Petroclival meningiomas: update of current treatment and consensus by the EANS skull base section.

BACKGROUND: The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient's counselling. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.

BACKGROUND: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. PATIENTS AND METHODS: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). RESULTS: NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(-)] (defined as <10-6) in post-ASCT BM cases (n = 26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) cases (n = 7) where MRD was not detected by ASO-PCR (P = 0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10-7) (n = 19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents (n = 49) had a significantly better PFS (P = 0.001) and tended to have a better OS (P= 0.214) than those that were untreated (n = 33). CONCLUSIONS: Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.

Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: multicenter prospective randomized controlled trial.

BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. RESULTS: No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

Learning curve for endoscopic submucosal dissection of esophageal neoplasms.

There is a significant learning curve for endoscopic submucosal dissection of esophageal neoplasms that has not been fully characterized. This retrospective study included 33 consecutive superficial esophageal neoplasms for analysis of the learning curve for esophageal endoscopic submucosal dissection based on a single, novice endoscopist's experience. The study was divided into three periods (T1, T2, and T3) of 10 endoscopic submucosal dissection procedures in chronological order, with 13 procedures in the last period. Patient factors (age, sex, coexistent esophageal varices, or submucosal fibrosis) and tumor factors (location at upper esophagus, involving >3/4 esophageal circumference) for endoscopic submucosal dissection were not statistically different between the periods. The mean procedure time was 74.6 min/cm(2) , 23.4 min/cm(2) , and 10.5 min/cm(2) for T1, T2, and T3, respectively. The procedure time decreased over time (P = 0.02) and post hoc test revealed significant difference was only between T3 and T1 (P = 0.019). The en bloc resection rate was 50%, 100%, and 92.3% for T1, T2, and T3, respectively (P for trend = 0.015). R0 resection rate was 40%, 100%, and 84.6% for T1, T2, and T3, respectively (P for trend = 0.023). Two patients had complications: each one patient in T1 and T3 period experienced major bleeding during the procedure (P for trend = 0.875). None of the patients had esophageal perforation. The results of the study concluded that at least 30 cases of endoscopic submucosal dissection of esophageal neoplasms are needed for a novice endoscopist to gain early proficiency in this technique.

Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation.

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT.

Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

OBJECTIVE: Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. METHODS: In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. RESULTS: Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). CONCLUSION: Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH.

Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.

AIM: Physical growth in neurologically healthy preterm infants affects motor development. This study investigated the separate relationships between muscle and fat in infancy and later motor development and physical growth. METHODS: Muscle thickness and subcutaneous fat thickness of the anterior thigh were measured using ultrasound images obtained from neurologically healthy preterm infants at birth, 3, 6, 12 and 18 months' corrected age. We also obtained the Pediatric Evaluation of Disability Inventory and Alberta Infant Motor Scale scores at 18 months' corrected age to assess motor ability and motor delay. RESULTS: Thirty preterm infants completed the study protocol. There was a significant positive correlation between motor ability and increments in subcutaneous fat thickness during the first 3 and 6 months' corrected age (r = 0.48 and 0.40, p < 0.05, respectively), but not between motor ability and muscle thickness growth in any of the periods. A secondary, logistic regression analysis showed that increments in subcutaneous fat thickness during the first 3 months were a protective factor for motor delay. CONCLUSION: Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.

sLORETA-qm for interictal MEG epileptic spike analysis: comparison of location and quantity with equivalent dipole estimation.

OBJECTIVE: To determine whether quantitative modification of a standardised low-resolution brain electromagnetic tomography (sLORETA-qm) could be used as a reliable tool for quantitative analysis of magnetoencephalography (MEG) for analysis of the interictal epileptic spike. To verify the performance of sLORETA-qm, magnetic source location and quantity were compared with the equivalent current dipole (ECD) method. METHODS: A total of 50 sources from 10 patients with epilepsy were obtained. Analyses were performed after the MEG data were 3-70 Hz band-pass filtered. Time points for analysis were selected referring to waveform patterns and the isofield contour map. With the same spherical model, source estimation was conducted with two methods of analysis: ECD and sLORETA-qm. Distance from the centre of the spherical model and intensities were compared between the methods. RESULTS: There were no significant differences between the methods in the distance from the spherical model (paired t-test, p=0.8761). Source intensities between the methods were strongly correlated (Spearman's Rho=0.9803, p<0.001). CONCLUSIONS: sLORETA-qm was closely correlated with ECD concerning point source location and quantity in analysis of the interictal epileptic spike. SIGNIFICANCE: sLORETA-qm is a reliable quantifiable method without arbitrariness for analysis of the interictal epileptic spike.

Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation.

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic stem cell transplantation (SCT). Because our previous trial of preemptive therapy with foscarnet sodium (phosphonoformic acid; PFA) failed to prevent HHV-6 encephalitis, we conducted a prospective study to examine the safety of prophylactic PFA administration and elucidate the changes in the plasma HHV-6 DNA levels in the early post-SCT period. Plasma HHV-6 DNA was measured thrice weekly from day 6. PFA, 90 mg/kg/day, was administered from days 7 to 21 after bone marrow or peripheral blood SCT and to day 25 after umbilical cord blood transplantation. Of the 10 patients enrolled, 2 dropped out of the study, 1 because of early death, and 1 with a low glomerular filtration rate. Grade 3 or greater adverse events occurred in 9 of the 10 prophylactic PFA patients and in 7 of the 10 control patients who had clinical backgrounds similar to the study subjects and underwent SCT during the same period. Neurological disorders developed in none of the study subjects but in 4 of the 10 control patients, including 2 with HHV-6 encephalitis. HHV-6 reactivation occurred in 3 of the 10 study subjects. The prophylactic PFA regimen was thus safe and it may reduce the risk of limbic encephalitis, but is not considered to be potent enough to prevent HHV-6 reactivation.

Successful treatment of Trichosporon fungemia in a patient with refractory acute myeloid leukemia using voriconazole combined with liposomal amphotericin B.

Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML.

An effective training system for endoscopic submucosal dissection of gastric neoplasm.

BACKGROUND AND STUDY AIMS: A standard training system for endoscopic submucosal dissection (ESD) remains to be established. In this study, we evaluated the validity of our training program for gastric ESD. PATIENTS AND METHODS: Four trainees performed gastric ESD for a total of 117 lesions in 107 patients (27 to 30 consecutive lesions per trainee) at a tertiary referral center during 2 years in the training program. Trainees, who already had the fundamental skills and knowledge needed for ESD, each assisted at 40 gastric ESD procedures, then in 20 cases applied post-ESD coagulation (PEC) to gastric mucosal defects; they then began to perform ESD, starting with gastric antral lesions. Treatment outcomes, including mean procedure time, and rates of en bloc resection, en bloc plus R0 resections, complications, and self-completion, were evaluated, for the initial 15 and subsequent 12 to 15 cases. RESULTS: Overall rates of en bloc resection and en bloc plus R0 resection were as high as 100 % and 96.6 %, respectively. Regarding complications, seven cases of delayed hemorrhage (6.0 %) and three cases of perforation (2.6 %) occurred; all complications were solved endoscopically. The most frequent reason for operator change was lack of submucosal dissection skill. The self-completion rate was more than 80 % even in the early period, and did not increase for later cases. CONCLUSIONS: Our training system enabled novice operators to perform gastric ESD without a decline in clinical outcomes. Key features of this training are prior intensive learning and actual ESD during the learning period under expert supervision.

Pancreatitis-associated protein-I and pancreatitis-associated protein-III expression in a rat model of kainic acid-induced seizure.

The pancreatitis-associated protein (PAP) family (also known as the regenerating gene (Reg) family) is a group of 16 kDa secretory proteins structurally classified as the calcium dependent-type lectin superfamily. Some PAP family members are expressed in neurons following peripheral nerve injury and traumatic brain injury. To determine whether PAP family members are expressed in non-traumatic brain injury, expressions were analyzed following kainic acid (KA)-induced seizure. PAP-I (also known as Reg2 in rat and RegIII-beta in mouse) and pancreatitis associated protein-III (PAP-III; RegIII-gamma in mouse) messenger ribonucleic acid (mRNA) was transiently expressed in some restricted areas, such as the hippocampus and parahippocampal area; expression was observed immediately at a maximal level 1 day after seizure. Expression disappeared within 3 days after seizure. In situ hybridization (ISH) and immunohistochemistry revealed neuronal PAP-I and PAP-III expression in the hippocampal dentate gyrus, perirhinal and entorhinal cortices, and the posterior cortical nucleus of the amygdala. The number of PAP-III mRNA-positive neurons was significantly greater than PAP-I mRNA-positive neurons. The majority of positive neurons co-localized with c-Jun, but not with glutamic acid decarboxylase (GAD). These results may suggest that PAP-I and PAP-III induction in non-GABAergic neurons would protect neurons against damage following seizure.

Significant relationship between local angle at fused segments and C2-7 angle: Average duration of longer than 20 years after anterior cervical discectomy and fusion.

BACKGROUND: The authors have focused their attention to the radiological durability of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF) using autologous bone grafting. MATERIALS AND METHODS: Among the patients who underwent ACDF with trans-unco-discal (TUD) approach between 1976 and 1997, 22 patients (16 males and 6 females) made return visits for a clinical evaluation. Patients with trauma or previously treated by anterior cervical fusion or by posterior decompression were excluded from the present study. Clinical evaluation included adjacent segment degeneration (ASD), osseous fusion, local angle at the fused segments and C2-7 angle of cervical spine. RESULTS: The duration after ACDF ranged from 13 to 34 years with an average of 21.3 ± 7.0 years. A single level fusion was done on 8 patients, 2 levels on 11 patients, 3 levels on 2 patients, and 4 levels on 1 patient. Imaging studies indicated that 12 of the 22 patients (54.5%) were graded as having symptomatic ASD. Osseous bony fusion at ACDF was recognized in all cases. None of the patients demonstrated kyphotic malalignment of the cervical spine. Average degrees of local angle at the fused segments and the C2-7 angle were 7.06 and 17.6, respectively. Statistical analysis indicated a significant relationship between the local at the fused segments and C2-7 angles. CONCLUSIONS: Sagittal alignment of the cervical spine was durable long after ACDF when the local angle at the fused segments was well stabilized.

Normal variation of diffusion tensor parameters of the spinal cord in healthy subjects at 3.0-Tesla.

AIMS: The purposes of the present study were to clarify the normal variation and to determine the normal reference values of diffusion tensor (DT) parameters (mean diffusivity [MD] and fractional anisotropy [FA]) of the spinal cord in single-shot fast spin-echo-based sequence at 3.0-Tesla (3T). MATERIALS AND METHODS: Thirty healthy subjects (mean age = 44.2 years, range = 20-72 years) were enrolled for this study. Mean values of MD and FA in six spinal levels (C2/3, C3/4, C4/5, C5/6, C6/7, and C7/Th1) were measured. Mean values, variances, and distributions of the MD and FA in each spinal level were analyzed. Age-dependent change of MD and FA as well as correlation between MD and FA was also analyzed. RESULTS: At all spinal levels, the values can be considered to be Gaussian distribution in MD but not in FA. A significant statistical negative correlation was observed between aging and the values of MD (r = 0.429, P = 0.018), but insignificant between the values of FA (P = 0.234). A slight significant statistical negative correlation was observed between the values of MD and FA (r = 0.156, P = 0.037). One way repeated measures analysis of variance indicated the significant difference between the spinal levels in both MD (P = 0.003) and FA (P < 0.0001). CONCLUSIONS: The analyzed data in the present study would be helpful for comparison when investigating the spinal condition of spinal disorders.