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BACKGROUND: The postoperative prognosis of patients with interstitial lung disease (ILD) and lung cancer is poor. Recently, the ILD-gender-age-physiology (GAP) index was identified as a clinical prognostic factor for patients with ILD. This study investigated the ILD-GAP index and oncological factors regarding postoperative outcomes. METHODS: We retrospectively reviewed 87 lung cancer patients with comorbid ILD who underwent curative resection at our institution between April 2005 and December 2019. Short-term postoperative outcomes and overall survival (OS) based on the ILD-GAP index were examined. OS rates after surgery were calculated using the Kaplan-Meier method, and group differences were analyzed using the Log-Rank test. Univariate and multivariate analyses for OS were performed using the Cox regression model. RESULTS: Multivariate analyses revealed ILD-GAP index ≥ 4 [Hazard ratio, 3.349; 95% confidence interval 1.375-8.155; P = 0.008] as a factor associated with OS. In the ILD-GAP index ≥ 4 group, no deaths occurred from primary lung cancer, with respiratory-related deaths being the most common, and exacerbation of ILD was more frequent (P = 0.007). Regarding perioperative results, a significant difference was observed in 90-day mortality (2.7% vs. 23.0% [P = 0.022]), and more patients required home oxygen therapy (14.9% vs. 69.2% [P < 0.001]) in the ILD-GAP index ≥ 4 group. CONCLUSIONS: An ILD-GAP index ≥ 4 indicated a poor prognostic factor for patients with surgically treated lung cancer. Careful consideration of surgical indications is essential for patients with an ILD-GAP index ≥ 4.
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PURPOSE: New approaches to endoscopic thyroid surgery have been developed to improve cosmetic results, one of which is video-assisted neck surgery (VANS). The present study investigates the safety and effectiveness of thyroidectomy by VANS as oncologic surgery for papillary thyroid carcinoma (PTC). METHODS: The subjects of this retrospective study were 121 patients with PTC, who underwent hemi-thyroid lobectomy and central lymph node dissection via open surgery (n = 102) or VANS (n = 19) at Tokushima University Hospital between 2011 and 2023. We performed 1:1 propensity score matching and then compared the surgical outcomes between the two matched groups. RESULTS: Propensity score matching generated 18 distinct examination pairs. The VANS group had significantly less blood loss (P = 0.003), but a longer operative time (P < 0.001) than the open thyroidectomy group. There were two cases of transient recurrent laryngeal nerve paralysis and one case of recurrence in the lateral regional lymph nodes in the VANS group. However, no significant differences were observed in the incidence of complications (P = 0.243) or recurrence (P = 0.500) between the two groups. CONCLUSION: VANS is a safe and effective surgical procedure for PTC, but longer follow-up is needed to assess tumor recurrence.
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BACKGROUND: Accurate diagnosis of the tracheobronchial invasion of advanced esophageal cancer is essential to select appropriate treatment and improve prognosis; however, it is difficult using the conventional modalities. This study aimed to clarify the diagnostic usefulness of convex probe endobronchial ultrasound (CP-EBUS) for the diagnosis of the tracheobronchial invasion of advanced esophageal cancer. METHODS: We conducted a cadaveric study to clarify the changes in ultrasonic and histopathologic findings in the esophageal tumor and tracheal invasion models. Additionally, we examined CP-EBUS for patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected on contrast-enhanced computed tomography (CE-CT) scan. We retrospectivity evaluated the diagnosis of CP-EBUS, comparing the pathological findings and treatment outcomes. RESULTS: Cadaveric esophageal tumor and tracheal invasion models showed the disappearance of the third layer observed with CP-EBUS and histologically proven interruption of the adventitia. This indicated that the third layer corresponded with the tracheal adventitia. We examined 40 patients with advanced thoracic esophageal cancer in whom tracheobronchial invasion was suspected. The precise diagnosis was pathologically confirmed in 9 of 14 patients diagnosed with cT3 who underwent radical surgery. 20 of 26 cases diagnosed with cT4b received definitive chemoradiotherapy, and 4 cases received salvage surgery and pathologically confirmed precise diagnosis. CONCLUSION: CP-EBUS is extremely useful for diagnosing the tracheobronchial invasion of advanced esophageal cancer. It could be an effective modality for determining treatment strategies in cases with a marginal surgical indication.
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Neoplasias Esofágicas , Neoplasias Pulmonares , Broncoscopia , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Humanos , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVE: CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis. METHODS: Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics. RESULTS: We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001). CONCLUSION: CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.
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Broncoscopia , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X/métodos , Humanos , Pontuação de Propensão , Estudos RetrospectivosRESUMO
Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.
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Cromatos/efeitos adversos , Metilação de DNA/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Proteína 1 Homóloga a MutL/genética , Idoso , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Humanos , Instabilidade de Microssatélites/efeitos dos fármacos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/efeitos dos fármacosRESUMO
BACKGROUND: pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. METHODS: We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. RESULTS: Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). CONCLUSIONS: The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.
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Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Fatores de Risco , Carga TumoralRESUMO
BACKGROUND: Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low. OBJECTIVES: This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT). METHODS: Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B. RESULTS: Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay. CONCLUSIONS: Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.
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Broncoscopia/instrumentação , Biópsia Guiada por Imagem/métodos , Radiografia Intervencionista/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Broncoscopia/estatística & dados numéricos , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Biópsia Guiada por Imagem/instrumentação , Biópsia Guiada por Imagem/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia Intervencionista/estatística & dados numéricos , Radiografia TorácicaRESUMO
BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.
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Neoplasias Esofágicas/cirurgia , Trato Gastrointestinal/fisiopatologia , Estado Nutricional/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Adrenomedulina/sangue , Idoso , Proteína C-Reativa/metabolismo , Defecação/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Esofagectomia/efeitos adversos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Panax , Extratos Vegetais/uso terapêutico , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Albumina Sérica/metabolismo , Redução de Peso/efeitos dos fármacos , Zanthoxylum , ZingiberaceaeRESUMO
Malignant pleural mesothelioma sometimes accompanies intractable neumothorax due to the visceral pleural invasion of the tumor. A 68-years-old man was found to have massive pleural effusion and pleural mass combined with pneumothorax by computed tomography(CT). CT guided biopsy revealed the mass to be malignant pleural mesothelioma. Since continuous air leakage was observed by chest drainage, pleurodesis by OK-432 twice and bronchial occlusion by Endobronchial Watanabe Spigot (EWS)were performed. But air leakage continued, and the surgery was performed, however the treatment failed to stop the air leakage. Finally, the intrapleural administration of diluted fibrin glue was challenged and the air leakage stopped immediately after the treatment.
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Adesivo Tecidual de Fibrina/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Mesotelioma/diagnóstico por imagem , Pneumotórax/terapia , Adesivos Teciduais/uso terapêutico , Idoso , Biópsia , Drenagem , Evolução Fatal , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/complicações , Mesotelioma/patologia , Mesotelioma Maligno , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Recidiva , Tomografia Computadorizada por Raios XRESUMO
Despite advances in science and technology, lung cancer remains a major public health issue. The discovery of early diagnostic and prognostic markers is still needed to reduce the mortality rate of lung cancer, which is the highest among all cancer types. Aberrations in the DNA methylation system have an important role in human cancer and are promising for the development of early diagnostic and prognostic markers. The present study focused on zinc finger protein (ZNF)577, whose encoding gene was indicated to exhibit promoter hypermethylation together with 9 other genes in lung adenocarcinoma (LADC) in a previous study by our group. ZN577 is a member of the ZNG family and its functional role has so far remained elusive. LADC tissue samples surgically resected at Tokushima University Hospital (Tokushima, Japan) between April 1999 and November 2013 were collected. A total of 73 tumors and 27 paired tumor-adjacent normal tissues were examined for DNA methylation and mRNA expression of ZNF577. A total of 149 LADC tissue samples were collected and evaluated by immunohistochemistry (IHC) for the tissue expression of ZNF577. High methylation (n=27, P<0.0001) and low mRNA expression levels (n=27, P<0.031) of ZNF577 were identified in LADC tissues, and it was demonstrated that methylation levels were inversely correlated with mRNA expression levels (P=0.0116, ρ=-0.2515). Among the LADC tissues, lepidic-patterned samples had lower methylation levels of ZNF577 than other pathological types. In addition, mRNA expression levels of ZNF577 were significantly higher in females, non-smokers and stage I samples. Overall survival [P<0.0001; area under curve (AUC)=0.8658] and disease-free survival (DFS; P<0.0004; AUC=0.7232) rates were significantly higher in the ZNF577 high mRNA expression group than in the ZNF577 low mRNA expression group. Among the 149 LADC samples examined by IHC, 105 were negative and 44 were positive for the tissue expression of ZNF577. Cox regression analysis showed poorer DFS (hazard ratio: 3.917; P=0.023) in patients with lower expression of ZNF577. In conclusion, higher methylation levels of ZNF577 were observed in LADC tissues than in normal lung tissue and low mRNA expression of ZNF577 was associated with unfavorable prognosis.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Biomarcadores Tumorais , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , RNA Mensageiro , Humanos , Feminino , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Prognóstico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Idoso , Pessoa de Meia-Idade , RNA Mensageiro/genética , Regiões Promotoras Genéticas , Adulto , Idoso de 80 Anos ou maisRESUMO
Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of NPTX2 were examined. The DNA methylation rate of the NPTX2 gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of NPTX2 was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high NPTX2 DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.
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BACKGROUND: Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported. CASE PRESENTATION: A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications. CONCLUSION: The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.
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Doença Relacionada a Imunoglobulina G4 , Neoplasias do Mediastino , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/diagnóstico , Doença Relacionada a Imunoglobulina G4/cirurgia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Toracoscopia/métodos , Tomografia Computadorizada por Raios XRESUMO
Background: Although thyroid tumors with tracheal stenosis are occasionally encountered, severe tracheal stenosis caused by benign thyroid tumors is rare. We herein describe a case in which a silicone tracheal stent was placed for severe tracheal stenosis induced by a giant goiter due to Graves' disease. Case Description: A 93-year-old woman had been receiving thiamazole treatment for Graves' disease with a thyroid goiter for 32 years. She emergently presented to the hospital with sudden difficulty breathing and the temporary loss of consciousness. Although marked stridor was heard, the patient's respiratory status was stable in the first visit. Computed tomography revealed a giant thyroid goiter that extended to the mediastinum. The trachea was compressed by the sternal notch and thyroid gland, resulting in severe stenosis, and the tracheal lumen was only 1 mm. Surgical thyroidectomy was expected to be difficult due to the high risk of complications associated with the large size of the goiter and advanced age of the patient. Therefore, we decided to place a tracheal stent. A silicone stent (Dumon tube®) was inserted into the site of tracheal stenosis under general anesthesia. After stent placement, respiratory distress symptoms improved, and no complications were observed. Three months after stent placement, the stent opening side was narrowed due to defective granulation and, thus, was cauterized with argon plasma coagulation. Conclusions: We encountered a patient who was treated by tracheal silicone stent placement for severe tracheal stenosis induced by a giant goiter due to Graves' disease. A silicone stent effectively secures the airway for benign thyroid tumors that cause severe airway stenosis.
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BACKGROUND: We previously reported that S-1 and low-dose docetaxel (DOC) (N-1 study, phase II trial) could be a well-tolerated and effective neoadjuvant chemotherapies (NACs) for patients with operable breast cancer. Herein, we analyzed the long-term outcomes and developed clinicopathological and molecular predictors of pathological complete response (pCR). PATIENTS AND METHODS: Eighty-three patients received S-1 (40 mg/m2 orally on days 1-14) and DOC (40 mg/m2 intravenously on day 1) every 3 weeks for 4 to 8 cycles. Disease-free survival (DFS) and overall survival (OS) were analyzed for each population with a pCR status. To assess the relationship between pCR and clinicopathological factors such as tumor-infiltrating lymphocytes (TILs, 1+ <10%, 2+ 10%-50%, and 3+ >50%) and nuclear grade (NG), microarray was used to compare the microRNA profiles of the pCR and non-pCR groups using core needle biopsy specimens. RESULTS: With a median follow-up duration of 99.0 (range, 9.0-129.0) months, the 5-year DFS and OS rates were 80.7% and 90.9%, respectively. The 5-year OS rate of the pCR group was significantly better than that of the non-pCR group (100% vs. 86.2%, p = .0176). Specifically, in triple-negative patients, the difference was significant (100% vs. 60.0%, p = .0224). Multivariate analysis revealed that high TILs (≥2-3+) and NG 2-3 independently predicted pCR. Microarray data revealed that 3 miRNAs (miR-215-5p, miR-196a-5p, and miR-196b-5p) were significantly upregulated in the pCR group. CONCLUSION: Our NAC regimen achieved favorable long-term outcomes and significantly improved OS in the pCR group. High TILs, NG 2-3, and some miRNAs may be predictors of pCR.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Docetaxel , Combinação de Medicamentos , Terapia Neoadjuvante , Ácido Oxônico , Tegafur , Humanos , Feminino , Docetaxel/administração & dosagem , Terapia Neoadjuvante/métodos , Ácido Oxônico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Tegafur/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Adulto , Idoso , Linfócitos do Interstício Tumoral/imunologia , Seguimentos , Taxoides/administração & dosagem , Intervalo Livre de Doença , Resultado do Tratamento , Prognóstico , MicroRNAs/genéticaRESUMO
UNLABELLED: The diagnostic potential of histological atypia grades in distinguishing between primary lung tumors and renal pulmonary metastases. OBJECTIVE: In cases of pulmonary resection for renal cell carcinoma patients, both the preoperative and perioperative diagnosis of lung cancer may be complicated by the need to distinguish between a primary lung tumor and metastatic renal tumor. The degree of histological atypia (grade) of the suspected metastatic focus may indicate the source of the lesion. The aim of this study was to evaluate the preoperative and perioperative diagnostic potential of histological atypia in determining the origin of lung tumors. STUDY DESIGN: Five cases that involved surgery for suspected lung metastasis from renal cell carcinoma were investigated. RESULTS: In cases for which the precise diagnosis of the metastatic focus was uncertain, histological atypia of the metastatic focus was of grade 3, whereas that of the primary renal cancer was of grade 1 or 2. CONCLUSION: These findings suggest that lung metastases with grade 3 histological atypia are suspected to be primary lung tumors on the basis of preoperative imaging, and preoperative distinction between primary lung tumors and metastases from renal cell carcinoma is therefore difficult. In such cases, the choice of operative method needs to be very carefully considered.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Gradação de Tumores , Neoplasias Primárias Múltiplas/patologia , Pneumonectomia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Período Pré-OperatórioRESUMO
Introduction: The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Methods: Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. Results: The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Conclusions: Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.
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Background: Multimodal transbronchial biopsy (TBB) may have improved diagnostic yield for peripheral pulmonary lesions suspected as lung cancer. Radial endobronchial ultrasound (R-EBUS) provides real-time imaging and confirmation of the location of the lesions. Cone-beam computed tomography (CBCT) can confirm that the forceps tip has reached the lesion before biopsy. Methods: Patients with peripheral pulmonary lesions and a positive computed tomography (CT) bronchus sign (based on slice thickness of 1 mm) were prospectively enrolled. An ultrathin bronchoscope (UTB) and R-EBUS probe were advanced to the target bronchus. Thereafter, forceps were advanced, and CBCT was performed. R-EBUS was performed for re-navigation, if possible. The obtained EBUS and CBCT images were classified into "within" (type 1), "adjacent to" (type 2), or "far from" (type 3), based on the probe or forceps tip. Results: For 20 lesions, the diagnostic yield was 85%. The primary EBUS images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. The primary CBCT images were of types 1, 2, and 3 in 12, 6, and 2 cases, respectively. Primary EBUS and CBCT image types were equivalent in 14 cases. Of the 12 cases with type 1 primary EBUS image, 9 cases had a type 1 primary CBCT image, while 3 cases exhibited positional misalignment of the forceps tip. Re-navigation was required in 8 cases with types 2 and 3 primary CBCT images. Conclusions: CBCT-guided TBB using an UTB and EBUS may enable real-time positioning guidance and better re-navigation in the diagnosis of peripheral pulmonary lesions.
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We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 (DPP6) has been identified as the most significantly hypermethylated CGI in LADC. DPP6 is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that DPP6 is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper- and hypomethylation, respectively. The present study investigated the methylation and expression levels of DPP6 and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of DPP6 in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of DPP6 were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in DPP6 were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.
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OBJECTIVE: Patients with lung cancer generally undergo minimally invasive surgery, such as video-assisted thoracoscopic surgery (VATS). This study examined the changes in health conditions and symptoms of patients with lung cancer using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ) C-30 questionnaires after surgery. METHODS: This was a longitudinal descriptive study. One hundred and three patients with lung cancer who underwent lung resection at Tokushima University Hospital between 2012 and 2021 were eligible. They completed EORTC QLQ-C30, QLQ-LC13, the Cancer Dyspnea scale (CDS), and pulmonary-ADL (P-ADL) before and 1, 3, and 6 months after surgery. RESULTS: Regarding functional scale scores, impairments in physical and role functions persisted for 6 months after surgery. In symptom scale scores, fatigue, pain, dyspnea, and appetite loss continued for 6 months after surgery. In CDS, sense of effort, discomfort, and total dyspnea scale scores were elevated for 6 months after surgery. In P-ADL, most ADL were impaired 1 month after surgery, but recovered by 3 months. The dyspnea index of ADL was lower for 6 months after surgery. CONCLUSIONS: Impairments in health conditions and symptoms persisted for 6 months after surgery despite its minimally invasive nature. J. Med. Invest. 70 : 388-402, August, 2023.