Impact of Flagging/Risk Stratification System on Complications in Hospitalist Hip Fracture Co-management: Retrospective Cohort Study.

Purpose: Hip fractures are associated with high morbidity and mortality, the rates of which can be improved by comprehensive care. To improve hospitalist co-management of hip fractures, we designed and implemented hip fracture template (HFT), a flagging and risk stratification algorithm system. It includes consideration of perioperative management and preventative measures against hip fractures. We examined its effect on morbidity in patients with hip fractures and the factors associated with complications. Methods: We conducted a retrospective cohort study of patients who underwent surgery for hip fracture. The primary outcome was the perioperative complication rate, comparing patients managed with and without HFT. Multivariate analysis was adjusted for age, gender, and any significant variables shown in univariate analysis. Results: HFT was used in 121 patients and not used in 147 patients. In univariate analysis, patients were less likely to have complications if HFT was used (19.0% vs. 29.9%, P = 0.047), but there was no difference in length of stay (17 days vs. 17 days, P = 0.27) or in-hospital-mortality (0.8% vs. 0.7%, P = 1.00) between the groups. In adjusted analysis, patients managed by HFT had lower likelihood of complications (OR 0.55, 95% CI 0.31-0.98). Among patients managed by HFT, those with revised cardiac risk index (RCRI) ≥ 1 were more likely to have complications in both univariate (42.1% vs. 14.7%, P = 0.01) and adjusted analysis (OR 3.37, 95% CI 1.03-10.84). Conclusion: Patients with hip fractures managed with HFT were less likely to have complications, especially those with RCRI ≥ 1, suggesting benefits of using HFT.

Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer.

Cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN), are caused by high-risk human papillomavirus (HPV) viral infection and are highly susceptible to host immunity targeting of HPV viral proteins, which include both foreign antigens and cancer antigens expressed by tumors. Immunotherapy that induces Th1 immunoreactivity against viral proteins is expected to take advantage of this immunological regression mechanism. However, although cancer immunotherapies for cervical cancer and CIN have been developed over the past several decades, none have been commercialized. Most of these immunotherapies target the viral cancer proteins E6 and E7, which are generally the same. The reasons for the underdevelopment of HPV-targeted immunotherapy differ depending on whether the target is invasive cancer or CIN. We here summarize the developmental history of cancer immunotherapy for CIN and discuss strategies for solving the problems that led to this underdevelopment. We note that CIN is a mucosal lesion and propose that inducing mucosal immunity may be the key.

[Considerations for Perioperative Management of Patients with Complicated Respiratory Dysfunction].

This article describes the perioperative complications, perioperative risk assessment, and perioperative management of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease, especially idiopathic pulmonary fibrosis( IPF), which are the leading diseases in respiratory dysfunction. In COPD, testing for forced expiratory volume during the first second and pulmonary diffusing capacity is important and an algorithm for testing has been presented by the Japanese Association for Chest Surgery. Acute exacerbation of IPF is the leading cause of postoperative mortality in Japan, and risk factors are being analyzed. To reduce the occurrence of postoperative complications, it is important to carry out a risk assessment, select appropriate surgical strategy, and implement a well-planned perioperative management.

Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3.

BACKGROUND: Although many human papillomavirus (HPV)-targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. METHODS: In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16-positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. RESULTS: In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7-specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. CONCLUSION: This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16-positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. TRIAL REGISTRATION: jRCT2031190034.

Immune-mediated Necrotizing Myopathy in a Patient with Microscopic Polyangiitis: A Case Report.

We herein report a case of immune-mediated necrotizing myopathy (IMNM) in a patient with microscopic polyangiitis (MPA). A 77-year-old Japanese woman presented with a 2-day history of proximal muscle weakness and myalgia, with elevated serum creatinine kinase (CK) levels. Findings of a muscle biopsy were compatible with IMNM; however, anti-SRP and anti-HMGCR antibodies were negative. She also had peripheral neuropathy with elevated serum MPO-ANCA titers, leading to a diagnosis of MPA. IMNM can be a pathological result of MPA muscle involvement.

Long-term Survival after Treatment of Synchronous Isolated Right External Iliac Lymph Node Metastasis from Ascending Colon Cancer: A Case Report.

BACKGROUND: Synchronous isolated external iliac lymph node metastasis of ascending colon cancer is extremely rare, and its treatment strategy has not been established. In this report, we present a case of long-term survival after surgical resection and adjuvant chemotherapy for ascending colon cancer with synchronous isolated right external iliac lymph node metastasis. CLINICAL CASE: A 65-year-old woman with anorexia and anemia was referred to our hospital. Colonoscopy and computed tomography revealed a three-quarter circumferential type 2 tumor from the cecum to the ascending colon, along with regional and right external iliac lymph node swelling. We diagnosed ascending colon cancer with right external iliac artery lymph node metastasis. An open right hemicolectomy with D3 and right external iliac lymph node dissections were performed. Results of histopathological examination showed that both lymph nodes were metastasized from ascending colon cancer. The patient received eight courses of capecitabine and oxaliplatin therapy as adjuvant chemotherapy. At 60 months after surgery, the woman has not had a recurrence. CONCLUSIONS: Surgical resection and adjuvant chemotherapy may be an effective treatment strategy for synchronous isolated right external iliac lymph node metastases from ascending colon cancer.

1-Oleoyl-lysophosphatidylethanolamine stimulates RORγt activity in TH17 cells.

Metabolic fluxes involving fatty acid biosynthesis play essential roles in controlling the differentiation of T helper 17 (TH17) cells. However, the exact enzymes and lipid metabolites involved, as well as their link to promoting the core gene transcriptional signature required for the differentiation of TH17 cells, remain largely unknown. From a pooled CRISPR-based screen and unbiased lipidomics analyses, we identified that 1-oleoyl-lysophosphatidylethanolamine could act as a lipid modulator of retinoid-related orphan receptor gamma t (RORγt) activity in TH17 cells. In addition, we specified five enzymes, including Gpam, Gpat3, Lplat1, Pla2g12a, and Scd2, suggestive of the requirement of glycerophospholipids with monounsaturated fatty acids being required for the transcription of Il17a. 1-Oleoyl-lysophosphatidylethanolamine was reduced in Pla2g12a-deficient TH17 cells, leading to the abolition of interleukin-17 (IL-17) production and disruption to the core transcriptional program required for the differentiation of TH17 cells. Furthermore, mice with T cell-specific deficiency of Pla2g12a failed to develop disease in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Thus, our data indicate that 1-oleoyl-lysophosphatidylethanolamine is a lipid metabolite that promotes RORγt-induced TH17 cell differentiation and the pathogenicity of TH17 cells.

[Robot-assisted Minimally Invasive Surgery for Mediastinal Tumors].

The subxiphoid approach in thymectomy provides better visibility around the left brachiocephalic vein than the lateral thoracic approach. Robot-assisted thoracoscopic surgery is easier to parform than video- assisted thoracoscopic surgery for surgery of the upper mediastinum, because the forceps can be moved with many joints. Robot-assisted thymectomy using the subxiphoid approach may be less traumatic and less invasive than median sternotomy. We must continue to devise surgical procedures to make oncologically curative surgery more minimally invasive.

Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma.

Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenocarcinoma cases annotated with the predominant histological subtypes and three normal lung cases using the Infinium BeadChip. Unsupervised hierarchical clustering analysis revealed three subgroups with different methylation levels: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME). Micropapillary pattern (MPP)-predominant cases and those with MPP components were significantly enriched in HME (p = 0.02 and p = 0.03, respectively). HME cases showed a significantly poor prognosis for recurrence-free survival (p < 0.001) and overall survival (p = 0.006). We identified 365 HME marker genes specifically hypermethylated in HME cases with enrichment of "cell morphogenesis" related genes; 305 IME marker genes hypermethylated in HME and IME, but not in LME, with enrichment "embryonic organ morphogenesis"-related genes; 257 Common marker genes hypermethylated commonly in all cancer cases, with enrichment of "regionalization"-related genes. We extracted surrogate markers for each epigenotype and designed pyrosequencing primers for five HME markers (TCERG1L, CXCL12, FAM181B, HOXA11, GAD2), three IME markers (TBX18, ZNF154, NWD2) and three Common markers (SCT, GJD2, BARHL2). DNA methylation profiling using Infinium data was validated by pyrosequencing, and HME cases defined by pyrosequencing results also showed the worse recurrence-free survival. In conclusion, lung adenocarcinomas are stratified into subtypes with distinct DNA methylation levels, and the high-methylation subtype correlated with MPP-predominant cases and those with MPP components and showed a poor prognosis.

Penetrating Trauma-Induced Perilymphatic Fistula: A Case Report and Literature Review.

This article highlights the importance of early identification and surgical treatment for extremely rare traumatic perilymphatic fistula (TPF) caused by an earpick, which can pose the risk of irreversible hearing loss. Herein, we have described two cases of TPF and reviewed the literature primarily based on surgical treatment for penetrating ear trauma-induced TPF.  We highlight the case of two females who sustained an accidental penetrating injury in the ear caused by the introduction of an earpick, leading to hearing loss and dizziness. Pure tone audiometry detected elevation of the bone-conduction thresholds. Computed tomography of Labyrinth revealed pneumolabyrinth in one case. Both patients underwent exploratory surgery, we completely repositioned the stapes that had invaginated into the vestibule in one case, in the other case, we reconnected the disarticulated incudostapedial joint and sealed perilymph fistula caused by rupture of the oval window. Both patients achieved hearing improvement and complete relief from the vestibular symptoms. The literature review indicated that a scar on the posterior aspect of the tympanic membrane was found in 44.4% of cases. Hearing improvement was observed in 45.5% and 25.0% of cases with invagination of stapes and fractured footplates by fistula repair, respectively. In terms of handling stapes dislocation, the hearing improvement rate was better in cases of complete stapes repositioning (66.7%) than those of complete or partial stapes removal (16.7%). Preoperative mild bone-conduction hearing loss or localized pneumolabyrinth are favorable factors for satisfactory hearing. When surgery is performed within 11 days of the injury, satisfactory hearing improvement can be expected.

M2 tumor-associated macrophages resist to oxidative stress through heme oxygenase-1 in the colorectal cancer tumor microenvironment.

M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34). Moreover, we generated M0 and M2 macrophages from peripheral blood monocytes and evaluated their resistance to oxidative stress using the in vitro viability assay. Analysis of GSE33113, GSE39582, and The Cancer Genome Atlas (TCGA) datasets indicated that mRNA expression of HMOX1 (heme oxygenase-1 (HO-1)) was significantly positively correlated with M2-TAM signature (r = 0.5283, r = 0.5826, r = 0.5833, respectively). The expression level of both Nrf2 and HO-1 significantly increased in M2-TAMs compared to M1- and M1/M2-TAMs in the tumor margin, and the number of Nrf2+ or HO-1+M2-TAMs in the tumor stroma significantly increased more than those in the normal mucosa stroma. Finally, generated M2 macrophages expressing HO-1 significantly resisted to oxidative stress induced by H2O2 in comparison with generated M0 macrophages. Taken together, our results suggested that an increased frequency of M2-TAMs infiltration in the CRC-TME is related to Nrf2-HO-1 axis mediated resistance to oxidative stress.

[An Abscopal Effect after Palliative Radiotherapy in a Patient with a Locally and Lymph Node Recurrent Gastric Cancer].

Radiotherapy is known to have a high local effect for cancer treatment. However, several reports that radiotherapy could stimulate the anti-tumor effect by releasing endogenous signals and cytokines, increasing the presentation of tumor associated antigens on dendritic cells, and proliferating tumor antigen-specific cytotoxic T lymphocytes have been shown. A tumor regression in both non-irradiated and irradiated fields have observed, which is called"abscopal effect". We report a case of the abscopal effect in adenocarcinoma of the stomach with locally and lymph node recurrence after surgery. A 59-year-old Japanese male was diagnosed with residual stomach cancer and underwent total gastrectomy and distal pancreatectomy. Three months after the surgery, a local recurrence and the involvement of para-aortic lymph node were diagnosed using computed tomography. The chemotherapy treatment(S-1, cisplatin, trastuzumab)was prescribed. However, the disease has progressed. Paclitaxel and ramucirumab were given for second-line, nivolumab for third-line and irinotecan for fourth-line. During that, tumor at local recurrent site invaded to the portal vein. The patients received 50 Gy in 25 fractions of radiotherapy. A remarkable reduction of the mass was shown. In addition to this, we observed that spontaneous shrinking of the para-aortic lymph node metastasis, which was located out of the radiation field. We observed a rare radiation-induced abscopal effect. Radiotherapy might represent a potential candidate for a combination with immunotherapy. A combination of immunotherapy as well as chemotherapy with radiotherapy represents a promising therapeutic strategy.

Hemophagocytic syndrome in a patient with long-term stable pulmonary sarcoidosis with progressive spleen and bone marrow lesion.

An 83-year-old woman with asymptomatic pulmonary sarcoidosis presented to our hospital with fever and malaise for three months. Abdominal CT showed splenomegaly, and bone marrow examination revealed non-caseating granulomas. Pancytopenia was diagnosed due to bone marrow and splenic lesions of sarcoidosis. Steroid pulses were administered, but the patient died without response to treatment. Pathological autopsy results showed non-caseating granulomas and hemophagocytosis in the spleen and bone marrow. This suggested hemophagocytic syndrome, which was not suspected before death, in addition to sarcoidosis. In patients with splenomegaly and pancytopenia with history of pulmonary sarcoidosis, hemophagocytic syndrome should be considered in differential diagnosis.

Postoperative pain and quality of life after lung cancer surgery: a prospective observational study.

BACKGROUND: We aimed to identify the factors associated with postoperative pain, quality of life, and development of chronic pain after lung cancer surgery, including pain sensation threshold, fentanyl sensitivity, and surgical procedures. METHODS: We conducted a single-center prospective observational study involving lung cancer patients. Brief pain inventory, including nine items concerning pain and quality of life, was investigated at 1 week, 1 month, and 3 months postoperatively. Pain sensation threshold and fentanyl sensitivity were assessed preoperatively. RESULTS: Of the 146 patients who were enrolled, 100 who met our criteria were analyzed. Thoracoscopic surgery was performed in 42 patients and minimally invasive thoracotomy in 58 patients. Pain sensation threshold and fentanyl sensitivity were normally distributed among the patients and were not significantly associated with brief pain inventory scores at each postoperative time-point. The average pain score 1 week after the operation was significantly higher in the thoracotomy group than in the thoracoscopic surgery group (P<0.050). The worst pain scores did not differ between the groups at all the examination periods. Pain sensation threshold, fentanyl sensitivity, and surgical procedures were not related to the incidence of post-thoracotomy pain syndrome. CONCLUSIONS: Individual pain sensation threshold and fentanyl sensitivity were not associated with subjective postoperative pain score, quality of life score, or development of post-thoracotomy pain syndrome.

Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more.

Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. We reviewed the perspective of MDSCs with emerging evidence in this review. Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs.

Immunoglobulin G4-related inflammatory pseudotumor of the right ventricle with right coronary artery occlusion.

Immunoglobulin G4-related inflammatory pseudotumors are usually benign. Such tumors of cardiac origin are extremely rare, with no primary cardiac tumors reported to date. We report a case of a 77-year-old woman, with a medical history of diabetes, hypertension, and hyperlipidemia, who was diagnosed with a malignant cardiac tumor on preoperative imaging and had a confirmed pathological diagnosis of immunoglobulin G4-related inflammatory pseudotumor. She was examined for atherosclerosis obliterans, and coronary computed tomography revealed obstruction of the right coronary artery and a cardiac tumor in the right atrium. A suspected malignant tumor measuring 40 mm (maximum standardized uptake value: 12.2) bordering the right atrium was detected using 18F-fluorodeoxyglucose positron emission tomography. Her tumor was in contact with the heart, making biopsy impossible. She was diagnosed with malignancy on preoperative imaging and underwent tumor resection, tricuspid valve replacement, right atrial and right ventricular plasty, coronary artery bypass, lung resection, and diaphragmatic repair. However, the final pathological diagnosis was immunoglobulin G4-related inflammatory pseudotumor. Preoperative diagnosis of immunoglobulin G4-related inflammatory pseudotumor is extremely difficult; however, if the condition is diagnosed preoperatively, chemotherapy or steroid therapy should be administered, and patients who do not respond to chemotherapy should be considered for surgical treatment. Learning objective: Immunoglobulin G4-associated inflammatory pseudotumor is extremely rare. Preoperative imaging diagnosis of immunoglobulin G4-associated inflammatory pseudotumor is extremely difficult, and pathology with biopsy is the only definitive diagnosis. However, if we could make an accurate preoperative diagnosis, patients should be treated with chemotherapy or steroids, and surgical treatment should be considered for patients who do not respond to chemotherapy or steroids.

Prediction of Nodal Metastasis in Lung Cancer Using Deep Learning of Endobronchial Ultrasound Images.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valid modality for nodal lung cancer staging. The sonographic features of EBUS helps determine suspicious lymph nodes (LNs). To facilitate this use of this method, machine-learning-based computer-aided diagnosis (CAD) of medical imaging has been introduced in clinical practice. This study investigated the feasibility of CAD for the prediction of nodal metastasis in lung cancer using endobronchial ultrasound images. Image data of patients who underwent EBUS-TBNA were collected from a video clip. Xception was used as a convolutional neural network to predict the nodal metastasis of lung cancer. The prediction accuracy of nodal metastasis through deep learning (DL) was evaluated using both the five-fold cross-validation and hold-out methods. Eighty percent of the collected images were used in five-fold cross-validation, and all the images were used for the hold-out method. Ninety-one patients (166 LNs) were enrolled in this study. A total of 5255 and 6444 extracted images from the video clip were analyzed using the five-fold cross-validation and hold-out methods, respectively. The prediction of LN metastasis by CAD using EBUS images showed high diagnostic accuracy with high specificity. CAD during EBUS-TBNA may help improve the diagnostic efficiency and reduce invasiveness of the procedure.

Targeting of Nrf2 improves antitumoral responses by human NK cells, TIL and CAR T cells during oxidative stress.

BACKGROUND: Adoptive cell therapy using cytotoxic lymphocytes is an efficient immunotherapy against solid and hematological cancers. However, elevated levels of reactive oxygen species (ROS) in the hostile tumor microenvironment can impair NK cell and T cell function. Auranofin, a gold (I)-containing phosphine compound, is a strong activator of the transcription factor Nrf2. Nrf2 controls a wide range of downstream targets important for the cells to obtain increased resistance to ROS. In this study, we present a strategy using auranofin to render human cytotoxic lymphocytes resistant toward oxidative stress. METHODS: Melanoma patient-derived tumor infiltrating lymphocytes (TIL) and healthy donor-derived NK cells and CD19-directed CAR T cells were pretreated with a low dose of auranofin. Their resistance toward oxidative stress was assessed by measuring antitumoral responses (killing-assay, degranulation/CD107a, cytokine production) and intracellular ROS levels (flow cytometry) in conditions of oxidative stress. To confirm that the effects were Nrf2 dependent, the transcription level of Nrf2-driven target genes was analyzed by qPCR. RESULTS: Pretreatment of human TIL and NK cells ex vivo with a low-dose auranofin significantly lowered their accumulation of intracellular ROS and preserved their antitumoral activity despite high H2O2 levels or monocyte-derived ROS. Furthermore, auranofin pretreatment of CD19 CAR-T cells or TIL increased their elimination of CD19 +tumor cells or autologous tumor spheroids, respectively, especially during ROS exposure. Analysis of Nrf2-driven target genes revealed that the increased resistance against ROS was Nrf2 dependent. CONCLUSION: These novel findings suggest that Nrf2 activation in human cytotoxic lymphocytes could be used to enhance the efficacy of adoptive cell therapy.

Delayed visit and treatment of lung cancer during the coronavirus disease 2019 pandemic in Japan: a retrospective study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on cancer care remains a concern. We aimed to evaluate access to diagnosis and treatment for lung cancer during the pandemic. METHODS: Times (days) from lung cancer symptom onset or referral to visit (pre-visit time), from visit to diagnosis (pre-diagnosis time), and from diagnosis to treatment (pre-treatment time) during the pandemic were compared with the times during the pre-pandemic period. RESULTS: The number of patients diagnosed with lung cancer was 82 and 75 during the pandemic and pre-pandemic periods, respectively. The percentage of patients with advanced-stage cancer was higher (65.9% vs. 46.7%), the percentage of patients treated with surgery was lower and the percentage treated with medication was higher (24.4% vs. 41.3% and 57.3% vs. 40.0%, respectively), the pre-visit time was longer (28.2 vs. 11.4 days), and the pre-treatment time for surgery was longer (67.3 vs. 45.6 days) during the pandemic compared with the times during the pre-pandemic period, respectively. CONCLUSIONS: The COVID-19 pandemic resulted in delayed diagnoses, which could have led to patients being diagnosed with advanced disease. The pandemic also resulted in delayed therapy owing to the requirement for available intensive care unit beds for emergencies, including surgery.

[Lung Transplantation at a Low Volume Center].

The number of lung transplantation performed in Japan is extremely low compared to other countries, whereas we have 10 facilities certified as cadaveric lung transplantation in Japan, meaning that there are low volume centers. By August 2021, we performed lung transplantation in 21 cases for 12 years, therefore, our facility should be considered as low volume center. Surgical outcomes at low volume centers are generally considered poor. However, the overall five-year survival rate of total cases was 84.8%, and that of cadaveric cases was 94.4% in our hospital. It was better than the average of about 73% of all facilities in Japan. These data suggested that the accreditation system in Japan is functioning well. On the other hand, there may be a disparity between facilities. At our facility, we are actively performing inverted lung transplantation so as not to lose the opportunity for transplantation, and we have performed it in three cases so far and have achieved good results.