LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study.

BACKGROUND: Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor; novel LAG3 immune checkpoint inhibitors (ICIs) exhibit therapeutic activity in melanoma. The role of LAG3and ICIs of LAG3 are unknown in malignant pleural mesothelioma (MPM). This study aimed to uncover the prognostic landscape of LAG3 in multiple cancers and investigate the potential of using LAG3 as an ICIs target in patients with MPM. METHODS: We used The Cancer Genome Atlas (TCGA) cohort for assessing mRNA expression and our cohort for immunohistochemical expression. TCGA cohort were analyzed using the Wilcoxon rank-sum test to compare mRNA expression between normal and tumor tissues in multiple cancers. We used 86 MPM cases from TCGA and 38 MPM cases from our cohort to analyze the expression of LAG3 in tumor-infiltrating lymphocytes. The mean LAG3 mRNA expression was set as the cut-off and samples were classified as positive/negative for immunohistochemical expression. Overall survival (OS) of patients with MPM was determined using the Kaplan-Meier method based on LAG3 mRNA and immunohistochemical expression. OS analysis was performed using the multivariate Cox proportional hazards model. The correlation of LAG3 expression and mRNA expression of tumor immune infiltration cells (TIICs) gene markers were estimated using Spearman correlation. To identify factors affecting the correlation of LAG3 mRNA expression, a multivariate linear regression model was performed. RESULTS: LAG3 mRNA was associated with prognosis in multiple cancers. Elevated LAG3 mRNA expression was correlated with a better prognosis in MPM. LAG3 expression was detected immunohistochemically in the membrane of infiltrating lymphocytes in MPM. LAG3 immunohistochemical expression was correlated with a better prognosis in MPM. The multivariate Cox proportional hazards model revealed that elevated LAG3 immunohistochemical expression indicated a better prognosis. In addition, LAG3 mRNA expression was correlated with the expression of various gene markers of TIICs, the most relevant to programmed cell death 1 (PD-1) with the multivariate linear regression model in MPM. CONCLUSIONS: LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM. TRIAL REGISTRATION: This study was registered with UMIN000049240 (registration day: August 19, 2022) and approved by the Institutional Review Board (approval date: August 22, 2022; approval number: 2022-0048) at Tokyo Women's Medical University.

Optimal threshold score of aortic valve calcification for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography.

OBJECTIVES: This study evaluated the association between aortic valve calcification (AVC) and aortic stenosis (AS) by scoring the AVC to determine the threshold scores for significant AS on non-electrocardiographic (ECG)-gated computed tomography (CT). METHODS: We retrospectively analyzed the AVC scores of 5385 patients on non-contrast non-ECG-gated CT, who underwent transthoracic echocardiography (TTE) from March 1, 2013, to December 26, 2019, at our institution. Multivariable logistic regression models were used to identify potential risk factors for significant AS. The thresholds for significant AS were computed using receiver operator characteristic (ROC) curves, based on the AVC scores after propensity score matching. RESULTS: A significant association was found between AS and age (p < 0.001; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), female sex (p < 0.001; OR, 4.5; 95% CI, 2.75-7.36), bicuspid aortic valve (p < 0.001; OR, 23.2; 95% CI, 7.35-72.9), and AVC score (AVC score/100) (p < 0.001; OR, 1.82; 95% CI, 1.71-1.95). All sex-specific AVC thresholds for significant AS (moderate and over AS severity, moderate and over AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.939-0.968; sensitivity, 84.6-96%; specificity, 84.2-97.1%). CONCLUSIONS: We determined the optimal AVC threshold scores for significant AS, which may aid in diagnosing significant asymptomatic AS on incidental detection of AVC through non-ECG-gated CT for non-cardiac indications. KEY POINTS: • Increased frequency of non-electrocardiographic (ECG)-gated computed tomography (CT) for non-cardiac indications has led to the increased incidental identification of aortic valve calcification (AVC). • It is important to identify patients with significant aortic stenosis (AS) who require additional echocardiographic assessment on incidental detection of AVC via non-ECG-gated CT. • We determined the AVC thresholds with high sensitivity and specificity to identify significant AS on non-ECG-gated CT, which could lead to early diagnosis of asymptomatic significant AS and improved prognosis.

[Improved Surgical Technique for Closing the Tracheocutaneous Fistula].

The tracheocutaneous fistula is a late complication after tracheotomy decannulation, which decreases the quality of life. Though several procedures to close tracheocutaneous fistula were reported, postoperative wound dehiscence was frequently noted. We developed new surgical technique to prevent this complication and report a case in which the technique was successfully applied. This surgical technique is useful simple method to be effective, and safe.

[Outcomes of Surgical Cases of Solitary Rib Metastases in Renal Cell Carcinoma].

BACKGROUND: Aggressive surgical treatment for renal cell carcinoma (RCC) bone metastasis has shown good results. METHODS: Since January 1995, four patients underwent surgery at our institution for rib metastasis of operated RCCs. Of these patients, three were male and one was female. The patients had a mean age of 67.5 years. Except one patient who presented with rib metastasis at the time of diagnosis of RCC, the average period of metastasis to the ribs after RCC surgery was 24.3 months. All patients underwent resection of metastasized tumors involving the ribs, with or without chest wall involvement. The clinical features of the surgical treatment for RCC bone metastasis were retrospectively analyzed. RESULTS: The mean time to tumor recurrence was 22.3 months postmetastasectomy. All patients developed other bone metastases and underwent multidisciplinary therapy. After metastasectomy, the four patients survived for 19~93 months. CONCLUSION: Surgical treatment for patients with rib metastases of RCC may contribute in prolonging survival.

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

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

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

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

[Outcomes of Surgical Treatment by Modified Transmanubrial Approach].

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

Intraoperative robotic surgical system-related problems in robot-assisted thoracoscopic surgery.

BACKGROUND: Malfunctions of robotic instruments during robotic surgery are well known to occur; however, detailed reports on the inherent problems associated with robotic instruments and robotic surgical systems are scarce. The objective of this study was to retrospectively investigate the intraoperative problems associated with robotic surgical systems and robotic instruments. MATERIALS AND METHODS: This was a single-center retrospective study. Between April 2012 and December 2022, 544 patients with consecutive lung malignancies and/or mediastinal tumors underwent robot-assisted thoracoscopic surgery. Among these, 15 cases had intraoperative problems associated with the robotic surgical system. Human error was defined as a problem caused by the incorrect operation of the robotic surgical system and human factors as problems in which the robotic surgical system stopped owing to damage to the instruments of the robotic surgical system or the self-diagnosis of the robotic surgical system. We retrospectively investigated the causes of intraoperative problems in these cases. RESULTS: There were 4 cases (0.7%) with problems related to the robotic surgical system, 2 of which were human errors, and 11 (2.0%) with problems related to robotic surgical instruments, 6 of these were related to instruments and 5 were related to robotic staplers. Five of these were related to human factors. CONCLUSION: Teams performing robot-assisted thoracoscopic surgery should be familiar with the features of robotic surgical systems and various robotic devices, be aware of reported problems during robot-assisted thoracoscopic surgery, and be prepared for emergencies.

Accuracy of aortic valve calcification volume score for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography compared to the Agatston scoring system.

BACKGROUND: Considering the absence of reports validating the precision of the volume score and the relationship between the volume and Agatston scores, this study evaluated the accuracy of the volume score compared to the Agatston score for the quantitative measurement of aortic valve calcification (AVC) on non-electrocardiographic-gated computed tomography (CT). METHODS: We retrospectively analysed the AVC scores of 5385 patients who underwent transthoracic echocardiography between March 1, 2013 and December 26, 2019 â€‹at our institution, using non-contrast non-electrocardiographic-gated CT. The thresholds for significant aortic stenosis (AS) were computed using receiver operating characteristic curves based on the AVC scores. The area under the curve (AUC) of the Agatston and volume scores for significant AS were compared to evaluate the accuracy of the scoring method. RESULTS: All sex-specific AVC thresholds of the volume score for significant AS (moderate and high AS severity, moderate and high AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.978-0.996; sensitivity, 94.2-98.4%; specificity, 90.1-100%). No significant differences in the AUC were observed between the Agatston and volume scores for significant AS in male and female patients. CONCLUSION: All volume score threshold values showed high sensitivity and specificity for identifying significant AS. The accuracy of the test for AVC thresholds of the volume score for significant AS was comparable to that of the Agatston score. Our findings raise questions about the significance of weighting calcium density in the Agatston score for assessing AS severity.

Quantitative biomarkers for distinguishing bone metastasis and benign bone marrow lesions using turbo spin echo T1- and T2-weighted Dixon imaging at 3.0 T.

Objective: To assess the diagnostic performance and calculate the optimal threshold for quantitative biomarkers to differentiate bone metastasis and benign bone marrow lesions using turbo spin echo (TSE) Dixon images with a 3.0 T scanner. Materials and methods: Each 100 patients diagnosed with bone metastases and variable benign bone marrow lesions on spine MRI were included retrospectively. Images included in-phase (IP), opposed-phase (OP), water images (WI), and fat images (FI) by the TSE Dixon technique with T1WI and T2WI using a 3.0 T scanner. Regions of interest (ROI) of the lesions were manually drawn by two musculoskeletal radiologists independently, and the average signal intensity was recorded. The signal reduction rate from IP to OP (%drop) and a fat fraction (%fat) were calculated. Results: All biomarkers showed a significant difference between metastatic and benign lesions (P < 0.001). When comparing the AUCs, the %drop of T1WI had the highest AUC (0.934). Although the AUC of %fat from T2WI was significantly lower than that of other biomarkers, the %drop of T2WI was not significantly different from the %drop of T1WI (p = 0.339). The optimal threshold of %drop to differentiate metastatic and benign lesions was 22.0 in T1WI and 15.9 in T2WI. The inter-reader agreement was excellent for all biomarkers (0.82-0.86). Conclusion: While %drop of T1WI showed the highest diagnostic performance to differentiate bone metastasis from benign lesions, the %drop of T2WI showed a comparable ability using a threshold 15.9.

Comparison of different approaches in complete thoracoscopic segmentectomy of lung lower lobe.

Background: Safe and oncologically acceptable segmentectomy outcomes were reported for early-stage lung cancer. The high-resolution computed tomography allowed us to find detailed structures inside the lungs, such as the pulmonary ligaments (PLs). Hence, we have presented the relatively anatomically challenging thoracoscopic segmentectomy, for the resection of the lateral basal segment, the posterior basal segment, and both segments through the PL as a PL approach. This study aimed to retrospectively examine the lung lower lobe segmentectomy, excluding the superior and basal segments (from S7 to S10), using the PL approach as an option to treat the lower lobe tumors of the lung. We then compared the efficacy of the PL approach in terms of safety with the interlobar fissure (IF) approach. The characteristics of the patients, intra- and postoperative complications, and surgical outcomes were analyzed. Methods: Of the 510 patients who underwent segmentectomy for malignant lung tumors from February 2009 to December 2020, 85 were included in this study. Among them, 41 underwent a complete lung lower lobe thoracoscopic segmentectomy, excluding S6 and basal segments (from S7 to S10), using the PL approach, and the remaining 44 used the IF approach. Results: The median age in 41 patients in the PL group was 64.0 years (range, 22-82), and that in 44 patients in the IF group was 66.5 years (range, 44-88), with significant differences in gender between these groups. Video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery were performed on 37 and 4 patients in the PL group and 43 and 1 patient in the IF group, respectively. Postoperative complication frequency was not significantly different between these groups. The most common complications were the air leaks that persisted for over 7 days in 1 and 5 patients in the PL and IF groups, respectively. Conclusions: Complete thoracoscopic segmentectomy of the lower lobe, excluding S6 and basal segments, using the PL approach is a reasonable option for lung lower lobe tumors compared with the IF approach.

Complete thoracoscopic S9 and/or S10 segmentectomy through a pulmonary ligament approach: a retrospective study.

BACKGROUND: The high resolution of computed tomography has found the pulmonary ligaments that consists of a double serous layer of visceral pleura, forms the intersegmental septum, and enters the lung parenchyma. This study aimed to investigate the clinical feasibility of thoracoscopic segmentectomy (TS) of the lateral basal segment (S9), posterior basal segment (S10), and both through the pulmonary ligament (PL). METHODS: Between February 2009 and November 2021, 542 patients underwent segmentectomy for malignant lung tumors at Tokyo Women's Medical University Hospital (Tokyo, Japan). This study included 51 patients. Among them, 40 underwent a complete TS of the S9, S10, or both by the PL approach (PL group), and the remaining 11 by the interlobar fissure approach (IF group). RESULTS: Patients' characteristics did not significantly differ between the two groups. In the PL group, 34 underwent video-assisted thoracoscopic surgery (VATS), and 6 underwent robot-assisted thoracoscopic surgery. In the IF group, all 11 underwent VATS. Operation duration, estimated blood loss, and postoperative complication frequency were not significantly different between these groups, but the maximum tumor diameter showed a significant difference. CONCLUSIONS: Complete TS of the S9, S10, and both through the PL is a reasonable option for tumors located in such segments. This approach is a feasible option for performing TS.

Clinical significance of chest CT for the exclusion of COVID-19 in pre-admission screening: Is it worthwhile using chest CT with reverse-transcription polymerase chain reaction test?

BACKGROUND: A single reverse-transcription polymerase chain reaction (RT-PCR) test is not sufficient to exclude COVID-19 in hospital pre-admission screening. However, repeated RT-PCR tests are time-consuming. This study investigates the utility of chest computed tomography (CT) for COVID-19 screening in asymptomatic patients. METHODS: Between April 2020 and March 2021, RT-PCR testing and chest CT were performed to screen COVID-19 in 10 823 asymptomatic patients prior to admission. Chest CT findings were retrospectively evaluated using the reporting system of the Radiological Society of North America. Using RT-PCR results as a reference, we assessed the diagnostic efficacy of chest CT during both the low- and high-prevalence periods of the COVID-19 pandemic. RESULTS: Following a positive RT-PCR test, 20 asymptomatic patients (0.18%) were diagnosed with COVID-19; in the low-prevalence period, 5 of 6556 patients (0.076%) were positive; and in the high-prevalence period, 15 of 4267 patients (0.35%) were positive. Of the 20 asymptomatic COVID-19 positive patients, chest CT results were positive for COVID-19 pneumonia in 8 patients. Chest CT results were false-positive in 185 patients (1.7% false-positive rate, and 60% false-negative rate). Pneumonia that was classified as a "typical appearance" of COVID-19 reported as false-positives in 36 of 39 patients (92.3%). Across the study period, the diagnostic efficacy of "typical appearance" on chest CT were characterized by a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 15%, 99.7%, 99.7%, 7.7%, and 99.8%; 20%, 99.6%, 99.6%, 4%, and 99.9%; and 13.3%, 99.7%, 99.7%, 14.3%, and 99.7%, in the entire study, low-, and high-prevalence periods, respectively. CONCLUSIONS: Addition of chest CT to RT-PCR testing provides no benefit to the detection of COVID-19 in asymptomatic patients.

Preoperative predictive criteria for mastoid extension in pars flaccida cholesteatoma in assessments using temporal bone high-resolution computed tomography.

OBJECTIVES: We aimed to clarify the usefulness of high-resolution computed tomography (HRCT) and establish HRCT criteria for presurgical assessment of the mastoid extension in pars flaccida cholesteatomas of the middle ear. METHODS: Retrospective observational study. Patients who underwent primary surgery for pars flaccida cholesteatoma and those who underwent temporal bone HRCT for pretreatment evaluation were reviewed. The distance in the anterior-most portion of the mastoid sinus on HRCT was measured, and the presence of surgically verified mastoid extension of cholesteatoma was evaluated. All cases were subclassified as M+ (surgically mastoid extension-positive) or M- (surgically mastoid extension-negative). RESULTS: A total of 107 patients with pars flaccida cholesteatoma were included. The distance in the M+ cases was significantly longer than that in the M- cases, and the cutoff value was 3.6 mm. The difference between the ipsilateral/diseased-side distance and the contralateral/evaluable side (difference value) in M+ cases was larger than that in M- cases, with a cutoff value of 0.6 mm. The inter-rater reliability of this distance measurement was excellent, regardless of imaging experience. CONCLUSIONS: The cutoff values of the distance and the difference value can be used for pretreatment HRCT evaluation of mastoid extension in middle ear cholesteatoma with relatively high accuracy, regardless of the experience and skill levels of the evaluator.

Stress Responses of Shade-Treated Tea Leaves to High Light Exposure after Removal of Shading.

High-quality green tea is produced from buds and young leaves grown by the covering-culture method, which employs shading treatment for tea plants (Camellia sinensis L.). Shading treatment improves the quality of tea, but shaded tea plants undergo sudden exposures to high light (HL) at the end of the treatment by shade removal. In this study, the stress response of shaded tea plants to HL illumination was examined in field condition. Chl a/b ratio was lower in shaded plants than nonshaded control, but it increased due to exposure to HL after 14 days. Rapid decline in Fv/Fm values and increases in carbonylated protein level were induced by HL illumination in the shaded leaves on the first day, and they recovered thereafter between a period of one and two weeks. These results revealed that shaded tea plants temporarily suffered from oxidative damages caused by HL exposure, but they could also recover from these damages in 2 weeks. The activities of antioxidant enzymes, total ascorbate level, and ascorbate/dehydroascorbate ratio were decreased and increased in response to low light and HL conditions, respectively, suggesting that the upregulation of antioxidant defense systems plays a role in the protection of the shaded tea plants from HL stress.

Manipulation of long-shaft stapler in robotic-assisted thoracoscopic surgery lung resection.

The number of robotic surgical procedures for thoracic disease is increasing. The automatic linear stapler has become a necessary device in endoscopic surgery. A 67-year-old man with a history of smoking was referred to our hospital for an abnormal finding on chest x-ray. Computer tomography of the chest revealed a ground glass nodule in the right middle lobe. We performed right middle wedge resection through the assistant port using a long-shaft stapler (LSS). Because the nodule was diagnosed as an adenocarcinoma on the intraoperative frozen section, the patient underwent robotic-assisted thoracoscopic surgery (RATS) right middle lobectomy using the da Vinci® Xi system. The pulmonary arteries, veins, right middle bronchus and minor fissure were divided using the LSS through the utility thoracotomy or assistant port. The postoperative course was uncomplicated. This case suggests that the LSS can be used in RATS lung resection for cancer.

A successful surgical repair of intraoperative pneumothorax and the diffuse dissection of visceral pleura during liver transplantation surgery via trans-diaphragmatic approach.

BACKGROUND: Pneumothorax during surgery under general anesthesia is a life-threatening situation for the patient because it can progress easily to the tension pneumothorax due to positive pressure ventilation unless appropriate treatments such as inserting a drainage tube in the thoracic cavity are initiated. The authors experienced a case of intraoperative pneumothorax and the diffuse dissection of visceral pleura during liver transplantation surgery, and achieved successful repair by a trans-diaphragmatic approach without changing patient's body position. CASE PRESENTATION: A 66-year-old male with multiple liver and renal cysts caused by autosomal dominant polycystic kidney disease (ADPKD) was admitted to the authors' hospital for treating the infection of the liver cysts. The infection was unable to be controlled by conservative treatments. Therefore, the patient was planned to undergo living-donor liver transplantation. Intraoperatively, the liver was found to swell markedly and to firmly adhere to the right diaphragm. After the extraction of the liver, because the right diaphragm swelled markedly, pneumothorax was suspected. Chest tube was inserted immediately, and the small incision was made in the right diaphragm. Thoracoscopic observation revealed that (1) the visceral pleura of the bottom of the right lung widely expanded like a giant cyst due to the dissection from the lung parenchyma and (2) a large air leakage from a pin hole appeared in the dissected pleura. After the completion of the liver transplantation, the thoracoscopic leakage-closing operation was performed through the right diaphragm incision. Because the dissection of visceral pleura was too wide to perform plication or cystectomy by a stapler or sutures, the dissected pleura was opened, and absorbable fibrin sealant patches and fibrin glue were put or injected between the lung parenchyma and the pleura. Although, after being observed postoperatively, prolonged minor air leakage disappeared by a conservative drainage treatment, and the cyst on the bottom of the right lung disappeared on chest computed tomography (CT). CONCLUSIONS: Although intraoperative pneumothorax and broad dissection of visceral pleura during laparotomy is a complicated situation, the authors successfully repaired air leakage via a trans-diaphragmatic approach without changing the patient's body position.