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.

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.

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.

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.

Quantitative analysis of MEG using modified sLORETA for clinical application.

OBJECTIVE: To determine whether standardised low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm) can be used for quantitative analysis in magnetoencephalography (MEG). METHODS: Somatosensory evoked fields (SEFs) were obtained from 10 hemispheres of five healthy volunteers stimulated on the median nerve at 0.75, 1.0, 1.25, 1.5, 1.75 and 2.0 x threshold of thenar muscle twitch (TMT). N20 m intensity changes were analysed quantitatively using sLORETA-qm. Then, SEFs were measured with stimulation on the median nerve at 1.5 x TMT from 47 hemispheres in 24 subjects. sLORETA-qm intensity and the equivalent current dipole (ECD) moment of N20 m were calculated, and relationships between the values were evaluated. RESULTS: sLORETA-qm intensity increased linearly with stimulus intensity between 0.75 and 1.5 x TMT, and tended to reach a plateau or decrease at higher stimulus intensities. The distribution of sLORETA-qm intensity after natural logarithmic transformation was normal and a close correlation was found between the ECD moment and sLORETA-qm intensity (r(s)=0.91, p<0.001). CONCLUSIONS: The results of this study focusing on N20 m suggested that sLORETA-qm is reliable for quantitative analysis of MEG as well as ECD models. SIGNIFICANCE: sLORETA-qm appears promising for quantitative analyses of MEG for which ECD models are inappropriate.

Morphologic evaluation of the caudal end of the inferior petrosal sinus using 3D rotational venography.

BACKGROUND AND PURPOSE: The inferior petrosal sinus (IPS) is the main transvenous access route used to examine or treat lesions involving the cavernous sinus. To carry out these procedures successfully, one must have a detailed knowledge of the anatomy of the venous system around the junction of the IPS and the internal jugular vein (IJV). MATERIALS AND METHODS: Eighty-three sides in 63 patients (26 men, 37 women; mean, 56.5 years of age) were examined by using 3D rotational venography (3DRV). RESULT: The drainage patterns of the IPS could be classified into the following 6 types, with emphasis on the level of IPS-IJV junction: type A, the IPS drains into the jugular bulb in 1/83 sides (1.2%); type B, the IPS drains into the IJV at the level of the extracranial opening of the hypoglossal canal in 29/83 sides (34.9%); type C, the IPS drains into the lower extracranial IJV in 31/83 sides (37.3%); type D, the IPS forms a plexus and has multiple junctions to the IJV near the jugular foramen in 5/83 sides (6.0%); type E, the IPS drains directly into the vertebral venous plexus (VVP) with no connection to the IJV in 3/83 sides (3.6%); and type F, the IPS is absent in 14/83 sides (16.9%). Each type is also characterized by the way of anastomosis with the VVP. CONCLUSION: This classification seemed to be rational from the embryologic viewpoint, and it may be useful in establishing treatment strategies that involve endovascular manipulation via the IPS.

Atypical spinal dural arteriovenous fistula with supply from the lateral sacral artery.

We report a dural arteriovenous fistula (AVF) that developed at a site on the midline dorsal surface of the dura mater that had been damaged by repeated lumbar punctures. A 61-year-old male patient had undergone repeated lumbar punctures and discectomy for severe lumbago 40 years before the present admission. After surgery, the lumbago symptoms resolved. However, 30 years after the operation, he started to experience dysaesthesia, motor weakness in both legs, and urinary disturbance. Physical examination revealed bilateral leg weakness, diminished deep tendon reflexes in the patellar and Achilles tendons bilaterally, and decreased superficial sensation below L1. Magnetic resonance imaging revealed swelling with intramedullary high intensity and multiple flow voids around the conus and spinal cord on T(2)-weighted images, and adhesive arachnoiditis. Spinal angiography revealed an AVF between the left lateral sacral artery and the S1 radicular vein at the site of the previous operation. Surgery was conducted to carry out excision of the dural AVF at the shunting point, the arterialized intradural vein, and lysis of the arachnoiditis. This case of dural AVF may have been caused by repeated lumbar punctures.

Reduced-intensity unrelated cord blood transplantation for treatment of metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor effect.

We report a 69-year-old man with cytokine-resistant metastatic renal cell carcinoma treated with reduced-intensity unrelated cord blood transplantation. The patient achieved durable donor engraftment with minimal graft-versus-host disease. The patient showed regression of metastatic disease, providing the first evidence of a graft-versus-tumor effect on a solid tumor resulting from cord blood graft.

Hemangioblastoma of hippocampus without von Hippel-Lindau disease: case report and review of literature.

A rare case of hemangioblastoma located in the region of hippocampus is reported. A 27-year-old female presented with a single episode of generalized convulsion. The vascular and cherry red color hemangioblastoma was resected by a temporo-zygomatic approach. There has been no recurrence of tumor at a follow-up of 11 years.

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.

Hypocholesterolemic action of a novel delta8-dihydroabietamide derivative, THD-341, in rats.

The hypocholesterolemic properties of THD-341, N-(2,6-dimethylphenyl)-delta8-dihydroabietamide, were studied in rats. THD-341 reduced serum cholesterol levels in cholesterol-cholate-fed rats at a concentration of less than 0.001% in the diet or an oral dose of less than 3 mg/kg, once a day. When compared in terms of the 50% inhibitory dose for serum cholesterol elevation (ID 50%, % in diet), THD-341 (0.0008%) was comparable to D-thyroxine (0.0005%), more potent than estradiol (0.003%), and far more potent than clofibrate (0.2%), beta-sitosterol (0.8%), cholestyramine (2%), or nicotinic acid (3%). A daily intravenous injection of THD-341 was also effective (ID 50%: 7 mg/kg). THD-341 reduced serum and liver cholesterol in rats made hypercholesterolemic by 0.3% dietary thiouracil or 0.25% dietary cholate. Liver cholesteriol was more profoundly affected than the serum cholesterol. In normal rats, cholesterol was reduced in liver but not in serum. Its mechanism of action is unknown but the results suggest that THD-341 inhibits cholesterol absorption or re-absorption.

Effect of THD-341, a new hypocholesterolemic agent, on experimental atherosclerosis in rabbits.

The influence of THD-341, N-(2,6-dimethylphenyl)-delta8-dihydroabietamide, upon the formation and regression of atherosclerosis and on serum and liver lipid levels has been studied. When rabbits were fed a 1% cholesterol diet for 7 weeks, THD-341 added at a dietary level of 0.01% during the last 4 weeks almost completely prevented the formation of atherosclerotic lesions and the elevation of serum and liver cholesterol levels. When the drug was fed for 10 weeks, either in the normal or cholesterol diet, to rabbits with pre-established atherosclerosis induced by cholesterol feeding for 11 weeks, it did not affect the extent or severity of the lesions but inhibited the progression of lipid deposition in the aorta in a group fed the cholesterol diet during the final 10-weeks period. The reduction of serum and liver cholesterol levels was greater in the drug-treated groups than in the normal rabbit chow-fed group.