Katsunori Kagohashi

Liver metastasis at the time of initial diagnosis of lung cancer.

In order to evaluate clinicopathological features associated with liver metastases from lung cancer, we reviewed our experience of lung cancer patients seen in our division. Of the 1073 lung cancer patients diagnosed between October 1976 and May 2002, 62 (5.8%) patients had liver metastasis. The incidence of liver metastasis was 17.5% in small-cell lung cancer (SCLC) patients, whereas the incidence in non-small-cell lung cancer patients was 3.8%. Of the 62 patients, 17 had sole liver metastasis, and the remaining 45 had synchronous spread to the liver and one or more other organs. Six of 12 squamous cell carcinoma patients and 10 of 28 SCLC patients had sole liver metastasis. However, 19 of 20 adenocarcinoma patients showed liver metastasis with one or more other organs. In morphological liver metastasis, 26 of the 28 SCLC patients had multiple nodules, whereas 16 of the 34 non-small-cell lung cancer patients had a solitary liver nodule (p=0.0006). Liver is a possible site of extrathoracic spread of disease for some patients with lung cancer, especially with SCLC. When the histological types are squamous cell carcinoma or SCLC, it would also be considered likely that an isolated liver mass represents a metastasis even though there is no metastatic disease elsewhere.

Lung cancer in patients aged 80 years and over

OBJECTIVES The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. METHODS From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the <70 age group), 70-79 years (the 70-79 age group), and 80 years or older (the > or =80 age group). Time trends were also studied in two-time intervals: first study period up to 1997, which represents past practice standards, the second study period up to 2007, which represents contemporary practice. RESULTS Patients aged 80 years and older comprised 7.5% of 2775 consecutive patients with lung cancer, and there was a rapid increase in the proportion of patients aged 80 years or older from the earlier to the later time period. The > or =80 age group had higher proportion of poor performance status (PS) and comorbid disease than the <70 age group and the 70-79 age group. Unchanged proportion of patients with poor PS and advanced disease at presentation were observed in the > or =80 age group. The > or =80 age group was less likely to be subjected to surgery or chemotherapy, and had inferior outcomes when compared with the 70-79 age group and the <70 age group. Survival improvement was not observed in the > or =80 age group. Multivariate analysis showed good PS, early clinical stage and surgery were favorable prognostic factors in the > or =80 age group. CONCLUSION In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.

Endostatin levels in exudative pleural effusions.

Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Although serum levels of endostatin have extensively been studied in patients with malignant diseases, endostatin in pleural effusion has not been fully evaluated. In order to determine whether endostatin is present in pleural effusion, and to determine whether endostatin levels vary in pleural effusion of different etiology, we measured levels of endostatin in 38 malignant pleural effusion due to lung cancer patients and 29 patients with non-malignant disease using an ELISA kit. Free form of endostaitn was measurable (>11.2 pg/ml) in 26 of 38 malignant and 13 of 29 non-malignant pleural effusion. Endostatin levels in the 38 malignant pleural effusion were significantly higher than those in patients with the 29 patients with non-malignant diseases (p = 0.0131). However, there was not statistically significant difference between the patients with pleuropneumonia and those with tuberculous pleurisy (p = 0.2194). In malignant pleural effusion due to lung cancer, the pleural effusion endostatin levels did not differ when the histological types of lung cancer were considered(p = 0.0674). Endostatin was present in both malignant and non-malignant pleural effusion, and elevated levels of endostatin were observed in malignant pleural effusion. Although the mechanisms are unclear, elevated levels of endostatin in pleural effusion may represent the local productions of endostatin in pleural space.

Interstitial lung disease in patients with small cell lung cancer.

Interstitial lung disease (ILD) and lung cancer are two of the most common respiratory diseases. The aim of this study was to demonstrate the prognostic significance of the presence of ILD in patients with small cell lung cancer (SCLC). All the patients with SCLC who were admitted to our hospitals over a 23-year period up to 2008 were retrospectively analyzed. During the study period, 332 SCLC patients were consecutively admitted to our hospitals. Among them, 15 (4.5%) were diagnosed as having both SCLC and ILD. In univariate and multivariate analysis, female sex, early stage, good performance status, and chemotherapy were favorable prognostic factors. The presence of ILD was confirmed as an unfavorable prognostic factor. Existing ILD adversely affects the outcome of SCLC. When deciding whether to offer a standard therapy that may increase treatment-related mortality, the patient’s medical condition, including ILD, should be taken into consideration.

Production of CA125 by human lung cancer cell lines

CA125, which until recently was considered an ovary specific tumor marker, is elevated in the serum of patients with many pathological conditions, including lung cancer. In order to investigate the production of CA125 by human lung cancer cell lines, cell culture and immunochemical staining were performed in three cell lines. Our results showed the cell surface expression of CA125 in both adenocarcinoma and large cell carcinoma cell lines and the production of CA125 in culture medium. This is considered as evidence for in vitro production of CA125 by human lung cancer, and suggests that CA125 elevation is not only the result of ovarian cancer but may be due to other pathological conditions, including lung cancer.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41–57 days) and 5.3 months (134–181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Serum KL-6 levels in lung cancer patients with or without interstitial lung disease

Background: It is not known whether lung cancer patients with interstitial lung disease (ILD) might have higher serum levels of KL‐6, a high molecular weight glycoprotein classified as a polymorphic epithelial mucin. In addition, prognosis of these patients with elevated serum KL‐6 levels might be poorer than that with normal KL‐6 levels, but it has not been well clarified. Methods: Serum KL‐6 levels in 273 lung cancer patients with or without ILD, and prognostic significance of elevated serum KL‐6 levels in these patients were studied using uni‐ and multivariate analyses. Results: Serum KL‐6 levels were elevated (>500 U/ml) in 73.5% of lung cancer patients with ILD and in 33.7% of those without ILD. Serum KL‐6 levels in lung cancer patients with ILD were significantly higher than those without ILD. In lung cancer patients with ILD, elevated serum KL‐6 has no prognostic significance, but in those without ILD, however, it was one of the unfavorable prognostic factors. Conclusions: Elevated serum KL‐6 levels can be observed in lung cancer patients both with and without ILD. Having ILD has strong prognostic impact in patients with lung cancer. In those without ILD, however, elevated KL‐6 levels may be related to poor prognosis. J. Clin. Lab. Anal. 24:295–299, 2010.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44–80 days] compared with the younger group (median, 46 days; 95% CI: 35–53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142–239 days vs. median, 146 days; 95% CI: 114–185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.

Squamous Cell Carcinoma Antigen in Lung Cancer and Nonmalignant Respiratory Diseases

Study Objectives Squamous cell carcinoma antigen (SCC) has been found in elevated amounts in patients with squamous cell lung cancer (SQLC). Elevated levels have also been found among patients with nonsquamous cell lung cancer (NSQLC) and in subjects with nonmalignant pulmonary disease (NMPD). The purpose of the current study was to evaluate SCC levels among a large number of patients with SQLC, NSQLC, and NMPD. Six hundred thirty-nine lung cancer patients, including 201 SQLC patients and 299 patients with NMPD, who were diagnosed at our hospital up to 2006 were entered. Serum SCC levels were measured with a commercially available kit. Results Elevated levels (>1.5 ng/ml) of SCC were observed in 52.7% of SQLC patients, but in only 14.2% of NSQLC patients. There was a statistically significant difference in positive rate between SQLC and NSQLC patients. None of the NSQLC patients had serum SCC levels greater than 40.0 ng/ml. Among subjects with NMPD, 28.4% had elevated levels of SCC. However, none of the NMPD patients had serum SCC levels greater than 20.0 ng/ml. Conclusions Serum levels of SCC can be elevated (<20.0 ng/ml) in some NMPD patients without coexisting SQLC. Patients with NSQLC and NMPD with elevated SCC levels greater than 40 ng/ml may have coexisting SQLC or squamous cell carcinoma in an extrapulmonary site.

Patients With Lung Cancer With Metachronous or Synchronous Gastric Cancer

BACKGROUND There are few reports of treatment and outcome for patients with metachronous or synchronous lung and gastric cancers. To evaluate them, we conducted a retrospective study. PATIENTS AND METHODS The medical records of patients with lung cancer who previously or simultaneously had gastric cancer seen in our division between January 1979 and July 2008 were reviewed. RESULTS Forty-five (3.2%) of 1391 patients had previous or simultaneous gastric cancer. The proportion of men was higher among patients with lung cancer with gastric cancer than those without (P = .0006). There was a significant difference in age at the time of diagnosis of lung cancer between the 45 patients with gastric cancer and the 1346 patients without it (P = .0344). The proportion of smokers was higher among lung cancer patients with gastric cancer than those without (P = .0015). Twenty-seven of 45 patients had smoking-related cell types of lung cancer: squamous cell carcinoma and small-cell lung cancer. The proportion of these 2 cell types was higher in patients with lung cancer with gastric cancer than those without (P = .02). The diagnosis of gastric cancer preceded the diagnosis of lung cancer in 33 patients, and the median duration from the diagnosis of gastric cancer to that of the lung cancer was 6 years. CONCLUSION For patients with gastric cancer, smoking cessation, a chest radiograph at least yearly for several years, and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended, especially in elderly men with gastric cancer and smoking habit.