Diagnostic method of mass spectrometry for detecting lymph node metastasis of non-small cell lung cancer.

BACKGROUND: Histopathology by pathologists is essential in the diagnosis of non-small cell lung cancer (NSCLC). However, auxiliary diagnostic procedures for malignant tumor have continued to evolve. Despite the poor prognosis of patients with NSCLC, the application of the latest procedures and technologies to the field of lung cancer has lagged. Mass spectrometry was used to detect trace amounts of peptides in human tissue with high accuracy. The aim of this study was to establish a method for diagnostic mass spectrometry to identify lymph node metastasis by detecting cytokeratin (CK)19, a useful biomarker in lung cancer. METHODS: We collected 81 lymph nodes with positive expression of CK19 in patients who underwent radical surgical resection in the Department of Thoracic Surgery at Iwate Medical University between May 2020 and December 2022. An X500R instrument was used for sample analysis. A positive result for lymph node metastasis as the detection at least two product ions (FGPGVAFR and ILGATIENSR) from CK19 was defined. RESULTS: Our study indicated a high diagnostic efficiency for mass spectrometry, with 87.5% sensitivity and 91.2% specificity. The mutual concordance of mass spectrometry methods and histopathological diagnosis was 90.1%. CONCLUSIONS: Mass spectrometry offers high diagnostic accuracy and can be clinically applied to auxiliary diagnostic procedures for lymph node metastasis from NSCLC.

Optimal period of smoking cessation to reduce the incidence of postoperative pulmonary complications in lung cancer.

OBJECTIVES: Postoperative pulmonary complications (PPCs) provoke an extended hospital stay and increased postoperative mortality. Although several factors can cause PPCs, smoking is the only factor that can be adjusted within a short period of time preoperatively. However, the optimal period of smoking cessation to reduce the risk of PPCs remains unclear. METHODS: A total of 1260 patients with primary lung cancer who underwent radical pulmonary resection between January 2010 and December 2021 were analysed retrospectively. RESULTS: We classified patients into 2 groups: non-smokers (patients who had never smoked) and smokers (patients who had ever smoked). The frequency of PPCs was 3.3% in non-smokers and 9.7% in smokers. PPCs were significantly less frequent in non-smokers than in smokers (P < 0.001). When smokers were classified according to the duration of smoking cessation, the frequency of PPCs was significantly lower for a duration of 6 weeks or more than for <6 weeks (P < 0.001). In a propensity score analysis performed for 6 or >6 and <6 weeks' smoking cessation in smokers, the frequency of PPCs was significantly lower for smokers with 6 or more weeks' smoking cessation than for smokers with <6 weeks' smoking cessation (P = 0.002). A multivariable analysis identified <6 weeks' smoking cessation as a significant predictor of PPCs for smokers (odds ratio: 4.55, P < 0.001). CONCLUSIONS: Smoking cessation for 6 or more weeks preoperatively significantly reduced the frequency of PPCs.

Evaluation of pulmonary artery bleeding during thoracoscopic pulmonary resection for lung cancer.

BACKGROUND: Bleeding from the pulmonary artery (PA) can be fatal in video-assisted thoracoscopic surgery (VATS) for lung cancer. We evaluated intraoperative PA injury and assessed precautions for thoracoscopic anatomic pulmonary resection. METHODS: We retrospectively analyzed a total of 1098 patients who underwent radical surgery for lung cancer utilizing complete VATS from January 2010 to December 2021. RESULTS: A total of 16 patients (1.5%) had PA injury during VATS, while hemostasis was performed by conversion to thoracotomy in eight patients (50.0%). Although there was a significantly greater operation time and blood loss for patients in the PA injury group (318.4 vs. 264.9 min, p = 0.001; 550.3 vs. 60.5 g, p ≤ 0.001, respectively), there was no significant different for the chest tube insertion duration and length of postoperative hospital stay (4.9 vs. 7.8 days, p = 0.157; 10.6 vs. 9.9 days, p = 0.136, respectively). There was a significant difference observed for the surgical procedure related to the left upper lobectomy in the PA injury group (43.8 vs. 18.8%, p = 0.012), with the primary causative PA determined to be the left anterior segmental PA (A3 ) (31.3%). CONCLUSIONS: VATS is both feasible and safe for lung cancer treatment provided the surgeon performs appropriate hemostasis, although fatal vascular injury could potentially occur during VATS. Surgeons need to be aware of the pitfalls regarding PA dissection management.

No-drain management after thoracoscopic lung wedge resection with a novel intraoperative sealing test.

OBJECTIVE: Although previous studies have reported the safety of no-drain management after thoracoscopic wedge resection, most of those studies were non-inferiority trials. The aim of this study was to evaluate whether no-drain management with an optimal sealing test affects post-operative complications in patients after thoracoscopic wedge resection. METHODS: A total of 906 patients who underwent thoracoscopic lung wedge resection for various disorders except secondary pneumothorax between 2011 and 2020 were analyzed. According to intraoperative findings from the sealing test, patients were divided into groups with chest drain placement (Drain group, n = 514) or no-drain management (no-drain group, n = 392). Our intraoperative sealing test used a flexible drain (Blake®, 19-Fr; Ethicon, Somerville, NJ) connected to the chest drain bag (- 10 cmH2O) to monitor intrathoracic pressure and detect occult alveolar air leakage. Propensity score matching was conducted to balance baseline characteristics of the two groups and reduce selection bias. RESULTS: A total of 250 pairs were matched and standardized differences suggested proper matching had been achieved. Mean length of post-operative hospital stay (4.6 days vs. 3.2 days, p < 0.001) was significantly lower in the no-drain group. Total post-operative complication rates were significantly lower in the no-drain group (6.4% vs. 2.4%, p = 0.03). CONCLUSIONS: No-drain management after thoracoscopic wedge resection was associated with fewer post-operative complications and shorter hospital stay in selected patients. Our novel intraoperative sealing test may be useful for no-drain management of select patients.

Utility of mass spectrometry and artificial intelligence for differentiating primary lung adenocarcinoma and colorectal metastatic pulmonary tumor.

BACKGROUND: Rapid intraoperative diagnosis for unconfirmed pulmonary tumor is extremely important for determining the optimal surgical procedure (lobectomy or sublobar resection). Attempts to diagnose malignant tumors using mass spectrometry (MS) have recently been described. This study evaluated the usefulness of MS and artificial intelligence (AI) for differentiating primary lung adenocarcinoma (PLAC) and colorectal metastatic pulmonary tumor. METHODS: Pulmonary samples from 40 patients who underwent pulmonary resection for PLAC (20 tumors, 20 normal lungs) or pulmonary metastases originating from colorectal metastatic pulmonary tumor (CRMPT) (20 tumors, 20 normal lungs) were collected and analyzed retrospectively by probe electrospray ionization-MS. AI using random forest (RF) algorithms was employed to evaluate the accuracy of each combination. RESULTS: The accuracy of the machine learning algorithm applied using RF to distinguish malignant tumor (PLAC or CRMPT) from normal lung was 100%. The algorithms offered 97.2% accuracy in differentiating PLAC and CRMPT. CONCLUSIONS: MS combined with an AI system demonstrated high accuracy not only for differentiating cancer from normal tissue, but also for differentiating between PLAC and CRMPT with a short working time. This method shows potential for application as a support tool facilitating rapid intraoperative diagnosis to determine the surgical procedure for pulmonary resection.

Validation of completion lobectomy after wedge resection for ≤20 mm non-small cell lung cancer.

BACKGROUND: Completion lobectomy after wedge resection is occasionally performed when final histopathology shows an unexpected primary lung cancer even though the primary lesion has already been resected. The objective of this study was to assess the necessity of completion lobectomy after wedge resection for ≤20 mm non-small cell lung cancer (NSCLC). METHODS: Between 2006 and 2016, a total of 112 patients with NSCLC underwent wedge resection in our department. After exclusions, 40 patients were analyzed. Of these, 17 patients underwent completion lobectomy and 23 patients underwent wedge resection alone. Age, sex, tumor size, histology, other malignant diseases and final surgical procedure were used as prognostic variables. Survival analyses were confirmed using the Kaplan-Meier method and log-rank test. RESULTS: Median follow-up was 70.4 months. No significant difference in 5-year overall survival (OS) and relapse-free survival (RFS) were seen in patients who underwent wedge resection alone compared to the completion lobectomy group (OS: 72.6% vs. 62.5%, P=0.34; RFS: 64.2% vs. 50.0%, P=0.35). Multivariate analysis identified age (>65 years old) and male sex as independent prognostic factors for OS and RFS. CONCLUSIONS: Completion lobectomy after wedge resection did not impact OS or RFS compared with wedge resection alone in patients with ≤20 mm NSCLC. These findings suggested that selected patients may not require resection of the remaining lobe or lymph node dissection after initial wedge resection.

Low-grade fibromyxoid sarcoma arising from the lung: A case report.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype that most commonly arises in young adults. This tumor typically presents in the deep soft tissues of the proximal extremities or trunk as a painless mass. Although the most common site of LGFMS metastasis is the lung, it is rarely the primary site. Here, we report a case of primary pulmonary LGFMS. A 22-year-old asymptomatic man was referred to our hospital for investigation of a lung mass that had been discovered incidentally. Computed tomography (CT) showed a well-defined mass 4.0 cm in diameter in the upper lobe of the right lung. Malignancy was suggested by focal uptake of 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET). Following surgery, postoperative histological analysis of the resected specimen demonstrated LGFMS based on histological and immunohistological findings. In particular, mucin 4 showed diffuse positivity in the spindle-shaped tumor cells. In conclusion, LGFMS can arise in the lungs, and physicians should consider this entity as a differential diagnosis for solitary lung mass in young adults.

Correlation with spontaneous pneumothorax and weather change, especially warm front approaching.

BACKGROUND: Primary spontaneous pneumothorax (PSP) occurs more frequently in young, tall men, with approximately 10,000 times video-assisted thoracoscopic surgery (VATS) annually in Japan is undergoing for surgical treatment. The underlying mechanisms remain unclear, but several reports have suggested correlation with weather conditions. This study aimed to evaluate the relationship between onset of PSP and changes in weather. METHODS: We retrospectively analyzed data from 112 patients who underwent VATS for PSP in Iwate, Japan from 1 January 2010 to 14 June 2020. Of the 3,818 days in this study period, the day on which the patient became aware of symptoms was classified as the PSP onset day (n=112), and all others were classified as PSP non-onset day (n=3,706). Meteorological data were collected from airbase station using an online source for the same place and same time. Logistic regression modeling was used to obtain predicted risks for the onset of PSP with respect to weather conditions. RESULTS: Among the meteorological parameters, significant differences were mainly found at 2 days before onset for increasing average temperature [odds ratio (OR): 1.97, P=0.018], minimum temperature (OR: 1.97, P=0.018), average humidity (OR: 1.58, P=0.043), and decreased the sunshine time (OR: 2.26, P=0.012). No significant difference was observed in atrophic pressure at 2 days before onset. CONCLUSIONS: Onset of PSP may correlate with the increased temperature and humidity, seen with an approaching of warm front.

Utility of the powered stapler for radical pulmonary resection: a propensity score-matched analysis.

PURPOSE: Anatomical pulmonary resection, such as lobectomy, is a common procedure. Staplers play an important role in dividing an incomplete interlobular fissure, especially in thoracoscopic surgery. This study evaluates the effectiveness of a powered stapler for reducing the need for intraoperative fibrin glue and the incidence of air leakage after radical pulmonary resection. METHODS: The subjects of this retrospective study were 478 patients who underwent radical pulmonary resection. Propensity score analysis generated two matched pairs of 177 patients treated using powered and manual staplers, respectively. RESULTS: The need for fibrin glue intraoperatively during radical pulmonary resection was significantly less in the powered-stapler group (47.5%) than in the manual-stapler group (58.8%, p = 0.033). The incidence of postoperative air leakage following radical pulmonary resection was also significantly lower in the powered-stapler group (2.8%) than in the manual-stapler group (10.7%, p = 0.003). Logistic regression analysis identified use of the powered stapler as a factor independently associated with both non-use of fibrin glue intraoperatively (odds ratio, 0.63; p = 0.040) and no postoperative air leakage (odds ratio, 0.26; p = 0.010). CONCLUSION: Using a powered stapler to divide the incomplete interlobular fissure decreased the need for additional intraoperative management using fibrin glue and reduced postoperative air leakage in radical pulmonary resection.

Mandibular Fracture in a Patient Taking a Direct Oral Anticoagulant.

ABSTRACT: A 74-year-old man presented with hemorrhage from the mandible after an injury caused by a 5 × 3 × 3-cm metal square column flying from a 45-ton press machine that struck the right side of his face. He is a known atrial fibrillation patient and is on rivaroxaban, a direct oral anticoagulant. An approximately 8-cm Y-shaped wound with persistent hemorrhage was observed in the right mandible, and the mandible was displaced between the right mandibular canine and first premolar. Although the patient showed no dyspnea, the sublingual region showed a slight dark purple swelling; fiberoptic nasal intubation was performed. Computed tomography at 3.5 hours after the injury revealed a comminuted fracture of the right mandibular body, edema at the floor of the mouth, nasal cavity, upper pharynx to hypopharynx, and the pharyngeal airway around the endotracheal tube. Open reduction and internal fixation were performed. Rivaroxaban was started again 3 days after surgery.

Prediction formula for predicted diffusion capacity of lung for carbon monoxide in pulmonary surgery.

OBJECTIVES: Diffusion capacity of the lung for carbon monoxide (DLCO) is a useful value for perioperative risk assessment of non-small cell lung cancer (NSCLC). The percentage of the predicted DLCO (%DLCO: DLCO/predicted DLCO × 100) is often evaluated by setting cutoff values as in the clinical field, but several formulae are available for calculating the predicted DLCO, and the %DLCO thus varies depending on the formula used to predict DLCO. We examined differences in %DLCO calculated using several commonly used prediction formulae. METHODS: A total of 490 eligible patients who underwent completed video-assisted thoracoscopic surgery (c-VATS), especially radical pulmonary lobectomy, for NSCLC were analyzed retrospectively. Predicted DLCO was calculated using the prediction formulae described by Burrows, Nishida, Cotes, and Kanagami, then the relationships with postoperative complications were evaluated. RESULTS: The %DLCO from Nishida's formula was two-thirds the value of that from Burrows' (p < 0.05). On logistic regression analysis, predicted postoperative %DLCO (ppo-DLCO) based on the formulae of Burrows, Cotes and Kanagami were independent factors related to postoperative pulmonary complications after c-VATS lobectomy for NSCLC (odds ratios 2.46, 1.79 and 2.33, p = 0.005, 0.043 and 0.009, respectively). CONCLUSIONS: The %DLCO is a useful index for surgical risk assessment of c-VATS lobectomy for NSCLC, while the results differ markedly between individual prediction formulae. Specification of the formula used is necessary in cases considering risk evaluations.

Surgical treatment strategies for refractory unresectable pulmonary fistula.

We present several surgical treatments that we commonly use for unresectable pulmonary fistula, which is the several combination devices using PGA sheet, fibrin glue and autologous tissue. Although the small number of cases, these resulted successfully control the pulmonary fistula.

Submandibular Gland Hemangioma.

Hemangioma in the submandibular gland or submandibular space is rare. A 31-year-old woman was referred to our department. She became aware of painless swelling in the right submandibular gland at 9 months ago. The right submandibular gland showed swelling with no tenderness, and the palpation was softer than the normal submandibular gland. Magnetic resonance imaging short T1 inversion recovery (STIR) sequence showed a 38 × 29 mm well-circumscribed, lobulated mass with high signal intensity attached with the submandibular gland. Computed tomography showed phlebolith formation. A clinical diagnosis of suspected hemangioma in submandibular gland was made, and submandibular gland excision including mass was performed with submandibular approach without complications. No unusual bleeding during the surgery was observed. Pathological finding indicated that thick walled vessels containing smooth muscle were proliferated with dilatation. Some vascular lumen included phlebolith calcification. Although the boundary with the submandibular gland was mainly clear, some parts were irregularly occupied with a component of hemangioma. The final diagnosis was venous hemangioma in submandibular gland. No postoperative recurrence was recognized in 1-year follow-up. A search of PubMed revealed that only 18 cases associated with hemangioma in the submandibular gland in 12 English articles. Literature review indicated that (1) approximately 70% patients showed painful swelling and (2) x-ray or computed tomography may indicate the phlebolith calcification. It may make an erroneous diagnosis of sialolithiasis. Magnetic resonance imaging finding would be needed for the diagnosis.

Development of a New Magnetometer for Sentinel Lymph Node Mapping Designed for Video-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer.

BACKGROUND: We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed. CONCLUSIONS: The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.

C-reactive protein inhibits expression of N-cadherin and ZEB-1 in murine colon adenocarcinoma.

Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in cancer cell invasion and metastasis. We previously demonstrated that cancer cell migration is inhibited by C-reactive protein (CRP), which is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we evaluated the effect of CRP on cancer cell migration and expression of mesenchymal and epithelial markers of EMT and of related transcription factors. MCA-38 murine colon adenocarcinoma cells were subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1 µg of recombinant mouse CRP or vehicle (phosphate-buffered saline) subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for evaluation using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. There was no statistical difference in tumor size between the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor-bearing mouse model. CRP may thus be a potentially useful tool for preventing cancer progression through suppression of EMT.

New CT criteria for nodal staging in non-small cell lung cancer.

OBJECTIVE: The purpose of our study was to develop a simple noninvasive technique for nodal staging using routine preoperative computed tomography (CT). MATERIALS AND METHODS: The institutional review board approved this retrospective study, and written informed consent to perform the initial and follow-up CT studies was obtained from all patients. Preoperative CT findings (n=218 patients with resectable non-small cell lung cancer) and pathological diagnoses after surgical resection were evaluated. Using CT images, lymph node section area, circumference, and lesion attenuation values (LAVs) were drawn freehand, and the short axis (SA) and long axis (LA) were measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze the section area, circumference, and LAVs. RESULTS: Based on ROC curves, two cut-off values, lymph node section area >30 mm(2) and circumference >25 mm, showed greater sensitivity for nodal staging than the conventional criterion of lymph node SA ≥10 mm or the LA, SA/LA ratio or LAVs. Using lymph node section area >30 mm(2) for diagnosis, the sensitivity, specificity, and accuracy of nodal staging were 90.5%, 56.3%, and 58.3%, respectively. Using lymph node circumference >25 mm, the values were 76.2%, 70.4%, and 70.8%, respectively. CONCLUSION: Lymph node section area >30 mm(2) and circumference >25 mm can serve as supportive criteria used by radiologists and surgeons to determine nodal staging. If these CT criteria are met, use of a more sensitive procedure such as positron emission tomography or mediastinoscopy is recommended. CONCISE ABSTRACT: CT is used routinely during preoperative management of lung cancer. Based on ROC analyses, the cut-off values for surface area, circumference, the SA/LA ratio, and LAVs for diagnosis of lymph node metastasis were 30 mm(2), 25 mm, 0.65, and 50 Hounsfield units, respectively. Our findings indicate that lymph node surface area >30 mm(2) and circumference >25 mm are supportive criteria that can be used by radiologists and thoracic surgeons to determine nodal staging and surgical indications.

Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer.

Cyclin family proteins act in association with cyclin-dependent kinases (CDK) at cell cycle checkpoints to regulate the eukaryotic cell cycle. CyclinB2 contributes to G2/M transition by activating CDK1 kinase, and cyclin B2 inhibition induces cell cycle arrest. CyclinB2 is overexpressed in various human tumors, though the relationship between cyclin B2 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. In the present study, therefore, we investigated the relationship between cyclin B2 mRNA expression and the prognosis of patients with non-small cell lung cancer (NSCLC). We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of cyclin B2 mRNA in tumor samples from 79 patients with NSCLC. We then correlated the cyclin B2 mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed cyclin B2. The 5-year overall survival rates among patients with adenocarcinoma of lung expressing lower levels of cyclin B2 mRNA were significantly better than the corresponding rates among patients expressing higher levels (p = 0.004). Multivariate Cox proportional hazard analyses revealed that gender ((hazard ratio (HR), 9.81; p = 0.044)), n2 (HR, 146.26; p ≤ 0.001), and cyclin B2 mRNA high (HR, 7.21; p = 0.021) were independent factors affecting the 5-year overall survival rates. However, there was no significance in the 5-year overall survival rates among the patients with squamous cell carcinoma between expressing lower and higher level of cyclin B2 mRNA. Stronger expression of cyclin B2 mRNA in tumor cells is an independent predictor of a poor prognosis in patients with adenocarcinoma of lung.

Hoarseness caused by arytenoid dislocation after surgery for lung cancer.

The patient was a 64-year-old woman with no history of laryngeal disorders. She underwent video-assisted right lower lobectomy and node dissection for lung cancer. Using a stylet while the patient was under general anesthesia, tracheal intubation with a 35-French gauge left-sided double-lumen endobronchial tube was successfully performed on the first attempt. The patient developed slight hoarseness on postoperative day 1, and we initially suspected recurrent laryngeal nerve paralysis caused by the surgery, which we elected to treat conservatively. However, because her hoarseness had not improved 4 months after surgery, we evaluated her vocal cords using laryngoscopy. This revealed severe dysfunction of the right vocal cord and arytenoid dislocation, which we treated through reduction using a balloon catheter. By 6 months, the patient's vocal cord mobility had improved. Arytenoid dislocation is a rare complication, but should be suspected when patients have right vocal fold paralysis after lung cancer surgery.

Diagnostic imaging in the preoperative management of lung cancer.

Surgical resection is the accepted standard of care for patients with non-small cell lung cancer (NSCLC). Several imaging modalities play central roles in the detection and staging of the disease. The aim of this review is to evaluate the utility of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and PET/CT for NSCLC staging. Radiographic staging refers to the use of CT as a non-invasive diagnostic technique. However, while the vast majority of patients undergo only CT, CT is a notoriously inaccurate means of tumor and nodal staging in many situations. PET/CT clearly improves the staging, particularly nodal staging, compared to CT or PET alone. In addition, as a result of the increased soft-tissue contrast, MRI is superior to CT for distinguishing between tissue characteristics. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which is a minimally invasive technique, also has pathological diagnostic potential. Extensive research and the resultant improvements in the understanding of genetics, histology, molecular biology and oncology are transforming our understanding of lung cancer, and it is clear that imaging modalities such as CT, MRI, PET and PET/CT will have an important role in its preoperative management. However, thoracic surgeons should also be aware of the limitations of these techniques.

Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-ß1.

BACKGROUND: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with fibrous stromal invasion are newly introduced subtypes of small lung adenocarcinoma. AIS is a small localized adenocarcinoma in which growth is restricted to neoplastic cells along preexisting alveolar structures without fibrous stromal invasion. In MIA, by contrast, tumor cells have infiltrated the myofibroblastic stroma. Transforming growth factor (TGF)-ß is known to be produced by progressor tumors, and excessive TGF-ß contributes to a pathological excess of tissue fibrosis. TGF-ß1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-ß1 expression and clinicopathological microinvasion in patients with small lung adenocarcinoma. METHODS: The study participants were 45 patients who underwent curative surgery for AIS and MIA 3 cm or less in size. Those tumors were assessed based on immunohistochemical staining using anti-TGF-ß1 antibody. The TGF-ß1 status was assessed immunohistochemically using the Allred 8-unit system. RESULTS: The rates of TGF-ß1 positivity in the AIS and MIA groups were 27.3% and 65.2%, respectively (P <0.05). The median of Allred score was 0.5 (range 0-5) in the AIS group and 3.0 (range 0-6) in the MIA group (P = 0.0017). CONCLUSIONS: We suggest that TGF-ß1 expression is likely to be significantly stronger in patients with MIA than in those with AIS, and the increased expression may be associated with minimal invasion and infiltration of the myofibroblastic stroma.