Bone morphogenetic protein-7 (BMP-7) is a signalling molecule belonging to the transforming growth factor--superfamily. Recent studies have demonstrated the clinical impact of BMP-7 expression in various human cancers. However, there have been few reports detailing this in gastric cancer. We immunohistochemically investigated the expression of BMP-7 in 233 gastric cancer patients to disclose the clinicopathological features of BMP-7-positive gastric cancer. Immunohistochemically, in human gastric cancer, BMP-7 expression was identified in cellular membranes but also in the cytoplasm of cancer cells. Bone morphogenetic protein-7-positive expression was found in 129 of 233 patients (55%). Bone morphogenetic protein-7 expression was correlated with tumour size, nodal involvement, lymphatic invasion, venous invasion and histology (P<0.05). Bone morphogenetic protein-7 expression was significantly correlated with patient postoperative outcome, especially in the undifferentiated group. Multivariate analysis revealed BMP-7 expression as one of the independent prognostic factors next to the depth of invasion and nodal involvement (P<0.01). From the data collected, it would be appropriate to conclude on the possible regulation of gastric cancer progression by autocrine or paracrine BMP-7 loops. We can use BMP-7 expression as one of the strong predictors of risk of tumour recurrence in gastric cancer.

Although osimertinib is a key drug in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, the safety in hemodialysis patients has not been established. A 76-year-old man was diagnosed with NSCLC with EGFR deletion mutation in exon 19. After treatment failure with first- and second-generation EGFR tyrosine kinase inhibitors, a T790M mutation was revealed by liquid biopsy. Hemodialysis was started three times a week because chronic renal failure worsened during treatment. Although the subsequent administration of osimertinib (80 mg daily) resulted in a tumor shrinkage and a gradual increase in the plasma concentration of osimertinib, which resulted in grade 3 general fatigue, reducing the dosage of osimertinib decreased its plasma concentration, leading to an improvement in his adverse event. Subsequently, with by adjusting the dosage while periodically measuring the plasma concentration of osimertinib, a stable therapeutic effect was sustained over the long term with no symptoms. Periodic plasma concentration measurements may be indispensable for successful treatment with osimertinib in hemodialysis patients.

Background: Perioperative treatment of locally advanced non-small cell lung cancer (NSCLC) is attracting attention. The effect of neoadjuvant tyrosine kinase inhibitor (TKI) therapy on postoperative long-term outcomes in patients with driver gene mutations remains unclear. The aim of this study was to clarify the long-term survival outcomes of patients with stage III NSCLC harboring driver gene mutations who received preoperative TKI therapy. Methods: Between January 2016 and December 2018, 10 patients with clinical stage III NSCLC with driver gene mutations were treated with TKIs [epidermal growth factor receptor (EGFR) mutation, n=9; anaplastic lymphoma kinase (ALK) fusion, n=1]. One patient refused surgery. The remaining nine patients received sequential chemotherapy followed by surgery. Postoperatively, six patients received adjuvant chemotherapy, and TKIs were readministered in four patients. Results: The main adverse events of TKIs were grade 3 liver damage and grade 3 skin rash, which required a change in the drug from gefitinib to afatinib and dose reduction, respectively. In all 10 patients, the radiological response to TKIs was greater than the partial response, and nine patients underwent radical surgery. Although viable cancer cells remained in all patients with EGFR mutations, a pathological complete response was obtained in the patient with ALK fusion. No mortality or major morbidity was observed perioperatively. Of the patients who underwent surgery, 3 were alive without recurrence, while 6 had distant metastasis, including 5 with brain metastasis. Seven of the nine patients who underwent surgery were still alive after a median follow-up period of 77.2 months. Conclusions: Successful long-term outcomes were achieved after sequential targeted therapy and chemotherapy, followed by surgery for stage III NSCLC. However, it is noteworthy that postoperative treatment may have also contributed to minimizing postoperative recurrence.

Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-β superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer. This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed. In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012). Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.

Introduction Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. Methods Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. Results Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2 ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2 ng/ml (n = 28). Patients with postoperative CEA > 6.2 ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. Conclusion The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2 ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

Background/Aim: The prognostic impact of adjuvant cytotoxic chemotherapy for patients with resectable locally advanced non-small cell lung cancer (NSCLC) who underwent surgery after neoadjuvant chemotherapy remains unclear. Patients and Methods: A retrospective chart review was performed to identify patients who underwent surgery following neoadjuvant therapy for clinical T3N0 or N1-N2 resectable NSCLC between 2011 and 2016 at our hospital. Survival outcomes were analyzed with the Kaplan–Meier method and a Cox proportional hazard model. Results: Thirty-eight patients were identified. The median recurrence-free survival (RFS) was 50.6 months and overall survival (OS) was 75.2 months. Patients who had undergone adjuvant chemotherapy were not associated with a favorable RFS (hazard ratio=1.01, p=0.98) or OS (hazard ratio=0.72, p=0.55), as compared with those who had not. However, subgroup analysis revealed that hazard ratio based on RFS and OS varied greatly between subgroups, suggesting that selected patients might benefit from adjuvant therapy, while others might be harmed by it. For example, in surgical-pathological stage III disease, adjuvant therapy showed a favorable RFS (HR=0.22, 95%CI=0.02-2.57, p=0.23) and OS (HR=0.36, 95%CI=0.03-4.01, p=0.40). Conversely, in surgical-pathological stage 0-II disease, adjuvant therapy showed an unfavorable RFS (HR=1.40, 95%CI=0.49-3.96, p=0.53) and OS (HR=0.95, 95%CI=0.29-3.12, p=0.93). Conclusion: Regardless of the negative findings in our overall patient cohort, our results may be beneficial in identifying patients who may likely benefit from adjuvant therapy. This contribution could assist the planning of large-scale prospective studies.