Hidehiko Shimokawa

Overexpression of MACC1 mRNA in lung adenocarcinoma is associated with postoperative recurrence

OBJECTIVE The purpose of this study was to clarify the role and clinical significance of metastasis associated in colon cancer 1 in resected stage I non-small cell lung cancers. METHODS Tumor specimens were collected from 146 consecutive patients who underwent a complete resection for stage I lung adenocarcinoma from 1998 to 2007 at the University of Occupational and Environmental Health. We analyzed the expression of metastasis associated in colon cancer 1 mRNA of primary lung adenocarcinomas by real-time reverse transcriptase-polymerase chain reaction. RESULTS The average postoperative observation period was 49.4 months. Thirteen (8.9%) of 146 patients had recurrences after surgery. Overexpression of metastasis associated in colon cancer 1 mRNA was identified in 62 patients (42.5%). Metastasis associated in colon cancer 1 was overexpressed in 9 (69.2%) of 13 patients and 53 (39.9%) of 133 patients with and without recurrence, respectively (P = .004). The median metastasis associated in colon cancer 1 copy number was 3.0 and 1.4 in patients with and without tumor recurrence, respectively. Metastasis associated in colon cancer 1 overexpression was associated with poorer disease-free survival according to the survival analysis (P = .033). CONCLUSIONS Metastasis associated in colon cancer 1 gene overexpression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma after surgery.

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer

PURPOSE This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. SUBJECTS This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008. RESULTS The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19-88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p<0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213-5.442, p=0.014). CONCLUSION A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion.

Clinical Significance of IGF1R Expression in Non-Small-Cell Lung Cancer

BACKGROUND The purpose of the current study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGF1R) in NSCLC. PATIENTS AND METHODS Tumor specimens were collected from 285 patients who underwent complete resection for adenocarcinoma (AD, n = 182), squamous cell carcinoma (SCC, n = 77), and other histologic types of cancer (n = 26) of the lung. The expression of IGF1R and Ki-67 was evaluated by immunohistochemical (IHC) analysis. RESULTS Positive expression of IGF1R was detected in 87 (30.5%) of 285 cases, of which 43 (23.6%) of 182 cases were AD, 36 (46.8%) of 77 cases were SCC, and 8 (30.8%) of 26 cases were other histologic types (SCC vs. AD, p < .001; SCC vs. non-SCC, p < .001). Positive IGF1R expression was also identified in 20 (44.4%) and 67 (27.9%) of the patients with and without recurrence, respectively (p = .027). Multivariate logistic regression models indicated that positive staining for IGF1R expression was an independent factor in AD associated with tumor recurrence (p = .040) but not in NSCLC, SCC, and other types of cancer. A positive IGF1R expression tended to demonstrate a poor disease-free survival (DFS) in NSCLC according to the Kaplan-Meier DFS curves (p = .053). The tumors showing a positive expression of IGF1R were observed more frequently in tumors with a positive expression of Ki-67 than in the tumors with a negative expression of Ki-67 (p = .010). CONCLUSION IGF1R expression was associated with reduced DFS correlating with postoperative recurrence. In addition, a significant relationship was also observed between IGF1R and Ki-67 expression in NSCLC. However, in subgroup analysis, a significant correlation was not observed. IGF1R expression predicts postoperative recurrence in patients with AD, but not in those with non-AD of NSCLC.

TS expression predicts postoperative recurrence in adenocarcinoma of the lung

BACKGROUND Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers for either selecting appropriate candidates or for predicting clinical recurrence exist. METHODS Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expressions in the primary lung adenocarcinoma by immunohistochemisty. RESULTS The strong expression of TS and DHFR was identified in 39 (21.3%) and 120 (65.6%) patients, respectively. The strong TS expression was identified in 11 (39.3%) of 28 patients and 28 (18.1%) of 155 patients in patients with and without recurrence, respectively (p=0.012). The strong DHFR expression was also identified in 23 (82.1%) and 97 (62.6%) of the patients with and without recurrence, respectively (p=0.045). Logistic regression models indicated the strong TS expression to be an independent factor for tumor recurrence. The strong TS and DHFR expression was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis demonstrated the strong TS expression to be independently associated with an increased risk for poor DFS. CONCLUSIONS The strong TS expression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma following surgery.

What factors predict recurrence of a spontaneous pneumothorax

BackgroundThe purpose of this retrospective study was to identify the risk factors for postoperative recurrence for the patients with a spontaneous pneumothorax (SP). A total of 214 patients were studied over a period of five years. Of these patients, 189 (88.3%) and 25 (11.7%) underwent video assisted thoracoscopic surgery (VATS) and an open approach for treatment, respectively. There were 35 (16.4%) postoperative recurrences.MethodsThe data on patient characteristics, surgical details, and perioperative outcomes were analyzed. We compared the clinicopathological characteristics between recurrent and non-recurrent cases, and used logistic regression models to predict the risk factors for postoperative recurrence.ResultsThe differences in the age, gender, lesion site, location, ipsilateral SP (ISP), and contralateral SP (CSP) did not reach statistical significance between the two groups. However, the incidence of recurrence was higher in the subjects without any smoking history, and who had comorbidities, and a history of surgery for ISP. Concerning intraoperative factors, there were no significant differences with regard to the approach, buttress stapling, covering, surgeon, or length of the operation. The postoperative recurrence rate was higher in the patients who had been hand-stitched compared to those who had undergone instrument-based repair for blebs. There were no significant differences in the perioperative outcomes. The logistic regression models indicated that non smokers, those with comorbidities, and those who had previously undergone surgery for ISP had a higher rate of postoperative recurrence.ConclusionsWe conclude that a history of no smoking, the existence of comorbidities, previous surgery for ISP, and hand stitching increase the risk of postoperative recurrence. Therefore, surgeons must be aware of these risk factors, and more carefully monitor such patients for recurrence.

Results of a surgical resection for patients with stage IV non--small-cell lung cancer.

PURPOSE This study retrospectively investigated the clinical significance of surgical treatment for stage IV non-small-cell lung cancer (NSCLC). SUBJECTS There were 36 patients who underwent surgical resection for stage IV NSCLC between 1999 and 2008. RESULTS The patients included 22 males and 14 females. All patients had either synchronous distant metastasis or pleural dissemination. The mean age of the patients was 65.8 years (range, 18 to 90 years). The histological types included 29 adenocarcinomas, 5 squamous-cell carcinomas and 2 large-cell carcinomas. The organs of metastasis were bone in 5 patients, brain in 4, adrenal gland in 4, axillary lymph nodes in 3, liver in 2, and 1 patient had a contralateral pulmonary metastasis. The number of metastases was one site in 13, two sites in 3, three sites in 1, and five sites in 2 patients. The patients with bone metastasis were treated with radiation, and the patients with brain metastasis underwent stereotaxic radiosurgery. The patients with either adrenal metastasis, axillary lymph node metastasis, or contralateral lung metastasis underwent surgical resection. Among the patients with distant metastasis, the 5-year survival rate was 30.1 %. There were 17 patients with pleural dissemination. The 5-year survival rate in these patients was 25.3%. The overall 5-year survival rate after surgery in the patients with stage IV disease was 26.8%. CONCLUSION Selected patients who can undergo surgical resection for the primary tumor and effective local therapy for metastatic lesions still have a chance to obtain long-term survival. Surgical treatment for NSCLC with oligometastatic disease can be considered as one arm of multidisciplinary treatment.

Serum Level of Osteopontin as a Prognostic Factor in Patients Who Underwent Surgical Resection for Non-Small-Cell Lung Cancer

BACKGROUND OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection. PATIENTS AND METHODS The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL. RESULTS The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321). CONCLUSION The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC.

Primary Gas Gangrene of the Pancreas : Report of a Case

Spontaneous gas gangrene of the pancreas, caused by an infection of Clostridium perfringens, is an extremely rare but severe form of acute pancreatitis. A 67-year-old man complaining of severe epigastric pain with diffuse guarding underwent an emergency laparotomy. During surgery, hemorrhagic pancreatic necrosis was observed with a large amount of peripancreatic gas. Cultures demonstrated C. perfringens. The identification of hemolysis and the accumulation of peripancreatic gas on computed tomography, which were both caused by an infection of C. perfringens, led us to make a diagnosis of clostridial infection of the pancreas.

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines

Abstract Background. This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection. Patients and methods. We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines. Results. Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively. Conclusions. The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.

Epidermal Growth Factor Receptor-GEP100-Arf6 Axis Affects the Prognosis of Lung Adenocarcinoma

The overexpression of Arf6 and GEP100 is responsible for the invasive activity that is crucial for the activation of the epidermal growth factor receptor (EGFR) signaling pathways in human cancer. However, whether or not the expression of the EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer has yet to be fully determined. Tumor specimens were collected from 182 patients who underwent a complete resection for lung adenocarcinoma. We analyzed phospho-EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively. Significant associations between p-EGFR and GEP100 expression and vessel invasion were identified. The expression of these individual molecules was not associated with any statistically significant differences in survival. However, triple positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with an increased risk of death based on the multivariate analysis. The EGFR-GEP100-Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma. The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of patients after surgery.