Aggressive surgical treatment with bony pelvic resection for locally recurrent rectal cancer.

BACKGROUND: In the current era of total mesorectal excision, local relapse remains a main cause of recurrence. Although standard treatment for locally recurrent rectal cancer (LRRC) has not been established, R0 resection represents the only potentially curative treatment. However, extended surgery accompanying bony pelvic resection is technically demanding and is still challenging. METHODS: Studied were 35 patients with LRRC who underwent combined resection of bony pelvis between August 2006 and October 2013. Safety and prognostic factors for survival were analyzed. Median follow-up was 33 months. RESULTS: Sacrectomy was performed in 32 patients and 3 patients underwent combined resection of the pubis and ischium. The dominant operative procedure was total pelvic exenteration in 30 (86%) patients. R0 resection was achieved in 27 (77%) patients. No patients died. Pelvic sepsis was the most frequent complication (40%). Recurrence developed in 20 (57%), with the lung the most frequent site (10 patients). Three-year local relapse-free survival (LRFS) and disease-free survival (DFS) were 72.1% and 32.7%, respectively. On multivariate analysis, R1 resection was the only independent risk factor for local recurrence (p = 0.010), and concomitant liver metastasis and initial non sphincter-preserving surgery were independent predictors of worse DFS (p = 0.008 and p = 0.042, respectively). CONCLUSIONS: Aggressive surgical treatment combined with bony resection for carefully selected patients with LRRC was safe with a high rate of R0 resection and favorable LRFS. However, DFS was not satisfactory even after R0 resection and the main cause was lung metastasis. Preventing distant recurrence might be a key to improve survival.

Total spondylectomy following carbon ion radiotherapy to treat chordoma of the mobile spine.

The main form of treatment of a chordoma of the mobile spine is total en bloc spondylectomy (TES), but the clinical results are not satisfactory. Stand-alone carbon ion radiotherapy (CIRT) for bone and soft-tissue sarcomas has recently been reported to have a high rate of local control with a low rate of local recurrence. We report two patients who underwent TES after CIRT for treating a chordoma in the lumbar spine with good medium-term outcomes. At operation, there remained histological evidence of viable tumour cells in both cases. After the combination use of TES following CIRT, neither patient showed signs of recurrence at the follow-up examination. These two cases suggest that CIRT should be combined with total spondylectomy in the treatment of chordoma of the mobile spine.

Can you diagnose for vertebral fracture correctly by plain X-ray?

INTRODUCTION: A wrong diagnosis of latent vertebral fracture is often made when it is based on plain X-ray imaging. Magnetic resonance imaging (MRI) has a high degree of accuracy for the definite diagnosis. This study was designed to identify ways to support improvements in the diagnostic accuracy of plain X-ray (X-P). METHODS: We studied X-P and MRI images of 120 women and men (age range: 50-96 years). Five orthopedists and two radiologists interpreted front and lateral thoracolumbar X-Ps and MRI images. The correct diagnosis rate for the presence and location of incident vertebral fractures and the correct diagnosis rate according to morphological classifications were analyzed. RESULTS: A correct diagnosis of incident fractures was made in 51.5% of cases overall. Diagnoses of non-incident fracture based on X-P in those cases with incident fracture based on MRI (false positive) occurred in 24.8% of the patients, while diagnoses of incident fracture based on X-P in those cases without incident fracture based on MRI (false negative) occurred in 6.5% of the patients. The application of morphological classifications (the primary osteoporosis diagnostic criteria and Yoshida's classification) resulted in the correct diagnosis rate being significantly higher in the group without prevalent fracture even when there were morphological changes (wedge, indented, protruding type) in the anterior bone cortex. Odds ratios were investigated for factors that would affect the correct diagnosis rate, including age, body weight, lumbar vertebrae bone mineral density, and examiner ability. In an overall investigation, age (OR=0.660), body weight (OR=2.082), and examiner ability (p=0.0205) affected the correct diagnosis rate. CONCLUSION: The correct diagnosis rate for incident vertebral fractures with X-Ps was low (24.8%) and in cases with prevalent fractures, the rate was even lower (16.8%), but the number of prevalent fractures and BMD did not exert an effect. One key improving the correct diagnosis rate may be to pay attention to morphological changes in the anterior bone cortex.

Does xanthine oxidase contribute to the hydroxyl radical generation in ischemia and reperfusion of the cochlea?

We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2-thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and allopurinol, on the threshold shift of the compound action potential (CAP) after transient ischemia of the cochlea. Transient ischemia of 30 min duration was induced in albino guinea pigs via a skull base approach. The animals were treated with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from 10 min before the onset of ischemia to 4 h after the termination of ischemia. Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did not affect the post-ischemic cochlear dysfunction. These results imply that the hydroxyl radical plays an important role in generation of cochlear dysfunction induced by ischemia-reperfusion and that xanthine oxidase may not be the primary source of this radical.

Poly(adenosine diphosphate-ribose) synthetase inhibitor 3-aminobenzamide alleviates cochlear dysfunction induced by transient ischemia.

The present study was undertaken to determine the possible deleterious role played by poly(adenosine diphosphate-ribose) synthetase (PARS) in cochlear ischemia-reperfusion injury. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by pressing the labyrinthine artery at the porus acusticus internus. The animals were given intravenous 3-aminobenzamide (a PARS inhibitor) or physiological saline solution I minute before the onset of reperfusion. The compound action potential thresholds were measured before the onset of ischemia and 4 hours after the onset of reperfusion. A statistically significant reduction in the postischemic compound action potential threshold shift was observed in the animals treated with 3-aminobenzamide after 15 or 30 minutes of ischemia, whereas no statistical difference was found after 60 minutes of ischemia. These results suggest that excessive activation of PARS exerts deleterious effects on the cochlear injury induced by transient ischemia.

Effect of 7-nitroindazole upon cochlear dysfunction induced by transient local anoxia.

The purpose of the present study was to further elucidate how nitric oxide (NO) is involved in cochlear anoxia-reperfusion injury. Transient local anoxia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by transiently compressing the labyrinthine artery through a skull base approach. 7-Nitroindazole (7NI), a relatively selective neuronal nitric oxide synthase (nNOS) inhibitor. was intraperitoneally administered to the guinea pigs 30 minutes before the onset of local anoxia. The compound action potential (CAP) thresholds were measured before the administration of 7NI and 4 hours after the onset of reperfusion. A statistically significant reduction in the postanoxic CAP threshold shift from the preadministration value was observed in the 7NI-administered animals as compared with the control animals after 15- and 30-minute periods of anoxia. These results confirm the involvement of NO and nNOS in the cochlear injury induced by transient local anoxia.

The contribution of phospholipase A2 to the cochlear dysfunction induced by transient ischemia.

The objective of the present study was to examine whether mepacrine, a commonly used phospholipase A2 inhibitor, decreases ischemic damage to the cochlea. Transient ischemia of the cochlea was induced in albino guinea pigs for 15, 30 or 60 min by pressing the labyrinthine artery at the porus acusticus internus. The animals were intraperitoneally given mepacrine or physiological saline solution (PSS) 20 min prior to ischemia. Although mepacrine failed to alleviate the post-ischemic threshold shift of compound action potential (CAP) in case of 60 min ischemia, a statistically significant reduction in the CAP threshold shift was observed in the mepacrine-treated animals after 15 and 30 min ischemia. However, there was no statistically significant difference in the post-ischemic threshold shift of cochlear microphonic between the mepacrine-given and the PSS-given animals. Furthermore, mepacrine partially alleviated ischemia-induced swelling of radial afferent dendrites of primary auditory neurons. These results suggest that excessive activation of phospholipase A2 plays an injury-producing role at least by enhancing excitotoxicity in ischemia-reperfusion injury of the cochlea.

Effect of A1 adenosine receptor agonist upon cochlear dysfunction induced by transient ischemia.

The present study was undertaken to determine whether 2-chloro-N6-cyclopentyladenosine (CCPA), a highly selective A1 adenosine receptor agonist, attenuated cochlear dysfunction induced by transient ischemia or not. Ischemia of different durations (15, 30 or 60 min) was induced in 46 albino guinea pigs by transiently pressing the labyrinthine artery. CCPA or physiological saline solution was intraperitoneally administered to the animals 15 min prior to ischemia. The post-ischemic CAP threshold shift from the pre-administration value was measured 4 h after the onset of reperfusion to assess post-ischemic cochlear dysfunction. A statistically significant reduction in the CAP threshold shift was seen in CCPA-given animals after 15- and 30-min ischemia, whereas there was no statistical difference after 60-min ischemia. These results suggest that A1 adenosine receptor agonist exerts a protective effect on the cochlear injury induced by transient ischemia of intermediate duration.

The protective effect of the sympathetic nervous system against acoustic trauma.

OBJECTIVE: the cochlea is innervated by the sympathetic nerve fibers. However, the functions of those fibers in the cochlea are still controversial. The present study was designed to determine whether the sympathetic nervous system (SNS) exerts a protective or enhancing effect on acoustic trauma. METHODS: acoustic overstimulation (either of 110, 115, or 130 dB SPL for 10 min) was performed in guinea pigs during electrical stimulation of the ipsilateral cervical SNS, after its surgical elimination or in the non-treated condition. The threshold shift of the compound action potential (CAP) from the pre-exposure value was measured at 1 h and at 1 week after acoustic overstimulation. Two-way analyses of variance (ANOVAs) were completed for the SNS conditions and the frequencies. RESULTS: although no significant difference was found at 1 h after overstimulation among these three groups, the CAP threshold shift at 1 week (110 and 115 dB SPL) was significantly smaller in the SNS stimulation group than in the other two groups. CONCLUSION: a protective effect was observed in the SNS stimulation group 1 week after the exposure to acoustic overstimulation of moderate intensity (from 110 to 115 dB SPL for 10 min).

Effect of nitric oxide synthase inhibitor on cochlear dysfunction induced by transient local anoxia.

To evaluate whether nitric oxide (NO) plays a role in the mechanism of generation of cochlear dysfunction induced by anoxia and reperfusion, the effects of a nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine, were examined using 71 albino guinea pigs. Transient cochlear anoxia of different duration (15, 30 or 60 min) was induced by pressing the labyrinthine artery and compound action potential (CAP) was measured before and 4 h after anoxia. N-nitro-L-arginine (1-30 mg/kg) administered intraperitoneally 1 h before the onset of anoxia alleviated the cochlear dysfunction when the anoxic period was 15 or 30 min. No beneficial effect was observed, however, in the 60-min anoxia. These results indicate that NO contributes to the generation of anoxia-induced cochlear dysfunction and that NOS inhibitor has a protective effect on the cochlear injury induced by anoxia of moderate duration.

The effect of mannitol upon cochlear dysfunction induced by transient local anoxia.

Transient local anoxia of the cochlea was induced by pressing the labyrinthine artery, and compound action potential (CAP) or endocochlear potential (EP) was measured before and after transient local anoxia ranging from 5 to 60 min using 106 albino guinea pigs. The complete interruption of the cochlear blood flow by this procedure and its full restoration after releasing the pressure on the artery was confirmed by a laser-Doppler flowmeter. The anoxia of less than 10 min induced no post-anoxic cochlear dysfunction, whereas the anoxia of a longer duration induced an irreversible dysfunction of the cochlea. It was evident that the post-anoxic recovery of the CAP threshold was worse as the anoxia period was prolonged, and CAP was almost completely abolished after 60-min anoxia. In animals which were administered mannitol intravenously just after the restoration of the cochlear blood circulation, the recovery of the CAP threshold was significantly better than that in the control animals, when the animals were subjected to local anoxia of 15- to 30-min duration. No beneficial effect, however, was observed in the 60-min anoxia group. In conclusion, local anoxia of 10 min or longer caused cochlear dysfunction, which was partially but significantly alleviated by mannitol.

Effect of acoustic overstimulation on the hydropic ear.

The effect of acoustic overstimulation (2 kHz pure tone) on the compound action potential (CAP) threshold was investigated at frequencies ranging from 2 to 16 kHz using albino guinea pigs, both normal and with experimentally induced endolymphatic hydrops. The hydropic ears were less susceptible to acoustic overstimulation than the normal ears. As the CAP threshold was raised, the frequency exhibiting the greatest CAP threshold shift increased in both animal groups. The tendency was more noticeable in the hydropic ears than in the normal ears. These results are discussed from the aspect of cochlear hydrodynamics.

Distortion-product otoacoustic emissions in experimentally induced hydropic ears.

The postoperative changes of distortion-product otoacoustic emissions (DPOAEs) and cochlear potentials were examined using 15 albino guinea pigs in which endolymphatic hydrops was induced by obliterating the endolymphatic sac. DPOAEs (geometric mean: 4,6 and 8 kHz) were measured once before and every week after surgery. At the 2nd (n = 5), 4th (n = 5) and 12th (n = 5) postoperative weeks, endocochlear potential (EP) and compound action potential (CAP) were measured. Although the reduction in DPOAEs at 8 kHz was first detected at the 12th week, the amplitude of DPOAEs at 4 and 6 kHz was already reduced at the first week and decreased gradually thereafter. In contrast to these results, the CAP threshold was not elevated at the 2nd week and a slight increase was first detected at the 4th week. The results obtained in the present study suggest that DPOAEs are more sensitive than CAP in detecting the presence of hydrops.

[Solute movement across the round window membrane in comparison with that across the blood-labyrinth barrier].

The permeability of the normal round window membrane of the guinea pig to trimethylphenylammonium (TMPA) was assessed using ion-selective electrodes and compared with the rate of TMPA entry from the systemic blood circulation into the scala tympani (ST) of the cochlea across the so-called blood-labyrinth barrier. While the round window niche was irrigated with artificial perilymph containing 1 mM TMPA, the TMPA concentration in ST of the basal turn rose rapidly so as to reach 20-50% of the irrigating medium concentration in one hour. Following this procedure, the concentration declined significantly faster when the niche was subsequently irrigated with TMPA-free artificial perilymph than when the niche was left free of any fluid. This result shows that the membrane is fairly permeable to TMPA in both directions. Furthermore, TMPA entry from blood to STs of the basal and third turns was observed while the plasma TMPA concentration was maintained at about 0.5 mM by continuous intravenous infusion of isotonic 50 mM TMPA medium (1 part 150 mM TMPA + 2 parts lactated Ringer solution). TMPA appeared to distribute evenly from the blood to both turns at a much slower rate than across the round window membrane. In another experiment, the round window niche was irrigated with TMPA-free artificial perilymph during the intravenous infusion of 50 mM TMPA medium. The TMPA concentration increase in ST of the basal turn was greatly suppressed, whereas that of the third turn was not affected for at least an hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmaceutical characterization of corticosteroid suppository treatment for ulcerative colitis.

The dose and method of administration of a corticosteroid given for the treatment of patients with ulcerative colitis are determined according to the range of the diseased area and its severity. In this study, we prepared a hydrophilic suppository consisting of water-soluble prednisolone sodium succinate (PSL-SS) and a hydrophilic base, polyethylene glycol (PEG), and a hydrophobic suppository consisting of water-insoluble prednisolone (PSL) and a hydrophobic base, Witepsol (WT). We determined the spread of the drugs after intrarectal administration and their therapeutic effect. When rats received the hydrophilic suppository, the drug spread farther oral than when they received the hydrophobic suppository. Moreover, more than half of the PSL-SS recovered was observed to have changed into PSL. A therapeutic effect on the colitis induced in rats by acetic acid was noted in the area up to 10 cm from the anus in the case of the hydrophilic suppository, while the effect of the hydrophobic suppository was seen only in the area up to 2.5 cm from the anus. In patients with ulcerative colitis, the hydrophilic suppository showed retrograde spread to a site 34.4 +/- 5.3 cm from the anus, while the hydrophobic suppository spread to a site 19.0 +/- 2.4 cm from the anus. These results suggest that a hydrophobic suppository should be used for patients in whom inflammation is confined to the rectum, and a hydrophilic suppository used for patients in whom inflammation reaches the rectum and the middle part of the sigmoid colon.

Protein profiles of perilymph and endolymph of the guinea pig.

Results of protein separation of guinea pig plasma, perilymph, and endolymph by means of high-resolution two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis are presented. Several proteins are present in perilymph at levels in basic accord with the total protein gradient with respect to plasma; however, others are present in perilymph at levels comparable to plasma levels, and one protein low molecular weight protein, PLS:33, is eight times higher. In addition, a high molecular weight protein is shown to be present at similar levels in the two compartments. These findings indicate that ultrafiltration cannot be the sole mechanism of perilymph production. Endolymph proteins are uniformly five to eight times lower than perilymph levels, essentially following the total protein concentration gradient between the two compartments. This supports the view that endolymph is derived from perilymph rather than directly from blood.

Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors.

We described a 5-month-old girl with Aicardi syndrome accompanied by auditory disturbance and multiple brain tumors. She was admitted to our hospital because she suffered from intractable flexor spasms. Physical examination revealed craniofacial asymmetry, left auricular deformity, scoliosis, and remarkable hypotonia with psychomotor retardation. Abnormal ophthalmological findings included chorioretinopathy with pale and round-shaped peripapillary lacunae, and there was modified hypsarrhythmia in her EEG. MRI revealed multiple brain tumors in the 3rd and the lateral ventricles which are considered to be choroid plexus papilloma with agenesis of the corpus callosum. ACTH therapy was administered because of the intractable seizures. After ACTH therapy, the thresholds of waves I and V were much improved. The interpeak latency of waves I-V of the left ear and the peak latency of wave I of the right ear had been lengthened. Acoustic reflex with contralateral stimulation showed no response in the left ear. These findings indicate that the auditory system is also involved in the Aicardi syndrome and that ACTH is effective for its dysfunction.

[Effect of motilin agonist, EM-523 on gastrointestinal motility].

In this study, we investigated the effect of EM-523, one of the erythromycin derivatives, on gastrointestinal motility in conscious dogs, in which force transducers were chronically implanted in the gastrointestinal tract. As a result, intravenous administration of EM-523 (1-10 micrograms/kg) induced phase III-like contractions in the stomach, and the EM-523-induced contractions migrated along the entire small intestine. EM-523 also stimulated the lower esophageal sphincter and the gallbladder motility, quite similar to exogenous motilin. Furthermore, we have investigated the effects of EM-523 both in postoperative ileus dogs and truncally vagotomized dogs. The dogs 1 to 4-day after the operation showed continuous and irregular contractions in the entire gastrointestinal tract, instead of typical interdigestive contractions. In these conditions, EM-523 induced strong phasic contractions in the stomach and duodenum, although these contractions did not always migrate along the small intestine. In the vagotomized dogs, spontaneous phase III contractions tended to be weaker than those in the normal dogs. EM523 induced phase III-like contractions in vagotomized dogs as in the normal dogs, and the contractile activities were improved. These results indicated that EM-523 may be useful as a gastroprokinetic drug for postoperative ileus and the patients with vagotomy.

The effect of furosemide on the endocochlear potential in ears with experimentally induced endolymphatic hydrops.

The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery.