Shunki Hirayama

Prognostic Impact of CD204-Positive Macrophages in Lung Squamous Cell Carcinoma: Possible Contribution of Cd204-Positive Macrophages to the Tumor-Promoting Microenvironment

Introduction: Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma. Methods: We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs. Results: A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis. Conclusions: CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.

Forkhead box P3 regulatory T cells coexisting with cancer associated fibroblasts are correlated with a poor outcome in lung adenocarcinoma

Recently, an association between tumor infiltrating Forkhead box P3 regulatory T cells (Treg) and an unfavorable prognosis has been clinically shown in some cancers, but the mechanism of Treg induction in the tumor microenvironment remains uncertain. The aims of the present study were to examine the relationship between Treg and patient outcome and to investigate whether Treg induction is influenced by the characteristics of cancer‐associated fibroblasts (CAF) in lung adenocarcinoma. The numbers of Treg in both the tumor stroma and the tumor nest were counted in 200 consecutive pathological stage I lung invasive adenocarcinoma specimens. To examine whether the characteristics of CAF influence Treg induction, we selected and cultured CAF from low Treg and high Treg adenocarcinoma. The number of Treg was much higher in the stroma than in the nest (P < 0.01). Patients with high Treg had a significantly poorer prognosis than those with low Treg (overall survival: P = 0.03; recurrence‐free survival: P = 0.02; 5‐year overall survival: 85.4% vs 93.0%). Compared with the CAF from low Treg adenocarcinoma, culture supernatant of the CAF from high Treg adenocarcinoma induced more Treg (P = 0.01). Also, CAF from high Treg adenocarcinoma expressed significantly higher mRNA levels of transforming growth factor‐β (P = 0.01) and vascular endothelial growth factor (P = 0.01), both of which are involved in Treg induction. Our studies suggest the possibility that CAF expressing immunoregulatory cytokines may induce Treg in the stroma, creating a tumor‐promoting microenvironment in lung adenocarcinoma that leads to a poor outcome.

Distinct clinicopathological characteristics and prognosis based on the presence of ground glass opacity component in clinical-stage IA lung adenocarcinoma

Introduction: We evaluated differences in the clinicopathologic characteristics and prognosis based on the presence of ground glass opacity (GGO) components in small‐sized lung adenocarcinoma. Methods: We retrospectively investigated 634 lung adenocarcinomas classed as c‐stage IA in the eighth edition TNM classification. Staging was defined according to the solid component size measured by thin‐section computed tomography. All tumors were grouped into either a GGO or solid group, based on the presence of a GGO component. Results: Of the cases, 215 (34%) were classed as c‐stage IA1 (T1mi: 88, T1a‐GGO: 102, T1a‐solid: 25), 255 (40%) as c‐stage IA2 (T1b‐GGO: 122, T1b‐solid: 133), and 164 (26%) as c‐stage IA3 (T1c‐GGO: 44, T1c‐solid: 120). Among the 546 c‐stage IA cases excluding the T1mi lesions, Cox regression analysis revealed that presence of GGO was an independently significant prognosticator (p = 0.024). The result was validated in 494 c‐stage IA lung adenocarcinomas with a nonpredominant GGO component, showing the presence of GGO as a significant prognosticator (p = 0.048). When we evaluated the prognostic impact of GGO presence in each clinical stage, the 5‐year overall survival (OS) was significantly different between the GGO and solid groups (IA1: 97.8% versus 86.6%, p = 0.026; IA2: 89.3% versus 75.2%, p = 0.007; IA3: 88.5% versus 62.3%, p = 0.003). Furthermore, the 5‐year overall survival b was distinct in parallel similar pathologic findings when comparing a lepidic versus an invasive component (IA1: 97.9% versus 85.6%, p = 0.031; IA2: 86.1% versus 69.4%, p = 0.007; IA3: 77.5% versus 55.8%, p < 0.001). Conclusions: Clinicopathologic and oncologic outcomes were disparate based on the presence of a GGO component in the eighth edition TNM classification of c‐stage IA lung adenocarcinoma.

Limb-Shaking Transient Ischemic Attack Induced by Middle Cerebral Artery Dissection after Lung Surgery

We report a case of limb-shaking transient ischemic attack (TIA) caused by a dissection of the middle cerebral artery (MCA) following lung surgery under general anesthesia. An 81-year-old male patient who underwent lobectomy for lung cancer suddenly developed transient shaking movements of the neck and the left upper distal limb on postoperative day 1. On the basis of the double-barrel appearance of the right M1 segment of the MCA, a diagnosis of MCA dissection was made. Physicians should be aware that limb-shaking TIA is sometimes caused by MCA dissection and could be precipitated by any condition, including lung surgery under general anesthesia.