PRR11 immunoreactivity is a weak prognostic factor in non-mucinous invasive adenocarcinoma of the lung.

INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity. RESULTS: PRR11 immunoreactivity demonstrated a tendency to associate with an aggressive phenotype (tumor size, vascular invasion, and adjuvant therapy) and some effect on overall survival (Hazard ratio 1.51). CONCLUSIONS: PRR11 may be a weak prognostic indicator of overall survival of patients with non-mucinous invasive adenocarcinoma of the lung.

A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation.

Diffusion-weighted imaging vs STIR turbo SE imaging: capability for quantitative differentiation of small-cell lung cancer from non-small-cell lung cancer.

OBJECTIVE: To compare the capability of differentiation of small-cell lung cancer (SCLC) from non-SCLC (NSCLC) between diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR) turbo spin-echo imaging. METHODS: The institutional review board of Kobe University Hospital, Kobe, Japan, approved this study, and written informed consent was obtained from each patient. 49 patients with NSCLC (30 males and 19 females; mean age, 66.8 years) and 7 patients with SCLC (5 males and 2 females; mean age, 68.6 years) enrolled and underwent DWI and STIR. To quantitatively differentiate SCLC from NSCLC, apparent diffusion coefficient (ADC) values on DWI and contrast ratios (CRs) between cancer and muscle on STIR were evaluated. ADC values and CRs were then compared between the two cell types by Mann-Whitney's U-tests, and the diagnostic performances were compared by McNemar's test. RESULTS: There were significant differences of mean ADC values (p < 0.001) and mean CRs (p = 0.003). With adopted threshold values, the specificity (85.7%) and accuracy (85.7%) of DWI were higher than those of STIR (specificity, 63.3%; p = 0.001 and accuracy, 66.1%; p = 0.001). In addition, the accuracy of combination of both indexes (94.6%; p = 0.04) could significantly improve as compared with DWI alone. CONCLUSION: DWI is more useful for the differentiation of SCLC from NSCLC than STIR, and their combination can significantly improve the accuracy in this setting. ADVANCES IN KNOWLEDGE: Pulmonary MRI, including DWI and STIR, had a potential of the suggestion of the possibility as SCLC.

A variant form of myelodysplastic syndrome with Ph- minor-BCR/ABL transcript.

This study concerns a patient with minor (m)-BCR/ABL transcript-positive and Philadelphia (Ph) chromosome-negative myelodysplastic syndrome (MDS). The patient was a 78-year-old man whose condition was diagnosed as refractory anemia with excess of blasts in transformation. Molecular genetic studies, using reverse transcriptase polymerase chain reaction analysis detected m-BCR/ABL messenger RNA. We used spectral karyotyping to analyze metaphase cells but could not detect a Ph chromosome. Fluorescence in situ hybridization, however, revealed fusion signals of BCR and ABL probes on an apparently normal chromosome 22.

Association of p53 gene mutation and telomerase activity in resectable non-small cell lung cancer.

PURPOSE: Mutation of the p53 gene and deregulation of telomerase may be essential for canceration in some malignant diseases. However, relationships between these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). METHODS: Frozen sections of 40 surgically resected NSCLC specimens were used. DNA extracted from fresh tumor specimens was analyzed with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts on SSCP were reamplified, and the PCR products were directly sequenced. In addition, the telomerase activity of the same specimens was analyzed quantitatively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and pathologic parameters were evaluated using a statistical analysis system. RESULTS: Mutations of the p53 gene relevant to an altered protein were confirmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene mutation was significantly higher than that of the 21 specimens negative for p53 gene mutation. Furthermore, the degree of cell differentiation was significantly correlated with both p53 gene mutation and high telomerase activity. CONCLUSIONS: p53 gene mutation and high telomerase activity cooperate to induce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occurrence of p53 gene mutation and high telomerase activity may be relevant to the grade of malignancy in NSCLC.

Unconventional superconductivity in electron-doped layered Li0.48(THF)yHfNCL.

We report magnetic susceptibility measurements on a layered superconductor Li0.48(THF)0.3HfNCl having Tc approximately 26 K. The present study revealed that (a) the Fermi level density of states is small, N*(EF) approximately 0.25 states/(eV spin f.u.), (b) mass enhancement is negligible, gamma; approximately 1, (c) electron-phonon coupling is weak, lambda(ep)<<1, (d) exchange enhancement is negligible, 1/(1+F(a)0) approximately 1, and (e) electronic density parameter is large, r(2D)s approximately 10.3 (i.e., low-carrier density). It is difficult to explain the origin of the high Tc in terms of the conventional phonon (BCS) mechanism of superconductivity.

Endoluminal laser application under percutaneous cardiopulmonary support in severe tracheal stenosis.

Laser ablation under bronchoscopic guidance was conducted on 2 patients with severe tracheal stenosis. Case 1 was a 57-year-old man admitted to our emergency unit because asphyxia. Bronchoscopy showed the lumen occluded at the bifurcation by tracheal cancer. Case 2 was a 62-year-old woman who underwent tracheostomy elsewhere for respiratory failure caused by a brain contusion and was treated for 3 months. After transfer to our emergency unit, bronchoscopy showed severe tracheal stenosis. Tracheoplasty conducted under bronchoscopy used a noncontact Nd:YAG laser at an output of 10-40 W and irradiation time of 1 second per shot. Total irradiation energy was 1700-1900 J. Percutaneous cardiopulmonary support was used during the laser procedure due to asphyxia. All procedures were completed satisfactorily and clinical symptoms improved dramatically in both cases. Laser tracheoplasty under bronchoscopic guidance treated severe stenosis safely and completely. Percutaneous cardiopulmonary support was very useful in preventing severe respiratory failure or asphyxia during this procedure.

Importance of the control of lung recurrence soon after surgery of pulmonary metastases.

PURPOSE: In this study, we investigated factors that determined prognosis in patients who underwent surgery for metastatic lung tumors, focusing on early relapse of metastatic lung lesions after surgery, and considered countermeasures for improving long-term results based on this study. PATIENTS: This study was performed in patients with metastatic lung tumors who underwent surgery during the 22 years after November 1975 in this department. RESULTS: The 1-year, 3-year, and 5-year survival rates in all patients were 70%, 42%, and 37%, respectively. On comparison among the groups, there were no significant differences by gender, age, organ with the primary lesion, disease-free interval, number of metastases, or surgical procedure. However, prognosis was significantly poorer in patients with recurrent metastatic lung lesions. Prognosis was especially poor in patients with recurrence within 6 months after pneumonectomy, and this was an important factor that worsened the surgical results. CONCLUSIONS: As the mechanism of early recurrence of lung metastasis after surgery for metastatic lung tumor, multiple micrometastases (dormancy) that cannot be detected during surgery for metastatic lung tumor may be present in the lung. Establishment of a method of controlling an increase in dormant metastasis may lead to improvement of surgical results of metastatic lung tumors.

Video-assisted blebectomy using a flexible scope and a bleb implement.

We describe herein our new technique of performing video-assisted thoracic surgery (VATS) using a flexible scope and a bleb implement which allows for a reduction in the risk of overlooking small and flat blebs in patients with a spontaneous pneumothorax (SP). This technique was performed in 26 consecutive patients with a SP. A skin incision about 18 mm long was made in the area over which the patients had specified preoperatively, and meticulous observation of the apex and superior segment was performed using a bleb implement. Partial pneumonectomy with endoscopic staplers and laser ablation were carried out for pleural lesions. We found that VATS combined with a flexible scope and a bleb implement resulted in better visibility for detection and removal of any small and flat blebs.

Analysis of mutant p53 and telomerase activity in non-small cell lung cancer.

The number of mutant p53 protein-positive tumor cells in primary non-small cell lung carcinoma (NSCLC) cases were quantitated by flow cytometry (FCM) and the relationships of these data to various factors were evaluated. Furthermore, the method of quantitating telomerase activity was investigated. Forty patients with primary lung carcinoma encountered between December 1995 and December 1997 were investigated. Among these cases, telomerase activity was measured. Using PAb421, cells were reacted with fluorescent antibody and fluorescence was quantitated by FCM. Fluorescence index (FI) was estimated in relation to the positivity rates of negative controls and were quantitatively evaluated. FI values of normal lung tissue were obtained from normal lung tissue excised from young patients with pulmonary bulla. Values that were 2SD or more above the mean value of normal lung tissue (> 2.19) were regarded as mutant p53-positive, and 14 (35.0%) of 40 lung carcinoma cases were positive by this criterion. Of 13 poorly differentiated carcinoma cases, seven cases (53.8%) were positive, which was significantly high. Furthermore, the telomerase activity was converted to numerical values in 40 cases using the telomelic repeat amplication protocol (TRAP) method as well as the total product generated (TPG) method. The mean TPG value of the 40 cases was 75.21 +/- 15.63. Among these cases, the mean value of fourteen p53-positive cases was 124.49 +/- 37.19, which was higher than that of 26 negative cases, 48.68 +/- 10.88, showing a significant difference. The method used in this study was considered a useful method that allows accurate and objective evaluation of mutant p53 expression. It was suggested that mutant p53 expression may affect the degree of tumor cell differentiation. Consequently, it was confirmed in this study that mutant p53 expression and telomerase activity were closely associated in lung cancer.

An availability of video-assisted thoracic surgery for the resection of pulmonary metastases.

We report the use of video-assisted thoracic surgery (VATS) as a treatment for pulmonary metastases. Eight patients with metastatic lung cancer were treated with VATS techniques. These patients included 5 males and 3 females whose ages ranged from 34 to 61 years (average: 47.4). Their primary diseases were seminoma (n = 3), renal cell carcinoma (n = 2), colon carcinoma (n = 1), mammary carcinoma (n = 1) and choriocarcinoma (n = 1). Computed tomography (CT) scans with current generation scanners were performed preoperatively and revealed one metastatic lesion in each of five cases and two lesions in each of the other three cases. In one case, one lesion was located in each of the lungs. Tumor size ranged from 5 to 30 mm in diameter, and all lesions were in the peripheral field of the lung. VATS was carried out with three surgical ports for three cases, two surgical ports for one case, and only one port for two cases. For all cases, an endo-stapler was utilized. In two cases, the preoperative point-marking technique for tumors was employed under the guidance of CT imaging. All patients were discharged from the hospital with no complications, and were followed up with no evidence of lung recurrence. Our criteria in selecting patients for the VATS removal of metastatic lung tumors are as follows: 1) tumors are less than 30 mm in diameter in the peripheral lung, 2) the number of tumors detected by CT scan, etc., is one or two. We conclude that VATS is a good candidate for the resection of lung metastases in the selected cases. Long term outcome remains to be solved in the future.

Role of pleural lavage cytology before resection for primary lung carcinoma.

OBJECTIVE: To investigate the role of pleural lavage cytology (PLC) in resection for primary lung carcinoma. SUMMARY BACKGROUND DATA: The prognostic significance of PLC before manipulation is still controversial. METHODS: Cytology of pleural lavage immediately after thoracotomy but before any manipulation of the lung was examined in 500 consecutive patients with lung cancer with no pleural effusion who underwent pulmonary resections. Eighteen patients who already had pleural dissemination were excluded from this study. RESULTS: Eighteen of 482 patients (3.7%) had positive cytologic findings. The positivity of PLC was significantly correlated with histology, extension of tumor to pleura, and presence of lymphatic permeation or vascular involvement by tumor. Positive lavage findings were seen only in adenocarcinoma. Because 6.3% of the patients with adenocarcinoma had positive cytologic findings, it is vital to perform PLC before curative resections for lung cancer, especially adenocarcinoma. The 5-year survival rates of the patients having negative and positive lavage findings were 52.9% and 14.6%, respectively. The prognosis of the patients with positive lavage findings was as poor as that of the patients with stage IIIB disease and that of the patients with malignant effusion. CONCLUSIONS: Positive findings on PLC indicate exfoliation of cancer cells into the pleural cavity, which is an essential prognostic factor. In addition, we should regard positive cytologic findings as a subclinical malignant pleural effusion that is pathologic stage T4.

[Long-term results following resection for T3 non-small cell lung cancer].

Surgical intervention is routinely employed for non-small cell lung cancer, whenever no distant metastasis is found. However, its surgical results depend on the staging of the lung cancer, and surgery for stage III disease is less effective compared with stage I or II disease. For patients with stage III, some treatments such as induction chemotherapy have been tried to support the surgery. Recently, T3 lung cancer is divided in two category of staging, T3N0 is evaluated to be stage II B and T3N1-2 is stage III A. In this study, we classified T3 diseases by some factors, and examined long-term survival of each group. As a result, we concluded that mediastinal invasion and N2 involvement were risk factors to early failure. On the contrary, patients with adjacent lobe invasion and resection of two lobes led to the prolonged survival rather than lobectomy with partial resection of adjacent lobe.

Vascular endothelial growth factor increased by pulmonary surgery accelerates the growth of micrometastases in metastatic lung cancer.

BACKGROUND: The use of surgery for metastatic lung cancer has been established recently and the indications have been extended to multiple and bilateral lung metastases. However, in some patients, secondary lung metastasis appears soon after the first pulmonary surgery, making curative treatment very difficult. Postoperative weakness of tumor angiogenesis suppression mechanisms seems to play an important role in the recurrence of lung metastases. To verify this hypothesis, we performed a clinical and an experimental study. RESULTS AND CONCLUSION: The clinical study revealed that serum vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increased after pulmonary surgery. The experimental study showed that VEGF played an important role in the rapid growth of dormant micrometastases of the lung. These results suggested that the postoperative increase of VEGF disrupted angiogenesis suppression and induced the growth of dormant micrometastases early in the postoperative period. It was also demonstrated that this effect of VEGF on micrometastases was abolished by AGM-1470, an angiogenesis inhibitor. In conclusion, postoperative treatment with AGM-1470 might inhibit the early recurrence of malignant tumors.

The prognostic factor of the surgically treated metastatic lung cancer.

Surgical treatment for metastatic lung tumor has also been aggressively performed to treat multiple or bilateral lesions recently. However, in some patients, metastatic pulmonary foci have recurred after surgery for metastatic lung tumor. These foci could not be controlled even after performing thoracotomy several times in some patients. In this study, we examined prognostic factors in patients undergoing surgery for metastatic lung tumor with respect to early relapse of metastatic pulmonary foci after surgery, and discussed strategies for improving long-term results. This study included 120 patients who underwent surgery for metastatic lung tumor in our department between November 1975 and November 1997. Overall, the 5-year survival rate was 37.1%. When results were compared among groups, there were no significant differences related to age, gender, primary organ, DFI, number of metastatic foci or surgical technique. However, the prognosis was significantly poorer in patients with recurrent metastatic pulmonary foci after surgery. Especially in patients with early relapse within 6 months after resection of the lung, the prognosis was markedly poor. Early relapse was an important factor involved in unfavorable surgical outcomes. The mechanism involved in the early relapse of metastatic pulmonary foci after surgery for metastatic lung tumor may be associated with the presence of several micrometastases that could not be recognized during surgery for metastatic lung tumor, that is, dormancy, in the lung. Surgical outcomes in patients with metastatic lung tumor will be improved if a method of controlling this increase in dormant metastases is established.

[A surgical case for the huge chronic expanding hematoma developed in the thoracic cavity].

We report a case of operation against chronic expanding hematoma developed in the pleural cavity of the patient who were treated as anaplastic anemia. 69-year-old man had been underwent thymectomy because of the thymoma and hemogenic pleural effusion 8 years ago. Then, last year, he was pointed out severe thrombocytopenia and underwent transfusion of thrombocyte. In the same period, chest X-ray examination revealed development of the tumor-like shadow in the left lung field. The abnormal shadow has enlarged, so the patient admitted us. X-ray findings revealed the huge tumor occupied completely the left pleural space. He was also pointed out severe pancytopenia (WBC: 2,600/mm3, RBC: 172 x 10(4)/mm3, thrombocyto: 1.9 x 10(4)/mm#), and the examination of bone marrow revealed anaplastic anemia. Thoracotomy was underwent, and the tumor was resected. Pathological diagnosis of the tumor was huge hematoma. Negative pressure in the pleural space would keep the hemorrhage and make hematoma huge. The hematoma in the pleural space should be resected as soon as the diagnosis is decided.

[Characteristics of home parenteral nutrition and effectiveness of 3 way valved PICC in regional medical care].

Home medical care is becoming a greater matter of concern along with the increasing population of elderly persons. The various difficulties in home care are also found in regional care, and it could be said that in Japan regional care serves as an "advanced model" for home medical care. Ohya Town is located in the mountains of northern Hyogo Prefecture. It has a population of about 5,000 of which 32% is elderly people. There is no railroad, and it takes around 30 minutes to travel to the central hospital from the area. The three town clinics are in contact with each other and with the central hospital concerning medical information. The characteristics of Home Parenteral Nutrition in this underpopulated district are discussed and reported in reference mainly to cases in which the 3 way valved peripherally inserted central venous catheter (Groshong Catheter) is used, in comparison with HPN cases in the city university hospital.