T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non–small cell lung cancer

AbstractObjective: Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. Method: The prognosis of 545 patients with non–small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. Results: The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (≤5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). Conclusions: A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non–small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.J Thorac Cardiovasc Surg 2001;122:907-1

The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction

BACKGROUND: The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson’s disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway. CASE PRESENTATION: A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments. CONCLUSION: This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer

Phase II Study of Pleurodesis using Sterile Graded Talc in Patients with Secondary Intractable Pneumothorax: Protocol for a Multicentre, Open-label Single-arm Trial

A pneumothorax can be primary or secondary. A high proportion of patients with secondary spontaneous pneumothorax are the elderly who are in poor general condition due to their impaired cardiac and pulmonary functions as well as due to other complications. Therefore, it may be difficult for these patients to undergo surgical procedures; in addition, the elderly may be at high risk for postoperative pulmonary fistula due to severe adhesions and emphysema complications. These non-operative and high-risk cases may be treated with pleurodesis (a procedure that involves instillation of a chemical or irritant into the thoracic cavity through an injection), bronchoscopic bronchial embolisation, or other procedures. In Japan, no device is currently approved for performing pleurodesis, but an approval of one device is expected soon. This will be an open-label, single-arm multicentre study conducted among 30 patients with secondary intractable pneumothorax who are not indicated to undergo surgery. The primary endpoint will be presence or absence of chest tube removal. The secondary endpoints will be the disappearance/decrease of air leakage, grade of dyspnoea, and duration of drainage. This study will assess the safety and efficacy of sterile graded talc pleurodesis in patients with secondary intractable pneumothorax.This research is (partially) supported by the Project Promoting Clinical Trials for Development of New Drugs and Medical Devices (Japan Medical Association) and Early/Exploratory Clinical Trial Center Development Projects from the Japan Agency for Medical Research and Development (AMED). This study is registered in the Center for Clinical Trials, Japan Medical Association (JMA-IIA00272)

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Long-term survival with repeat resection for lung oligometastasis from pancreatic ductal adenocarcinoma: a case report

Abstract Background Long-term survival after resection of metastases from pancreatic ductal adenocarcinoma is rare. Case presentation A 54-year-old man underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM). Three years after radical resection of the primary tumor, a tiny nodule was found in the lower lobe of the left lung. Despite treatment with GEM, it increased gradually, but no other metastases were found. Eighteen months after the first indication of the nodule, wedge resection was performed. Pathological examination of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy was again performed for lung oligometastases at 77 and 101 months after PD. The patient has been asymptomatic without tumor recurrence for 4 years since the last pulmonary resection. Conclusions In PDAC, the treatment strategy for oligometastasis is controversial. However, a few cases of long-term survival after pulmonary metastasectomy for oligometastasis of PDAC have been reported. More such cases need to be studied to address this issue effectively