Intermittent hypoxia induces turbinate mucosal hypertrophy via upregulating the gene expression related to inflammation and EMT in rats.

PURPOSE: Chronic intermittent hypoxia (IH) plays a pivotal role in the consequences of obstructive sleep apnea (OSA). It has been demonstrated that IH impairs nasomaxillary complex growth to reduce nasal airway cavity size in rodent models. Although turbinate dysfunction with inflammatory mucosal hypertrophy is related to OSA, the role of IH in turbinate hypertrophy with inflammation-driven fibrosis is unknown. Here, we aimed to clarify the pathogenesis of inflammatory mucosal hypertrophy and epithelial-mesenchymal transition (EMT) in the nasal turbinate under IH. METHODS: Seven-week-old male Sprague-Dawley rats were exposed to IH (4% O2 to 21% O2 with 0% CO2) at a rate of 20 cycles/h. RESULTS: Hypertrophy of the turbinate mucosa occurred after 3 weeks, with the turbinate mucosa of the experimental group becoming significantly thicker than in the control group. Immunostaining showed that IH increased the expression of TGFß and N-cadherin and decreased E-cadherin expression in the turbinate mucosa. Quantitative PCR analysis demonstrated that IH enhanced the expression of not only the inflammatory markers Tnf-a, Il-1b, and Nos2 but also the EMT markers Tgf-b1, Col1a1, and Postn. CONCLUSIONS: Collectively, these results suggest that IH induced turbinate hypertrophy via upregulation of gene expression related to inflammation and EMT in the nasal mucosa.

Intermittent hypoxia retards mandibular growth and alters RANKL expression in adolescent and juvenile rats.

OBJECTIVES: Chronic intermittent hypoxia (IH), a common state experienced in obstructive sleep apnoea (OSA), retards mandibular growth in adolescent rats. The aim of this study was to elucidate the differential effects of IH on mandibular growth in different growth stages. MATERIALS AND METHODS: Three-week-old (juvenile stage) and 7-week-old (adolescent stage) male Sprague-Dawley rats underwent IH for 3 weeks. Age-matched control rats were exposed to room air. Mandibular growth was evaluated by radiograph analysis, micro-computed tomography, real-time polymerase chain reaction and immunohistology. Tibial growth was evaluated as an index of systemic skeletal growth. RESULTS: IH had no significant impact on the general growth of either the juvenile or adolescent rats. However, it significantly decreased the total mandibular length and the posterior corpus length of the mandible in the adolescent rats and the anterior corpus length in the juvenile rats. IH also increased bone mineral density (BMD) of the condylar head in adolescent rats but did not affect the BMD of the tibia. Immunohistological analysis showed that the expression level of receptor activation of nuclear factor-κB ligand significantly decreased (in contrast to its messenger ribonucleicacid level) in the condylar head of adolescent rats with IH, while the number of osteoprotegerin-positive cells was comparable in the mandibles of adolescent IH rats and control rats. LIMITATIONS: The animal model could not simulate the pathological conditions of OSA completely and there were differences in bone growth between humans and rodents. CONCLUSIONS: These results suggest that the susceptibility of mandibular growth retardation to IH depends on the growth stage of the rats.

[Surgical Cases of Solitary Lesion after Surgery for Primary Lung Cancer].

Lung nodules during postoperative follow-up of lung cancer are generally suspected to be its recurrence, but some cases are diagnosed as non-malignant disease. From January 2001 to November 2018, we experienced 5( 4.5%) new non-malignant lesions in 112 lung cancer patients who underwent a lung resection. The average period from first to second lung surgery was 36.2 months (range:3-64), and computed tomography findings before the second surgery were solid nodules in four cases and groundglass opacity in one case. The average maximum standardized uptake value of the lesions on fluorodeoxyglucose positron emission tomography was 4.29 (range:0-10.85). The diagnosis after the second surgery was pulmonary cryptococcosis in 2 cases, nontuberculous mycobacteriosis in 1 case, inflammatory mass in 1 case, and pneumonia in 1 case. The differential diagnosis between these diseases and lung cancer recurrence is discussed in the present study.

Mediastinal paraganglioma successfully resected by robot-assisted thoracoscopic surgery with en bloc chest wall resection: a case report.

BACKGROUND: Robot-assisted thoracoscopic surgery (RATS) is useful for surgery in the apical region of the chest cavity, as it narrows towards the head. Here, we describe a nonfunctional, rib-invasive paraganglioma arising in the posterior mediastinum that was successfully removed using RATS combined with chest wall resection. CASE PRESENTATION: A 31-year-old woman presented with a posterior mediastinal mass on chest computed tomography (CT) scan during a medical check-up 2 years prior. Positron emission tomography/computed tomography scan with F-18 fluorodeoxyglucose revealed a mass associated with standardized uptake maximum value of 2.69. With a preoperative diagnosis of neurogenic tumor by CT-guided percutaneous fine-needle aspiration biopsy, we performed robot-assisted tumor resection combined with chest wall resection. The wristed instruments of the robotic surgical system have increased range of motion and enabled the tumor resection without organ injury in the thoracic cavity. Histopathology examination revealed a non-functional paraganglioma with rib invasion. CONCLUSIONS: RATS is a useful technique, enabling safer and easier resection of a mediastinal tumor adjacent to surrounding organs.

[Usefulness of Long Shaft Stapler in Robot-assisted Thoracic Surgery Lung Resection].

Since national health insurance began to cover robot-assisted thoracoscopic surgery (RATS) for malignant lung tumors, malignant mediastinal tumors, and benign mediastinal tumors in Japan starting in 2018, the number of RATS performed domestically has increased rapidly. In the case of undiagnosed lung tumor, it is necessary to perform a thoracoscopic lung biopsy in the port arrangement for RATS lung resection in the case of undiagnosed lung tumor. The 2 ports are placed in the same 8th intercostal space and a 3 cm utility thoracotomy is added to the 4th or 5th intercostal space for the thoracoscopic lung biopsy. Because the assistant uses the stapler from the port, the distance to the target area increases. When it is converted to RATS for malignant lung diseases, the utility thoracotomy is often hidden by the robot arm and all ports placed in the 8th intercostal space are far from the target area. Furthermore, the assistant working space outside the patient's body is limited by the robot arms. The Signia stapling system has an adapter to extend the shaft. By attaching the adapter, the shaft can be extended by 10 cm. This permits easy handling of the stapler during both thoracoscopic biopsy and RATS lung resection.

Thoracoscopic surgical case of an ectopic mediastinal parathyroid adenoma detected by chance: a case report.

BACKGROUND: Ectopic mediastinal parathyroid tumor (EMPT) is a rare cause of primary hyperparathyroidism (PHPT); it is difficult to resect using the cervical approach. We describe a case of using video-assisted thoracic surgery (VATS) for EMPT resection. CASE PRESENTATION: A 67-year-old woman with a history of postoperative thyroid cancer had no symptoms. She was diagnosed with PHPT and underwent thyroid cancer surgery. She had serum calcium and intact parathyroid hormone (PTH) levels of 11.1 mg/dL and 206 pg/mL, respectively. Chest computed tomography showed a 10-mm nodule in the anterior mediastinum. Technetium-99 m methoxyisobutyl isonitrile scintigraphy showed an abnormal uptake lesion in the anterior mediastinum. She was diagnosed with PHPT caused by EMPT and underwent VATS. The pathological examination confirmed parathyroid adenoma. Her serum calcium and intact PTH levels were normal from 15 min after tumor resection. She has had no recurrence of EMPT. CONCLUSIONS: The VATS approach was effective for the resection of EMPT.

[Reinforcement Materials for Thoracic Surgery].

Recently, various types of artificial and biological materials have been used for hemostasis or control of air leakage in thoracic surgery. These reinforcement materials are essential for thoracic surgery. Therefore, surgeons must know their characteristics and appropriate usage. In this review, the authors describe the recent development of reinforcement materials in thoracic surgery.

[Usefulness of Continuous Suction Unit in Detecting Air Leakage for Pneumothorax].

A 66-year-old male with spontaneous pneumothorax underwent chest tube drainage in other hospital. After tube drainage, chest X-ray showed that the lung fully expanded and an air leakage was not visible. However, clamping the chest tube led to the collapse of the lung, and he transferred to our hospital. A continuous suction unit with pressure and bubbling time history monitoring system was used to detect intermittent air leakages( MS-009T). He underwent video-assisted thoracoscopic surgery. An air leakage from the right lung successfully closed. A new continuous suction unit was useful in detecting an air leakage which could not be confirmed by visual inspection.

Effect of collagen vascular disease-associated interstitial lung disease on the outcomes of lung cancer surgery.

PURPOSE: This study compared the effect of collagen vascular disease-associated interstitial lung disease (CVD-ILD) with that of idiopathic interstitial pneumonias (IIPs) on the outcomes of lung cancer surgery. METHODS: This study retrospectively reviewed the medical records of patients who underwent surgery for non-small cell lung cancer (NSCLC) and compared the data of 16 patients with CVD-ILD with those of 70 patients with IIPs. The patterns of interstitial lung disease (ILD) on chest computed tomography were classified into usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) patterns. RESULTS: The numbers of UIP and NSIP patterns were 10 (62.5%) and 6 (37.5%) patients in CVD-ILD group, and 62 (88.6%) and 8 (11.4%) patients in IIPs group, respectively. A postoperative acute exacerbation (AE) appeared in 1 patient (6.3%) in the CVD-ILD group and 6 patients (8.6%) in the IIPs group. No significant differences in the incidence of postoperative AE and mortalities were observed between the two groups. The five-year overall survival rates of the CVD-ILD and IIPs groups were 37.5 and 49.2%, respectively. CONCLUSIONS: Surgery for NSCLC in CVD-ILD patients appear to cause no increase in postoperative AE and mortality in comparison to that seen in IIPs patients. Similar to IIPs, CVD-ILD might therefore affect the prognosis of resected NSCLC.

Surgery for non-small cell lung cancer in patients with a history of cardiovascular surgery.

PURPOSE: To clarify if previous cardiovascular surgery (CVS) affects the postoperative outcome of surgery for non-small cell lung cancer (NSCLC). METHODS: We reviewed, retrospectively, the medical records of 36 patients with a history of CVS, who underwent lung cancer surgery at a single institution (study group; SG) and compared their characteristics and postoperative outcomes with those of patients without a history of CVS history (control group; CG), and also with those of patients with coexisting cardiovascular diseases in the CG (specified control group; SCG). Finally, we used a thoracic revised cardiac risk index (ThRCRI) to evaluate the risk of perioperative cardiovascular events. RESULTS: There was a significant difference in the ThRCRI classifications between the SG and the SCG (p < 0.0001). There were no significant differences in the incidence of intraoperative and postoperative complications between the SG and CG, or between the SG and SCG. The 5-year survival rates of the SG, CG, and SCG were 69.3, 73.9, and 65.4 % in all stages, and 83.5, 82.2, and 70.4 % in stage I, respectively. CONCLUSIONS: Previous CVS did not increase the number of perioperative cardiovascular events in this study and had no significant influence on the prognosis of patients undergoing resection of NSCLC.

Intermittent hypoxia causes mandibular growth retardation and macroglossia in growing rats.

INTRODUCTION: In this study, we aimed to examine the role of intermittent hypoxia (IH) in dentofacial morphologic changes in growing rats. METHODS: Seven-week-old male rats were exposed to IH at 20 cycles per hour (nadir of 4% oxygen to peak of 21% oxygen) for 8 hours per day for 6 weeks. Control rats were exposed to normoxia (N). Maxillofacial growth was compared between the 2 groups by linear measurements on cephalometric radiographs. To examine the dental arch morphology, study models and microcomputed tomography images of the jaws were taken. Additionally, tongue size was measured. RESULTS: The gonial angle and the ramus of the mandible were smaller in the IH group than in the N group, whereas the body weights were not different between the 2 groups. Morphometric analysis of the dentition showed a significantly wider mandibular dentition and narrower maxillary dentition in the IH than in the N group. The relative width (+4.2 %) and length (tongue apex to vallate papillae, +3.5 %) of the tongue to the mandible were significantly greater in the IH group than in the N group. CONCLUSIONS: IH induced dentofacial morphologic discrepancies in growing rats.

[Application of Ultrasonography in Detecting Multiple Schwannomas from a Single Intercostal Nerve;Report of a Case].

A 31-year-old man was referred to our hospital for chest abnormal shadow on a routine health checkup. Two nodular lesions were found at the 2nd intercostal space by computed tomography. Chest wall ultrasonography showed 2 masses suspecting tumors. Tumors were resected through 3-cm skin incision with the assistance of thoracoscope. Pathological diagnosis was both schwannomas. Ultrasonography was useful in resecting chest wall tumor.

Lethal ventricular tachycardia triggered after femoral fracture repair in an obese man with insulin-resistant diabetes.

An obese man (height, 178 cm; weight, 160 kg; body mass index, 50.5 kg/m2) with a history of recurrent ventricular tachycardia (VT), cardiomyopathy, coronary sclerosis, and insulin-resistant diabetes suffered a right femur fracture in a vehicular accident. His fracture was repaired the following day, but shortly after surgery, his serum potassium (K+) level increased, presumably due to K+ leakage from the injured muscles, leading to persistent VT and death. An autopsy revealed severe cardiac hypertrophy, moderate coronary sclerosis, and histological findings of myocardial hypercontraction, but not myoglobin-related renal failure, pulmonary thrombosis, lipid emboli, or inflammation. The hyperkalemia was not corrected by glucose-insulin infusion and led to the death of the patient due to the preexisting cardiomyopathy, coronary sclerosis, and a predisposition to VT. In addition to the autopsy, the analysis of the clinical course was indispensable for determining the cause of death as hyperkalemia-related VT.

[Outcomes of Surgical Treatment by Modified Transmanubrial Approach].

OBJECTIVE: The aim of this study is to evaluate the useful and safety of surgical treatment by modified transmanubrial approach(MTA). METHODS: Between January 2000 and May 2014, 10 patients underwent surgical treatment by MTA. Among these patients, we retrospectively reviewed the medical records of 6 patients who had vascular invasion of tumor. We evaluated postoperative outcomes of MTA. RESULTS: All patients were men, with a median age of 56 years. Pathological diagnoses were as follows:thymic carcinoma in 2, thyroid cancer in 2, primary lung cancer in 1, mediastinal lymph node metastasis of thyroid cancer in 1 patient. The median operative time was 468 minutes. The median bleeding was 1,723.5 ml. Four patients underwent angioplasty, including direct suture in 1, graft replacement artificial blood vessel in 3 patients. Right auricle-innominate vein bypass was performed in 3 patients. The median hospitalization term was 29 days. R0 resection was archived in all cases. CONCLUSION: The surgical treatment by MTA is useful and safety for anterior apical tumor and mediastinal tumor invading adjacent vessels. Because of a small number of sample size, further investigation well be needed.

[Hemoptysis caused by bleeding into a bleb].

A man in his 40s was admitted to our hospital for hemoptysis. A chest computed tomography showed a mediastinal mass adjacent to the left side wall of the ascending aorta with infiltrative shadows of the left upper lobe. In spite of medical treatment, hemoptysis continued, and the surgery was performed. The thoracoscopic findings showed hematoma in the bullous cavity. Partial resection of the left upper lobe was performed. Histopathological findings in the resected specimen revealed a bleb that was filled with blood.

Intermittent-hypoxia induced autophagy attenuates contractile dysfunction and myocardial injury in rat heart.

Sleep apnea syndrome (SAS) is considered to be associated with heart failure (HF). It is known that autophagy is induced in various heart diseases thereby promotes survival, but its excess may be maladaptive. Intermittent hypoxia (IH) plays pivotal role in the pathogenesis of SAS. We aimed to clarify the relationships among IH, autophagy, and HF. Rats underwent IH at a rate of 20cycles/h (nadir of 4% O2 to peak of 21% O2 with 0% CO2) or normal air breathing (control) for 8h/d for 3weeks. IH increased the cardiac LC3II/LC3I ratio. The IH induced upregulation of LC3II was attenuated by the administration of an inhibitor of autophagosome formation 3-methyladenine (3-MA), but enhanced by an inhibitor of autophagosome-lysosome fusion chloroquine (CQ), showing enhanced autophagic flux in IH hearts. Electron microscopy confirmed an increase in autophagosomes and lysosomes in IH. With 3-MA or CQ, IH induced progressive deterioration of fractional shortening (FS) on echocardiography over 3weeks, although IH, 3-MA, or CQ alone had no effects. With CQ, IH for 4weeks increased serum troponin T levels, reflecting necrosis. Western blotting analyses showed dephosphorylation of Akt and mammalian target of rapamycin (mTOR) at Akt (Ser2448, 2481) sites, suggesting the activation of autophagy via Akt inactivation. Conclusions. IH-mediated autophagy maintains contractile function, whereas when autophagy is inhibited, IH induces systolic dysfunction due to myocyte necrosis. General significance. This study highlighted the potential implications of autophagy in cardio-protection in early SAS patients without comorbidity, reproduced in normal rats by 3~4weeks of IH.

Immunohistochemical study of the autophagy marker microtubule-associated protein 1 light chain 3 in normal and steatotic human livers.

AIM: Autophagy has been implicated in lipid droplet (LD) turnover. Adipose differentiation-related protein (ADRP) and microtubule-associated protein 1 light chain 3 (LC3) monitor LD and autophagosomes, respectively. We examined whether immunohistochemical staining of ADRP and LC3 can monitor LD and autophagy, and if so, whether autophagy is related to LD turnover in post-mortem human livers. METHODS: We performed conventional immunohistochemistry of LC3 in paraffin-embedded human livers with different severities of steatosis, obtained at autopsy. Double immunofluorescence microscopy using anti-LC3 and anti-ADRP antibodies was performed to elucidate the relationship between autophagy and LD turnover. RESULTS: LC3 immunohistochemistry reproducibly delineated puncta in normal human livers, which were preferentially located around the central venal zone. The extent of LC3 immunostaining reduced with progressing steatosis. Double immunofluorescence for ADRP and LC3 demonstrated an inverse relationship between ADRP positive areas and LC3 positive areas, as well as the co-localization of ADRP and LC3 on a part of small LD but not large LD. CONCLUSION: These findings suggest that impaired autophagy promotes steatosis and that autophagy may be implicated in LD turnover.

Lethal pulmonary air embolism caused by the removal of a double-lumen hemodialysis catheter.

Pulmonary air embolisms due to the removal of a central venous catheter are rare, but catheter removal is known to be a high risk factor for air embolism. In particular, the removal of a large catheter, such as a double-lumen hemodialysis catheter, can allow a large amount of air to enter into the bloodstream, which often results in sudden death. So, during catheter removal, special care should be taken to prevent air from entering blood vessels, for example, to ensure that the patient's head is tilted downward, that they have inhaled and are holding their breath, and that a covering gauze and inert ointment have been applied to the exit site. We report a lethal case of pulmonary air embolism caused by the removal of a double-lumen catheter from the right internal jugular vein of a patient who was sitting up and had not been instructed to hold their breath.

Gestational intermittent hypoxia reduces mandibular growth with decreased Sox9 expression and increased Hif1a expression in male offspring rats.

Introduction: Maternal obstructive sleep apnea (OSA) during pregnancy is the risk factor for impaired fetal growth with low birth weight in the offspring. However, it is unclear whether gestational intermittent hypoxia (IH, a hallmark of maternal OSA) has long-term detrimental consequences on the skeletal development of offspring. This study aimed to investigate postnatal maxillofacial bone growth and cartilage metabolism in male and female offspring that were exposed to gestational IH. Methods: Mother rats underwent IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) for 8 h per day during gestational days (GD) 7-20, and their male and female offspring were analyzed postnatally at 5 and 10 weeks of age. All male and female offspring were born and raised under normoxic conditions. Results: There was no significant difference in whole-body weight and tibial length between the IH male/female offspring and their control counterparts. In contrast, the mandibular condylar length was significantly shorter in the IH male offspring than in the control male offspring at 5 and 10 weeks of age, while there was no significant difference in the female offspring. Real-time polymerase chain reaction (PCR) showed that gestational IH significantly downregulated the mRNA level of SOX9 (a chondrogenesis marker) and upregulated the mRNA level of HIF-1α (a hypoxia-inducible factor marker) in the mandibular condylar cartilage of male offspring, but not in female offspring. Conclusion: Gestational IH induced underdeveloped mandibular ramus/condyles and reduced mRNA expression of SOX9, while enhancing mRNA expression of HIF-1α in a sex-dependent manner.

Presurgical planning using a three-dimensional pulmonary model of the actual anatomy of patient with primary lung cancer.

OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) for both lobectomy and segmentectomy has been used widely for early stage nonsmall cell lung cancer (NSCLC). The objective of this study was to investigate the clinical feasibility of surgical planning using patient's actual three-dimensional (3D) pulmonary model for the thoracoscopic surgical treatment of early stage NSCLC. METHODS: We examined 57 patients with stage IA NSCLC ≤ 2 cm in diameter. Based on patient's actual 3D pulmonary model created by using a homemade software program called CTTRY (Tokyo Women's Medical University, Tokyo, Japan), both the location of and extent of tumor invasion were assessed, and a suitable type of VATS lung resection for an individual was selected. RESULTS: By the 3D models, tumors in 47 patients were localized within one segment, and other tumors (10 patients, 18%) were involved in multiple segments. VATS lung resections consisted of a single segmentectomy were performed in 25 patients; upper division resections, 9; lingulectomy, 5; extended segmentectomy, 7; single subsegmentectomy, 6; and multiple subsegmentectomy, 5. All 57 patients underwent successful VATS lung resection without massive bleeding. CONCLUSION: Presurgical planning based on patient's actual 3D pulmonary model is useful for patients with stage IA NSCLC ≤ 2 cm in diameter and for selecting an appropriate VATS lung resection for an individual.