Ikuo Kamiyama

Value of the Glasgow Prognostic Score as a Prognostic Factor in Resectable Non–Small Cell Lung Cancer

Background: Over the past decade, the Glasgow prognostic score (GPS), which is based on serum C‐reactive protein and albumin levels, has been reported to be associated with the prognosis of patients with several types of inoperable and operable cancers. However, its applicability to operable non–small cell lung cancer (NSCLC) has not yet been established. Methods: We retrospectively collected data from patients with pathological stage I or II NSCLC who underwent complete resection. A total of 1048 patients were categorized as either GPS‐0 (n = 817 [78.0%]), GPS‐1 (184 [17.6%]), or GPS‐2 (47 [4.5%]). Survival curves were estimated using the Kaplan‐Meier method, and the Cox proportional hazard model was used to analyze the relationship between prognosis and GPS status. Results: The 5‐year overall survival (OS) rates were 91.2%, 78.3%, and 75.8% for GPS‐0, GPS‐1, and GPS‐2, respectively. There were significant differences in OS between GPS‐0 and GPS‐1 (p < 0.001) and between GPS‐0 and GPS‐2 (p < 0.001). Ten variables demonstrated to be associated with OS in a univariate analysis were subjected to a multivariate analysis. The results showed that male sex (p = 0.031), vascular invasion (p < 0.001), lymph node metastasis (p < 0.001), and GPS (p = 0.025) were significantly associated with OS. Conclusions: A high GPS is significantly associated with poor OS. Although the biological mechanism that underlies this association is not clear, this inflammation‐based score may be a useful indicator of the prognosis in patients with resectable NSCLC.

Prognostic significance of hypoxic PET using 18 F-FAZA and 62 Cu-ATSM in non-small-cell lung cancer

OBJECTIVES Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) (n=45) and/or (62)Cu-diacetyl-bis (N4)-methylsemithiocarbazone ((62)Cu-ATSM) (n=22). All received (18)F-fluorodeoxyglucose ((18)F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively. RESULTS A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of (18)F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs ((18)F-FAZA, p<0.01; (62)Cu-ATSM, p<0.04), but not with that of (18)F-FDG. The patients with a higher accumulation had significantly poorer overall survival [(18)F-FAZA, HR (hazard ratio), 9.50, p<0.01; (62)Cu-ATSM, HR, 4.06, p<0.05] and progression free survival ((18)F-FAZA, HR, 5.28, p<0.01, (62)Cu-ATSM, HR, 2.72, p<0.05). CONCLUSION Both (18)F-FAZA and (62)Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.

Original ArticleNon–Small Cell Lung CancerValue of the Glasgow Prognostic Score as a Prognostic Factor in Resectable Non–Small Cell Lung Cancer

Background: Over the past decade, the Glasgow prognostic score (GPS), which is based on serum C‐reactive protein and albumin levels, has been reported to be associated with the prognosis of patients with several types of inoperable and operable cancers. However, its applicability to operable non–small cell lung cancer (NSCLC) has not yet been established. Methods: We retrospectively collected data from patients with pathological stage I or II NSCLC who underwent complete resection. A total of 1048 patients were categorized as either GPS‐0 (n = 817 [78.0%]), GPS‐1 (184 [17.6%]), or GPS‐2 (47 [4.5%]). Survival curves were estimated using the Kaplan‐Meier method, and the Cox proportional hazard model was used to analyze the relationship between prognosis and GPS status. Results: The 5‐year overall survival (OS) rates were 91.2%, 78.3%, and 75.8% for GPS‐0, GPS‐1, and GPS‐2, respectively. There were significant differences in OS between GPS‐0 and GPS‐1 (p < 0.001) and between GPS‐0 and GPS‐2 (p < 0.001). Ten variables demonstrated to be associated with OS in a univariate analysis were subjected to a multivariate analysis. The results showed that male sex (p = 0.031), vascular invasion (p < 0.001), lymph node metastasis (p < 0.001), and GPS (p = 0.025) were significantly associated with OS. Conclusions: A high GPS is significantly associated with poor OS. Although the biological mechanism that underlies this association is not clear, this inflammation‐based score may be a useful indicator of the prognosis in patients with resectable NSCLC.

Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell Substitute

A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core–shell structured hemoglobin-albumin cluster designated as “HemoAct”, is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion.

Prognostic Factors Based on Clinicopathological Data Among the Patients with Resected Peripheral Squamous Cell Carcinomas of the Lung

Introduction: Although the incidence of peripheral squamous cell carcinomas (p-SqCCs) of the lung has increased over recent years, clinicopathological factors influencing prognosis of resected p-SqCCs remain unclear. Methods: We examined 280 patients who underwent complete resection of SqCCs and analyzed the clinicopathological features in relation to their overall survival (OS) and recurrence-free survival (RFS) according to the primary location. Results: Multivariate analysis of all stages of p-SqCCs patients revealed that high serum squamous cell carcinoma antigen (SCC) level (OS; p < 0.01, RFS; p < 0.01), vascular invasion (OS; p < 0.01, RFS; p < 0.01), pleural invasion (OS; p = 0.03, RFS; p = 0.01), nodal metastasis (OS; p = 0.02) and complication with lung disease (OS; p < 0.01) were independently unfavorable prognostic factors. Among stage I p-SqCCs patients, high serum SCC level (OS; p < 0.01, RFS; p < 0.01), vascular invasion (RFS; p < 0.01) and pleural invasion (RFS; p = 0.01) were also strongly correlated with poor prognosis independently. When we reevaluated the survival rate, T1 p-SqCCs with high serum SCC level or vascular invasion can be upgraded to T2a. Patients with stage IB had a significantly poorer prognosis than stage IA (5-year RFS; 61.4 % versus 76.6 %, p < 0.05). Conclusion: High serum SCC level, pleural and vascular invasions were independent poor prognostic factors for completely resected p-SqCCs. T1 p-SqCCs with high serum SCC level or vascular invasion should be upgraded to T2a, which accurately reflect survival status among patients with p-SqCCs.

Comprehensive Immune Profiling of Lung Adenocarcinomas Reveals Four Immunosubtypes with Plasma Cell Subtype a Negative Indicator

Lung cancer is a complex disease with variable outcomes. Immune cells from 114 cases were quantified immunohistochemically, identifying four immunosubtypes of lung adenocarcinoma (CD8, mast cell, macrophage/DC, and plasma cell) that could potentially be useful for therapy selection. Neoplastic cancer cells and cancer stroma (including infiltrating immune cells) determine the biology and prognosis of cancer. Various types of adaptive and innate immune cells are known to infiltrate the cancer stroma. However, the patterns and spatial distribution of immune cell infiltration as well as its association with tumor histology remain poorly understood. To address these issues, we comprehensively analyzed the infiltrating immune cells present in lung adenocarcinoma. The principal types of both adaptive and innate infiltrating immune cells were immunohistochemically evaluated in the predominant histologic components of 111 lung adenocarcinomas. The same analysis was also carried out on 143 samples of histologic subtypes making up more than 20% of tumors. As a result, plasma cells and B cells with interfollicular distribution were almost exclusively observed in invasive histologic subtypes, while an increased number of mast cells were observed in noninvasive histologic subtypes. Cluster analysis revealed four distinct immunosubtypes (CD8, mast cell, macrophage/dendritic cell, and plasma cell subtypes) based on the infiltrating immune cell profiles. These immunosubtypes correlated with histologic subtypes, and univariate and multivariate analyses identified the plasma cell subtype as an independent negative prognostic factor. These plasma cells may be one of the major producers of the immunosuppressive cytokine IL35 in cancer stroma. Cancer Immunol Res; 4(3); 234–47. ©2016 AACR.

Prognostic Impact of Preoperative Tumor Marker Levels and Lymphovascular Invasion in Pathological Stage I Adenocarcinoma and Squamous Cell Carcinoma of the Lung

Introduction: Some unfavorable prognostic factors for stage I non–small-cell lung cancers have been reported; however, they are not reflected in the current Tumor–Node–Metastasis classification. Methods: We retrospectively reviewed 629 patients who underwent complete resection of pathological stage I adenocarcinomas (ADs) or squamous cell carcinomas (SQs) at two institutes between 1996 and 2011. The correlation between clinicopathological characteristics and survival rates was analyzed to identify prognostic factors. Results: Multivariate analysis indicated that among ADs, high serum carcinoembryonic antigen levels (p = 0.04 for overall survival [OS]; p < 0.01 for recurrence-free survival [RFS]; p = 0.02 for disease-specific survival [DSS]), lymphatic permeation (p < 0.01 for RFS and DSS), and vascular invasion (p < 0.01 for OS and RFS; p = 0.03 for DSS) were independent prognostic factors. Among SQs, high squamous cell carcinoma antigen (SCC) (p < 0.05 for OS), and vascular invasion (p < 0.05 for RFS and DSS) were independently prognostic. We suggest that among completely resected tumors less than or equal to 5 cm without lymph node metastasis, the current stages IA and IB AD with high serum carcinoembryonic antigen levels, lymphatic permeation, or vascular invasion should be upgraded to stage IB and IIA, respectively. The current stage IA SQ with high SCC antigen levels or vascular invasion should be upgraded to stage IB. These reclassifications accurately reflect survival status (p < 0.04 in all comparisons). Conclusions: Some important differences in prognostic factors were observed between AD and SQ. High preoperative serum tumor marker levels and lymphovascular invasion should be included as additional criteria in the forthcoming Tumor–Node–Metastasis staging.

Impact of comorbidity index on morbidity and survival in non-small cell lung cancer.

Background The number of surgeries in older patients with comorbidities is constantly growing. The present study examined the impact of comorbidity on postoperative complications and long-term survival in patients with completely resected non-small cell cancer. Methods Between 2004 and 2008, 423 patients with non-small cell lung cancer underwent complete resection. A retrospective comparison of perioperative mortality, morbidity, Charlson comorbidity index (CCI), and postoperative length of hospital stay was performed. Results The number of patients with CCI 0, 1–2, and ≥3 was 226, 170 and 27, respectively. The 5-year overall survival was 88% among patients with CCI 0, and 84% in those with CCI ≥1 (p = 0.05) in all pathological stages. The CCI 0 group had significantly better overall survival than CCI 0 group and 30 (15%) in the CCI ≥1 group (p = 0.024). Length of stay was shorter in the CCI 0 group (11 ± 5 days) than in the CCI ≥1 group (15 ± 19 days, p = 0.015). Conclusions A high CCI correlated with higher postoperative morbidity and longer length of stay. We identified better a prognosis in patients with CCI 0 compared to those with CCI 1–2.

Dry pleurisy complicating solitary pulmonary nodules caused by Mycobacterium avium: a case report

IntroductionMycobacterium avium complex (MAC) lung disease presenting as a solitary pulmonary nodule (MAC-SPN) is often asymptomatic, is more common in middle to old age, and mimics lung cancer or tuberculoma. We report herein a case of MAC-SPN in an immunocompetent young adult patient, presenting with persistent chest pain and a subacutely progressive nodule with high intense 18F-fluorodeoxyglucose uptake. Histological examination of resected specimens revealed pleurisy, which is a rare finding of MAC-SPN.Case presentationA 36-year-old Japanese male presented with chest pain and a subacutely progressive pulmonary nodule. Positron emission tomography-computed tomography showed high intense 18F-fluorodeoxyglucose uptake in the nodule. Owing to his continuous chest pain and subacutely progressive nodules, wedge resection was performed using video-assisted thoracoscopic surgery. Histological examination revealed an epithelioid granuloma and pleurisy, and the lung tissue culture was positive for mycobacteria identified as M. avium.ConclusionThis is the first report of MAC-SPN occurring with persistent chest pain, suggesting that MAC should be considered in the differential diagnosis of a solitary pulmonary nodule, even for patients who experience persistent chest pain. As in the present case, surgical resection with video-assisted thoracoscopic surgery is a reasonable approach to the diagnosis and treatment of MAC-SPN with possible malignancy, especially as MAC can be diagnosed using resected lung tissue culture with histological confirmation.

Survival predictors after resection of lung metastases of head or neck cancers

Pulmonary metastasectomies are performed for a variety of cancers, though few reports have examined their merit for head and neck cancers. This study examined the relationship between clinical and pathological characteristics and survival after resection of lung metastases of these cancers.