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Acute pulmonary embolism is a serious perioperative complication. Current guidelines focus on hemodynamic stabilization and rapid restoration of pulmonary artery blood flow. However, various complications, most notably bleeding, are associated with treatment of the embolism. We report a case of acute pulmonary embolism with cardiopulmonary arrest during orthopedic surgery. Prompt thrombolysis and gaining control of both thrombolytic therapy-induced bleeding from the wound and a hepatic cyst enabled the patient to recover without neurological deficits.

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P

We evaluated the image quality and diagnostic performance of late iodine enhancement (LIE) in dual-source computed tomography (DSCT) with low kilo-voltage peak (kVp) images and a denoise filter for the detection of acute myocardial infarction (AMI) in comparison with late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). The Hospital Ethics Committee approved the study protocol. Before discharge, 19 patients who received percutaneous coronary intervention after AMI underwent DSCT and 1.5 T MRI. Immediately after coronary computed tomography (CT) angiography, contrast medium was administered at a slow injection rate. LIE-CT scans were acquired via dual-energy CT and reconstructed as 100-, 140-kVp, and mixed images. An iterative three-dimensional edge-preserved smoothing filter was applied to the 100-kVp images to obtain denoised 100-kVp images. The mixed, 140-kVp, 100-kVp, and denoised 100-kVp images were assessed using contrast-to-noise ratio (CNR), and their diagnostic performance in comparison with MRI and infarcted volumes were evaluated. Three hundred four segments of 19 patients were evaluated. Fifty-three segments showed LGE in MRI. The median CNR of the mixed, 140-, 100-kVp and denoised 100-kVp images was 3.49, 1.21, 3.57, and 6.08, respectively. The median CNR was significantly higher in the denoised 100-kVp images than in the other three images (P

To address a possible link between systemic and coronary inflammation in the setting of acute coronary syndromes, the authors examined both levels of 3 inflammatory mediators such as high sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, and matrix metalloproteinase (MMP)-9 in patients with the early phase of acute myocardial infarction (AMI). In total, 20 patients with AMI showing minimal elevation of cardiac enzymes were studied. Before angioplasty, peripheral blood and culprit coronary thrombus were sampled to compare systemic and coronary levels of hs-CRP, IL-6, and MMP-9. Relation of systemic levels of hs-CRP and IL-6 to culprit coronary morphology was also evaluated by the use of intravascular ultrasound. Systemic and coronary levels of hs-CRP were nearly equivalent (4.3 +/- 5.0 vs 4.7 +/- 5.4 mg/L, p = 0.279), whereas IL-6 and MMP-9 showed higher in coronary levels than in systemic levels (169 +/- 154 vs 93 +/- 107 microg/mL, p = 0.002 and 164 +/- 116 vs 103 +/- 94 ng/mL, p = 0.018, respectively). Systemic levels of hs-CRP were correlated with coronary levels of IL-6 (r = 0.566, p = 0.009). Culprit coronary plaque area demonstrated a positive relation with systemic levels of hs-CRP (r = 0.466, p = 0.038) and also IL-6 (r = 0.707, p0.001). The present study may provide an important insight into the link between systemic and coronary levels of inflammation, which is also associated with vulnerable coronary morphology in the setting of acute coronary syndromes.

Two rare cases, each with a solitary brain metastasis from breast cancer with extensive nodal metastases as the first site of distant metastasis, were locally treated with surgery and irradiation. The outcome of the two treated cases indicated an excellent and non-recurrent post-therapeutic survival period of more than 3 and 8 years, respectively. In a 50-year-old woman (Case 1), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with doxorubicin and tegafur-uracil (UFT) and hormonal therapy with tamoxifen for left breast cancer. The brain metastasis was treated twice surgically followed by radiotherapy. One year and 6 months later, local recurrence of the brain metastasis appeared and was treated surgically again. No other treatment was done thereafter. Since then, no other distant or lymph node metastasis occurred, and to date her outcome has been non-eventful for 8 years and 5 months. In a 63-year-old woman (Case 2), a solitary brain metastasis was found to have developed after standard radical mastectomy and adjuvant chemotherapy with cyclophosphamide, epirubicin and fluorouracil (CEF) for right breast cancer. The brain metastasis was treated locally with surgery and irradiation of 50 Gy. She thereafter received no further treatments. Since then neither distant metastases nor local recurrence have developed, and to date the post-treatment outcome has been uneventful for 37 months. Our findings suggest that patients who developed a solitary brain metastasis as the first site of distant metastasis from breast cancer have a chance of achieving long-term disease-free survival when treated with aggressive local therapy, even in the presence of extensive lymph node metastases at the primary surgery site for breast cancer.

Objective The aim of this study was to evaluate the efficacy of the objective radiologic analysis of high-resolution computed tomographic images of small peripheral non-small cell lung cancer and to select the candidates for curative limited resection. Methods High-resolution computed tomographic images of 146 surgically resected T1 N0 M0 peripheral non-small cell lung cancers were analyzed by using National Institutes of Health image software and classified on the basis of the percentage of ground-glass opacity within the tumor. Results Eighty-seven percent of tumors with ground-glass opacity ratios of 90% to 100% (type I) were diagnosed as noninvasive bronchioloalveolar carcinoma, whereas 55.6% of tumors with ground-glass opacity ratios of 50% to 89% (type II) consisted of adenocarcinoma. Tumors with ground-glass opacity ratios of 50% or more (type I/II) had no nodal involvement, whereas nodal metastases were identified in 20.0% of tumors with ground-glass opacity ratios of 10% to 49% (type III) and 24.4% of tumors with ground-glass opacity ratios of less than 10% (type IV). No tumors with ground-glass opacity ratios of 50% or more showed vessel infiltration, except for one lesion with a ground-glass opacity ratio of 50%. The 3-year disease-free survival was 97.7% for type I/II, 86.1% for type III, and 78.5% for type IV tumors. Conclusions The objective quantitative radiologic analysis with National Institutes of Health image software exhibited a good correlation with the histologic classification, pathologic invasiveness, and postoperative outcome of small peripheral lung cancer. Patients with tumors that have ground-glass opacity ratios of greater than 50% are considered to be possible candidates for limited pulmonary resection.

We report a rare and unique case of possible extrapulmonary tuberculosis in an 83-year-old man who had cardiac tamponade and paroxysmal atrial flutter. The patient was admitted to our hospital because of syncope. The cardiac tamponade and paroxysmal atrial flutter were treated by pericardiocentesis and drainage of bloody pericardial fluid. Mycobacterium tuberculosis was not detected in diagnostic specimens, nor was any evidence of malignancy found. The remarkable elevation of adenosine deaminase and the predominance of lymphocytes in the pericardial fluid, considering the past history of tuberculosis, led to a diagnosis of extrapulmonary tuberculosis. After receiving standard antituberculous therapy by ethambutol, isoniazid, and rifampicin, the patient recovered and has remained well up to the present day. Thirty-six months have passed since his recovery without the recurrence of cardiac tamponade or any other cardiac events.

Background With recent advances in low-dose helical computed tomography (CT), detection of ground-glass opacity (GGO) has increased. The aim of this study was to correlate high-resolution CT (HRCT) findings with pathologic features and to evaluate the efficacy of thoracoscopic limited resection for focal GGO, which were selected based on HRCT findings. Methods Focal GGO lesions were classified into two subtypes based on HRCT findings: pure type and mixed type. Ninety-six patients with persistent GGO 2 cm or less in diameter underwent pulmonary resection from January 1997 to December 2001. Among these, thoracoscopic wedge resection was performed prospectively between June 2000 and December 2001 in 33 patients with pure GGO lesions that were 1 cm or less. Results Thoracoscopic wedge resection was completed with complete safety. The histologic diagnoses of these 33 lesions were adenocarcinoma in 1, bronchioloalveolar carcinoma (BAC) in 23, and atypical adenomatous hyperplasia (AAH) in 9. No patients have had any evidence of tumor recurrence to date. Of the total 96 GGO lesions, 93.0% (53/57) of pure GGO 1 cm or less were BAC or AAH, whereas 38.5% (15/39) of pure GGO larger than 1 cm or mixed GGO were adenocarcinoma. Conclusions Pure GGO 1 cm or less was characteristic of noninvasive lesions. Thoracoscopic limited resection for small GGO lesions selected by HRCT was valid.

This study was designed to compare the efficacy of bevantolol, a beta(1)-selective blocker with alpha-blockade and vasodilating activity, with that of metoprolol, a beta(1)-selective receptor blocker, for the treatment of idiopathic dilated cardiomyopathy (DCM). Forty-one patients with DCM were enrolled to receive either bevantolol or metoprolol in addition to the standard therapy for DCM. They were classified into two groups: 16 patients were treated with bevantolol and 25 were treated with metoprolol. Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured before treatment and after 6 months of treatment. Left ventricular dimension at end-diastole and end-systole was significantly lower and fractional shortening was significantly higher after treatment than before treatment in both groups. The plasma ANP and BNP levels were significantly decreased in both groups. Changes in all variables, except for systolic blood pressure, showed no significant differences between the two groups. In conclusion, bevantolol showed parallel beneficial effects to those of metoprolol on cardiac function and natriuretic peptides in patients with DCM.

Arterial compliance is associated with the first stage of hypertension and atherosclerosis. We propose here a compliance index, which measures pulsating renal blood flow distribution using a power Doppler ultrasound (US). We assessed the relationship between the compliance index and blood pressure and between the compliance index and risk factors of atherosclerosis. The subjects consisted of 136 consecutive patients (96 males, 40 females) who underwent a physical checkup. Ages ranged from 40 to 60 years with a mean of 50.1 years. Patients with past renal disease and/or renal dysfunction were excluded. Using a power Doppler US combined with an ECG-gated and echo-tracking system, we recorded the vascular distribution of the renal parenchyma at 8 to 10 time points during an interval of the R wave of the ECG. Using a color pixel counting technique, we calculated the area (A) corresponding to the colored vascular distribution at power Doppler US. The relationships between A and the time points (t) were fitted to a quadratic equation. The compliance index of renal parenchymal vessels was obtained by twice differentiating the quadratic equation obtained above (d2A/dt2), and taking the result as a new hemodynamic index. In the univariate correlation analysis, the compliance index was correlated with age (r=-0.26, p=0.002), systolic blood pressure (r=-0.33, p=0.0001), diastolic blood pressure (r=-0.45, p

Insulin-like growth factor-1 (IGF-1) is important in the hypertrophic response of the myocardium, so the present study was designed to elucidate whether the circulating levels of IGF-1 and its binding proteins (IGFBPs) are related to the disease condition of patients with hypertrophic cardiomyopathy (HCM), in particular the occurrence of congestive heart failure (CHF). The study group comprised 124 patients with HCM and 15 healthy control subjects. The HCM patients were subdivided into 3 groups: 39 with hypertrophic obstructive cardiomyopathy (HOCM), 67 with hypertrophic non-obstructive cardiomyopathy (HNCM), and 18 with HCM and a history of CHF (HF-HCM, n=18). Serum levels of IGF-1 and IGFBPs (IGFBP-1 and -3) were compared between groups. IGF-1 levels were significantly higher in patients with HOCM and HNCM, and lower in patients with HF-HCM than in control subjects (p

This study was performed to evaluate whether thallium-201 myocardial scintigraphy (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the usefulness of beta-blocker therapy in patients with dilated cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before beta-blocker therapy. Patients were classified into group A, if their cardiac function improved, and group B, whose function remained unchanged. Two types of extent score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES-2) and mean-3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated, and according to ES and ES difference, DCM cases were classified into 3 groups: mild-defect type (mild-type), moderate-defect type (moderate-type) and severe-defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated, and the percent washout ratio of myocardial MIBG was obtained from these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type cases. A significant relation was observed between the defect type on Tl-201 and the response to beta-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and washout ratio were not significantly different in the 2 groups. Tl-201 may be useful for predicting the response to beta-blocker therapy in patients with DCM.

A 65-year-old Japanese woman with dilated cardiomyopathy, hypothyroidism and refractory sustained ventricular tachycardia experienced a near-death hypoglycemic syncope. The attack seemed to be induced by a high level of serum insulin, probably due to cibenzoline and by concomitant use of an angiotensin converting enzyme inhibitor (ACEI). Additionally, decreased food intake because of a severe toothache may have contributed to the deterioration of her condition. This case warns cardiologists that a combined cibenzoline and ACEI therapy can provoke serious adverse effects such as hypoglycemic syncope in the elderly. Therefore, the possibility of a hypoglycemic attack associated with these drugs should be explained to patients who are in poor condition.

The effect of cibenzoline on left ventricular diastolic function was investigated in patients with hypertrophic cardiomyopathy (HCM). Before and 2 h after an oral administration of 200 mg of cibenzoline, echocardiographic, apexcardiographic and gated radionuclide angiographic studies were performed in 12 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 7 with hypertrophic nonobstructive cardiomyopathy (HNCM). After administration of cibenzoline, the left ventricular pressure gradient decreased from 96+/-33 mmHg to 29+/-22 mmHg (

This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.

The clinicopathologic characteristics of atypical adenomatous hyperplasia (AAH) remain unclear. A total of 137 patients underwent resection for adenocarcinoma of the lung at our institution. Examination of resected lung tissue showed that in addition to adenocarcinoma AAH was present in 26 cases and was not present in 111 cases. All nonsmokers with AAH ( n =13) had earlier-stage disease (stage IA, IB, IIA, and IIB) and no history of respiratory disease. Among patients with stage IA disease, the relapse-free and overall survival curves for those with AAH ( n =14) tended to be better than for those without AAH ( n =40), but the difference was not statistically significant ( P =0.056 and 0.087, respectively). Concurrent presence of AAH may be a favorable prognostic indicator in patients with stage IA adenocarcinoma.

This study sought to compare the clinical usefulness of the hyperventilation plus cold stress test or the hyperventilation combined with accelerated exercise test with other single tests in patients with coronary spastic angina. The study examined 24 patients (23 men, mean age 66 years) with angiographically confirmed coronary spastic angina and less than 50% stenosis. Moreover, none had spontaneous ST segment elevation before the study. Under no medication for at least 24 h prior, 4 procedures were performed from 09.00 h to 11.00 h: (i) a hyperventilation test for 5 min (HV(5)); (ii) HV(5) combined with a cold stress test for the last 2 min (HV(5)+CS(2)); (iii) a treadmill exercise test based on Bruce's protocol (TM(3)); and (iv) a treadmill exercise test accelerated at 1 min intervals according to Bruce's protocol immediately after HV(5) (HV(5)+TM(1)). The rate of appearance of chest pain and ischemia-induced ECG changes due to HV(5)+TM(1) were significantly higher than the other 3 tests. HV(5)+CS(2) was not superior to HV(5) alone. The incidence of provoked ST segment elevation due to HV(5)+TM(1) was higher than with the other 3 procedures. Thus, in patients with coronary spastic angina, no spontaneous ST segment elevation and near normal coronary arteries, HV(5)+CS(2) was no more useful than HV(5) alone. It is recommended that the newly designed HV(5)+TM(1) combination test be used for documenting evidence of ischemia in patients with coronary spastic angina, low disease activity and near normal coronary arteries.

To the Editor: The new onset of right bundle branch block (RBBB) was identified as a potent predictor of adverse outcome in patients with ST-segment elevation myocardial infarction (STEMI) in the thrombolytic era ([1][1]). In the primary percutaneous coronary intervention (PCI) era ([2][2]), well

An 80-year-old woman being treated with anti-hypertensive drugs developed eruption and itching of the skin. High fever and lymph node enlargement subsequently developed in spite of discontinuing all antihypertensive drugs, and she was admitted to our hospital. At the initial examination, multiple papules were noted over the entire body, and the skin showed thickening and lichenification with scratch marks. There was also generalized enlargement of the superficial lymph nodes. From these findings, her condition was diagnosed as chronic prurigo due to drug allergy. Laboratory tests showed inflammatory findings, anemia and a high serum level of IgE. Analysis of the surface marker of peripheral lymphocytes revealed no abnormalities. Bacteriologic cultures of blood revealed methicillin-resistant Staphylococcus aureus (MRSA). Histologic examination of the lymph nodes revealed chronic reactive lymphadenitis with a follicular pattern. She was strongly suspected of having MRSA septicemia, and so combination chemotherapy with vancomycin, minocycline and cefoperazone/sulbactam was started. However, 1 month after initiation of chemotherapy, the low-grade fever, eruption and moderate inflammatory findings persisted, and culture of the eruptions revealed MRSA. The prurigo was therefore considered to be the source of the septicemia, and daily application of diflucortolone ointment containing 3% acetic acid was started. Thereafter, the clinical and laboratory findings showed a rapid improvement. MRSA infections usually occur in compromised patients who are receiving antibiotics during prolonged hospitalization. The present case, who did not have any underlying disease, indicates that old-age is also an important factor for the development of MRSA septicemia.

341:217–225. 6. Hochman JS, Tamis JE, Thompson TD, Weaver WD, White HD, Van de Werf F, Aylward P, Topol EJ, Califf RM. Sex, clinical presentation, and outcome in patients with acute coronary syndromes. N Engl J Med 1999;341:226–232. 7. Hasdai D, Behar S, Wallentin L, Danchin N, Gitt AK, Boersma E, Fioretti PM, Simoons ML, Battler A. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin: The Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J 2002;23:1190–1201.

A 72-year-old woman who had idiopathic interstitial pneumonia was admitted due to general fatigue. Echocardiography revealed asymmetric septal hypertrophy and systolic anterior movement of the mitral valve. In addition, Doppler echocardiography revealed a pressure gradient of 52 mmHg in the left ventricular outflow tract. Hypertrophic obstructive cardiomyopathy was diagnosed. Because she had a respiratory disease, she was treated with cibenzoline instead of beta-blockers. After treatment her pressure gradient decreased to 10 mmHg, but respiratory symptom remained unchanged. This finding suggests that cibenzoline is useful for patients with hypertrophic obstructive cardiomyopathy complicated with respiratory disease.

An 18-year-old male patient with biventricular hypertrophic obstructive cardiomyopathy (HOCM) had successful reduction of the pressure gradients by cibenzoline. At 11 months after birth, he was first diagnosed with cardiac murmurs and by the age of 5 years, he was diagnosed with subpulmonic infundibular stenosis with a pressure gradient of 10 mmHg by cardiac catheterization. At the age of 14, re-catherterization revealed hypertrophic cardiomyopathy with isolated obstruction of the right ventricular outflow tract, with a pressure gradient of 70 mmHg, but no obstruction in the left ventricle. He began daily treatment with 30 mg propranolol. At the age of 18, he was admitted for cardiac evaluation. An echocardiogram revealed left mid-ventricular and subpulmonic obstructions associated with pressure gradients of 88 mmHg and 65 mmHg, respectively. A single oral dose of 200 mg of cibenzoline decreased the pressure gradients in the left and right ventricles (38 mmHg and 36 mmHg, respectively). He was then given 300 mg daily of cibenzoline, and both pressure gradients remained low without any complications 8 months later at the time of discharge. (Circ J 2002; 66: 1173 -1175)

After 1990's, the development of new generation anti-cancer agents produced encouraging improvement of prognosis in inoperable or relapsed stomach cancer and colorectal cancer. However, non-hematological toxicity, such as peripheral neuropathies, become a new dose-limiting toxicity. In several new generation drugs, measures for controlling peripheral neuropathy had not been established besides dose modification or schedule modification. We tried to control the peripheral neuropathy induced by anti-cancer agents with the assistance of an adjuvant analgesics ladder. A total of 18 digestive cancer patients who presented with peripheral neuropathy of grade 1 or more(NCI-CTCAE ver 3.0), in the chemotherapy including Taxol or Oxaliplatin, were enrolled. The first stage of the adjuvant analgesics ladder was set as the antidepressant(amoxapin), the second stage was anticonvulsive drugs(valproic acid or clonazepam) and the third stage was antiarrhythmic drug(mexiletine). In each stage, if the drug turned out to be ineffective after two / weeks follow-up, it shifted to the next stage. The response rate of each step was 61.1%(11/18)of the first stage, 50.0%(5/10)of the 2nd stage, 50.0%(2/4)of the 3rd stage, and the overall response rate was 77.8%. The discontinuance of cancer treatment by peripheral neuropathy was observed only in 1 patient 5.5%(1/18)in the Taxol administered group. The toxicity profile was skin eruption and drowsiness, but the skin eruption was observed only in 1 patient at the 3rd stage and the drowsiness in 2 patients at the 2nd stage. It appears that the method to control the peripheral neuropathy induced by anti-cancer agents with the assistance of adjuvant analgesics ladder was effective and safe, but a large-scale clinical trial was warranted.

Intussusception is rare in adults. We describe a 47-year-old man with ileal schwannoma that led to ileocolic intussusception. Abdominal ultrasonography, abdominal CT scan and barium enema confirmed an ileal tumor. Colonoscopy revealed a peduncular submucosal tumor (SMT) 75 mm long with an ulcerated apex at the ascending colon. The provisional diagnosis was a gastrointestinal stromal tumor of the terminal ileum. Ileocecal resection was carried out and the tumor was histologically diagnosed as schwannoma. Abdominal pain resolved postoperatively. This case reminds us that ileal schwannoma should be included in the differential diagnosis of intussusception caused by an SMT in the intestine.

Background Although video-assisted thoracoscopic surgery (VATS) has been applied to pulmonary resection for pulmonary metastases, the clinical validity of this approach remains controversial. The purpose of this study was to evaluate the validity and problems of VATS for pulmonary metastasectomy. Methods From January 1993 to December 2003, VATS for pulmonary metastasectomy was performed in 53 resections for 48 patients at our institution. The medical records of these patients were retrospectively reviewed. Results The primary tumor was colorectal cancer in 23 patients, renal cell carcinoma in 6, breast cancer in 6, germ cell tumor in 5, head and neck cancer in 2, and others in 6. Thirty-six cases had a solitary lesion, 8 had unilateral multiple lesions, and 9 had bilateral multiple lesions. The following procedures were performed: 7 lobectomies, 5 segmentectomies, and 41 wedge resections. There was no major postoperative morbidity related to VATS. At a median follow-up period of 29.0 months, 13 patients were alive without recurrences. The 3-year overall survival rate and the 3-year intrathoracic disease-free survival rate were 59.8% and 33.4%, respectively. Five cases had recurrence at the surgical stump or at the port sites, but these recurrences have not been found in the recent period since June 1997. Intrathoracic recurrences within 3 months after VATS occurred in four. Conclusion VATS for pulmonary metastases is not superior to the conventional open thoracotomy and is not recommended as a standard procedure. Further studies with a larger number of cases performed by skilled surgeons familiar with VATS are needed.

Since positive coronary artery remodeling with large plaque burden is associated with subsequent coronary events, the authors tested their hypothesis that secondary prevention of coronary events by a statin may be associated with inhibition of the process of positive coronary artery remodeling in underlying coronary atherosclerotic lesions in patients with coronary artery diseases. They evaluated the intravascular ultrasound imaging in angiographically normal coronary lesions at baseline and after 6 months of therapy in 64 patients with coronary artery diseases. External elastic membrane area was defined as the vessel area, and the difference between the vessel and lumen area was calculated as plaque area. The relative echogenicity of coronary plaque to adventitia was evaluated as acoustic characteristics of coronary plaque. Twenty-five patients were treated with a statin and 39 patients did not receive a statin. In patients treated with a statin, plaque area decreased by 12% (p=0.013) compared to an increase in plaque area of 13% (p=0.023) in those who did not receive a statin. The vessel area was not enlarged in patients treated with a statin but did show positive remodeling in patients who had plaque progression without a statin. The relative echogenicity of plaque was unchanged in patients treated with a statin but significantly decreased in patients not receiving a statin. A statin may prevent positive coronary artery remodeling via inhibition of plaque progression in underlying coronary atherosclerotic lesions in patients with coronary artery diseases.

Background The aim of this study was to identify the clinical characteristics of multiple primary adenocarcinomas and to evaluate the efficacy of surgical treatments. Methods Three-hundred sixty-nine patients who underwent pulmonary resection for adenocarcinoma from January 1994 to December 2002 were reviewed. Results Thirty-one patients (8.4%) were determined to have multiple primary adenocarcinomas that could be detected on chest x-rays or computed tomography (CT). Twenty-six patients were synchronous and five patients were metachronous with a median interval of 59.0 months. Forty-nine (72.1%) of the total 68 lesions exhibited ground-glass opacity on high-resolution CT (HRCT). Pathologically well-differentiated adenocarcinoma with mixed bronchioloalveolar pattern was the most common subtype (39.7%). Taking into consideration pulmonary function, size, location, and HRCT findings of the lesions the procedures performed were lobectomy with mediastinal lymph-node dissection for 32 patients, segmentectomy with hilar node dissection for 8 patients, and wedge resection for 28 patients. Of 17 patients with bilateral synchronous cancers, simultaneous bilateral pulmonary resection was performed in 14 patients including simultaneous bilateral video-assisted thoracic surgery (VATS) in 11 patients. After a median follow-up period of 27.7 months, the 3-year overall survival rate was 92.9% and the 3-year disease-free survival rates of synchronous cancer and metachronous cancer were 77.9% and 100%, respectively. Conclusions The incidence of multiple primary adenocarcinomas was relatively common. Early radiographic detection and surgical excision could yield a favorable prognosis. The use of VATS, even for synchronous bilateral patients, was a safe and beneficial procedure.

Atypical adenomatous hyperplasia (AAH) has been reported to be a precancerous lesion of pulmonary adenocarcinoma. Cyclooxygenase-2 (COX-2), Fas and Fas ligand (FasL) are believed to be involved in the pathogenesis and progression of cancer.We examined the expression of COX-2, Fas and FasL in 31 tissue specimens of adenocarcinoma and 9 of AAH using an immunohistochemical method.COX-2 staining was observed in 20 (65%) specimens of adenocarcinoma and 2 (22%) of AAH. There was a significant difference in incidence of expression between these two groups (p = 0.025). All tumor specimens obtained from three patients with simultaneous multiple adenocarcinoma showed positive COX-2 staining. In two patients having both adenocarcinoma and AAH, COX-2 expression was detected in adenocarcinoma but not in AAH. Fas was expressed in 5 (16%) adenocarcinoma and 2 (22%) AAH specimens. FasL was detected in 3 (9.7%) adenocarcinoma and 1 (11%) AAH specimen.These findings suggest that COX-2 might play a role in the progression from AAH to adenocarcinoma.

To examine the effect of the addition of a beta-blocker in the treatment of chronic heart failure due to dilated cardiomyopathy, we compared the change of left ventricular remodeling and the prognosis between patients treated with angiotensin-converting enzyme inhibitors and patients who had beta-blockers added to angiotensin-converting enzyme inhibitors. Fifty-seven patients were treated with an angiotensin-converting enzyme inhibitor in addition to combination therapy with furosemide, spironolactone and digoxin. In 60 patients, a beta-blocker was administered in addition to combination therapy with furosemide, spironolactone, digoxin and an angiotensin-converting enzyme inhibitor. Changes of left ventricular dimensions at end-diastole and end-systole, fractional shortening, cardiac events and death were examined during the follow-up periods. The mean follow-up periods were 4.9 +/- 4.1 years in the angiotensin-converting enzyme inhibitor group and 3.9 +/- 2.5 years in the beta-blocker group, respectively. Baseline hemodynamic characteristics showed no significant differences between the two groups. After the treatment, the heart rate significantly decreased in both groups and the systolic blood pressure increased in the beta-blocker group. Both left ventricular dimensions at end-diastole and end-systole significantly decreased in both groups. Fractional shortening increased from 17.0 +/- 7.6 to 19.8 +/- 8.9% (p = 0.017) in the angiotensin-converting enzyme inhibitor group and from 16.6 +/- 7.2 to 24.7 +/- 8.0% (p0.0001) in the beta-blocker group, respectively. Changes of left ventricular dimensions at end-diastole and at end-systole, and fractional shortening were all greater in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group. The event-free rate and the cumulative survival rate during the follow-up periods were markedly better in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group (p = 0.0019 and p = 0.0099, respectively). These results indicate that the suppression of left ventricular remodeling and the improvement of prognosis in patients with dilated cardiomyopathy are markedly stronger in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group. Thus, beta-blocker should be added to patients with dilated cardiomyopathy treated with an angiotensin-converting enzyme inhibitor.

I myocardial matrix metalloproteinase (MMP) activity has been reported to occur in clinical and experimental forms of dilated cardiomyopathy.1–3 Proinflammatory cytokines, such as tumor necrosis factor(TNF), are important regulators of MMP gene expression. Previous experimental studies have shown that TNFstimulates myocardial MMP activity and can lead to degradation of the extracellular matrix in the myocardium.4 However, few clinical studies of the relation between circulating MMP and TNFlevels in idiopathic dilated cardiomyopathy (IDC) have been conducted. Recently, we reported the presence of increased circulating TNFin patients with IDC, and that blockers could reduce the increased circulating TNFlevels in IDC.5,6 The present study further clarifies the relation between circulating levels of MMPs and TNFin patients with IDC. • • • We studied 34 consecutive patients with IDC between January 1999 and December 2001. The diagnosis of IDC was based on patient history, physical examination, electrocardiogram, echocardiogram, and cardiac catheterization. All patients underwent coronary angiography during the study period, and patients with epicardial coronary artery disease were excluded. Patients who had clinical or laboratory evidence of infections, neoplasms, autoimmune disease, or liver or renal dysfunction were also excluded from this study. Ten age-matched subjects who had no evidence of organic cardiac disease and no cardiac dysfunction were retrospectively selected as the control group. All subjects participated in this study after giving informed consent, and the protocol was approved by the Human Investigations Committee of our institution. In 20 patients who were poor responders to treatment with angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers for 6 months, carvedilol, a nonselective blocker, was administered orally in addition to combination therapy after their hospital admission. In 18 patients with New York Heart Association functional class II or III congestive heart failure, the initial dosage was 2.5 mg twice daily; the doses were increased at weekly intervals for 8 weeks. In 2 patients in New York Heart Association functional class IV, the initial dosage was 1.0 mg twice daily; the doses were increased at weekly intervals for 12 weeks. The target dose was 25 mg/day, considering the weight of patients in this study of 75 kg. If a decrease in systolic blood pressure to 90 mm Hg or a decrease in heart rate at rest to 60 beats/min occurred, increments in dose were discontinued. As a result, the mean final dose of carvedilol was 19.2 mg. Maintenance of final doses was continued for an additional 6 months. Blood samples from patients were collected for measurement before and 6 months after initiation of carvedilol therapy. After bed rest for 30 minutes, peripheral venous blood samples were collected into chilled tubes and immediately centrifuged at 4°C. The serum samples were stored at 80°C until assay. Serum levels of TNFwere measured by enzyme-linked immunosorFrom The Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime, Japan. Dr. Ohtsuka’s address is: The Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 7910295, Japan. E-mail: tohtsuka@m.ehime-u.ac.jp. Manuscript received October 24, 2002; revised manuscript received and accepted December 30, 2002. FIGURE 1. Serum levels of TNF, MMP-1, MMP-3, and MMP-9 in 10 age-matched normal control subjects (NC) and in 34 patients with IDC. *p

A 70-year-old man referred for treatment of a left lower lung tumor was shown in chest computed tomography to have a homogeneous round tumor 45 mm in diameter with an enhanced thin wall in the lower lobe of the left lung. No specific finding was seen in material obtained by transbronchial and computed tomography (CT)-guided lung tissue biopsy, so the presumptive diagnosis was a lung abscess. Despite antibiotics administered for 2 weeks, radiography showed the tumor had grown, necessitating left lower lobectomy. The permanent section was diagnosed as diffuse large B-cell lymphoma. Because CT findings for the tumor suggested a lung abscess and the central part of the tumor consisted of fibrotic and necrotic tissue, we had difficulty establishing a final diagnosis. The literature showed primary pulmonary lymphomas yielded a variety of findings radiographically, making surgery paramount for ascertaining a final diagnosis.

We reviewed the clinical courses of 25 patients who underwent pulmonary resection for metastatic lesions from colorectal cancer between January 1991 and December 2001. The cumulative survivals at 3 and 5 years were 72% and 63%, respectively. Sex, site of the primary tumor, presence of extrapulmonary metastases, disease-free interval, location of pulmonary metastases (PM), number of PM, size of PM, mode of operation, pre-thoracotomy serum carcinoembryonic antigen level, and post-thoracotomy chemotherapy were not found to be statistically significant prognostic factors. Age (70 yearsor =) was a predictor of a shorter survival duration by univariate analysis (p = 0.02). Recurrence was observed in 19 patients, 11 of which were lung recurrences. Eight patients underwent repeated pulmonary resection. The median survival in these 8 patients was 23 months after second pulmonary operation. Surgical treatment for pulmonary metastases from colorectal cancer in selected patients might improve prognosis.

The overexpression of eukaryotic initiation factor 4E (eIF4E), a key regulator of protein synthesis, is involved in the malignant progression of various human cancers. We investigated eIF4E expression in atypical adenomatous hyperplasia (AAH) and adenocarcinomas of the human peripheral lung. On the basis of the WHO criteria with minor modifications, adenocarcinomas were classified as bronchioloalveolar carcinoma (BAC), mixed subtypes with a bronchioloalveolar pattern and minor invasion (early MX), and mixed subtypes with a papillary pattern and marked invasion (overt MX). eIF4E immunohistochemistry was performed in 143 tissue samples (31 AAH, 38 BAC, 43 early MX, and 31 overt MX). Both tumoral and stromal eIF4E levels were elevated from AAH, BAC, and early MX to overt MX and significantly associated with histological grade (P0.001 and P0.001, respectively). Tumoral and stromal eIF4E staining intensities were significantly correlated (P0.01). Immunoblot analysis of 51 tissue samples (2 AAH, 11 BAC, 18 early MX, and 20 overt MX) demonstrated that eIF4E expression in adenocarcinomas was 3.4-7.4-fold higher than in normal lung and that its expression progressively increased in the following order: AAH (lowest expression), BAC, early MX, and overt MX (highest expression). Multiple regression analysis revealed that both tumoral and stromal eIF4E expressions were significant independent factors for the histological subtype (P0.01 and P0.01, respectively). These results suggest that translational control is dysregulated during the development of peripheral lung adenocarcinoma and that progressive increases of tumoral and stromal eIF4E may be part of a positive feedback loop for malignant progression.

A multi-center trial of exemestane 25 mg, an oral aromatase irreversible inactivator, was conducted to evaluate its efficacy and safety in 33 postmenopausal patients, and to investigate the pharmacokinetics/serum hormone levels in 16 postmenopausal patients, respectively, with breast cancer and anti-estrogen resistance. Exemestane 25 mg was given once daily for up to 48 weeks (maximum). The objective of this study was to confirm the reproducibility of the results shown in two studies in other countries with similar patients, to investigate the possibility of extrapolating the overseas data to Japanese. The response rate (CR + PR) was 24.2% (8.33%), which exceeded the minimum number (6 cases) required to evaluate efficacy. The response rate in this study was very similar to that observed in the two international open studies. Adverse events (subjective/objective symptoms), in which a causal relationship with exemestane administration could not be excluded, were observed in 26 cases (78.8%). Of these, hot flushes, increased sweating, fatigue, and insomnia occurred in more than 10% of patients, which was similar to that observed in the two international open studies. Abnormal laboratory results occurring in more than 10% of patients, in which a causal relationship with exemestane administration could not be excluded, were as follows: lymphocyte count decrease, alkaline phosphate increase, GOT increase, GPT increase, gamma-GTP increase, triglyceride increase, and inorganic phosphate increase, most of which were either grade 1 or 2. A remarkable decrease in serum hormone concentration was observed only for estrogen. The values of AUC0-infinity at day 1 and AUC0-24 h at day 29 (steady state) were similar, suggesting no accumulative effect of exemestane. These results demonstrate the anti-tumor effect and safety of exemestane in postmenopausal anti-estrogen resistant breast cancer patients. The reproducibility of the results of the two foreign studies was verified in Japanese patients, and it is concluded that the foreign trial data on exemestane can be extrapolated to Japanese.

This study sought to clarify the relationship between magnesium (Mg) deficiency and coronary artery spasm provoked by pharmacologic agents in patients with a recent acute myocardial infarction (AMI). Twenty-three consecutive patients suffering from AMI were investigated with a Mg retention test (Mg: 0.1 mmol/kg for 4 h) in both the acute phase (within I week (3+/-2 days) of onset) and the subacute phase (3-4 weeks (24+/-6 days) of the onset). Early coronary arteriography was performed in all patients. Coronary stenosis in the infarct-related artery was less than 90% in all patients in the subacute phase. The spasm provocation test was performed in the subacute phase and coronary spasm was defined as transient subtotal or total occlusion in association with angina or electrocardiographic ST-segment deviation. Coronary artery spasm was provoked in only 13 of the 23 patients. Compared with the control subjects (12 patients without coronary artery disease or coronary spasm), the 24-h Mg retention was significantly higher in patients with AMI (acute phase: 78+/-27%, subacute phase: 66+/-32%, vs control: 48+/-12%, p

A 28-year-old man was admitted to hospital for investigation of a 2-week history of angina occurring on exertion. Coronary angiography showed an isolated left coronary ostial stenosis and left main trunk plasty was performed 2 weeks later. The pathological diagnosis of the left coronary ostial stenosis was fibromuscular dysplasia, which makes this a rare case.

We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.

Background . Whether video-assisted thoracic surgery (VATS) improves postoperative pulmonary function is still controversial. We compared postoperative pulmonary function after VATS lobectomy and standard lobectomy. Methods . Eleven patients who had undergone standard lobectomy and 10 patients who had undergone VATS lobectomy were studied. Arterial blood gas analyses were performed on the 4th, 7th, and 14th postoperative days. Pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1.0 ), and peak flow rate (PFR) were measured on the 7th and 14th postoperative days (early phase), and approximately 1 year after surgery (late phase). Results . Pulmonary function, as assessed with arterial oxygen partial pressure (PaO 2 ) ( p = 0.054), arterial oxygen saturation (O 2SAT ) ( p = 0.063), FVC ( p = 0.10), and FEV 1.0 ( p = 0.08), was better after VATS lobectomy than after thoracotomy on the 7th postoperative day. PFR was significantly better after VATS on both the 7th and 14th postoperative days ( p = 0.008 and p = 0.03, respectively). Conclusions . VATS lobectomy had advantages on early postoperative pulmonary function. We conclude that VATS lobectomy is a beneficial alternative to standard thoracotomy, especially for patients with poor pulmonary reserve.

Since there are no large-scale surveys of how cancer patients perceive unproven therapy in Japan, we wanted to clarify this issue by means of a cross-sectional questionnaire conducted among cancer patients. The survey revealed that 32% of cancer patients used unproven therapy without having sufficient information about it. There was a lack of communication between cancer patients and their physicians on topics relating to alternative medicine. Issues that we have to solve are concerned with the education of cancer patients, lay people and physicians on the meaning and role of alternative medicine and on the necessity for scientific evaluation of medical treatments in Japan.

A 66-year-old woman with a 7-year history of Parkinsons' disease was admitted to our hospital because of a high fever and disturbance of consciousness. She had been treated with levodopa/benserazide hydrochloride and trihexyphenidyl hydrochloride until admission. On admission, the patient was comatose, her temperature was 40.5 degrees C, her blood pressure was 54/-mmHg, and her pulse rate was 130 beats/min. Laboratory tests showed leukocytosis, a high level of creatine kinase in serum and evidence of hyperosmolar non-ketotic diabetic coma (blood glucose, 1,080 mg/dl) and of disseminated intravascular coagulation (DIC). A continuous insulin infusion, antibiotics, nafamostat mesilate, and urinastatin were given, after which the DIC, hyperglycemia, and the level of consciousness were improved. However, levels of creatine kinase, myoglobin, transaminase, and amylase in serum continued to increase, and multiple organ failure was suspected. Furthermore, she became less responsive, diaphoretic, and tremulous; fever and mild rigidity developed. The peak creatine kinase and myoglobin were 11,095 U/l and 12,520 ng/ml, respectively. A diagnosis of malignant syndrome was made, and treatment with levodopa/carbidopa and dantrolene was begun. Within several days, the clinical and laboratory findings improved. We report here a rare case of malignant syndrome associated with DIC followed by diabetic coma in an elderly patient with Parkinsons' disease during L-dopa therapy. Timely diagnosis and treatment of malignant syndrome are important in the management of elderly patients with Parkinsons' disease, because DIC and multiple organ failure may occur in the early stages of malignant syndrome.

Platelet-derived endothelial cell growth factor may play a role in tumor development through its angiogenic action. To clarify the relationship between expression of platelet-derived endothelial cell growth factor and microvessel density in the development of human colon carcinoma, we examined 80 early-stage colon carcinomas using microscopy and immunohistochemistry. Localization of platelet-derived endothelial cell growth factor was assessed by immunocytochemistry, while microvessel count was evaluated by either HE staining or Factor VIII immunostaining. Among the examined carcinomas, 35 were classified as m carcinomas including carcinoma in situ, whereas 45 were sm carcinomas. Fifteen (42.9%) of the 35 m and 30 (66.7%) of the 45 sm carcinomas demonstrated high vascular density, whereas 20 (57.1%) m and 15 (33.3%) sm carcinomas showed moderate or low vascular density. Vascular density was higher in sm carcinomas than in m carcinomas and there was a significant correlation between depth of invasion and vascular density. Of the 45 highly vascularized carcinomas, 44 expressed platelet-derived endothelial cell growth factor. There was a statistically significant correlation between the frequency of platelet-derived endothelial cell growth factor expression and microvessel density (P = 0.012). These data demonstrate that microvessel density may be associated with the depth of cancer invasion and that platelet-derived endothelial cell growth factor may play an important role in the early stage of colon cancer development through angiogenesis.

A 47-year-old man was admitted to our hospital for abrupt onset of hemoptysis and dyspnea. Chest roentgenography revealed a left lower mass shadow with obstruction of the left main bronchus. However, on the third hospital day, he expectorated a coagulum-like substance which resembled bronchial tree, and his symptoms then dramatically subsided. Except for small amounts of bleeding from left B10a, the endobronchus was intact on bronchoscopic examination, and the pathologic diagnosis of the tumor using resected material was fibrous histiocytoma of low-grade malignancy. In addition, given the similarity in histologic findings between the expectorated substance and resected tumor, the expectorated substance was considered to be a part of the tumor which had grown along the endobronchial tree.(Internal Medicine 35: 724-727, 1996)

We describe an 87-year-old woman with a large ileal gastrointestinal stromal tumor (GIST) causing hemoperitoneum. A CT scan demonstrated a large heterogeneous mass measuring about 13 cm multiply 11 cm in the pelvis and hemoperitoneum, with a non-uniform enhancement pattern. The mass was diagnosed as a GIST originating from the gastrointestinal tract. She underwent an urgent laparotomy and an ileal GIST with a rupture was found 130 cm from the anal to the Treitz's ligament. Hemoperitoneum caused by ileal GIST rupture is a rare condition. Bleeding in the large tumor leading to rupture of the capsule might cause hemoperitoneum in the present case.