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Cancer Gene Therapy Jun 2024This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30...
This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.
Topics: Humans; Glioblastoma; Male; Female; Middle Aged; Adult; Taiwan; Mutation; Aged; Retrospective Studies; Young Adult; Brain Neoplasms; High-Throughput Nucleotide Sequencing; Prognosis
PubMed: 38418842
DOI: 10.1038/s41417-024-00746-y -
Scientific Reports Feb 2024A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The...
A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (v K, v) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.
Topics: Humans; Contrast Media; Feasibility Studies; Magnetic Resonance Imaging; Brain Neoplasms; Brain
PubMed: 38418818
DOI: 10.1038/s41598-024-53871-x -
World Neurosurgery May 2024Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to...
BACKGROUND
Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to recurrence. Our purpose was to identify main factors affecting the time to recurrence to assist preoperative treatment decision-making strategy and to define a tailored clinical and neuroradiological follow-up.
METHODS
Data of 35 patients with intracranial meningioma recurrences have been retrospectively reviewed. Demographic (patient age at initial diagnosis and sex), radiologic (meningioma location, pattern of regrowth and topography of recurrences at first reoperation), pathologic (WHO grade and Ki67-MIB1 at initial surgery and at first reoperation, progesterone receptor [PR] expression), and surgical (extent of resection at initial surgery according to Simpsons grading system, number of reoperations) factors were analyzed.
RESULTS
Time to recurrence ranged from 20 to 120 months. Extent of resection at initial surgery was Simpson grade I in 7 patients (20%), grade II in 10 (28.5%), grade III in 14 (40%), and grade IV in 4 (11.5%). Longer median time to recurrence was observed for skull base localization (P < 0.01), Simpson grades I and II versus grades III (P = 0.01) and IV (P = 0.02), values of Ki67-MIB1 ≤ 4% (P = 0.001), and PR > 60% (P = 0.03); conversely, sex, age, number of reoperations, unchanged/progression of Ki67, and/or World Health Organization grade between first surgery and reoperation did not correlate in statistically significant way with time to recurrence.
CONCLUSIONS
The extent of resection and the Ki67-MIB1 represent the most important factors predicting shorter recurrence time of intracranial meningiomas. Patients with incomplete (Simpson grades III and IV) resection and high Ki67-MIB1 values, especially at non-skull base localization and with low PR values, require a closer short-term clinical and radiologic follow-up in the first years after surgery.
Topics: Humans; Meningioma; Female; Male; Middle Aged; Neoplasm Recurrence, Local; Meningeal Neoplasms; Aged; Retrospective Studies; Adult; Time Factors; Reoperation; Neurosurgical Procedures; Aged, 80 and over; Follow-Up Studies; Young Adult; Ki-67 Antigen
PubMed: 38417623
DOI: 10.1016/j.wneu.2024.02.087 -
Journal of Medical Radiation Sciences Apr 2024Because of the co-location of critical organs at risk, base of skull tumours require steep dose gradients to achieve the prescribed dosimetric criteria. When available,...
INTRODUCTION
Because of the co-location of critical organs at risk, base of skull tumours require steep dose gradients to achieve the prescribed dosimetric criteria. When available, proton beam therapy (PBT) is often considered a desirable modality for these cases, but in many instances, compromises in target coverage are still required to achieve critical organ at risk (OAR) tolerance doses. A number of techniques have been proposed to further improve the penumbra of PBT. In the current study, we propose a novel, collimator-free treatment planning technique that combines high-energy shoot-through proton beams with conventional Bragg peak spot placement. The small spot size of the high-energy pencil beams provides a sharp penumbra at the target boundary, and the Bragg peak spots provide a higher linear energy transfer (LET) boost to the target centre.
METHODS
Three base of skull chordoma patients were retrospectively planned with three different PBT treatment planning techniques: (1) conventional intensity-modulated proton therapy (IMPT); (2) high-energy proton arc therapy (HE-PAT); and (3) the novel technique combining HE-PAT and IMPT, referred to as single high-energy arc with Bragg peak boost (SHARP). The Monaco 6 treatment planning system was used.
RESULTS
SHARP was found to improve the PBT penumbra in the plane perpendicular to the HE-PAT beams. Minimal penumbra differences were observed in the plane of the HE-PAT beams. SHARP reduced dose-averaged LET to surrounding organs at risk.
CONCLUSION
A novel PBT treatment planning technique was successfully implemented. Initial results indicate the potential for SHARP to improve the penumbra of PBT treatments for base of skull tumours.
Topics: Humans; Proton Therapy; Protons; Radiotherapy Dosage; Retrospective Studies; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Neoplasms
PubMed: 38400611
DOI: 10.1002/jmrs.769 -
Medicina (Kaunas, Lithuania) Feb 2024Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and... (Review)
Review
Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap". From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks ( = 0.008) and a shorter duration of the postoperative lumbar drain ( = 0.003), if applied. Total or partial SMF resulted in fewer local complications ( = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required.
Topics: Humans; Plastic Surgery Procedures; Sphenoid Sinus; Quality of Life; Pituitary Neoplasms; Postoperative Complications; Surgical Flaps; Sinusitis; Necrosis; Osteonecrosis; Mycoses; Retrospective Studies
PubMed: 38399569
DOI: 10.3390/medicina60020282 -
International Journal of Molecular... Feb 2024A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as... (Review)
Review
A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.
Topics: Male; Female; Humans; Young Adult; Adult; Parathyroid Neoplasms; Jaw Neoplasms; Hyperparathyroidism; Fibroma; Transcription Factors; Tumor Suppressor Proteins; Adenoma
PubMed: 38396977
DOI: 10.3390/ijms25042301 -
HNO Apr 2024Extended endoscopic endonasal surgery (EEES) is an essential part of treatment of various pathologies of the anterior skull base. In addition to significant improvements...
BACKGROUND
Extended endoscopic endonasal surgery (EEES) is an essential part of treatment of various pathologies of the anterior skull base. In addition to significant improvements in the quality of life of affected patients and a lower complication profile compared to open skull base surgery, the therapeutic results are comparable if the indications are correct.
MATERIALS AND METHODS
Data of all endoscopic endonasal skull base procedures performed at the University Skull Base Center Hamburg under the direction of the Department of Otorhinolaryngology between June 2018 and November 2022 were retrospectively collected.
RESULTS
A total of 50 cases were identified. Of these, 56% (28/50) were malignant tumors, 24% (12/50) were benign pathologies with direct skull base involvement, and 20% (10/50) were anterior skull base defects with rhinoliquorrhea. In 96% (48/50) of cases, the preoperatively set goal of surgery (representative biopsy, complete resection, closure of the skull base defect) could be achieved. Complications grade III or higher according to Clavien-Dindo occurred in 4/50 cases. During the observation period, n = 5 olfactory neuroblastomas were diagnosed, all of which were exclusively and successfully operated on endoscopically.
CONCLUSION
In recent years, the spectrum of endoscopically resectable pathologies of the anterior skull base has steadily expanded. In particular, midline-related tumors such as olfactory neuroblastoma or iatrogenic/idiopathic skull base defects with cerebrospinal fluid rhinorrhea are treated completely endoscopically with very good results. Nevertheless, there are also limitations to this technique. Due to high variance in the scope of frontobasal surgery, the extent, and the complex anatomy, as well as the overlapping responsibilities of the specialist disciplines, establishment of certified skull base centers and bundling of frontobasal surgery at these centers is highly relevant for quality assurance.
Topics: Humans; Retrospective Studies; Quality of Life; Skull Base; Endoscopy; Cerebrospinal Fluid Rhinorrhea
PubMed: 38393669
DOI: 10.1007/s00106-024-01438-7 -
Indian Journal of Pathology &... Apr 2024Sinonasal teratocarcinosarcoma (SNTCS) is an extremely rare and aggressive malignant tumor arising in the sinonasal tract, having a combined clinicopathological feature...
Sinonasal teratocarcinosarcoma (SNTCS) is an extremely rare and aggressive malignant tumor arising in the sinonasal tract, having a combined clinicopathological feature of teratoma and carcinosarcoma. It shows a male predominance and affects adults with an age range of 18-79 years and a mean age of 60 years. Here, we report a case of SNTCS in a 14-year-old male patient who presented with swelling over the upper right alveolus and pain in the right jaw for 2 months. The tumor was completely removed by right total maxillectomy with orbital mess reconstruction, and postoperative radiotherapy with chemotherapy was given. The follow-up of the patient for 2 years has shown evidence of recurrence and is now on palliative care.
Topics: Humans; Male; Adolescent; Carcinosarcoma; Teratoma; Paranasal Sinus Neoplasms; Histocytochemistry; Nose Neoplasms; Microscopy; Treatment Outcome; Tomography, X-Ray Computed
PubMed: 38391375
DOI: 10.4103/ijpm.ijpm_1164_21 -
Extranodal nasal-type NK/T-cell lymphoma with CD20 positive: A case report and review of literature.Indian Journal of Pathology &... Apr 2024Extranodal nasal-type natural killer (NK)/T-cell lymphoma is a type of non-Hodgkin lymphoma. Neoplastic lymphocytes are positive for CD4, CD56, and CD20, a specific... (Review)
Review
Extranodal nasal-type natural killer (NK)/T-cell lymphoma is a type of non-Hodgkin lymphoma. Neoplastic lymphocytes are positive for CD4, CD56, and CD20, a specific B-cell marker. CD20 positive NK/T-cell lymphoma is rare, with only nine reported cases. This paper reports a case of nasal-type NK/T-cell lymphoma with CD20 positivity in a 47-year-old woman. The patient presented with bilateral nasal congestion and bloody nasal cavity secretions for 2 months. Computed tomography revealed thickening of the nasal mucosa and posterior wall of the nasopharyngeal crest, and the left and right cervical lymph nodes were enlarged. On histopathology, the lesion was composed of medium-sized atypical lymphoid cells and vascular infringement. Immunohistochemical staining showed that the tumor cells were positive for CD20, CD3, CD56, and Epstein-Barr virus (EBV)-encoded RNA in situ hybridization. The patient was treated with radiotherapy for 2 months and is currently well.
Topics: Humans; Female; Antigens, CD20; Middle Aged; Lymphoma, Extranodal NK-T-Cell; Immunohistochemistry; Tomography, X-Ray Computed; Herpesvirus 4, Human; In Situ Hybridization; Microscopy; Histocytochemistry; CD56 Antigen; CD3 Complex; Treatment Outcome; Biomarkers, Tumor; Radiotherapy; RNA, Viral; Nose Neoplasms
PubMed: 38391360
DOI: 10.4103/ijpm.ijpm_32_22 -
Indian Journal of Pathology &... Apr 2024
Topics: Humans; Histocytochemistry; Microscopy; Nose; Nose Neoplasms; Palliative Care; Tomography, X-Ray Computed
PubMed: 38391338
DOI: 10.4103/ijpm.ijpm_888_22