Shuichi Tsukamoto

High vascularity in the peripheral region of non-small cell lung cancer tissue is associated with tumor progression

OBJECTIVES We attempted to determine if the degree of angiogenesis can serve as a prognostic factor in the case of completely resected non-small cell lung cancer patients, with special reference to the center and the periphery of the tumor tissue. METHOD For 255 Japanese patients who underwent completely resected non-small cell lung cancer (NSCLC), micro vessel density (MVD) was assessed by visual quantification of microvessels immunostained with anti-CD34 monoclonal antibody in 5 m section. Vascular endothelial growth factor (VEGF) was also immunostained on the same paraffin block specimen. RESULTS MVD at the center (MVD-c) and that at the periphery (MVD-p) were frequently different in each individual although a weak positive correlation was observed (r=0.499, P<0.0001). One hundred and one patients with high MVD-p, but not the 107 patients with high MVD-c, showed a significantly higher proportion of advanced stage, larger tumor size and nodal metastasis as compared with MVD. The 5 year survival rate and median survival time for the high MVD-p group were significantly lower than that of low the MVD-p group (43.0%/31 months vs 48.6%/54 months, P=0.0256). As to the relationship among vascular endothelial growth factor (VEGF) and MVD, expression of VEGF was not associated with the degree of MVD. However, patients with high grade MVD-p showed an unfavorable prognosis in cases of high expression of VEGF. CONCLUSION High MVD-p is associated with advancement of NSCLC, and it was particularly apparent in conjunction with high VEGF expression.

Reduced expression of cell-cycle regulator p27Kip1 correlates with a shortened survival in non-small cell lung cancer

BACKGROUND The cell cycle progression is governed by a family of cyclin-dependent kinases, which are regulated by associated cyclins and by phosphorylation. p27, a cyclin-dependent kinase inhibitor, regulates the progression from G1 into the S phase by binding and inhibiting cyclin/cdks. Although p27 mutations in human tumors are extremely rare, a reduced expression of p27 might to lead to a progression of cancer cells. METHODS We examined tissues that had been surgically excised from 161 unselected Japanese patients with non-small cell lung cancer, and investigated the p27 protein expression by immunohistochemistry. RESULTS A reduced expression of the p27 protein was found in 63 cases (39.0%). Statistical correlation was found between the reduced p27 expression and advanced stage, although no correlation was found between the level of p27 expression and the gender, T factor, N factor or histological differentiation. The 5-year survival rate in the reduced group was 35.4%, which was statistically poorer than the 63.2% rate in the normal group (P=0.0016), in patients with complete resection. In a multivariate analysis, the level of p27 expression was found to be an independent prognostic indicator. CONCLUSIONS We demonstrated the expression of p27 protein to be a biological prognostic indicator which can indicate the subsets of patients with either a good or poor prognosis, in patients who underwent surgical resection.

Prediction of the prognosis and surgical indications for pulmonary metastectomy from colorectal carcinoma in patients with combined hepatic metastases

BACKGROUND The value of surgical treatment for patients with pulmonary and hepatic metastases from colorectal carcinoma is controversial. The purpose of this study was to analyze our initial experience with this aggressive strategy, and to define the prognosis and the surgical indications. METHODS The records of 35 patients who underwent surgical treatments for both hepatic and pulmonary metastases from colorectal carcinoma, from January 1997 to December 2008, were retrospectively analyzed. RESULTS There were 18 females and 17 males with a median age was 62.0 years. The primary colorectal neoplasm was located at the colon in 23 patients (65.7%) and in the rectum in 12 patients (34.3%). The overall 5-year and 10-year survival rates were 65.3% and 31.5% from the date of primary colorectal resection, respectively. For patients who underwent metachronous hepatic and pulmonary surgical treatment, the 10-year survival rate was 40.9%, which was significantly better than that of those undergoing synchronous hepatic and pulmonary surgical treatment (p=0.0265). Patients who have pulmonary less than ten of metastasis thus seemed to have a better prognosis than those with more than ten, but the difference was quite significant (p=0.0719). In a multivariate Cox proportional hazards model, synchronous hepatic and pulmonary metastases was identified as an independent predictor of adverse survival (p=0.0073). CONCLUSIONS The results of our study suggest that hepatic and pulmonary surgical treatment can provide a better prognosis for patients with metachronous hepatic and pulmonary metastases from colorectal carcinoma. We believe that aggressive metastasectomy can be an option for selected patients, even if a patient has been previously treated for hepatic and pulmonary metastases from colorectal carcinoma.

Invasive Thymoma with Long-Term Survival by Extensive Reoperation

The recurrence of invasive thymoma is often observed; however, no accepted treatment of recurrent invasive thymoma has yet been established. We herein report a 41-year-old woman with invasive thymoma and pleural dissemination who demonstrated long-term survival after undergoing 4 operations. Based on our findings, reoperation is thus suggested in patients with intrathoracic recurrence and long-term survival can be expected.

Spontaneous Pneumothorax Complicating Lung Metastasis from Lingual Carcinoma

We report a patient with pneumothorax caused by a metastatic tumour from carcinoma of the tongue, which had given rise to a bronchopleural fistula with subsequent induction of pneumothorax. Although rare, pulmonary metastasis should be considered in the aetiology of spontaneous pneumothorax. Despite advanced disease, surgical treatment may be feasible.

A phase II randomized trial of adjuvant chemotherapy with S-1 versus S-1 plus cisplatin for completely resected pathological stage II/IIIA non-small cell lung cancer

OBJECTIVES Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC. PATIENTS AND METHODS We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year. RESULTS A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P =  0.1695 and P =  0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%). CONCLUSIONS Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

An Unusual Cause of a Persistent Pulmonary Infiltrate and Weight Loss

Accessible online at: http://BioMedNet.com/karger A 71-year-old smoker was admitted for investigation of suspected lung cancer. He had had a history of coughing for several weeks, the chest roentgenogram showed a vague infiltrate in the lingula and he was put on a course of oral antibiotics. Over a period of 2 months the patient lost 10 kg and the infiltrate did not resolve. Before bronchoscopy a CT scan (fig. 1) was performed, which confirmed the chest roentgenogram findings but did not reveal a tumor. Bronchoscopy surprisingly revealed a grain of maize at the entrance of each lingular segment (fig. 2). Both foreign bodies could be passed with the closed forceps and removed by drawing back the opened forceps with the help of a strong cough from the patient. The lingular infiltrate disappeared subsequently and while treating a painful buccal ulcer, a substantial increase in weight was noticed. In this case the combination of weight loss and a persistent pulmonary infiltrate was not the result of a bronchial tumor, as we expected, but due to an ill-fitting dental prosthesis, which caused the painful buccal ulcer and possibly also favoured aspiration. Our patient, who was very fond of maize salad, could not remember a coughing fit while eating in the past few days or weeks. Even without a typical history, aspiration should always be considered as a possible cause of a pulmonary infiltrate, especially in elderly patients. Figure 3 shows the moderately inflamed entrance to the lingular segments after the procedure. 2