[Influence of preoperative antithrombotic therapy on clinicopathological parameters in patients with lung cancer].

Cancer is known to promote its own development/proliferation and protect itself against attacks from immune system cells by activating the blood coagulation system. However, antithrombotic therapy inhibits the blood coagulation system. We investigated the blood coagulation system-mediated influence of preoperative antithrombotic therapy on the clinicopathological parameters of lung cancer. In patients who underwent antithrombotic therapy, there was a significant association between prothrombin time-international normalized ratio (PT-INR and positive findings on a thoracic lavage cytodiagnosis (p = 0.02). In these patients, the proportion of those with positive findings on a thoracic lavage cytodiagnosis was significantly higher than in those who did not undergo antithrombotic therapy (P = 0.0003). These results suggest that cancer progression is promoted by antithrombotic therapy through the inhibition of the blood coagulation system.

[Association between hemostasis/coagulation-system parameters and clinicopathological factors in patients with primary lung cancer].

Previous studies have gradually clarified the relationship between cancer and blood coagulation disorder and its mechanism. Various studies have also reported the association between lung cancer and coagulation disorder. However, it is rare to measure most hemostasis/coagulation-system test parameters in clinical practice. In this study, we investigated the association of hemostasis/coagulation-system test parameters, such as the prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time, and platelet count, which are routinely measured as preoperative examination parameters in patients with lung cancer, with the histopathologically evaluated stage of lung cancer. Although the mean values of hemostasis/coagulation-system parameters in all subjects were within the normal ranges, there were significant changes with respect to the clinico-pathological factors, showing a specific tendency. In patients in whom the histopathological stage was advanced, the APTT was prolonged, or the platelet count was increased.

Human lung microvascular endothelial cells as potential alternatives to human umbilical vein endothelial cells in bio-3D-printed trachea-like structures.

BACKGROUND: We have been trying to produce scaffold-free structures for airway regeneration using a bio-3D-printer with spheroids, to avoid scaffold-associated risks such as infection. Previous studies have shown that human umbilical vein endothelial cells (HUVECs) play an important role in such structures, but HUVECs cannot be isolated from adult humans. The aim of this study was to identify alternatives to HUVECs for use in scaffold-free structures. METHODS: Three types of structure were compared, made of chondrocytes and mesenchymal stem cells with HUVECs, human lung microvascular endothelial cells (HMVEC-Ls), and induced pluripotent stem cell (iPSC)-derived endothelial cells. RESULTS: No significant difference in tensile strength was observed between the three groups. Histologically, some small capillary-like tube formations comprising CD31-positive cells were observed in all groups. The number and diameters of such formations were significantly lower in the iPSC-derived endothelial cell group than in other groups. Glycosaminoglycan content was significantly lower in the iPSC-derived endothelial cell group than in the HUVEC group, while no significant difference was observed between the HUVEC and HMVEC-L groups. CONCLUSIONS: HMVEC-Ls can replace HUVECs as a cell source for scaffold-free trachea-like structures. However, some limitations were associated with iPSC-derived endothelial cells.

Comparison of survival between anatomic and non-anatomic liver resection in patients with hepatocellular carcinoma: significance of surgical margin in non-anatomic resection.

AIMS: Anatomic resection, i.e., systematic removal of a liver segment confined by portal branches, is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). The procedure may reduce tumour recurrence and enhance survival of HCC patients. To determine the significance of anatomic resection for HCC patients, we retrospectively conducted a comparative analysis between anatomic (AR) and non-anatomic liver resection (NAR) in 113 Japanese HCC patients with a solitary tumour, a tumour located within one segment, absence or invasion of distal to second order branches of the portal vein, and absence or invasion of peripheral branches of the hepatic vein. METHODS: Patients were divided into two groups, AR group (n = 49) and NAR group (n = 64). RESULTS: The prevalence of liver damage Grade B in the NAR group was significantly greater than in the AR group (p < 0.05). Tumour-free and overall survival following liver resection was not significantly different between AR and NAR groups. In the NAR group, tumour-free and overall survival in patients with tumour exposure at the surgical margin was significantly lower than with a surgical margin greater than 0 mm (not exposed) (p < 0.05). Survival between the AR and NAR groups without tumour exposure at the surgical margin was similar. CONCLUSIONS: Anatomic resection is the theoretical aim. In HCC patients with impaired liver functions, limited liver resection without tumour exposure may provide longer tumour-free and overall survival.

[How to treat arrhythmias in thoracic surgery].

After major noncardiac thoracic operations, various types of arrhythmia would occur. Particularly atrial fibrillation (Af), have remained one of the most frequent complications. In the literatures, risk factors for post operative Af have identified age, male, extent of pulmonary resection and mediastinal lymph node dissection. When we would meet the patients complicated with arrhythmia, the etiology of it must be identified and treated before operations. If accidental arrhythmia occurred during or after operations, the etiology of arrhythmia as hypoxia, hypercapnea, electrolyte disorder, overhydration and cardiac ischemia would be checked and cleared at first. Then appropriate drugs should be considered to use due to the type of arrhythmia. In supraventricular tachyarrhythmia, especially Af, landiolol and verapamil would be effective for the rate control and disopyramide and procaineamide for the defibrillation. Lidocaine and propranolol would be an appropriate choice for ventricular tachyarrhythmia during operations. For ventricular tachyarrhythmia related with acute myocardial infarction, lidocaine and mexiletine would be proper. In bradyarrhythmias a temporary pacing should be the first choice for urgent therapy. A prompt assessment and an adequate therapy must be mandatory for the arrhythmias after major noncardiac thoracic operations.

[Surgical treatment for stage IV lung cancer].

OBJECTIVE: To find out the optimal surgical indication in stage IV lung cancer patients, we evaluated them retrospectively. METHODS & RESULTS: From 1975 to 2005, 62 patients without multiple metastases were operated at our hospital. The most common histological type was adenocarcinoma (67.7%). The metastatic lesions were lung (33.9%), brain (24.2%), liver, bone, adrenal gland and so on. The overall survival rate of stage IV lung cancer was 10.4% at 5-year. Five-year survival for patients with lung or brain metastasis who had no lymph node metastasis were significantly more superior than those with lymph node metastasis (p=0.0389, 0.0021). Four of 62 patients had 5-year survival. Two were lung and the others were brain and adrenal gland metastasis without lymph node metastasis. CONCLUSION: Stage IV lung cancer with lung or brain or adrenal gland metastasis without lymph node metastasis should be resected.

Expression of p-STAT3 in human colorectal adenocarcinoma and adenoma; correlation with clinicopathological factors.

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule implicated in the regulation of growth and malignant transformation. Constitutive activation of STAT3 is seen in several tumour derived cell lines, and in a wide variety of human malignancies. AIMS: To examine the relation between p-STAT3 (activated form of STAT3) expression and clinicopathological factors in human colorectal adenocarcinoma and adenoma. METHODS: Immunohistochemical analyses were carried out on tissues from 44 colorectal adenomas and 95 colorectal adenocarcinomas, comprising 18 intramucosal carcinomas and 77 invasive carcinomas. RESULTS: Seventy seven of these 139 samples (55.4%) showed immunoreactivity for p-STAT3. Positive staining for p-STAT3 was seen in 69 of the 95 carcinomas. Only eight of the 44 adenomas showed immunopositivity for p-STAT3, resulting in a significant difference between total adenocarcinomas and adenomas (p < 0.001). Among the 95 cases of colorectal adenocarcinoma, p-STAT3 immunoreactivity was significantly correlated with the depth of tumour invasion (p < 0.05), venous invasion (p < 0.05), lymph node metastasis (p < 0.05), and increasing stages of the Dukes' classification (p < 0.01). Expression of p-STAT3 was detected by Western blot analysis in two different cultured human colorectal carcinoma cell lines and six colon carcinoma tissue samples obtained at surgery. CONCLUSION: This is the first study to report a significant correlation of p-STAT3 expression with the depth of tumour invasion. These findings suggest that p-STAT3 expression is an important factor related to carcinogenesis and/or tumour invasion of colorectal adenocarcinoma.

Comparative study of survival of patients with hepatocellular carcinoma predicted by different staging systems using multivariate analysis.

AIMS: In a previous pilot study, we reported the usefulness of the modified the Cancer of the Liver Italian Program (CLIP) score for patients with hepatocellular carcinoma (HCC). To determine the best staging system for predicting the survival of HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 210 Japanese HCC patients who underwent hepatic resection. METHODS: We compared the survival as predicted by various staging systems, including tumour node metastasis (TNM) stage of the American Joint Commission on Cancer (AJCC) and the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), CLIP score and our modified CLIP score using protein induced by vitamin K absence or antagonist II (PIVKA-II). RESULTS: Univariate analysis showed that discrimination of disease-free survival in the early and advanced stages by the JIS score and modified CLIP score was clearer than by the Japanese or AJCC TNM or the original CLIP score. Discrimination between stages of overall survival by all staging systems was significant. Multivariate analysis showed that the JIS, CLIP and modified CLIP scores were better staging systems for predicting survival than the Japanese and AJCC TNM. The modified CLIP score showed the lowest Akaike information criteria statistical value for disease-free and overall survival, which means the best discrimination ability for patient survival compared with the JIS score and CLIP score. CONCLUSIONS: A staging system that combines tumour factors, sensitive tumour marker(s) and hepatic function is the best predictor of prognosis of HCC patients.

Usefulness of intraoperative diagnosis of hepatic tumors located at the liver surface and hepatic segmental visualization using indocyanine green-photodynamic eye imaging.

BACKGROUND: To improve the diagnostic accuracy for hepatic tumors on the liver surface, we investigated the usefulness of an indocyanine green-photodynamic eye (ICG-PDE) system by comparison with Sonazoid intraoperative ultrasonography (IOUS) in 117 patients. Hepatic segmentation by ICG-PDE was also evaluated. METHODS: ICG was administered preoperatively for functional testing and images of the tumor were observed during hepatectomy using a PDE camera. ICG was injected into portal veins to determine hepatic segmentation. RESULTS: Accurate diagnosis of liver tumors was achieved with ICG-PDE in 75% of patients, lower than with IOUS (94%). False-positive and false-negative diagnosis rates for ICG-PDE were 24% and 9%, respectively. New small HCCs were detected in 3 patients. The ICG fluorescent pattern in tumors was strong staining in 41%, weak staining in 13%, rim staining in 20% and no staining in 26%. Hepatocellular carcinoma predominantly showed strong staining (61%), while rim staining predominated in cholangiocellular carcinoma (60%) and liver metastasis (55%). Hepatic segmental staining was performed in 28 patients, proving successful in 89%. CONCLUSION: ICG-PDE is a useful tool for detecting the precise tumor location at the liver surface, identifying new small tumors, and determining liver segmentation for liver resection.

Expression of tissue factor mRNA in cardiac xenografts: clues to the pathogenesis of acute vascular rejection.

BACKGROUND: Acute vascular rejection destroys vascularized xenografts over a period of hours to days and is now considered the major hurdle to the clinical application of xenotransplantation. The hallmark of acute vascular rejection is diffuse intravascular coagulation; however, the pathogenesis of coagulation is a matter of controversy. One line of evidence points to activated endothelial cells and another to activated inflammatory cells as a source of tissue factor and thus as a primary cause of this lesion. The distinction between the two mechanisms inducing coagulation in the xenograft provides an opportunity for specific intervention. METHODS: To explore these mechanisms, we studied the expression of tissue factor mRNA by in situ reverse transcriptase-polymerase chain reaction in relation to the histopathologic manifestations of acute vascular rejection in guinea pig hearts transplanted into rats treated by cobra venom factor to avoid the hyperacute rejection. RESULTS: Three hours after transplantation and before the deposition of fibrin, tissue factor mRNA was expressed in the endothelial cells lining small and medium blood vessels and in smooth muscle cells of guinea pig cardiac xenografts. Sixteen hours after transplantation, while rat tissue factor mRNA was expressed only in occasional infiltrating cells, cardiac xenografts showed prominent deposits of fibrin in small vessels. Maximum expression of tissue factor on rat infiltrating cells was observed 48 hr after transplantation. CONCLUSIONS: These results suggest that in acute vascular rejection, coagulation is initiated on the donor vascular system, while the procoagulant characteristics of infiltrating cells may reflect a response to tissue injury rather than a cause.

Twenty-four-hour preservation in gamma-hydroxybutyrate improves lung function in a canine single-lung allotransplantation.

BACKGROUND: We investigated the effect of gamma-hydroxybutyrate (GHB) when added to the low-potassium University of Wisconsin (LPUW) solution used for the preservation of canine lung for 24 hr. We also examined the effect of pretreatment of donor and recipient dogs with GHB on lung function after transplantation. METHODS: Two groups were investigated. In the LPUW group, donor lungs were flushed with LPUW solution without GHB. In the GHB group, donor and recipient dogs were pretreated with GHB, and donor lungs were flushed with LPUW containing GHB. RESULTS: Posttransplant graft function was best in the GHB group. At 1 hr after reperfusion, PaO2 in the GHB group (475.7+/-96.2 mmHg) was significantly higher than in the LPUW group (188.3+/-102.7 mmHg, P<0.05). Furthermore, the use of GHB resulted in a significant increase in lung compliance (28.3+/-6.5 ml/cm H2O) compared with LPUW group (21.5+/-2.8 ml/cm H2O). CONCLUSIONS: Our results suggest that GHB is potentially useful for functional improvement of hypothermically preserved canine lung allografts after reperfusion.

Expression of proliferating cell nuclear antigen in bronchial epithelium after lung transplantation in the rat.

BACKGROUND: The normal, mature airway epithelium in experimental animals has a very slow cell turnover and minimal proliferation. The aim of this study was to investigate the expression of proliferating cell nuclear antigen (PCNA) as an index of bronchial cell proliferation in the Brown Norway to Lewis rat pulmonary allograft model with or without immunosuppression. METHODS: Brown Norway left lungs were transplanted into Lewis recipients. Some recipients were treated with a high dose of cyclosporine and FK506. Lewis-to-Lewis donor-recipient combination was performed as a control. Lungs were excised on postoperative days 3 and 5. Routinely processed, paraffin-embedded sections were prepared and stained by PCNA. Counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchial surface epithelium were compared with the histologic grade of rejection. RESULTS: The PCNA index (percent of nuclei immunostaining for PCNA) in bronchial surface epithelium was significantly higher in allografts (21.0% +/- 3.1% at 3 days, 31.4% +/- 9.8 % at 5 days, p < 0.05) than in isografts (5.4% +/- 3.0% at 3 days, 4.7% +/- 4.6% at 5 days). The PCNA index was also greater in the perivascular infiltrates of rejecting lungs (23.9% +/- 3.7% at 3 days, 29.1% +/- 6.6% at 5 days). However, in the cyclosporine- and FK506-treated groups, the PCNA index in bronchial surface epithelium was suppressed to less than 5% at 3 and 5 days. Even at 50 days after transplantation, PCNA-positive cells were rare in bronchial epithelium of FK506-treated grafts. CONCLUSIONS: Bronchial epithelium in isografts has a relatively low rate of proliferation. In rejection, allografts have a very rapid cell turnover and proliferation. Proliferating epithelium may be a consequence of immune events or it may contribute to the pathogenesis of those events.

Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer.

PURPOSE: The prognostic value of altered blood group factor and Lewis-related carbohydrate antigen expression in breast cancers has not been fully determined. METHODS: To this end, breast carcinoma samples from 87 radical mastectomy patients with primary cancer were analyzed by immunohistochemistry for the ABH factors, Le(a), sialyl Le(a), Le(x), and sialyl Le(x). RESULTS: It was found that ABH, Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens were expressed in 25 (21.8%), 26 (22.6%), 26 (22.6%), 36 (31.3%), and 37 specimens (32.2%), respectively. Tumors with lymph node metastasis expressed Le(x) or sialyl Le(x) antigens more frequently than those without lymph node metastasis ( P=0.0020 or P=0.039, respectively). The survival time of patient s after surgery was significantly shorter for those whose tumors expressed Le(x) or sialyl Le(x) than for those without Le(x)- or sialyl Le(x)-positive tumors ( P=0.0028 and P=0.0029, respectively). Cox's multiple regression analysis revealed that sialyl Le(x) expression was an independent prognostic factor for patient survival regardless of primary tumor (T factor) and lymph node (N factor) status (hazards ratio, 3.80). CONCLUSIONS: Thus, expression of sialyl Le(x) antigen in tumor cells is associated with poor prognosis in patients with breast cancer and must be considered in the design of future therapeutic trials.

A case of solitary pulmonary lymphangioma.

Solitary pulmonary lymphangiomas are rare benign lesions thought to result from the development of abnormally proliferating lymphatic vessels. This report describes a case of solitary pulmonary lymphangioma resected under video assisted thoracoscopic surgery and diagnosed using histological and immunohistochemical investigations.

Platelet-derived endothelial cell growth factor expression is an independent prognostic factor in colorectal cancer patients after curative surgery.

AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas. METHODS: PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had received curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68. RESULTS: PD-ECGF expression in the normal mucosa was 34.4+/-15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group (P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. CONCLUSIONS: The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.

The Japanese integrated staging score using liver damage grade for hepatocellular carcinoma in patients after hepatectomy.

AIMS: The new Japanese staging system for hepatocellular carcinoma (HCC), the Japan integrated staging (JIS) score, accounts for both Child-Pugh classification and Japan tumour node metastasis (TNM) staging. However, in HCC patients who undergo hepatectomy, liver function is relatively good and a better prognostic classification of hepatic function is necessary. METHODS: The present study was designed to analyse the modified JIS score using liver damage grade by the Liver Cancer Study Group of Japan instead of the Child-Pugh classification (using the category indocyanine green retention rate at 15 min [ICG(R15)] instead of encephalopathy), and to compare the Japan TNM stage in 101 patients who underwent resection of HCC. RESULTS: The liver damage grade showed significantly better discrimination of disease-free and overall survival than did the Child-Pugh classification. The modified JIS score system showed significant differences of disease-free and overall survivals in each score and this system was superior for discriminating survivals compared with the TNM staging. CONCLUSIONS: The combined staging system of hepatic function, particularly ICG(R15), and tumour stage provides a better prediction of prognosis. The JIS score using the liver damage grade was a useful predictor of prognosis of HCC patients who underwent hepatic resection.

Coexistence of lung cancer and tuberculoma in the same lesion: demonstration by high resolution and contrast-enhanced dynamic CT.

We report a case of coexistence of lung cancer and tuberculoma in the same lesion. The component parts of lung cancer and tuberculoma were identified on the basis of morphology on high-resolution CT as well as enhancement patterns and time-attenuation curves by contrast-enhanced dynamic CT.

Completion pneumonectomy for recurrent or second primary lung cancer.

OBJECTIVE: We studied 8 patients undergoing completion pneumonectomy for recurrent or second primary lung cancer. METHODS: Subjects were men who averaged 62 years of age. Of these 6 had p-stage I, and 2 p-stage II disease at initial operation. At the second operation, we diagnosed 3 with second primary lung cancer and 5 with recurrent lung cancer. We predicted postoperative pulmonary function by calculating the predicted forced expiratory volume in 1.0 second (FEV1.0) from residual numbers of subsegments after completion pneumonectomy. All predicted FEV1.0 in our 8 cases ranged from 544 to 926 (773 +/- 144) ml/m2. RESULTS: Six patients experienced postoperative complications and morbidity was 75%. One patient undergoing completion sleeve pneumonectomy after radiation therapy for local carina recurrence died on 7th postoperative day due to anastomotic dehiscence and pneumonia. Overall operative mortality was 12.5% (1/8). Four remain alive and actuarial 5-year survival was 37.5%. CONCLUSIONS: Careful consideration is needed in determining operative indications for completion pneumonectomy for patients after radiation therapy. Patients with recurrent squamous cell carcinoma who have p-stage I disease at initial operation and those with second primary lung cancer and p-stage I or II disease can expect relatively a long-term survival, and we concluded that completion pneumonectomy could be conducted in these cases with a satisfactory prognosis.