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1.
Jpn J Clin Oncol ; 54(2): 121-128, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-37952098

RESUMO

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.


Assuntos
Carcinoma Adenoide Cístico , Carcinoma Mucoepidermoide , Neoplasias Pulmonares , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Neoplasias Pulmonares/patologia , Glândulas Salivares/patologia , Pulmão/patologia , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/patologia , Carcinoma Mucoepidermoide/cirurgia
2.
Surg Today ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691222

RESUMO

PURPOSES: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. METHODS: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. RESULTS: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. CONCLUSIONS: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

3.
Ann Surg Oncol ; 30(6): 3781-3788, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36847957

RESUMO

BACKGROUND: Many inflammatory and nutritional markers have been used to predict prognosis in lung cancer. The C-reactive protein (CRP)-to-lymphocyte ratio (CLR) is a useful prognostic factor in various cancers. However, the prognostic value of preoperative CLR in patients with non-small cell lung cancer (NSCLC) remains to be established. We examined the significance of the CLR compared with known markers. METHODS: A total of 1380 surgically resected NSCLC patients treated at two centers were recruited and divided into derivation and validation cohorts. After CLRs were calculated, patients were classified into high and low CLR groups based on the cutoff value determined by receiver operating characteristics curve analysis. Subsequently, we determined the statistical associations of the CLR with clinicopathological factors and prognosis and further analyzed its prognostic impact by propensity-score matching. RESULTS: Of all the inflammatory markers examined, CLR yielded the highest area-under-the-curve value. The prognostic impact of CLR remained significant after propensity-score matching. Prognosis was significantly worse in the high-CLR group than in the low-CLR group (5-year, disease-free survival [DFS]: 58.1% vs. 81.9%, P < 0.001; 5-year overall survival [OS]: 72.1% vs. 91.2%, P < 0.001). The results were confirmed in the validation cohorts. Multivariable analysis also showed high CLR as an independent factor for both DFS and OS (DFS: hazard ratio [HR] 1.42, P = 0.027; OS: HR 1.95, P = 0.0037). CONCLUSIONS: Preoperative CLR is a useful marker for predicting the prognosis of NSCLC patients who have undergone surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/patologia , Proteína C-Reativa/metabolismo , Pontuação de Propensão , Linfócitos/patologia , Estudos Retrospectivos
4.
Invest New Drugs ; 41(1): 168-172, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36331673

RESUMO

BACKGROUND: The efficacy and safety of the anti-EGFR antibody necitumumab combined with gemcitabine and cisplatin (N + GC) in the first-line treatment of advanced lung squamous cell carcinoma (LSCC) have been proven. However, the efficacy and safety of N + GC in the second line or later treatment remain unclear. METHODS: Eleven patients who received N + GC for advanced-stage or recurrent LSCC were enrolled. We retrospectively assessed the patients' clinical characteristics and efficacy and safety of treatment. RESULTS: The median patient age was 73 years (range, 63-77 years). The cohort included nine (81.8%) men and two (18.2%) women. Two (18.2%) patients had postoperative recurrence, and one (9.1%), three (27.3%), one (9.1%), and four (36.4%) patients were diagnosed with stage IIIA, IIIB, IVA, and IVB disease, respectively. Concerning the best overall response, partial response was achieved in five (45.5%) patients, four (36.4%) patients displayed stable disease, and two (18.2%) patients were not evaluable. Median progression-free survival was 6.8 months (range, 1.4-10.3 months). The grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in six (54.5%), three (27.3%), and two (18.2%) patients, respectively. Additionally, grade 3 skin reaction, rash, lung infection, duodenal ulcer, and febrile neutropenia were observed in one (9.1%) patient each. Two (18.2%) patients required treatment interruption because of adverse events. CONCLUSION: N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Gencitabina , Cisplatino/efeitos adversos , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Resultado do Tratamento , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Pulmão/patologia
5.
BMC Cancer ; 22(1): 503, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524214

RESUMO

BACKGROUND: Many studies have recently reported the association of concomitant medications with the response and survival in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy. However, the clinical impact of statin therapy on the outcome of cancer immunotherapy in patients with NSCLC is poorly understood. METHODS: In our database, we retrospectively identified and enrolled 390 patients with advanced or recurrent NSCLC who were treated with anti-programmed cell death-1 (PD-1) monotherapy in clinical practice between January 2016 and December 2019 at 3 medical centers in Japan to examine the clinical impact of statin therapy on the survival of patients with NSCLC receiving anti-PD-1 monotherapy. A propensity score-matched analysis was conducted to minimize the bias arising from the patients' backgrounds. RESULTS: The Kaplan-Meier curves of the propensity score-matched cohort showed that the overall survival (OS), but not the progression-free survival (PFS), was significantly longer in patients receiving statin therapy. However, a Cox regression analysis in the propensity score-matched cohort revealed that statin therapy was not an independent favorable prognostic factor, although it tended to be correlated with a favorable outcome. CONCLUSIONS: Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. These findings should be validated in further prospective studies with larger sample sizes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Pontuação de Propensão , Estudos Prospectivos , Estudos Retrospectivos
6.
Int J Cancer ; 149(2): 473-482, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720422

RESUMO

The gastrointestinal microbiota was reported as an important factor for the response to cancer immunotherapy. Probiotics associated with gastrointestinal dysbiosis and bacterial richness may affect the efficacy of cancer immunotherapy drugs. However, the clinical impact of probiotics on the efficacy of cancer immunotherapy in patients with nonsmall cell lung cancer (NSCLC) is poorly understood. The outcomes of 294 patients with advanced or recurrent NSCLC who received antiprogrammed cell death-1 (PD-1) therapy (nivolumab or pembrolizumab monotherapy) at three medical centers in Japan were analyzed in our study. We used inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves showed that progression-free survival (nonuse vs use: hazard ratio [HR] [95% confidence interval {CI}] = 1.73 [1.42-2.11], log-rank test P = .0229), but not overall survival (nonuse vs use: HR [95%CI] = 1.40 [1.13-1.74], log-rank test P = .1835), was significantly longer in patients who received probiotics. Moreover, the IPTW-adjusted univariate analyses showed that nonuse or use of probiotics was significantly associated with disease control (nonuse vs use: odds ratio [OR] [95%CI] = 0.51 [0.35-0.74], P = .0004) and overall response (nonuse vs use: OR [95%CI] = 0.43 [0.29-0.63], P < .0001). In this multicenter and retrospective study, probiotics use was associated with favorable clinical outcomes in patients with advanced or recurrent NSCLC who received anti-PD-1 monotherapy. The findings should be validated in a future prospective study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Probióticos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Sinergismo Farmacológico , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/genética , Masculino , Mutação , Recidiva Local de Neoplasia , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Probióticos/farmacologia , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
7.
Cancer Immunol Immunother ; 70(6): 1745-1753, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33389013

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become a standard therapy in non-small cell lung cancer (NSCLC). Although lung cancer adjoining emphysematous bullae (Ca-ADJ) were reported to express higher programmed cell death-ligand 1 (PD-L1), the predictive impact of Ca-ADJ on the response to ICIs is unknown. METHODS: Two hundred and fifty-seven advanced or recurrent NSCLC patients treated with ICI monotherapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients' background, adjusted Kaplan-Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. RESULTS: Of the 257 patients, 55 had Ca-ADJ. Patients with Ca-ADJ were significantly associated with younger age (P = 0.0343), male sex (P = 0.0070), and smoking (P = 0.0080). The objective response rate of cases with Ca-ADJ was significantly higher than that of those without Ca-ADJ (36.4% vs. 20.8%, respectively; P = 0.0167). The disease control rate of cases with Ca-ADJ was also significantly higher than tumors without Ca-ADJ (63.6% vs. 47.5%, respectively; P = 0.0341). The IPTW-adjusted Kaplan-Meier curves showed that patients with Ca-ADJ had significantly longer progression-free survival (PFS) and overall survival (OS) than those without Ca-ADJ (P = 0.0407 and P = 0.0126, respectively). On IPTW-adjusted Cox analysis, Ca-ADJ was an independent predictor of PFS and OS (P < 0.0001 and P < 0.0001, respectively). CONCLUSIONS: Patients with Ca-ADJ may be good candidates for ICIs. These findings should be validated prospectively.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/mortalidade , Enfisema Pulmonar/mortalidade , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Enfisema Pulmonar/complicações , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/patologia , Estudos Retrospectivos , Taxa de Sobrevida
8.
Ann Surg Oncol ; 28(6): 3046-3054, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33084992

RESUMO

BACKGROUND: Three immune-nutritional parameters exist for malignant tumors using serum C-reactive protein (CRP) and albumin: the Glasgow prognostic score (GPS), the modified GPS (mGPS), and the CRP-albumin ratio (CAR). However, it remains unclear which of the three parameters is the most predictive of prognosis. Therefore, this study compared the clinical and prognostic significance of these parameters for non-small cell carcinoma (NSCLC). METHODS: The study retrospectively enrolled 596 NSCLC patients who underwent surgical resection at the authors' institution from January 2010 to December 2015 and investigated the clinicopathologic significance of GPS, mGPS, and CAR. The optimal cutoff value for CAR was determined by a receiver operating curve (ROC). RESULTS: The median age of the patients was 69 years. Lymph node metastases were identified in 99 patients, and 455 patients had a diagnosis of stage 1 disease. The positivity for GPS was 7.6%, and that of mGPS (score, 1 or 2) was 12.2%. Of the 596 patients, 480 patients (80.5%) were classified in the high CAR group. In univariate survival analyses, all three parameters were associated significantly with postoperative survival. The multivariate analyses showed CAR to be an independent prognostic factor. Additionally, survival analyses of the stage 1 subgroup were performed because CAR was higher for patients with an advanced stage of disease or lymph node metastases. In these subgroup analyses, CAR also was an independent prognostic factor. CONCLUSION: As the most prognostic index, CAR may be useful among the immunonutritional parameters using CRP and albumin for resected NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Albuminas , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Prognóstico , Estudos Retrospectivos
9.
Ann Surg Oncol ; 28(2): 685-694, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32676867

RESUMO

BACKGROUND: The pack-year index, which is calculated by multiplying a smoking period by the number of cigarette packs smoked per day, is frequently used to investigate the risk of developing lung cancer. Notably, however, whether the smoking period or the number of packs per day is more predictive of postoperative prognosis remains unclear in non-small cell lung cancer (NSCLC) patients who receive curative lung resection. PATIENTS AND METHODS: Initial screening included 2055 consecutive lung cancer patients who had underwent curative lung resection between 2000 and 2016 at a single center in Japan. Data from 1134 NSCLC patients with smoking history were ultimately analyzed. Time-dependent areas under the curve (AUCs) were used to compare diagnostic accuracy. RESULTS: On univariate analysis, the number of packs smoked per day was not a significant predictor of disease-free survival (DFS; p = 0.2387) or overall survival (OS; p = 0.1357). On multivariable analysis, smoking period was an independent predictor of DFS and OS (both p < 0.0001). Time-dependent smoking period AUCs were superior to those of number of packs smoked per day. On subgroup analyses, patients with a smoking period ≥ 40 years had significantly shorter DFS and OS than those with a smoking period of < 40 years, independent of sex, clinical stage, and histological type. CONCLUSIONS: Smoking period was a significant prognostic indicator in NSCLC patients who underwent curative lung resection, which should be validated in further prospective and/or multicenter studies with large sample sizes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Japão , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fumar/efeitos adversos
10.
Int J Cancer ; 147(8): 2327-2334, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32356560

RESUMO

Immunotherapy targeting programmed cell death-1 (PD-1) has become a standard pharmacological therapy. Although tumor mutation burden level was reported to depend on the tumor location in nonsmall cell lung cancer (NSCLC), predictive impact of the tumor location on the response to anti-PD-1 therapy is unknown. Two hundred and seventeen advanced or recurrent NSCLC patients treated with anti-PD-1 therapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients' background, adjusted Kaplan-Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. Of the 217 patients, 132, 27, and 58 had primary NSCLC in upper, middle, and lower lobes, respectively. Patients with NSCLC in upper lobe were significantly associated with younger age (P = .0070) and smoker (P = .0003). The epidermal growth factor receptor-wild type and tumor location in upper lobe were independent predictors of disease control (P = .0175 and P = .0425, respectively). The IPTW-adjusted Kaplan-Meier curves showed that patients with NSCLC in the upper lobes had significantly longer progression-free survival (PFS) and overall survival (OS) than those in middle/lower lobes (P = .0026 and P = .0015, respectively). On IPTW adjusted Cox analysis, NSCLC in the upper lobe was an independent predictor of PFS and OS (P = .0078 and P = .0034, respectively). Patients with primary NSCLC in the upper lobes may be good candidates for anti-PD-1 therapy. These findings should be validated prospectively.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/imunologia , Idoso , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/parasitologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Intervalo Livre de Progressão
11.
Ann Surg Oncol ; 26(5): 1544-1551, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30798450

RESUMO

BACKGROUND: CD44 isoforms serve as a marker for cancer stem cells. CD44 variant 9 (CD44v9) contributes to the defense against reactive oxygen species, resulting in resistance to chemoradiotherapy. However, the significance of CD44v9 in patients with lung adenocarcinoma is unknown. METHODS: We used immunohistochemical analysis to retrospectively analyze CD44v9 expression in 268 surgically resected lung adenocarcinomas and investigated the association between CD44v9 expression and patients' clinicopathological features. RESULTS: The expression of CD44v9 in 193 of 268 (72.0%) patients was significantly associated with early-stage cancer, low-grade tumors, absence of vessel and pleural invasion, and a mutated epidermal growth factor receptor (EGFR) gene. Multivariate logistic analysis revealed that CD44v9 expression was significantly associated with early-stage disease [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.14-0.59; p < 0.001] and mutant EGFR (OR 2.53, 95% CI 1.06-6.04; p = 0.036). The percentage of CD44v9-positive tumors was higher in the earlier stages of disease; however, there was no significant difference in the survival of patients in each stage of disease who had positive or negative CD44v9 expression. CONCLUSION: CD44v9 was highly expressed in EGFR-mutant tumors, particularly in early-stage lung adenocarcinoma, suggesting that CD44v9 expression may play an important role in EGFR-mutant tumors.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Receptores de Hialuronatos/metabolismo , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Isoformas de Proteínas , Estudos Retrospectivos , Taxa de Sobrevida
12.
Ann Surg Oncol ; 26(6): 1916-1924, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30815801

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression on lung cancer cells is a prognostic marker and a predictive biomarker for response to immunotherapy. However, previous clinical trials have suggested that other programmed cell death 1 ligands, including programmed death-ligand 2 (PD-L2), might have clinical impacts. This study aimed to analyze the prognostic significance of PD-L2 expression in lung adenocarcinoma patients. METHODS: The study included 433 patients who underwent surgical resection for lung adenocarcinoma between 2003 and 2012 at Kyushu University Hospital. Both PD-L1 and PD-L2 expression were evaluated by immunohistochemistry. The cutoff value for PD-L2 positivity was set at 1% according to a time-dependent receiver operating characteristic curve for 5-year survival. RESULTS: Of the 433 patients, 306 (70.7%) were positive for PD-L2. No significant association between PD-L1 and PD-L2 expression was observed (P = 0.094). The multivariate analysis showed that the independent predictors of PD-L2 positivity were never-smoker status (P = 0.002), poor differentiation grade (P = 0.008), and advanced stage (P = 0.048). The PD-L2-positive patients had significantly shorter disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016). Both PD-L1 and PD-L2 positivity were independent predictors of OS (P < 0.001 and P = 0.027, respectively). In the subgroup analysis of the PD-L1-negative patients, PD-L2 positivity was significantly associated with shorter DFS (P = 0.018). CONCLUSIONS: The study demonstrated that the clinical characteristics of patients with PD-L1 expression may differ from those of patients with PD-L2 expression, and that both might contribute to poor prognoses. The potential role of PD-L2 expression as a predictive biomarker for response to immunotherapy should be investigated in future studies.


Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Ann Surg Oncol ; 26(6): 1925-1933, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30815803

RESUMO

BACKGROUND: Immunotherapy targeting programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has shown dramatic therapeutic effects for lung squamous cell carcinoma (SCC), and PD-L1 expression has been shown not only to be a predictive biomarker for response to immunotherapy but also a prognostic factor for lung SCC. However, the clinical significance of programmed death-ligand 2 (PD-L2), another PD-1 ligand, remains unclear. Therefore, we analyzed PD-L2 expression by immunohistochemistry in surgically resected primary lung SCC. PATIENTS AND METHODS: PD-L1 and PD-L2 expression on tumor cells were analyzed in 211 primary lung SCC specimens by immunohistochemistry. Additionally, numbers of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes were also examined. RESULTS: The rates of positive PD-L2 expression were 77.3% and 67.3% using 5% and 10% cut-off values, respectively. Low PD-L2 expression on tumor cells was statistically associated with histological type (non-keratinizing/keratinizing) and lymphatic invasion. PD-L2-positive patients had significantly longer postoperative survival time (log-rank test; p = 0.0170 at 5% cut-off and p = 0.0500 at 10% cut-off). Furthermore, survival analysis according to PD-L1 and PD-L2 expression revealed that PD-L1-positive and PD-L2-negative patients had the most unfavorable prognosis. CONCLUSIONS: PD-L2 protein expression was associated with prognosis in primary lung SCC patients. PD-L2 expression might be a potential biomarker for response to PD-1/PD-L1-targeted immunotherapy, which should be investigated in future studies.


Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Int J Clin Oncol ; 24(11): 1333-1349, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31522313

RESUMO

INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.


Assuntos
Neoplasias Colorretais/diagnóstico , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Animais , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/terapia , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Cães , Neoplasias Esofágicas/cirurgia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Humanos , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/terapia , Cuidados Pós-Operatórios , Receptores CXCR4/metabolismo , Procedimentos de Cirurgia Plástica/métodos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
15.
Thorac Cardiovasc Surg ; 67(2): 147-150, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28582790

RESUMO

BACKGROUND: Pleuroperitoneal communication is a serious complication in patients receiving continuous ambulatory peritoneal dialysis. However, few single-institutional reports discuss the details of pleuroperitoneal communication in continuous ambulatory peritoneal dialysis patients regarding the intraoperative findings, postoperative course, and outcomes. METHODS: We retrospectively reviewed the records of consecutive pleuroperitoneal communication patients who were treated surgically from September 2008 to March 2016. RESULTS: All four patients had right-sided hydrothorax. The time from introduction of continuous ambulatory peritoneal dialysis to the diagnosis of hydrothorax ranged from 1 to 12 months (average: 5.5 months). Case 1 and case 4 had bleblike lesions near the center of the diaphragm; case 2 had a small hole located near the cardiophrenic angle, and case 3 had thinning of the diaphragm near the cardiophrenic angle. All lesions except for case 3 were directly closed with absorbable suture and reinforced by fibrin glue and a polyglycolic acid sheet. In case 3, the thinned diaphragm was reinforced using fibrin glue, a sealing sheet, and pericardial fat pad tissue. Continuous ambulatory peritoneal dialysis was reinitiated an average period of 11 days (range: 4-15 days) postoperatively. During postoperative follow-up, there was no recurrence of hydrothorax. Continuous ambulatory peritoneal dialysis was continued for an average of 16.7 months (range: 3-34 months) after surgical treatment. CONCLUSIONS: Surgical treatment for pleuroperitoneal communication is a safe and acceptable procedure and could greatly benefit continuous ambulatory peritoneal dialysis patients.


Assuntos
Hidrotórax/cirurgia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Doenças Peritoneais/cirurgia , Doenças Pleurais/cirurgia , Adolescente , Idoso , Humanos , Hidrotórax/diagnóstico , Hidrotórax/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Peritoneais/diagnóstico , Doenças Peritoneais/etiologia , Doenças Pleurais/diagnóstico , Doenças Pleurais/etiologia , Estudos Retrospectivos , Resultado do Tratamento
17.
Ann Surg Oncol ; 25(6): 1555-1563, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29500763

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM), a devastating neoplasm, is traditionally considered to be resistant to antitumor therapy. Identification of clinical prognostic indicators is therefore needed. Although the C-reactive protein/albumin ratio (CAR) has been used to predict the prognosis of many types of malignancy, its utility in patients with MPM is unknown. METHODS: The data of 100 patients diagnosed as having MPM from 1995 to 2015 at the National Kyushu Cancer Center and Kyushu University were analyzed. The CAR was calculated as serum C-reactive protein concentration divided by albumin concentration. A cutoff for CAR was set at 0.58 according to a receiver operating characteristics curve for 1-year survival. RESULTS: Thirty-five of the 100 (35.0%) patients were classified as having a high CAR. A high CAR was significantly associated with advanced clinical stage (p < 0.001) and chemotherapy alone (p = 0.002). Patients with a high CAR had significantly shorter overall survival (OS) (p < 0.001) and disease- or progression-free survival (DFS/PFS) (p < 0.001). These associations between CAR and prognosis remained significant after propensity score-matching. In multivariate analysis, a high CAR was an independent predictor of shorter OS and DFS/PFS (p = 0.003 and p = 0.008, respectively). Multivariate analyses of the subgroups of patients who had received chemotherapy and of patients who had undergone surgery also showed that a high CAR was an independent predictor of shorter OS and DFS/PFS. CONCLUSIONS: CAR is an independent predictor of prognosis in MPM patients. This prognostic index contributes to clinicians' ability to predict benefit from treatment. Further larger, prospective studies are necessary to validate these findings.


Assuntos
Proteína C-Reativa/metabolismo , Mesotelioma/sangue , Neoplasias Pleurais/sangue , Albumina Sérica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pleurais/patologia , Neoplasias Pleurais/terapia , Prognóstico , Intervalo Livre de Progressão , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
18.
Ann Surg Oncol ; 25(5): 1229-1236, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29327178

RESUMO

BACKGROUND: A relationship between sarcopenia diagnosed by skeletal muscle area (SMA) and poor prognosis in cancer patients has recently been reported. This study aimed to clarify the clinical significance of postoperatively decreased SMA in patients with early non-small cell lung cancer (NSCLC). METHODS: This study selected 101 patients with pathologic stage 1 NSCLC who had undergone pre- and postoperative (~ 1 year) computed tomography scans and lobectomy between 2005 and 2010 at Kyushu University Hospital. The post/pre ratio was defined as the postoperative normalized SMA (cm2/m2) at the 12th thoracic vertebra level divided by the preoperative normalized SMA. The cutoff value for the post/pre ratio was set at 0.9. RESULTS: The study classified 31 patients (30.7%) as having decreased SMA. Poor performance status (PS) was significantly associated with decreased SMA (p = 0.048). The patients with decreased SMA had a significantly shorter disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001) than the other patients. Decreased SMA was found to be an independent prognostic factor for DFS (p = 0.010) and OS (p = 0.0072). The independent risk factors for skeletal muscle loss included poor PS (PS ≥ 1) and obstructive ventilatory impairment [forced expiratory volume (FEV) 1% < 70%]. CONCLUSIONS: Skeletal muscle loss after surgery is significantly associated with postoperative poor outcomes for patients with early NSCLC. Patients with poor PS, obstructive ventilatory impairment, or both need careful support to maintain their skeletal muscle mass. Future prospective studies may clarify whether physical activity and nutritional support improve postoperative prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Músculo Esquelético/patologia , Sarcopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/fisiopatologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Período Pós-Operatório , Período Pré-Operatório , Fatores de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
19.
Fukuoka Igaku Zasshi ; 107(7): 136-40, 2016 07.
Artigo em Japonês | MEDLINE | ID: mdl-29226664

RESUMO

We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on the second day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primary lung cancer was referred to our department for surgery. The second day after left lung segmentectomy, she showed respiratory discomfort symptoms and exhibited hoarseness and stridor, which were revealed as the subglottic stenosis by bronchoscopy. During the emergency airway management, she went into cardiopulmonary arrest. We performed cardiopulmonary resuscitation and simultaneous urgent tracheotomy.


Assuntos
Parada Cardíaca/etiologia , Laringoestenose/terapia , Complicações Pós-Operatórias , Idoso , Feminino , Humanos , Pneumonectomia/efeitos adversos , Traqueotomia , Resultado do Tratamento
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