Laparoscopic Groin Hernia Repair Using the Totally Extraperitoneal Approach: A Retrospective Study and Our Experience.

Background Recently, laparoscopic totally extraperitoneal (TEP) inguinal hernia repair has been considered one of the most effective and widely performed techniques for repairing inguinal hernias by avoiding entry into the peritoneal cavity. Its indications have evolved and expanded to almost encompass the entire range of groin hernias. This retrospective study aims to determine the outcomes and postoperative complications in patients undergoing TEP inguinal hernia repair performed by a single surgeon for groin hernias at a single center. Methodology We retrospectively evaluated the prospectively collected data of 900 patients who underwent elective TEP repair over 18 years at a single center performed by a single surgeon from April 2004 to February 2023. Patients were evaluated for age, sex, type of hernia, time taken for surgery, open from laparoscopy, intra and postoperative complications, hospital stay, and days taken to resume regular activity. Results The mean age of the 900 patients was 59 years (range = 21-83 years). The mean age of males and females was 59 and 56 years, respectively. The mean operative time was 40 and 55 minutes for a unilateral and bilateral hernia, respectively. In total, 369 (41%) patients had a right-sided groin hernia, 382 (42%) patients had a left-sided groin hernia, and 149 (16.5%) patients had bilateral groin hernias. A total of 121 (13%) patients had occult hernias, and 17 patients underwent concurrent TEP and transurethral resection of the prostate. Of the 900 patients, 20 (2.2%) had a recurrent hernia after a previous open inguinal hernia repair. Seven (0.8%) patients had a recurrence of hernias post-TEP and subsequently underwent open inguinal hernia repair. Seven (0.7%) patients needed conversion from TEP to the transabdominal pre-peritoneal approach. Only minor complications were noted intra and postoperatively. The average time of hospitalization was 24 hours. The time to resume normal activities was five (±1) days. Conclusions Our experience suggests that TEP repair with mesh fixation is a safe and effective procedure with a marginal recurrence rate. Apart from the obvious cosmetic benefits of minimal tissue invasion, a significant advantage of TEP is the visualization of the contralateral groin along with the surgical repair of a hernia, if required, in the same sitting and without the insertion of any extra trocars.

Medulloblastoma group 3 and 4 tumors comprise a clinically and biologically significant expression continuum reflecting human cerebellar development.

Medulloblastoma is currently subclassified into distinct DNA methylation subgroups/subtypes with particular clinico-molecular features. Using RNA sequencing (RNA-seq) in large, well-annotated cohorts of medulloblastoma, we show that transcriptionally group 3 and group 4 medulloblastomas exist as intermediates on a bipolar continuum between archetypal group 3 and group 4 entities. Continuum position is prognostic, reflecting a propensity for specific DNA copy-number changes, and specific switches in isoform/enhancer usage and RNA editing. Examining single-cell RNA-seq (scRNA-seq) profiles, we show that intratumoral transcriptional heterogeneity along the continuum is limited in a subtype-dependent manner. By integrating with a human scRNA-seq reference atlas, we show that this continuum is mirrored by an equivalent continuum of transcriptional cell types in early fetal cerebellar development. We identify distinct developmental niches for all four major subgroups and link each to a common developmental antecedent. Our findings show a transcriptional continuum arising from oncogenic disruption of highly specific fetal cerebellar cell types, linked to almost every aspect of group 3/group 4 molecular biology and clinico-pathology.

Single-cell DNA sequencing identifies risk-associated clonal complexity and evolutionary trajectories in childhood medulloblastoma development.

We reconstructed the natural history and temporal evolution of the most common childhood brain malignancy, medulloblastoma, by single-cell whole-genome sequencing (sc-WGS) of tumours representing its major molecular sub-classes and clinical risk groups. Favourable-risk disease sub-types assessed (MBWNT and infant desmoplastic/nodular MBSHH) typically comprised a single clone with no evidence of further evolution. In contrast, highest risk sub-classes (MYC-amplified MBGroup3 and TP53-mutated MBSHH) were most clonally diverse and displayed gradual evolutionary trajectories. Clinically adopted biomarkers (e.g. chromosome 6/17 aberrations; CTNNB1/TP53 mutations) were typically early-clonal/initiating events, exploitable as targets for early-disease detection; in analyses of spatially distinct tumour regions, a single biopsy was sufficient to assess their status. Importantly, sc-WGS revealed novel events which arise later and/or sub-clonally and more commonly display spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. These findings reveal diverse modes of tumour initiation and evolution in the major medulloblastoma sub-classes, with pathogenic relevance and clinical potential.

Concurrent laparoscopic totally extraperitoneal inguinal hernia repair and transurethral resection of prostate: Breaking with convention - A retrospective study.

AIM: This study aimed to evaluate concurrent laparoscopic totally extraperitoneal (TEP) inguinal hernia repair and transurethral resection of the prostate (TURP) with determination of outcomes. MATERIALS AND METHODS: This retrospective study was conducted at our hospital, from June 2011 to June 2020. Over 9 years, 17 patients with co-existing uncomplicated unilateral or bilateral inguinal hernia (primary/recurrent) and significant benign prostatic hypertrophy were operated in the same sitting. The following outcomes were compared: duration of the surgery, conversion to open hernia surgery, intraoperative and post-operative complications, duration of hospital stay, recurrence, time taken to resume normal activity and cost of the treatment. RESULTS: This study included 17 patients with a mean age of 65 years (range of 50-87 years). The average time taken for the surgery was 115 min with no conversion to open hernia repair. The mean post-operative stay was 3.7 days. There were four patients (23.5%) with seromas identified at day 10, only two remained at 6 weeks and none at 12 weeks. None had significant bleeding intraoperatively or postoperatively. There was no superficial or deep wound infection (including mesh infection). There was no recurrence of inguinal hernia. Two patients (11.7%) developed post-TURP urethral stricture and underwent cystoscopic stricturoplasty, 3 and 2.5 months after the initial procedure. The time taken to resume normal activity was 7 (±1) days. The hospital cost is reduced by 25% as compared to the sum of costs when both the operations are done separately. CONCLUSION: Concurrent TEP inguinal hernia repair and TURP is a practical, safe and cost-effective procedure.

The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia.

Focal cortical dysplasia (FCD) is one of the most common malformations causing refractory epilepsy. Dysregulation of glutamatergic systems plays a critical role in the hyperexcitability of dysplastic neurons in FCD lesions. The pharmacoresistant nature of epilepsy associated with FCD may be due to a lack of well-tolerated and precise antiepileptic drugs that can target glutamate receptors. Here, for the first time in human FCD brain slices, we show that the established, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, perampanel has potent antiepileptic action. Moreover, we demonstrate that this effect is due to a reduction in burst firing behavior in human FCD microcircuits. These data support a potential role for the treatment of refractory epilepsy associated with FCD in human patients.

Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.

BACKGROUND: Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease. METHODS: We undertook large-scale integrated characterization of the molecular features of rMB-molecular subgroup, novel subtypes, copy number variation (CNV), and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n = 107), alongside an independent reference cohort sampled at diagnosis (n = 282). rMB events were investigated for association with outcome post-relapse in clinically annotated patients (n = 54). RESULTS: Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. Non-infant MBSHH displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (eg, CDK amplifications) and novel (eg, USH2A mutations) events. Importantly, many hallmark features of MB were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (eg, SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (eg, DNA damage signaling) and specific events (eg, 3p loss) predicted survival post-relapse. CONCLUSIONS: rMB is characterised by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.

Retroperitoneal fibrosis masquerading as pelvi-ureteric junction obstruction - Laparoscopic management.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare fibro-inflammatory condition which is characterized by development of extensive fibrosis throughout the retroperitoneum. It is classically centred over the anterior surface of the fourth and fifth lumbar vertebrae. It results in entrapment and extrinsic compression of retroperitoneal structures. PRESENTATION OF THE CASE: We present the case of a 69 years old man who was reported to have right pelvi - ureteric junction obstruction on computed tomography, but turned out to have RPF. DISCUSSION: Retroperitoneal fibrosis commonly causes obstructive uropathy (either unilateral, bilateral or progressing from unilateral to bilateral) and if untreated, renal failure. It has high response/remission rates to glucocorticoid therapy. However, relapse rates are also high. Hence, close surveillance with serial laboratory and imaging investigations, after achieving remission, is key to long term disease control. CONCLUSION: Although classical imaging findings, supportive laboratory markers and suggestive/diagnostic histopathology appearances for RPF are well documented, its accurate preoperative diagnosis is not always an assured certainty.

Emergency Laparoscopic Management of Perforative Peritonitis: A Retrospective Study.

Background Peritonitis was previously considered a contraindication for minimally invasive surgery due to the risk of malignant hypercapnia partial pressure of carbon-dioxide (PCO2) and toxic shock syndrome. The objective of this retrospective study was to evaluate the role of laparoscopic surgery (LS) in selected patients with perforative peritonitis and to study its feasibility, safety, and outcomes. Patients and methods This was a retrospective study of 25 patients spanning over five years from 2015 to 2020. This study comprised all patients who were diagnosed with perforative peritonitis on preoperative physical/clinical examination, radiological evaluations, and who were stable enough to withstand pneumoperitoneum. Patients were evaluated for causes, operative time, duration of hospital stay, intra-, and postoperative complications, time taken to resume normal activity, and conversion to open surgery. Data was extracted from the hospital electronic medical records, for the above-mentioned parameters. Results Twenty-five patients with perforative peritonitis underwent diagnostic and therapeutic LS in our institute. The mean age was 46 years (35-79 years). Ten patients (40%) were diagnosed with gastro-duodenal perforation. Out of these ten patients, ninepatients (90%) were managed totally laparoscopically, while one patient (10%) required conversion to open surgery. There were 15 patients (60%) with small bowel perforation. Thirteen of the 15 patients were managed laparoscopically, with the remaining two requiring conversion to open surgery. The average time taken for the procedure was 90 minutes. The mean time to initiate the postoperative peroral liquid diet was 3.4 days. The mean postoperative stay was 6.9 days. The time taken to resume normal activity was 10-12 days. Conclusions Laparoscopic management is feasible and safe for patients with perforative peritonitis. Careful patient selection and the surgeon's experience with the procedure are critical determinants of success.

Role of Laparoscopy in the Surgical Management of Acute Small Bowel Obstruction: Fact or Fiction?

BACKGROUND:  Laparotomy (open surgery) is considered the standard approach for acute small bowel obstruction (ASBO). However, with the advent of minimally invasive surgery, the laparoscopic approach is gaining popularity. There is no consensus on the appropriate setting for laparoscopic therapy for small bowel obstruction (SBO). AIM AND OBJECTIVES:  The purpose of this study is to evaluate the outcomes of laparoscopic surgery for ASBO. PATIENTS AND METHODS: We retrospectively evaluated the prospectively collected data of all the 38 patients who had undergone laparoscopy for ASBO, performed by a single surgeon at our institution, due to adhesions (30 patients), internal hernias (five patients), midgut malrotation (one patient), ileo-ileal intussusception (one patient), and superior mesenteric artery (SMA) syndrome (one patient) from 2012 to 2020. Data were extracted from the hospital electronic medical records (EMR) for the following parameters of each individual patient: age, sex, clinical presentation, preoperative investigation findings, final diagnosis, surgical details, operating time, time to postoperative oral feeds, length of hospital stay, complications, recurrences, and time taken to resume normal activity. A preoperative abdominal contrast-enhanced computed tomography (CECT) was performed in all the cases. Patients with peritonitis and septic shock were excluded from the study.  Results: The mean age of the 38 patients was 58 years (ranged between 33 and 83 years) with a standard deviation (SD) of 16.5. The mean age of the female patients in the study was 60.5 years with an SD of 16.6, while the mean age of the male patients was 54.9 years (SD = 16.2). The age difference between male and female patients in the study was not statistically significant (p = 0.36). The mean operating time was 74.4 minutes (range: 60-90 minutes, with an SD of 7.2). The mean time to oral liquid/soft diet was 2.5 days. The mean postoperative stay was 5.7 days. Three patients (8%) underwent conversion to open surgery, out of which two patients had multiple complex bowel-to-bowel and bowel-to-parietes adhesions, and in one patient, massive distension of small bowel caused technical difficulties. CONCLUSION: Laparoscopic management of ASBO is feasible, effective, and safe. Optimum surgical techniques, the surgeon's experience with the procedure, and stringent patient selection criteria enable a high probability of success.

Broad ligament hernia: Two contrasting ways to a common goal - Two case reports with review of literature.

INTRODUCTION: Broad ligament hernia (BLH) is a rare but potentially life threatening condition. One of the two cases described here is the only reported case of BLH in recent literature, where marsupialisation was done. These two case reports comprise the only reported side by side pictorial comparison of the two laparoscopic surgical therapeutic options for BLH. PRESENTATION OF CASES: Both patients presented with classical symptoms and signs of acute intestinal obstruction. Imaging confirmed obstructed left BLH in case 2 and indicated a complete small bowel obstruction in case 1. Both cases were successfully managed laparoscopically. Both patients had an uneventful immediate postoperative recovery and have not had recurrence over a mean follow up period of 34.5 months. DISCUSSION: BLH is rare among all types of internal herniae. It accounts for only 4% of internal herniae and is a difficult condition to diagnose. The advent of computed tomography has increased chances of accurate preoperative diagnosis. CONCLUSION: BLH can be successfully managed by minimally invasive surgery, even in the acute setting. When tightly entrapped bowel is unyielding; it is better not to risk injury to it by aggressive attempts at its reduction. It is safer to attempt widening of the defect into which it is entrapped, whenever feasible.

Branch Pulmonary Artery Jailing During Patent Ductus Arteriosus Stenting: Recruitment and Immediate Outcomes.

BACKGROUND: Branch pulmonary artery (PA) occlusion during patent ductus arteriosus (PDA) stenting procedure is the main reason why branch PA origin stenosis was considered as a contraindication for PDA stenting. This study was designed to assess the incidence of branch PA jailing during PDA stenting for cyanotics with duct-dependent pulmonary circulation and its immediate outcome. METHODS: All the completed PDA stenting patients in our hospital between April 2017 and June 2019 were retrospectively analyzed for branch PA jailing and its outcome. RESULTS: Of 63 completed PDA stenting, there was branch PA jailing in 13 (20.6%) patients, all successfully recruited either by strut dilatation or by surgery. The median duration of ventilation was 16 (interquartile range [IQR]: 8-22) hours for jailed patients and 17.5 (IQR: 5.25-34.25) hours for nonjailed patients (P = .978). Median intensive care unit [ICU] stay was 69 (IQR: 47.75-96) hours for jailed patients and 79.5 (IQR: 66.75-135.25) hours for nonjailed patients (P = .394). Procedural mortality was 1 (7.6%) for jailed patients and 3 (6%) for nonjailed patients. Since all the jailed pulmonary arteries were recruited, there was proportionate growth of branch PA till the most recent follow-up. CONCLUSION: Jailing of branch PA does not increase the ventilation duration, ICU stay, or mortality risk if recruited immediately. Proportionate growth of branch PAs can be achieved in spite of jailing, if addressed aggressively. Branch PA stenosis should not be considered as a contraindication for PDA stenting.

Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics.

AIMS: Application of advanced molecular pathology in rare tumours is hindered by low sample numbers, access to specialised expertise/technologies and tissue/assay QC and rapid reporting requirements. We assessed the feasibility of co-ordinated real-time centralised pathology review (CPR), encompassing molecular diagnostics and contemporary genomics (RNA-seq/DNA methylation-array). METHODS: This nationwide trial in medulloblastoma (<80 UK diagnoses/year) introduced a national reference centre (NRC) and assessed its performance and reporting to World Health Organisation standards. Paired frozen/formalin-fixed, paraffin-embedded tumour material were co-submitted from 135 patients (16 referral centres). RESULTS: Complete CPR diagnostics were successful for 88% (120/135). Inadequate sampling was the most common cause of failure; biomaterials were typically suitable for methylation-array (129/135, 94%), but frozen tissues commonly fell below RNA-seq QC requirements (53/135, 39%). Late reporting was most often due to delayed submission. CPR assigned or altered histological variant (vs local diagnosis) for 40/135 tumours (30%). Benchmarking/QC of specific biomarker assays impacted test results; fluorescent in-situ hybridisation most accurately identified high-risk MYC/MYCN amplification (20/135, 15%), while combined methods (CTNNB1/chr6 status, methylation-array subgrouping) best defined favourable-risk WNT tumours (14/135; 10%). Engagement of a specialist pathologist panel was essential for consensus assessment of histological variants and immunohistochemistry. Overall, CPR altered clinical risk-status for 29% of patients. CONCLUSION: National real-time CPR is feasible, delivering robust diagnostics to WHO criteria and assignment of clinical risk-status, significantly altering clinical management. Recommendations and experience from our study are applicable to advanced molecular diagnostics systems, both local and centralised, across rare tumour types, enabling their application in biomarker-driven routine diagnostics and clinical/research studies.

Unmasking the great masqueraders: Concurrent isolated large cecal endometrioma and solitary extra-uterine retroperitoneal cellular leiomyoma - A case report with review of literature.

INTRODUCTION: Cecal endometriosis is an infrequent cause of right iliac fossa pain. The extra-uterine retroperitoneal cellular leiomyoma is a rare tumor. The concurrent existence of both these rare conditions is a unique event. PRESENTATION OF CASE: We hereby report the case of a 44-year-old woman who had concurrent large isolated cecal endometrioma, which was diagnosed pre-operatively on imaging to be pelvic endometriosis/hematosalpinx and solitary retroperitoneal cellular leiomyoma, which was incidentally identified. Both the conditions were managed successfully by laparoscopy. DISCUSSION: Cecal endometriosis is difficult to diagnose pre-operatively as there are far commoner clinical conditions that cause similar signs and symptoms. Often it gets mistaken for these conditions and gets diagnosed incidentally 'on table' during surgeries being performed purportedly to treat them. CONCLUSION: Although definitive diagnosis can only be obtained after histopathology, laparoscopy can be considered a standard diagnostic modality for both these conditions.

Huge pelvic retroperitoneal cyst masquerading as hydrosalpinx: A case report with review of the literature.

Primary retroperitoneal cysts (RPCs) are a rare surgical entity and are mostly detected incidentally. Usually, they are asymptomatic. At times, they may attain a huge size and may present with a large abdominal lump. Often, they pose a dilemma at diagnosis and for management. Though the laparoscopic approach has been described for their surgical excision, open surgery is still the preferred approach. We herein present a case of a voluminous retroperitoneal pelvic cystic mass in a 40-year-old female, which was diagnosed as hydrosalpinx on a magnetic resonance imaging scan. The patient was referred to us by the specialist in gynecologic laparoscopy after the incidental discovery of the RPC during his surgical intervention, purportedly for large hydrosalpinx. At our hospital, 4 days after the above intervention, she underwent laparoscopic complete excision of the cyst. Her postoperative recovery was uneventful and she was discharged on postoperative day 3 without any complications. Histopathology was suggestive of Mullerian inclusion cyst. This case report aims to share a rare case of a large primary retroperitoneal pelvic cystic lesion, which caused a diagnostic challenge preoperatively but was eventually managed successfully, laparoscopically.

Malignant intracerebral nerve sheath tumor in a patient with Noonan syndrome: illustrative case.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) within the neuroaxis are rare, usually arising from peripheral and cranial nerves. Even more scarce are cranial subclassifications of MPNSTs termed "malignant intracerebral nerve sheath tumors" (MINSTs). These tumors are aggressive, with a strong tendency for metastasis. With this presentation, alongside resistance to adjunctive therapy, complete excision is the mainstay of treatment, although it is often insufficient, resulting in a high rate of mortality. OBSERVATIONS: The authors report the case of an adult patient with a history of Noonan syndrome (NS) presenting with slowly progressive right-sided hemiparesis and right-sided focal motor seizures. Despite initial imaging and histology suggesting a left frontal lobe high-grade intrinsic tumor typical of a glioblastoma, subsequent molecular analysis confirmed a diagnosis of MINST. The patient's neurological condition improved after gross-total resection and adjuvant chemo-radiation; he remains on follow-up. LESSONS: MINSTs are rare neoplasms with a poor prognosis; management options are limited, with surgery being the cornerstone of treatment. Reports on rare tumors such as this will increase awareness of this particular pathology and disclose clinical experience. In this case, the authors were unable to establish a definite cause-and-effect relation between NS and MINST. Nevertheless, it remains the first reported case in the literature.

Solid Component Volume as a Proxy to Identify Distinct Hemangioblastoma Populations.

BACKGROUND: Posterior fossa hemangioblastomas usually consist of a small solid nodule with a large cyst, while more rarely they present as a large solid mass with a small or absent cyst, which can be surgically challenging. We sought to investigate the potential existence of multiple distinct hemangioblastoma populations using tumor volumetric data as an indicator. METHODS: We conducted a retrospective review of surgically treated hemangioblastomas between 2005 and 2019 in our unit, including clinical notes, preoperative magnetic resonance imaging volumetric analysis of the solid component of the tumor, and pathology. Finite Gaussian mixture modeling was applied on the solid component volume dataset to identify potential underlying Gaussian distributions with their associated characteristics. Nonparametric Mann-Whitney U tests were used to investigate significance of differences (P < 0.05) in solid component volume and different variables (Von Hippel-Lindau disease, extent of resection, outcome). RESULTS: A total of 68 consecutive patients were included. Solid component volumes followed a multimodal distribution (median = 1287 mm3, interquartile range of 3428 mm3). The best-fit finite Gaussian mixture modeling model identified 3 statistically significant different (P = 0.001) potential mixture components: X1 (219 ± 187 mm3), X2 (2686 ± 1299 mm3), and X3 (10,800 ± 5514 mm3). The second-best model detected 2 significantly different (P = 9.99e-08) mixture components Y1 (222 ± 189 mm3) and Y2 (5391 ± 5094 mm3). A significant difference in solid component volume was found between patients with favorable and unfavorable outcome (P = 0.002). CONCLUSIONS: This study has shown preliminary evidence that large solid hemangioblastomas may constitute a completely distinct population, rather than a variant of one large group of hemangioblastomas.

Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study.

BACKGROUND: Disease relapse occurs in around 30% of children with medulloblastoma, and is almost universally fatal. We aimed to establish whether the clinical and molecular characteristics of the disease at diagnosis are associated with the nature of relapse and subsequent disease course, and whether these associations could inform clinical management. METHODS: In this multicentre cohort study we comprehensively surveyed the clinical features of medulloblastoma relapse (time to relapse, pattern of relapse, time from relapse to death, and overall outcome) in centrally reviewed patients who relapsed following standard upfront therapies, from 16 UK Children's Cancer and Leukaemia Group institutions and four collaborating centres. We compared these relapse-associated features with clinical and molecular features at diagnosis, including established and recently described molecular features, prognostic factors, and treatment at diagnosis and relapse. FINDINGS: 247 patients (175 [71%] boys and 72 [29%] girls) with medulloblastoma relapse (median year of diagnosis 2000 [IQR 1995-2006]) were included in this study. 17 patients were later excluded from further analyses because they did not meet the age and treatment criteria for inclusion. Patients who received upfront craniospinal irradiation (irradiated group; 178 [72%] patients) had a more prolonged time to relapse compared with patients who did not receive upfront craniospinal irradiation (non-irradiated group; 52 [21%] patients; p<0·0001). In the non-irradiated group, craniospinal irradiation at relapse (hazard ratio [HR] 0·27, 95% CI 0·11-0·68) and desmoplastic/nodular histology (0·23, 0·07-0·77) were associated with prolonged time to death after relapse, MYC amplification was associated with a reduced overall survival (23·52, 4·85-114·05), and re-resection at relapse was associated with longer overall survival (0·17, 0·05-0·57). In the irradiated group, patients with MBGroup3 tumours relapsed significantly more quickly than did patients with MBGroup4 tumours (median 1·34 [0·99-1·89] years vs 2·04 [1·39-3·42 years; p=0·0043). Distant disease was prevalent in patients with MBGroup3 (23 [92%] of 25 patients) and MBGroup4 (56 [90%] of 62 patients) tumour relapses. Patients with distantly-relapsed MBGroup3 and MBGroup4 displayed both nodular and diffuse patterns of disease whereas isolated nodular relapses were rare in distantly-relapsed MBSHH (1 [8%] of 12 distantly-relapsed MBSHH were nodular alone compared with 26 [34%] of 77 distantly-relapsed MBGroup3 and MBGroup4). In MBGroup3 and MBGroup4, nodular disease was associated with a prolonged survival after relapse (HR 0·42, 0·21-0·81). Investigation of second-generation MBGroup3 and MBGroup4 molecular subtypes refined our understanding of heterogeneous relapse characteristics. Subtype VIII had prolonged time to relapse and subtype II had a rapid time from relapse to death. Subtypes II, III, and VIII developed a significantly higher incidence of distant disease at relapse whereas subtypes V and VII did not (equivalent rates to diagnosis). INTERPRETATION: This study suggests that the nature and outcome of medulloblastoma relapse are biology and therapy-dependent, providing translational opportunities for improved disease management through biology-directed disease surveillance, post-relapse prognostication, and risk-stratified selection of second-line treatment strategies. FUNDING: Cancer Research UK, Action Medical Research, The Tom Grahame Trust, The JGW Patterson Foundation, Star for Harris, The Institute of Child Health - Newcastle University - Institute of Child Health High-Risk Childhood Brain Tumour Network (co-funded by The Brain Tumour Charity, Great Ormond Street Children's Charity, and Children with Cancer UK).

Occlusal Analysis Using T-Scan in Patients With Condylar Fractures When Managed by Closed Method.

The aim of the study is to assess the occlusion in mandibular condyle fractures using T-Scan and analyze the data obtained. Twenty patients underwent non-surgical management for condylar fractures were treated with Erich arch bar and guiding elastics, and periodically subjected to T-Scan III evaluations. The data obtained was analyzed with the clinical evaluation conducted. There were 18 males and 2 females. Mean age of the patients was 25.4 ±â€Š7.4 years. There were statistically no significant changes in Centre of Force values, in Bite Force at First Contact (P < 0.05) during the study period. There were significant differences in Maximum Bite Force between preoperative and postoperative values, preoperative and sixth-month values, postoperative and first-month values, first-month and sixth-month values. There were significant (P < 0.05) differences in Bite Force at Maximum Intercuspation between preoperative and third month, preoperative and sixth-month values, postoperative and sixth-month values, first-month and consequent follow-ups. Subjective evaluation of occlusion revealed significant differences (P < 0.05) between preoperative and 1-month, preoperative and postoperative, postoperative and 1-month values. All patients improved by the end of 6 months with regards to their mouth opening. The center of force does not alter significantly in post trauma period. Mouth opening improves significantly at the end of 6-month period post-operative. Improvement in maximum bite force and maximum intercuspation take place simultaneously. Mouth opening improved significantly. Subjective evaluation of occlusion does not change significantly after the third month evaluation. Longer follow-ups would help us in understanding when or if the bite forces equilibrate after a condylar trauma.

Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.

The "isomorphic subtype of diffuse astrocytoma" was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.