OBJECTIVES: The aim of this study was to analyse the survival of non-small cell lung cancer (NSCLC) patients with adjacent lobe invasion (ALI) with emphasis on the interlobar fissure status at the tumour invasion point. METHODS: We retrospectively evaluated 2097 consecutive patients with surgically resected NSCLC from July 1993 through April 2006. Of these, 90 (4.3%) patients had tumours with ALI. We divided ALIs into two types by histological examination using elastic stains: direct ALI beyond the incomplete fissure (ALI-D, n = 18) and ALI across the interlobar fissure (ALI-A, n = 72), and compared the clinicopathological features and survival. RESULTS: The patients with ALI demonstrated an intermediate survival between T2a and T2b tumours (5-year overall survival: T2a, 61.0%; ALI, 59.6%; T2b, 49.2%). There were distinct survival differences between the patients with ALI-A and ALI-D (5-year overall survival: ALI-D, 85.7%; ALI-A, 52.0%; P = 0.010). The survival of patients with ALI-A was not statistically different from that of patients with T2b tumours, regardless of the tumour size (P = 0.846). The survival of the patients with ALI-D did not statistically differ from those with T1a or T1b tumours (P = 0.765 and 0.418, respectively). CONCLUSIONS: Our results indicate that the interlobar fissure status affects the survival of the patients with ALI. ALI should be examined by elastic stains and only ALI-A should be classified as true ALI. We propose that ALI-A tumours with a size of ≤5 cm should be assigned to T2b, but ALI-D tumours do not require an adjustment of the T descriptor.

We describe the successful treatment of pulmonary aspergilloma by limited thoracoplasty used simultaneously with single-stage cavernostomy and a muscle transposition flap. An 80-year-old man with dyspnea on effort and hemoptysis consulted our hospital. Chest computed tomography revealed a thick wall cavity containing a fungus ball surrounded by a crescent of air and diseased lung parenchyma, indicating complex pulmonary aspergilloma (CPA). As curative pulmonary resection was considered too invasive for this patient, limited thoracoplasty with simultaneous single-stage cavernostomy and myoplasty was performed as an alternative treatment. During the operation, transposition flap of the latissimus dorsi muscle was created by preserving the feeding artery. Fungus, in the ball that was removed, proved to be aspergilloma by culture and histopathological examination. On postoperative day 15, the patient was discharged uneventfully, and 4 months after surgery, no relapse of the aspergilloma has been observed.We consider that limited thoracoplasty with simultaneous single-stage cavernostomy and a muscle transposition flap is effective for treatment of high-risk CPA.

The operative indications for rib fracture repair have been a matter of debate. However, several reports have suggested that flail chest, pain on respiration, and chest deformity/defect are potential conditions for rib fracture repair. We describe our experience of rib fixation in a patient with severe chest deformity due to multiple rib fractures.A 70-year-old woman was admitted with right-sided multiple rib fractures (2nd to 7th) and marked chest wall deformity without flailing caused by an automobile accident. Collapse of the chest wall was observed along the middle anterior axillary line. At 11 days after the injury, surgery was performed to repair the chest deformity, as it was considered to pose a risk of restrictive impairment of pulmonary function or chronic intercostal pain in the future. Operative findings revealed marked displacement of the superior 4 ribs, from the 2nd to the 5th, and collapse of the osseous chest wall towards the thoracic cavity. After exposure of the fracture regions, ribs fixations were performed using rib staplers. The total operation time was 90 minutes, and the collapsed portion of the chest wall along the middle anterior axillary line was reconstructed successfully.

Background The blood pressure response to the rapid removal of fluid during hemodialysis is complex and the pathophysiological mechanisms underlying intradialytic hypotension are not clear and sometimes these mechanisms render dialysis difficult to continue. Purpose We analyzed the changes in blood pressure and sympathetic nerve tone and attempted to clarify whether the dynamic pattern of this relationship reflects cardiovascular dysfunction. Methods The dynamic pattern of sympathetic nerve activity throughout dialysis was analyzed by frequency analysis of RR intervals recorded by 24 hours Holter electrocardiography in 64 patients and 3 minutes ECG every 15 minutes during dialysis in 121 stable end-stage renal failure patients who underwent maintenance hemodialysis. Blood pressure and fluid volume removed was measured every 15-30 minutes during dialysis and the average value of the ratio of low to high frequency components (LF/HF) was calculated as an index of sympathetic nerve tone. The relationship between removed fluid volume, systolic blood pressure (Bp) and LF/HF was analyzed. Results The patients were classified into 3 groups based on the correlation between the LF/HF and Bp as follows: positive (52 cases), inverse (54 cases), and not significant (NS; 61 cases). Eighteen patients who showed multiple arrhythmias, atrial fibrillation and other artifacts or noises were eliminated as they were inadequate for frequency analysis of RR intervals. The positive group was characterized by a hypotension-resistant response with a low LF/HF, whereas the inverse group was characterized by a hypotension-prone response with high LF/HF. These results suggest that cardiovascular dysfunction is responsible for the inverse correlation. Conclusion Analysis of the relationship between sympathetic nerve tone and Bp is effective in predicting the existing of cardiovascular dysfunction.

We have previously reported the efficacy of the Patient Oriented Clerkship (POC) in the clinical clerkship in Showa University Hospitals, by a trial with old four-year pharmacy program students. In the unique clerkship, each student has a patient in charge, and follows his/her clinical conditions throughout the rotation. The aim of the POC is that having the students learn spontaneously (Active Learning) and actively (Adult Learning) promoted by student's commitment and responsibility by communicating with patients and health professionals in a team. As the POC requires students both Active Learning and Adult Learning, we define the POC as Active Adult Learning (AAL). Having a patient in charge for each student gives them many opportunities to participate in the medical team and foster their problem solving skills. Our previous study eventually showed positive results of the POC in the one-month short clerkship in the four-year program. On the other hand, the effect of the unique hospital clerkship in the new six-year program is not known. We conducted a student survey to clarify the learning effect in the new six-year education system which was revised and 2.5 month clinical clerkship was scheduled according to the model core clerkship curriculum. This report is the first report to show a challenge of the AAL/POC clerkship in the new six-year pharmacy education program.

During the metastatic process, cancer cells interact with vascular adventitial fibroblasts (VAF), which are the main components of the outermost connective tissue layer of blood vessels. This activity suggests the presence of a specific tumor microenvironment in the perivascular area. The s.c. coinjection of human lung adenocarcinoma cell lines (A549, PC-14, and CRL-5807) and human VAF (hVAF) resulted in a high rate of tumor formation, compared with the coinjection of these cell lines and human lung tissue-derived fibroblasts (hLF). A cDNA microarray analysis revealed a higher expression level of podoplanin in hVAFs than in hLFs (4.7-fold). Flow cytometry analysis also showed a higher expression level of podoplanin in hVAFs (43% ± 17.5%) than in hLFs (16% ± 10.3%). Sorted podoplanin-positive hVAFs displayed enhanced tumor formation, lymph node metastasis, and lung metastasis of A549 compared to sorted podoplanin-negative hVAFs. Knockdown of podoplanin in hVAFs decreased the augmenting effect of tumor formation and in vitro colony formation. The overexpression of podoplanin in hVAFs hastened the tumor formation of A549, compared with control hVAFs. Furthermore, the analysis of small-sized human lung adenocarcinoma (n = 112) revealed that patients with podoplanin-positive cancer-associated fibroblasts had a significantly higher rate of lymph node metastasis and a high risk of recurrence. These results indicate a promotive effect of hVAFs mediated by podoplanin on cancer progression and suggest that the perivascular environment may constitute a specific niche for tumor progression.

BACKGROUND We retrospectively analyzed pulmonary adenocarcinoma patient survival in our single-institution database to evaluate the impact of solid adenocarcinoma components (SAC) on survival and to propose a method of incorporating SAC into the T classification in future staging systems. METHODS We reviewed 504 consecutive patients with surgically resected pulmonary adenocarcinoma for their clinicopathologic characteristics and prognoses, stratifying patients according to predominant adenocarcinoma subtype. We also stratified patients with an SAC-containing tumor according to the ratio of SAC in analyzing outcome. RESULTS Patients with SAC (SAC+) had significantly poorer prognoses than patients without any SAC (SAC-), irrespective of SAC ratio. Patient groups stratified by pathologic T classification up to T2b could be divided into four categories according to SAC status in decreasing order of survival:(I) T1a/SAC-;(II) T1b/SAC-;(III) T1a/SAC+, T1b/SAC+, and T2a/SAC-; and (IV) T2a/SAC+ and T2b/SAC-. CONCLUSIONS Pulmonary adenocarcinoma patients with any amount of SAC had worse prognoses than those without any SAC. The presence of SAC was an independent unfavorable prognostic factor, comparable to other pathologic findings indicating invasion. Solid adenocarcinoma component was an upstaging factor in T classification for T1 and T2a pulmonary adenocarcinomas. If SAC is present, we propose T1 and T2a tumors should be classified as T2a and T2b, respectively.

Adult onset neuroblastoma arising in the mediastinum, except posterior mediastinum is extremely rare. We report a case of surgically resected neuroblastoma in the superior mediastinum. A 64-year-old male was admitted to a local hospital, after an abnormal shadow had been detected on a chest radiogram on a routine medical checkup. Computed tomography (CT) examination revealed the tumor located in the superior mediastinum. Preoperatively, we suspected malignant lymphoma or lymph node metastasis from an unknown primary site. We resected the mediastinal tumor for both definitive diagnosis and local treatment. The tumor was composed of sheets of small round cells positive for CD56, NSE, chromogranin A, and vimentin, but negative for AE1/3, CK5/6, CK7, CD3, CD20, CD79a, c-kit, S-100, SMA and CD99. N-myc gene amplification was also confirmed and supported diagnosis of neuroblastoma. Chest CT seven months after surgery revealed multiple recurrences in lymph nodes.

Metastatic tumor formation via vessel route begins with cancer cell extravasation from vessel lumen, migration into the connective tissue surrounding vessels, and invasion into target organ parenchyma. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) have been recognized to play an important role in metastatic process, however, how and where these biological changes take place in the early phase of metastatic tumor development has never been clarified. We morphologically evaluated 34 small intrapulmonary metastases formed after cancer cell extravasation from lymphatics (lymphogenic metastasis) and 40 formed in the absence of extravasation (aerogenous metastasis) in human specimens and found that isolated or small clusters of invasive cancer cells (tumor budding) were frequently observed in lymphogenic metastasis (24/34; 71%), but were never observed within aerogenous metastasis. We immunostained 34 lymphogenic metastases for 13 molecular markers of EMT and MET and scored the immunostaining intensity of cancer cells floating in lymphatic vessels (LV), migrating into the connective tissue surrounding vessels (bronchovascular bundle; BVB), and growing in lung parenchyma (LP). Cancer cells within BVBs stained more weakly for E-cadherin (p<0.001), beta-catenin (p<0.001), and Geminin (p<0.001) and more strongly for MMP-7 (p=0.046) and Laminin-5 gamma2 (p=0.037) than tumor cells in LVs. However, cancer cells in LP exhibited resurgent E-cadherin (p=0.011), beta-catenin (p<0.001), and Geminin (p=0.037) expression and reduced MMP-7 (p=0.038) and Laminin-5 gamma2 (p=0.001) expression in comparison with cancer cells in BVBs. Our results suggested that in the early phase of metastatic tumor formation cancer cells undergo dynamic phenotypic change associated with EMT and subsequent MET.

OBJECTIVES: Although ischemic electrocardiographic (ECG) changes during dipyridamole or adenosine infusion have been reported as a marker for severe coronary artery disease (CAD), few studies have focused on ST-segment changes with adenosine triphosphate (ATP)-loading myocardial single-photon emission computed tomography (SPECT). METHODS AND SUBJECTS: Between January 2003 and August 2008, 4650 consecutive patients underwent ATP-loading SPECT. After 1412 patients with left bundle branch block, pacemaker rhythm, or previous coronary revascularization were excluded, 16 out of 3238 patients (0.5%) showed ischemic ST-segment depression during ATP-loading myocardial SPECT. They were aged 67+/-11 years; 10 were men and 6 women. Of these patients, 8 demonstrated perfusion abnormalities, whereas the remaining 8 showed normal myocardial perfusion imaging. In 6 of the 8 patients with abnormal SPECT, coronary angiography was performed, revealing left main trunk disease in 1 patient, 3-vessel disease in 4, 1-vessel disease with proximal left ascending artery occlusion in 1, and an insignificant lesion in 1. By contrast, no major cardiac event was observed in the 8 patients with normal SPECT during follow-up for an average of 2 years. CONCLUSION: The prevalence of ischemic ST-segment changes during ATP loading is very rare. However, this finding should be taken into account since almost half of the patients, particularly those with perfusion abnormalities, may have severe CAD which requires coronary revascularization.