Pulmonary interstitial glycogenosis in Birt-Hogg-Dubé syndrome-associated lung cysts: A new insight into the pathogenesis?

Multiple lung cysts are one of the major features of Birt-Hogg-Dubé syndrome (BHD), but little is known about their nature and pathogenesis. We report a case of a woman diagnosed with BHD lung cysts who exhibited pulmonary interstitial glycogenosis (PIG), a mesenchymal abnormality hitherto undescribed in this disease, in specimens resected at 14 and 29 years of age. Histopathologically, oval to spindle clear cells were seen in the subepithelial interstitial tissue of septal structures and the walls of the cysts. They had abundant periodic acid-Schiff-positive cytoplasmic glycogen. Immunohistochemically, these cells were positive for a few markers of mesenchymal stem cell-like lineage, including vimentin, CD44, and CD10, and negative for markers of epithelial or specific mesenchymal differentiation; these results were consistent with the reported immunophenotype of PIG cells. These PIG cells were more abundant in her specimen at age 14 years than in the second specimen from adulthood. The present case suggests that BHD lung cysts belong to a group of pulmonary developmental disorders characterized by combined PIG and alveolar simplification/cystic change. Disorders with PIG may persist until adulthood and may be of clinical and pathological significance.

A neuroendocrine tumor within an anterior mediastinal mature teratoma: a case report.

BACKGROUND: Mature teratomas are benign germ cell tumors. On rare occasions, they have been associated with somatic malignancies and are termed rare germ cell tumors with a somatic-type malignancy (GCTSM). Mature teratomas commonly comprise adenocarcinomas; only seven previous cases of mature teratomas with neuroendocrine tumors have been reported to date. Here, we report a patient with a neuroendocrine tumor whithin a mature teratoma. CASE PRESENTATION: A 26-year-old man visited our department complaining of chest tightness. Contrast-enhanced computed tomography (CT) scans showed a strongly enhanced lesion within a 10-cm encapsulated cystic lesion in the anterior mediastinum. Positron emission tomography (PET) scans showed no areas of significant 18F-fluorodeoxyglucose (18F-FDG) accumulation. He underwent complete tumor resection via the transsternal approach. Histopathological examination of the specimen indicated a neuroendocrine tumor contained within a mature teratoma. CONCLUSIONS: In this case, a neuroendocrine tumor was contained within a mature teratoma. Our patient had no specific symptoms and his serum markers were within the normal range. Although PET is beneficial for diagnosing other GCTSM, it is not useful in detecting a neuroendocrine tumor. Therefore, the preoperative diagnosis of neuroendocrine tumors contained within mature teratomas remains challenging. However, GCTSM should be suspected in patients exhibiting CT findings of a mediastinal tumor, measuring ≥ 6 cm, in addition to characteristic GCTSM findings. Moreover, surgery should be performed carefully in such cases.

[Massive Hemorrhage from the Delayed Diaphragmatic Injury due to the Rib Fracture after the Blunt Chest Trauma:Report of a Case].

We report a case of delayed diaphragmatic injury caused by lower rib fractures. A 56-year-old male was referred to our hospital due to the fractures of right lower ribs. Chest X-ray revealed pneumothorax, and the patient was hospitalized for follow-up. On the sixth day after the injury, the patient suddenly complained of chest pain and respiratory distress, and then shock status developed. Chest computed tomography (CT) revealed massive pleural effusion. An emergency operation was performed. The injury of the diaphragm was found. Fracture of the lower rib can cause diaphragmatic injury leading to massive hemorrhage.

One-Year Incidences of Venous Thromboembolism, Bleeding, and Death in Patients With Lung Cancer (Cancer-VTE Subanalysis).

Introduction: This subanalysis aimed to provide real-world data on venous thromboembolism (VTE) from patients with lung cancer in the Cancer-VTE Registry. Methods: The primary outcome was the number of baseline VTE events in patients with lung cancer. The 1-year cumulative incidences of symptomatic VTE; composite VTE (symptomatic and incidental VTE requiring treatment); bleeding; cerebral infarction, transient ischemic attack, and systemic embolic events; and all-cause death were calculated. Clinical trial registration: UMIN000024942. Results: The study enrolled a total of 2377 patients with lung cancer; of these, 119 (5.0%) had VTE (six [0.3%], symptomatic, and 113 [4.8%], asymptomatic) and 14 (0.6%) had pulmonary embolism at baseline. During the follow-up period (mean, 337.7 d), the incidence was 0.6% for symptomatic VTE, 1.8% for composite VTE, 1.5% for bleeding events, 1.3% for cerebral infarction, transient ischemic attack, and systemic embolism, and 19.1% for all-cause death. Composite VTE frequency did not vary by anticancer drug type. Patients with (versus without) VTE at baseline had higher hazard ratios (HRs) for composite VTE (unadjusted HR: 5.29; Gray test p < 0.001) and symptomatic VTE (unadjusted HR: 4.89; Gray test p = 0.007). Patients with VTE at baseline had higher HRs for bleeding events (unadjusted HR: 3.27; Gray test p = 0.010) and all-cause death (unadjusted HR: 2.73; log-rank test p < 0.001) than patients without. In multivariable analysis, patients with baseline VTE prevalence and Eastern Cooperative Oncology Group Performance Status of 2 had increased composite VTE risk during cancer therapy. There were no other risk factors for composite VTE. Conclusions: Our findings emphasize the importance of VTE screening at cancer diagnosis.

Intrapericardial Ectopic Goiter: A Very Unusual Presentation.

Mediastinal ectopic goiter is a thyroid tumor that lies entirely below a plane extending from the superior surface of the first thoracic vertebra to the suprasternal notch, and commonly lies in the vicinity of the thymus. Intrapericardial ectopic goiter is extremely rare. We present an extremely rare case of a 63-year-old woman with an intrapericardial ectopic goiter and review the pertinent literature.

Clinical impact of perioperative atrial fibrillation on long-term recurrence of malignancy.

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

Rosai-Dorfman disease of thymus with elevated serum anti-acetylcholine receptor antibody: a case report.

Rosai-Dorfman disease is a rare disorder of histiocytic proliferation in lymph nodes and at extranodal sites. We herein describe a patient with isolated Rosai-Dorfman disease in the thymus with elevated anti-acetylcholine receptor antibody. We examined the relationship between Rosai-Dorfman disease and elevated anti-acetylcholine receptor antibody. To our knowledge, elevated anti-acetylcholine receptor antibody has not been reported in isolated thymic Rosai-Dorfman disease.

[Contralateral Pneumothorax after Surgery for Idiopathic Hemopneumothorax;Report of a Case].

A 17-year-old man came to the hospital complaining of right back pain. He had a history of an emergency operation for a left idiopathic hemopneumothorax. A chest X-ray revealed right lung collapse and suggested pleural adhesion at the apex of the right lung. He was diagnosed with right spontaneous pneumothorax and the surgical treatment was performed, because pleural adhesion may cause the hemothorax. During surgery, several pleural adhesion bands were found in the thoracic cavity between the right lung apex and chest wall. Spontaneous pneumothorax with a pleural adhesion at the apex is considered to be the indication for surgery because of the risk of hemothorax.

[Birt-Hogg-Dubé Syndrome Diagnosed with Surgery;Report of Three Cases].

Birt-Hogg-Dubé (BHD) syndrome is an autosomal and predominantly inherited disorder. We report 3 cases of BHD syndrome. Case 1:A 24-year-old man was admitted to our hospital due to left-sided spontaneous pneumothorax. He had a previous drainage history of right-sided spontaneous pneumothorax. In operation, we resected the cyst at segment 8 of the left lung and covered the lung using polyglycolic acid( PGA) sheet. Case 2:A 47-year-old man was admitted to our hospital due to right-sided spontaneous pneumothorax. He had a previous surgical history of right-sided spontaneous pneumothorax and left-sided spontaneous pneumothorax. In operation, we resected the cyst at segment 8 of the right lung and covered the lung using fibrin glue-coated collagen fleece. Case 3:A 60-year-old man was admitted to our hospital due to left-sided spontaneous pneumothorax. He had 2 times of previous drainage history of left-sided spontaneous pneumothorax. In operation, we resected the cysts at lingular division of the lung and covered the lung using PGA sheet. On genetic analysis, all 3 cases were diagnosed with the BHD syndrome.

A rare post-lobectomy complication of right-to-left shunt via foramen ovale.

BACKGROUND: Various complications can cause hypoxemia after pulmonary resection for lung cancer, but intracardiac shunt that becomes symptomatic and causes severe hypoxemia postoperatively is very rare. We report a case that presented platypnea-orthodeoxia syndrome (POS) due to right-to-left shunt via patent foramen ovale (PFO). CASE: A 71-year-old man with a lung cancer in the left upper lobe was referred to our hospital. Left upper lobectomy was performed. Dyspnea developed postoperatively, which was worsened by sitting or standing and relieved in a recumbent position. Contrast transesophageal echocardiogram (TEE) and right intracardiac catheterization revealed a right-to-left shunt via PFO. Open-heart closure of PFO was performed and the patient was free from POS. CONCLUSIONS: Postoperative intracardiac shunt via PFO can cause severe hypoxemia after lung resection. POS suggests the possibility of intracardiac shunt and careful observation is needed.

Perioperative Atrial Fibrillation in Noncardiac Surgeries for Malignancies and One-Year Recurrence.

BACKGROUND: Perioperative atrial fibrillation (POAF) in noncardiac surgeries is common. However, it is unclear whether such atrial fibrillation (AF) recurs in the long term. METHODS: This study was a prospective, single-center, observational study that included patients who underwent noncardiac surgeries for malignancies. Patients were followed up for 1 year to evaluate the incidence of AF, ischemic stroke, and mortality. An event-triggered recorder was used in patients with POAF. The incidences were compared according to the presence of POAF. RESULTS: Of 752 consecutive patients, 77 (10.2%) developed POAF and wore an event recorder for 19 (12-30) days. AF and ischemic stroke at 1 year were observed in 24 patients (31.1%) and 2 patients (2.6%) with POAF and 4 patients (0.6%) and 3 patients (0.4%) without POAF, respectively. Of the 24 patients with POAF and AF recurrence, 22 (92%) were asymptomatic. Anticoagulation was prescribed in 67 patients (87%) with POAF. Multivariate Cox regression analysis demonstrated that a higher AF recurrence rate in patients with POAF was associated with hypertension (hazard ratio, 2.79; 95% confidence interval, 1.06-7.38) and serum creatinine level (hazard ratio for 20 µmol/L increase, 2.32; 95% confidence interval, 1.16-4.62). CONCLUSIONS: AF recurs in approximately 30% of patients with POAF with malignancy in the subsequent year; most recurrences are asymptomatic.

Incidence and complications of perioperative atrial fibrillation after non-cardiac surgery for malignancy.

BACKGROUND: Perioperative atrial fibrillation (POAF) is one of the common arrhythmias in the setting of non-cardiac surgeries for malignancy. As POAF may cause subsequent adverse events, it is important to confirm its characteristics and risk factors. MATERIALS AND METHODS: The prospective cohort study of surveillance for perioperative atrial fibrillation recurrence (PREDICT AF RECURRENCE) is an ongoing prospective, single-center, observational study that aims to illustrate the clinical impact of POAF in major non-cardiac surgery for malignancy. Patients who planned to undergo non-cardiac surgery for definitive/suspected malignancy were registered. Those with a history of AF and atrial flutter were excluded. Any 30-day complications included acute myocardial infarction, congestive heart failure, bleeding, thrombosis, any infection, and acute kidney injury. The primary endpoint was an incidence of POAF. RESULTS: The present study included 799 patients (age, 68 ± 11; male, 62%). Of these, 80 patients (10.0%) developed POAF. Notably, 66 patients (83%) had no symptoms. Any 30-day complications occurred in 180 patients (23%) (with POAF: 34 (43%); without POAF: 146 (20%); p < 0.001). POAF in 17 patients (50%) was preceded by the development of complications. No patient developed cardiogenic shock and/or acute heart failure. The association between 30-day complications and POAF development were analyzed using the multivariate adjusted model (odds ratio: 2.84; 95% confidence interval: 1.74-4.62; p < 0.001). CONCLUSION: Ten percent of patients who underwent non-cardiac surgery for malignancy developed POAF, which was strongly associated with perioperative complications. As a majority were asymptomatic, careful observation using electrocardiography monitoring is important to avoid oversights. CLINICAL TRIAL REGISTRATION: UMIN ID: UMIN000016146.

The study protocol for PREDICT AF RECURRENCE: a PRospEctive cohort stuDy of surveIllanCe for perioperaTive Atrial Fibrillation RECURRENCE in major non-cardiac surgery for malignancy.

BACKGROUND: A previous retrospective cohort study established the relationship between perioperative atrial fibrillation (POAF) and subsequent mortality and stroke. However, the details regarding the cause of death and etiology of stroke remain unclear. METHODS: The prospective cohort study of surveillance for perioperative atrial fibrillation recurrence in major non-cardiac surgery for malignancy (PREDICT AF RECURRENCE) registry is an ongoing prospective cohort study to elucidate the long-term recurrence rate and the clinical impact of new-onset POAF in the setting of head and neck, non-cardiac thoracic, and abdominal surgery for malignancy. In this study, cardiologists collaborate with a surgical team during the perioperative period, carefully observe the electrocardiogram (ECG) monitor, and treat arrhythmia as required. Furthermore, patients who develop new-onset POAF are followed up using a long-term Holter ECG monitor, SPIDER FLASH-t AFib®, to assess POAF recurrence. DISCUSSION: Even if patients with malignancy survive by overcoming the disease, they may die from any preventable cardiovascular diseases. In particular, those with POAF may develop cardiogenic stroke in the future. Because details of the natural history of patients with POAF remain unclear, investigating the need to continue anticoagulation therapy for such patients is necessary. This study will provide essential information on the recurrence rate of POAF and new insights into the prediction and treatment of POAF. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR): UMIN000016146 ; Data of Registration: January 7, 2015.

Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.

Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease, and connective tissue disease. Most cases of such aneurysm occur in the trunk or major branches of the pulmonary artery, while the peripheral type is less common. The treatment modalities are medical therapy, surgery, and percutaneous catheter embolization. The mortality rate associated with rupture is approximately 50%. We encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm secondary to pneumonia and cavity formation during chemotherapy for acute myeloid leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT) scan and pulmonary angiography were very useful. He was treated with right middle and lower lobectomy. After 1-month follow-up, he could restart additional chemotherapy.

Giant bulla formation in the lung because of a check-valve mechanism.

The pathogenesis of bulla formation has not yet been demonstrated in pathologic examinations or through direct visualization during thoracotomy or thoracoscopic surgery. We present two cases of giant bulla formation after pneumothorax because of cryptogenic organizing pneumonia and lung abscess. The case findings suggested that the pathogenesis was attributable to a check-valve mechanism, secondary to bronchiolitis obliterans, or the presence of an obstructing air leakage due to a lung fistula. The lung fistula had been covered by inflammatory membranes consisting of blood and/or fibrous precipitates with detached visceral pleura.

Thoracoscopic modified pleural tent for spontaneous pneumothorax.

OBJECTIVES: We developed a modified pleural tent (m-tent) procedure and used it in our hospital in almost 30 consecutive patients with spontaneous pneumothorax. The objective of this study was to clarify the feasibility and effectiveness of a thoracoscopic m-tent for the treatment of spontaneous pneumothorax. METHODS: From July 2013 to November 2014, 107 patients with spontaneous pneumothorax were treated in our institution. Eighty-nine of these patients were analysed retrospectively. The inclusion criteria for thoracoscopic m-tent for spontaneous pneumothorax were multiple and widespread bullae, postoperative relapse and secondary spontaneous pneumothorax. The surgical procedures were usually performed through three ports. After bullectomy, an m-tent is made to strip the parietal pleura off the chest wall from about the level of the fourth or fifth rib to the apex, and two or three ligations are then applied to fix the pleural tent and lung parenchyma. Patients in whom an m-tent was not indicated underwent bullectomy plus coverage using absorbable materials. RESULTS: Twenty-seven patients underwent bullectomy plus m-tent (m-tent group) and 62 underwent bullectomy plus coverage over a staple line using an absorbable material such as a polyglycolic acid sheet or nitrocellulose sheet (coverage group). No severe postoperative complications were observed in either group. The m-tent and coverage groups showed significant differences in operation time (129 vs 86 min, mean), haemorrhage (12.8 vs 7.2 ml), postoperative hospital stay (3.7 vs 2.9 days) and postoperative painkiller intake (8.6 vs 6.8 days). Recurrence was observed in 1 (3.7%) and 2 patients (3.2%), respectively. CONCLUSIONS: The thoracoscopic m-tent procedure requires a longer operation, a longer hospital stay and greater painkiller intake. However, these differences are acceptable, and an m-tent should be considered as an option for pleural reinforcement in spontaneous pneumothorax, especially in patients who are complicated with severe pulmonary emphysema, widespread bullae or recurrent pneumothorax.

Prognostic impact of pleural invasion in 1488 patients with surgically resected non-small cell lung carcinoma.

OBJECTIVE: This study aimed to verify the prognostic impact of pleural invasion according to the revised TNM classification, seventh edition. METHODS: The study consisted of 1488 patients with surgically resected non-small cell carcinoma. The degree (pl0-3) and location of pleural invasion were examined using hematoxylin and eosin- and elastica van Gieson-stained slides, and outcome was compared with stratification by several clinicopathological factors. RESULTS: The 5-year overall survival rates of 1008, 260, 85 and 135 patients with pl0, pl1, pl2 and pl3 tumours were 80, 60, 55 and 52%, respectively. Overall survival differed significantly between patients with pl0 tumours and those with pl1 tumours (P < 0.0001). The difference was significant for patients with 1<≤ 2 cm (P = 0.004), 2<≤ 3 cm (P = 0.003) and 3<≤ 5 cm (P = 0.02) tumours. The overall survival of pl0 patients was also significantly better in patients with adenocarcinoma (P < 0.0001) than squamous cell carcinoma (P = 0.043). The overall survival of pl0 patients was significantly better in patients without lymph node metastasis (P < 0.0001) than in those with lymph node metastasis. The 5-year overall survival rates of patients with interlobar, lateral, mediastinal and diaphragmatic pl3 tumours were 65, 51, 51 and 40%, respectively. Overall survival did not differ significantly among these four groups. CONCLUSIONS: Outcome differs between patients with pl0 tumours and those with pl1-3 tumours, particularly among patients with 1<≤ 2 cm, 2 <≤ 3 cm and 3<≤ 5 cm tumours, adenocarcinoma histology and no lymph node metastasis. The location of pl3 pleural invasion did not affect outcome significantly.

A case of malignant peritoneal mesothelioma revealed with limitation of PET-CT in the diagnosis of thoracic metastasis.

A 47-year-old man was referred to our hospital because of a 2-month history of dry cough, 2-kg weight loss, and a feeling of abdominal fullness. The PET-CT scan depicts the intense standard uptake values (SUVs) of the anterior and subphrenic lymphnodes, and intraperitoneal cavity, especially in the omentum, while, no uptake was found in the pleural cavity. Based on the pathological findings of the open lung biopsy specimens, he was diagnosed with malignant peritoneal mesothelioma of epithelioid type with thoracic metastasis. The present case demonstrated the some of the limitations of PET-CT in the diagnosis of malignant mesothelioma, which failed to detect pleural involvement despite aggressive invasion by this tumor.

Which is the better prognostic factor for resected non-small cell lung cancer: the number of metastatic lymph nodes or the currently used nodal stage classification?

INTRODUCTION: This retrospective study was conducted to evaluate the prognostic significance of the number of metastatic lymph nodes (nN) in resected non-small cell lung cancer (NSCLC) in comparison with the currently used pathologic nodal (pN) category in the staging system. METHODS: A total of 1659 patients who underwent potentially curative resection for NSCLC from 2000 to 2006 were included in this study. The association between the nN and survival was explored, and the results were compared with those using the location-based pN stage classification. RESULTS: The patients were divided into four categories according to the number of metastatic nodes: nN0, absence of metastatic nodes; nN1, metastasis in one to two nodes; nN2, metastasis in three to six nodes; and nN3, metastasis in seven or more nodes. The 5-year overall survival for nN0, nN1, nN2, and nN3 was 89.2%, 65.1%, 42.1%, and 22.4%, respectively (p < 0.001). The nN category could be used to subdivide pN1 and pN2 patients into two (nN1 and nN2) and three (nN1, nN2, and nN3) prognostically distinct subgroups, respectively. Multivariate analysis showed the nN category was an independent prognostic factor for resected NSCLC. The difference in overall survival between pN1 and pN2 was not significant (55.4% versus 47.8%, p = 0.245). Patients in each nN category could not be subdivided into different prognostic subgroups according to the pN classification. CONCLUSIONS: The nN category in this study was shown to be a better prognostic determinant than the location-based pN stage classification.