Exacerbation Of Interstitial Pneumonia Research Articles

Successful resection of bilateral parafalcine meningioma with unilateral interhemispheric and contralateral transfalcine approach under nonintubated spontaneous breathing conditions: illustrative case.

The best surgical approach for resecting bilateral parafalcine meningioma, as well as the optimal anesthesia and airway management for craniotomy in patients with interstitial pneumonia (IP) for preventing postsurgical exacerbation, remains unclear. A 66-year-old female with a history of multiple relapses of IP underwent craniotomy for resection of a 4.5-cm bilateral parafalcine meningioma located just beneath the inferior sagittal sinus. To avoid mechanical ventilation or high-concentration oxygenation, the entire procedure was performed under nonintubated spontaneous breathing conditions with a supraglottic airway/laryngeal mask airway (SGA/LMA) device. Half of the tumor was resected using the ipsilateral interhemispheric approach, while the remaining half was resected using the contralateral transfalcine approach (CTA). No brain retractors were required. Preoperative embolization contributed toward reducing blood loss and surgery duration. During most of the operation, additional oxygen administration was not required. The postoperative course was uneventful, without exacerbation of the IP. This case demonstrated the utility and feasibility of a unilateral interhemispheric approach combined with CTA for resection of a bilateral parafalcine meningioma. Additionally, this case provides an alternative method of airway and anesthesia management with an SGA/LMA device and nonintubated spontaneous breathing for the prevention of postoperative acute exacerbation of IP.

Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report

BackgroundAccelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location.Case presentationAn elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules.ConclusionThe present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

Risk factors for in‐hospital mortality in patients with advanced lung cancer with interstitial pneumonia undergoing systemic chemotherapy: A retrospective and observational study using a nationwide administrative database in Japan

BackgroundThe safety profile of systemic chemotherapy for lung cancer patients with interstitial pneumonia (IP) in clinical practice remains unclear. Using Diagnostic Procedure Combination (DPC) data from the Japanese administrative database, we investigated the mortality of hospitalized lung cancer patients with IP as they underwent a course of systemic chemotherapy nationwide.MethodsThe DPC data of patients with stage IIIB or IV lung cancer as defined by the Union for International Cancer Control Tumor‐Nodes‐Metastases 6th and 7th editions from April 2014 to March 2016 were obtained. Among those patients, only patients with concomitant IP and receiving systemic chemotherapy without radiotherapy were included.ResultsAmong 1524 included patients, 70 (4.6%) died in the hospital. Multivariate analysis revealed that low activities of daily living (ADL) scores on admission (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.24–4.12, p = 0.008) and high‐dose corticosteroid therapy following chemotherapy (HR 2.62, 95% CI 1.44–4.77, p = 0.002) were strongly associated with in‐hospital mortality. It was determined that patients possibly received high‐dose corticosteroids for IP exacerbations; these patients had a higher in‐hospital mortality rate of 67.7% (21/31 patients) and a significantly shorter median survival time of 55 days (95% CI 31–69 days, p < 0.001) than those who did not receive high‐dose corticosteroids.ConclusionAcute exacerbation of IP treated with systemic high‐dose corticosteroids is significantly associated with in‐hospital mortality, and a low ADL score on admission is a risk factor for in‐hospital mortality in lung cancer patients with IP who undergo systemic chemotherapy.

Effect of photodynamic therapy (PDT) on a rat model of bleomycin-induced interstitial pneumonia

BackgroundEven if lung cancer is detected at an early stage, surgery may be difficult in patients with severe comorbidities, like interstitial pneumonia (IP). Radiation therapy cannot be performed due to the high risk of acute IP exacerbation. Therefore, an effective alternative, such as photodynamic therapy (PDT), is required. To prove that acute exacerbation is not induced after PDT in peripheral lung cancer, we investigated the effects of PDT on IP rat models. MethodsBleomycin (BLM) was administered intratracheally. Seven days after administration, left thoracotomy was performed. Talaporfin sodium was injected, and diode laser irradiation (664 nm, 150mW, 100J/cm2) was performed. Seven days after PDT, the whole blood and left lungs were collected. A total of 23 rats, comprising BLM + PDT (n = 4), BLM + non-PDT (n = 10), non-BLM + PDT (n = 2), non-BLM + non-PDT (n = 5), and two rats that died immediately after PDT were observed. Serum levels of Krebs von den Lungen-6, surfactant protein-D, lactate dehydrogenase, and serum C-reactive protein were measured. Fibrosis and macrophage scorings, and the ​​collagen fibers percentage were examined by staining with hematoxylin and eosin, Elastica van Gieson, anti-α smooth muscle antibody, and anti-CD68 antibodies. ResultsThere was no remarkable difference in the values of each marker in fibrosis and macrophage scores with or without PDT. In case of death, fibrosis was mild, and PDT was not affected. ConclusionsIn IP rat models, PDT did not induce lung fibrosis or acute exacerbation.

P8‐47: Autoantibody positivity is a risk factor for chemotherapy‐induced exacerbation of interstitial pneumonia in lung cancer

P8‐47: Autoantibody positivity is a risk factor for chemotherapy‐induced exacerbation of interstitial pneumonia in lung cancer

Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case\u2013control study

PurposeThe immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis.MethodsEleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects.ResultsThe odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease.ConclusionThe administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Predicting Respiratory Complications Following Lobectomy Using Quantitative CT Measures of Emphysema.

PurposeIn performing surgery for lung cancer, emphysema is a risk factor related to postoperative respiratory complications (PRC). However, few studies have addressed the risk of radiological emphysematous volume affecting PRC. The aim of this study was to investigate the relationship between emphysematous volume as measured on 3-dimensional computed tomography and PRC.Patients and MethodsWe reviewed 342 lung cancer patients undergoing lobectomy between 2013 and 2018. The percentage of low attenuation area (LAA%) was defined as the percentage of the lung area showing attenuation of −950 Hounsfield units or lower. Preoperative factors including age, sex, body mass index, smoking index, respiratory function, tumour histology, and LAA% were evaluated. PRC included pneumonia, atelectasis, prolonged air leakage, empyema, hypoxia, ischemic bronchitis, bronchopleural fistula, and exacerbation of interstitial pneumonia. Uni- and multivariable analyses were performed to investigate the relationship between independent clinical variables and postoperative adverse events.ResultsMedian LAA% was 5.0% (range, 0–40%) and PRC was observed in 50 patients (14.6%). Patients who presented with PRC showed significantly high LAA% compared to those without complications (median: 8.1% vs 3.8%; p < 0.001). Based on univariable analysis, age, sex, smoking index, percentage of forced expiratory volume in 1 s (FEV1.0%), histology, and LAA% were significant predictors for PRC. Multivariable analysis revealed higher LAA% as a significant risk factor for PRC (odds ratio = 1.040; 95% confidence interval, 1.001–1.080; p = 0.046).ConclusionIn addition to respiratory function with spirometry, LAA% can be used as a predictor of PRC.

Survival benefits of salvage surgery for primary lung cancer based on routine clinical practice.

BackgroundPremeditated induction chemotherapy followed by surgical resection is accepted as safe and effective. Studies on salvage surgery in patients with incompletely cured lung cancer are lacking. This study aimed to demonstrate the safety and efficacy of salvage surgery.MethodsWe conducted a retrospective multi‐institutional cohort study on patients who underwent salvage surgery for advanced (stage III and IV) non‐small cell lung cancer (NSCLC) between January 2005 and December 2016 at the 14 hospitals of the Chubu Lung Cancer Surgery Study Group. A total of 37 patients were assigned to the salvage surgery group; a lobectomy with mediastinal lymph node dissection was performed. The survival benefit was assessed using the Kaplan–Meier method and the Cox proportional hazard model.ResultsAlthough postoperative complications were observed in 11 patients (29.7%), surgery‐related death occurred in only one patient (mortality rate: 2.7%) resulting from respiratory failure caused by interstitial pneumonia exacerbation. Postoperative recurrence was observed in 22 patients (61.1%), the incidence of brain metastasis being high (nine patients: 40.9%). The five‐year survival rate from the first day of treatment was 60%. The survival of the postoperative pathological stage (s'‐stage) I group was significantly better (five‐year survival rate: 80.9%) than that of the other groups (p < 0.05). S’‐stage was the most significant factor (p < 0.01) associated with long‐term survival.ConclusionsSalvage surgery is a feasible therapeutic modality for advanced lung cancer. Downstaging to s'‐stage I with previous treatment was most important for survival. Complete resection (R0) should be the goal because surgical procedures were tolerated despite intense treatment.

Pulmonary Adenosquamous Cell Carcinoma With Systemic Lymphadenopathy due to Immunoglobulin G4-Related Disease: A Case Report

A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage. J Med Cases. 2021;12(4):164-171 doi: https://doi.org/10.14740/jmc3649

Clinical Outcomes of Proton Beam Therapy for Stage I Lung Cancer in Patients with Interstitial Pneumonia: A Multi-Institutional Retrospective Study in Japan

Stereotactic body radiotherapy (SBRT) is a standard option for medically inoperable stage I non-small cell lung cancer (NSCLC). However, interstitial pneumonia (IP) is considered to be a relative contraindication for SBRT. The rates of Grade ≥3 pneumonitis after SBRT in patients with IP have been reported to range from 10% to 38%. Proton beam therapy (PBT) might have an advantage in treating patients with IP. The purpose of this study is to clarify the safety and the effectiveness of PBT for Stage I NSCLC in patients with IP. Six hundred sixty-nine patients with histologically or clinically diagnosed Stage I NSCLC according to the 7th edition of UICC received passive-scattering PBT from April 2004 and December 2013 at 8 institutions in Japan. Of them, 51 patients with comorbidity of IP, which was diagnosed by CT findings, were identified and retrospectively analyzed survivals, local control, and adverse events. Forty-six (90.2%) of 51 patients were male, with a median age of 75 years (range, 60–89 years). Ten (19.6%) patients required corticosteroids or immunosuppressants, and 4 (7.8%) patients received long-term oxygen therapy. NSCLC was histologically confirmed in 32 (62.7%) patients. Clinical T stages included T1a (n = 19; 37.2%), T1b (n = 14; 27.4%), and T2a (n = 18; 35.3%). The total irradiation doses of PBT ranged from 89.3 to 131.3 Gy (RBE) BED10 (median, 109.6 Gy (RBE)). The median follow-up period was 25.1 months (range, 3.1-65.9 months) for all patients. The 2-year overall survival, disease specific survival, progression-free survival, and local progression-free rates for all patients were 71.6% (95% confidence interval [CI]: 56.9–82.8%), 83.9% (95% CI: 69.7–92.1%), 52.2% (95% CI: 38.2–65.9%), and 82.0% (95% CI: 66.5–91.2%), respectively. The incidence of Grade 2, 3, 4, and 5 pneumonitis including exacerbation of IP was 13.7%, 0%, 0%, and 3.9%, respectively. The incidence of Grade 3 dermatitis was 2.0%. No Grade 4 or severe adverse events, other than pneumonitis, were observed. PBT for Stage I NSCLC in patients with IP seems to be tolerable and effective.

Thoracoscopic surgery under local anesthesia for high-risk intractable secondary spontaneous pneumothorax.

To evaluate the outcomes of thoracoscopic surgery for intractable secondary spontaneous pneumothorax (SSP) under local anesthesia in high-risk patients and report intraoperative findings useful for identifying air leakage points. We analyzed outcomes of 14 consecutive thoracoscopic operations under local anesthesia for high-risk SSP from 2015 to 2019. Suspicious lesions were determined based on intraoperative direct or indirect detections. Direct detection involved identifying pleural fistulas or air bubbles. Indirect detection involved finding thin and transparent bullae without any other suspicious lesions. Identifications of culprit lesions were confirmed by arrest or significant decrease in air leakage after surgical repair. All surgical repairs were followed by immediate single pleurodesis for a definitive cure and prevention of recurrence. Success was defined as the removal of the thoracic tube by surgical repair combined with immediate postoperative single pleurodesis. The main underlying pulmonary diseases were emphysema (n = 7), carcinoma (n = 3), interstitial pneumonia (IP) (n = 3), and nontuberculous mycobacterial infection (n = 1). A leakage point was identified in 13 cases (six on direct and seven on indirect detections). Success was achieved in nine cases (four on direct and five on indirect detections). Adverse events included one case of acute exacerbation of IP and one case of carbon dioxide narcosis. Thoracoscopic surgery under local anesthesia can be the worthwhile definitive modality, among few remaining treatments, for highly fragile patients with SSP. Detecting air leakage directly and the presence of thin and transparent bullae without any other suspicious lesions can be clues for identifying culprit lesions.

P2.05-09 FDG-PET for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery

Acute exacerbation of interstitial pneumonia (IP) is a critical complication after lung cancer resection. Although FDG-PET is commonly used for preoperative assessment of lung cancer, its role for predicting acute exacerbation of IP after lung cancer resection is unclear. We retrospectively analyzed data of lung cancer patients that underwent surgical resection at Gunma University Hospital between 2008 and 2016. We analyzed data from patients with IP based on computed tomography findings (IP group). As control, we also analyzed data in patients with no underlying lung disease (normal group) and with emphysema (emphysema group). Patients with sufficient FDG-PET data were selected and a final of 92 patients in the IP group, 21 patients in the normal group, and 20 patients in the emphysema group were enrolled in analysis. The FDG-PET values were measured at the aorta and the basal lung. Aorta values were used for reference and we calculated the basal/aorta ratio and analyzed correlation with preoperative factors, including acute exacerbation of IP and mortality. The basal/aorta ratio was significantly higher in the IP group when compared to normal and emphysema group (both p<0.01). The incidence of acute exacerbation of IP was 10.9%, and the sensitivity and specificity of basal/aorta value for predicting acute exacerbation of IP were 70.0% and 77.2%, respectively (cutoff of basal/aorta ratio at 0.833). Patients were further classified into high basal/aorta ratio group (n=35) and low basal/aorta ratio group (n=57). The incidence of acute exacerbation of IP was significantly higher in the high basal/aorta ratio group (p=0.035). We also compared the value of basal/aorta ratio in comparison to the existing IP acute exacerbation score. Patients were divided into low score (less than 10, n=64) and high score (higher or equal to 11, n=28). The sensitivity and specificity for predicting acute exacerbation of IP was 60.0% and 82.3%, respectively, and there was no significant difference between the high and low score groups (p=0.062). The basal/aorta ratio of FDG-PET values showed a significant correlation with the incidence of postoperative acute exacerbation of IP. Since FDG-PET is commonly used for preoperative assessment of lung cancer in Japan, it may be used not only for lung cancer staging but also for surgical indication in IP patients with lung cancer by preoperatively detecting patients at high risk for acute exacerbation.

A case of drug-induced hypersensitivity syndrome induced by salazosulfapyridine combined with SIADH caused by interstitial pneumonia

We present a case of a patient with drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine combined with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by interstitial pneumonia (IP). A 67-year-old man with a past history of rheumatism (RA) presented with right hemiparalysis and aphasia as the chief complaints. A diagnosis of left embolic cerebral infarction following trial therapy for RA based on computed tomography findings was made, and external decompression was performed. Salazosulfapyridine was newly started on day 7. Dabigatran was started on day 37. On day 41, the patient developed fever. On day 42, edema and erythema appeared on his face, and erythema and rash appeared on his trunk and extremities, with gradual transition to erythroderma. The drug eruption was initially attributed to the dabigatran. Various symptoms of organ dysfunction (enteritis, myocarditis, interstitial pneumonia, hepatic disorder, stomatitis, and others) then appeared and persisted; hence, a diagnosis of DIHS associated with human herpes virus 6 and cytomegalovirus infection induced by salazosulfapyridine was suggested, and the oral administration of salazosulfapyridine was discontinued on day 53. Hyponatremia was observed in association with exacerbation of IP. Due to low serum osmotic pressure and prompt improvement of the serum sodium level by fluid restriction, the SIADH was attributed to IP. In this case, steroid pulse therapy followed by gradual decrease therapy prevented worsening of the condition.

Postoperative acute exacerbation of interstitial pneumonia in pulmonary and non-pulmonary surgery: a retrospective study

BackgroundAcute exacerbation of interstitial pneumonia (AE-IP) is a serious complication of pulmonary surgery in patients with IP. However, little is known about AE-IP after non-pulmonary surgery. The aim of this study was to determine the frequency of AE-IP after non-pulmonary surgery and identify its risk factors.MethodsOne hundred and fifty-one patients with IP who underwent pulmonary surgery and 291 who underwent non-pulmonary surgery were retrospectively investigated.ResultsAE-IP developed in 5 (3.3%) of the 151 patients in the pulmonary surgery group and 4 (1.4%) of the 291 in the non-pulmonary surgery group; the difference was not statistically significant. A logistic regression model showed that serum C-reactive protein (CRP) was a predictor of AE-IP in the non-pulmonary surgery group (odds ratio 1.187, 95% confidence interval 1.073–1.344, P = 0.002).ConclusionsThis is the first study to compare the frequency of AE-IP after pulmonary surgery with that after non-pulmonary surgery performed under the same conditions. The results suggest that the frequency of AE-IP after non-pulmonary surgery is similar to that after pulmonary surgery. A high preoperative C-reactive protein level is a potential risk factor for AE-IP after non-pulmonary surgery.

Postoperative empyema following lung cancer surgery.

Postoperative empyema following lung cancer surgery is a serious complication. Occurrence rate of postoperative empyema following lung cancer surgery, patient background, surgical procedures, date of empyema onset, treatment, and prognosis of 4772 patients who underwent lung cancer surgery between 2008 and 2012 were investigated.Postoperative empyema following lung cancer surgery was found in 43 patients (0.9%). The occurrence rate of postoperative empyema was significantly higher in patients with the following factors: male gender, extended surgery such as pneumonectomy, bi-lobectomy and thoracotomy, squamous cell carcinoma, and an advanced pathologic stage of II and above. Chest drainage, video-assisted thoracic surgery debridement, fenestration, and thoracoplasy were performed, where 29 patients were cured (67.5%) and 5 patients (11.6%) died from thoracic empyema-related complications. Nine patients were not cured and died due to cancer or other diseases during treatment. When comparing cured and non-cured patients, it is indicated that squamous cell carcinoma, administration of steroids, history of interstitial pneumonia, presence of bronchial stump fistula, exacerbation of interstitial pneumonia and presence of non-fermenting Gram-negative bacilli led to a significantly low prognosis. The five-year overall survival rate was 34.9%.

OK-432 pleurodesis for the treatment of pneumothorax in patients with interstitial pneumonia.

Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin. We retrospectively evaluated the efficacy and safety of pleurodesis using OK-432 in 39 patients treated for IP-related pneumothorax between January 2006 and May 2017. Five to 10 Klinische Einheit (KE) of OK-432 was injected through the chest tube of each patient. Pleurodesis was considered successful if 1) the chest tube was removed without air leaks and 2) there was no recurrence of pneumothorax within 4 weeks after tube removal, and no additional treatment was required. OK-432 pleurodesis was performed 46 times in 39 patients. The median number of OK-432 intrapleural injections received was 1 (range, 1-6), and median dose was 10 KE (range, 5-55 KE). The success rate was 63% (29/46) and recurrence rate was 17.4% (8/46). Grade 5 adverse events were observed in eight patients, including two patients who developed acute exacerbation of IP. Patients in whom the first OK-432 pleurodesis was successful had a significantly longer median survival time than patients in whom it was unsuccessful (322 days vs. 70 days, p = 0.036). Our results show that OK-432 pleurodesis is an effective treatment for pneumothorax associated with IP; however, clinicians should be aware of the possibility of adverse events, especially in patients who are critically ill.

A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia

BackgroundIdiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers.MethodsPatients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies.ResultsSixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43–0.94], p = 0.022).ConclusionsThe ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.

P3.16-004 Surgery for Patients with Lung Cancer Associated with Interstitial Pneumonia

Treatment of patients with lung cancer associated with interstitial pneumonia (IP) is difficult because of post-operative complications or treatment-related deaths. Indeed, post-operative acute exacerbation of IP in patients with lung cancer and IP is associated with a high mortality rate. In our institute, we have unified surgical methods and improved peri-operative management of such patients since 2013. In the current study, we retrospectively studied the clinical features, surgical methods, and peri-operative management, and analyzed the clinicopathologic features of patients with lung cancer associated with IP. We selected patients with lung cancer associated with IP who underwent surgery from January 2004 to May 2017. A presumptive diagnosis of IP or an IP pattern on computed tomography (CT) was confirmed histologically by examination of resected specimens and/or the presence of the clinical diagnostic criteria. Acute exacerbation of IP was defined according to the guidelines of the Japanese Respiratory Society when the following criteria were fulfilled within 1 month: (1) increased respiratory distress; (2) fibrosis, newly developed ground glass opacity and infiltrative shadow on high-resolution computed tomography (HRCT); and (3) >10 Torr decrease in PaO2 under the same oxygenation conditions. (4) no evidence of pulmonary infection, heart failure, pneumothorax, and pulmonary embolism. We studied the following clinicopathologic features in patients with lung cancer associated with IP: gender, age, surgical methods, pathologic stages, mortality rate, and post-operative complications, including acute exacerbation of IP. Fifty-three patients underwent surgery. The mean age was 70.8 years (50 males and 3 females). Forty-three, 1, and 9 patients underwent lobectomies, a segmentectomy, and partial resections, respectively. Twenty-three, 17, and 13 patients were stage I, II, and III, respectively. Eight patients had post-operative acute exacerbations of IP and there were three in-hospital deaths caused by acute exacerbations. Of note, there have been no in-hospital deaths since 2013. It is possible to prevent severe post-operative complications in patients with lung cancer associated with IP with the aid of intra-operatively and optimal peri-operative management.

Treatment of a case with anti-MDA5 antibody positive clinically amyopathic dermatomyositis complicated with stomach cancer and colon cancer

A 74-year-old woman noticed an edematous erythema on the right upper eyelid two months before her first medical examination, and slight fever, arthralgia and edematous erythema on the forearms and palms around the time of the first medical examination. She presented with typical skin lesions of dermatomysitis including Gottron’s signs and a heliotrope rash without any abnormal muscle symptoms. An examination by gastrointestinal endoscopy and a computed tomography scan of the chest revealed that she was complicated with stomach cancer (Stage ⅠA), colon cancer (Stage Ⅰ) and interstitial pneumonia (IP). She was diagnosed with anti-MDA5 antibody positive clinically amyopathic dermatomyositis (CADM) complicated with two cancers. Because the IP became aggravated, she was treated with corticosteroids at an initial dose of 1 mg/kg/day and immunosuppressive therapies. Tacrolimus was discontinued due to thrombocytopenia and, she also had an allergic reaction to cyclophosphamide. The administration of azathioprine at a dose of 75mg/day prevented the exacerbation of IP. We were able to be taper the dose of corticosteroids, and endoscopic stomach surgery and abdominal rectal surgery was performed. The anti-MDA5 antibody is a characteristic myositis-specific autoantibody associated with CADM and IP, which may cause a poor prognosis. CADM complicated with malignancy occurs less frequently than similarly complicated dermatomyositis and, to the best of our knowledge, this is the first case of CADM complicated with two cancers.

Early Detection of the Acute Exacerbation of Interstitial Pneumonia after the Surgical Resection of Lung Cancer by Planned Chest Computed Tomography.

BackgroundTo improve postoperative outcomes associated with interstitial pneumonia (IP) in patients with lung cancer, the management of the postoperative a cute exacerbation of IP (PAEIP) was investigated.MethodsPatients with primary lung cancer were considered to be at risk for PAEIP (possible PAEIP) based on a preoperative evaluation. The early phase of this study was from January 2001 to December 2008, and the late phase was from January 2009 to December 2014. In the early phase, chest computed tomography (CT) was performed for patients for whom PAEIP was suspected based on their symptoms, whereas in the late phase, chest CT was routinely performed within a few days postoperatively. The numbers of possible PAEIP cases, actual PAEIP cases, and deaths within 90 days due to PAEIP were compared between both phases.ResultsIn the early and late phases, surgery was performed in 712 and 617 patients, 31 and 72 possible PAEIP cases were observed, nine and 12 actual PAEIP cases occurred, and the mean interval from the detection of PAEIP to starting treatment was 7.3±2.3 and 5.0±1.8 days, respectively. Five patients died in the early phase, and one patient died in the late phase. Significantly fewer PAEIP-related deaths were observed in the late phase (p<0.05).ConclusionIdentifying patients at risk for PAEIP by routine postoperative CT examinations led to the early diagnosis and treatment of PAEIP, resulting in the reduction of PAEIP-related mortality.