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.

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.

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.

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.

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.

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.

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.

Understanding psychiatric illness through natural language processing (UNDERPIN): Rationale, design, and methodology.

Introduction: Psychiatric disorders are diagnosed through observations of psychiatrists according to diagnostic criteria such as the DSM-5. Such observations, however, are mainly based on each psychiatrist's level of experience and often lack objectivity, potentially leading to disagreements among psychiatrists. In contrast, specific linguistic features can be observed in some psychiatric disorders, such as a loosening of associations in schizophrenia. Some studies explored biomarkers, but biomarkers have yet to be used in clinical practice. Aim: The purposes of this study are to create a large dataset of Japanese speech data labeled with detailed information on psychiatric disorders and neurocognitive disorders to quantify the linguistic features of those disorders using natural language processing and, finally, to develop objective and easy-to-use biomarkers for diagnosing and assessing the severity of them. Methods: This study will have a multi-center prospective design. The DSM-5 or ICD-11 criteria for major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorder and for major and minor neurocognitive disorders will be regarded as the inclusion criteria for the psychiatric disorder samples. For the healthy subjects, the absence of a history of psychiatric disorders will be confirmed using the Mini-International Neuropsychiatric Interview (M.I.N.I.). The absence of current cognitive decline will be confirmed using the Mini-Mental State Examination (MMSE). A psychiatrist or psychologist will conduct 30-to-60-min interviews with each participant; these interviews will include free conversation, picture-description task, and story-telling task, all of which will be recorded using a microphone headset. In addition, the severity of disorders will be assessed using clinical rating scales. Data will be collected from each participant at least twice during the study period and up to a maximum of five times at an interval of at least one month. Discussion: This study is unique in its large sample size and the novelty of its method, and has potential for applications in many fields. We have some challenges regarding inter-rater reliability and the linguistic peculiarities of Japanese. As of September 2022, we have collected a total of >1000 records from >400 participants. To the best of our knowledge, this data sample is one of the largest in this field. Clinical Trial Registration: Identifier: UMIN000032141.

Autologous Multilayered Fibroblast Sheets Can Reinforce Bronchial Stump in a Rat Model.

Bronchopleural fistula is one of the most serious postoperative complications caused by the incomplete healing of a bronchial stump. Fibroblasts play an important role in wound healing by facilitating connective tissue formation and inducing angiogenesis. We developed a method for production of multilayered fibroblast sheets that secreted some growth factors and promoted wound healing. The present study aimed to assess the treatment effect of multilayered fibroblast sheets on bronchial stump healing. In this rat model, left pneumonectomy was performed, and multilayered fibroblast sheets derived from autologous oral mucosal tissues were transplanted to the bronchial stump. The changes in the bronchial stump were examined macroscopically, histologically, and mechanically. The fibroblast sheets promoted the formation of thick connective tissues around the bronchial stump. The formed connective tissues were accompanied by new blood vessels, and fibrosis was observed over time. Then, 7 days after the transplantation of the fibroblast sheets, the bronchial wall became significantly thicker, and the area of the blood vessels for the bronchial wall tissues was significantly larger in the experimental group than in the control group. In addition, the burst pressure in the bronchial stump was significantly higher in the experimental group than in the control group. Bronchial stumps were reinforced by the transplantation of multilayered fibroblast sheets derived from autologous oral mucosal tissues.

IRF3 Knockout Results in Partial or Complete Rejection of Murine Mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MESO) has a poor prognosis despite aggressive treatment with surgery, radiation and chemotherapy, and novel therapeutic approaches are needed. IRF3 is a downstream molecule of the cGAS/STING signaling pathway, but its roles have not been investigated in MESO. METHODS: Various murine mesothelioma cell lines were inoculated into wild type (WT) and IRF3 knockout (IRF3KO) mice to compare tumor growth. AE17-bearing mice were treated with local radiotherapy (LRT) to evaluate the effect on tumor growth, and immune cell infiltration was analyzed by flow cytometry 20 days after tumor inoculation. TCGA data were used to examine the relationship between mRNA expression of IRF3 and genes of the cGAS/STING signaling cascade on prognosis in MESO. Correlations between gene expression of IRF3, cGAS/STING signaling pathway, and immune checkpoints were analyzed in TCGA MESO and our scRNA-Seq data from MESO patients. RESULTS: In mouse mesothelioma models, AK7, RN5 and ZiP3 were completely rejected in IRF3KO mice 20 days after the tumor challenge. AE17tumor volume was slightly larger than WT mice around day 10 before shrinking and becoming significantly smaller than WT mice on day 20. LRT accelerated tumor shrinkage of AE17 tumors in IRF3KO mice. Compared with WT mice, the number of macrophages infiltrating the tumor of IRF3KO mice was significantly reduced, and CD4+ T cells and CD8+IFNγ+ T cells were significantly increased. TCGA data showed that IRF3 expression was an unfavorable prognostic factor in MESO patients. IRF3 expression, the cGAS/STING signaling pathway, and immune checkpoints were positively correlated. CONCLUSION: IRF3 could play a critical role in the tumor immune microenvironment of MESO.

Blocking the GITR-GITRL pathway to overcome resistance to therapy in sarcomatoid malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

Triple-modality therapy maximizes antitumor immune responses in a mouse model of mesothelioma.

Malignant pleural mesothelioma (MPM) is an intractable disease with an extremely poor prognosis. Our clinical protocol for MPM of subablative radiotherapy (RT) followed by radical surgery achieved better survival compared to other multimodal treatments, but local relapse and metastasis remain a problem. This subablative RT elicits an antitumoral immune response that is limited by the immunosuppressive microenvironment generated by regulatory T (Treg) cells. The antitumor effect of immunotherapy to simultaneously modulate the immune activation and the immune suppression after subablative RT has not been investigated in MPM. Herein, we demonstrated a rationale to combine interleukin-15 (IL-15) superagonist (IL-15SA) and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonist (DTA-1) with subablative RT in mesothelioma. IL-15SA boosted the systemic expansion of specific antitumoral memory CD8+ T cells that were induced by RT in mice. Their effect, however, was limited by the up-regulation and activation of Treg cells in the radiated tumor microenvironment. Hence, selective depletion of intratumoral Treg cells through DTA-1 enhanced the benefit of subablative RT in combination with IL-15SA. The addition of surgical resection of the radiated tumor in combination with IL-15SA and DTA-1 maximized the benefit of RT and was accompanied by a reproducible abscopal response in a concomitant tumor model. These data support the development of clinical trials in MPM to test such treatment options for patients with locally advanced or metastatic tumors.

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.

The project for objective measures using computational psychiatry technology (PROMPT): Rationale, design, and methodology.

INTRODUCTION: Depressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. New technology allows quantification of features that clinicians perceive as reflective of disorder severity, such as facial expressions, phonic/speech information, body motion, daily activity, and sleep. METHODS: Major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders as well as healthy controls are recruited for the study. A psychiatrist/psychologist conducts conversational 10-min interviews with participants ≤10 times within up to five years of follow-up. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms. DISCUSSION: The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity. TRIAL REGISTRATION: UMIN000021396, University Hospital Medical Information Network (UMIN).

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.

Postoperative Complications and Cancer Recurrence: Impact on Poor Prognosis of Lower Lobe Cancer.

BACKGROUND: Previous reports suggest that lung cancer in the lower lobe is associated with a poorer prognosis than upper lobe disease. However, the reason remains controversial. We evaluated the relationship among the affected lobe, postoperative infectious complications, and cancer recurrence in patients who underwent lobectomy for clinical stage I lung cancer. METHODS: We retrospectively reviewed 422 cases of resected lung cancer. We recorded the postoperative complications that developed within 30 days after surgery. The covariates included in the outcome analysis were patient demographic variables, surgical approach, laterality, affected lobe, tumor size, histologic type, tumor grade, pleural lavage cytology, pleural invasion, lymphovascular invasion, and lymph node metastasis. RESULTS: Lower lobectomy was associated with significantly poorer recurrence-free (excluding nonspecific death) and overall survival than upper lobectomy. According to a stepwise multiple Cox proportional hazards analysis, lower lobectomy, lymph node metastasis, tumor grade, and pleural invasion were independent predictors of recurrence. The following postoperative complications were significantly associated with cancer recurrence and predominantly developed after lower lobectomy: any grade ≥3 complications (n = 61), space/organ surgical site infection of any grade (n = 55), and any infection requiring antibiotics (n = 61). CONCLUSIONS: The current study revealed a significant relationship among the site of resection (upper or lower lobe), cancer recurrence, and occurrence of infectious complications. We must clarify the role of preventing infectious complications in improving the early- and long-term outcomes of lower lobe cancer.

Intercostal block vs. epidural analgesia in thoracoscopic lung cancer surgery: a randomized trial.

OBJECTIVES: To explore the best strategy for combatting pain after thoracoscopic lobectomy for cancer. METHODS: We conducted a randomized-controlled trial to compare two major analgesic procedures-intercostal nerve block and epidural analgesia-in patients scheduled to undergo thoracoscopic lobectomy and lymphadenectomy. High-dose oral celecoxib was started 3 h after operation in intercostal nerve block group or after withdrawal of epidural analgesia in epidural analgesia group. The primary endpoint was postoperative pain and adverse events, and the secondary endpoint was the length of the analgesic procedure and physiological function on postoperative day 1. RESULTS: This study was closed before accumulating the necessary sample size. We eventually analyzed 21 patients undergoing intercostal nerve block and 22 patients undergoing epidural analgesia. Although the incidence of postoperative adverse events and postoperative complications was comparable between the groups, the incidence of procedure-related troubles was significantly higher in the epidural analgesia group than in the intercostal nerve block group. The length of the analgesic procedure was significantly shorter in the intercostal nerve block group than in the epidural analgesic group. The postoperative pain during postoperative days 0-7, as evaluated by a visual analog scale, was not significantly different between the groups. Likewise, postoperative physiological function, as evaluated by vital capacity and walking distance, was not significantly different between the groups. CONCLUSION: Although our limited sample size compromised our ability to draw definitive conclusions, intercostal nerve block followed by high-dose oral celecoxib seems to be an option for patients undergoing thoracoscopic lobectomy for lung cancer.

Prognostic influence of tumor microenvironment after hypofractionated radiation and surgery for mesothelioma.

OBJECTIVE: Cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) can contribute to the benefit of hypofractionated radiation, but programmed cell death pathways (programmed cell death 1 and programmed cell death ligand 1 [PD-1/PD-L1]) may provide a mechanism of tumor immune escape. We therefore reviewed the influence of PD-1/PD-L1 and CD8+ TILs on survival after accelerated hypofractionated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM). METHODS: Sixty-nine consecutive patients undergoing the protocol of Surgery for Mesothelioma after Radiation Therapy (SMART) between November 2008 and February 2016 were analyzed for the presence of PD-L1 on tumor cells, PD-1 on inflammatory cells, and CD8+ TILs. Comparison was made with a cohort of patients undergoing extrapleural pneumonectomy after induction chemotherapy (n = 14) and no induction (n = 2) between March 2005 and October 2008. PD-L1 expression on tumor cells ≥1% was considered positive. CD8+ TILs and PD-1 expression were scored as a percentage of positive cells. RESULTS: PD-L1 was negative in 75% of MPM after completion of SMART. CD8+ TILs ranged between 0.24% and 8.47% (median 2%). CD8+ TILs ≥2% was associated with significantly better survival in epithelioid MPM (median survival 3.7 years vs 2.3 years in CD8+ TILs <2%; P = .02). PD-L1 positivity was associated with worse survival in biphasic MPM (median survival, 0.4 years vs 1.5 years in biphasic PD-L1 negative tumors; P = .07) after SMART. Multivariate analysis demonstrated that epithelioid MPM, nodal disease, and CD8+ TILs were independent predictors of survival after SMART. CONCLUSIONS: The influence of tumor microenvironment on survival differs between epithelioid and nonepithelioid MPM. CD8+ TILs is an independent factor associated with better survival in epithelioid MPM treated with SMART.

No Drain After Thoracoscopic Major Lung Resection for Cancer Helps Preserve the Physical Function.

BACKGROUND: We previously proved that omitting chest tube drainage in select patients undergoing thoracoscopic major lung resection for cancer was safe. The aim of the present study was to clarify the impact of omitting postoperative chest tube drainage on preserving the early postoperative ventilatory capacity and exercise capacity. METHODS: The subjects of this retrospective study were 116 patients undergoing either thoracoscopic radical segmentectomy (n = 18) or lobectomy (n = 98). Whether chest tube drainage was to be performed was determined from the predefined criteria. We routinely measured the vital capacity and 6-minute walking distance preoperatively, at postoperative day 1 and at postoperative day 7. Postoperative pain was assessed daily by the visual analogue scale, and the number of analgesic agents used until postoperative day 7 was recorded. RESULTS: Postoperative chest tube drainage was omitted in 53 patents (46%). Omitting chest tube drainage was associated with a substantial reduction in both the postoperative pain and the number of analgesic agents used on postoperative day 0 and 1. In addition, omitting chest tube drainage was associated with a preservation of vital capacity and the 6-minute walking capacity on postoperative day 1. The vital capacity, the 6-minute walking distance, and the pain as measured on postoperative day 1 were substantially correlated with each other. CONCLUSIONS: Omitting chest tube drainage results in reducing the pain, preservation of the ventilatory capacity, and preservation of exercise capacity in the early postoperative period in patients undergoing thoracoscopic major lung resection for cancer.

Who will benefit from thymectomy for myasthenia gravis? Is there any role for this procedure in elderly patients?

BACKGROUND: The proportion of elderly patients with myasthenia gravis (MG) is increasing over time. Thoracoscopic extended thymectomy has been shown to achieve a superior short-term outcome to transsternal procedures. Therefore, the long-term clinical outcome should be re-examined, particularly in elderly patients. METHODS: We evaluated the long-term clinical outcomes after extended thymectomy in 30 MG patients with or without thymoma. Twenty-one (70%) patients underwent surgery by 65 years of age, and the remaining 9 (30%) underwent surgery after 65 years of age. Univariate and multivariate logistic regression analyses were used to determine the influence of various factors on the improvement in MG symptoms. RESULTS: The characteristics in the elderly patients were comparable to those in the younger patients, except for the age at surgery. Symptoms of MG improved in 4 of the 9 (44%) elderly patients and in 18 of the 21 (86%) younger patients (P=0.0192). One elderly patient who underwent transsternal thymectomy died suddenly on postoperative day 3, probably due to a MG crisis: no pathological abnormalities were detected by an autopsy. A multivariate analysis identified an age at thymectomy of <65 years (P=0.0237) and a duration from the onset to thymectomy of <1 year (P=0.0405) as independent factors associated with the improvement of MG symptoms. Indeed, 4 of the 5 (80%) elderly patients who underwent thymectomy within 1 year after the onset had a favorable long-term outcome. CONCLUSIONS: Thymectomy can be an option even in elderly patients, provided the operation is performed early after the onset.