Defining and targeting tumor-associated macrophages in malignant mesothelioma.

Defining the ontogeny of tumor-associated macrophages (TAM) is important to develop therapeutic targets for mesothelioma. We identified two distinct macrophage populations in mouse peritoneal and pleural cavities, the monocyte-derived, small peritoneal/pleural macrophages (SPM), and the tissue-resident large peritoneal/pleural macrophages (LPM). SPM rapidly increased in tumor microenvironment after tumor challenge and contributed to the vast majority of M2-like TAM. The selective depletion of M2-like TAM by conditional deletion of the Dicer1 gene in myeloid cells (D-/-) promoted tumor rejection. Sorted SPM M2-like TAM initiated tumorigenesis in vivo and in vitro, confirming their capacity to support tumor development. The transcriptomic and single-cell RNA sequencing analysis demonstrated that both SPM and LPM contributed to the tumor microenvironment by promoting the IL-2-STAT5 signaling pathway, inflammation, and epithelial-mesenchymal transition. However, while SPM preferentially activated the KRAS and TNF-α/NFkB signaling pathways, LPM activated the IFN-γ response. The importance of LPM in the immune response was confirmed by depleting LPM with intrapleural clodronate liposomes, which abrogated the antitumoral memory immunity. SPM gene signature could be identified in pleural effusion and tumor from patients with untreated mesothelioma. Five genes, TREM2, STAB1, LAIR1, GPNMB, and MARCO, could potentially be specific therapeutic targets. Accordingly, Trem2 gene deletion led to reduced SPM M2-like TAM with compensatory increase in LPM and slower tumor growth. Overall, these experiments demonstrate that SPM M2-like TAM play a key role in mesothelioma development, while LPM more specifically contribute to the immune response. Therefore, selective targeting of monocyte-derived TAM may enhance antitumor immunity through compensatory expansion of tissue-resident TAM.

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

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

Radiation Impacts Early Atherosclerosis by Suppressing Intimal LDL Accumulation.

RATIONALE: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT. OBJECTIVE: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms. METHODS AND RESULTS: Ldlr-/- mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery. Atherosclerosis was studied in the ascending aortic arch and compared with mice without BMT. In BMT mice, neutral lipid and myeloid cell topography were lower in lesions after feeding a cholesterol-rich diet for 3, 6, and 12 weeks. Lesion coalescence and height were suppressed dramatically in mice post-BMT, whereas lateral growth was inhibited minimally. Targeted radiation to the upper thorax alone reproduced the BMT phenotype. Classical monocyte recruitment, intimal myeloid cell proliferation, and apoptosis did not account for the post-BMT phenotype. Neutral lipid accumulation was reduced in 5-day lesions, thus we developed quantitative assays for LDL (low-density lipoprotein) accumulation and paracellular leakage using DiI-labeled human LDL and rhodamine B-labeled 70 kD dextran. LDL accumulation was dramatically higher in the intima of Ldlr-/- relative to Ldlr+/+ mice, and was inhibited by injection of HDL mimics, suggesting a regulated process. LDL, but not dextran, accumulation was lower in mice post-BMT both at baseline and in 5-day lesions. Since the transcript abundance of molecules implicated in LDL transcytosis was not significantly different in the post-BMT intima, transcriptomics from whole aortic arch intima, and at single-cell resolution, was performed to give insights into pathways modulated by BMT. CONCLUSIONS: Radiation exposure inhibits LDL entry into the aortic intima at baseline and the earliest stages of atherosclerosis. Single-cell transcriptomic analysis suggests that LDL uptake by endothelial cells is diverted to lysosomal degradation and reverse cholesterol transport pathways. This reduces intimal accumulation of lipid and impacts lesion initiation and growth.

Double cancer of primary hepatic angiosarcoma and hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

AIM: Primary hepatic angiosarcoma (PHA) is extremely rare, and its imaging findings are similar to those of other liver tumors including hepatocellular carcinoma (HCC). Here, we report a case of hepatitis C virus (HCV)-related HCC followed by PHA that showed remarkable clinical response to atezolizumab plus bevacizumab (Atezo/Bev) therapy. CASE PRESENTATION: A 78-year-old man with recurrent HCC had a liver tumor with lymphadenopathy. Although considered as HCC recurrence, microscopic examination of the resected liver and lymph node showed PHA. Three months later, a solitary lung nodule was newly detected and subsequently resected. The pathological diagnosis was poorly differentiated HCC. Therefore, the patient was finally diagnosed with double cancer of PHA and HCC. Thereafter, he developed a new liver tumor with lymphadenopathy and received Atezo/Bev therapy. Liver tumor biopsy was carried out before the treatment. The pathological diagnosis was angiosarcoma. The patient showed a partial response after two courses of Atezo/Bev therapy. CONCLUSION: To our best knowledge, this report is the first case to present HCV-related HCC followed by PHA and to show that Atezo/Bev therapy is beneficial for PHA.

Foxp3+ Regulatory T Cell Depletion after Nonablative Oligofractionated Irradiation Boosts the Abscopal Effects in Murine Malignant Mesothelioma.

Increasing evidence indicates that local hypofractionated radiotherapy (LRT) can elicit both immunogenic and immunosuppressive local and systemic immune responses. We thus hypothesized that blockade of LRT-induced immunosuppressive responses could augment the antitumor effects and induce an abscopal response. In this study, we found that the upregulation of Foxp3+ regulatory T cells (Tregs) in the mesothelioma tumor microenvironment after nonablative oligofractionated irradiation significantly limited the success of irradiation. Using DEREG mice, which allow conditional and efficient depletion of Foxp3+ Tregs by diphtheria toxin injection, we observed that transient Foxp3+ Treg depletion immediately after nonablative oligofractionated irradiation provided synergistic local control and biased the T cell repertoire toward central and effector memory T cells, resulting in long-term cure. Furthermore, this combination therapy showed significant abscopal effect on the nonirradiated tumors in a concomitant model of mesothelioma through systemic activation of cytotoxic T cells and enhanced production of IFN-γ and granzyme B. Although local control was preserved with one fraction of nonablative irradiation, three fractions were required to generate the abscopal effect. PD-1 and CTLA-4 were upregulated on tumor-infiltrating CD4+ and CD8+ T cells in irradiated and nonirradiated tumors, suggesting that immune checkpoint inhibitors could be beneficial after LRT and Foxp3+ Treg depletion. Our findings are applicable to the strategy of immuno-radiotherapy for generating optimal antitumor immune responses in the clinical setting. Targeting Tregs immediately after a short course of irradiation could have a major impact on the local response to irradiation and its abscopal effect.

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

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

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

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

Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells.

Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2-83 years old). Gene expression of key soluble factors was compared between CDCs derived from young and elderly patients. Among these factors, SFRP1, a gene encoding a Wnt antagonist, was significantly up-regulated in CDCs from elderly patients (≥65 years old). sFRP1 levels was increased significantly also in CDCs, whose senescent phenotype was induced by anti-cancer drug treatment. These results suggest the participation of sFRP1 in CSC aging. We show that the administration of recombinant sFRP1 induced cellular senescence in CDCs derived from young patients, as indicated by increased levels of markers such as p16, and a senescence-associated secretory phenotype. In addition, co-administration of recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess sFRP1 in elderly patients causes CSC aging.

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

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

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

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

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

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

Prediction of postoperative dyspnea and chronic respiratory failure.

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

Assessment of volume reduction effect after lung lobectomy for cancer.

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

Association of sleep-disordered breathing with decreased cognitive function among patients with dementia.

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type-4 portable monitor, is suitable. In this study, a type-4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep-disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep-disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early-stage dementia.

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

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

Effectiveness of warm-up and dynamic balance training in preventing anterior cruciate ligament injuries in college gymnasts: a 3-year prospective study for one team.

BACKGROUND: The effect of trunk stability and dynamic balance warm-up exercises on physical functional improvement remains unelucidated. This study examined whether exercises could prevent anterior cruciate ligament (ACL) injury and improve trunk muscle activation and dynamic balance in gymnasts. METHODS: This comparison study, involving gymnastics practice sessions, included 31 university gymnasts and was conducted in two periods: 1 year of observation followed by 2 years of intervention. Participants performed a trunk and dynamic balance warm-up exercise program during the intervention. The effect of exercise on the incidence of ACL injury was evaluated. In addition, the paired t-test was used to compare the Y-balance distance and the changes in muscle thickness associated with trunk muscle activation at rest and during plank. RESULTS: ACL injury risk during the intervention was significantly lower, with a relative risk of 0.23 (P=0.02, 95% CI: 0.06-0.88). Changes in muscle thickness with activation of the transversus abdominis (P<0.01, mean difference 4.1, 95% CI: 9.97-28.07, Cohen's d=0.52), internal oblique (P<0.01, mean difference 5.2, 95% CI: 9.72-21.55, Cohen's d=0.65), and external oblique (P<0.01, mean difference 5.5, 95% CI: 20.44-39.09, Cohen's d=0.71) muscles were significantly higher during the intervention. The Y-balance distance was also significantly greater in the posterior medial reach (P<0.01, mean difference 3.3, 95% CI: 1.56-6.26, Cohen's d=0.46) during the intervention. CONCLUSIONS: Exercise-based warm-up programs may decrease ACL injuries. It can improve physical functions, such as the rate of change in trunk muscle thickness and the posterior medial distance during Y balance.

Microscopic feature of lymph node anthracosilicosis adherent with pulmonary artery: a case report.

BACKGROUND: Although thoracic surgeons occasionally encounter dense adhesions of interlobar lymph node anthracosilicosis with the pulmonary artery, adhesiolysis may be challenging. Besides, characteristic microscopic features of the adherent lesion remain limited. CASE PRESENTATION: During a thoracoscopic right upper lobectomy of a patient with stage IA3 primary lung adenocarcinoma, several interlobar lymph nodes adhered to the posterior ascending branch of the pulmonary artery to the right upper lobe were noted. After an unplanned conversion to a thoracotomy to avoid massive bleeding, the pulmonary artery branch was safely isolated. Microscopic examination revealed lymph node anthracosilicosis proximal to the peripheral pulmonary artery wall, with granulomatous inflammation. The adventitial stroma of the pulmonary artery developed into dense and borderless fibrous tissue with dust-laden macrophages. CONCLUSIONS: Our pathological findings on lymph node anthracosilicosis provide substantial evidence that adhesions between lymph nodes and the pulmonary artery walls may develop into dense and borderless fibrous tissue. This finding would remind thoracic surgeons that adhesiolysis could cause injury to the pulmonary artery.

Laparoscopic-assisted thoracoscopic repair of latent traumatic diaphragmatic hernia: A case report.

Surgical approaches for traumatic diaphragmatic hernia include transabdominal, transthoracic, and thoracoabdominal. Selection of the optimal approach depends on the timing and organ damage, often minimally invasive approaches with laparoscopy or thoracoscopy are performed. A 47-year-old man with blunt chest trauma was diagnosed with left traumatic diaphragmatic hernia 1 month after the trauma. The prolapsed omentum was detached from the chest wall and around the hernia orifice and returned to the abdominal cavity by coordinated thoracoscopic and laparoscopic manipulations. The 4 × 2 cm herniation in the diaphragm was sutured closed from the thoracic side while preventing re-prolapse of the omentum and abdominal organs from the abdominal side. A combined thoracoscopic and laparoscopic approach can be effective in confirming organ damage, repositioning of prolapsed organs, and safe repair of the diaphragm in latent traumatic diaphragmatic hernia.

Postoperative changes in a bronchial stump following covering with free fat tissue in a rat model.

OBJECTIVES: Covering the bronchial stump with free fat tissue has been used as minimally invasive prophylaxis against bronchial stump fistulas; however, postoperative changes in the bronchial stump have not been well validated. Our goal was to examine changes in the bronchial stump in response to covering with free fat tissue in a rat model. METHODS: A left pneumonectomy was performed on 16 Wistar/ST rats, 12 of which had a bronchial stump covered with free subcutaneous fat tissue. Four rats that underwent a left pneumonectomy alone were sacrificed on postoperative day 7, and the 12 rats whose bronchial stumps were additionally covered with fat tissue were sacrificed on postoperative days 7, 14 and 56. Macroscopic and histological changes and pressure resistance of the bronchial stumps due to coverage with free fat tissue were examined. RESULTS: None of the rats showed macroscopic infection or necrosis in the thoracic cavity at the time of the rethoracotomy. The normal bronchial stumps remained mostly exposed, whereas the bronchial stumps covered with fat tissue were well-coated with tissue mass. Histologically, fibrous connective tissue containing microvessels gradually formed around the bronchial stump covered with fat tissue, and some of the tissue masses still had normal fat structures 56 days postoperatively. Covering with fat tissue significantly increased the pressure resistance of the bronchial stump 7 days postoperatively and further increased with time. CONCLUSIONS: Covering the bronchial stump with free fat tissue formed fibrous connective tissue around the bronchial stump and reinforced its closure.

[Diagnosis and treatment in circadian rhythm sleep disorders].

Circadian rhythm sleep disorders (CRSD) are characterized by misalignment between major sleep episode and desired sleep phase, or symptoms associated with internal desynchronization between endogenous circadian rhythm and overt sleep-wake rhythm. Endogenous circadian rhythm is mainly regulated by master circadian clock located in the suprachiasmatic nucleus. Light entrains the circadian clock according to a phase-response curve. Furthermore, social time cue affects human sleep-wake rhythm. Instructions concerning sleep hygiene including light environment play fundamental role for the treatment in CRSD. In addition, light therapy and oral melatonin administration have application to delayed sleep phase type. Diagnostic classification and treatment in each types of CRSD are reviewed in this article.