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Background: Nuclear protein in testis (NUT) carcinoma (NC) of the lung is a rare cancer that occurs mainly in young adolescents and adults. NC is genetically characterized by NUTM1 rearrangements, which usually take the form of BRD4-NUT fusions. The prognosis for NC is dismal, and treatment with conventional chemotherapeutic regimens is ineffective. Case Description: We herein describe the case of a 53-year-old woman with recurrent NC of the lung 14 years after surgery for nasal cavity cancer. Chest computed tomography revealed a 5.5-cm tumor in the lower lobe of the left lung. We completely resected the recurrent lung NC via thoracotomy. Immunohistochemistry (IHC) of the lung and nasal cavity cancers showed diffuse strong expression of NUT. RNA-seq of the lung NC revealed NUTM1 rearrangement, with a fusion of BRD4 exon 10 to NUTM1 exon 4. This breakpoint has never been reported before. In addition, IHC revealed elevated expression of parathyroid hormone-like hormone in the lung NC but not in the nasal cavity NC, indicating that the lung and nasal cavity NCs were metachronous multiple primary cancers. Conclusions: We experienced a rare recurrence of lung NC 14 years after the initial surgery. The BRD4-NUT fusion consisted of a new breakpoint. Furthermore, the expression pattern of parathyroid hormone-like hormone (PTHLH) suggested that the NCs in the nasal cavity and lung may be metachronous multiple lung cancers. This extremely rare case highlighted the possibility of identifying less malignant NCs in patients with poorly differentiated tumors via fusion gene analysis and the need to develop more effective treatment strategies for this malignancy.
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Introduction. Invasive fungal infections require early diagnosis for treatment. Microscopic observation of biopsy and blood culture is the gold standard for the identification of the causative fungus, but it is difficult to identify the causative pathogen by a sterile abscess biopsy. Case Presentation. We present a case report of breakthrough invasive trichosporonosis in a 65-year-old Japanese male with acute myeloid leukaemia receiving antifungal prophylaxis. Blood cultures showed no fungal growth, and a liver biopsy and a removed spleen with abscess showed fragmented fungi, but no fungal identification was possible. This report demonstrates that retrospective analyses were able to identify the causative fungus. Conclusion. We narrowed down the candidate fungi by deep sequencing of the ITS1 region of fungal genome and confirmed that the fungus observed in the specimen was Trichosporon asahii by in situ hybridization using a DNA probe targeting 26S rRNA.
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BACKGROUND: A multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate. CASE PRESENTATION: We report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient's age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery. CONCLUSIONS: We report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.
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BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC), but specific outcomes of ICIs treatment among patients with postoperative recurrence of NSCLC remain unclear. The objective of the study was to compare the efficacy of ICIs and chemotherapy with conventional chemotherapy only in patients with postoperative recurrence of epidermal growth factor receptor (EGFR) wild-type NSCLC. PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent anatomical lung resection at the Nagoya University Hospital and were treated for postoperative recurrence of wild-type EGFR NSCLC. This study evaluated the prognosis for postoperative recurrence, including ICIs treatment and other clinicopathological factors. RESULTS: Of the 83 patients included in the analysis, 20 patients underwent chemotherapy and 63 patients underwent chemotherapy combined with ICIs. The combination of ICIs and chemotherapy significantly prolonged survival after recurrence (median survival: 33.1 months vs. 22.0 months, p=0.01). In the ICIs group, no significant differences in survival were detected between patients with different programmed death ligand 1 (PD-L1) status (Tumor Proportion Scores: <1%, 1%-49%, ≥50%, p=0.27). Multivariate analysis revealed that postoperative distant recurrence was a significant poor prognostic factor for survival after recurrence (HR=1.85, 95% CI=1.06-3.25, p=0.03), and combining ICIs with chemotherapy significantly improved survival after recurrence (HR=0.43, 95% CI=0.24-0.78, p<0.01). CONCLUSION: Combination of ICIs with chemotherapy significantly prolonged survival of postoperative recurrence with wild-type EGFR NSCLC regardless of PD-L1 status.
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Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Prognóstico , Adulto , Resultado do TratamentoRESUMO
INTRODUCTION: A minimally invasive alternative to surgery for treating pneumothorax has been developed, aiming to reduce risks while maintaining efficacy. This study conducted basic experiments using Ex vivo and in vivo pig lung employing a super-thin catheter for treatment. This new device injects fibrin glue directly into the responsible lesion to close the air leak, which has two features; thin design and double-lumen. METHODS: The experimental setup involved utilizing trachea and both lung specimens from pigs under positive pressure ventilation. To simulate pneumothorax, artificial fistulas were created on the lung surfaces. The super-thin catheter, guided through a bronchoscope near the fistula, was used to embolize the peripheral bronchus by injecting a fibrin preparation. Then, an air leak test was conducted afterward to assess the efficacy of the treatment. Additionally, a similar pneumothorax model was induced in alive pig under general anesthesia to evaluate its curability. RESULTS: In the extracted pig lungs, embolization was performed in 21 cases, resulting in the cessation of air leaks in 19 cases, corresponding to a 90.5% cure rate. Notably, no major adverse events occurred with the treatment devices. Similarly, in living pigs, pneumothorax was successfully treated, with no recurrence observed up to the seventh postoperative day. CONCLUSION: The novel treatment device utilizing a super-thin catheter offers a minimally invasive and highly curative option for pneumothorax. These promising results suggest the potential for further development and human clinical trials, which could revolutionize the treatment of pneumothorax, reducing risks and improving outcomes.
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Massive haemoptysis is a life-threatening condition whose cause needs to be identified rapidly so that prompt interventions can ensue. Bronchial occlusion with endobronchial Watanabe spigots (EWSs) may be useful when endovascular treatment or surgery proves to be difficult. An 84-year-old woman developed massive haemoptysis during percutaneous mitral valve repair for refractory heart failure due to severe mitral regurgitation (MR). Interventional radiology (IVR) and surgery were contraindicated, and bronchial occlusion with EWSs was attempted to control bleeding. The bleeding was so persistent that it was difficult to secure the visual field without aspiration with a bronchoscope. Herein, we report a two-scope technique, also used in cryobiopsy of peripheral lung lesions, to control bleeding and perform bronchial occlusion with EWSs.
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PURPOSE: To develop a comorbidity risk score specifically for lung resection surgeries. METHODS: We reviewed the medical records of patients who underwent lung resections for lung cancer, and developed a risk model using data from 2014 to 2017 (training dataset), validated using data from 2018 to 2019 (validation dataset). Forty variables were analyzed, including 35 factors related to the patient's overall condition and five factors related to surgical techniques and tumor-related factors. The risk model for postoperative complications was developed using an elastic net regularized generalized linear model. The performance of the risk model was evaluated using receiver operating characteristic curves and compared with the Charlson Comorbidity Index (CCI). RESULTS: The rate of postoperative complications was 34.7% in the training dataset and 21.9% in the validation dataset. The final model consisted of 20 variables, including age, surgical-related factors, respiratory function tests, and comorbidities, such as chronic obstructive pulmonary disease, a history of ischemic heart disease, and 12 blood test results. The area under the curve (AUC) for the developed risk model was 0.734, whereas the AUC for the CCI was 0.521 in the validation dataset. CONCLUSIONS: The new machine learning model could predict postoperative complications with acceptable accuracy. CLINICAL REGISTRATION NUMBER: 2020-0375.
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Toxoplasma gondii is a global protozoan pathogen. Clonal lineages predominate in Europe, North America, Africa, and China, whereas highly recombinant parasites are endemic in South/Central America. Far East Asian T. gondii isolates are not included in current global population genetic structure analyses at WGS resolution. Here we report a genome-wide population study that compared eight Japanese and two Chinese isolates against representative worldwide T. gondii genomes using POPSICLE, a novel population structure analyzing software. Also included were 7 genomes resurrected from non-viable isolates by target enrichment sequencing. Visualization of the genome structure by POPSICLE shows a mixture of Chinese haplogroup (HG) 13 haploblocks introgressed within the genomes of Japanese HG2 and North American HG12. Furthermore, two ancestral lineages were identified in the Japanese strains; one lineage shares a common ancestor with HG11 found in both Japanese strains and North American HG12. The other ancestral lineage, found in T. gondii isolates from a small island in Japan, is admixed with genetically diversified South/Central American strains. Taken together, this study suggests multiple ancestral links between Far East Asian and American T. gondii strains and provides insight into the transmission history of this cosmopolitan organism.
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Genoma de Protozoário , Filogenia , Toxoplasma , Toxoplasma/genética , Toxoplasma/classificação , Humanos , América do Norte , Genoma de Protozoário/genética , Toxoplasmose/parasitologia , China , América Central , Japão , Haplótipos , Variação Genética , Recombinação GenéticaRESUMO
An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.
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Carcinoma de Células Escamosas , Achados Incidentais , Neoplasias Pulmonares , Pericárdio , Pneumonectomia , Humanos , Masculino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pneumonectomia/efeitos adversos , Pericárdio/transplante , Idoso de 80 Anos ou mais , Resultado do Tratamento , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Toracotomia , Tomografia Computadorizada por Raios X , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/diagnóstico por imagem , Estadiamento de NeoplasiasRESUMO
Strain TC023T, a Gram-positive, long, rod-shaped, spore-forming anaerobe, was isolated from the faeces of a heart failure mouse model. The strain formed greyish-white coloured colonies with a convex elevation on brain-heart infusion medium supplemented with 0.1â% sodium taurocholate, incubated at 37â°C for 2 days. Taxonomic analysis based on the 16S rRNA gene sequence showed that TC023T belonged to the genus Turicibacter, and was closely related to Turicibacter bilis MMM721T (97.6â%) and Turicibacter sanguinis MOL361T (97.4â%). The whole genome of the strain has a G+C content of 37.3âmol%. The average nucleotide identity and genome-to-genome distance between TC023T and Turicibacter bilis MMM721T were 77.6â% and 24.3â%, respectively, and those with Turicibacter sanguinis MOL361T were 75.4â% and 24.3â%, respectively. These genotypic, phenotypic, and biochemical analyses indicated that the isolate represents a novel species in the genus Turicibacter, and the name Turicibacter faecis sp. nov. is proposed. The type strain is TC023T (RIMD 2002001T=TSD 372T).
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Modelos Animais de Doenças , Fezes , Insuficiência Cardíaca , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Animais , RNA Ribossômico 16S/genética , Fezes/microbiologia , Camundongos , DNA Bacteriano/genética , Insuficiência Cardíaca/microbiologia , Genoma Bacteriano , Masculino , Ácidos GraxosRESUMO
Introduction Advancements in bipolar hemiarthroplasty (BHA) implants in the mid-1990s contributed to favorable short-term outcomes for osteonecrosis of the femoral head (ONFH), particularly in cases without acetabular cartilage lesions. Nevertheless, long-term results remain unclear. In this study, we investigated (i) the impact of new-generation BHA implants and (ii) the effect of the preoperative stage on long-term outcomes in young patients with ONFH. Methods The records of consecutive patients with ONFH who underwent cementless BHA were retrospectively reviewed. Patients aged ≥60 years, with <10 years of follow-up, or who underwent acetabular reaming during surgery were excluded. Radiographical and clinical outcomes of patients who received first-generation BHAs and new-generation BHAs (developed after 1998) were compared by stratifying based on preoperative stage 2/3A and 3B/4, according to the Japanese Investigation Committee classification. Results Overall, 50 hips from 39 patients (mean age: 44.6 years; 64% male) with an average follow-up of 18.6 years were included. The frequency of advanced-stage patients was significantly higher in the first-generation BHA group than in the new-generation group. Regarding postoperative outcomes, the first-generation BHA group had higher acetabular erosion grades (p<0.001) and more femoral component loosening than those in the new-generation group (p<0.001). Revisions were performed in eight hips (seven in the first-generation and one in the new-generation BHA groups, p<0.001). In the new-generation BHA group, there were no significant differences in patient background between stage 2/3A and 3B/4 groups, and only one case in the stage 3B/4 group required revision. In the new-generation group, the grade of acetabular erosion was significantly higher for stage 3B/4 than stage 2/3A (p<0.001); other radiographical and clinical outcomes did not differ significantly between stages. Conclusion New-generation BHAs have significantly better implant survival rates for early-stage ONFH than those of first-generation BHAs. These findings indicate that BHA is an acceptable treatment option for early-stage ONFH in young patients.
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BACKGROUND: Aging is associated with muscle atrophy, as typified by sarcopenia. Loss of abdominal muscle strength can cause abdominal wall laxity. The purpose of this study was to investigate the relationship between the sacral vertebra-abdominal wall distance (SAD) and movement performance using a simple lateral spine X-ray image for measuring the SAD. METHODS: In this retrospective study, we included women aged ≥ 65 years who were attending the outpatient clinic for osteoporosis at our hospital. A total of 287 patients (mean age ± SD, 76.8 ± 7.1 years) with measured SAD were included in the analysis. Patients were divided into two groups based on SAD cutoff (160 mm) and age (75 years), respectively. The patients were examined using the two-foot 20 cm rise test, 3 m Timed Up and Go (TUG) test, two-step test, open-eyed one-leg standing time, and spinal alignment. Normally distributed data are expressed as means (standard deviations) and non-normally distributed data as medians (interquartile range), depending on the results of the Kolmogorov-Smirnov test. Student's t-test and χ2 test were used for between-group comparisons. Regression analysis was performed with SAD as the objective variable. A two-sided p < 0.05 was considered statistically significant. RESULTS: The shorter SAD group performed better in the two-step test, TUG test, and open-eyed one-leg standing time (p < 0.001) as well as in the two-foot 20 cm rise test (p < 0.01) compared to the longer SAD group. Spinal alignment was better in the shorter SAD group than in the longer SAD group, with a shorter sagittal vertical axis (p < 0.001), smaller pelvic tilt (p < 0.001), and greater sacral slope (p < 0.05). CONCLUSION: SAD was associated with posterior pelvic tilt and movement performance parameters. In addition to testing for osteoporosis, movement performance parameters should be evaluated in women with osteoporosis who are aged ≥ 65 and have greater SAD (≥ 160 mm in this study). The SAD is a new assessment method, and further research is required to verify its validity and reproducibility. This is the first attempt to determine how age and SAD affect movement performance in older adults.
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Parede Abdominal , Osteoporose , Humanos , Feminino , Idoso , Sacro , Estudos Retrospectivos , Reprodutibilidade dos TestesRESUMO
Pregnancy is a major life event for most women that causes extensive physiological changes. Hence, it is associated with additional risks in women with congenital heart disease. No reports of pregnancy or a baby born to a woman with isolated right ventricular hypoplasia without an atrial septal defect have been published. In this case, the patient's right ventricle was very small with no contractility. The right atrium was highly enlarged, and its contractility resulted in pulmonary circulation without pulmonary hypertension. The size increased post-delivery than that before pregnancy. Fortunately, a healthy infant was born without any right heart failure symptoms.
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Extended-spectrum ß-lactamase-producing non-O1 Vibrio cholerae was isolated from edible Mastacembelus sp. in Vietnam. The genome sequence was sequenced using DNBSEQ-G400 and MinION Mk1b. A plasmid of approximately 183-kb encoding blaCTX-M-55 and blaTEM-1 was detected.
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Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.
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Amianto , Mesotelioma Maligno , Humanos , Amianto/toxicidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/genética , Análise de SobrevidaRESUMO
Aim: Altered gut microbiota has been proposed as one of the causes of exacerbation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) from the perspective of the gut-lung axis. We aimed to evaluate gut microbiota in mechanically ventilated patients with COVID-19 prior to using antibiotics. Methods: We retrospectively selected for enrollment COVID-19 patients who required mechanical ventilation on admission but who had not used antibiotics before admission to observe the influence of SARS-Cov-2 on gut microbiota. Fecal samples were collected serially on admission and were evaluated by 16S rRNA gene deep sequencing. Results: The phylum of Bacteroidetes decreased, and those of Firmicutes and Actinobacteria increased in COVID-19 patients compared with those in healthy controls (p < 0.001). The main commensals of Bacteroides, Faecalibacterium, and Blautia at the genus level were significantly decreased in the COVID-19 patients, and opportunistic bacteria including Corynebacterium, Anaerococcus, Finegoldia Peptoniphilus, Actinomyces, and Enterococcus were increased (p < 0.001). α-Diversity and ß-diversity in COVID-19 patients significantly changed compared with those in the healthy controls. Conclusion: The commensal gut microbiota were altered, and opportunistic bacteria increased in patients with severe COVID-19 who required mechanical ventilation on admission.
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OBJECTIVES: The management for pneumothorax patients involves surgical intervention, nevertheless postoperative recurrences are often encountered. To reduce the rates of recurrence, thoracic surgeons have experimented with various novel techniques, such as pleural abrasion, chemical pleurodesis, and staple line coverage with absorbable sheets, in addition to bullectomy. And in recent years, there have been reports of the effectiveness of the use of intraoperative glucose intrapleural spray (GIS) containing 50 ml of 50% glucose solution in addition to bullectomy. However, information on the effects and adverse events of GIS is limited. Current study was aimed to assess the efficacy and safety of GIS in preventing recurrence of pneumothorax. PATIENTS AND METHODS: We conducted a retrospective study with 74 cases of bullectomy with or without GIS between 2018 and 2021 at Okazaki City Hospital. Of these cases, 50 received GIS (GIS group) while 24 were treated conservatively (C group). RESULT: The GIS group consisted of 46 males and 4 females, whereas the C group consisted of 23 males and 1 female, with mean ages of 38.5 ± 5.7 years and 30.5 ± 6.7 years, respectively. The GIS group exhibited a mean increase in blood glucose of 23.8 mg/dL postoperatively, and postoperative infections were observed in 2 cases in the GIS group (4.0%) and 2 cases in the C group (8.3%). The NRS scores of the patients in the GIS group and the C group three hours postoperatively were 4.0 and 3.1, respectively (p = 0.28). No prolongation of postoperative drainage period by GIS was observed (1.2 days and 1.4 days in the GIS and C groups, respectively). Postoperative recurrence occurred in two patients from the C group. The postoperative total drainage volumes were 341.8 ± 25.2 ml and 74.2 ± 25.5 ml in the GIS and C groups, respectively, showing a significant increase in drainage volume (p < 0.01). None of them presented dehydration-related symptoms. CONCLUSIONS: The use of intraoperative glucose intrapleural spray is effective and safe in terms of preventing recurrences and postoperative complications.
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Pneumotórax , Masculino , Humanos , Feminino , Adulto , Pneumotórax/terapia , Glucose/uso terapêutico , Estudos Retrospectivos , Pleurodese/métodos , Cirurgia Torácica Vídeoassistida/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Recidiva , Resultado do TratamentoRESUMO
INTRODUCTION: No evidence exists for postoperative adjuvant therapy in elderly or renal dysfunction patients with non-small-cell lung cancer (NSCLC) who are unfit to receive cisplatin (CDDP). Herein, we evaluated the efficacy of postoperative adjuvant therapy for CDDP-unfit patients. MATERIALS AND METHODS: We defined CDDP-unfit patients as those aged ≥75 years or with renal dysfunction based on criteria established by expert panels and from prospective studies. CDDP-fit patients comprised all others. Between 2010 and 2020, among 1,423 patients with pathological stage II-III (8th edition of the AJCC-TNM Classification) NSCLC, 454 were identified as unfit for CDDP. Following propensity score matching in CDDP-unfit patients with and without postoperative adjuvant therapy, we analyzed the overall survival (OS) and disease-free survival (DFS) of each group and assessed the impact of adjuvant therapy on survival. RESULTS: OS was significantly better in patients who received adjuvant therapy than in those who did not (5-year OS rate: 76.1 % vs. 50.0 %, p < 0.01) among 255 propensity score-matched patients. DFS was also significantly better in patients who received adjuvant therapy than in those who did not (5-year OS: 54.6 % vs. 35.1 %, p < 0.01). CONCLUSIONS: Our findings suggest that postoperative adjuvant therapy could be beneficial for CDDP-unfit patients aged ≥75 years or with renal dysfunction. Future studies for CDDP-unfit patients should be designed based on the results of this study to determine the potential benefits of adjuvant therapy.
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Carcinoma Pulmonar de Células não Pequenas , Nefropatias , Neoplasias Pulmonares , Idoso , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/patologia , Prognóstico , Estudos Prospectivos , Quimioterapia Adjuvante/métodos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Forkhead box P3 (Foxp3)-expressing regulatory T (Treg) cells play essential roles in immune homeostasis but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of the transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically downregulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the downregulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis.