Phase I/II trial of a biweekly combination of S-1 plus docetaxel in patients with previously treated non-small cell lung cancer (KRSG-0601).

BACKGROUND: Combination of S-1, an oral fluorouracil derivative, plus docetaxel against non-small cell lung cancer (NSCLC) showed promising efficacy but clinically problematic emesis. A phase I/II study utilising a new schedule for this combination was conducted. METHODS: A biweekly regimen of docetaxel on day 1 with oral S-1 on days 1-7 was administered to previously treated NSCLC patients. Doses of docetaxel/S-1 were escalated to 30/80, 35/80, and 40/80 mg m(-2), respectively, and its efficacy was investigated at the recommended dose below maximum tolerated dose (MTD). RESULTS: In phase I study employing 13 patients, dose-limiting toxicities were febrile neutropenia and treatment delay, with the respective MTDs for docetaxel 40 mg m(-2)/S-1 80 mg m(-2). In the phase II study, 34 patients were treated with docetaxel 35 mg m(-2)/S-1 80 mg m(-2) for a median cycle of 6. The response and disease control rates were 34.3% (95% confidence interval (CI), 18.6-50.0%) and 62.9% (95% CI, 46.8-72.9%), respectively. Median progression-free survival was 150.5 days. Haematologic grade 4 toxicities were observed in neutropenia (11.8%) and thrombocytopenia (2.9%). Regarding non-haematologic toxicities, including emesis, there were no grade 3/4 side effects. CONCLUSION: Combination of 1-week administration of S-1 with biweekly docetaxel is safe and active for NSCLC.

Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course.

AIMS: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking-related interstitial lung disease. METHODS AND RESULTS: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P < 0.01) with lower lobe predominance. There were significant correlations (P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone (P < 0.01). CONCLUSIONS: AEF is an important smoking-related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important.

Behavioral planning in the prefrontal cortex.

Recent studies have presented evidence that the prefrontal cortex plays a crucial role in every aspect of the cognitive processes necessary for behavioral planning: processing and integration of perceived or memorized information, associative learning, reward-based behavioral control, behavioral selection/decision-making and behavioral guidance. We propose that the creation of novel information is the means by which the prefrontal cortex operates to achieve executive control over behavioral planning. The prefrontal cortex is the site of operation of nodal points, where neural circuits integrate currently available or memorized information to generate the information that is necessary to perform an action. The prefrontal cortex also regulates the flow of information through multiple nodes to meet behavioral demands.

Integration of target and body-part information in the premotor cortex when planning action.

To plan an action, we must first select an object to act on and the body part (or parts) to use to accomplish our intention. To plan the motor task of reaching, we specify both the target to reach for and the arm to use. In the process of planning and preparing a motor task, information about the motor target and the arm to use must be integrated before a motor program can be formulated to generate the appropriate limb movement. One of the structures in the brain that is probably involved in integrating these two sets of information is the premotor area in the cerebral cortex of primates. The lateral sector of the dorsal premotor cortex is known to receive both visual and somatosensory input, and we show here that neurons in this area gather information about both the target and the body part, while subsequent activity specifies the planned action.

Neuronal activity in the primate prefrontal cortex in the process of motor selection based on two behavioral rules.

This study examined neuronal activity in the prefrontal cortex (PF) involved in the process of motor selection in accordance with two behavioral rules. We trained two monkeys to select a target based on the integration of memorized and current sensory information. Initially, a sample cue (triangle or circle) appeared at one of three locations (top, left, or right) for 1 s. After a 3-s delay, one of two types of choice cue appeared. The first type asked the monkeys to reach for a target by matching the location (location-matching task). The second type asked the monkeys to reach for a target by matching the shape (shape-matching task). The choice cue for location matching consisted of either three circles or three triangles, and the choice cue for shape matching consisted of a circle and a triangle. When the color of the choice cue changed from red to green 1.5 s later (GO signal), the monkeys touched the correct object to obtain a reward. We found cue-, delay-, choice-, and movement-related neuronal activity in the lateral prefrontal cortex. During the sample cue presentation and delay periods, we found selective neuronal activity for the location or shape of the sample cue. Shape-selective neurons were located more anteriorly in the ventral bank of the principal sulcus and inferior convexity area, whereas location-selective neurons were more posteriorly. After the choice cue appeared, we found three main types of neuronal activity in the critical period when the subject selected the future target: 1) activity reflecting past sensory information (the location or shape of the sample cue presented 3 s earlier), 2) activity selective for the configuration of the current choice cue, and 3) activity reflecting the properties (location or shape) of the future target. During the motor-response period, we found neuronal activity selective for the location or shape of the reaching target. When muscimol was microinjected into the ventral bank of principal sulcus and inferior convexity area, the performance of both tasks was impaired. Furthermore, we found that the wealth of neuronal activity in the PF that seemed to play a role in motor selection was rarely seen in the primary motor cortex.

Reacquisition deficits in prism adaptation after muscimol microinjection into the ventral premotor cortex of monkeys.

A small amount of muscimol (1 microl; concentration, 5 microg/microl) was injected into the ventral and dorsal premotor cortex areas (PMv and PMd, respectively) of monkeys, which then were required to perform a visually guided reaching task. For the task, the monkeys were required to reach for a target soon after it was presented on a screen. While performing the task, the monkeys' eyes were covered with left 10 degrees, right 10 degrees, or no wedge prisms, for a block of 50-100 trials. Without the prisms, the monkeys reached the targets accurately. When the prisms were placed, the monkeys initially misreached the targets because the prisms displaced the visual field. Before the muscimol injection, the monkeys adapted to the prisms in 10-20 trials, judging from the horizontal distance between the target location and the point where the monkey touched the screen. After muscimol injection into the PMv, the monkeys lost the ability to readapt and touched the screen closer to the location of the targets as seen through the prisms. This deficit was observed at selective target locations, only when the targets were shifted contralaterally to the injected hemisphere. When muscimol was injected into the PMd, no such deficits were observed. There were no changes in the reaction and movement times induced by muscimol injections in either area. The results suggest that the PMv plays an important role in motor learning, specifically in recalibrating visual and motor coordinates.

[A case of sleeve resection of the left main bronchus for tuberculous bronchial lesion].

A 31-year-old woman was admitted to our center with left chest pain and dyspnea after treatment of pulmonary tuberculosis. Chest X-ray film showed atelectasis of left lower lobe and left deviation of the mediastium. Bronchofiberscopy revealed obstruction of the left main bronchus. Chest MRI showed intermediate intensity at the left main bronchus and very high intensity at the peripheral bronchus. We performed sleeve resection of the left main bronchus and anastomosed end to end with absorbable monofilament sutures. Postoperative course was uneventful. Bronchoplasty for tuberculous obstructive lesion is a useful procedure.

Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex.

Task-dependent selectivity of movement-related neuronal activity in the primate prefrontal cortex. J. Neurophysiol. 80: 3392-3397, 1998. We studied movement-related neuronal activity in the dorsolateral prefrontal cortex from the perspective of a general role for the prefrontal cortex in controlling motor behavior to achieve a specific goal according to the requirements of a given task. Monkeys were trained to perform two delayed motor tasks. The first task involved reaching for a target that matched the shape of a cue. The second task involved reaching for a target that matched the location of the cue. A majority (54%) of 175 movement-related prefrontal neurons exhibited preference for either the target shape or the type of task requirements. Sixty-four neurons (36%) were selectively active while reaching for a circle or a triangle. On the other hand, the activity of 59 neurons (34%) depended on whether the task required matching the shape or the location. These properties, characterizing the movement-related neuronal activity in the prefrontal cortex, rarely were found in the arm area of the primary motor cortex. Only 1 of 130 movement-related neurons (0.8%) showed task selectivity, and none showed target-shape selectivity.

Neuronal activity in the claustrum of the monkey during performance of multiple movements.

1. We studied neuronal activity in the claustrum of monkeys during performance of three different arm movements. We verified recording sites of claustral neurons by histological confirmation of microlesions. For the sake of comparison, we also recorded from the arm area of the precentral motor cortex (MI). Selection of the movements was either visually guided or determined by memorized information. 2. A striking property of claustral neurons is their nonselective relation to the three movements (push, pull, and turn a manipulandum). A vast majority (70%) of movement-related neurons exhibited increase of discharge in relation to all three movements, whereas only 16% were active in relation to one of the three movements. By contrast, about one-half of neurons in the MI were active in relation to a single movement. In both areas, the movement-related activity was similar regardless of whether the movements were selected by visual signals or by memory. 3. The study is the first to reveal involvement of claustral neurons in motor execution, and their activity property suggests that the way they are involved is different from that of MI neurons.

[A case of a synchronous triple primary lung cancer with hamartoma].

We present a case of synchronous triple primary lung cancer. 69-year-old male admitted after mass examination with the tumor shadows on right S3, left S4 and left S8. Further examinations confirmed as squamous cell carcinoma of right S3 and left S8 and as benign tumor of left S4 with right hillar lymph nodal swelling. In addition to these lesion, bronchofiberscopy revealed the squamous cell carcinoma of left basal bronchus. The secondlook operation was planned for bilateral primary lung cancer. At first, patient underwent right S3 segmentectomy with regional lymph nodes dissection. Two month later, left thoractomy was performed, followed by left lower lobectomy. Histopathological examination defined as well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma, squamous cell carcinoma in situ and hamartoma for right S3, left S8, left basal bronchus and left S4, respectively. Lymph node metastasis was found only in #121. Although tumors were resected with good curability, respiratory function was depressed and performance status deteriorated. It is important to attention to the preservation of respiratory function for the surgical treatment to multiple lesions and the combined therapy with radiation, chemotherapy and/or laser may be considered.

Enhancement of the intracranial arterial wall at MR imaging: relationship to cerebral atherosclerosis.

PURPOSE: To investigate the relationship between intracranial arterial wall enhancement and atherosclerosis. MATERIALS AND METHODS: Intracranial vertebral arteries of 30 patients and carotid arteries of 62 patients were studied with spin-echo magnetic resonance imaging with contrast enhancement and spatial presaturation. Arterial wall enhancement was graded as follows: stage 1, no substantial enhancement; stage 2, faint or thin area of enhancement; stage 3, definite and thick area of enhancement. RESULTS: In vertebral arteries, stage 3 enhancement was seen in 11 patients (mean age, 73.7 years) and stage 1 in eight (mean age, 56.4 years). In carotid arteries, stage 3 enhancement was seen in 13 patients (mean age, 71.0 years) and stage 1 in 21 patients (mean age, 39.0 years). In both arteries, stage was well correlated with age (P < .05). CONCLUSION: Arterial wall enhancement is related to aging and is probably due to neovascularity in association with atherosclerotic plaques. This finding may permit assessment of intracranial atherosclerosis and other vascular diseases.

A huge immature cervical teratoma in a newborn: report of a case.

A neonate with a large cervical mass was transferred to our hospital at 4 days of age. A computed tomography scan showed a contrast-enhanced solid mass with multiple cystic elements and fine calcification. Ultrasonography also revealed a predominantly solid mass with calcification, containing multiple cysts. These studies suggested a teratoma, but could not rule out a hemangioma. The tumor was removed on the 12th day of life. A pathological study revealed an immature teratoma that demonstrated fetal type cartilage and an immature neural tube. The operative complete removal of a cervical teratoma in neonates is recommended as soon as possible. The management of a pediatric cervical teratoma should also be similar to that of a sacrococcygeal teratoma. The incidence of cervical teratoma in all pediatric teratomas ranges from 2.3%-9.3% in the West, and from 1.6%-8.3% in Japan.

[A case of small adenocarcinoma of the lung with giant bullae].

A 52-year-old male underwent right upper lobectomy for giant bullae which involved almost half of thoracic cavity and covered over the right upper lobe. Postoperative histopathological examination revealed emphysematous bullae of right upper lobe and adenocarcinoma (6 mm in diameter) was found in the bullae wall under the pleura. Since there was no metastasis in bronchial lymph nodes of upper lobe, additional procedure for lymph node dissection was not performed. Patient has been healthy for eight years after operation and there is no evidence of recurrent tumor. It is difficult to define the small lesion of neoplasma with giant bullae of lung. Therefore, the patient involved with bullae may require preoperative and intraoperative attentive investigation for possible malignant lesions.

[Anesthesia for pectus excavatum].

The incidence of arrhythmia, postoperative complication and pulmonary oxygenation (PaO2) were studied in 48 patients with pectus excavatum scheduled for the Ravitch operation under halothane-nitrous oxide-oxygen (GOF) and enflurane-nitrous oxide-oxygen (GOE) anesthesia. Preoperative abnormalities of ECG were observed in 36 of 18 cases. Main abnormalities were incomplete right bundle branch block, left atrium enlargement, and sinus arrhythmia. Ventricular arrhythmia was observed in 4 of 12 cases during GOF anesthesia, whereas no arrhythmia was observed during GOE anesthesia. In postoperative chest X-ray, pulmonary atelectasis (60%), pleural effusion (48%), and pneumothorax (8%) were observed. The results suggest that GOE is more advantageous for pectus excavatum operation than GOF. Postoperative pulmonary surveillance is important for pectus excavatum operation.

[A study of five cases of traumatic diaphragmatic rupture].

During the last 5 years, 5 cases of traumatic diaphragmatic rupture were surgically treated. These cases were reported and the literature concerning traumatic diaphragmatic hernia in the last one decade in Japan, including 80 cases was studied. The purpose of this study is to discuss the most important early diagnostic tools and to consider the choice of incision and approach. The following two results were gotten. (1) Plain chest X-ray, computed tomography and ultrasonography were the most valuable diagnostic tools. (2) The choice of incision and approach depends on the stage at which the rupture is recognized (early or late), the site of rupture and associate injuries.

Surgery of giant bulla with tube drainage and bronchofiberoptic bronchial occlusion.

A case of emphysematous bullae and right lung cancer is presented. At first, left giant bulla was managed by minithoracotomy and tube drainage combined with bronchofiberoptic bronchial occlusion to preserve the respiratory function. Four weeks later, right lung cancer was successfully resected.

[Two cases of wedge pneumonectomy in primary lung cancer involved into carina].

Right wedge pneumonectomy was performed on two cases of primary lung cancer involved into carina. A 59-year-old male involved with primary lung cancer was found with bloody sputum. Preoperative data confirmed as the superficial spread type of squamous cell carcinoma in carinal lesion and tumor was resectable with wedge pneumonectomy. In the second case, abnormal shadow was pointed out on chest X-ray film of a 61-year-old male patient. Preoperative examination defined as primary lung cancer of rt-S6 with subcarinal lymph node metastasis. The operation indicated wedge pneumonectomy with patch plasty using the wall of right main bronchus. Although wedge pneumonectomy is not common compared to sleeve pneumonectomy, if available this procedure is technically easier and post-operative management may be more successful. Wedge pneumonectomy limits resectable area, because the continuation of tracheo-bronchial wall must be remained in part. Therefore, the indication of this procedure for surgical treatment of lung cancer is limited. However, when this procedure indicates to selected case with limited lesion of carina, this may be an useful procedure as surgical treatment of primary lung cancer.

[A case of omentopexy for bronchial fistula and pyothorax following the right completion pneumonectomy with combined resection of pericardium, diaphragm and chest wall].

A 68-year-old male underwent the right completion pneumonectomy with combined resection of pericardium, diaphragm and chest wall. Three months later, he was diagnosed as a bronchial fistula with bloody sputum and decreasing of right pleural effusion level on chest X-ray film. The conservative therapy with pleural drainage and endoscopic practice with fibrin matrix was failed to close a fistula and pyothorax was developed. Therefore, surgical treatment with simple omentopexy without thoracoplasty and/or muscle transposition was performed onto fistula and SILASTIC sheet used for the repair of diaphragm at initial operation was left in the thoracic cavity. Although pleural fluid remained the contamination with bacteria for one month postsurgically, infection did not develop and fistula closed successfully. Moreover, infection did not prolong in the presence of artificial SILASTIC sheet followed by simple omentopexy. Omentopexy may be very useful for the treatment of bronchial fistula with the presence of infection.