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Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

PURPOSE AND METHODS The major purpose of this study was to determine whether the survival rate in young lung cancer patients after surgical treatment differs from that in older patients. An analysis was performed for all patients with bronchogenic carcinoma who underwent surgery at Mie University Hospital from 1965 to 1990. RESULTS Of 803 patients, 24 (2.99%) were 33 to 39 years old. At the time of surgery, the disease was diagnosed as stage I in seven patients (29%), stage II in four (17%), stage IIIa in seven (29%), stage IIIb in two (8%), and stage IV in four (17%), while 46.3% of the patients older than 40 years of age had either stage IIIa, IIIb, or IV disease. All of the 24 patients less than 40 years of age underwent thoracotomy: curative resection in 14 cases, palliative resection in sex, and probe-thoracotomy in four. The 5-year survival rate for all stages of disease was 31.4% in these 24 patients, and 41.9% in 603 patients greater than 40 years of age. The 5-year survival rate for stage I disease was 35.7% in the seven younger patients and 78.0% in the 207 older patients; for stage II, it was 25.5% in the four younger patients and 40.6% in the 98 older patients; for stage III, it was 33.3% in the nine younger patients and 15.6% in the 250 older patients; and for stage IV, it was 25% in the four younger patients and 6.6% in the 48 older patients. There were no significant differences in survival rate between the two age groups for all patients or for those with each stage of disease. CONCLUSION Although younger patients tended to have more advanced disease, long-term survival in these patients did not differ from that of older patients.

ABC (angry backfiring C-nociceptor) syndrome-like pain disorder categorized in sympathetic independent pain appeared after amputation during spinal anesthesia. A 69-year-old female who had undergone amputation of the right leg below knee 5 months before, received amputation of the left leg below knee this time because of diabetic neuropathy and gangrene of her both legs. There were no complications in her right leg after the former amputation. Spinal anesthesia was maintained in the left one-side by hyperbaric local anesthetic. After changing the body position from left lateral to supine, the left leg was completely anesthetized and the right leg was incompletely anesthetized with only loss of cold sensation. In this state, she had pain in her right leg, and this pain was relieved by intravenous lidocaine administration. It was indicated that this type of pain was caused by the presence of ABC syndrome probably after right leg amputation.

We describe an autopsy case of parkinsonism with bradykinesia, muscle rigidity, and dementia as major symptoms. The patient had developed bradykinesia at the age of 62, and then muscle rigidity, a parkinsonian posture, bradylalia, and dementia gradually appeared. Neurological examination revealed rigidity in the neck and limbs, with motion and speech being generally slow. He lacked involuntary movements including alien hand, tremor, chorea, and dystonia. Vertical gaze palsy, both upward and downward was noted, but other cranial nerves were intact. He was diagnosed as suffering from PSP clinically based on vertical gaze palsy, bradykinesia, instability on standing and gait, and dementia. Levodopa was only transiently effective. Within three years he became bed-ridden and in a state of akinetic mutism. At age 65 he died from pneumonia. Neuropathology revealed severe neuronal degeneration and gliosis in the substantia nigra. Because atrophy of the tegmentum of brainstem, dentate nuclei, inferior olivary nuclei was very mild and Alzheimer neurofibrillary tangles in the brainstem were relatively few, PSP was ruled out. Cortical neuronal degeneration was not apparent, but in the deep layer of cingulate gyrus, frontal lobe, and insula, there were several ballooned neurons. Gallyas-Braak silver staining showed no tuft-shaped astrocytes, specific for PSP, but it disclosed astrocytic plaques in the basal ganglia and the cerebral cortex. At present, astrocytic plaques are recognized as a hallmark of corticobasal degeneration (CBD), along with ballooned neurons in the cerebral cortex. The present case thus illustrates that CBD has a wide spectrum and may include cases in which degeneration of cerebral cortex is very mild.

Multi-facility joint randomized clinical trials for cancer treatment are the most common method of current clinical study. However, the difference in the rate of participation in multi-facility randomized clinical trials may damage the resulting general validity. Therefore, we studied whether the rate of participation in randomized clinical trials is different between university hospitals and other general hospitals using a questionnaire (with anonymity preserved). There were 744 subjects from university hospitals and 339 from general hospitals participating in the study. The results showed that 10.9 percent of those from university hospitals were willing to participate, against 28.1 percent who were not. Of those from general hospitals (public hospitals in this study) 10.6 percent answered that they would participate and 27.4 percent that they would not. Little difference was found in the rate of participation in randomized clinical trials between university hospitals and other general hospitals. The focus is thus on doctors to solve the possible differences between the facilities in further multi-facility joint studies.

SMON (subacute myelo-optico-neuropathy) may result from clioquinol neurotoxicity. An 81-year-old woman underwent internal fixation for left intertrochanteric fracture. She had been diagnosed as having SMON twenty years previously. Sensory examination revealed paresthesia and decreased deep sensation in the lower extremity. A recent neuropathological report shows that in long-term SMON of about fifteen years, degeneration is located from the medulla oblongata to T5-6. We performed spinal anesthesia of which the level of analgesia was below T5-6 in the present case. The level of anesthesia was determined by the pinprick test, and was recognized as below T10. Postoperatively, both the sensory level of analgesia and vital signs remained stable. There was no worsening of neurological findings after spinal anesthesia, including the postoperative period. In conclusion, spinal anesthesia which was limited to below the level of degeneration could be applied in a case of long-term SMON.

A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.

We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.

Cerebrovascular stroke is one of the major complications in cardiovascular surgery with cardiopulmonary bypass. The purpose of this study was to evaluate the usefulness of preoperative 99mTc-ethyl cysteinate dimer (ECD) SPECT and acetazolamide (diamox) enhancement to predict neurological complications in cardiovascular surgery. Eighteen patients with coronary disease, valvular disease or aortic aneurysm were studied before the operations. Regional cerebral blood flow and perfusion reserve were evaluated using ECD SPECT before and after the intravenous administration of diamox (1 g). Three cases with moderate to severe baseline abnormalities and poor perfusion reserve had cerebral infarction postoperatively. Twelve cases with good to fair perfusion reserve had no neurological complication. Three cases having poor perfusion reserve had the operations with more intensive brain protection, in which higher perfusion pressure to the brain was maintained during cardiopulmonary bypass, and no neurological complication was observed. In conclusion, patients who have moderately or markedly abnormal baseline flow with poor perfusion reserve may have some risk of neurological complications in cardiovascular surgery. ECD SPECT with diamox enhancement may give information useful for selection of operation procedures.

A 66-year-old man was revealed an abnormal shadow in the chest roentgenogram. Definitive diagnosis was not obtained by chest CT and bronchofiberscopy. Three months later, the shadow showed a rapid increase. We made a diagnosis of lung cancer by needle biopsy. Extended radical operation for the tumor was performed. The tumor with invasion to the chest wall and the mediastinum was completely resected with reconstruction of the chest wall and SVC. Postoperative pneumonia and respiratory failure were occurred, and patient died four months later.

It is now possible experimentally to measure myocardial blood flow of the beating heart using a helium-neon (He-Ne) laser Doppler flowmeter. A myocardial probe was redesigned to reduce its size and weight, and a method devised of fixing the probe to the beating cardiac surface to allow its clinical application. This modified laser flowmeter was used on 36 patients with ischaemic heart disease to measure myocardial blood flow before and after revascularization. Flow was measured in the right and left ventricles while patients were in a haemodynamically stable state as determined by electrocardiography, heart rate, blood pressure and double product (heart rate x systolic blood pressure). No significant difference was found between the mean(s.e.m.) preoperative and postoperative flow volume at the anterior wall of the right ventricle (77(15) versus 81 (12)ml/min per 100 g), which did not undergo revascularization, but mean(s.e.m.) myocardial blood flow at the ischaemic left ventricle increased significantly (from 68(15) to 88(13) ml/min per 100 g; P0.01). There was also no significant difference between preoperative and postoperative values of haemodynamic parameters of coronary blood flow. In conclusion, a means to measure myocardial blood flow with He-Ne laser Doppler flowmetry has been devised which shows coronary artery bypass grafting to increase myocardial blood flow in the ischaemic myocardium.

We have developed the protocol for selective cerebral perfusion (SCP) and pharmacological cerebral protection, and used it successfully in cases of aortic arch aneurysm. The subjects of the present study were 34 patients (28 males, 6 females) whose aortic arch aneurysm were surgically treated. Preoperative brain CT and brain scintigram showed high incidence of brain ischemia. However only 4 patients experienced a neurological episode. We conclude that our SCP technique and pharmacological cerebral protection are useful component to surgery of the aortic arch.

Between January 1983 and June 1990, there were 48 patients who underwent surgery for mitral regurgitation due to degenerative diseases. Among these, 20 patients received mitral valve repair. Overall operative mortality was 5% for patients who underwent valve repair, and 7.1% for those who underwent valve replacement. We standardized a maneuver for valve repair in August 1988 in an attempt to expand its indications. There were 35 patients who underwent surgery prior to that date (group 1), and 13 patients after that date (group 2). There were nine patients (25.7%) in group 1 and 2 patients (84.6%) in group 2 who underwent valve repair. Among these, one patient (11%) in group 1 died within 30 days after the operation, but there were no surgical deaths for any patients in group 2. In addition, one patient (11%) in group 1 and one (9%) in group 2 required another operation for valve replacement. Doppler echocardiographic studies performed postoperatively in 18 patients who had undergone valve repair showed that 13 (72.2%) had no regurgitation, 4 (22.2%) had trivial regurgitation, and 1 (5.6%) had mild regurgitation. Postoperative valve area as determined by continuous-wave Doppler echocardiography was 3.7 +/- 1.1 cm2 (mean +/- SD) for patients who had undergone reconstruction and 3.1 +/- 0.7 cm2 for those who had undergone replacement.

Postoperative pulmonary complications cause the decrease of the flow of remaining pulmonary circulation. We examined the effects of the difference of resected lobes on the postoperative course and remaining pulmonary circulation of the lobectomized lung cancer patients using a pulmonary digital subtraction angiography. In all cases with preoperative pulmonary complications, circulatory flow of the remaining lung on the operated side significantly decreased. In the cases without preoperative pulmonary complications, only the cases performed left upper lobectomy developed the decrease of the circulatory flow on the operated side. This seemed to be chiefly caused by a postoperative continual atelectasis of the remaining lower lobe due to kinking of the bronchus. On the other hand, the postoperative decrease of the residual pulmonary circulatory flow on the operated side was not developed in the cases undergoing a segmentectomy, even with pulmonary complications. Therefore, for any case requiring a left upper lobectomy or the case with an impaired lung requiring any type of lobectomy, contralateral pulmonary function should be exactly evaluated preoperatively.

Ten cases of central airway obstruction mainly caused by extrinsic compression due to the growth of extratracheal malignant tumors or longitudinal extension of tracheal adenoid cystic carcinomas, underwent palliative intubation subsequent to endoscopic Nd-YAG laser treatment. Mean length of the severe stenosis in these cases was 4.4 cm (3-7 cm). Sole application of endoscopic Nd-YAG laser to the stenosis failed relief of the symptom and an immediate palliative intubation was recommended. Mean time of the temporary intubation was 7 days (4-11 days). Airway was maintained by this intubation and also retained enough after extubation. Therefore, it seemed that, in a palliative treatment of the central airway severe stenosis, usefulness of the combination management of Nd-YAG laser with following temporary intubation was revealed. However, in order to maintain the airway for recurrence of the obstruction, use of indwelling airway stents seemed a better application. The longest period of follow-up in the cases treated by indwelling airway stents was 6 months and one of the cases is a now in comfortable state.

We studied surgical results of 14 cases of ischemic mitral regurgitation. There was no surgical death in 10 cases with left ventricular aneurysm, and their clinical symptoms improved except 3 with the combined operation of left ventricular aneurysmectomy, mitral annuloplasty and bypass grafting. The range of the abnormal contracting segment significantly decreased after surgery except in 3 cases in whom clinical status was not improved. Three of 4 cases which underwent bypass grafting and mitral annulo-valvuloplasty survived, but one of them died of graft-versus-host disease. In the three survived cases, severe mitral regurgitation disappeared. We have concluded as follows: In cases of left ventricular aneurysm, a sufficient aneurysmal resection is very important to control the mitral regurgitation, and the additional procedures of mitral annuloplasty and bypass grafting are essential. The mitral valve replacement is recommended in case of the complete disruption of the papillary muscle. Mitral valvuloplasty combined with annuloplasty is suitable to control the regurgitation in the regional mitral prolapse due to the torn chordae.

"Postoperative erythroderma", the pathogenesis of this disease have solved as graft-versus-host disease (GVHD) due to blood transfusion, is fatal and impossible to cure for the time being. Therefore the prevention against the disease is very important. One woman and three men who underwent an operation and blood transfusion at our department died of this disease. They fell into high fever on 11-13 days, erythroderma on 12-16 days, liver dysfunction on 14 days, and leukocytopenia on 17-19 days, after surgery and transfusion. Eventually, they all suffered from thrombocytopenia, diarrhea, renal dysfunction, and sepsis which led to death. The clinical course, macroscopic and microscopic findings of them coincided with those of GVHD. Since 1989, we have tried following methods for prevention of postoperative erythroderma: Reducing blood transfusion, especially fresh blood and fresh thrombocyte plasma, by using predeposited autologous blood, autologous washed erythrocytes collected from the operative area before and after extracorporeal circulation (ECC), concentrated residual blood from the ECC using a hemoconcentrater, and 1,500 rad of cobalt-irradiation of fresh blood, fresh thrombocyte plasma, and blood collected within 7 days prior to the transfusion. Postoperative erythroderma has not been experienced by introduction of these methods since 1989.

From 1977 to 1988, 390 cases of lung cancer were resected in our hospital. In 12 patients (3.1%) a postoperative bronchopleural fistula developed. This complication occurred more commonly after right pulmonary resection than left and most common after right pneumonectomy. Moreover, that had occurred following right pneumonectomy was most fatal. After right middle and lower lobectomy, this complication occurred at the same rate as after pneumonectomy and also caused a fatal result. On the other hand, after the resection of single lobe, the rate of the occurrence of a bronchopleural fistula was lower. And, even if it had developed, the fistula sometimes could be healed by a conservative treatment only. In one of our cases the fistula was successfully treated by intra-bronchial gluing through a bronchofiberscope.

The surgical treatment of pulmonary adenocarcinoma was studied on the basis of the postoperative long-term results in 211 cases. The overall five-year survival rate was 42% for adenocarcinoma and 48% for squamous cell carcinoma, and there was no significant difference. In stage I, as the degree of differentiation became lower, the prognosis became poorer. In stage III, the five-year survival rate was 50% for the alveolar cell type and 32% for the well differentiated type. The prognosis was better than in the moderately or poorly differentiated types. The prognosis of T1N0 cases was 79% in T1, but it was significantly lower 39% for T2 cases. Among T3 or T4 cases other than N2, the two-year survival rate was 15%, and the longest survival recorded was 32 months. The results were also poor in 9 cases undergoing extensive surgery, with the two-year survival rate being only 10%. Of the N2 cases undergoing extensive surgery all died within a year, except for one case surviving two years following panpleuro-pneumonectomy. In N2, the prognosis was significantly worse if there were two or more foci of mediastinal lymph node metastasis or if subcarinal lymph node metastasis was present. In the long surviving cases, cancer-bearing survivors were about twice as common as with squamous cell carcinoma. Recurrence was usually by distant metastasis (mainly to the brain), being twice as common as local recurrence. Therefore, in adenocarcinoma the significance of postoperative adjuvant therapy was considered to be greater than in squamous cell carcinoma.

Machado-Joseph disease (MJD), one of the most common types of hereditary spinocerebellar degeneration caused by abnormal expansion of the CAG repeat in the MJD1 gene, presents atrophy of the infratentorial structures neuropathologically and neuroradiologically. Although a significant positive correlation has been reported between infratentorial atrophy and the number of expanded CAG repeat units, the exact changing course of brainstem size in the individual case remains to be resolved. We investigated seven cases of genetically confirmed MJD longitudinally by magnetic resonance imaging with observation periods of 4.5-10.6 years. Measurement of the midsagittal areas of infratentorial structures disclosed progressive atrophy of the pontine base and cerebellum, which correlated significantly with age, whilst midbrain and pontine tegmentum showed atrophy with no significant progression, suggesting it was better identified as 'small size' and might have mostly been completed before the initial symptoms. Such differences between regions in atrophy progression must be caused by a difference in the neuropathological course.

Stab wounds of the chest occupy an important position in penetrating thoracic injuries in Japan. A retrospective review of 117 patients with stab wounds of the chest admitted to our hospital over the past 12 years (from 1975 to 1987) revealed some factors that might influence their mortality. Seven patients died from trans-diaphragmatic injuries of intra-abdominal organs. The management of intra-abdominal injuries was very important in thoracic stab wounds. Many of the patients with stab wounds of the precordial chest (danger zone) had cardiac or major vascular injuries, and the mortality rate of them was high. The mortality rate of the patients with stab wounds of the right lateral thorax was high, because many of them had trans-diaphragmatic liver injuries. We thought that right lateral thorax as well as precordial chest is the danger zone in thoracic stab wounds. Survival rate in the patients whose circulatory condition had been unstable when they admitted was very low. Five DOA (dead on arrival) patients with stab wounds of the chest required emergency room thoracotomy (ERT). One of them survived. Survival rate in the DOA patients with stab wounds of the chest was higher than that in the DOA patients with blunt thoracic injuries. ERT for cardiac insufficiency following stab wounds of the chest was thought an effective procedure for surviving. Survival rate of the patients with cardiac stab wounds was 63.6 per cent.

Mucocele of the appendix is rare and mainly found incidentally at surgery or autopsy. Clinically, this tumor is known to cause pseudomyxoma peritonei or intussusception in adults. We present a case of adult intussusception with a leading mass of appendiceal mucocele. Computed tomography was useful in resolving the nature of the leading mass.

Three hundred and one patients undergoing aortic surgery (247 aneurysm cases and 54 arteriosclerotic obstruction cases) were evaluated in respect to the treatment for the associated coronary artery stenosis. Twenty-four among total cases (8%) showed the presence of coronary artery stenosis; 16 cases among aneurysm cases (6.5%) and 8 cases among arteriosclerotic obstruction cases (14.8%). Coronary revascularization was performed in 10 cases and the early operate death was observed in one case. Two abdominal aneurysm cases and 4 arteriosclerotic obstruction cases received two-staged aortic and coronary operation, since either aortic or coronary lesion was considered lethal. However, 3 cases of dissecting aneurysm (type I or II), and case of arteriosclerotic obstruction case having left ventricular aneurysm received simultaneous aortic and coronary surgery, since both of the lesions were highly lethal. These data are consistent with the conclusion that the combined aortic and coronary lesion should be treated with the two-staged operation, and that the simultaneous aortic and coronary surgery should be performed only when the both lesions are lethal.

To evaluate graft patency and myocardial viability after aorto-coronary (AC) bypass surgery, 58 patients (29 with old myocardial infarction and 29 with effort angina) underwent symptom-limited exercise 201T1 myocardial SPECT using a bicycle ergometer before and after surgery. The results were as follows: 1. The overall angiographic graft patency was 87% (97 of 112 grafts). 2. According to the stress SPECT images, graft patencies were 98% for areas with postoperative improvement by 201T1 uptakes, 79% for areas with unchanged patterns, and 53% for areas with worsened patterns. In spite of patent grafts, among cases with worsened 201T1 uptakes the etiologies included perioperative infarction, anastomotic strictures, and poor run-off distal to the anastomoses. 3. Following patency of grafts, postoperative normalized perfusion patterns were observed in 69% (27 of 39 segments) of segments with persistent preoperative low uptakes and 25% (4 of 16 segments) of segments with persistent preoperative defects. Thus, exercise 201T1 myocardial SPECT proved a useful diagnostic means of assessing graft patency and effectiveness. However, after AC bypass surgery, 25% of the regions which had persistent defects before surgery exhibited normal perfusion patterns. These findings suggest that persistent defects may represent hypoperfusion of viable myocardium, and that we should carefully diagnose myocardial scars.