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.

Covid-19-associated fungal osteomyelitis of jaws and sinuses: An experience-driven management protocol.

Invasive fungal co-infections with COVID-19 are currently being reported at an alarming rate. Our study explores the importance of early identification of the disease, probable etiopathogenesis, clinical and radiological features and a treatment protocol for COVID-19 Associated Fungal Osteomyelitis of Jaws and Sinuses (CAFOJS). A one-year prospective study from June 2020 to May 2021 was conducted among CAFOJS diagnosed patients at a tertiary care center in South India. Demographic details, COVID-19 infection and treatment history, time taken for initiation of symptoms after COVID-19 diagnosis, medical history and clinical features were recorded. All patients were managed with a standard diagnostic and intervention protocol which included pre-operative and post-operative administration of Inj. Amphotericin B 50 mg (liposomal), early aggressive surgical debridement and tab. Posaconazole GR 300 mg OD for 90 days after discharge. Thirty-nine (78%) patients were diagnosed with CAFOJS out of 50 osteomyelitis patients. 35 patients (90%) were diabetic and 21 patients (54%) were known to receive steroids during the COVID-19 treatment. Sole existence of Mucorales spp. was seen in 30 patients (77%), Aspergillus fumigatus in 2 patients (5%), Curvularia spp. in 2 patients (5%). Concomitant existence of Mucorales and Aspergillus fumigatus was reported in two patients (5%) and Candida albicans in three patients (8%). Patients underwent treatment with standard protocol and no recurrence noted. CAFOJS is a clinical entity with aggressive presentation and warrants early diagnosis and treatment. LAY SUMMARY: Invasive fungal infections of head and neck region cause necrosis of bones affected by it, especially maxilla. Early diagnosis and treatment are advocated in such infections due to its aggressive clinical presentation compared to similar infections before COVID-19 pandemic.

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.

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.

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.

The aortic arch in tetralogy of Fallot: types of branching and clinical implications.

INTRODUCTION: Tetralogy of Fallot is the most common form of cyanotic CHD, with an incidence of 421 cases per million live births, constituting around 10% of CHD. Variations in aortic arch anatomy associated with tetralogy of Fallot, other than the incidence of right aortic arch (13-34%), are not frequently reported. A comprehensive analysis of a large number of tetralogy of Fallot cases is required to arrive at a compendious description of aortic arch anatomy. MATERIALS AND METHODS: All patients with a diagnosis of tetralogy of Fallot who had CT or MRI either pre or post procedures between 1 January 2010 and 31 December 2019 at our hospital were included in the study. Using radiology consultants' reports and analysis of individual images, we identified the various morphological patterns of aortic arches prevalent in these patients. RESULT: Out of 2684 patients who met the inclusion criteria, 1983 patients had left aortic arch (73.9%), 688 patients had right aortic arch (25.7%), four patients had cervical aortic arch (0.15%), eight patients had double aortic arch (0.3%), one patient had an aorto-pulmonary window (0.04%), and none of the patients had interrupted aortic arch. Sub-classification and clinical implications of the arch variations are described. CONCLUSION: Up to 10% of tetralogy of Fallot patients may have significant anatomical variations of aortic arch that would necessitate changes or additional steps in their surgical or interventional procedures.

Anatomic classification of the right aortic arch.

The term right aortic arch is used for an aorta that arches over the right bronchus. Right aortic arch was classified into two types by Felson et al, based on branching patterns, with a proposed embryological explanation, and into three types by Shuford et al. Other anatomical variants of right aortic arch were described later, including isolated left brachiocephalic artery and aberrant left brachiocephalic artery. We have classified right aortic arch anatomy into 10 variants, supported by radiological evidence, and with reference to possible embryology. This classification will help in understanding the morphological basis for the formation of different types of right aortic arch and the course of the recurrent laryngeal nerve in such cases.

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.

Are Facial Asymmetry and Condylar Displacement Associated With Ramal Height and Treatment Outcomes in Unilateral Condylar Fracture When Managed by the Closed Method?

PURPOSE: This study measured the mandibular ramal height in patients with unilateral condylar fractures managed by the closed method using elastic intermaxillary fixation. Its correlation with facial asymmetry and condylar displacement was assessed. This will determine whether the treatment outcome is in favor of the closed or open method. MATERIALS AND METHODS: A prospective cohort study was performed. The study included patients with unilateral condylar fractures who reported to SDM Craniofacial Surgery and Research Centre, Dharwad, India. All patients in the study were managed by the closed method (nonsurgically using arch bars and elastic intermaxillary fixation). Standardized panoramic radiographs were used to assess ramal height and condylar displacement in the sagittal plane. Posteroanterior mandible and reverse Towne radiographs were used to assess facial asymmetry and condylar displacement in the coronal plane before treatment; immediately after treatment; and at 3, 6, and 12 months of follow-up. Data were subjected to statistical analysis using the analysis-of-variance test and the Pearson correlation coefficient method. RESULTS: The study included 25 patients with unilateral condylar fractures managed by closed treatment; they showed a significant reduction in ramal height on the affected side by 1.15 mm (P = .0001) at 12 months' follow-up. The change in facial asymmetry was reported as 1.05 mm (P = .0016) at 12 months' follow-up. Its correlation with ramal height was noted to be insignificant (P = .07). The only significant correlation noted between facial asymmetry and condylar displacement was in the coronal plane at 12 months' follow-up (P = .04). CONCLUSIONS: A weak positive correlation was noted among the assessed values on radiographs obtained during the 12-month follow-up. Facial symmetry was not greatly affected when the ramal height at the time of injury on the fractured side was reduced by 3.25 ± 0.6 mm.

Orbital Observation Chart: Significant in Orbital Fractures or Not?

PURPOSE: The study was conducted to assess the efficacy of orbital chart in detecting postoperative complications of orbital fractures. MATERIALS AND METHODS: A retrospective study was conducted in the Department of OMFS, SDM College of Dental Sciences, Dharwad from January 2011 to December 2016. It included all the patients with orbital fractures who underwent surgical intervention for reduction of the fracture in the study. We recorded data for the type of fracture, type of intervention, and orbital and ocular changes. Orbital changes measured and charted for 5 parameters which were: pain, proptosis, visual acuity, size of the pupil, and pupillary reaction to direct light reflex. RESULTS: Two hundred thirty-six patients with orbital fractures underwent surgical intervention during these 5 years. The prevailing type of fracture for which they required orbital intervention remains zygomatic complex fractures (69%). The treatment protocol depended on the pattern and displacement of fracture and age of the patient. Pain was the most common symptom among these parameters (15.7%). CONCLUSION: Orbital chart monitoring represents a straightforward and effective method to detect any complications after surgical management of orbital fractures.

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. ß-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP.

Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study.

BACKGROUND: International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. METHODS: In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0-16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3-16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. FINDINGS: Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MBWNT remained unchanged and each remaining consensus subgroup was split in two. MBSHH was split into age-dependent subgroups corresponding to infant (<4·3 years; MBSHH-Infant; n=65) and childhood patients (≥4·3 years; MBSHH-Child; n=38). MBGrp3 and MBGrp4 were each split into high-risk (MBGrp3-HR [n=65] and MBGrp4-HR [n=85]) and low-risk (MBGrp3-LR [n=50] and MBGrp4-LR [n=73]) subgroups. These biological subgroups were validated in the independent cohort. We identified features of the seven subgroups that were predictive of outcome. Cross-validated subgroup-dependent survival models, incorporating these novel subgroups along with secondary clinicopathological and molecular features and established disease risk-factors, outperformed existing disease risk-stratification schemes. These subgroup-dependent models stratified patients into four clinical risk groups for 5-year progression-free survival: favourable risk (54 [25%] of 215 patients; 91% survival [95% CI 82-100]); standard risk (50 [23%] patients; 81% survival [70-94]); high-risk (82 [38%] patients; 42% survival [31-56]); and very high-risk (29 [13%] patients; 28% survival [14-56]). INTERPRETATION: The discovery of seven novel, clinically significant subgroups improves disease risk-stratification and could inform treatment decisions. These data provide a new foundation for future research and clinical investigations. FUNDING: Cancer Research UK, The Tom Grahame Trust, Star for Harris, Action Medical Research, SPARKS, The JGW Patterson Foundation, The INSTINCT network (co-funded by The Brain Tumour Charity, Great Ormond Street Children's Charity, and Children with Cancer UK).

Histological Assessment of the Carotid Sheath in Patients With Oral Squamous Cell Carcinoma.

PURPOSE: During surgical management of the neck using various types of neck dissection, the carotid sheath is removed, in particular, the part adjacent to the jugular lymph node chain, with the intention of preventing recurrence from the lymphatics present within it. The role of the carotid sheath as a potential origin for nodal recurrence has not been proved thus far. Working in a tissue plane between the carotid sheath and the neurovascular structures of the neck can lead to a greater chance of damage to these structures. Also, the carotid sheath is a strong fibroelastic tissue barrier that shields the internal jugular vein and carotid artery from saliva and local infection during the postoperative period. Thus, this study investigated the histopathology of the carotid sheath in patients with oral squamous cell carcinoma (OSCC) and assessed the pathologic infiltration of the carotid sheath when grossly uninvolved. PATIENTS AND METHODS: Pathologic infiltration and histopathologic characteristics of the entire length of the carotid sheath were assessed in 30 biopsy-proved cases of OSCC; these patients underwent surgical excision of the lesion in addition to neck dissection from 2013 to 2015 in the craniofacial unit of the authors' institution. RESULTS: The carotid sheath consisted of fibrofatty tissue and interspersed nerve bundles. Neutrophilic infiltration and dilated lymphatic channels were seen in all 30 cases. Miniature lymph nodes adherent to the carotid sheath were seen in 5 cases and some lymphoid aggregates were seen in 15 cases. The carotid sheath in all 30 cases (metastatic and nonmetastatic) was free from tumor deposit and lymphatic tumor emboli, which are indicators of tumor cell infiltration. CONCLUSION: Indicators of tumor cell infiltration were not found in any of the 30 cases. The result did not vary with the age or gender of the patient, tumor size, location, staging or grading of the tumor, or even when there were metastatic lymph nodes in the gross specimen. Hence, the role of the carotid sheath as a potential origin for nodal recurrence is questionable and its removal needs reconsideration.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

AIMS: Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. METHODS: We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. RESULTS: Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P < 0.01). Information was more frequently recorded regarding circumstances of death and body position/location than clinical epilepsy history and investigations. CONCLUSION: Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes.

Spontaneous and tetracosactide-induced anti-ACTH antibodies in man.

CONTEXT: During a clinical trial of regular tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antitetracosactide (ACTH1-24 ) antibodies. DESIGN: Anti-ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves' disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. RESULTS: Bands at approximately 4 and 6 kDa, corresponding to ACTH1-24 and full-length ACTH1-39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections. CONCLUSION: Our study demonstrates that repeated administration of depot tetracosactide can lead to anti-ACTH1-24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti-ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well-described phenomenon of resistance to chronic ACTH therapy.

Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature.

Cartilaginous metaplasia in ependymomas is extremely rare and only few cases have been reported in the literature. We describe a case of a 5-year-old patient with a 5th recurrence of 4th ventricle ependymoma. He was previously treated with 4 resections, chemotherapy and radiotherapy. Histopathology revealed well-differentiated chondroid tissue occupying almost the entire lesion. Near total resection was achieved for the 5th time, but the patient died 3 months later achieving a total survival of 48 months, the 3rd longest reported in literature. Multiple resections of tumour recurrence provided a new insight in this very rare tumour, as it gave us the opportunity to observe the progression of tumour aggressiveness from grade II to grade III and finally to chondroid metaplasia. Cartilaginous metaplasia in posterior fossa ependymomas is a very atypical and challenging tumour with poor overall prognosis.

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.

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.

Correction: Emergency Laparoscopic Management of Perforative Peritonitis: A Retrospective Study.

[This corrects the article DOI: 10.7759/cureus.20121.].