Case of embryonal tumor multilayered rosettes in a patient with neurofibromatosis type 1.

BACKGROUND: ETMR is a unique and highly malignant brain tumor mostly occurring in infants. This report provides a comprehensive overview of the clinical presentation, histological aspects, radiological features, and therapeutic options of ETMR. Being the first report on the co-occurrence of NF1 with ETMR, it highlight the challenges of managing a patient with complex medical conditions. CASE REPORT: We present a case of a 3 and 1/2-year-old girl with neurofibromatosis type 1 (NF1), later diagnosed with a supratentorial brain tumor reported as an embryonal tumor with multilayered rosettes (ETMR), along with possible co-occurrence of constitutional mismatch repair deficiency (CMMRD) on immunohistochemistry (IHC); however, germline testing was not performed. Even though NF1 can be associated with tumors such as gliomas, the literature has no previous case reports of ETMR coexisting with NF1. CONCLUSION: Exploring the link between NF1 and ETMR with CMMRD is crucial to improving and establishing more treatment protocols. Therefore, reporting each case's unique features would be essential in developing appropriate treatment protocols.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Pakistan National Guidelines for Pediatric High-Grade Gliomas.

Pediatric high-grade glioma (pHGG) is highly malignant central nervous system tumor and constitute 10% of the pediatric gliomas. Effective treatment needs a functioning multi-disciplinary team including pediatric neuro oncologist, neurosurgeon, neuroradiologist, neuropathologist and radiation oncologist. Despite surgical resection, radiotherapy and chemotherapy, most HGG will recur resulting in early death. A significant proportion of HGG occurs in context of cancer predisposition syndromes like Constitutional Mismatch Repair Deficiency (CMMRD) also known as Biallelic Mismatch Repair Deficiency (bMMRD) characterized by high mutational burden. The incidence of HGG with CMMRD is one per million patients. bMMRD is caused by homozygous germline mutations in one of the four Mis Match Repair (MMR) genes (PMS2, MLH1, MSH2, and MSH6). The use of TMZ is now avoided in CMMRD related HGG due to its limited response and known ability to increase the accumulation of somatic mutations in these patients, increasing the risk of secondary tumors. HGG should be managed under the care of multidisciplinary team to receive optimum treatment. This is particularly important for low middle-income countries (LMIC) with limited resources like Pakistan.

Exploring the Causes of Wastage of Blood and Its Components in a Tertiary Care Hospital Blood Bank.

Background Blood donated by healthy people is extremely important as it is integral in emergent situations. The authors aimed to address and highlight the main causes of the wastage of donated blood and its components. Methodology A cross-sectional study was conducted at a blood bank of a tertiary care center between January 2019 and March 2020. All the information regarding blood donated and blood components during the study period was documented on a predefined proforma. The blood bags which were seropositive, reached their shelf-life expiry, expired due to non-utilization, or quantity was non-sufficient were discarded. Blood showing any changes of either hemolysis or turbidity was also discarded. Other reasons for discarding blood units included leakage (damage to or fault in the blood bag), hemolytic reasons, or miscellaneous reasons. Results A total of 9308 blood donations were received as donations during the study period. Out of the total donations, 7,988 (85.8%) were subjected for component formation including red cell component (RCC), fresh frozen plasma (FFP), and platelets. A total of 23,964 components were prepared using the donated blood. Out of these 2128 (8.87%) units were discarded. Upon stratifying the discarded blood according to the type of component, it was found that platelets made up 1148 (53.9%) units, red cell component composed 324 (15.2%) units, and fresh frozen plasma composed 313 (14.7%) units of discarded blood. Seropositive was reported to be 32.3%. Of this, the red cell component made up 276 (85.2%) units. Conclusion The present study reported a discard rate of 8.87%. Of these, the majority was composed of platelets due to the shortest shelf life. Leakage of blood bags remained a predominant cause for the discard of blood components. Seropositivity for hepatitis B, C, and human immunodeficiency virus (HIV) was reported in almost 30% units of donated blood. Further large-scale studies should be conducted to reassess how wastage of donated blood can be minimized.

Predictors of treatment outcome of Wilms Tumour in low-income country; single centre experience from Pakistan.

BACKGROUND: Wilms tumor (WT) represents around 85% of pediatric renal tumors. In high-income countries, 5-years survival of WT is above 90% but survival in developing countries is inferior. OBJECTIVE: To identify the predictors of treatment outcome of WT in a developing country. METHODS: A retrospective study conducted at the pediatric oncology department, Combined Military Hospital Rawalpindi, Pakistan. All newly diagnosed WT cases from 1st January 2012 who completed their treatment before 31st August 2019 were evaluated. Treatment was based on SIOP Wilms Tumour 2001/UK version 5. Patients presenting before nephrectomy received pre-operative chemotherapy. The postoperative chemotherapy regimen was decided according to the stage, risk stratification and metastatic status of the patient. RESULTS: Data of 84 cases, including 40 (47.6%) males and 44 (52.4%) females was analyzed. The mean diagnostic age was 38.87 ± 28.66 months and 68 (81%) cases were less than five years of age. The commonest presenting features were abdominal mass in 75 (89.3%) cases. The right kidney was affected in 43 (51.2%) cases. Stage I disease was documented in 27 (32.1%) cases, stage II in 25 (29.8%), stage III in 13 (15.5%), and stage IV in 17 (20.2%) cases. In univariate analysis, advanced stage (P = < 0.001) and metastatic disease (P=< 0.001) adversely affected the treatment outcome. Multivariate analysis demonstrated that advanced stage WT was associated with the worst outcome (P= < 0.05). Four (4.8%) cases had treatment-related mortality (TRM). With a median follow-up time of 28.26 ± 23.03 months, OS and EFS were 66 (78.6%) and 63 (75.0%) respectively. DISCUSSION: Delayed presentation with advanced-stage metastatic disease is quite common in the developing courtiers and is the major contributor to decreased EFS and OS. In the present study, 20.2% cases had metastatic disease, which is similar to reported from other developing countries. OS decreased from 92.6% in stage I to 47.1% in stage IV disease (P=< 0.001) and EFS decreased from 92.6% in stage I to 43.8% in stage IV disease (P=< 0.001). Very similar results are reported by a regional study [17]. Results in stage I and II disease are comparable to documented in the western world and inferior in advanced-stage disease. The strength of the present study is that multiple factors, affecting the treatment outcome of WT over almost seven years period were evaluated. CONCLUSIONS: Stage of the disease is the most important prognostic factor. Delayed presentation with metastatic disease has a poor outcome.

Mortality in paediatric acute myeloid leukaemia.

OBJECTIVE: To analyse the common causes of death in paediatric acute myeloid leukaemia cases at a tertiary care facility. METHODOLOGY: The retrospective study was conducted at the Paediatric Oncology Department of the Combined Military Hospital, Rawalpindi, Pakistan, and comprised newly-registered cases of acute myeloid leukaemia aged <18 years from January 1, 2012, onwards and who completed their treatment before January 31, 2019. Data was retrieved from medical records and was analysed using SPSS 23. RESULTS: Of the 206 cases, 130(63.1%) were males and 76(36.9%) were females. Overall mean age at diagnosis was 5.96±3.57 years (range: 9 months to 15 years). Of the total, 6(2.9%) patients died before the start of treatment. Of the remaining, 43(21.5%) patients died during 1st induction chemotherapy, and 16(8%) during the post-induction period, with overall treatment-related mortality being 65(31.5%). The main cause of death during the first two weeks of induction was infection, while infection followed by multi-organ failure was the main cause of mortality in the second phase. A total of 130(63%) patients completed the treatment. Overall survival was 81(62.3%) while disease-free survival was 77 (59.2%). CONCLUSIONS: Overall treatment-related mortality rate in paediatric acute myeloid leukaemia cases was found to be high. Pregnancies achieved by IVF/ICSI, being complicated with severe OHSS could be related to gestational hypertension.