 reduced the risk of postoperative delirium in the patients who were classified as MMSE ≤26. Further phase III studies with a larger sample size are required in order to clarify the effects of TJ-54 against postoperative delirium.

Thoracoscopic left mediastinal lymph node dissection

In Japan, the use of video-assisted thoracoscopic surgery (VATS) for primary lung cancer is increasing. However, it is not easy to perform mediastinal lymph node dissection using VATS as effectively as it is performed using thoracotomy. Herein, I have presented two techniques for subcarinal lymph node dissection from the left thoracic cavity: one involves the retraction of the lower bronchus towards the visceral and cranial side before inferior pulmonary vein resection to secure the view of the right lower portion. The other involves the separation of lymph nodes from the right main bronchus before separation from the left bronchus, to prevent the lymph nodes from falling down and interrupting the right-side view. Moreover, I have also described a technique that facilitates left upper mediastinal lymph node dissection. It involves traction of a thoracic cardiac branch from the recurrent laryngeal nerve allowing visualization of the bottom of the #4L lymph node, so that it can be dissected easily. There has been no observation of recurrent nerve paralysis using this procedure.