Ryosuke Kaku

Decrease in performance status after lobectomy mean poor prognosis in elderly lung cancer patients

BACKGROUND Surgery remains the best treatment for obtaining cure in patients with resectable lung cancer, regardless of age. In elderly patients, however, the presumed fear of decreased performance status (PS) after lobectomy has resulted in the delivery of sub-optimal cancer surgery. Surgical decision making for such patients would become easier if post-lobectomy survival benefits and changes in PS were well defined. METHODS We reviewed patients aged 75 years or older who received lobectomy for non-small cell lung cancer (NSCLC) at our hospital between January 2004 and December 2014. Eastern Cooperative Oncology Group PS was preoperatively and postoperatively assessed in 137 patients. Patients were classified into 2 groups based on the change in PS: in Group 1, postoperative and preoperative PS were the same; in group 2, postoperative PS was less than preoperative PS. We compared the characteristics of patients in groups 1 and 2. RESULTS Overall 5-year survival was 47.4% in group 1 and 0% in group 2 (P<0.001). History of cardiac ischemia (P=0.001) and squamous cell carcinoma (P=0.015) were identified as significant predictors of reduced postoperative PS. CONCLUSIONS Our results show that maintenance of PS after lobectomy is expected to be associated with a good prognosis. However, reduction of PS after lobectomy indicates an extremely poor prognosis in elderly patients with lung cancer. History of cardiac ischemia and squamous cell carcinoma are possible risk factors for decreasing PS. Thus, careful patient evaluation and selection are needed when deciding whether to use lobectomy in clinical practice.

Thymoma-Associated Graft-Versus-Host–Like Disease With Skin Manifestations Improved by Complete Resection of Thymoma

A 69-year-old woman with refractory skin eruptions, which had first appeared 3 years previously, was examined, and an anterior mediastinal tumor was detected. The tumor was resected, and a diagnosis of type B2 thymoma, stage III disease (according to the World Health Organization classification), was made. Retrospectively, histologic findings of the skin before the operation were consistent with graft-versus-host disease. The final diagnosis of her skin lesions was thymoma-associated graft-versus-host-like disease. The skin lesions improved gradually during the 1-month period after resection with only a topical steroid, and further improvement was seen at 3 months.

Simultaneous resection of pulmonary tumor following cardiovascular surgery.

BACKGROUND A pulmonary tumor is occasionally detected on a chest computed tomography (CT) scan before cardiovascular surgery. PURPOSE In this study, we examined clinical courses of patients who had undergone the simultaneous resection of a pulmonary tumor following cardiovascular surgery. METHODS From 2008 to 2013, 18 patients (13 men and 5 women) with a median age of 69.8 years underwent the wedge pulmonary resection for a lung tumor through a median thoracotomy following cardiovascular surgery in our hospital. Cardiovascular surgeries consisted of off-pump coronary artery bypass grafting (CABG) in six patients, aortic valve replacement and/or mitral valve plasty in 10 patients, total arch replacement in 10 patients and descending aorta replacement in 10 patients. RESULTS No complications associated with pulmonary resections were observed. Pathological examination revealed that 15 patients (83.3%) were diagnosed with lung cancers including 13 adenocarcinomas and two squamous cell carcinomas, with the clinical stages of 1A in 13 patients, 2A in one patient and 2B in one patient. Among them, five patients received the radical pulmonary resection subsequently, whereas 10 patients were unable to receive it due to their poor cardiopulmonary function. Kaplan-Meier analysis of patients with lung cancer revealed that the 5-year survival rate and progression-free survival (PFS) rate after 3 years from the surgery were 46.2% and 73.8%, respectively. CONCLUSION The simultaneous resection of pulmonary tumor following cardiovascular surgery is safely performed, and is useful for the pathological diagnosis of the tumor. Further studies are warranted, however, this procedure may contribute to controlling the progression of lung cancer in patients with cardiovascular disease with comorbidities.

A surgical case of eosinophilic angiocentric fibrosis of the lung.

Eosinophilic angiocentric fibrosis (EAF) is an uncommon inflammatory disease that develops from the respiratory organs and affects them. Almost all reports about EAF describe lesions affecting the upper respiratory tract. We present the first case of EAF of the lung treated by surgical excision. A 69-year-old female consulted our hospital following the detection of an abnormal chest shadow with chronic cough. Chest computed tomography showed a pulmonary growing mass in the right hilar area, which corresponded to an enhanced accumulation on positron emission tomography. We doubted a pulmonary malignant tumor and performed a right upper lobectomy. Pathological and other clinical presentations revealed EAF of the lung without coexisting systemic diseases. The patient had an uncomplicated postoperative course, and the presenting cough had improved. EAF can involve the lung and cause symptomatic airway obstruction. For a hilar region mass with imaging characteristics similar to those of lung cancer, a differential diagnosis must be considered.

Abstract 4945: The cancer-associated fibroblasts-targeted strategycan augment the potency of the dendritic cell-based vaccine immunotherapy.

The dendritic cell (DC) -based vaccine immunotherapy has been a promising cancer immunotherapy, but has been insufficient to eradicate the tumor in patients with advanced cancer. This can result from the complicated tumor microenvironment (TME) that is implicated in suppression of anti-tumor immune responses. Several immune cell types in TME, such as Tregs, myeloid derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs), have been reported to regulate anti-tumor immune responses negatively. Cancer-associated fibroblasts (CAFs) are also primary stromal cells in TME, and contribute to tumor growth and metastases through the secretion of TGF-β and stromal cell-derived factor-1 (SDF-1). We considered that TME-targeted strategies should be innovated for the development of the potent cancer immunotherapy. On the basis of these viewpoints, we focused on the role of CAFs in TME, and hypothesized that inhibition of CAFs would lead to improvement of systemic anti-tumor immune responses and enhancement of the potency of the DCs-based vaccine immunotherapy. In this study, we applied tranilast in order to inhibit CAFs, the anti-fibrotic and -allergic agent that is used clinically and has been shown to inhibit fibroblast in the scar tissue. In in vitro studies, we examined effects of tranilast on CAFs that were isolated from established EG7 (mouse lymphoma cells) tumors. As results, tranilast was able to suppress the proliferation of CAFs, and decrease the production of SDF-1 as well as TGF-β from CAFs. Regarding the effect on Tregs, tranilast was able to decrease the induction of them from spleen cells of normal mice. Based on these results, we confirmed that tranilast could inhibit the function of CAFs. Next, we examined the association between inhibition of CAFs and anti-tumor immune responses in tumor-bearing mouse model. C57BL/6 mice bearing EG7 were administered tranilast into the established tumor in combination with tumor antigen-loaded DCs vaccination, and were evaluated anti-tumor immune responses. As results, the population of CAFs was decreased by targeting them, leading to lower expressions of TGF-β as well as SDF-1 in TME. Inhibition of CAFs in TME resulted in the decreased distributions of Tregs in TME and tumor-draining lymph nodes (TDLs). On the induction of effector cells, antigen-specific CD8+ cells producing IFN-γ were significantly increased in TDLs and spleen through inhibition of CAFs in TME. In these mice, systemic antigen-specific cytotoxic responses were augmented, leading to suppression of tumor growth as compared with mice in control groups. These results demonstrate that CAFs are associated with immune suppression, and inhibition of CAFs functions in TME can augment systemic anti-tumor immune responses. Our mouse models provide a new rationale with TME-targeted strategies for enhancing the potency of the DCs-based vaccine immunotherapy. Citation Format: Yasuhiko Ohshio, Ryosuke Kaku, Keiko Ishida, Masayuki Hashimoto, Shoji Kitamura, Koji Teramoto, Jun Hanaoka, Noriaki Tezuka. The cancer-associated fibroblasts-targeted strategycan augment the potency of the dendritic cell-based vaccine immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4945. doi:10.1158/1538-7445.AM2013-4945