Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia.

BACKGROUND: Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation. METHODS: Ki67 (clone, MIB-1) liver parenchyma expression was measured by immunohistochemical staining of samples from living donors and patients with biliary atresia to assess its value in predicting outcomes after KP. RESULTS: Of 35 children with biliary atresia, 13 were native liver survivors (NLS), 17 were non-NLS, and five had primary LT. The median proportion of Ki67 immunostained areas in donors and patients with biliary atresia at KP was 0·06 and 0·99 per cent respectively. Univariable analysis identified a high proportion of Ki67 areas, high Ki67 cell numbers and high Ki67-positive/leucocyte common antigen-positive cell numbers at KP as significant predictors of poor native liver survival after KP (hazard ratio 9·29, 3·37 and 12·17 respectively). The proportion of Ki67 areas in the non-NLS group was significantly higher than that in the NLS group (1·29 versus 0·72 per cent respectively; P = 0·001), and then decreased at LT (0·32 per cent versus 1·29 per cent at KP; P < 0·001). CONCLUSION: This study has demonstrated the clinical data and time course of Ki67 expression in patients with biliary atresia. High Ki67 expression at KP may be an important predictor of native liver survival following the procedure.

ANTECEDENTES: La atresia biliar (biliary atresia, BA) es una enfermedad pediátrica rara que consiste en una obstrucción biliar de etiología desconocida, y es la indicación pediátrica más frecuente de trasplante hepático (liver transplantation, LT). Sin embargo, no existe consenso para predecir los resultados de la portoenterostomía de Kasai (Kasai portoenterostomy, KP) en base a los hallazgos histológicos hepáticos. El Ki67 es un biomarcador conocido para medir y controlar la proliferación celular. MÉTODOS: Se midieron los niveles de expresión del parénquima hepático de Ki67 (clon, MIB-1) por tinción inmunohistoquímica de las muestras de cinco donantes vivos y 35 pacientes con BA, para evaluar su valor predictivo de los resultados de la KP. RESULTADOS: Los pacientes con BA incluían 13 sobrevivientes con hígado nativo (native liver survivors, NLS), 17 no NLS y 5 pacientes que se sometieron inicialmente a LT. La proporción media de las áreas de expresión de Ki67 en donantes y pacientes con BA en KP fue de 0,06% y 0,99%, respectivamente. El análisis univariado identificó una alta proporción de áreas de Ki67, un alto número de células Ki67, un alto número de células Ki67 positivas (+)/leucocitos (LCA/CD45) + en KP como predictores significativos de una peor supervivencia del hígado nativo después de KP (cociente de riesgos instantáneos, hazard ratio, HR 9,29, 3,37 y 12,17, respectivamente). La proporción de las áreas Ki67 fueron significativamente superiores en los pacientes sin NLS que en los pacientes con NLS (P = 0,001). Entre los pacientes sin hígado nativo, los niveles de Ki67 disminuyeron posteriormente de acuerdo con la presencia de una lesión hepática irreparable, tales como son los hígados con BA en LT (en KP versus en LT = 1,29% versus 0.32%; P < 0,001). CONCLUSIÓN: Demostramos los datos clínicos y la evolución temporal de la expresión de Ki67 en los pacientes con BA. El alto nivel de expresión de Ki67 en KP puede ser un predictor importante para la supervivencia del hígado nativo después de KP.

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Perioperative considerations and anesthesia management in patients with obstructive sleep apnea undergoing ophthalmic surgery.

Obstructive sleep apnea (OSA) is a disorder characterized by breathing cessation caused by obstruction of the upper airway during sleep. It is associated with multiorgan comorbidities such as obesity, hypertension, heart failure, arrhythmias, diabetes mellitus, and stroke. Patients with OSA have an increased prevalence of ophthalmic disorders such as cataract, glaucoma, central serous retinopathy (detachment of retina, macular hole), eyelid laxity, keratoconus, and nonarteritic anterior ischemic optic neuropathy; and some might require surgery. Given that OSA is associated with a high incidence of perioperative complications and more than 80% of surgical patients with OSA are unrecognized, all surgical patients should be screened for OSA (eg, STOP-Bang questionnaire) with comorbidities identified. Patients suspected or diagnosed with OSA scheduled for ophthalmic surgery should have their comorbid conditions optimized. This article includes a review of the literature and highlights best perioperative anesthesia practices in the management of ophthalmic surgical patients with OSA.

The efficacy of ultrasound-guided type-I and type-II pectoral nerve blocks for postoperative analgesia after breast augmentation: A prospective, randomised study.

PURPOSE: The present study was planned to evaluate the efficacy and safety of ultrasound-guided Pecs I and II blocks for postoperative analgesia after sub-pectoral breast augmentation. METHODS: Fifty-four adult female patients undergoing breast augmentation were randomly divided into two groups: the control group (Group C, n=27) who were not subjected to block treatment and Pecs group (Group P, n=27) who received Pecs I (bupivacain 0.25%, 10mL) and Pecs II (bupivacain 0.25%, 20mL) block. Patient-controlled fentanyl analgesia was used for postoperative pain relief in both groups, and the patients were observed for the presence of any block-related complications. RESULTS: The 24-h fentanyl consumption was smaller in Group P [mean±SD, 378.7±54.0µg and 115.7±98.1µg, respectively; P<0.001]. VAS scores in Group P were significantly lower at the time of admission to the post-anaesthetic care unit and at 1, 2, 4, 8, 12, and 24h (P<0.001). The rates of nausea and vomiting were higher in Group C than in Group P (9 vs 2, P=0.018). Hospital stay duration was shorter in Group P than in Group C (24.4±1.2h vs 27.0±3.1h, P<0.001). No block-related complications were recorded. CONCLUSIONS: Combine used of Pecs I and II blocks provide superior postoperative analgesia in patients undergoing breast augmentation and shortens hospital stay.

Duodenal Ulcer as a Postoperative Complication in the Donor in Living-Donor Liver Transplantation.

INTRODUCTION: Donor safety is one of the most important factors in living-donor liver transplantation. Duodenal ulcer (DU) is a common postoperative complication. Here we aimed to reveal the risk factors associated with postoperative DU in the donors. METHODS: Between April 2007 and March 2017, 318 cases underwent donor hepatectomy for liver transplantation at Kumamoto University Hospital. We classified the donors into two groups: a DU group and a non-DU group. DU was defined as mucosal break with unequivocal depth requiring an endoscopic procedure. The characteristics and clinical factors of the donors were retrospectively analyzed. RESULTS: Postoperative DU occurred in 17 donors during the study period. The mean interval after donor hepatectomy to occurrence of DU was 124.8 ± 185.4 days. The two groups were comparable in terms of age at time of the donor hepatectomy (P = .45). The male-to-female ratio (P = .03) was significantly different between the two groups and left-side hepatectomy was performed more often in the DU group (P = .003). Multivariable logistic regression revealed that left-side hepatectomy was independently associated with postoperative DU in the donors. CONCLUSIONS: These findings indicated that left-side hepatectomy is a risk factor for postoperative DU in the donors.

Measurement of thickness of film deposited on the plasma-facing wall in the QUEST tokamak by colorimetry.

After several experimental campaigns in the Kyushu University Experiment with Steady-state Spherical Tokamak (QUEST), the originally stainless steel plasma-facing wall (PFW) becomes completely covered with a deposited film composed of mixture materials, such as iron, chromium, carbon, and tungsten. In this work, an innovative colorimetry-based method was developed to measure the thickness of the deposited film on the actual QUEST wall. Because the optical constants of the deposited film on the PFW were position-dependent and the extinction coefficient k1 was about 1.0-2.0, which made the probing light not penetrate through some thick deposited films, the colorimetry method developed can only provide a rough value range of thickness of the metal-containing film deposited on the actual PFW in QUEST. However, the use of colorimetry is of great benefit to large-area inspections and to radioactive materials in future fusion devices that will be strictly prohibited from being taken out of the limited area.

Living Donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis Type 1: Two Reported Cases.

BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an inherited disease characterized by cholestatic features. We report two patients with PFIC1 who underwent liver retransplantation. CASE REPORT: One patient was a 3-year-old female who underwent liver transplantation for PFIC1. She presented with severe diarrhea and fatty liver, and went into liver failure. She therefore underwent liver retransplantation and external biliary diversion 8 years after the initial liver transplantation. The explanted liver was histologically diagnosed with chronic rejection. Her intractable diarrhea stopped after the retransplantation. She was diagnosed with a fatty liver 8 months after the retransplantation and died 4 years after retransplantation due to bleeding from an ileostomy. The other patient was a 3-year-old male. This patient underwent liver retransplantation due to liver cirrhosis caused by steatohepatitis 9 years after the initial liver transplantation. The biliary tract was not diverted. He also experienced severe diarrhea after the retransplantation and requires home parenteral nutrition due to an eating disorder. CONCLUSIONS: Liver transplantation is the only treatment to resolve life-threatening issues due to PFIC1, but requires further improvement as a therapeutic modality.

Management of isolated infraorbital neuralgia by ultrasound-guided infraorbital nerve block with combination of steroid and local anesthetic.

Patients with isolated peripheral branch neuralgia of trigeminal nerve usually receive traditional treatment such as medical therapy and interventional procedures targeting the entire trigeminal nerve or related ganglions. However, if the intractable pain is limited to a certain branch, the patient may also benefit from a peripheral and nerve-targeted interventional approach. Here, we report the management of a patient with isolated infraorbital neuralgia by ultrasound-guided infraorbital nerve block with steroid and local anesthetic combination. 48years-old male patient diagnosed with trigeminal neuralgia was resistant to medical therapy for 3years. The pain site was isolated to the area of the right nasal wing, right lateral incisor, the upper right canine and the first premolar teeth. His pain was an electric shock-like, throbbing and stabbing with a pain score of 8-9 according to numeric rating scale (NRS) and 18 according to the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS). Following a diagnostic ultrasound-guided infraorbital nerve block with 1% lidocaine, the block was repeated twice with 15mg lidocaine and 1.5mg dexamethasone in a total volume of 1.5mL in a month. The patient's NRS and LANSS scores decreased to 2 and 8, for approximately 21months until this report was written. We suggest that ultrasound-guided infraorbital nerve block with dexamethasone and lidocaine combination may present as an initial interventional treatment option in patients with isolated infraorbital neuralgia.

The effect of paracetamol on postoperative nausea and vomiting during the first 24 h after strabismus surgery: a prospective, randomised, double-blind study.

CONTEXT: Strabismus surgery is one of the most common ophthalmic surgical procedures in children and is associated with significant postoperative nausea and vomiting (PONV). OBJECTIVE: We evaluated the effect of intravenous paracetamol on PONV in children after strabismus surgery. DESIGN: Prospective, placebo-controlled, randomised double-blind study. SETTING: University hospital. PATIENTS: Ninety children, between 2 and 14 years scheduled for strabismus surgery, were recruited. Eighty-six completed the study. INTERVENTIONS: After induction of anaesthesia, intravenous dexamethasone 0.1 mg kg was administered to all. The patients were enrolled to receive either intravenous physiological saline (group S) or paracetamol 15 mg kg (group P). MAIN OUTCOME MEASURE: Incidence of PONV in the first 24 h postoperatively. RESULTS: General and clinical characteristics of the children were similar in both groups. PONV during the first 24 h was significantly higher in group S in comparison with group P (group S vs. group P, 33 vs. 14.6%, respectively, P = 0.038 for nausea; 24.4 vs. 7.3%, respectively, P = 0.030 for vomiting). The number of analgesic administrations during the first 24 h was higher in group S compared with group P (1.31 ±â€Š0.85 and 0.73 ±â€Š0.6, respectively, P = 0.001). The repeat number of postoperative analgesic administrations was significantly different between groups during the first 24 h (P = 0.005), but during 24-48 h was not significant. CONCLUSION: Intraoperative administration of intravenous paracetamol decreases the incidence of PONV during the first 24 h in children after strabismus surgery.

Remifentanil versus fentanyl in combination with midazolam for retrobulbar block in cataract surgery.

OBJECTIVE: To compare the effects of fentanyl or remifentanil in combination with midazolam on hemodynamic parameters, pain, and satisfaction profile in cataract surgery. METHODS: This randomized, double blind, prospective study was conducted between 10 and 20th July 2005 at Kudret Eye Hospital, Ankara, Turkey. Patients scheduled for cataract surgery by the phacoemulsification technique were randomly enrolled to receive sedation with midazolam 1 mg intravenous iv either with fentanyl 25 microgram group 1, n=54 or remifentanil 0.3 microgram/kg group 2, n= 46. Heart rate, systolic and diastolic arterial pressure values were recorded as baseline, after retrobulbar injection, and during the operation. We evaluated recall of retrobulbar block, pain during injection and operation, satisfaction of patient and surgeon, and the adverse effects. RESULTS: There were statistically significant alterations in systolic and diastolic arterial pressure measurements within and between groups, whereas all kept in the clinically normal range. Twenty-four percent of patients in group 1 and 15.2% in group 2 did not even remember the retrobulbar injection. The pain scores during retrobulbar injection and operation were similar in both groups. Also, satisfaction of patients and surgeon was high and comparable between groups. CONCLUSION: Remifentanil and fentanyl are both efficient and comparable opioid adjuncts to midazolam providing low injection pain and high satisfaction level with hemodynamic stability in cataract surgery under retrobulbar injection.

A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene.

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.

Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy.

BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE: To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. RESULTS: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

[Quantitative evaluation of the effect of 3,4-diaminopyridine in a patient with Lambert-Eaton myasthenic syndrome using dynamic dynamometry].

We reported a 72-year-old woman with Lambert-Eaton myasthenic syndrome. The chief complaint was weakness and atrophy of the thigh muscles, which prevented her from climbing stairs even with a handrail. Sensory and autonomic function was normal without amblygeustia. There was no malignancy found, and her serum anti-V/Q type voltage-gated calcium channel antibody was negative. Administration of 3,4-diaminopyridine (DAP), known to accelerate acetylcholine release, was very effective and she became able to climb stairs without a handrail. For evaluation of the therapeutic effect of DAP, the initial compound muscle action potential (ICMAP) on evoked electromyogram has been recommended because it provides highly sensitive and reproducible results. Unfortunately this method is usually applied to several particular distal muscles for technical reasons. In the present case, evaluation of the quadriceps femoris muscle was most important because it was most responsible for her disability. We attempted to measure the angular velocity and the angular acceleration on knee extension movement using dynamic dynamometry. The angular velocity improved from 124 to 162 deg/sec and the angular acceleration from 220 to 390 deg/sec2. The results were more sensitive and more relevant to her demonstrable ADL improvement than grasping power increase and ICMAP improvement recorded at the distal muscles.

[Skeletal muscle pathology of chronic graft versus host disease accompanied with myositis, affecting predominantly respiratory and distal muscles, and hemosiderosis].

We report the muscle pathology in a 43-year-old woman who died of chronic graft versus host disease (GVHD) complicated by myositis and systemic transfusional hemosiderosis, after an allogeneic bone marrow transplantation and a donor leukocyte transfusion for acute myelogenous leukemia. Despite cyclosporin A treatment, fatal ventilatory failure progressed while she was still ambulant. Autopsy revealed the presence of chronic GVHD mildly involving the liver, skin, pericardium, pancreas, and salivary glands, in addition to skeletal muscles. Myopathic changes with mild inflammation and prominent iron deposition were found in the tibialis anterior muscle and, to a lesser degree, in the diaphragm and the intercostal muscle. There were iron deposits in both macrophages and sarcoplasm in the tibialis anterior. The iliopsoas and pectoralis major muscles showed prominent type 2 fiber atrophy; inflammation and iron deposition were minimal in the iliopsoas, but none in the pectoralis. Although we ascribed respiratory failure largely to GVHD myositis, weakness of the lower leg appeared to be aggravated by iron deposition superimposing the underlying GVHD myositis.

[Spontaneous improvement of subacute exacerbation in a case of sensory ataxic neuropathy associated with Sjögren's syndrome].

We reported a 66-year-old man with Sjögren's syndrome (sicca syndrome) presenting a sensory ataxic neuropathy, which showed spontaneous remission. He developed difficulty in standing and walking during recent several months. Neurological examinations showed sensory ataxia with areflexia in all extremities and mild distal-dominant decrease in the superficial sensation. Laboratory examinations of blood, urine, and cerebrospinal fluid were all unremarkable; the blood levels of vitamin B1, B2, B6 and B12 were low normal. Sensory nerve action potentials and somatosensory evoked potentials were absent. Cervical cord MRI revealed no abnormal signals. Severe loss of myelinated fibers and scattered myelin ovoids were seen in sural nerve biopsy. Tentative diagnosis at admission was subacute sensory neuropathy associated with malignancy. Screening examinations for malignancy were undertaken and all revealed negative. Because of coexisting sicca symptoms and positive Shirmer test (0 mm), a lip biopsy was performed and a diagnosis of Sjögren's syndrome was confirmed. Sensory ataxia improved gradually. Two years later, blood B1 levels were low but he remained able to walk. This case is an uncommon example of spontaneous symptomatic remission in sensory ataxic neuropathy associated with Sjögren's syndrome.

[Therapeutic trial of beta 2-adrenergic agonist clenbuterol in muscular dystrophies].

We report the outcome of trial of clenbuterol in four adult muscular dystrophy patients. One patient with Becker type, one with Miyoshi type, and two with facioscapulohumeral type were given clenbuterol (30 or 40 micrograms/day) for 6 to 18 months. We evaluated muscle strength of isometric contraction, grip and pinch power, compound muscle action potentials of intrinsic muscles, vital capacity, urinary creatinine excretion, and muscle CT. Power and volume of well preserved muscles increased mostly, while those of atrophic muscles did not improve. Vital capacity increased in two patients. No improvement of ADL was observed presumably because ADL was mainly determined by the most atrophic and weak muscles. Irrespective of type of muscular dystrophy, administration of clenbuterol may be beneficial in early stage of the disease.