What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection?

PURPOSES: Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease. METHODS: We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.3%) patients with a mortality rate of 43.9% (72/164). Univariate and multivariate analyses were carried out to identify possible risk factors of fatal AEIP. We then analyzed the 164 patients who developed postoperative AEIP and identified the preoperative and postoperative risk factors. RESULTS: A multivariate regression analysis identified that the sex, percent vital capacity, neoadjuvant radiation, preoperative history of AEIP, preoperative use of steroids, usual interstitial pneumonia pattern on CT, and surgical procedures were independent preoperative risk factors for death due to AEIP. ILD patients with emphysema somehow showed a lower risk of fatal AEIP than those without emphysema in this study. CONCLUSIONS: This study revealed eight risk factors for fatal AEIP.

Adherence and feasibility of 2 treatment schedules of S-1 as adjuvant chemotherapy for patients with completely resected advanced lung cancer: a multicenter randomized controlled trial.

BACKGROUND: We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients. METHODS: Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival. RESULTS: From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1-3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). CONCLUSIONS: The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin. TRIAL REGISTRATION: This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

[Ultrasonically activated coagulating shears and the vessel sealing system in thoracic surgery].

While the recent emergence of energy-based surgical techniques has made surgical procedures less invasive, the safety and proper usage have yet to be investigated. Here we review the experimental and clinical use of ultrasonically activated coagulating shears and a vessel sealing system in thoracic surgery. Both energy devices have been reported to be safe for use with the pulmonary artery and vein, with a burst pressure above 100 mmHg. Although their combined use with a ligature at a central site appeared to be adequate, the long-term durability has yet to be verified. The thoracic duct was reported to be sealed with sufficient burst pressure using these energy devices, which are expected to provide an alternative treatment for chylothorax. There have also been a few reports of their usage with the lung parenchyma, but their clinical adaptation is seemingly limited.

Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma.

A ciliated muconodular papillary tumor has been reported to be a peripheral low-grade malignant tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation. Although ciliated muconodular papillary tumors have not yet been classified according to the World Health Organization classification, they can pose diagnostic and therapeutic problems. Here we report a resected case of ciliated muconodular papillary tumor with computed tomography findings reminiscent of adenocarcinoma, showing a small irregular nodule adjacent to the intersegment pulmonary vein. There was no uptake of F-18 fluorodeoxyglucose positron emission tomography. The patient underwent surgical resection, and a lobectomy was performed because intraoperative needle biopsy suggested neoplastic proliferation. No EGFR mutations were detected. No recurrence was noted during 24-month follow-up after lobectomy.

Histopathological implications of Aspergillus infection in lung.

This paper opens with a discussion on the significance of invasive fungal infections in advanced contemporary medicine, with an emphasis on the intractability of disease management and the difficulties of diagnosis. This is followed by a discussion concerning classification, histopathological features, and pathophysiology. While it has been largely accepted that Aspergillus species is recognized by cellular receptors and attacked by neutrophils, the radiological and macroscopic findings linking infection with neutropenia remain unconfirmed. In an effort to gain a better understanding of the pathophysiology and pathogenesis of invasive aspergillosis, we wish to emphasize the utility of radiological and histopathological examinations since these can provide detailed information on the extremely complex interaction between the causative microbes and tissue responses. A review of noninvasive or semi-invasive aspergillosis is also provided, with particular emphasis on chronic necrotizing pulmonary aspergillosis, which is recognized as a transition form of simple pulmonary aspergilloma and invasive pulmonary aspergillosis, although few findings have been reported in this area.

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion, resembling extraskeletal myxoid chondrosarcoma: Case report with a review of Literature.

Reported herein is an extremely rare case of primary pulmonary myxoid sarcoma (PPMS). A 31-year-old man presented with a 2.7 cm-sized pulmonary tumor surrounded by capsule-like fibrosis. The patient has been free of disease for 5.8 years after surgery. This tumor focally showed endobronchial features, and consisted of reticular cords of oval, short spindle, or polygonal cells with swollen vesicular nuclei accompanied by an abundant myxoid stroma, closely resembling extraskeletal myxoid chondrosarcoma. Tumor cells were diffusely positive for vimentin and focally positive for epithelial membrane antigen, but were negative for cytokeratin, TTF-1, Napsin A, S-100 protein, CD34, desmin, smooth-muscle actin, CD10, p63, calponin, h-caldesmon, c-kit, HMB-45, synaptophysin, or glial fibrillary acid protein. Our reverse transcription-polymerase chain reaction using the formalin-fixed, paraffin-embedded tumor tissues detected EWSR1-CREB1 fusion transcript, but could not demonstrate EWSR1-ATF1 fusion or EWSR1/TAF15/TFG-NR4A3 fusion. These findings indicate that the current tumor is an additional case of PPMS with EESR1-CREB1 fusion, recently reported by Thway et al. Some cases of PPMS can behave in an indolent manner.

Clinical characteristics of acute respiratory deterioration in pulmonary fibrosis associated with lung cancer following anti-cancer therapy.

BACKGROUND AND OBJECTIVE: To clarify the clinical characteristics and risk factors for acute respiratory deterioration following anti-cancer therapy in patients with pulmonary fibrosis (PF) and lung cancer. METHODS: Patients with primary lung cancer and PF were identified by review of medical records. Of the 865 consecutive patients with primary lung cancer who had been treated between June 1999 and September 2007, 53 were diagnosed as having PF. This retrospective study analysed the prevalence of and risk factors for acute respiratory deterioration after treatment of lung cancer in these patients. RESULTS: Acute respiratory deterioration was found in 10 (24%) of the 41 patients who received anti-cancer therapy, and six (60%) of these patients died of respiratory failure. The incidence of acute respiratory deterioration was 28% (8/29) after chemotherapy and 16% (2/12) after surgery. Mortality after acute respiratory deterioration was 50% (4/8) among patients with idiopathic PF and 100% (2/2) among the patients with PF associated with rheumatoid arthritis. Logistic regression analysis revealed that a higher smoking index (cigarettes smoked per day x years of smoking) was a significant risk factor for acute respiratory deterioration (odds ratio: 1.002, P = 0.025). CONCLUSIONS: Patients with lung cancer who have pre-existing PF should be carefully managed because of their high risk for developing acute respiratory deterioration after anti-cancer therapy.

[The role of positron emission tomography in the detection of incidental gastrointestinal tract lesions in patients examined for lung cancer].

The purpose of this study was to clarify the clinical characteristics of lung cancer patients with abnormal accumulation in the gastrointestinal tract by fluoro-2-deoxyglucose positron emission tomography (PET). Of the 968 consecutive patients with primary lung cancer who underwent PET from October 2005 through September 2009, 26 patients had local abnormal accumulation in the gastrointestinal tract. We retrospectively compared the localization of abnormal accumulation in the gastrointestinal tract, standardized uptake value (SUV) max (1 hour), and the final clinical diagnosis. The site of abnormal accumulation was the esophagus in 1 case, the stomach in 8 and the small intestine to large intestine in 17. In 15 out of 26 (57%) cases with true PET positive results, there was esophageal cancer in 1 case, gastric cancer in 2, gastrointestinal stromal tumor in 1, colon cancer in 8, and 1 each of metastasis to the stomach, small intestine and large intestine from lung cancer. In 11 cases with false PET-positive results, there was a stomach polyp in 1 case, gastritis in 3, colon polyp in 1, diverticulitis in 1 and normal physiologic accumulation in 5. There were no differences in mean SUV max among malignant lesions, benign lesions, and normal physiologic accumulation. We should perform endoscopy of the digestive tract to detect malignant lesions with high incidence rates when PET shows localalized abnormal accumulation in the gastrointestinal, tract in patients with lung cancer.

Usefulness of fluoro-2-deoxyglucose positron emission tomography for investigating unexplained rising carcinoembryonic antigen levels that occur during the postoperative surveillance of lung cancer patients.

BACKGROUND: Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) has been useful for the detection of recurrent lung cancer. However, such technology is expensive and is not always widely available. In this study, we evaluated the selected use of FDG-PET for lung cancer patients with re-elevated levels of serum carcinoembryonic antigen (CEA) after curative surgery. METHODS: Among 327 patients who underwent curative resection for primary lung cancer from May 2002 through March 2007, 199 had adenocarcinoma, of whom 78 (39%) had elevated levels of serum CEA before treatment. After surgery, the level was monitored every 1 to 3 months. Re-elevation of CEA was recognized in 39 (50%) patients, 22 of whom underwent FDG-PET and were included in this study. FDG-PET images were visually inspected, and abnormally increased FDG uptake was interpreted as recurrence. The sensitivity, specificity, positive predictive value, and negative predictive value of PET in detecting recurrent lung cancer were determined. RESULTS: FDG-PET correctly identified 14 out of 15 relapses and gave true negative results in six out of seven remissions, i.e., one false-negative and one false-positive were observed. The sensitivity, specificity, positive predictive value, and negative predictive value were 93%, 86%, 93%, and 86%, respectively. CONCLUSION: In 64% of the patients with unexplained increased CEA levels, FDG-PET provided decisive diagnostic clues guiding further diagnostic and therapeutic interventions. The selected use of FDG-PET for patients with re-elevated serum CEA levels after surgery can be a practical and effective mode of surveillance for detecting recurrent lung cancer.

[Usefulness of FDG-PET for diagnosis of lung cancer associated with interstitial pneumonia].

AIM: The aim of this study was to demonstrate the usefulness of FDG-PET for diagnosis of lung cancer associated with interstitial pneumonia (IP), clinicopathologically. SUBJECTS AND METHODS: 32 patients with IP-associated lung cancer (IP-LC group) and 26 patients with IP not associated with lung cancer (IP group) underwent 18-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnostic procedure from April 2004 through October 2007. Standard uptake values (SUV) were compared between IP and lung cancer fields in two groups. In addition, expression of Glut-1, MIB-1, and p53 in the resected lung tissues (n=10) were analyzed. RESULTS: There was a significant difference in SUVs between lung cancer fields and IP fields. However, it was difficult to distinguish the fields of well-differentiated adenocarcinoma from IP by SUV. Red blood cells in the vessels along the alveolar walls, hyperplastic alveolar type II cells, and squamous metaplastic cells in the fibrotic lung tissues revealed expression of Glut-1. In addition, hyperplastic alveolar type II cells and metaplastic cells also revealed expression of MIB-1 and p53. CONCLUSION: The elevation of SUV in IP fields can be caused by neovascularization and/or hyperplasia of alveolar type II cells and metaplastic cells in the fibrotic lesions.

[Efficacy of fluoro-2-deoxyglucose positron emission tomography imaging in response evaluation of patients with small cell lung cancer (pilot study)].

The purpose of this study was to assess the feasibility of PET/CT in response evaluation of patients with small cell lung cancer (SCLC). Among the 25 patients with primary small cell lung cancer who had been treated from August 2004 through to May 2008, we compared the response evaluation between conventional CT and fluoro-2-deoxyglucose positron emission tomography (FDG-PET), [CMR (Complete Metabolic Response), PMR (Partial Metabolic Response), SMD (Stable Metabolic Disease), PMD (Progressive Metabolic Disease)] before and after the treatment. Response assessment was discordant in 2 out of 25 cases (8%) after the first cycle of chemotherapy and in 3 out of 19 cases (16%) after the fourth cycle of chemotherapy. Two discordant cases after the first cycle of chemotherapy were PR and SD respectively by CT but both were found to be PMD by PET. Two out of three discordant cases after the fourth cycle of chemotherapy were PR by CT but both found to be CMR by PET. These results suggest that FDG-PET is useful for response assessment of early diagnosis of recurrence and prognostic outlook in small cell lung cancer, however further cases need to be collected.

[An autopsied case of mucinous bronchioloalveolar carcinoma associated with multiple thin-walled cavities].

A 82-year-old man was found to have mucinous bronchioloalveolar carcinoma associated with a cavity 10-cm in size in the right lower lobe, and he underwent a surgical lobectomy in April 2005 (pT2N0M0). Seven months after the surgery, chest images showed multiple metastases with thick-walled cavities in bilateral lung fields. The serial HRCT showed that thick-walled cavity lesions transformed into thin-walled cystic cavities associated with decreasing serum CEA levels. The patient's condition was good with best supportive care for 24 months from the time of recurrence. Subsequent progression of the thick-walled cavities into thin-walled cavities, was acompanied by re-elevation of serum CEA levels, and he died of respiratory failure 5 months after re-exacerbation. Macroscopic findings at autopsy showed multiple cavities in both lungs. Microscopic findings of the right lung showed desquamative mucinous bronchioloalveolar carcinoma cells lining the thick-walled cavity surface, and a single layer of tumor cells proliferating in the thin-walled cavity surface. Tumor cells with excessive mucus and necrosis were observed in the thick-walled cavities. It is suggested that thick-walled cavities were formed as a result of avascular necrosis and destruction of the pulmonary alveoli by excessive mucus, and thin-walled cavities were formed as a result of a check-valve mechanism.

Lobectomy for lung cancer in a myelodysplastic syndrome patient with decreasing platelet aggregation: report of a case.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders of the bone marrow. Most patients with MDS have a high risk of bleeding. Thrombocytopenia and defective platelet aggregation contribute to bleeding. We report a surgical case of a patient with lung cancer concomitant with MDS. CASE PRESENTATION: A 72-year-old man presented to our hospital because of an abnormal shadow on chest x-ray suggesting a primary lung cancer. A peripheral blood smear examination found giant platelets without thrombocytopenia. He was diagnosed with MDS by bone marrow biopsy, and showed defective platelet aggregation despite a normal bleeding time. The patient underwent left lower lobectomy and transfusion of platelets because of chest wall bleeding. CONCLUSIONS: We demonstrated that ordering platelet preparations might be desirable for an MDS patient with defective platelet aggregation who will undergo surgery, even for a normal platelet count and bleeding time.

Long-acting muscarinic antagonist and long-acting ß2-agonist therapy to optimize chronic obstructive pulmonary disease prior to lung cancer surgery.

Bronchodilators are essential for the perioperative management of patients with chronic obstructive pulmonary disease (COPD) undergoing surgery for lung cancer. The objective of the present study was to examine whether the usage of a long-acting ß2-agonist (LABA) with a long-acting muscarinic antagonist (LAMA) could optimize preoperative lung function and reduce the risk for postoperative pulmonary complications. Thirty-two consecutive patients with moderate-to-severe COPD who underwent a lobectomy for lung cancer and received preoperative LAMA (n=19) or LAMA/LABA (n=13) therapy between January 2005 and December 2015 were enrolled in this retrospective study. The improvement of preoperative pulmonary function and the postoperative morbidity were compared between the patients with preoperative LAMA, and LAMA/LABA therapy. Increases in the forced expiratory volume in one second (FEV1) were significantly larger in the LAMA/LABA group than in the LAMA group (0.26±0.05 l vs. 0.07±0.05 l; P=0.0145). More patients in the LAMA/LABA group than in the LAMA group showed a marked improvement of >10% in %FEV1 after bronchodilators (85 vs. 32%; P=0.0046). The incidence of postoperative pneumonia was significantly lower in the LAMA/LABA group than in the LAMA group (0 vs. 26%; P=0.044). In conclusion, the present study showed that preoperative LAMA/LABA therapy was associated with larger improvements in preoperative pulmonary function and less postoperative pneumonia than LAMA therapy. These results may lead to greater improvements in FEV1 and less postoperative pneumonia by encouraging preoperative LAMA/LABA therapy in this patient population.

[Usefulness of FDG-PET for the diagnosis of postoperative recurrence of lung cancer].

No standardized postoperative follow-up strategy has been established for lung cancer patients, although CT and tumor markers are often employed. We conducted a retrospective study evaluating fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of postoperative recurrence of lung cancer. We evaluated 28 patients with suspected postoperative recurrence of lung cancer, who underwent FDG-PET between July 2004 and November 2005. Of these, 15 showed positive PET finings. Recurrence of lung cancer cases confirmed in 14 of these and the remaining case showed a postoperative scar. Thirteen patients with no findings on PET scan have demonstrated no evidence of recurrence during follow-up periods between 10 to 23 months. The negative predictive value was therefore 100%. FDG-PET in addition to chest CT and tumor markers for the diagnosis of the postoperative recurrence of lung cancer is considered to be beneficial in terms of avoiding excessive radiation exposure and limiting medical costs, but further evaluation in more patients is necessary.

Resection of pulmonary endometriosis using video-assisted thoracoscopic surgery under preoperative CT-guided marking.

Pulmonary endometriosis is a gynecological disorder in which endometrial tissue grows outside of the uterine cavity. Usually, the ectopic implants are located in the pelvis and manifest as dysmenorrhea, chronic pelvic pain, or infertility. Pulmonary endometriosis sometimes occurs in the pleurae and can result in catamenial pneumothorax; however, true pulmonary endometriosis, tissue growing in the lung itself, is rare. We report a 22-year-old patient with pulmonary endometriosis and catamenial hemoptysis. Pulmonary endometriosis was proved histologically and treated successfully by wedge resection using video-assisted thoracoscopic surgery.

Diffuse fluorodeoxyglucose-positron uptake in the bone marrow of a patient with granulocyte colony-stimulating factor-producing pleomorphic carcinoma of the lung: A case report.

The current study presents the case of a 66-year-old male presenting with fever and chest pain. Chest enhanced computed tomography scanning revealed a mass shadow in the right upper lobe with chest wall invasion. 18-Fluorodeoxyglucose-positron emission tomography (FDG-PET) identified the localized uptake of the mass lesion in the right upper lobe, in addition to diffuse uptake by the bone marrow. The laboratory data on admission revealed marked leukocytosis and an elevated C-reactive protein level (CRP). Serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin 6 were increased. Based on a clinical diagnosis of non-small cell lung cancer (c-T3N0M0 stage IIB), the patient underwent right upper lobectomy with chest wall resection. The histological examination showed a pulmonary pleomorphic carcinoma. Immunohistochemical analysis of the resected tumor tissues revealed positive staining for G-CSF. The patient's high-grade fever, leukocytosis, and elevated CRP level rapidly subsided following the resection. This confirmed that the tumor was a G-CSF-producing pulmonary pleomorphic carcinoma. Five months after the resection, the diffuse FDG uptake in the bone marrow was absent, even with the presence of a small pulmonary metastasis and marginal serum G-CSF elevation. Diffuse FDG uptake in bone marrow induced by G-CSF producing pleomorphic carcinoma must be taken into consideration, in order for it not to be misinterpreted as diffuse bone marrow metastases or hematologic malignancy.

Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with multiple pure ground-glass opacities: a case report.

BACKGROUND: Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell lymphoma that is a type of non-Hodgkin lymphoma and a type of primary pulmonary malignant lymphoma. MALT lymphomas affecting the lung show various findings on chest computed tomography, which range from typical nodules or areas of consolidation to findings that are extremely rare in pulmonary MALT lymphomas, such as pure ground-glass opacities throughout the lung. CASE PRESENTATION: A 35-year-old woman was found to have a few shadows with ground glass opacities on chest computed tomography (CT) in 2012. A shadow in right S10 that was initially very small increased in size over time, and was 14 × 8 mm in 2015. Other shadows also appeared. Because lung adenocarcinoma was suspected, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Histopathological examination of the right S10 and other lesions revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact. Immunohistochemical staining showed that tumor cells were positive for CD20, CD79a, and BCL2 expression. The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT. CONCLUSIONS: We think that the ground glass opacities on CT were accounted for by MALT lesions that contained intact alveolar air spaces. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.