Effectiveness of Stitch With Pledget to Prevent Prolonged Air Leak in Thoracoscopic Lung Resection.

INTRODUCTION: We previously demonstrated the usefulness of combining stitching with covering to seal alveolar air leaks in an animal model. This study aimed to clarify the effectiveness and feasibility of this sealing method in the clinical setting. METHODS: Data of 493 patients who underwent thoracoscopic anatomical resection between 2013 and 2020 for lung cancer were retrospectively reviewed. Prolonged air leak was defined as chest drain placement lasting 5 d or longer due to air leak. Until July 2017 (early study period), we covered air leaks using mesh. However, for sealing (late study period), we additionally stitched leaks with pledget in patients at high risk of prolonged air leak. The pneumostasis procedure, intraoperative confirmation test of pneumostasis, and chest tube management were uniform during both periods. RESULTS: The incidence of prolonged air leak was significantly lower in the late than in the early period (3.6% versus 12.5%), whereas pulmonary emphysema was more severe in the late period compared to the early period. Intraoperative failure of sealing air leaks was significantly reduced in the late period than in the early period. In both univariate and propensity score matching analysis, the study period was a significant predictor of prolonged air leak. CONCLUSIONS: The combination of stitching and covering with mesh may contribute to reducing prolonged air leak incidence in patients undergoing thoracoscopic anatomical lung resection for lung cancer.

Localization of macrophages and dendritic cells in human thoracic lymph nodes: An immunohistochemical study using surgically obtained specimens.

Both dendritic cells (DCs) and macrophages are bone marrow-derived cells that perform antigen presentation. The distribution of DCs and CD68-positive macrophages were immunohistochemically examined in 103 thoracic nodes obtained from 23 lung cancer patients (50-84 years old) without metastasis. Among three antibodies tested initially-CD209/DCsign, fascin, and CD83-DCsign was chosen as the DC marker. For comparison, 137 nodes from 12 patients with cancer metastasis were also examined histologically. In patients without metastasis, DCs were found as (1) clusters along the subcapsular sinus and in a border area between the medullary sinus and cortex (mean sectional area of multiple nodes at one site, 8.4%) and, (2) rosette-like structures in the cortex (mean number in multiple nodes at one site, 20.5). Notably, DC clusters and rosettes contained no or few macrophages and were surrounded by smooth muscle actin (SMA)-positive, endothelium-like cells. The subcapsular linear cluster corresponded to 5%-85% (mean, 34.0%) of the nodal circumferential length and was shorter in older patients (p = 0.009). DC rosettes, solitary, or communicating with a cluster, were usually connected to a paracortical lymph sinus. Few differences were found between nodes with or without metastasis, but DC cluster sometimes contained abundant macrophages in cancer metastasis patients. The subcapsular DC cluster is not known in the rodent model, in which the subcapsular sinus is filled with macrophages. This quite different, even complementary, distribution suggests no, or less, cooperation between DCs and macrophages in humans.

BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.

Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC.

Differential diagnosis of pulmonary infections in immunocompromised patients using high-resolution computed tomography.

OBJECTIVES: The aims of this study were to compare the high-resolution computed tomography (HRCT) findings of pulmonary infections in immunocompromised patients and to assess the usefulness of HRCT in the differential diagnosis of these infections. METHODS: A total of 345 immunocompromised patients with pulmonary infections were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (123 cases), pneumocystis pneumonia (PCP) (105 cases), fungal pneumonia (80 cases), tuberculosis (15 cases), cytomegalovirus pneumonia (11 cases), and septic embolism (11 cases). Two chest radiologists retrospectively evaluated the computed tomography (CT) images, which consisted of 22 findings including ground-glass attenuation, consolidation, nodules, and thickening of the bronchial wall and interlobular septum. Associations between the CT criteria and infections were investigated using χ2 test; multiple logistic regression analyses were conducted to identify the significant indicator for each infection. The area under the curve (AUC) of each model was calculated. RESULTS: Bronchial wall thickening was a significant indicator for bacterial pneumonia (p = 0.002; odds ratio [OR], 2.341; 95% confidence interval [CI], 1.378-3.978). The presence of a mosaic pattern and the absence of nodules were significant indicators for PCP (p < 0.001; OR, 9.808; 95% CI, 4.883-13.699, and p < 0.001; OR, 6.834; 95% CI, 3.438-13.587, respectively). The presence of nodules was a significant indicator for fungal infection (p = 0.005; OR, 2.531; 95% CI, 1.326-4.828). The AUC for PCP was the highest (0.904). CONCLUSIONS: HRCT findings are potentially useful for the differential diagnosis of some pulmonary infections in immunocompromised patients. KEY POINTS: • Differential diagnosis of pulmonary infections in immunocompromised patients could be established with the help of high-resolution computed tomography. • Bronchial wall thickening was a significant indicator for bacterial pneumonia. • The presence of a mosaic pattern and the absence of nodules were significant indicators for pneumocystis pneumonia.

Successful treatment of myxedema coma with a combination of levothyroxine and liothyronine.

Myxedema coma is a rare endocrine emergency resulting from the decompensation of severe hypothyroidism, which is associated with a high mortality rate. It is characterized by the deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation. Early disease diagnosis and advancements in intensive supportive care have reduced the mortality rate. Besides intensive supportive care, appropriate management of the underlying thyroid hormone deficiency is essential. However, as the disease is rare and unrecognized, evidence-based treatment of myxedema has not yet been established in many countries. An 84-year-old Japanese man with a history of Hashimoto's thyroiditis was referred to our hospital. On arrival, conscious disturbance, hypothermia, hypotension, and hypoventilation were observed. He had discontinued thyroid hormone replacement therapy for a year. He was diagnosed with myxedema coma. Immediately, he received intensive supportive care and a combination therapy of 200 µg levothyroxine and 50 µg liothyronine until the fifth hospital day. Subsequently, monotherapy with levothyroxine was continued at a dose of 150 µg daily. The thyroid hormone level reached the normal range a few days later, and cardiovascular disease did not develop during hospitalization. This case demonstrated the efficacy of the combination of levothyroxine and liothyronine in treating myxedema coma.

Unclassifiable Infectious Complications after Lobectomy for Cancer: Etiology, Risks, and Outcomes.

BACKGROUND: Although infectious complications occur occasionally after lung lobectomy, some of them are overlooked if the pathogen or origin is unidentifiable. METHODS: We retrospectively reviewed 425 patients who underwent lobectomy for lung cancer. Infectious complications developed in 61 patients who consequently underwent empiric therapy: 44 had an identifiable focus and 17 did not irrespective of systemic surveillance. RESULTS: The 17 patients without an identifiable focus were predominantly patients with squamous cell carcinoma, a smoking history, large tumor size, and undergoing lower lobectomy. These 17 patients were able to be distinguished from those without infectious complications with a sensitivity of 88% and a specificity of 98% based on the patient's body temperature, C-reactive protein, and white blood cell count. The median onset of the 17 patients was 8 days (5-30 days) after operation. None of these 17 patients had air leak for more than 3 days, major cardiopulmonary complications, superficial surgical site infection, organ-specific symptoms (e.g., cough and diarrhea), or increased dead space size. Inflammatory markers were normalized by antibiotics alone in 14 of the 17 patients, while the condition of the remaining 3 worsened to empyema that required some intervention. One patient eventually died after thoracoscopic debridement. CONCLUSION: Postoperative acute onset of infectious complication without any specific symptoms or any identifiable focus should be included in a separate category of complications. We must clarify the pathology of this complication (e.g., occult bronchopleural fistula), but for now, careful management is mandatory, as therapeutic failure can lead to a fatal outcome.

Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study.

BACKGROUND: We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. METHODS: Chemotherapy-naïve patient with stage IIIB-IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. RESULTS: Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0-12.6), and overall survival was 48.0 (95% CI, 32.9-63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4-16.3) and 7.9 (95% CI, 1.1-14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. CONCLUSIONS: In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000005569 . Registered date: May 8, 2011.

Predicting the response to a bronchodilator in patients with airflow obstruction and lung cancer.

BACKGROUND: The aim of the present study was to clarify the predictors of the response of patients with resectable lung cancer and untreated airflow obstruction to tiotropium, an antimuscarinic bronchodilator. METHODS: Tiotropium was administered to 29 preoperative patients with untreated airflow obstruction. The forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured before and after the introduction of tiotropium. The response to tiotropium was determined based on the percentage gain in the FEV1. The volume of the total lung area (TLV) and the low-attenuation area (LAA) was measured by deep inspiratory computed tomography based on the predefined thresholds for attenuation values. RESULTS: The introduction of tiotropium resulted in a 15% gain in the FEV1 (P < 0.001). A univariate regression analysis revealed that the FVC/TLV was the best predictor of the gain in FEV1, followed by the FEV1/FVC. Based on the results of a multiple regression analysis, a regression equation to predict a gain in the FEV1 was generated using the FVC, TLV, and LAA. A receiver operating characteristic curve analysis revealed that this equation led to the highest area under the curve for predicting a major response to tiotropium, followed by the FVC/TLV and FEV1/FVC. Postoperatively, six of the 20 minor responders experienced a progression of dyspnea. In contrast, none of the major responders experienced a progression of dyspnea (P < 0.05). CONCLUSIONS: We developed an equation for predicting the response to tiotropium using parameters obtained from spirometry and quantitative computed tomography. A large-scale study to validate the usefulness of this equation is warranted.

Size-capacity mismatch in the lung: a novel predictor for complications after lung cancer surgery.

BACKGROUND: The aim of the present study was to make a combined pulmonary functional and anatomical assessment using spirometry and computed tomography (CT) to clarify the best predictor for cardiopulmonary complications after thoracoscopic major lung resection for cancer. METHODS: We retrospectively reviewed our prospective database of 304 patients undergoing thoracoscopic major lung resection for cancer. The total lung volume (TLV) was measured preoperatively using deep-inspiratory CT by summing the voxels representing -600 to -1024 Hounsfield units. Forced vital capacity (FVC) was measured by spirometry. FVC/TLV was used to diagnose a lung size-function mismatch. We compared among FVC/TLV, conventional spirometric parameters, and the risk of postoperative cardiopulmonary complications. RESULTS: Postoperative cardiopulmonary complications developed in 25 of 304 patients (8.2%). There were no cases of operative mortality. A stepwise logistic regression analysis revealed that a history of smoking and low FVC/TLV were independent risk factors for postoperative cardiopulmonary complications in various preoperative measurements. According to a receiver-operating characteristic analysis, FVC/TLV was the only variable that was statistically useful for predicting complications (area under the receiver-operating characteristic curve > 0.7). CONCLUSIONS: Lung size-function mismatch was identified as the best predictor for cardiopulmonary complications after major lung resection for cancer among various spirometry- and CT-derived parameters. The usefulness of this parameter in screening for patients who are at risk of complications should be validated by a multicenter, large-scale study because it can be obtained through routine preoperative work.

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

BACKGROUND: To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. METHODS: The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). RESULTS: Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). CONCLUSIONS: The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis.

Enhanced tumor growth in the remaining lung after major lung resection.

BACKGROUND: Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. METHODS: We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. RESULTS: The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. CONCLUSIONS: Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery.

Chaos of radiative heat-loss-induced flame front instability.

We are intensively studying the chaos via the period-doubling bifurcation cascade in radiative heat-loss-induced flame front instability by analytical methods based on dynamical systems theory and complex networks. Significant changes in flame front dynamics in the chaotic region, which cannot be seen in the bifurcation diagrams, were successfully extracted from recurrence quantification analysis and nonlinear forecasting and from the network entropy. The temporal dynamics of the fuel concentration in the well-developed chaotic region is much more complicated than that of the flame front temperature. It exhibits self-affinity as a result of the scale-free structure in the constructed visibility graph.

Prediction of postoperative dyspnea and chronic respiratory failure.

BACKGROUND: Even among patients considered to be functionally eligible for major lung resection, some experience postoperative dyspnea. Based on our previous study with quantitative computed tomography (CT), we hypothesized that postoperative dyspnea is associated with the collapse of the remaining lung, and thus, prediction of the postoperative lung volume may contribute to risk assessment for postoperative dyspnea. METHODS: We measured the emphysematous lung volume and functional lung volume (FLV) separately on whole lung CT using an image analysis software in 290 patients undergoing major lung resection for cancer between January 2006 and December 2012. The postoperative FLV was predicted by a stepwise multiple regression analysis. RESULTS: Fourteen patients complained of postoperative dyspnea (complicated group), five of them presented with chronic respiratory failure. The postoperatively measured FLV was significantly lower in the complicated group than in the control group (P < 0.01). The postoperative FLV could be calculated using preoperative variables, including the forced vital capacity, number of resected segments, FLV, and emphysematous lung volume. The predicted postoperative FLV was significantly lower in the complicated group than in the control group (P < 0.01, area under the curve = 0.78; sensitivity 86%; specificity 73%). The predicted postoperative FLV was also useful in distinguishing complicated patients from matched-control patients who had similar preoperative pulmonary function (P = 0.02). CONCLUSIONS: Postoperative dyspnea is likely accompanied by a collapse of the remaining lung. Quantitative assessment of the lung morphology on preoperative CT is useful to screen for patients at risk of postoperative dyspnea.

Assessment of volume reduction effect after lung lobectomy for cancer.

BACKGROUND: Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. METHODS: We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. RESULTS: Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. CONCLUSIONS: A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function.

Surgery for undiagnosed ground glass pulmonary nodules: decision making using serial computed tomography.

BACKGROUND: Although long-term observation of ground glass nodules on computed tomography facilitates the ability to distinguish malignant lesions from benign lesions, the resulting treatment delay can increase the rate of cancer recurrence. We reviewed our surgical cases of pathologically undiagnosed lung nodules possessing ground glass to clarify the clinical impact of selecting surgical candidates based on serial computed tomography, not preoperative biopsy results. METHODS: A consecutive series of 100 patients with clinically suspected lung cancer possessing ground glass among our prospective database of 262 surgical cases of suspected lung cancer were retrospectively reviewed. RESULTS: Surgical indication was determined based on the interval change in the outer diameter or internal attenuation of the lesions in 53 patients (increasing lesions), while that was determined based on the specific marginal or internal features of the lesions in 47 patients (non-increasing lesions). The length of preoperative follow-up was significantly longer in the patients with increasing lesions than in the patients with non-increasing lesions (27 vs. 3 months, P < 0.001). The final pathological diagnoses consisted of 97 adenocarcinomas and three non-malignant lesions. All increasing lesions were adenocarcinomas. Surgical biopsy contributed in avoiding futile lobectomy in patients with non-malignant lesions, while that caused false-negative result in one patient with an increasing lesion. Postoperative recurrence occurred in two patients. CONCLUSIONS: In a surgical series, serial computed tomography-diagnosed ground glass lesions are highly suggestive of adenocarcinoma, especially increasing lesions. Despite spending a long-term preoperative follow-up period without a pathological diagnosis, the surgical outcome is satisfactory. Surgical biopsy for increasing lesions is generally futile.

[Structural evaluation of the remaining lung after partial pulmonary resection by the stapling device].

The stapling device can excise the lung parenchyma without causing bleeding or air leak, while it causes shrinkage of the remaining lung. So, the stapling is thought to make the local pleura fragile due to excessive tension around the stump. However, little has been proven regarding these issues by experimental study. We evaluated morphologies in the remaining lung of pigs just after and 2 months after partial lung resection with stapler. As a result, the remaining lungs recovered their size to fill the thoracic cage in 2 months. Interestingly, the visceral pleura of the remaining lungs extended almost equally regardless of the distance from the stump, without causing bullous degradation. The alveoli proximal to the stump had higher alveolar density, shorter linear intercept, thicker alveolar wall than the ones distal to the stump just after resection, however, these differences were not found 2 months postoperatively. In summary, although lung excision by stapler results in shrinkage of the remaining lung temporally, it was found that the remaining lung recovered its size without adverse morphological change.

Prognostic Outcome of Pulmonary Resection for Pulmonary Metastases from Gastric Cancer.

PURPOSE: Regardless of the devastating outcomes of pulmonary resection for metastases from gastric cancer, a handful of patients survive long after pulmonary metastasectomy. This study aimed to identify a good candidate for pulmonary resection for metastases from gastric cancer. METHODS: Between 2005 and 2023, 564 patients underwent pulmonary metastasectomy in our department, of which 12 patients underwent pulmonary resection for metastases from gastric cancer. Variables evaluated were the number and size of metastatic lesions, surgical procedure, disease-free interval (DFI), and the serum carcinoembryonic antigen at pulmonary metastasectomy. RESULTS: The DFI following gastrectomy ≤12.5 months group had a significantly worse overall survival (OS) than the other group (p = 0.005). A comparison between DFI following gastrectomy ≤12.5 months group and DFI following gastrectomy >12.5 months group showed a significant difference in serum carcinoembryonic antigen (CEA) value at pulmonary metastasectomy (p = 0.048). The serum CEA value at pulmonary metastasectomy >5.8 ng/ml group had a significantly worse OS than the other group (p = 0.001). CONCLUSION: Pulmonary metastasectomy can be indicated in some patients with metastasis from gastric cancer who have longer DFI from gastrectomy and lower serum CEA at pulmonary metastasectomy.

A case of attempted transbronchial spigot insertion for fistulous pyothorax in the residual pleural airspace after pleurectomy/decortication for malignant pleural mesothelioma.

Pleurectomy/decortication for malignant pleural mesothelioma is a relatively recent surgical approach for which there is a dearth of information on complications, especially in the late postoperative period. A 70-year-old man was diagnosed with right epithelioid malignant pleural mesothelioma and underwent pleurectomy/decortication. Computed tomography at 6 months after surgery revealed nodules on the surface of the right lung. These nodules gradually increased in size and were diagnosed as recurrent disease. Immunotherapy was started, but treatment was discontinued a few days after the first course due to pneumonitis. Subsequent oral prednisolone therapy for about 2 months ameliorated pneumonitis, but fistulous pyothorax developed. During attempted transbronchial occlusion of the responsible bronchus, some spigots penetrated the empyema cavity. Open window thoracotomy was performed on the following day. This case suggests that if there is no change in diameter between the proximal and distal parts of the responsible bronchus, transbronchial occlusion should not be chosen.

Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.

PURPOSE: Tegafur-uracil (UFT) is the standard postoperative adjuvant therapy for stage IB lung adenocarcinoma (LUAD) in Japan. This study aimed to determine whether UFT is effective in stage IB LUAD with and without epidermal growth factor receptor (EGFR) mutations. METHODS: This retrospective study included 169 patients with stage IB LUAD who underwent complete resection at our department between 2010 and 2021. We investigated the clinicopathological and prognostic impact of EGFR mutations as well as the postoperative use of UFT. RESULTS: EGFR mutation-positive cases tended to show a higher cumulative recurrence rate than EGFR mutation-negative cases (p = 0.081), while overall survival was comparable between the groups (p = 0.238). In the entire cohort, UFT administration was not an independent prognostic factor in the multivariate regression analysis (p = 0.112). According to a stratification analysis, UFT administration was independently associated with favorable overall survival (p = 0.031) in EGFR mutation-negative cases, while it was not associated with recurrence-free survival (p = 0.991) or overall survival (p = 0.398) in EGFR mutation-positive cases. CONCLUSION: UFT administration can improve the prognosis of EGFR mutation-negative LUAD but not EGFR mutation-positive LUAD. Thus, clinical trials of adjuvant-targeted therapy for EGFR mutation-positive stage IB LUAD should also be conducted in Japan.

Fulminant myocarditis during postoperative adjuvant chemotherapy for lung cancer with atezolizumab: a case report.

BACKGROUND: Postoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab. CASE PRESENTATION: The patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient's shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient's history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range. CONCLUSION: Myocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.