Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group

Gefitinib (Iressatrade mark) is an epidermal growth factor receptor tyrosine kinase inhibitor that has been approved for the treatment of lung cancer in Japan, however, after marketing several cases of severe pulmonary toxicity were reported. The West Japan Thoracic Oncology Group conducted an independent survey of acute pulmonary toxicity and interstitial lung disease (ILD) caused by gefitinib in its member's institutions. The purpose of this study was to clarify the image characteristics of ILD caused by the molecular-targeting drug gefitinib. A total of 1976 patients had been treated with gefitinib between August and December 2002, and 102 of them were suspected of having acute pulmonary toxicity and ILD. A final definite diagnosis of gefitinib-induced ILD was made by at least three radiologists based on a review and analysis of the chest radiography and CT findings plus the clinical data in the medical records. The imaging findings were classified into four patterns: (A) a nonspecific area with ground-glass attenuation, (B) a multifocal area of airspace consolidations, (C) patchy distribution of ground-glass attenuation accompanied by interlobar septal thickening, and (D) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. CT as well as chest radiography had been performed in 65 of the 102 patients at the onset of ILD, and chest radiography alone had been performed in 26. After excluding 11 cases with insufficient data and 21 cases concluded to be other pulmonary diseases, 70 patients were diagnosed with gefitinib-induced ILD. Finally, the diagnostic image findings were classified as pattern A in 29 cases, pattern B in 7 cases, pattern C in 3 cases, pattern D in 20 cases and others in 11 cases. The CT images were classified as pattern A, B, C, and D in 24, 7, 1, and 12 cases, respectively. The mortality rate was significantly higher in the patients with pattern D than the other patterns. Pattern D were thought to represent the features of diffuse alveolar damage. In conclusion, the molecular-targeting drug gefitinib induces pulmonary toxicity at a certain rate and the imaging findings of ILD induced by gefitinib are similar to those of pulmonary toxicity induced by conventional antineoplastic agents.     

Hot environment and health problems of outdoor workers at a construction site

The aim of this research was to understand hot working environment at a construction site in summer and its effects on health of workers. In the subjective construction site, some measures, such as taking a break during work, setting tents and electric fans, and drinking cool water, had already been taken to reduce heat stress. Twelve male workers were examined. The WBGT outdoors during work varied from 23 to 34 degrees C. The time-motion study revealed that one subject worked exceeding 7 hours, and that the other one had little rest time and drank little water during work. Few items of subjective symptoms increased after work compared with before work. In blood chemical data, electrolytes and blood urea nitrogen did not change. Blood sugar before work was significantly higher than before lunch and after work. Two subjects showed serum osmotic pressures increased after work. Two had the tendency to increase the blood pressure during work. The measures seemed effective, because the effects of work were not remarkable in general. However, some problems were still pointed out. Thus, stricter work control and health care for workers are necessary, such as controlling working hours strictly and monitoring the water intake during work.     

Development of new surgical tools, Q-PAL and HP-Jet for endoscopy only used unilateral transnasal approach for pituitary adenomas

The aim of this study is to present surgical techniques and results of endoscope-assisted transnasal approach (TNA) for pituitary adenomas. It is a new alternative for Hardy's surgery (TSS). We performed TNA assisted by only endoscope through single nostril. METHOD: We enter the sphenoid sinus directly through the natural ostium and ablate neither the nasal septum nor the vomer bone. We found the hardest problem of this method resides in its deep and narrow working space which obstructs usage of two tools at same time. To overcome this problem we developed two surgical tools, Q-PAL and HP-Jet. Q-PAL is combination of PAL and suction. We place flexible PAL wire electrode through suction tube so as PAL tip protrudes from suction tip. This eliminates coagulation smoke which otherwise disturbs surgeons view. HP-Jet is a combination of a suction tool and an irrigator. The irrigator is connected to syringe containing saline. Saline is injected manually from tip bursting up tumor tissue with its jet pressure. It is safe and effective instrument suitable for extirpation of rather fragile tissue like adenomas existing in deep and blind spaces. CASES: Since 2004 we have operated on 16 patients using endoscopic TNA. Eight were non-functioning adenomas, and 8 functioning. RESULTS: Results of surgery were compared with those of 10 cases operated by TSS. More than 70% removal of adenoma was achieved in 75% of cases with TNA, but in only 71% with TSS. Postoperative CSF rhinorrhea was seen in one case. Four cases showed postsurgical transient diabetes insipidus. We had no case with postsurgical infection. With the help of instruments having multiple functions in single probe such as Q-PAL and HP-Jet, we can execute endoscopic TNA more smoothly and more safely.     

Outcome of carotid endarterectomy and stent insertion based on grading of carotid endarterectomy risk: a 7-year prospective study

OBJECT: The authors of this study prospectively compared periprocedural neurological morbidity and the appearance of lesions on diffusion-weighted (DW) magnetic resonance (MR) imaging in patients who had undergone carotid endarterectomy (CEA) or carotid artery stent placement (CASP) with distal balloon protection, based on a CEA risk grading scale. METHODS: Patients undergoing CEA (139 patients) and CASP (92 patients) were classified into Grades I to IV, based on the presence of angiographic (Grade II), medical (Grade III), and neurological (Grade IV) risks. Although not randomized, the CEA and CASP groups were well matched in terms of the graded risk factors except for a greater proportion of neurologically unstable patients in the CEA group (11 compared with 3%, p = 0.037). There were greater proportions of asymptomatic (64 compared with 34%, p = 0.006) and North American Symptomatic Carotid Endarterectomy Trial-ineligible patients (29 compared with 14%, p < 0.0001) in the CASP group. The overall rates of neurological morbidity with ischemic origin and the appearance of lesions on DW MR imaging after CEA were 2.2 and 9.3%, and those after CASP were 7.6 and 35.9% (nondisabling stroke only), respectively. The only disabling stroke was caused by an intracerebral hemorrhage attributable to hyperperfusion in one case (0.7%) of CEA. There were no deaths. There was no significant association between neurological morbidity and the risk grade in patients who had undergone CEA, although the incidence of lesions on DW imaging was significantly greater in the Grade IV risk group compared with that in the other risk groups combined (42.1 compared with 4.2%, p < 0.0001). After CASP, a higher incidence of neurological morbidity and lesions on DW imaging was noted for the Grade II and III risk groups combined as compared with that in the Grade I risk group, regardless of a symptomatic or an asymptomatic presentation (neurological morbidity: 10.5 compared with 3.1%, respectively, p = 0.41; and DW imaging lesions: 47.4 compared with 19.4%, p = 0.01). The incidence of lesions on DW imaging after CEA was significantly lower than that after CASP except for the Grade IV risk groups. CONCLUSIONS: Despite a higher incidence of DW imaging-demonstrated lesions in the Grade IV risk group, there was no significant association between the risk group and neurological morbidity rates after CEA. The presence of vascular and medical risk profiles conferred higher rates of neurological morbidity and an increased incidence of lesions on DW imaging after CASP. Considering that no serious nonneurological complications were noted, CEA and CASP appear to be complementary methods of revascularization for carotid artery stenosis with various risk profiles.     

Orthotopic bladder substitution

Orthotopic bladder substitution is the most desired form of urinary diversion because the patient can restore normal voiding after cystectomy. However, urethral recurrence must be seriously considered and the patients with a risk of urethral recurrence are not indicated. Each method of bladder substitution has merits and demerits. We compared the Mainz method and the Studer method of orthotopic bladder substitution we performed on 8 and 11 patients, respectively since 1992. The Studer orthotopic ileal bladder substitution has given better results with better voiding pattern and less complication rates. We consider the Studer ileal bladder substitution as a good technique to restore normal voiding after cystectomy.     

The administration of reserpine to rats for 75 weeks

The chronic toxicity and carcinogenicity of an antihypertensive agent, reserpine, on oral administration was examined in Wistar strain rats. Male and female rats were given diets containing 0, 30 or 60 ppm of reserpine for 75 weeks. The body weights of male and female rats on diets containing 60 ppm and 30 ppm reserpine were significantly lower (P < 0.001) than those of the controls. Benign and malignant tumors were found, but their incidences were not statistically significant. Moreover, no histopathological changes were found that were significantly related to reserpine administration.     

Endoscopic Reduction of Acute Gastric Volvulus in a Child

Abstract: An 11-year-old girl with cerebral palsy was admitted with complaints of frequent vomiting and upper abdominal distension. After plain X-ray examination and upper gastrointestinal contrast study, she was diagnosed as having acute mesenterioaxial volvulus of the stomach. Endoscopic reduction was successfully performed. We describe herein the technical details of the endoscopic reduction in this rare case. In non-infant pediatric patients with primary gastric volvulus, we recommend that endoscopic reduction be considered prior to surgical intervention.     

Synergistic Effects of Low-dose Hepatocarcinogens in Induction of Glutathione S-Transferase P-positive Foci in the Rat Liver

The effects of combined administration of hepatocarcinogens at low doses on the development of glutathione S -transferase P-form (GST-P)-positive foci of rat liver were examined utilizing a bioassay model which consists of a single injection of diethylnitrosamine (DEN, 200 mg/kg, ip), two-thirds partial hepatectomy at week 3 and a 6-week administration of test compounds. The chemicals used, 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), phenobarbital (PB), thioacetamide (TAA), N-ethyl-N-hydroxyethylnitrosamine (EHEN), benzo[ a ]pyrene (B[a]P), carbazole, and α-hexachlorocyclohexane (α-HCH) were incorporated in the diet, except for EHEN which was dissolved in the drinking water, at levels of 1/6 of the doses usually used. The combinations were: I) 2-AAF, 3'-Me-DAB, PB, TAA, EHEN and B[a]P, II) 2-AAF, 3'-Me-DAB and PB, III) TAA, EHEN and B[a]P, IV) 2-AAF, 3'-Me-DAB, carbazole, TAA, EHEN and a-HCH, V) 2-AAF, 3'-Me-DAB and carbazole, and VI) TAA, EHEN and α-HCH. All combinations, except for II, caused an increase in the area of the foci as evaluated by the ratios of areas in the combined administration groups to the sum totals of 3 or 6 individual data: I) 1.75, II) 0.81, III) 2.01, IV) 3.62, V) 1.34 and VI) 2.91. The non-synergistic effect in combination II might be related to PB induction of hepatic microsomal enzymes leading to enhanced enzymatical detoxification of 2-AAF and 3'-Me-DAB. The present results indicate that exposure to several chemicals of similar organotropism, even at doses lower than the apparent carcinogenic levels, might be critical to the carcinogenic process.