Duraplasty using a combination of a pedicled dural flap and collagen matrix in posterior fossa decompression for pediatric Chiari malformation type 1 with syrinx.

PURPOSE: In posterior fossa decompression for pediatric Chiari malformation type 1 (CM-1), duraplasty methods using various dural substitutes have been reported to improve surgical outcomes and minimize postoperative complications. To obtain sufficient posterior fossa decompression without cerebrospinal fluid-related complications, we developed a novel duraplasty technique using a combination of a pedicled dural flap and collagen matrix. The objective of this study was to describe the operative nuances of duraplasty using a combination of a pedicled dural flap and collagen matrix in posterior fossa decompression for pediatric CM-1. METHODS: We reviewed the clinical and radiographic records of 11 consecutive pediatric patients who underwent posterior fossa decompression with duraplasty using a combination of a pedicled dural flap and collagen matrix followed by expansile cranioplasty for CM-1. The largest area of the syrinx and the size of the posterior fossa were calculated. RESULTS: The maximum syrinx area was reduced by a mean of 68.5% ± 27.3% from preoperatively to postoperatively. Four patients (36.4%) had near-complete syrinx resolution (> 90%, grade III reduction), five (45.5%) had 50% to 90% reduction (grade II), and two (18.2%) had < 50% reduction (grade I). The posterior fossa area in the midsagittal section increased by 8.9% from preoperatively to postoperatively. There were no postoperative complications, including cerebrospinal fluid leakage, pseudomeningocele formation, or infection. CONCLUSION: Duraplasty using a combination of a pedicled dural flap and collagen matrix in posterior fossa decompression is a promising safe and effective surgical technique for pediatric CM-1 with syrinx.

Artificial intelligence in a prediction model for postendoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: In this study we aimed to develop an artificial intelligence-based model for predicting postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We retrospectively reviewed ERCP patients at Nagoya University Hospital (NUH) and Toyota Memorial Hospital (TMH). We constructed two prediction models, a random forest (RF), one of the machine-learning algorithms, and a logistic regression (LR) model. First, we selected features of each model from 40 possible features. Then the models were trained and validated using three fold cross-validation in the NUH cohort and tested in the TMH cohort. The area under the receiver operating characteristic curve (AUROC) was used to assess model performance. Finally, using the output parameters of the RF model, we classified the patients into low-, medium-, and high-risk groups. RESULTS: A total of 615 patients at NUH and 544 patients at TMH were enrolled. Ten features were selected for the RF model, including albumin, creatinine, biliary tract cancer, pancreatic cancer, bile duct stone, total procedure time, pancreatic duct injection, pancreatic guidewire-assisted technique without a pancreatic stent, intraductal ultrasonography, and bile duct biopsy. In the three fold cross-validation, the RF model showed better predictive ability than the LR model (AUROC 0.821 vs. 0.660). In the test, the RF model also showed better performance (AUROC 0.770 vs. 0.663, P = 0.002). Based on the RF model, we classified the patients according to the incidence of PEP (2.9%, 10.0%, and 23.9%). CONCLUSION: We developed an RF model. Machine-learning algorithms could be powerful tools to develop accurate prediction models.

Second-line immunosuppressant administration for steroid-refractory immune-related adverse events in patients with lung cancer.

BACKGROUND: Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases. METHODS: This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects. RESULTS: Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection. CONCLUSION: Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs.

Treatment optimization by monitoring vancomycin concentration in the serum and cerebrospinal fluid in a child with cystoperitoneal shunt-related infection caused by methicillin-resistant Staphylococcus aureus: a case report and literature review.

BACKGROUND: Cerebral ventricular shunt infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially strains with elevated minimum inhibitory concentration (MIC) values, have a poor prognosis. Monitoring serum vancomycin (VCM) levels with therapeutic drug monitoring and maintaining high VCM concentrations in the cerebrospinal fluid (CSF) are critical to treatment success. However, there have been a few reports about the CSF penetration and the pharmacokinetics of VCM in children. CASE PRESENTATION: Here, we report the case of a pediatric patient with cysto-peritoneal shunt-related meningitis caused by MRSA with an MIC of 2 µg/mL. The adequate VCM concentration was maintained by monitoring the VCM concentration in the CSF via the external ventricular drain, and frequent blood taking was avoided. VCM showed a good CSF penetration in our patient, and she was discharged without complications. DISCUSSION: Therapeutic drug monitoring of VCM concentration in the CSF may result in successful treatment even if MRSA shows a higher MIC. Therapeutic drug monitoring of VCM concentration in the CSF may also reduce the side effects.

Pediatric intraparenchymal meningioma in the basal ganglia treated with gross total resection: a case report and review of the literature.

INTRODUCTION: Intraparenchymal meningiomas in the basal ganglia are extremely rare, and to the best of our knowledge, only three case reports have been published to date. Owing to concerns regarding major vessels, gross total resection (GTR) is difficult to achieve; therefore, subtotal resection and radiation therapy are often chosen as treatment options. We present a pediatric case with an intraparenchymal meningioma in the left basal ganglia that was successfully treated with GTR. We also reviewed the relevant literature to discuss the pathogenesis, radiological findings, and treatment methods of this rare disease. CASE REPORT: A 4-year-old girl presented with progressive right facial paralysis, aphasia, and right incomplete hemiplegia. Imaging revealed a mass lesion in the left basal ganglia and unilateral obstructive hydrocephalus. Neuroendoscopic septostomy, tumor biopsy, and cerebrospinal fluid reservoir placement were performed, and the initial pathological diagnosis was suspected glioma. Thus, craniotomy was performed to remove the tumor, which was white, elastic, and well-defined. Intraoperative rapid pathology revealed a meningioma. Postoperatively, the patient experienced transient worsening of the right incomplete hemiplegia, which subsequently improved. The final pathological diagnosis was a fibrous meningioma. CONCLUSION: Surgery for intraparenchymal meningiomas in the basal ganglia is challenging owing to the proximity of major blood vessels; however, GTR may be preferable to subtotal resection, considering the possibility of recurrence. Even in cases of intraparenchymal tumors, it is important to consider meningioma as a differential diagnosis and to carefully plan the appropriate treatment.

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis.

BACKGROUND: Osimertinib-the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs. METHODS: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR). RESULTS: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs. CONCLUSION: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

Repair of refractory postoperative cerebrospinal fluid leakage using a reversed dermis flap in a pediatric lipomyelomeningocele patient.

INTRODUCTION: Cerebrospinal fluid (CSF) leak and pseudomeningocele are common complications after surgery for spinal dysraphism. CASE REPORT AND TECHNIQUE: We report a 6-month-old girl with a lumbosacral lipomyelomeningocele and accessory lower limb who developed a refractory cerebrospinal fluid leak and pseudomeningocele after lipomyelomeningocele repair and removal of the accessory limb. The pseudomeningocele was successfully repaired using a reversed dermis flap made from excess skin that covered the meningocele. CONCLUSION: This technique can be performed without using synthetic material or an additional surgical incision.

Pediatric takotsubo syndrome caused by hydrocephalus after posterior fossa tumor surgery.

Takotsubo syndrome (TTS) can develop after intense physical or emotional stress and is uncommon in children. We report a 2-year-old girl who developed TTS caused by acute hydrocephalus after posterior fossa tumor resection and required mechanical ventilation and administration of vasopressor/inotropic agents. Her cardiac function gradually recovered over the course of 2 weeks. Hydrocephalus after posterior fossa surgery can cause compression of the medulla oblongata, resulting in solitary nucleus dysfunction and TTS, a potentially life-threatening complication.

Primary Prophylaxis Indication for Docetaxel Induced Febrile Neutropenia in Elderly Patients with Non-Small Cell Lung Cancer.

In advanced non-small cell lung cancer (NSCLC), the reported incidence of febrile neutropenia (FN) caused by docetaxel (DTX) is 10-20% in clinical trial data. However, FN incidence caused by DTX in real-world setting remains unclear. We evaluated FN incidence caused by DTX and identify risk factors of FN in real-world setting. One hundred and seventy-one NSCLC patients treated with DTX were retrospectively analyzed and 44 (26%) developed FN. Multivariate analysis identified higher age (≥65 years) and prior history of FN as independent risk factors for FN. Primary prophylaxis for FN might be recommended in elderly patients with/without prior history of FN.

Microsurgical confirmation of parenchymal contamination of hair in a pediatric patient with a penetrating head injury.

Penetrating head injuries are rare, but can cause severe morbidity in children. In particular, penetrating head trauma with a wooden foreign body is considered to be likely to cause central nervous system infections because of its porosity and softness. However, actually confirming minute contaminations, such as skin debris or hair, in the brain parenchyma is rare. We report the case of a 2-year-old boy who presented with a penetrating head injury by a chopstick. During surgical removal of the chopstick, intraparenchymal hair contamination was confirmed under a surgical microscope. The postoperative course of the patient was uneventful. After 13 months of follow-up without any infectious events, the patient remains well and asymptomatic. The findings in the present case demonstrate that in the case of a penetrating head trauma with a wooden foreign body, surgical removal and active debridement should be the treatment of first choice.

Management and problems of prolonged survival with hydranencephaly in the modern treatment era.

PURPOSE: Hydranencephaly is a rare condition that occurs during embryogenesis after neurogenesis and is characterized by the near complete absence of the cerebral hemispheres. In general, patients with hydranencephaly have been considered to have a markedly reduced life expectancy. We present 4 patients with hydranencephaly who have survived for over 5 years. The management and problems encountered in these cases are discussed. METHODS: A retrospective review was conducted at our institution. Medical charts and radiographic studies were reviewed. Data including age at follow-up, sex, clinical complications, and surgical procedures were recorded. RESULTS: Six patients were radiologically diagnosed with hydranencephaly during the period from January 2000 to December 2012. Two patients were excluded from our study: one because of death from pneumonia at 1 year of age and another because of transfer to another hospital. Four patients (3 males and 1 female) were included in the analysis. All 4 patients underwent ventriculoperitoneal shunt (VPS) placement and shunt revision. VPS infection occurred in 3 of 4 cases, and bloody cerebrospinal fluid (CSF) was observed in 2 of 4 cases. One patient underwent successful choroid plexus cauterization (CPC) and shunt removal after shunt infection. CONCLUSIONS: Prolonged survival with hydranencephaly is not unusual in the modern treatment era. CSF shunt problems, such as recurring shunt malfunction and shunt infection, represent one of the major problems, and avoiding CSF shunt with CPC is particularly desirable in patients with hydranencephaly.

Barcode sequencing identifies resistant mechanisms to epidermal growth factor receptor inhibitors in circulating tumor DNA of lung cancer patients.

Most patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) will inevitably develop acquired resistance induced by treatment with EGFR tyrosine kinase inhibitors (EGFR-TKI). The mechanisms of resistance to EGFR-TKI are multifactorial, and the detection of these mechanisms is critical for treatment choices in patients who have progressed after EGFR-TKI therapy. We evaluated the feasibility of a molecular barcode method using next-generation sequencing to detect multifactorial resistance mechanisms in circulating tumor DNA and compared the results with those obtained using other technologies. Plasma samples were collected from 25 EGFR mutation-positive NSCLC patients after the development of EGFR-TKI resistance. Somatic mutation profiles of these samples were assessed using two methods of next-generation sequencing and droplet digital PCR (ddPCR). The positive rate for EGFR-sensitizing mutations was 18/25 (72.0%) using ddPCR, 17/25 (68.0%) using amplicon sequencing, and 19/25 (76.0%) using molecular barcode sequencing. Rate of the EGFR T790M resistance mutation among patients with EGFR-sensitizing mutations was shown to be 7/18 (38.9%) using ddPCR, 6/17 (35.3%) using amplicon sequencing, and 8/19 (42.1%) using molecular barcode sequencing. Copy number gain in the MET gene was detected in three cases using ddPCR. PIK3CA, KRAS and TP53 mutations were detected using amplicon sequencing. Molecular barcode sequencing detected PIK3CA, TP53, KRAS, and MAP2K1 mutations. Results of the three assays were comparable; however, in cell-free DNA, molecular barcode sequencing detected mutations causing multifactorial resistance more sensitively than did the other assays.

Endoscopic third ventriculostomy for hydrocephalus in osteopetrosis: a case report and review of the literature.

INTRODUCTION: There are very few reports in the literature associating in hydrocephalus in osteopetrosis. As a complication of shunt procedure, there are two reports on shunt malfunction due to osseous overgrowth at the burr hole in patients with osteopetrosis. We herein report a case of osteopetrosis with hydrocephalus that was successfully treated with endoscopic third ventriculostomy (ETV). CASE REPORT: At 5 months of age, a male patient presented with developmental delay. Head computed tomography (CT) demonstrated triventricular hydrocephalus with a cerebellar tonsillar herniation. At 7 months of age, he underwent suboccipital decompression with decompression of the foramen magnum. The hydrocephalus did not improve postoperatively, and the patient was transferred to our hospital. At 12 months of age, the hydrocephalus was successfully treated with ETV. The postoperative period was uneventful. Postoperative CT demonstrated an improvement in the ventricle size. CONCLUSIONS: The etiology of hydrocephalus in osteopetrosis is not completely understood; however, there have been several reports in which ETV was effective. ETV should be considered the treatment of choice for hydrocephalus in osteopetrosis, as it avoids the characteristic shunt complications that can occur in patients with osteopetrosis.

Efficacy of bevacizumab and erlotinib combination for leptomeningeal carcinomatosis after failure of erlotinib.

In patients with non-small-cell lung cancer harboring an epithelial growth factor receptor (EGFR) active mutation, central nervous system progression after a response to EGFR tyrosine kinase inhibitors is frequent. Central nervous system metastasis, especially leptomeningeal carcinomatosis (LMC), is a serious complication and no standard treatment has been established for LMC. Here, we report two cases in which the addition of bevacizumab to erlotinib enhanced the efficacy against LMC; as a result, radiographic abnormalities decreased markedly and symptoms were well controlled. This combination treatment may be useful to treat LMC in patients with EGFR-positive non-small-cell lung cancer.

Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors.

Post-radiation fibrosarcoma of the cerebrum associated with a prominent, lace-like, perivascular, desmoplastic change.

An intra-axial tumor measuring about 4 cm was excised from the right temporal lobe of a 35-year-old woman, who had a past history of resection of craniopharyngioma and postoperative radiation 21 years earlier. The tumor involved both the cortex and white matter, but was not attached to the dura mater. It consisted of a dense, interlacing, fascicular proliferation of atypical fibroblastic cells and was associated with an extensive, lace-like, desmoplastic change mainly involving the perivascular region around the tumor and overlying the subarachnoid space. The histopathological features of the desmoplastic change resembled meningioangiomatosis, but no proliferation of meningothelial cells was noted. The patient has been free from recurrence for 12 months since the operation. The association of primary cerebral fibrosarcoma with an extensive, lace-like, perivascular, desmoplastic change has not been documented in the literature. The radiation administered 21 years previously may have played some pathogenetic role in the perivascular desmoplastic change, and a malignant transformation of fibroblasts within the perivascular collagenous tissue is considered the most likely origin of the fibrosarcoma.

Anaplastic and meningothelial meningiomas in a single tumor: A "dedifferentiated meningioma"?

The patient was a 74-year-old man, who developed progressive cognitive impairment and gait instability. Neuroradiological examination demonstrated a large and predominantly extra-axial tumor spreading over the bilateral frontal base, indicative of olfactory groove meningioma. The greater part of the resected tumor consisted of a dense, patternless proliferation of large, round or polygonal cells, and compactly fascicular growth of spindle cells. Tumor cells showed markedly anaplastic cytological features. In small areas of the tumor, a typical meningothelial meningioma showing no cellular atypism was found. Both tumor components were closely juxtaposed and no pathological features of an intermediate grade (atypical meningioma) were noted. Shortly after the operation, the patient developed a local recurrence of the tumor and multiple metastases to the cerebrum, bone and skin. Anaplastic meningioma is a rare, highly malignant neoplasm which arises de novo or as a result of the progressive transformation of a low-grade meningioma. The coexistence of anaplastic and low-grade components in a single meningeal tumor has been rarely reported. This dimorphic appearance is reminiscent of "dedifferentiation", a phenomenon infrequently seen in various mesenchymal and salivary gland neoplasms. We think that the term "dedifferentiated meningioma" can be appropriately applied to tumors such as that reported herein.

[Association of Deep Venous Thrombosis with D-dimer Values in Patients with Hemorrhagic Stroke].

Pulmonary embolism(PE)in the early phase of stroke worsens the prognosis. It is necessary to detect deep venous thrombosis(DVT)to avoid PE. We conducted the D-dimer screening in order to detect DVT at an earlier stage. We retrospectively analyzed the clinical data of patients with hemorrhagic stroke who were admitted to the local stroke center, and investigated the complication rates of DVT, PE, D-dimer values, and risk factors of DVT. From October 2012 to August 2014, 261 patients were included. DVT was detected in 46 patients(17.6%)and anticoagulant therapy was started in 5 patients with central DVT. PE did not occur during this observation period. The D-dimer cutoff value for estimating the presence of the DVT was 8.9µg/mL, and the risk factors for DVT were older age, severe neurological disability, prolonged hospital stays, and subarachnoid hemorrhage. D-dimer screening is very useful to make earlier diagnosis and treatment of DVT.