Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II.

PURPOSE: Assessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). PATIENTS AND METHODS: The subjects were 16 patients who underwent SBRT for solitary HCC ≤3cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8-43 (median: 28) months, ages from 59-85 (median: 65) years. RESULTS: Changes in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself. CONCLUSIONS: This is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.

Development of water vapor transmission rate measuring device using a quadrupole mass spectrometer and standard gas barrier films down to the 10-6 g m-2 day-1 level.

Water vapor transmission rate (WVTR) measuring devices with a quadrupole mass spectrometer (QMS) have an advantage in measuring low WVTRs because measurements are taken under an extremely low background of water vapor by realizing ultrahigh vacuum conditions. Here, the reliability of the QMS measurements was improved by including a porous plug with known molecular conductance in the device to generate a reference molar flux for in situ QMS calibration. Then, standard gas barrier (SGB) films made from a clay-polyimide nanocomposite film were also developed and used to validate the measurement. The measurement results for the SGB films were on the extrapolated calibration curve obtained with the porous plug down to WVTR at the 10-6 g m-2 day-1 level within the estimated measurement uncertainty.

Predictive models for conversion of prediabetes to diabetes.

AIM: To clarify the natural course of prediabetes and develop predictive models for conversion to diabetes. METHODS: A retrospective longitudinal study of 2105 adults with prediabetes was carried out with a mean observation period of 4.7years. Models were developed using multivariate logistic regression analysis and verified by 10-fold cross-validation. The relationship between [final BMI minus baseline BMI] (δBMI) and incident diabetes was analyzed post hoc by comparing the diabetes conversion rate for low (< -0.31kg/m2) and high δBMI (≥ -0.31kg/m2) subjects after matching the two groups for the covariates. RESULTS: Diabetes developed in 252 (2.5%/year), and positive family history, male sex, higher systolic blood pressure, plasma glucose (fasting and 1h- and 2h-values during 75g OGTT), hemoglobin A1c (HbA1c) and alanine aminotransferase were significant, independent predictors for the conversion. By using a risk score (RS) that took account of all these variables, incident diabetes was predicted with an area under the ROC curve (95% CI) of 0.80 (0.70-0.87) and a specificity of prediction of 61.8% at 80% sensitivity. On division of the participants into high- (n=248), intermediate- (n=336) and low-risk (n=1521) populations, the conversion rates were 40.1%, 18.5% and 5.9%, respectively. The conversion rate was lower in subjects with low than high δBMI (9.2% vs 14.4%, p=0.003). CONCLUSIONS: Prediabetes conversion to diabetes could be predicted with accuracy, and weight reduction during the observation was associated with lowered conversion rate.

Patient outcomes of whole brain radiotherapy for brain metastases versus leptomeningeal metastases: A retrospective study.

AIM: Important factors typically associated with prognosis in brain metastases include Karnofsky performance status (KPS), extracranial or cerebellar localization and combination chemotherapy. However, few studies investigated the prognostic role of leptomeningeal metastases (LM) following whole brain radiotherapy (WBRT). On the basis of our experience suggesting better survival of asymptomatic patients with LM than those with brain metastases, we herein evaluated LM as a prognostic factor after WBRT. METHODS: Medical records of 206 patients (median age, 65 years) who received WBRT in 2007-2015 were retrospectively reviewed. The two most common cancers were of lung, breast origin in 78.5%, 10%, patients, respectively. Patients received parallel-opposed WBRT, with a dose of 20-40 Gy. Additional doses of 9-12 Gy were used in patients who were operated on or had single metastases. Overall survival (OS) was determined, and clinical parameters including age, KPS, symptoms, radiation dose, dose per fraction, type of metastasis, extracranial metastases, primary status and surgery plus WBRT were assessed as prognostic factors. RESULTS: The median survival was 6 months (range, 1-100), and 1- and 2-year survival rates were 28% and 17%, respectively. In univariate analysis, improved survival was associated with KPS of ≥70, absence of symptoms, radiation dose of ≥37.5 Gy, favorable primary lesion, LM, and surgery plus WBRT. Multivariate analysis revealed that these factors with the exception of radiation dose was significant prognostic factors for OS. CONCLUSION: We found that LM were independent prognostic factors for good clinical outcomes.

Prolonged Negative Pressure Wound Therapy Followed by Split-Thickness Skin Graft Placement for Wide Dehiscence of Clamshell Incision After Bilateral Lung Transplantation: A Case Report.

Clamshell incision is a standard approach for bilateral lung transplantation, providing a good operative field; however, once wide dehiscence occurs, its management is sometimes difficult because of intense immunosuppression and malnutrition of the recipient. A 22-year-old man with idiopathic pulmonary arterial hypertension underwent cadaveric bilateral lung transplantation through a clamshell incision using standard cardiopulmonary bypass. He developed wound dehiscence on postoperative day (POD) 20 that resulted in exposure of the bilateral fifth ribs and open pneumothorax. Considering the extreme malnutrition and emaciation of the recipient, we avoided initial closure of the dehiscence. After the debridement of necrotic tissue, negative pressure wound therapy was initiated on POD 25 and was continued for approximately 6 months with trafermin spray application. Eventually, the wound, including the fifth ribs, was completely covered with granulation tissue except for the wire tying the sternum. On POD 217, the patient underwent removal of the sternal wire followed by split-thickness skin grafting. His wound was successfully closed and he was discharged without activity limitation on POD 265.

Comparative study of treatment for distal radius fractures with two different palmar locking plates.

Few randomized trials have shown how the placement of a palmar locking plate affects outcomes. The purpose of this study was to compare clinical and radiological outcomes of fixation using locking plates with different concepts for placement relative to the watershed line in a prospective randomized trial. Sixty-four patients with a displaced distal radius fracture were divided into two groups according to the plates used for fixation: distal-type (AcuLoc(TM), Group A) and proximal-type (VariAx(TM), Group V). Wrist function including the range of motion and grip strength was compared at 1, 2, 3 and 6 months postoperatively. Loss of reduction was assessed radiologically. Both groups demonstrated overall satisfactory function at 6 months with no significant difference found between the groups. Minimal loss of reduction was demonstrated in both groups. Internal fixation using the palmar locking plates with two different placements provided satisfactory outcomes at 6-month follow-up, but our results indicate that plates placed distal to the watershed line may delay recovery of wrist motion.

Efficacy of mizoribine-tacrolimus-based induction therapy for pediatric lupus nephritis.

BACKGROUND: Recent advances in the management of lupus nephritis (LN) have also contributed to a favorable outcome in patients with pediatric-onset LN. Nevertheless, we believe that a more effective and less toxic treatment is needed to attain optimal control of pediatric-onset LN. METHODS: Seven consecutive children with biopsy-proven LN (four with class III/IV and three with class V) received multitarget induction therapy consisting of mizoribine (MZR), tacrolimus (Tac), and prednisolone (PDN). They were prospectively evaluated at three, six, and 12 months, and at the latest observation point after a mean period of 32 months. Post-treatment renal biopsy was performed in two patients with class III/IV. RESULTS: Despite gradually tapering the dose of concomitantly administered PDN, a significant improvement compared with baseline values was observed in the urinary, serological, and clinical assessment measures even at three months of treatment, and the favorable changes persisted throughout the treatment period in most of the study participants except for one. In two patients who underwent post-treatment renal biopsy, a marked histologic improvement was confirmed. No serious adverse events were observed. CONCLUSIONS: Multitarget therapy may be an attractive option for the treatment of pediatric-onset LN. Further studies involving a larger number of patients are needed.

Marked improvement of insulin sensitivity without enhancement of GLP-1 and insulin secretion after Roux-en-Y gastric bypass surgery in a mildly obese patient with diabetes.

Roux-en-Y gastric bypass is an option of treatment for morbidly obese patients with diabetes. However, the value of the operation in mildly obese patients is not established. We report the first prospective systematic endocrine and metabolic analysis in a mildly obese patient who underwent a Roux-en-Y gastric bypass. In a 49-year-old man with BMI 32.6 kg/m(2) having type 2 diabetes, intramucosal gastric cancer was treated by partial gastrectomy with Roux-en-Y gastric bypass. Pre-operatively, he received 53 U/day insulin and the HbA1c value was 63 mmol/mol: meal tolerance test showed diabetic hyperglycemia and low insulin sensitivity with attenuated insulin secretion and normal glucagon-like peptide 1(7-36) secretion. After the operation, hypoglycemic agent was stopped. Body weight reduced from 84.0 to 77.0 kg within 2 weeks and increased thereafter to 79.4 kg at 4 months later, when the degree of hyperglycemia was unchanged as indexed by a HbA1c value of 62 mmol/mol. Upon repeated meal tolerance test, no increase of glucagon-like peptide 1 and insulin secretion, but significantly improved hepatic and peripheral insulin sensitivity were found, compared to the preoperative meal tolerance test. Marked dissociation of endocrine and metabolic effects of Roux-en-Y gastric bypass, that is, absence of increased glucagon-like peptide 1/insulin secretion with improvement of insulin sensitivity, was found in a mildly obese patient with type 2 diabetes.

Clinical significance of intramedullary Gd-DTPA enhancement in cervical myelopathy.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated. SETTING: Four hospitals in Japan. METHODS: A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery. RESULTS: Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery. CONCLUSION: Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

Facet cyst haematoma in the lumbar spine: a report of four cases.

We present 4 cases of facet cyst haematoma in the ligamentum flavum of the lumbar spine. All patients presented with a one-to-3-month history of back pain or numbness in the legs, and sudden neurological deterioration. One also developed cauda equina syndrome and another developed radiculopathy. In all cases, magnetic resonance imaging showed a mass with high signal intensity on both T1- and T2-weighted images. Facet arthrography and computed tomography revealed communication between the mass and the neighbouring facet joint. The haematomas were removed en bloc with the ligamentum flavum. They were surrounded by the ligament and contained degenerated and lacerated elastic fibres but no synovial lining cells. Facet cyst haematoma is so-named because of bleeding from tissue adjacent to the facet joint into a pre-existing facet cyst.

Surface phonon dispersion of [Formula: see text].

Surface phonon dispersion of [Formula: see text]-B was measured using high resolution electron energy loss spectroscopy. With adsorption of excess boron, an ordered structure of [Formula: see text] is found at the B coverage of about 0.8 ML. Another structure of 4 × 4 appears mixed with the [Formula: see text] phase at a higher coverage. Using the phonon dispersion relations, the [Formula: see text] structure is inferred to consist of a planar boron network, as in the bulk. In contrast to the NbB(2)(0001) case, no surface core level shift of B 1s is observed on this [Formula: see text] surface, suggesting that the planar boron is not outermost.

One-stage lateral rhachotomy and posterior spinal fusion with compression hooks for Pott's paralysis in the elderly.

PURPOSE: To evaluate the safety and effectiveness of one-stage lateral rhachotomy and posterior fusion with compression hooks, for the treatment of Pott's paralysis in the elderly. METHODS: 11 elderly patients underwent lateral rhachotomy (costotransversectomy and pediculectomy) to debride the tuberculosis focus extending into the epidural space and to decompress the spinal cord. After debridement, the interbody cavity was packed with autologous iliac bone chips. For stabilisation, posterior fusion was performed using a compression lamina hook system. Patients were followed up for at least 2 years for complications. Neurological status was assessed using the Frankel score. The kyphotic deformity was measured on lateral radiographs taken before surgery and at follow-up. RESULTS: During separation of the adhesion around the abscess, a dural tear occurred in one patient and a pleural tear in another. Both tears were successfully repaired. One patient had mild pneumonia after surgery. The Frankel scores of the 11 patients improved from C or D before surgery to D or E after surgery. No relapse of spinal tuberculosis was encountered. The mean deformity angle was 25.5 degrees before surgery and 23.2 degrees at the final follow-up. Spinal fusion was achieved in all patients. CONCLUSION: Without the need of thoracotomy, one-stage lateral rhachotomy with posterior spinal fusion using compression hooks was an effective option for treating Pott's paralysis in the elderly.

The role of sex hormones in the kinetics of chondrocytes in the growth plate. A study in the rabbit.

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age. Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age.

Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption.

UNLABELLED: TNF-alpha is a major inflammatory factor that is induced in response to injury, and it contributes to the normal regulatory processes of bone resorption. The role of TNF-alpha during fracture healing was examined in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. The results show that TNF-alpha plays an important regulatory role in postnatal endochondral bone formation. INTRODUCTION: TNF-alpha is a major inflammatory factor that is induced as part of the innate immune response to injury, and it contributes to the normal regulatory processes of bone resorption. METHODS: The role of TNF-alpha was examined in a model of simple closed fracture repair in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. Histomorphometric measurements of the cartilage and bone and apoptotic cell counts in hypertrophic cartilage were carried out at multiple time points over 28 days of fracture healing (n = 5 animals per time point). The expression of multiple mRNAs for various cellular functions including extracellular matrix formation, bone resorption, and apoptosis were assessed (triplicate polls of mRNAs). RESULTS AND CONCLUSIONS: In the absence of TNF-alpha signaling, chondrogenic differentiation was delayed by 2-4 days but subsequently proceeded at an elevated rate. Endochondral tissue resorption was delayed 2-3 weeks in the TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice compared with the wild-type animals. Functional studies of the mechanisms underlying the delay in endochondral resorption indicated that TNF-alpha mediated both chondrocyte apoptosis and the expression of proresorptive cytokines that control endochondral tissue remodeling by osteoclasts. While the TNF-alpha receptor ablated animals show no overt developmental alterations of their skeletons, the results illustrate the primary roles that TNF-alpha function contributes to in promoting postnatal fracture repair as well as suggest that processes of skeletal tissue development and postnatal repair are controlled in part by differing mechanisms. In summary, these results show that TNF-alpha participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing.

Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon.

When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 50 mM KCl. It has been thought that TDP by glucose is a Ca2+-dependent phenomenon and only occurs when exposure to glucose is carried out in the presence of Ca2+. In contrast to this, we now demonstrate TDP under stringent Ca2+-free conditions (Ca2+-free buffer containing 1 mM EGTA). In fact, under these Ca2+-free conditions glucose caused an even stronger TDP than in the presence of Ca2+. TDP induced by glucose in the absence of extracellular Ca2+ was unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or tunicamycin, two inhibitors of protein acylation, eradicated TDP without affecting glucose metabolism. The TDP by glucose was not associated with an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) during subsequent treatment with high K+. Exposure of islets to forskolin under Ca(2+)-free conditions did not cause TDP despite a large increase in the cellular cAMP levels. In conclusion, glucose alone induces TDP under stringent Ca2+-free conditions when [Ca2+]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.

Construction of an expression system of insect lysozyme lacking thermal stability: the effect of selection of signal sequence on level of expression in the Pichia pastoris expression system.

Expression systems of human and silkworm lysozymes were constructed using the methylotrophic yeast Pichia pastoris as a host. The leader sequence and its prepro peptide of alpha-factor (a peptide pheromone derived from yeast) and the native signal sequences of these lysozymes, were used as secretion signals. When the alpha-factor leader is used as the signal sequence, human lysozyme is secreted at a much higher level than is silkworm lysozyme. On the other hand, silkworm lysozyme, when its native signal is used, is secreted more efficiently than human lysozyme. Therefore, we expected that human lysozyme cDNA with a silkworm native signal would be secreted more efficiently than human lysozyme with its native signal. However, its level of expression was not increased. This result indicates that the native signal of silkworm lysozyme does not promote the secretion of the lysozyme, but rather alpha-factor leader inhibits the secretion. Silkworm lysozyme with the alpha-factor leader is so unstable that it could be easily attacked by some proteases and our findings suggest that the level of expression of heterologous protein with signal peptides and its stability are greatly affected by the selection of the appropriate secretion signal sequence.

Up-regulation of neuroendocrine differentiation in prostate cancer after androgen deprivation therapy, degree and androgen independence.

The up-regulation of neuroendocrine (NE) differentiation after hormonal therapy, as well as the relationship between the degree of NE differentiation and androgen independence was investigated. One hundred and thirty-seven whole prostate specimens that were derived from surgery and autopsy (group A: no hormonal therapy, 44 patients; group B: with hormonal therapy less than 12 months, 25 patients; group C: with hormonal therapy more than 13 months, 68 patients) were studied. Neuroendocrine differentiation was evaluated by immunostaining with chromogranin A. The degree of NE differentiation was evaluated by the percentage area of positive NE cell expression (grade 0, negative; grade 1, 1-33%; grade 2, 34-66%; grade 3, 67-100%). The degree of NE differentiation was compared in androgen-independent and -dependent tumors in group C. Neuroendocrine differentiation was expressed as 31.8% in group A, 44% in group B and 70.5% in group C (p<0.001, Chi-squared test). Group C included 20 androgen-independent cases in which 3 cases were grade 0, 2 were grade 1, 6 were grade 2 and 9 were grade 3. Conversely, for androgen-dependent cases, there were 16, 16, 11 and 5 cases, respectively. Neuroendocrine cells, whether positive or not, alone was not significantly different (p=0.124, Chi-squared test); however, the percentage area of positive NE cell expression was significantly different between the androgen-independent and -dependent tumors (p=0.0044, Chi-squared test). Hormonal therapy may play an important role in the up-regulation of NE differentiation. As well as NE cell expression, whether positive or not, the degree of expression should also be observed to evaluate a poor prognosis, tumor progression and androgen independence.

Idiopathic herniation of the thoracic spinal cord: report of three cases.

STUDY DESIGN: Cases are reported and the literature is reviewed. OBJECTIVE: To present three cases involving idiopathic herniation of the thoracic cord. SUMMARY OF BACKGROUND DATA: Idiopathic spinal cord herniation is a very rare condition. Only 20 cases have been reported. The radiographic and intraoperative findings concerning this herniation remain insufficient, and its pathophysiology is less understood. METHODS: Idiopathic herniation of the thoracic spine was managed operatively in the three cases. The clinical, radiologic, and intraoperative features in these cases are described, and the pathophysiology of this disorder is discussed from a review of the literature. RESULTS: Two of the three patients had a defect in the inner layer of the duplicated ventral dura mater through which the spinal cord was herniated. The third patient had a ventral epidural cyst into which the spinal cord had protruded. Operative reduction of the spinal cord improved motor power in all three patients, although sensory disturbance remained unchanged. CONCLUSIONS: There should be several types of idiopathic spinal cord herniation. This is the first report of this herniation that focuses the abnormalities of the ventral dura mater, together with image and intraoperative findings.