Chest wall tuberculosis: precision surgery with indigo carmine in limited cases for safe and intuitive lesion excision.

In addition to treatment with antituberculosis drugs, complete surgical excision is important for the cure of chest wall tuberculosis. However, surgery is often challenging to perform due to different factors such as the strong adhesion of tuberculous lesions to the surrounding normal tissue, growth of neovascularization and presence of fragile necrotic tissues. Firm adhesions, bleeding and fragile tissue make it difficult to determine the boundary with normal tissue and completely excide the lesion. Moreover, ingenuity is required. Herein, we report the identification of the boundary between the lesion and normal tissue by injecting indigo carmine into the abscess to completely excide the lesion, which is considered an intuitive and safe method.

Factors related to post-thoracotomy pain following robotic-assisted thoracic surgery.

BACKGROUND: Robotic-assisted thoracic surgery (RATS) is a minimally invasive procedure; however, some patients experience persistent postoperative pain. This study aimed to investigate factors related to postoperative pain following RATS. METHODS: The data of 145 patients with lung cancer, who underwent RATS with a four-port (one in the sixth intercostal space [ICS] and three in the eighth ICS) lobectomy or segmentectomy between May 2019 and December 2022, were retrospectively analyzed. Factors associated with analgesic use for at least 2 months following postoperative pain (PTP group) were analyzed. RESULTS: Patients who underwent preoperative pain control for any condition or chest wall resection were excluded. Among the 138 patients, 45 (32.6%) received analgesics for at least 2 months after surgery. Patient height and transverse length of the thorax correlated with PTP in the univariate analysis (non-PTP vs. PTP; height, 166 vs. 160 cm; p < .001; transverse length of the thorax, 270 vs. 260 mm, p = .016). In the multivariate analysis, height was correlated with PTP (p = .009; odds ratio, 0.907; 95% confidence interval, 0.843-0.976). Height correlated with the transverse length of the thorax (r = .407), anteroposterior length of the thorax (r = .294), and width of the eighth ICS in the middle axillary line (r = .210) using Pearson's correlation coefficients. When utilizing a 165-cm cutoff value for height to predict PTP using receiver operating characteristic curve analysis, the area under the curve was 0.69 (95% confidence interval, 0.601-0.779). CONCLUSION: Short stature is associated with a high risk of postoperative pain following RATS.

Clinicopathological Significance of S100A14 Expression in Lung Adenocarcinoma.

BACKGROUND: Several studies have reported that S100A14 plays important roles during different steps of the tumorigenic process and tumor progression of several types of cancer. The aim of the present study was to investigate the clinicopathological and prognostic significance and functional roles of S100A14 in lung adenocarcinoma. PATIENTS AND METHODS: S100A14 expression was immunohistochemically studied in 166 consecutive resected lung adenocarcinomas, and its correlation with clinicopathological parameters was evaluated. Functional roles of S100A14 in lung adenocarcinoma were investigated based on invasion and migration assays on a small interfering (si)RNA-treated lung adenocarcinoma cell line. RESULTS: S100A14 expression was detected in 82 of the 166 (49.4%) lung adenocarcinomas. S100A14 expression was significantly correlated with sex, poorer tumor differentiation, higher disease stages, larger tumor size, lymph node metastasis, intratumoral vascular invasion, intratumoral lymphatic invasion, pleural invasion, and poorer prognosis. Invasion and wound healing assays showed that S100A14 siRNA knockdown cells had significantly decreased invasion and migration abilities compared with siRNA control cells. CONCLUSION: S100A14 is expressed in a subset of lung adenocarcinoma, and its expression is related to certain clinicopathological parameters. Furthermore, S100A14 expression was strongly correlated with migration and invasion in lung adenocarcinoma cells.

Effect of adjuvant chemotherapy after pulmonary metastasectomy on the prognosis of colorectal cancer.

BACKGROUND: Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastases may reduce recurrences and improve survival. We investigated the effects of adjuvant chemotherapy after curative resection of lung CRC metastases on prognosis. METHODS: We retrospectively reviewed records of our patients undergoing pulmonary metastasectomy from CRC between January 2000-March 2014. Data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: One-hundred (56 men; median age, 66 years) of 128 consecutive patients who underwent complete resection for first lung colorectal metastases were analyzed. Postoperative 5-year rates of overall survival (OS) and relapse-free survival (RFS) were 76% and 41%, respectively. Adjuvant chemotherapy strongly affected RFS and OS by multivariable analysis compared to surgery alone (RFS: HR, 0.49; 95% CI, 0.27-0.88; P = 0.016 and OS: HR, 0.35; 95% CI, 0.14-0.81; P = 0.014). Similar effects of adjuvant chemotherapy occurred in subgroups respectively classified according to number of lung metastases and preoperative serum carcinoembryonic antigen (CEA) level. CONCLUSIONS: Adjuvant chemotherapy after curative resection of lung metastases might strongly affect the prognosis of metastatic CRC patients. Even patients with single metastatic lesions and normal preoperative CEA level appeared to receive benefits from such chemotherapy. Narrowing of suitable candidates by predicting the effects of systemic chemotherapy and prospective randomized studies are needed.

Prognostic impact of uncertain parietal pleural invasion at adhesion sites in non-small cell lung cancer patients.

OBJECTIVES: Pleural invasion has been recognized as an important negative prognostic factor in non-small cell lung cancer (NSCLC), and therefore, accurate evaluation is required. However, when the visceral pleura adheres to the parietal pleura around a tumor and parietal pleural structures are destroyed and unrecognizable as a result of inflammation, it is often difficult to accurately evaluate pleural invasion, and classification of the T stage is unclear. To aid in categorization, we defined this status as pl1-3 and investigated the prognostic impact of the pl1-3 status on NSCLC. MATERIALS AND METHODS: We retrospectively examined the clinicopathological characteristics and prognoses of 929 NSCLC patients who underwent curative surgical resection. The pl1-3 status was defined as invasion beyond the elastic layer of the visceral pleura (pl1 or higher) but showing unclear parietal pleural invasion. We compared the prognoses of pl1-3 status NSCLC patients with that of patients with other pleural invasion statuses. RESULTS: Thirty-one patients (3%) had a pl1-3 status. The 5-year overall survival rate for pl1-3 patients was 58.9%, and the prognosis was significantly worse than pl1 (p=0.04). In pN0 cohort, pl1-3 disease had a significantly worse prognosis than pl1 and pl2 diseases (p=0.01 and 0.04, respectively) and a similar prognosis to pl3 disease. Furthermore, similar relationships were also observed after adjusting for other prognostic factors in multivariate analysis. Among the pl1-3 and pN0 patients, 11 (46%) developed recurrences (9 patients had distant metastasis, one had local recurrence, and one had both). Although the proportion of pl1-3 patients who underwent adjuvant therapy was similar to that of T3 patients, more individuals received oral tegafur-uracil treatment than intravenous chemotherapy. CONCLUSION: These results indicate that pl1-3 patients can be managed in the same manner as patients with T3 and pl3 disease. These results may be informative for treatment decisions during postoperative chemotherapy.

Prognostic significance of nestin expression in patients with resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy; relationship between nestin expression and epithelial to mesenchymal transition related markers.

INTRODUCTION: Although adjuvant platinum-based chemotherapy (AC) has been shown to improve survival of patients with completely resected stage II and stage IIIA non-small cell lung cancer (NSCLC), its effect is limited. Nestin is a class VI intermediate filament protein expressed in neural stem cells and several cancer cells including NSCLC. In the present study, we aimed to determine its prognostic significance concerning survival in NSCLC patients receiving AC. METHODS: Nestin expression in cancer cells was immunohistochemically studied in 90 patients with completely resected stage II and stage IIIA NSCLC treated with AC and its association with clinicopathologic parameters, including ABCG2, E-cadherin, and vimentin expression, was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival. RESULTS: Nestin expression was observed in 28 of the 90 (31.1%) NSCLCs. Clinicopathologically, nestin expression was associated with loss of E-cadherin expression (P = 0.006) and vimentin positive expression (P < 0.001). In survival analysis, nestin expression was significantly associated with a poorer prognosis (P = 0.028). Multivariable analysis confirmed that nestin expression is an independent prognostic indicator in NSCLC patients receiving AC (HR = 2.56; 95% CI, 1.23-5.30, P = 0.01). CONCLUSION: The present study reveals that nestin expression is a prognostic indicator of a poorer survival probability in NSCLC patients receiving AC, although its prognostic significance still requires confirmation with larger patient populations.

Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer.

BACKGROUND: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs. METHODS: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time. RESULTS: PD-L1 expression was significantly higher in tumors from men or current smokers. Squamous cell carcinoma histology was independently associated with high PD-L1 expression according to multivariate analysis (p = 0.015). The 5-year survival rate of patients was 70%, and the difference in the 5-year survival rate according to PD-L1 expression was not statistically significant (high expression group [67%] vs. low expression group [68%]); however, the squamous cell carcinoma group exhibited significantly lower 5-year survival rates as compared to the non-squamous cell carcinoma group (53 and 71%, respectively; p = 0.026). CONCLUSION: Here, we revealed high PD-L1 expression and poor prognosis observed in patients with surgically resected squamous NSCLC as compared with non-squamous NSCLC. Our results support the identification of patient subsets that most likely respond to anti-PD-1 therapy as the first step in precision medicine.

Impact of EGFR-Tyrosine Kinase Inhibitors on Postoperative Recurrent Non-Small-Cell Lung Cancer Harboring EGFR Mutations.

BACKGROUND: It is unclear whether there is a difference in the efficacy of treatment by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) between patients with postoperative recurrent non-small-cell lung cancer (NSCLC) and those with stage IV NSCLC harboring EGFR mutations. PATIENTS AND METHODS: The records of NSCLC patients harboring EGFR mutations who were treated with gefitinib or erlotinib were retrospectively reviewed, and the treatment outcomes were evaluated. Moreover, we performed an immunohistochemical analysis of PD-L1 expression in tumor lesions of the postoperative recurrence group. RESULTS: In 205 patients, both the progression-free survival (PFS) time (9.4 vs. 16.9 months) and the median survival time (24.7 vs. 37.4 months) were significantly longer in the postoperative group than in the stage IV group. Additionally, multivariate analysis identified that postoperative recurrence was an independent predictor of PFS and overall survival, as were performance status and smoking status. The PFS durations were 15.7 and 16.6 months for the high- and low-PD-L1 expression groups, respectively, and no significant difference was observed (P = 0.73). CONCLUSIONS: The findings of this study provide a valuable rationale for considering postoperative recurrence as a predictive factor for favorable PFS and overall survival in patients with NSCLC harboring activating EGFR mutations who receive EGFR-TKIs.

Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma.

BACKGROUND: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. MATERIALS AND METHODS: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. RESULTS: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinum- based chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). CONCLUSIONS: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.

S100A16 is a Prognostic Marker for Lung Adenocarcinomas.

BACKGROUND: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. MATERIALS AND METHODS: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post- translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. RESULTS: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma- derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). CONCLUSIONS: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.

Calnexin is a novel sero-diagnostic marker for lung cancer.

To develop sero-diagnostic markers for lung cancer, we generated monoclonal antibodies using lung adenocarcinoma (AC)-derived A549 cells as antigens by employing the random immunization method. Hybridoma supernatants were immunohistochemically screened for antibodies with AMeX-fixed and paraffin-embedded A549 cell preparations. Positive clones were monocloned twice through limiting dilutions. From the obtained monoclonal antibodies, one designated as KU-Lad-001 was recognized as calnexin (CANX) based on immunoprecipitation and MADLI TOF/TOF-MS analysis. To evaluate the utility of this antibody as a sero-diagnostic marker for lung cancer, we performed reverse-phase protein array analysis with samples of 195 lung cancer patients and 100 healthy controls. The CANX expression levels were significantly higher in lung cancer patients than in healthy controls (P<0.0001), and the area under the curve of ROC was 0.980, with 96.9% specificity and 99.0% sensitivity. Furthermore, since CANX was also detected in stage I disease, the serum CANX levels should be applicable markers discriminating lung cancer patients from healthy controls and possibly used in the detection of early lung cancer. To our knowledge, the present results provide evidence that CANX may be a novel sero-diagnostic marker for lung cancer.

Diagnostic and prognostic significances of MUC5B and TTF-1 expressions in resected non-small cell lung cancer.

To investigate the relationships between the expression of MUC5B and clinicopathological parameters, the expression of MUC5B was immunohistochemically studied. MUC5B expression was observed in 129 of 198 (65.2%) adenocarcinomas and in 4 of 49 (8.2%) squamous cell carcinomas (P < 0.00001). MUC5B expression was significantly associated with poorer differentiation (P = 0.0303), higher pathological TNM stage (p = 0.0153) and poorer prognosis of adenocarcinoma patients (P = 0.0017). Multivariable analysis with Cox proportional hazards models confirmed that MUC5B expression increased the hazard of death after adjusting for other clinicopathological factors (HR = 2.66; 95%CI, 1.26-5.61). We also immunohistochemically evaluated TTF-1 expression and found that the combination of MUC5B with TTF-1 is a useful marker for adenocarcinomas. The diagnostic accuracies of TTF-1 and MUC5B for adenocarcinoma were 83.8% and 70.4%, respectively. The accuracy increased to 94.3% when the two factors were combined. In survival analysis, the MUC5B(High)/TTF-1(-) group was significantly associated with a poorer outcome compared with the MUC5B(Low)/TTF-1(+) group (p < 0.0001). The present study suggested that the combination of MUC5B and TTF-1 expression is useful for discriminating adenocarcinomas from squamous cell carcinomas, yielding prognostic significance in patients with lung adenocarcinoma.

Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance.

The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

Acquisition of useful sero-diagnostic autoantibodies using the same patients'sera and tumor tissues.

Cancer tissues are comprised of various components including tumor cells and the surrounding tumor stroma, which consists of the extracellular matrix and inflammatory cells. Since the tumor stroma plays critical roles in tumor development, investigation of the tumor stroma in addition to tumor cells is important to identify useful tumor-associated markers. To discover novel and useful sero-diagnostic markers, a comparative study of tumor-associated autoantibodies (AAbs) in sera from lung adenocarcinoma (AC) patients was investigated by two-dimensional immunoblotting with AC cell lines or each autologous AC tissues. Autoantigens identified from tissue and cell line samples comprised 58 (45 antigens) and 53 spots (41 antigens), respectively. Thirty-six proteins including Transforming growth factor-beta-induced protein ig-h3 (BIGH3) and Hyaluronan and proteoglycan link protein 1 (HAPLN1) were detected only from tissues, 32 proteins only from cell lines, and 9 proteins from both. BIGH3 and HAPLN1 expressions were confirmed in the tumor stroma, but not in AC cell lines by immunostaining and immunoblotting. These data suggest that autologous tumor tissue and serum are important to coincidently detect AAbs derived from the tumor stroma in addition to tumor cells.

Clinical impact of lung age on postoperative complications in non-small cell lung cancer patients aged >70 y.

BACKGROUND: Surgery for elderly patients with primary lung neoplasms has become relatively common as populations age; however, the high frequency of postoperative complications has prevented its broad application. Recently, the Japanese Respiratory Society proposed lung age (LA) as an index of lung function, but reports on the association between LA and the risk factors for postoperative complications with non-small cell lung cancer (NSCLC) surgery have been limited. In this study, we analyzed the clinical applicability of LA for elderly patients with NSCLC. MATERIALS AND METHODS: We studied 320 patients aged >70 y underwent curative resections for NSCLC. LA was calculated based on the formula provided by the Japanese Respiratory Society, which depended on the patient's preoperative respiratory function and was divided into four age gap (AG) groups between the LA and the true age (TA). The categorical data were compared among the four groups. RESULTS: The numbers of patients in groups A, B, C, and D were 80, 77, 79, and 84, respectively. For the univariate analysis, the preoperative factors for postoperative complications were gender, AG, and smoking (P < 0.05). In a multivariate analysis, AG proved to be an independent factor. Although we found no significant differences, there was a tendency for the prognosis to worsen with an increase in the AG (P = 0.06). CONCLUSIONS: The AG was significantly associated with and an independent predictive factor for postoperative complications. We conclude that LA and AG are useful factors for predicting the risk of postoperative complications.

Off-the-job training for VATS employing anatomically correct lung models.

We evaluated our simulated major lung resection employing anatomically correct lung models as "off-the-job training" for video-assisted thoracic surgery trainees. A total of 76 surgeons voluntarily participated in our study. They performed video-assisted thoracic surgical lobectomy employing anatomically correct lung models, which are made of sponges so that vessels and bronchi can be cut using usual surgical techniques with typical forceps. After the simulation surgery, participants answered questionnaires on a visual analogue scale, in terms of their level of interest and the reality of our training method as off-the-job training for trainees. We considered that the closer a score was to 10, the more useful our method would be for training new surgeons. Regarding the appeal or level of interest in this simulation surgery, the mean score was 8.3 of 10, and regarding reality, it was 7.0. The participants could feel some of the real sensations of the surgery and seemed to be satisfied to perform the simulation lobectomy. Our training method is considered to be suitable as an appropriate type of surgical off-the-job training.

Does pneumothorax occurrence correlate with a change in the weather?

PURPOSE: There has been speculation that weather changes correlate with the incidence of spontaneous pneumothorax, although this has not been verified. Moreover, there are no significant data available on the meteoropathic pneumothorax in Asia. The aim of this study was to investigate the possible correlation and to compare our results to those of the United States and Europe. METHODS: From January 2000 to December 2009, 317 spontaneous pneumothorax cases with clear dates of onset were treated in our institution. Using the meteorological data of Fukuoka, Japan, the days with and without an occurrence of pneumothorax were statistically compared in terms of atmospheric pressure, the amount of precipitation, temperature, humidity, hours of sunshine, and occurrence of a typhoon and lightning. RESULTS: Multivariate analysis revealed that a decrease in the hours of sunshine, an increase in mean temperatures 2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.2 days before the incidence, and the days following a day with lightning were all significantly correlated with the occurrence of pneumothorax (P = 0.0083, 0.0032, 0.0351, respectively). However, typhoons, as an "unusual" weather condition, did not influence the incidence of pneumothorax (P = 0.983). CONCLUSIONS: Our results show strong similarities with reports from European countries despite the different climates. We conclude that the occurrence of pneumothorax appears to correlate with some weather conditions in Japan.