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We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after coronavirus disease 2019 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

Competing Interests: Conflicts of Interest HS belongs to an endowed department (NITORI Co., Ltd. and HOKUYAKU TAKEYAMA Holdings, Inc.). Other authors declare that they have no competing interests.

Background/objectives: Extramammary Paget disease (EMPD) is a rare, cutaneous intraepithelial adenocarcinoma typically treated with wide local excision. Unfortunately, a number of patients with metastases show poor responses to chemotherapy. While some studies have explored trastuzumab's effectiveness against EMPD positive for human epidermal growth factor receptor 2 (HER2), trastuzumab resistance (TR) may emerge after anti-HER2 therapy., Methods/subjects: In this study, we established TR EMPD patient-derived xenografts (PDX) that replicated the histological and HER2 expression traits of naive EMPD tumours., Results: Cancer gene analyses revealed a loss of the PTEN gene in TR tumours, which was further confirmed by immunohistochemical staining and immunoblotting to test for protein expression levels. Reduced PTEN levels correlated with increased protein kinase B (Akt) phosphorylation and p27 downregulation, suggesting a potential mechanism for trastuzumab resistance in EMPD cells. In the trastuzumab-sensitive EMPD-PDX mouse model, PTEN inhibitors partially restored trastuzumab-mediated tumour regression. The TR EMPD-PDX responded favourably to targeted therapy (lapatinib, abemaciclib, palbociclib) and chemotherapy (eribulin, docetaxel, trastuzumab deruxtecan)., Conclusions: This study demonstrates an innovative TR EMPD-PDX model and introduces promising antineoplastic effects with various treatments for TR EMPD tumours., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To introduce and evaluate the non-assistant help operation in dual-portal robotic-assisted thoracic surgery (neoDRATS), a novel technique designed to eliminate the need for skilled assistants by using all 4 robotic arms independently during anatomical lung surgery., Methods: Patients were placed in the lateral decubitus position under general anesthesia with single-lung ventilation. The da Vinci Xi Surgical System was used, with specific configurations for right- and left-side operations. The neoDRATS technique used a 4-cm working port and a 1.8-cm secondary port, with detailed guidelines for optimal setup and robotic arm manipulation., Results: The neoDRATS approach demonstrated successful surgical outcomes without the need for a skilled assistant. The use of a 0° camera and careful placement of instruments minimized interference within the thoracic cavity. The technique provided smooth operability and minimized postoperative discomfort. Video demonstrations of right and left upper lobectomies are provided to illustrate the approach., Conclusions: NeoDRATS offers a practical, safe, and minimally invasive alternative to conventional multiportal and uniportal robotic-assisted thoracic surgeries. This technique simplifies the surgical process, particularly in settings with limited availability of skilled assistants, and represents a significant advancement in robotic thoracic surgery. Further refinement and clinical integration of neoDRATS are anticipated as robotic innovations continue to evolve., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Epithelia consist of proliferating and differentiating cells that often display patterned arrangements. However, the mechanism regulating these spatial arrangements remains unclear. Here, we show that cell-cell adhesion dictates multicellular patterning in stratified epithelia. When cultured keratinocytes, a type of epithelial cell in the skin, are subjected to starvation, they spontaneously develop a pattern characterized by areas of high and low cell density. Pharmacological and knockout experiments show that adherens junctions are essential for patterning, whereas the mathematical model that only considers local cell-cell adhesion as a source of attractive interactions can form regions with high/low cell density. This phenomenon, called cell-cell adhesion-induced patterning (CAIP), influences cell differentiation and proliferation through Yes-associated protein modulation. Starvation, which induces CAIP, enhances the stratification of the epithelia. These findings highlight the intrinsic self-organizing property of epithelial cells., (© 2024 Mai et al.)

Background: Pleural mesothelioma, characterized by a dismal prognosis even with multimodal therapy, has seen emerging interest in immune checkpoint inhibitors (ICIs) due to their demonstrated efficacy. Here, we present a case of epithelioid-type pleural mesothelioma with chest wall invasion treated with definitive ICI therapy, resulting in a remarkable pretreatment effect., Case Presentation: A 46-year-old man was diagnosed with an abnormal chest shadow on a medical check, and a computed tomography scan showed pleural thickening at the dorsal right upper chest wall. One of the nodules was suspected to have invaded the chest wall. A needle biopsy revealed epithelioid-type pleural mesothelioma. After five cycles of nivolumab plus ipilimumab, he underwent right pleurectomy/decortication (P/D). Pathological examination revealed a significant treatment effect, showing numerous lymphocytes infiltrating the tumor nodule and viable tumor cells localized at approximately 6 mm., Conclusion: Although further accumulation of cases is required to evaluate the effectiveness and case selection, P/D after immunotherapy is a useful curative treatment option for advanced pleural mesothelioma., (© 2024. The Author(s).)

Background: Intravenously administered indocyanine green (ICG) accumulates in lung tumors, facilitating their detection via a fluorescence spectrum measurement. This method aids in identifying tumor locations that are invisible to the naked eye. We aim to determine the optimal ICG dose and administration method for accurate tumor identification during lung resection surgeries, utilizing a novel ICG fluorescence spectroscopy system for precise tumor localization. Materials and Methods: ICG should be dissolved in the provided solution or distilled water and administered intravenously approximately 24 h before surgery, beginning with an initial dose of 0.5 mg/kg. If the tumor detection rate is insufficient, the dose may be gradually increased to a maximum of 5.0 mg/kg to determine the optimal dosage for effective tumor detection. This fluorescence spectroscopy during surgery may reveal additional lesions that remain undetected in preoperative assessments. The primary endpoint includes the correct diagnostic rate of tumor localization. The secondary endpoints include the measurement of the intraoperative ICG fluorescence spectral intensity in lung tumors, the assessment of the operability and safety of intraperitoneal ICG administrations, the measurement of the ICG fluorescence spectral intensity in surgical specimens, the comparison of the spectral intensity in lung tissues during collapse and expansion, the correlation between ICG camera images and fluorescence spectral intensity, and the comparison of fluorescence analysis results with histopathological findings. The trial has been registered in the jRCT Clinical Trials Registry under the code jRCTs011230037. Results and Conclusions: This trial aims to establish an effective methodology for localizing and diagnosing malignant lung tumors, thereby potentially improving surgical outcomes and refining treatment protocols.

When performing thoracoscopic partial resections of nonpalpable lung tumors such as ground-glass opacities (GGOs) and small tumors, detecting the location of the lesion and assessing the resection margins can be challenging. We have developed a novel method to ease this difficulty, the One-stop Solution for a nonpalpable lung tumor, Marking, Resection, and Confirmation of the surgical margin in a Hybrid operating room (OS-MRCH), which uses a hybrid operating room wherein the operating table is seamlessly integrated with cone-beam computed tomography (CBCT). We performed the OS-MRCH method on 62 nodules including primary lung cancer presenting with GGO. Identification of the lesion and confirmation of the margin were performed in 58 of the cases, while nodules were detected in all. The frequency of computed tomography (CT) scans performed prior to resection was one time in 51 cases, two times in eight cases, and ≥3 times in three cases. Additional resection was performed in two cases. The median operative time was 85.0 minutes, and the median pathological margin was 11.0 mm. The key advantages of this method are that all surgical processes can be completed in a single session, specialized skill sets are not required, and it is feasible to perform in any facility equipped with a hybrid operating room. To overcome its disadvantages, such as longer operating time and limited patient positioning, we devised various methods for positioning patients and for CT imaging of the resected specimens. OS-MRCH is a simple, useful, and practical method for performing thoracoscopic partial resection of nonpalpable lung tumors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-25/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Background . Robotic-assisted thoracic surgery (RATS) is now standard for lung cancer treatment, offering advantages over traditional methods. However, RATS's minimally invasive approach poses challenges like limited visibility and tactile feedback, affecting surgeons' navigation through com-plex anatomy. To enhance preoperative familiarization with patient-specific anatomy, we devel-oped a virtual reality (VR) surgical navigation system. Using head-mounted displays (HMDs), this system provides a comprehensive, interactive view of the patient's anatomy pre-surgery, aiming to improve preoperative simulation and intraoperative navigation. Methods . We integrated 3D data from preoperative CT scans into Perspectus VR Education software, displayed via HMDs for in-teractive 3D reconstruction of pulmonary structures. This detailed visualization aids in tailored preoperative resection simulations. During RATS, surgeons access these 3D images through Tile-Pro TM multi-display for real-time guidance. Results . The VR system enabled precise visualization of pulmonary structures and lesion relations, enhancing surgical safety and accuracy. The HMDs offered true 3D interaction with patient data, facilitating surgical planning. Conclusions . VR sim-ulation with HMDs, akin to a robotic 3D viewer, offers a novel approach to developing robotic surgical skills. Integrated with routine imaging, it improves preoperative planning, safety, and accuracy of anatomical resections. This technology particularly aids in lesion identification in RATS, optimizing surgical outcomes.

Background: Robotic-assisted thoracic surgery (RATS) has gained increasing interest in recent years, with most procedures performed using the conventional multiportal approach. Uniportal RATS (URATS) approaches have recently been reported in the pursuit of minimally invasive procedures. However, URATS requires specific skills. Herein, we introduce dual-portal RATS (DRATS) performed with two incisions., Methods: Data of DRATS procedures performed from December 2022 to May 2023 were retrospectively reviewed. Twenty patients with lung cancer underwent anatomical lung resections via DRATS performed by our group at three institutes., Results: Among 20 cases of planned DRATS for anatomical pulmonary resections, there were no conversions to thoracotomy and no need for extra ports. The mean surgery time was 121±60 minutes and mean console time was 91±47 minutes. The mean intraoperative blood loss volume was 9.6±12.1 g. The mean duration of chest tube drainage and hospital stay were 2±1 and 5±2 days, respectively. The mean numerical rating scale for pain was 2±1 on the first postoperative day, 1±1 on the third day, and 1±1 at discharge. There were no postoperative complications or mortalities., Conclusions: Our primary experience shows that DRATS is safe and feasible for anatomical lung resection. We consider DRATS to be a very good preliminary step in the future transition to URATS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1141/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Bullous pemphigoid (BP) is the most common autoimmune blistering disorder. Several factors, including an antidiabetic (dipeptidyl peptidase-4 inhibitor [DPP-4i]), have been reported to trigger BP. To identify the genetic variants associated with BP, GWAS and HLA fine-mapping analyses were conducted. The 21 cases of noninflammatory BP induced by DPP-4i (i.e., DPP-4i-induced noninflammatory BP) and 737 controls (first cohort) and the 8 cases and 164 controls (second cohort) were included in the GWAS. Combining GWAS satisfied the genome-wide significant association of HLA-DQA1 (chromosome 6, rs3129763 [T/C]) with the risk of DPP-4i-induced noninflammatory BP (allele T carrier of 72.4% [21 of 29] in cases vs. 15.3% [138 of 901] in controls; dominant model, OR = 14, P = 1.8 × 10 -9 ). HLA fine mapping revealed that HLA-DQA1∗05 with serine at position 75 of HLA-DQα1 (Ser75) had the most significant association with the combined cohort of DPP-4i-induced noninflammatory BP (79.3% [23 of 29] cases vs. 16.1% [145 of 901] controls; dominant model, OR = 21, P = 2.0 × 10 -10 ). HLA-DQα1 Ser75 polymorphism was located inside the functional pocket of HLA-DQ molecules, suggesting the impact of HLA-DQα1 Ser75 on DPP-4i-induced noninflammatory BP., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In the last few decades, reduced-port video-assisted thoracic surgery (RP-VATS) has been developed to minimize surgical invasiveness. Nevertheless, VATS in children can occasionally be difficult because the lesion occupies a small thoracic cavity, limiting the working space. This study aimed to assess the feasibility of RP-VATS for the resection of mediastinal lesions in children in association with the tumor-to-thoracic height ratio (TTH ratio). We reviewed all patients aged ≤10 years who underwent resection for mediastinal lesions in our institute between January 2008 and August 2022. Patients who underwent diagnostic procedures were excluded from this study. The TTH ratio was calculated as tumor height divided by thoracic height. Seven patients in the RP-VATS group and six in the conventional procedures (multi-portal VATS or open surgery) group were included in this study. The TTH ratio was significantly lower in the RP-VATS group than in the conventional procedures group (median, 26.3% vs. 50.8%; P=0.007). The operating time (P=0.01) and duration of drainage (P=0.003) were significantly shorter and the blood loss (P=0.001) was significantly lower in the RP-VATS group than in the conventional procedures group. After adjusting for age, a lower TTH ratio was significantly associated with the completion of RP-VATS (odds ratio: 0.776; 95% confidence interval: 0.529-0.926; P=0.048). In conclusion, RP-VATS can be performed appropriately in carefully selected cases of pediatric mediastinal lesions. A low TTH ratio may predict the feasibility of RP-VATS. Further studies are warranted to determine the criteria for the indications of RP-VATS in children, so that more children can benefit from RP-VATS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-515/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Zonula occludens-1 (ZO-1) is a scaffolding protein of tight junctions, which seal adjacent epithelial cells, that is also expressed in adherens junctions. The distribution pattern of ZO-1 differs among stratified squamous epithelia, including that between skin and oral buccal mucosa. However, the causes for this difference, and the mechanisms underlying ZO-1 spatial regulation, have yet to be elucidated. In this study, we showed that epithelial turnover and proliferation are associated with ZO-1 distribution in squamous epithelia. We tried to verify the regulation of ZO-1 by comparing normal skin and psoriasis, known as inflammatory skin disease with rapid turnover. We as well compared buccal mucosa and oral lichen planus, known as an inflammatory oral disease with a longer turnover interval. The imiquimod (IMQ) mouse model, often used as a psoriasis model, can promote cell proliferation. On the contrary, we peritoneally injected mice mitomycin C, which reduces cell proliferation. We examined whether IMQ and mitomycin C cause changes in the distribution and appearance of ZO-1. Human samples and mouse pharmacological models revealed that slower epithelial turnover/proliferation led to the confinement of ZO-1 to the uppermost part of squamous epithelia. In contrast, ZO-1 was widely distributed under conditions of faster cell turnover/proliferation. Cell culture experiments and mathematical modelling corroborated these ZO-1 distribution patterns. These findings demonstrate that ZO-1 distribution is affected by epithelial cell dynamics., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)