Impact of accurate diagnosis of interstitial lung diseases on postoperative outcomes in lung cancer.

OBJECTIVE: The prognostic impact of interstitial lung disease (ILD) subclassification based on both high-resolution computed tomography (HRCT) scan findings and histopathological findings is unknown. METHODS: We retrospectively analyzed 104 patients who were diagnosed with clinical ILD according to HRCT scan findings and who underwent lung cancer surgery. Via an expert multidisciplinary discussion, we re-classified HRCT scan findings and validated the histopathological patterns of ILDs in lung specimens. RESULTS: There were several mismatches between HRCT scan findings and histological patterns. Moreover, 87 (83.7%) and 6 (5.8%) patients were diagnosed with definitive ILD and pathological non-ILD, respectively. Finally, 82 patients with idiopathic interstitial pneumonias (IIPs) were divided into the idiopathic pulmonary fibrosis (IPF) (n = 61) group and the other group (n = 21). The 5-year overall survival rate of the IPF group was significantly lower than that of the other group (22.8% vs 67.9%; p = 0.011). Sub-classification of IIPs was found to be an independent prognostic factor for overall survival in patients with lung cancer. CONCLUSION: An accurate diagnosis of IIPs/IPF according to both HRCT scan findings and histological patterns is important for providing an appropriate treatment among patients with lung cancer who presented with clinical ILD.

Necessity of Multi-Step Surgical Treatment for Patients with Interstitial Lung Disease and a Pneumothorax.

PURPOSE: A pneumothorax occurs in 3%-8% of patients with idiopathic pulmonary fibrosis. A pneumothorax may predict a poor outcome in patients with interstitial lung disease (ILD), and it is difficult to treat patients with ILD and a pneumothorax. PATIENTS AND METHODS: We retrospectively studied data from all 12 patients with ILD and a pneumothorax who underwent surgical treatment at Toho University Omori Medical Center Hospital between 2009 and 2021. RESULTS: Of the 12 patients, 2 had home oxygen therapy preoperatively and were classified with grade IV interstitial pneumonia (IP). Six patients had preoperative pleurodesis and two had postoperative one using auto-blood. Three patients (25%) had multi-step surgery ≥2, and 5 patients had surgical resection of bullae. No patients had postoperative acute exacerbations and all were discharged from the hospital in a stable condition. The 5-year overall survival rate for all patients was 70.0%. The median survival time was not reached. One patient with unclassified IP was doing well 116 months after surgery. CONCLUSION: Patients with ILD and a pneumothorax were shown to require multi-step surgical treatment and can anticipate long-term survival.

Surgical lung biopsy for interstitial lung diseases-a single center study of 129 patients.

Background: According to guidelines for the diagnosis and treatment of interstitial lung diseases (ILDs), a diagnostic surgical lung biopsy should be used to obtain the differential diagnosis of an ILD in patients with ILDs, which are difficult to distinguish clinically. However, the risk of developing postoperative complications such as postoperative pulmonary fistula or acute exacerbation is a concern. The purpose of this study was to evaluate the safety of surgical lung biopsy for the differential diagnosis of ILDs. Methods: From October 2007 to July 2019, 129 patients thought to have ILD underwent a surgical lung biopsy at Toho University Omori Medical Center. We conducted a retrospective study on the diagnosis and safety of surgical lung biopsy for patients with ILD. Results: The 30- and 60-day mortality was 0%. Postoperative complications occurred in 13 of 129 (10.1%) patients. The complications included pneumothorax in 8 (6.2%) patients after removal of the chest tube, postoperative pneumonia in 2 (1.0%), and acute exacerbation in 1 (0.8%). Postoperative pneumothorax was observed in 4 of 13 patients (30.7%) who underwent a biopsy of the apex of the lung (right S1, left S1+2), which was a significantly higher rate of postoperative pneumothorax than seen for patients undergoing biopsy at other sites (P=0.0086). Conclusions: Surgical lung biopsy for the differential diagnosis of an ILD was performed safely. However, biopsy sites for ILDs need to be carefully selected to avoid postoperative complications.

Multifocal locules including the anterior mediastinum side as a surgical indicator in pleural infection.

Background: The indication for and the timing of surgery in patients with pleural infection remains unclear. Determining the need for surgery in patients with pleural infection may help in the early consultation of surgeons. Methods: Data of 167 consecutive patients with pleural infection were retrospectively reviewed. To detect a surgical indicator, the variables of patients who required surgery were compared with those of patients who were cured by non-surgical therapy (n=94) and patients resistant to the non-surgical therapy (n=73; 62 underwent surgery, and 11 showed recurrence or disease-related death after non-surgical treatment). Prognosis and timing of surgery were analyzed by comparing three groups: patients who underwent surgery within 7 days of admission (n=33), patients who underwent surgery after 7 days of admission (n=29), and patients who underwent non-surgical therapy (n=105). Results: The presence of multifocal locules, including a locule on the anterior mediastinum side (LAMS) was a significant indicator of resistance to initial non-surgical therapy, as compared to the absence of locules (P<0.0001), a single locule (P<0.0001), or multifocal locules without a LAMS (P=0.0041). Recurrence and mortality were not observed in the patients who underwent surgery within 7 days of admission, and the hospitalization period (P=0.0071) and duration of C-reactive protein (CRP) improvement (P<0.0001) were significantly shorter in these patients compared with those who that underwent surgery after 7 days. Conclusions: In patients with pleural infection, the presence of multifocal locules, including a LAMS, was associated with resistance to non-surgical therapy. Early surgery should be considered for these patients to shorten the hospitalization period and improve the prognosis.

Time to Incurable Recurrence for Patients Treated With Pulmonary Metastasectomy for Colorectal Cancer.

BACKGROUND: Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence. METHODS: This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008. RESULTS: Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR. CONCLUSION: At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

Combination of mean CT value and maximum CT value as a novel predictor of lepidic predominant lesions in small lung adenocarcinoma presenting as solid nodules.

Lung adenocarcinomas presenting as solid nodules are occasionally diagnosed as lepidic predominant lesions. The aim of this study was to clarify the histological structure and to identify factors predictive of lepidic predominant lesions. We retrospectively reviewed 38 patients that underwent lobectomy for small (≤ 2 cm) adenocarcinoma presenting as solid nodules. Resected tumor slides were reviewed and histological components were evaluated. Clinical and radiological data were analyzed to identify factors predictive of lepidic predominant lesions. Of 38 solid nodules, 9 (23.7%) nodules were lepidic predominant lesions. Five-year disease-free survival (DFS) rates were 100% for lepidic predominant lesions (n = 9) and 74.6% for non-lepidic predominant lesions (n = 29). Mean CT values (p = 0.039) and maximum CT values (p = 0.015) were significantly lower in lepidic predominant lesions compared with non-lepidic predominant lesions. For the prediction of lepidic predominant lesions, the sensitivity and specificity of mean CT value (cutoff, - 150 HU) were 77.8% and 82.8%, respectively, and those of maximum CT value (cutoff, 320 HU) were 77.8% and 72.4%, respectively. A combination of mean and maximum CT values (cutoffs of - 150 HU and 380 HU for mean CT value and maximum CT value, respectively) more accurately predicted lepidic predominant lesions, with a sensitivity and specificity of 77.8% and 86.2%, respectively. The prognosis of lepidic predominant lesions was excellent, even for solid nodules. The combined use of mean and maximum CT values was useful for predicting lepidic predominant lesions, and may help predict prognosis.

Adenocarcinoma in situ detected on a thin-walled lung cavity: a case report.

BACKGROUND: Cavitary lesions pathologically diagnosed as adenocarcinoma in situ (AIS) have been rarely reported. The examination of these type of lesions is necessary for a better understanding of the mechanisms underlying their formation and development of more efficient diagnostic and treatment strategies. Here, we present the case of a patient with cavitary lung carcinoma, diagnosed as AIS, who underwent partial resection. CASE PRESENTATION: A 72-year-old man presented with an abnormal shadow on chest radiography. Computed tomography findings showed a nodule in the right upper lobe, which was later diagnosed as an adenocarcinoma via transbronchial biopsy. A thin-walled cavity with partial thickening in the right lower lobe was also noted. We suspected that the thin-walled cavitary lesion was malignant, and performed wedge resection during a right upper lobectomy. AIS was diagnosed based on the histopathological findings of the thickened part of the thin-walled cavity. CONCLUSIONS: This study highlights that, although rare, AIS may be observed in cavitary lung carcinoma cases, particularly in thin-walled lesions.

Perioperative Bypassing Agent Therapy for Pulmonary Pleomorphic Carcinoma with Acquired Hemophilia.

A 74-year-old man was admitted with lung cancer, and preoperative blood test showed abnormal activated partial thromboplastin time (APTT). Coagulation factor screening and APTT mixing test achieved a diagnosis of acquired hemophilia A (AHA). Bypassing agent therapy was indicated and lobectomy was successfully performed without bleeding complications. APTT returned to normal after the operation without any additional treatment for AHA. The pathogenesis of AHA is still unknown and there is no evidence for hemostatic strategy for AHA patients requiring surgery. This study supports the importance of hemostatic therapy and suggests that malignancy might cause AHA.

Surgical treatment for patients with idiopathic pulmonary fibrosis and lung cancer: postoperative acute exacerbation of idiopathic pulmonary fibrosis and outcomes.

Postoperative exacerbation of interstitial pneumonia in patients with interstitial lung disease and lung cancer has emerged as a serious problem. Therefore, we need to determine the risk factors for the development of postoperative exacerbation of interstitial pneumonia in this population. There are several subtypes of interstitial lung disease, which may lead to confusion about the treatment of patients with interstitial lung disease and lung cancer. Among the idiopathic forms of interstitial lung disease, we focused on idiopathic pulmonary fibrosis (IPF) and reviewed the surgical treatments used for patients with IPF and lung cancer.

Thoracoscopic resection of bilateral multiple superior mediastinal neurofibromas.

BACKGROUND: The indications for surgical resection concerning multiple bilateral neurofibromas in the superior mediastinum remain controversial, because vascular injury or development of postoperative Horne syndrome are concerned. CASE PRESENTATION: A 60-year-old woman presented with multiple nodules in her right neck and bilateral chest cavity tops which indicated neurofibromatosis. The thoracic masses grew slowly over 9 years, and she then underwent a 2-stage resection starting with the left to right side. Bilateral tumors were completely removed via video-assisted thoracic surgery. The patient's postoperative course was uneventful, without postoperative Horner syndrome. CONCLUSIONS: To the best of our knowledge, this is the first case of multiple bilateral superior mediastinal neurofibromas resected from the pulmonary apices via thoracoscopy. We selected a minimally invasive pure video-assisted thoracoscopic surgery approach and enucleated some tumors to avoid nerve injury. This approach may be safe and useful for multiple neurofibromas in patients with neurofibromatosis.

Intraoperative argon-plasma coagulation treatment for patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis. The present study assessed the effectiveness of argon plasma coagulation (APC) treatment in patients with MPM who underwent radical pleural decortication (PD). The clinical data from 11 patients who underwent radical PD treated with APC at Toho University Omori Medical Center from July 2015 to March 2020 were retrospectively analyzed. Clinical features, local recurrence, and clinical prognoses were evaluated. The median overall survival was 18.5 months, and the 1- and 2-year overall survival rates were 71.6 and 43.0%, respectively. One patient survived 5 years but had recurrent tumors. The median disease-free survival was 11.1 months. The 1- and 2-year disease-free survival rates were 49.9 and 12.5%, respectively. Three patients had no recurrences, two of whom were followed continuously (39.6 and 10.2 months). The present study revealed that APC treatment for MPM might be associated with good survival and prognosis. APC as an additional intraoperative treatment for patients with MPM may be further investigated with larger multi-center clinical trials to support its efficacy.

Micronodular Thymoma with Lymphoid Stroma: A Case Report.

BACKGROUND: Micronodular thymoma with lymphoid stroma (MNT) is a rare subtype of thymic neoplasms. Therefore, clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. CASE PRESENTATION: A 69-year-old woman was admitted to our hospital because of an abnormal shadow detected by chest radiography. Further imaging revealed an anterior mediastinal tumor measuring 65×28×15 mm. We performed thymectomy for diagnosis and treatment. Histopathological examination revealed spindle cells comprised multiple micronodules separated by abundant interstitial lymphocytes and lymphoid follicles. Immunohistochemical staining showed that the tumor was positive for cell adhesion molecule (CAM), cytokeratin (CK) 5/6, and terminal deoxynucleotidyl transferase. The histopathological diagnosis was MNT and the stage was I by the World Health Organization classification. The patient remained free of recurrence for seven years after surgery. CONCLUSION: When the lesion is completely resected, MNT has a good prognosis. Therefore, MNT is considered to be a borderline tumor with good prognosis and no reports of recurrences, distant metastasis, or tumor-related deaths exist thus far. However, preoperative diagnosis is difficult in most cases. Hence, complete surgical resection is recommended for suspicious mediastinal masses, if feasible, for both accurate diagnosis and to ensure long-term survival.

Necessity of Thin Section CT in the Detection of Pulmonary Metastases: Comparison between 5 mm and 1 mm Sections of CT.

BACKGROUND: The aim of this study was to evaluate the difference in the ability of 1-mm and 5-mm section Computed Tomography(CT) to detect pulmonary metastases in patients with pulmonary metastases. METHODS: We retrospectively analyzed the CT findings of 106 patients with pulmonary metastases due to malignancies treated at Toho University Omori Medical Center between 2013 and 2020. RESULTS: Cases with only one nodule evaluated by 5-mm section CT had significantly lower discordance with 1-mm section CT than cases with two or more nodules detected by a 5 mm section (p = 0.0161). After reference to a 1 mm section, cases with only one nodule reevaluated by 5-mm section CT had significantly lower discordance than cases with two or more nodules reevaluated using 5-mm section CT. In cases with only one nodule, reevaluation using a 5 mm section was consistent with evaluation using a 1 mm section. However, this was not observed in cases with two or more nodules, with a significant difference between one nodule and two or more nodules. CONCLUSIONS: If there are two or more nodules observed in 5-mm section CT it may be necessary to reevaluate using 1-mm section CT to determine the exact number of pulmonary metastases.

Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting ß2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. METHODS: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. RESULTS: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). CONCLUSIONS: We believe this treatment combination is optimal for patients with lung cancer and COPD.

Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial.

BACKGROUND: Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC. METHODS: Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity (RDI) was 79% for S-1 and 80% for cisplatin. The 2-year DFS rate was 42.1%, and 2-year OS rate was 83.3%. CONCLUSIONS: This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy. TRIAL REGISTRATION: This study was registered on the UMIN clinical study registration site (protocol ID: UMIN000016191) on December 1, 2015.

Diaphragm reconstruction by GORE DUALMESH in patients undergoing resection for thoracic malignancies.

BACKGROUND: We used GORE DUALMESH for the reconstruction of diaphragms in patients with thoracic malignancies. Here, we report the results. METHODS: Between July 2015 and August 2017, diaphragm reconstruction using 2-mm GORE DUALMESH was performed in 7 patients undergoing surgical resection for thoracic malignancies. After resection of the diaphragm, the mesh was trimmed to the size of defect and placed with the smooth surface facing the chest cavity and the rough surface facing the abdomen. It was fixed with interrupted sutures consisting of synthetic monofilament nonabsorbable 1-0 to 2 threads. RESULTS: Indications for resection were malignant pleural mesothelioma and primary lung cancer in 5 and 2 patients, respectively. Patients with malignant pleural mesothelioma underwent pleurectomy with decortication; patients with primary lung cancer underwent lung lobectomy. Right and left diaphragm reconstruction was performed for 4 and 3 patients, respectively. Neither complications related to diaphragm reconstruction nor displacement of mesh occurred during a follow-up period ranging from 11 days to 37 months. CONCLUSIONS: GORE DUALMESH is a good synthetic material for diaphragm reconstruction, because its smooth surface prevents adhesions to the lung and its rough surface allows adherence to abdominal tissue.

Long-term survival of airway silicone stents in patients with central airway stenosis or obstruction due to thoracic malignancy.

OBJECTIVES: Silicone airway stents are used to manage central airway stenosis or obstruction, although their impact on long-term survival remains unknown in patients with central airway stenosis or obstruction due to thoracic malignancy. In this study, we retrospectively analyzed the impact of silicone stents on survival. METHODS: We retrospectively analyzed clinical data of 106 patients with central airway stenosis or obstruction due to thoracic malignancy treated by stenting at Toho University Omori Medical Center between 1998 and 2018. RESULTS: Patients treated with silicone stents had significantly higher survival rates than patients treated with metallic stents (p = 0.0173). Silicone stents patients also had significantly more additional treatments for thoracic malignancy after stenting than metallic stents patients (p = 0.0007). Notably, significantly more silicone stents patients underwent chemoradiotherapy or radiotherapy (p = 0.0268, p = 0.0300). During multivariate analyses, the additional treatment, including chemoradiotherapy or radiotherapy, was an independent optimal prognostic factor. CONCLUSIONS: Silicone stents patients had significantly higher survival rates than metallic stents patients. Although stenting for airway stenosis or obstruction due to thoracic malignancy may be mainly palliative, additional treatments after stenting should be considered to improve the prognoses of patients with airway stenosis or obstruction due to thoracic malignancy.