Reduced induction of human ß-defensins is involved in the pathological mechanism of cutaneous adverse effects caused by epidermal growth factor receptor monoclonal antibodies.

Epidermal growth factor receptor inhibitors (EGFRIs) frequently cause cutaneous adverse effects such as papulopustular eruptions. However, the mechanism of the reactions remains unclear. To assess the pathological mechanism of cutaneous adverse reactions caused by EGFRIs, we investigated whether EGFRIs have an influence on the innate immune response of the skin. Levels of human ß-defensins (hBDs), which serve as the first line of defence against infection by pathogenic microorganisms, in the stratum corneum samples of patients treated with EGFR. monoclonal antibodies were measured before and after starting therapy. There were no obvious trends in hBD production in patients without eruptions, whereas a significant decrease in hBD1 and hBD3 production and a nonsignficant decrease in hBD2 production were observed in patients who developed papulopustular eruptions. Our results suggest that a reduction in hBD contributes to the increased incidence of papulopustular eruptions.

Basic evaluation of a novel 4D target and human body phantom.

Stereotactic body radiation therapy (SBRT) is usually verified with a dynamic phantom or solid phantom, but there is a demand for phantoms that can accurately simulate tumor dynamics within an individual that would allow customized validation in every patient. We developed a new 4D dynamic target phantom (multi-cell 4D phantom) that allows simulation of tumor movement in patients. The basic quality and dynamic reproducibility of this new phantom was verified in this investigation. The newly developed multi-cell 4D phantom comprises four main components: soft tissue, bones, lungs, and tumor (target). The phantom structure was based on computed tomography (CT) data of a male. In this study, we investigated the basic performance of a multi-cell 4D phantom. All the CT numbers of the phantom were very close to those of human data. The geometric maximum amplitudes were 4.57 mm in the lateral direction, 4.59 mm in the ventrodorsal direction, and 3.68 mm in the cranio-caudal direction. Geometric errors were 0.84, 0.58, and 0.40 mm, respectively. Movements of the abdominal surface were stable for 60 s. Repeated measurements show no actual differences in target movements between multiple measurements and indicated high reproducibility (r > 0.97). End-to-end tests using Gafchromic film revealed a gamma pass rate of 98% or above (2 mm/3%). Although our phantom performed limited reproducibility in the movement of the patient tumor at present, a satisfactory level of precision was confirmed in general. This is a very promising device for use in the verification of radiation therapy for moving targets.

International consensus (ICON) on treatment of Ménière's disease.

OBJECTIVE: To present the international consensus for recommendations for Ménière's disease (MD) treatment. METHODS: Based on a literature review and report of 4 experts from 4 continents, the recommendations have been presented during the 21st IFOS congress in Paris, in June 2017 and are presented in this work. RESULTS: The recommendation is to change the lifestyle, to use the vestibular rehabilitation in the intercritic period and to propose psychotherapy. As a conservative medical treatment of first line, the authors recommend to use diuretics and Betahistine or local pressure therapy. When medical treatment fails, the recommendation is to use a second line treatment, which consists in the intratympanic injection of steroids. Then as a third line treatment, depending on the hearing function, could be either the endolymphatic sac surgery (when hearing is worth being preserved) or the intratympanic injection of gentamicin (with higher risks of hearing loss). The very last option is the destructive surgical treatment labyrinthectomy, associated or not to cochlear implantation or vestibular nerve section (when hearing is worth being preserved), which is the most frequent option.

Post-operative infection of endoscopic submucosal dissection of early colorectal neoplasms: a case-controlled study using a Japanese database.

WHAT IS KNOWN AND OBJECTIVE: Endoscopic submucosal dissection of early colorectal neoplasms (ESD-ECN) is known to be an operation with risk of contamination, possibly requiring pre-operative antimicrobial prophylaxis for the prevention of post-operative infection. However, an evaluation of the need for pre-operative antimicrobial prophylaxis for ESD-ECN has yet to be reported. The objective of this study was to determine whether pre-operative antimicrobial prophylaxis is associated with a reduced incidence of post-operative infection following ESD-ECN. METHODS: The present retrospective case-controlled study utilized a database built from the medical records of 14 university hospitals throughout Japan. Patients who were admitted and discharged from the hospital from April 2012 to October 2013 and who had undergone ESD-ECN were included in the study. Patients who had been undergone any other operation during their course of hospitalization, and patients who were prescribed antimicrobial agents for reasons other than post-operative infection or for prophylaxis were excluded. Characteristics of the study population, pre-operative antimicrobial prophylaxis and antimicrobial therapy for post-operative infection were investigated. In addition, we compared the characteristics of patients with post-operative infection (PI) and those with no post-operative infection (NPI). Univariate analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS AND DISCUSSION: We obtained the records of 522 patients who had undergone ESD-ECN from the database. After application of exclusion criteria, 421 patients were enrolled. The post-operative infection rate was 1·2%. Peritonitis was found most to be the most common post-operative infection (44%). Pre-operative antimicrobial prophylaxis was used for 314 patients (75%), with a median duration of 3·0 (range 1-11) days. Cefotiam was most frequently prescribed for pre-operative antimicrobial prophylaxis (56%). Antimicrobial therapies were started 1-10 days after ESD-ECN for a duration of 1-14 days. Pre-operative antimicrobial prophylaxis was not associated with post-operative infection rate, with an OR (95% CI) of 0·73 (0·08-6·61). However, digestive tract perforation was shown to be associated with post-operative infection and had an OR (95% CI) of 17·1 (1·66-176·45). WHAT IS NEW AND CONCLUSION: Post-operative infection is an exceedingly rare event following ESD-ECN. Pre-operative antimicrobial prophylaxis had no significant effect on post-operative infection following ESD-ECN and thus may be unnecessary. Instead, prevention of digestive tract perforation may be more critical for the decrease in post-operative infections.

Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2-4 acute graft-versus-host disease.

BACKGROUND: Viral infections and their occult reactivation occasionally cause not only organ damage, but also exacerbation of acute graft-versus-host disease (aGVHD), which may increase transplantation-related mortality synergistically. To determine correlations between viral reactivation and transplantation-related complications, we performed various viral screening tests on the 30th day after allogeneic hematopoietic stem cell transplantation (HSCT), and assessed the clinical implications. PATIENTS AND METHODS: Between August 2007 and January 2013, 49 patients (37 men, 12 women) underwent HSCT in our hospital. The stem cell sources were bone marrow (n = 21), peripheral blood (n = 13), and cord blood (n = 15). The presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpesvirus (HHV) 6, and HHV7 in plasma samples prospectively collected from HSCT recipients on day 30 after HSCT was assayed by quantitative polymerase chain reaction, and the correlations with transplantation-related complications were evaluated. RESULTS: The positivities of CMV, EBV, HHV6, and HHV7 were 44.9%, 22.4%, 53.1%, and 18.3%, respectively. We analyzed transplantation-related complications, and a significant correlation was found only between HHV6 and grade 2-4 aGVHD from day 30 to day 100 (P < 0.001). Using a receiver operating characteristic curve, the area under the curve was calculated as 0.86 (95% confidence interval [CI], 0.74-0.98) between the viral load (VL) of HHV6 and grade 2-4 aGVHD. The sensitivity and specificity were 79% and 93%, respectively, when a cutoff value of 87 copies/mL was used. In multivariate analysis using the Fine and Gray proportional hazards model, the clinically determined high-risk patients (P = 0.004; hazard ratio [HR], 3.69; 95% CI, 1.52-9.00) and the positivity of HHV6 (P < 0.001; HR, 9.957; 95% CI, 2.68-37.06) were extracted as independent risk factors for the cumulative incidence of grade 2-4 aGVHD on or after post-HSCT day 30. The only risk factor extracted for the elevation of HHV6 VL >87 copies/mL was cord blood transplantation (P = 0.0032; odds ratio, 7.10; 95% CI, 1.98-30.00). CONCLUSION: All of the risk factors previously reported to predict severe aGVHD were obtained only during, but not after, HSCT. Our study suggests that the reactivation of HHV6 (≥ 87 copies/mL) at 30 days after HSCT is a possible predictive marker for grade 2-4 aGVHD on or after post-HSCT day 30.

A novel reduced-intensity umbilical cord blood transplantation using a recombinant G-CSF combined with high-dose Ara-C for active myeloid malignancies.

Non-remitting patients with hematologic myeloid malignancies have poor prognosis. To overcome this problem, we investigated the use of reduced-intensity preconditioning umbilical cord blood transplantation (RICBT) combined with recombinant G-CSF (rG-CSF) with high-dose Ara-C, fludarabine, melphalan, and 4 Gy of TBI in a phase I/II study in patients with non-remitting myeloid hematologic malignancies. Thirteen patients were enrolled, including 12 with non-remitting AML and one patient with blastic crisis CML (CML-BC). The patients' median age was 45 years, with a median comorbidity index of 4. All patients received 4/6 serological HLA-antigen matched unrelated umbilical cord blood. All patients were engrafted within 30 days after RICBT (median, 20 days; range, 14-29) and achieved complete remission without prior hematopoiesis. Common grade III non-hematologic toxicities included eight cases of transient mucositis (62%) and six cases of febrile neutropenia (46%). Transplant-related mortality was 7.7%. The 1-year overall survival was 28.6% in cases without post-RICBT treatment and 83.3% in cases with post-RICBT treatment. These data suggest that in active AML and CML-BC, the combination of rG-CSF with high-dose Ara-C and fludarabine/melphalan/4 Gy TBI with a reduced-intensity preconditioning regimen is well tolerated, secures engraftment and has significant anti-leukemia activity. In addition, performing post-RICBT treatment may provide high-quality long-term survival and remission.

Nationwide surveillance of antimicrobial consumption and resistance to Pseudomonas aeruginosa isolates at 203 Japanese hospitals in 2010.

PURPOSE: In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement. METHODS: We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan. RESULTS: Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R (2) (aR (2)) values of 0.23, 0.30, 0.22, and 0.35, respectively). CONCLUSION: This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption.

Outcomes analysis of ruptured distal anterior cerebral artery aneurysms treated by endosaccular embolization and surgical clipping.

Although endovascular surgery is now widely used to treat intracranial aneurysms, no comparative studies of clipping versus endovascular surgery to address distal ACA aneurysms at the same institution are available. We compared the results of these treatment modalities to address distal ACA aneurysms at our institution. We treated 68 patients with ruptured distal ACA aneurysms (endovascular surgery, n=13; clipping surgery, n=55). We performed a retrospective comparison of the treatment outcomes. To study the efficacy of endovascular surgery we classified all our cases into three types: type A were small-necked aneurysms, type B were wide-necked aneurysms on the parent artery, and type C were aneurysms in which the A3 portion of the ACA arose from the aneurysmal dome near the neck. Intraoperative hemorrhage occurred in 7.7% of aneurysms treated by endovascular surgery and in 34.5% treated by clipping surgery. In 7.7% of the endovascularly-treated aneurysms we noted coil migration during embolization surgery; venous infarction due to cortical vein injury occurred in 7.3% of clipped aneurysms. Of the endovascularly-treated aneurysms, 7.7% manifested post-embolization hemorrhage; 23.1% manifested coil compaction. In clipping surgery, postoperative rerupture occurred in 1.8% of the aneurysms; one patient presented with postoperative acute epidural hematoma. Clip dislocation was noted in 1.8% of aneurysms. Angiography was indicative of post-treatment vasospasm in 7.7% of aneurysms treated endovascularly and in 50.9% of the clipped aneurysms. The clinical outcome showed no significant difference between endovascular surgery and clipping surgery.

Meniere's attacks occur in the inner ear with excessive vasopressin type-2 receptors.

Meniere's disease is peculiar to humans and is characterised by episodic vertigo, fluctuating hearing loss and tinnitus, and attacks of the affliction occurring under conditions of stress. Its pathology was first revealed to be inner ear hydrops through temporal bone studies in 1938. Although subsequently proposed as a disorder of water metabolism in the inner ear, its pathogenesis remains unsolved. The present study aimed to assess the link between the inner ear pathology in Meniere's disease and vasopressin, an anti-diuretic stress hormone with a potential role in inner ear fluid homeostasis. Blood samples were obtained from Meniere's disease patients in the morning, before any surgical treatment, to examine plasma vasopressin (pAVP) levels, and then from inner ear tissue during surgical treatment, to examine vasopressin type-2 receptor (V2R) in the endolymphatic sac. pAVP and the relative V2R mRNA expression in the endolymphatic sac were examined using a real-time polymerase chain reaction. Relative cAMP activity in the endolymphatic sac was also examined using tissue culture and cAMP assay. Both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5-fold versus controls; P = 0.022) were significantly higher in Meniere's patients. cAMP activity was basally up-regulated (2.1-fold versus controls) and cAMP sensitivity to vasopressin application was largely elevated (4.9-fold versus controls) in Meniere's patients. We conclude that, in the pathogenesis of inner ear hydrops, resulting in Meniere's attacks, elevation of pAVP levels (probably as a result of stress) may present as a matter of consequence, but susceptibility of the V2R-overexpressed and cAMP-hypersensitized inner ear to pAVP elevation might be essential as the basis of this disease. Further experimental and clinical studies are needed to better clarify the relationship between Meniere's disease and stress.

Gene transfer in human skin with different pseudotyped HIV-based vectors.

Pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. In this study, the modification of HIV vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (VSV), the Zaire Ebola (EboZ) virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), Rabies or the rabies-related Mokola virus encoding LacZ as a reporter gene was evaluated qualitatively and quantitatively in human skin xenografts. High transgene expression was detected in dermal fibroblasts transduced with VSV-G-, EboZ- or MuLV-pseudotyped HIV vector with tissue irregularities in the dermal compartments following repeated injections of EboZ- or LCMV-pseudotyped vectors. Four weeks after transduction, double-labeling immunofluorescence of beta-galactosidase and involucrin or integrin beta1 demonstrated that VSV-G-, EboZ- or MuLV-pseudotyped HIV vector effectively targeted quiescent epidermal stem cells which underwent terminal differentiation resulting in transgene expression in their progenies. Among the six different pseudotyped HIV-based vectors evaluated, VSV-G-pseudotyped vector was found to be the most efficient viral glycoprotein for cutaneous transduction as demonstrated by the highest level of beta-galactosidase expression and genome copy number evaluated by TaqMan PCR.

Endovascular surgery for ruptured aneurysms with vasospasm.

SUMMARY: With the existence of vasospasm, it is recommended that direct clipping surgery for a ruptured aneurysm be delayed until its disappearance, but this may be associated with aneurysmal re-rupture resulting in a poor outcome for the patients. Indications for endovascular coil embolization in such cases are discussed. Since November in 2003, we have applied endovascular coil embolization in 11 consecutive patients with ruptured aneurysms and apparent vasospasm of the parent artery from two to 17 days (average: eight days) after initial subarachnoid hemorrhage. Three patients had aneurysmal re-rupture before treatment, but the other eight had only experienced the one episode of subarachnoid hemorrhage. With one exception, all endovascular procedures could be successfully performed, resulting in complete occlusion of aneurysms and remarkable dilatation of inserted spastic vessels without technical complications or aneurysmal re-rupture. For the one case of failure because of a tortuous artery, direct clipping surgery was performed after disappearance of vasospasm. Cerebral infarction occurred in four, but only one correlated with the distribution of catheterization, and neurological deficits had completely disappeared three months after the onset. This preliminary report concerning a small number of patients suggests that endovascular coil embolization is not contra-indicated for aneurysms with vasospasm requiring catheterization. A large study for confirmation is now warranted.

Global and systematic demonstration for the practical usage of a direct in vivo measurement system to evaluate wrinkles.

The global and systematic demonstration for the practical usage of a direct three-dimensional in vivo measurement system (PRIMOS) to evaluate wrinkles was investigated. Ten repetitive measurements of the corner of the eye of a subject showed that the coefficient of variation (CV)% value was 7.0% in a typical line-length roughness parameter R(a) (the arithmetic mean of roughness), and that the CV% value in a typical surface area roughness parameter S(a) was 2.4%. The relationships between the roughness values obtained from the corners of the eye and the age or wrinkle scores of Japanese women aged 10-70 years was examined. The values of several roughness parameters within the evaluation line length or surface area increased with age and showed a good correlation coefficient (r > 0.743). Similar relationships between the wrinkle scores and the values of roughness parameters were observed (r > 0.699). The roughness values were widely distributed even in the same wrinkle score because the measurement areas were limited and the values of skin roughness, including the microreliefs and/or small warts, were included in the calculation. However, changes in roughness values are considerable following treatment with potent active ingredients such as retinoic acid, so that this in vivo evaluation method is sufficient to objectively evaluate wrinkles. We conclude that the direct three-dimensional analysis of wrinkles in vivo should become a popular method to objectively evaluate wrinkles in clinical tests of wrinkle-smoothing ingredients or following cosmetic surgery to provide evidence of quantitative results.

Late-onset neuropsychological symptoms in a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts.

We herein report a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts (MLC) who developed late-onset neuropsychological symptoms. He demonstrated characteristic clinical features of MLC during childhood, such as slowly progressive megalencepaly, motor impairment with ataxia and spasticity, mild mental retardation, and well-controlled epilepsy. Thereafter, he showed specific neuropsychological symptoms, such as motor and vocal tics, compulsive behavior, perseveration, acquired stuttering, and dystonia since the age of 12. His performance abilities had been unchanged but his verbal abilities had degraded during the past 14 years. Higher cortical dysfunction tests revealed a frontal lobe dysfunction. On repeated brain MRI, a leukoencephalopathy with subcortical cysts remained stationary from infancy. On single photon emission computed tomography (SPECT), a hypoperfusion in the frontal lobe was detected at the age of 3.5 and 17, but the severity of hypoperfusion was also unchanged, respectively. Our results indicate that the frontal lobe dysfunction may be relevant to the late-onset neuropsychological symptoms with MLC.

Application of the liquid coil as an embolic material for arteriovenous malformations.

SUMMARY: The purpose of this paper is to clarify advantages and disadvantages of platinum liquid coils as an embolic material for AVMs. During the last eight years, 50 endovascular procedures using liquid coils were conducted in our institute for 19 cases with AVMs, 15 of which were located in the eloquent area. All but one presented with haemorrhage, the exception demonstrating repeated ischemic symptoms. Only liquid coils were used as the embolic material to obliterate the nidus and feeders. In ten of the 15 patients with AVMs located in the eloquent area and one case rejecting surgery, liquid coil embolization was applied one to 11 times (average 3.5 times) to achieve decrease in size and this was then followed by radiosurgery. The remaining eight AVM patients underwent total removal after liquid coil embolization. No complications were encountered during the peri-embolization period. In all cases, the purpose of embolization was to diminish the size to facilitate radiosurgery and decrease bleeding during surgery. The liquid coil has advantages as a material for embolization of AVMs; it is non-toxic and bioinart material; it seldom occludes normal minute vascular channels; when it used in a nidus, it seldom to migrates in the venous direction, and it has good radio-opacity and offers good marking for surgery. Appropriate applications include preoperative embolization or pre-radiosurgical embolization of AVMs, especially when staged embolizations are performed to reduce risk of perfusion pressure breakthrough in patients which are large or located in the eloquent area.

Vestibular function and vasopressin.

OBJECTIVE: To investigate the relation between the vestibular system and vasopressin (AVP). MATERIAL AND METHODS: We examined the effects of electrical and caloric vestibular stimulation on plasma AVP levels in anesthetized rats. Plasma AVP levels of patients with intractable Ménière's disease who were subjected to endolymphatic drainage and steroid instillation surgery (EDSS) or intratympanic gentamicin (GM) injection were measured before and after these interventions. RESULTS: Electrical vestibular stimulation increased plasma AVP levels in a current intensity-dependent manner. Plasma AVP levels were also increased by caloric stimulation with cold water. Plasma AVP levels decreased rapidly after EDSS, and were maintained at a low level even 6-12 months following EDSS or intratympanic GM injection. CONCLUSIONS: Vestibular activation or inhibition-induced imbalance of intervestibular activities increased plasma AVP levels in rats. Therefore, vestibular disorder would seem to increase plasma AVP and thus worsen endolymphatic hydrops. EDSS rapidly decreased plasma AVP and would seem to reduce hydrops. Inhibition of vertigo spells by EDSS or intratympanic GM injection would reduce a possible stress response, resulting in a decrease in plasma AVP levels a long time after the treatments. This resultant decrease in AVP would beneficially inhibit the formation and/or maintenance of hydrops and thus prevent vertigo spells.

How often should computed tomographic scans following cross-table lateral cervical films be performed?

PURPOSE: In patients with blunt trauma, a cross-table lateral cervical (CTLC) film is followed by a focused computed tomographic (CT) scan of the cervical spine to assess an area inadequately delineated by common techniques and suspected injuries, based on recent guidelines in the United States. The purpose of this study was to calculate the frequency of such supplemental CT scans and to evaluate the efficacy of the recent guidelines describing the use of CTLC films as an indicator of supplemental focused CT scanning in Japan. METHODS: A review of CTLC films was performed. 100 initial CTLC films with injuries and another 100 films without injuries were evaluated for the lowest vertebra visualised on the CTLC film. The frequency of abnormal signs on the CTLC films was then examined. RESULTS: Technically adequate CTLC films that showed the upper border of the T1 vertebra were not obtained from 70 patients with injuries and 63 patients without injuries. 88 patients with injuries and 28 patients without injuries had abnormal findings on CTLC films. Overall, 97 patients with injuries and 74 patients without injuries should have received supplemental CT scans. CONCLUSION: CTLC films require frequent supplemental use of CT, even for patients without cervical spine injuries. Thus, the guidelines that consider CTLC film as an indicator of the necessity for CT scanning are not efficient and need revision.

Definitive chemoradiotherapy for patients with malignant stricture due to T3 or T4 squamous cell carcinoma of the oesophagus.

We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.

Surgery for expansion of spinal tuberculoma during antituberculous chemotherapy: a case report.

We report a case of intramedullary spinal tuberculoma in a girl aged 2 years and 6 months. At the age of 18 months, the patient was hospitalized for 2 months with tuberculous meningitis. Tuberculomas then appeared in the thoracic spinal cord, and the patient developed paraparesis despite continuation of chemotherapy. Spinal magnetic resonance imaging demonstrated multiple ring-enhanced lesions in the cord on the T1-weighted image; on the T2-weighted image, the lesions had a bright core surrounded by a hypointense rim. Laminectomy and partial excision were performed, and the paraparesis improved. In addition to antituberculous chemotherapy and dexamethasone, surgical decompression was needed to treat the expansion of the spinal tuberculoma.

[Endolymphatic sac drainage and steroid-instillation surgery (EDSS) for intractable Meniere's disease].

Endolymphatic sac surgery is one of the most widely accepted techniques used to treat intractable Meniere's disease. To improve this surgery, we developed the following techniques: A simple mastoidectomy was used to expose the endolymphatic sac between the sigmoid sinus and inferior margin of the posterior semicircular canal. The sac was opened and filled with a mass of prednisolone. A bundle of absorbable gelatin films was then inserted into the sac lumen to expand it, followed by gelatin sponges dipped in a high concentration of dexamethasone. Long-term results (17-32 months) in 20 patients with intractable Meniere's disease treated with endolymphatic sac drainage and steroid-insertion surgery (EDSS) showed that definitive spells were completely controlled in 15 of 20 cases (75%); all reports of vertigo decreased; hearing improved in 12 of 20 cases (60%); and annoyance due to tinnitus decreased in 15 of 20 cases (75%). Steroids directly instilled into the endolymphatic cavity may thus be more effective with the diseased inner ear organs than those applied via any other route. Draining of endolymphatic fluid at the sac into the mastoid cavity also contributed to these satisfactory EDSS results.

[A case of esophageal carcinoma with multiple liver metastases successfully treated with nedaplatin (NDP) and 5-fluorouracil (5-FU) combined with radiotherapy].

A 78-year-old male patient had esophageal carcinoma with multiple liver metastases. Chemoradiotherapy was performed. The chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU), combined with infusion of nedaplatin (NDP). Radiation of the mediastinum was administered concomitantly with chemotherapy. The patient showed a complete response (CR) of the primary lesion and a partial response (PR) of the liver metastasis for 11 months. Since liver metastasis recurred after initial treatment, chemotherapy consisting of NDP infusion combined with vindesine sulfate (VDS) infusion was performed. The patient again showed PR. Grade 3 leukocytopenia occurred during treatment, but there were no major toxicities such as thrombocytopenia, nausea, renal dysfunction or esophagitis. Survival time was one year and 7 months. In conclusion, concurrent chemoradiotherapy including NDP is effective and safe for patients with esophageal carcinoma accompanied by multiple liver metastasis. This nonsurgical approach may be an option for standard care in such cases.