The Utility of Indigo Carmine and Lipiodol Mixture for Preoperative Pulmonary Nodule Localization before Video-Assisted Thoracic Surgery.

PURPOSE: To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS). MATERIALS AND METHODS: One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3-3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0-3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1-3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1-3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively. RESULTS: The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred. CONCLUSIONS: MIL was safe and useful for preoperative pulmonary nodule marking.

Importance of avoiding surgery delays after initial discovery of suspected non-small-cell lung cancer in clinical stage IA patients.

INTRODUCTION: The natural history of consolidation on computed tomography (CT) rarely includes invasive cancers, and evidence of the ideal timing for surgical intervention via long-term follow-up studies remains unknown. METHODS: Between January 2012 and June 2017, pulmonary resection was undertaken in 293 clinical IA patients who were followed-up for > 6 months after the first detection of potential non-small-cell lung cancer (NSCLC) opacities. We evaluated the corresponding HRs and compared the recurrence risk with the CT follow-up duration. RESULTS: HRs calculated for the longest intervals were compared between two patient subsets: a shorter-interval surgery group (SISG: 41.3%; mean follow-up interval, 13.5±5.3 months) and a longer-interval surgery group (58.7%; mean follow-up interval, 54.9±25.6 months). On Cox multivariate regression analyses, CT consolidation (ratio >0.5), an abnormal carcinoembryonic antigen and a triple-negative mutation showed an independent association with an unfavorable prognosis, as measured by disease-free survival after the first detection of potential NSCLC opacities. The longer-interval surgery group fared significantly better than the SISG in terms of 5-year overall survival after the first detection (99.3% vs 93.1%, P<0.01); the 3-year overall survival after the first detection was significantly shorter in the high-risk SISG (presence of two factors from the three) than that in the low-risk SISG (presence of 0 or one factor; 100% vs 73.3%, P<0.01). CONCLUSION: Our study indicates that the patients with potential NSCLC opacities who are able to wait for more than 2 years prior to pulmonary resection may be likely to have a favorable prognosis, whereas early judgment for surgical resection should be required for avoiding surgical delays.

Spontaneous regression of lung squamous cell carcinoma with synchronous mediastinal progression: A case report.

Spontaneous regression (SR) of cancer implies the partial or complete disappearance of malignant disease without or with adequate medical treatment. Typically, SR of cancer is a sporadic event, especially in non-small cell lung cancer (NSCLC). Although the underlying mechanism of SR remains unknown, stimulation of an immunological response has been proposed. Herein, we report the case of a 56-year-old woman exhibiting SR of NSCLC with a mediastinal disease. Despite regression of the primary site after a lung biopsy, simultaneous progression of mediastinal lymph node metastasis occurred. Specimens obtained by surgical resection pathologically confirmed both primary and metastatic sites. Reportedly, primary and metastatic tumors shrink synchronously in SR of metastatic NSCLCs. Thus, the fact that the SR of NSCLC can present inconsistent development in primary and metastatic sites should be considered, and direct intervention is recommended if physicians diagnose this phenomenon.

Contribution of smoking habit to the prognosis of stage I KRAS-mutated non-small cell lung cancer.

BACKGROUND: One of the known risk factors for non-small cell lung cancer (NSCLC) is somatic mutation in the Kirsten rat sarcoma (KRAS) gene. The relationship with smoking is well known. METHODS: We retrospectively studied the data of 92 patients who underwent pulmonary resection January 2003 and June 2012 and were diagnosed as KRAS-mutated pathological stage I adenocarcinoma. RESULTS: Among them, 33 patients who were non to light smoker (NLS) (smoking index, 0 to 400) were compared with 59 middle to heavy smoker (MHS) (> 400). The 5-year overall survival (OS) was significantly better in NLS (96.9%) than in MHS (80.0%); however, no significant difference was observed compared with wild-type KRAS (92.8%) (p= 0.66). The presence of p53 was significantly associated with smoking history (p< 0.01). The 5-year OS for NLS with p53-negative KRAS codon 12-mutated NSCLC (n= 28) was significantly better (96.3%) than that for MHS with both p53-positive and -negative KRAS mutation (p= 0.03 and p< 0.03, respectively). CONCLUSIONS: A non to light smoking habit might contribute to an improvement in prognosis that is equivalent to that of wild-type KRAS, and p53 mutation did not affect survival in smokers harboring KRAS codon 12.

Novel development of Spectra-A using indocyanine green for segmental boundary visibility in thoracoscopic segmentectomy.

BACKGROUND: Our previous report suggested that fluorescence thoracoscopic anatomical segmentectomy (TAS) using intravenous (IV) indocyanine green (ICG) injection is safe, feasible, and efficacious for identifying segmental boundaries. However, contrast visualization in the conventional indocyanine green mode (CIM) remains relatively obscure in smoking-related comorbidities. Our aim was to evaluate the safety and efficacy of recently released Spectra-A with CIM by simultaneous observation. MATERIALS AND METHODS: We postoperatively analyzed captive imaging using histogram counts in 29 patients who underwent TAS and previously reported that Δ indicates the index of visualization obtained by subtraction from its representative illuminated signal quantities of maximum pixels so that light-shade, intensity-removed image signals are obtained. RESULTS: Sixteen (55.2%) patients were male, and 13 (44.8%) were female. Segmental boundaries were successfully visualized in all patients (100%). The histogram count widths in dim and bright segments with CIM were 13.3 ± 3.8 and 52.5 ± 12.2, and those with Spectra-A were 19.4 ± 6.1 and 118.1 ± 37.4, respectively. The mean value was 4.3-fold higher for ΔSpa-A (61.4 ± 33.2) than for ΔCIM (14.2 ± 8.5) (P < 0.01). In 14 (48.3%) patients, the segmental boundary could not be clearly visualized using CIM but was explicitly identified using Spectra-A. CONCLUSIONS: Spectra-A is a safe and promising noninvasive alternative like CIM, and more effective because of overcoming the limitation of CIM, but its use should be studied further to determine its usefulness in identifying segmental boundaries.

Current outcomes of postrecurrence survival in patients after resection of non-small cell lung cancer.

BACKGROUND: Despite complete resection, patients with resectable non-small cell lung cancer (NSCLC) sometimes experience recurrence in various sites, generally with an unfavorable prognosis. Receptor tyrosine kinase inhibitors (TKIs) have produced a dramatic response in patients with advanced NSCLC harboring sensitive mutations. METHODS: We retrospectively investigated 281 patients with recurrence who underwent complete resection of their NSCLC between January 2005 and December 2013 with tumors in which the status of epidermal growth factor receptor (EGFR) mutation, KRAS mutation, and anaplastic lymphoma kinase (ALK) rearrangement was confirmed. Clinicopathological factors, including mode of recurrence, oncogenic status, and postrecurrence survival (PRS), were reviewed. We aimed to investigate the prognostic factors of PRS by univariate and multivariate analyses. RESULTS: Among the 281 patients, 135 patients (48.0%) with EGFR mutation, 33 (11.7%) with KRAS mutation, 13 (4.7%) with ALK rearrangement, and 100 (35.6%) with triple negative (TN) mutation were identified. Median survival time after recurrence was 26.1 months. In multivariate analysis, the presence of EGFR mutation, pStage I, the presence of both local and systemic therapies for recurrence, and longer time to recurrence (TTR) were significant favorable factors for PRS. With regard to the initial site of recurrence, the presence of pleural and/or bone recurrence reduced PRS significantly. The presence of pulmonary recurrence increased PRS, especially in patients with EGFR- or ALK-mutated tumors. CONCLUSIONS: This study documented the current outcomes of PRS. EGFR mutated status, pStage I, longer TTR and presence of multimodal therapy for recurrence were favorable factors for PRS.

Two cases of combined thoracoscopy and open chest surgery for locally advanced lung carcinoma.

Thoracoscopic surgery is becoming more widely used in thoracic surgery and has an increasingly important role to play. However, its use for locally advanced carcinoma (clinical stage T3-4) remains controversial. We adapted our procedure by combining thoracoscopy and open chest surgery (combination surgery) with the aim of reducing invasiveness while ensuring that the operation is safe and curative. Here we describe our experience. Case 1 was a man in his 60s who underwent induction chemoradiotherapy (cisplatin plus vinorelbine plus 40 Gy radiotherapy) followed by radical surgery for a left apical lung carcinoma with chest wall invasion. Case 2 was a woman in her 70s who repeatedly had pneumonia and who underwent radical surgery for left apical adenocarcinoma that was expected to have strong adhesions to the thoracic wall. A thoracotomy incision may be required in cases of stage T3-4 lung cancer to access the hilar region and dissect the resected tumor and surrounding organs. In such cases, adding thoracoscopy to either one of these procedures may enable the use of a smaller incision in the chest wall. In both cases, complete resection with no residual tumor or complications was achieved, with the patients being discharged 3-8 days postoperatively. Cases 1 and 2 both remain recurrence free after 1.5 and 3 years, respectively). This suggests that having a thorough understanding of the features of both thoracoscopic and open chest surgery and integrating the two may enable surgery to be safely and less invasively performed while ensuring a curative effect.

The eighth TNM classification system for lung cancer: A consideration based on the degree of pleural invasion and involved neighboring structures.

OBJECTIVES: The eighth tumor-node-metastasis (TNM) classification system for lung cancer has been used since January 2017 and must be applied to an individual institution's database. METHODS: We analyzed pathological stage data of 2756 patients who underwent resection of non-small-cell lung cancer, particularly in terms of the degree of visceral pleural invasion and involved neighboring structures. RESULTS: Few patients had stage IIA disease (103, 4%); stratification between stages IB and IIA was insufficient (p = 0.129). When T2a tumors were divided into PL1 and PL2 subgroups based on the degree of pleural invasion, there was a significant prognostic difference between the subgroups (p < 0.001). By incorporating T2a tumors with PL2 (T2a-PL2) into the T2b category, modified stages IB, IIA (234, 8%), and IIB were well stratified (IB vs. IIA, p < 0.001; IIA vs. IIB, p = 0.011). Focusing on T3 tumors with PL3 (T3-PL3) invading neighboring structures, multivariate analysis for surveying pT3N0-2M0 tumors revealed that completeness of resection (p = 0.002), implementation of any postoperative therapies (p = 0.003), and subcategorization of whether only the pleura was infiltrated or other deeper structures were also invaded (p = 0.024) were significant and crucial predictors. N2 disease showed worse outcome than N0-1 diseases, with marginal difference (p = 0.054). CONCLUSION: T2a-PL2 tumors could be categorized into a worse prognostic T2b category. For T3-PL3 tumors involving resectable neighboring organs, subcategorization of whether there is only pleura infiltration (T3a) or other deeper structure invasion (T3b) could be a practical consideration.

A case of second primary lung cancer diagnosed by surgical resection at salvage setting.

We report a case of metachronous second primary lung cancer; it was initially clinically favored as progression of primary disease and finally diagnosed as a second primary lung cancer by surgical resection at salvage setting. A 73-year-old man was diagnosed with stage IV lung adenocarcinoma at initial presentation. He underwent two lines of chemotherapy, and the tumors regressed dramatically. However, the residual lung mass shadow expanded after 22 months. We performed resection at salvage setting. The gene status and histological subtype were not identical with that of the primary tumor, suggesting this to be a second primary lung cancer.

Histological type predicts mediastinal metastasis and surgical outcome in resected cN1 non-small cell lung cancer.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients at cN1 have unfavorable outcomes. It has been reported that a substantial proportion of cN1 patients have occult mediastinal disease, and treatment guidelines suggest invasive preoperative mediastinal evaluation. However, the population that would most benefit from invasive staging has not been defined. The aims of this study are to identify factors predicting mediastinal metastasis and outcomes in cN1 NSCLC patients to select appropriate candidates for invasive mediastinal evaluation. METHODS: We retrospectively studied 164 patients with radiologically diagnosed cN1 NSCLC. Clinicopathological factors including radiological nodal findings were reviewed. Factors predicting the pN2 status, disease-free survival (DFS), and overall survival (OS) were investigated. RESULTS: Among 164 patients with cN1 disease, pN2 was diagnosed in 43 (26.4%). This pN2 subgroup included a higher proportion of cases with adenocarcinoma (AD) histology than the pN0/1 subgroup (60.5 vs. 38.8%, p = 0.012). Logistic regression analyses revealed AD as an independent predictor of the pN2 status, while radiological nodal findings were unrelated. Cox regression analyses identified lower preoperative serum CEA, non-AD, and pN0/1 status as favorable factors of DFS and adjuvant therapy to be associated with OS. Five-year DFS was much lower in the pN2 subgroup than the pN0/1 subgroup of AD patients (p < 0.001), while DFS was independent of pN status in non-AD patients. CONCLUSIONS: Adenocarcinoma is predictive of pN2 and poor prognosis in radiologically diagnosed cN1 NSCLC. Accurate mediastinal staging may be more beneficial for prognoses and optimal treatment planning in NSCLC patients with AD histology.

Adverse events of pulmonary vascular stapling in thoracic surgery.

OBJECTIVES: The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, adverse events (AEs) of stapling are occasionally experienced. The aim of this retrospective study was to analyse the AEs of stapling in pulmonary vascular surgery. METHODS: A retrospective multi-institutional review was conducted by the 29 institutions of the Central Japan Lung Cancer Surgery Study Group. All staplings of the pulmonary artery (PA) and vein in thoracic surgery were reviewed during the research period. RESULTS: Stapling of the PA and vein was performed 3393 times. The total number of AEs related to stapling was nine (0.27%). Eight events occurred intraoperatively and one occurred immediately after the operation. Intraoperative AE occurred more frequently than postoperative AE. AE in the PA occurred more frequently than in the pulmonary vein. The intraoperative AEs were oozing (n=3), stapling failure (n=2), laceration of the peripheral vasculature at compression (n=2) and technical injury of the vasculature at insertion (n=1). The causes of AEs were reported to be tissue fragility (n=3), stapler rocking during stapling (n=2), stapler-tissue thickness mismatch (n=2) and technical failure (n=1). The only postoperative AE was staple line rupture of the PV stump. No relationship was seen between the incidence of AE and cartridge colours, compression types of staplers or numbers of staple lines. CONCLUSIONS: Generally, stapling of the pulmonary vasculatures in recent thoracic surgery has been safe. Furthermore, the knowledge of the possible risks of pulmonary vascular stapling may help to decrease the AEs of stapling.

The value of pleural lavage cytology examined during surgery for primary lung cancer.

OBJECTIVES: The pleural invasion (PL) score is a useful prognostic indicator in lung cancer. However, in many cases, the cancer may exfoliate itself into the pleural cavity and may progress to a malignant pleural effusion without invading the parietal pleura. This stage is not currently evaluated, but it is detectable by means of the pleural lavage cytology (PLC). However, PLC's contribution to TNM staging has not yet been clarified. The purpose of this investigation was to demonstrate the usefulness of PLC in the precise staging of patients with such an occult pleural dissemination. METHODS: A total of 3231 patients who were included in a multi-institutional database were studied retrospectively. PLC was performed by washing the thoracic cavity with a small amount of physiological saline immediately after opening the thoracic cavity during lung cancer surgery. RESULTS: The incidence of positive PLC findings was 4.58%. In comparison with the negative group, the survival curves were significantly worse (P < 0.001) and the incidence of recurrence with pleuritis carcinomatosa was significantly higher (P < 0.001). According to the subset analysis, the survival difference was prominent in earlier stage groups and lower PL score groups. The positive findings were confirmed to be a significantly poor prognostic indicator (P = 0.016) by multivariate analysis using the Cox proportional hazard model (Cox analysis). However, integration of the positive findings with the PL score was attempted for the convenience of TNM staging. To find the accurate PL score for positive PLC findings, the Cox analysis was re-estimated using the PL score upgraded stepwise. The most reliable model with the highest score for the likelihood ratio χ(2) statistic was obtained by scoring positive findings as PL3. So, it was considered to be the most reliable conversion. CONCLUSIONS: Examining PLC in clinical practice is useful for detecting occult pleural dissemination before the appearance of a malignant pleural effusion. Evidence of positive findings should be treated as supplemental information to the precise diagnosis of TNM staging. Scoring positive PLC findings as PL3 (=T3) was appropriate.