Kaoru Kaseda

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.

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.

Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma

Histological vascular invasion (VI) by tumors is reportedly a risk factor influencing recurrence or survival after surgical treatment; however, few studies have evaluated which VI features affect recurrence or survival. The objective of this study was to evaluate how VI features affect recurrence in lung adenocarcinoma patients. We selected 106 patients with pathological stage I lung adenocarcinoma who showed VI and examined the properties of intravascular tumors associated with recurrence. First we investigated the relationship between the frequency of VI in a histological cross‐section and the incidence of recurrence; however, a significant impact was not observed. Microscopic examination revealed the intravascular tumors were composed of not only cancer cells but also non‐cancerous cells. To examine whether the characteristics of intravascular cancer cells and/or non‐cancerous cells have prognostic value, we examined the expression levels of epithelial–mesenchymal transition‐related markers in cancer cells and the numbers of infiltrating non‐cancerous cells, including macrophages, endothelial cells, and fibroblasts. High levels of E‐cadherin expression in the intravascular cancer cells were significant predictors of recurrence (P = 0.004), whereas the expressions of CD44, CD44 variant 6, and vimentin were not. Large numbers of intravascular CD204(+) macrophages (P = 0.016), CD34(+) microvessels (P = 0.007), and α‐smooth muscle actin (+) fibroblasts (P = 0.033) were also significant predictors of recurrence. Our results indicated VI with abundant stromal cell infiltrates might be a predictor of recurrence and suggested the tumor microenvironment created by cancer cells and stromal cells within the blood vessel may play an important role during the metastatic process.

Identification of false-negative and false-positive diagnoses of lymph node metastases in non-small cell lung cancer patients staged by integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography: A retrospective cohort study

The aim of this study was to evaluate the diagnostic accuracy of integrated 18 F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET/CT) in hilar and mediastinal lymph node (HMLN) staging of non‐small cell lung cancer (NSCLC), and to investigate potential risk factors for false‐negative and false‐positive HMLN metastases.

Clinical and pathological characteristics of EGFR mutation in operable early-stage lung adenocarcinoma

OBJECTIVES Over the past decade, the biological and clinical characteristics of lung cancer with epidermal growth factor receptor (EGFR) mutation have been well studied. However, most studies have focused on advanced inoperable cancer, and not on resected early-stage lung adenocarcinoma. We aimed to elucidate the differences in the clinicopathological characteristics and postoperative prognosis according to the EGFR mutation status in early-stage lung adenocarcinoma. MATERIALS AND METHODS We retrospectively collected clinical and pathological data from 369 patients with pathological stage I or II lung adenocarcinoma who underwent complete resection. Clinicopathological characteristics and postoperative prognosis were compared depending on the EGFR mutation status, using the Chi-squared test and the log-rank test, respectively. RESULTS AND CONCLUSION Of the 369 patients, 160 (43.3%) had EGFR mutation, of which 64 (40.0%) were exon 19 deletion (Del-19) and 90 (56.3%) were exon 21 point mutation L858R. Although there was no difference in overall survival (OS) between patients with and without EGFR mutation (p=0.086), tumors with EGFR mutation were associated with a lower consolidation to tumor ratio (CTR) (p <0.001) and a higher incidence of a lepidic growth pattern by pathological evaluation (p <0.001) compared to those without EGFR mutation. Among tumors with EGFR mutation, there was no difference in OS (p=0.140) between Del-19 and L858R. Tumors with L858R were associated with a lower CTR (p=0.046), and tended to have a higher incidence of a lepidic growth pattern by pathological evaluation (p=0.073) compared to those with Del-19. In conclusion, although EGFR mutation status was not a prognostic indicator after surgery in early-stage lung adenocarcinoma, L858R and Del-19 had different radiological and pathological features.

Aldehyde dehydrogenase 1 expression in cancer cells could have prognostic value for patients with non‐small cell lung cancer who are treated with neoadjuvant therapy: Identification of prognostic microenvironmental factors after chemoradiation

Prognostic factors for patients with non‐small cell lung cancer (NSCLC) who have been treated with neoadjuvant therapy have not been fully assessed. The purpose of this study was to analyze prognostic biomarkers in NSCLC after treatment with neoadjuvant therapy, with special reference to the immunophenotypes of both the cancer cells and stromal cells. A total of 52 patients with NSCLC who were treated with neoadjuvant therapy followed by complete resection were included. We examined the expressions of nine markers in the cancer cells and stromal cells. The 5‐year disease‐free survival rate of patients with high aldehyde dehydrogenase 1 (ALDH1) expression levels in their cancer cells was significantly lower than those with a low ALDH1 level (47.3% vs. 21.5%, respectively; P = 0.023). The other molecules expressed in cancer cells did not exhibit any prognostic value. In NSCLC without neoadjuvant therapy (case control, n = 104), expression of ALDH1 in cancer cells was not correlated with prognosis (P = 0.507). A multivariate analysis identified ALDH1 expression in cancer cells as significantly independent prognostic factors for disease‐free survival (P = 0.045). The current study indicated that the immunophenotypes of ALDH1 in cancer cells could have prognostic value for patients with NSCLC who are treated with neoadjuvant therapy.

Solitary pulmonary metastasis from occult papillary thyroid carcinoma.

Pulmonary metastases from thyroid carcinoma typically cause a micronodular or miliary pattern throughout both lungs. Metastasis consisting of a solitary pulmonary nodule measuring 20 mm in diameter is rare. Here we report a case of a 66‐year‐old woman without a history of papillary thyroid carcinoma who presented with a pulmonary nodule measuring 20 mm in diameter, found on chest computed tomography during a health checkup. The patient underwent a right lobectomy. Microscopic examination showed well‐differentiated papillary adenocarcinoma. Immunohistochemical findings were consistent with a diagnosis of pulmonary metastasis from papillary thyroid carcinoma. Solitary metastasis to the lung from occult thyroid carcinoma is quite rare, but if a pulmonary nodule is encountered in a patient without a history of thyroid carcinoma, the possibility must be considered.

Rosai-Dorfman disease mimicking mediastinal lymphoma

Rosai-Dorfman disease is rare and typically presents with cervical lymphadenopathy. The disease is generally indolent and self-limited, but it carries a poor or fatal prognosis when it is advanced or when it involves and compresses vital structures. We herein report a rare case of Rosai-Dorfman disease affecting only the mediastinal-hilar region in a 66-year-old woman.

Clinicopathological and prognostic features of surgically resected pathological stage I lung adenocarcinoma harboring epidermal growth factor receptor and K-ras mutation

This study aimed to evaluate mutations of the epidermal growth factor receptor (EGFR) and K‐ras genes and their clinicopathological and prognostic features in patients with resected pathological stage I adenocarcinoma.

Surgical resection of lung adenocarcinoma after crizotinib treatment: report of a case

A 45-year-old female was diagnosed as having lung adenocarcinoma harboring an anaplastic lymphoma kinase (ALK) rearrangement, stage IV (T2bN3M1b). She was treated with crizotinib as second-line chemotherapy. The clinical stage after crizotinib treatment was ycT2aN0M0, stage IB. We performed a left lower lobectomy and lymph node dissection aimed at local control and pathological confirmation of the remaining tumor. The final pathological stage was ypT2aN2M0, stage IIIA with Ef 1b. To the best of our knowledge, this is the first case report of surgical resection in ALK rearrangement-positive lung adenocarcinoma after crizotinib treatment.