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Acta Neuropathologica Oct 2020
Topics: Adolescent; Brain Neoplasms; Cerebellar Neoplasms; Female; Humans; Male; Medulloblastoma; Mutation, Missense; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Wnt Proteins; beta Catenin
PubMed: 32772175
DOI: 10.1007/s00401-020-02208-9 -
Internal Medicine (Tokyo, Japan) Dec 2020We herein report four patients with desquamative esophagitis that developed one to nine days after peripheral blood stem cell transplantation (PBSCT). Three patients...
We herein report four patients with desquamative esophagitis that developed one to nine days after peripheral blood stem cell transplantation (PBSCT). Three patients underwent allogeneic PBSCT for leukemia, and the other underwent autologous PBSCT for pineoblastoma. Esophagogastroduodenoscopy revealed mucosal sloughing and fresh blood in the esophagus. Fasting and intravenous proton pump inhibitor therapy in addition to blood transfusion improved the esophageal lesions within five to seven days in three patients. These cases indicate that desquamative esophagitis can occur in patients who receive hematopoietic stem cell transplantation. Although blood transfusions may be required, it can be resolved within seven days.
Topics: Adolescent; Adult; Blood Transfusion; Esophagitis; Fasting; Female; Hematopoietic Stem Cell Transplantation; Humans; Japan; Male; Proton Pump Inhibitors; Treatment Outcome; Young Adult
PubMed: 32759586
DOI: 10.2169/internalmedicine.4977-20 -
Asian Journal of Neurosurgery 2020The postoperative quality and span of life in posterior fossa tumors (PFTs) is complicated by the residual disease, progression, recurrence, disabilities, and mortality.
CONTEXT
The postoperative quality and span of life in posterior fossa tumors (PFTs) is complicated by the residual disease, progression, recurrence, disabilities, and mortality.
AIMS
The aim of this study is to analyze the link between histopathological type of tumor and outcome in an ethnic Himalayan population of India.
SETTINGS AND DESIGN
The histopathological records of 410 out of 589 patients were compared with their clinical outcome up to the 1 postoperative year in a single center which amounts to regional epidemiological value of PFTs.
MATERIALS AND METHODS
In this observational study, retrospectively postoperative records of 589 PFTs from November 1990 to December 2010 (20 years) were retrieved, scrutinized, and observed. The postoperative records of 410 patients with proved histopathological examination results were included.
STATISTICAL ANALYSIS USED
The statistical law of variance was applied wherever necessary.
RESULTS
About 63.2% of 410 operated PTFs were males while females predominated in meningiomas and pineoblastomas. About 31.7% of PFTs were children (below 18 years.). About 54.1% of the cases were histologically malignant. The residual tumors comprised 40.2%, and symptoms of disease progression occurred in 10.9%. The tumor recurrence occurred in 14.3% while 6.0% of the patients developed severe disability. The overall mortality was 11.4% up to the 1 postoperative year, with 18.9% in malignant patients. The first 1-year event-free survival (EFS) for all the patients was 66.0%. While the patients with malignancies had the first 1-year EFS of 47.7%, the histologically benign group had 87.7%.
CONCLUSION
The first 1-year postoperative EFS of histologically benign and some malignant PFTs both in children and adults such as pilocytic astrocytomas, ependymomas, and pineoblastomas was much better (87.7%) than other malignant PTFs.
PubMed: 32656120
DOI: 10.4103/ajns.AJNS_120_19 -
Neurosurgical Review Jun 2021Pineal region tumors commonly present with non-communicating hydrocephalus. These heterogeneous histological entities require different therapeutic regimens. We...
Pineal region tumors commonly present with non-communicating hydrocephalus. These heterogeneous histological entities require different therapeutic regimens. We evaluated our surgical experience concerning procurance of a histological diagnosis, management of hydrocephalus, and choice of antitumoral treatment. We analyzed the efficacy of neuroendoscopic biopsy and endoscopic third ventriculocisternostomy (ETV) in patients with pineal region tumors between 2006 and 2019 in a single-center retrospective cross-sectional study with regard to diagnostic yield, hydrocephalus treatment, as well as impact on further antitumoral management. Out of 28 identified patients, 23 patients presented with untreated hydrocephalus and 25 without histological diagnosis. One patient underwent open biopsy, and 24 received a neuroendoscopic biopsy with concomitant hydrocephalus treatment if necessary. Eighteen primary ETVs, 2 secondary ETVs, and 2 ventriculoperitoneal shunts (VPSs) were performed. Endoscopic biopsy had a diagnostic yield of 95.8% (23/24) and complication rates of 12.5% (transient) and 4.2% (permanent), respectively. ETV for hydrocephalus management was successful in 89.5% (17/19) with a median follow-up of more than 3 years. Following histological diagnosis, 8 patients (28.6%) underwent primary resection of their tumor. Another 9 patients underwent later-stage resection after either adjuvant treatment (n = 5) or for progressive disease during observation (n = 4). Eventually, 20 patients received adjuvant treatment and 7 were observed after primary management. One patient was lost to follow-up. Heterogeneity of pineal region tumor requires histological confirmation. Primary biopsy of pineal lesions should precede surgical resection since less than a third of patients needed primary surgical resection according to the German pediatric brain tumor protocols. Interdisciplinary decision making upfront any treatment is warranted in order to adequately guide treatment.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Cross-Sectional Studies; Disease Management; Female; Follow-Up Studies; Humans; Hydrocephalus; Infant; Male; Neuroendoscopy; Pineal Gland; Pinealoma; Retrospective Studies; Ventriculoperitoneal Shunt; Ventriculostomy
PubMed: 32504201
DOI: 10.1007/s10143-020-01323-1 -
Frontiers in Endocrinology 2020The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This... (Clinical Trial)
Clinical Trial
The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic modulation in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients ( = 5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including root mean square of the successive R-R interval differences (RMSSD) (39.7 ms, 95% CI 2.0-77.4, = 0.04), percentage of successive R-R intervals that differ by more than 50 ms (pNN50) (17.1%, 95% CI 9.1-25.1, = 0.003), absolute power of the high-frequency band (HF power) (1,390 ms, 95% CI 511.9-2,267, = 0.01), and sympathetic HRV indices like standard deviation of normal R-R wave interval (SDNN) (57.6 ms, 95% CI 15.2-100.0, = 0.02), and absolute power of the low-frequency band (LF power) (4,592 ms, 95% CI 895.6-8,288, = 0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin-non-proficient patients. NCT03885258.
Topics: Adolescent; Adult; Autonomic Nervous System; Central Nervous System Depressants; Child; Female; Follow-Up Studies; Heart; Heart Rate; Humans; Male; Melatonin; Pinealectomy; Pinealoma; Prognosis; Sleep Wake Disorders; Young Adult
PubMed: 32431667
DOI: 10.3389/fendo.2020.00239 -
Nature Communications Apr 2020Pineoblastoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER1. Presence of leptomeningeal metastases is indicative of...
Pineoblastoma is a rare pediatric cancer induced by germline mutations in the tumor suppressors RB1 or DICER1. Presence of leptomeningeal metastases is indicative of poor prognosis. Here we report that inactivation of Rb plus p53 via a WAP-Cre transgene, commonly used to target the mammary gland during pregnancy, induces metastatic pineoblastoma resembling the human disease with 100% penetrance. A stabilizing mutation rather than deletion of p53 accelerates metastatic dissemination. Deletion of Dicer1 plus p53 via WAP-Cre also predisposes to pineoblastoma, albeit with lower penetrance. In silico analysis predicts tricyclic antidepressants such as nortriptyline as potential therapeutics for both pineoblastoma models. Nortriptyline disrupts the lysosome, leading to accumulation of non-functional autophagosome, cathepsin B release and pineoblastoma cell death. Nortriptyline further synergizes with the antineoplastic drug gemcitabine to effectively suppress pineoblastoma in our preclinical models, offering new modality for this lethal childhood malignancy.
Topics: Animals; Autophagosomes; Autophagy; Cluster Analysis; Disease Models, Animal; Gene Deletion; Germ-Line Mutation; Humans; Integrases; Kaplan-Meier Estimate; Lysosomes; Mice; Neoplasm Metastasis; Nortriptyline; Pinealoma; Retinoblastoma Protein; Tumor Suppressor Protein p53
PubMed: 32286280
DOI: 10.1038/s41467-020-15585-2 -
Cancer Biology & Therapy Jun 2020Metastasis in the pineal region is a rare condition. To best of our knowledge, there is no case report of isolated pineal metastasis secondary to acute lymphocytic...
Metastasis in the pineal region is a rare condition. To best of our knowledge, there is no case report of isolated pineal metastasis secondary to acute lymphocytic leukemia (ALL). The aim of this study is to show the pineal gland involvement of ALL in a case for the first time in the literature. A 25-year-old male patient diagnosed with ALL 2 years ago presented with headache and visual impairment. Brain magnetic resonance imaging (MRI) revealed a well-defined solid lesion which was revealed intensive enhancement after contrast. On diffusion-weighted images, the lesion showed significant diffusion restriction. Three months after therapy, control MRI demonstrated a completely resorbed pineal lesion. The pineal region may be a possible site of metastasis and involvement due to the absence of a blood-brain barrier, and should not be overlooked in patients with not only solid cancers but also ALL.
Topics: Adult; Humans; Male; Pinealoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis
PubMed: 32208886
DOI: 10.1080/15384047.2020.1735605 -
Pediatric Blood & Cancer Jun 2020We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials.
BACKGROUND
We report the outcomes of patients with pineoblastoma and trilateral retinoblastoma syndrome enrolled on the Head Start (HS) I-III trials.
METHODS
Twenty-three children were enrolled prospectively between 1991 and 2009. Treatment included maximal surgical resection followed by five cycles of intensive chemotherapy and consolidation with marrow-ablative chemotherapy and autologous hematopoietic cell rescue (HDCx/AuHCR). Irradiation following consolidation was reserved for children over six years of age or those with residual tumor at the end of induction.
RESULTS
Median age was 3.12 years (range, 0.44-5.72). Three patients withdrew from the study treatment and two patients experienced chemotherapy-related death. Eight patients experienced progressive disease (PD) during induction chemotherapy and did not proceed to HDCx/AuHCR. Ten patients received HDCx/AuHCR; eight experienced PD post-consolidation. Seven patients received craniospinal irradiation (CSI) with a median dose of 20.7 Gy (range, 18-36 Gy) with boost(s) (median dose 27 Gy; range, 18-36 Gy); three received CSI as adjuvant therapy (two post-HDCx/AuHCR) and four upon progression/recurrence. The five-year progression-free survival (PFS) and overall survival (OS) were 9.7% (95% confidence intervals [CI]: 2.6%-36.0%) and 13% (95% CI: 4.5%-37.5%), respectively. Only three patients survived beyond five years. Favorable OS prognostic factors were CSI (hazard ratio [HR] = 0.30 [0.11-0.86], P = 0.025) and HDCx/AuHCR (HR = 0.40 [0.16-0.99], P = 0.047).
CONCLUSIONS
Within the HS I-III trials, CSI and HDCx/AuHCR were statistically associated with improved survival. The high PD rate during later induction cycles and following consolidation chemotherapy warrants consideration of fewer induction cycles prior to consolidation and the potential intensification of consolidation with multiple cycles of marrow-ablative chemotherapy and irradiation.
Topics: Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Infant; Male; Pineal Gland; Pinealoma; Prognosis; Prospective Studies; Survival Rate
PubMed: 32187454
DOI: 10.1002/pbc.28252 -
Acta Neuropathologica Feb 2020Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the...
Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors.
Topics: Adolescent; Adult; Age Factors; Brain Neoplasms; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; MicroRNAs; Mutation; Pineal Gland; Pinealoma; Registries; Survival Rate; Young Adult
PubMed: 31820118
DOI: 10.1007/s00401-019-02111-y