Defining High-risk Retinoblastoma: A Multicenter Global Survey.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

Precursor B-cell acute lymphoblastic leukaemia-a global view.

As haematologists, we always seek to follow standardised guidelines for practice and apply the best treatment within our means for our patients with blood diseases. However, treatment can never follow an exact recipe. Opinions differ as to the best approach; sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn has an impact on the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. Here we take a look at the precursor B-cell acute lymphoblastic leukaemia in an adolescent in a range of different settings from low- to high income countries with widely differing challenges for diagnosis, therpy and follow-up. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. Experts from around the world have been tasked to describe their management plan and rationale for a specific disease presentation. Here they explore the management of precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) in five different institutions worldwide with a focus on those with more or less strained economies. We end with a conclusion from an expert in the field comparing and contrasting these different management styles and considering their merits and limitations.

Locally produced personal protective equipment can offer hospital staff protection against Covid-19 if combined with surgical masks and rigorous personal protective equipment cleaning routine.

Locally made, washable and reusable personal protective equipment (PPE), used in combination with N95 masks that were reused safely, has proven to be a viable alternative to disposable gowns and caps for hospital staff in low- and middle-income countries. Muhimbili University Hospital's children's cancer ward in Dar es Salaam, Tanzania, developed locally made PPE and created rigorous cleaning and disinfecting protocols, when the daily use of imported, disposable materials were not an option. These items continue to protect staff, children and parents. The novel PPE approach was able to prevent staff from becoming infected during the pandemic despite the fact that several parents, and subsequently their children, became infected with Covid-19 during cancer treatment at the facility.

Case report: Xanthogranulomutous pyelonephritis presenting as "Wilms' tumor".

BACKGROUND: Xanthogranulomatous pyelonephritis (XGP) is a rare renal tumor that arises as a complication of chronic obstructive pyelonephritis of uncertain etiology. It is primarily an adult tumor seen occasionally in children associated with urinary tract obstruction due to congenital urological anomalies, nephrolithiasis, and recurrent urinary tract infections. Radiologically, it may show neoplastic features such as those seen in common pediatric renal malignancies like wilms' tumor and renal cell carcinoma. This overlap in radiological manifestation frequently leads to misdiagnosis and delay in appropriate intervention. We report a case of a 3 years old boy who presented with history of recurrent urinary tract infections and a left renal mass initially thought to be Wilms' tumor. CASE PRESENTATION: We present a case of a 3 years old boy admitted to the Pediatric oncology unit at Muhimbli National Hospital in Dar es Salaam, Tanzania with one year history of recurrent fever and urinary tract infection signs and symptoms refractory to antibiotic therapy. He was eventually found to have a left kidney mass detected at the District hospital by abdominal ultrasound performed to evaluate a flank mass that was felt by his mother. He was then referred to our unit for a suspicion of Wilms' tumor which finally turned out  to be a left kidney Xanthogranulomatous pyelonephritis. He underwent a successful left nephrectomy and was discharged from hospital in a stable clinical condition and remains asymptomatic at the time of submission of this case report. CONCLUSION: This case report underscores the need for clinicians attending a febrile child with a renal mass that can be confused with common pediatric renal malignancies such as Wilms' tumor to broaden their differential diagnosis. The case also underlines the significance of individualized patient evaluation because this patient would have otherwise received preoperative chemotherapy under the International Society of Pediatric Oncology (SIOP) guidelines if the diagnosis of Wilms tumor was not ruled out.

Evaluation and Outcome of Central Nervous System Involvement in Pediatric Acute Lymphoblastic Leukemia in Dar es Salaam, Tanzania.

BACKGROUND: Outcomes for acute lymphoblastic leukemia (ALL) in low-income countries lag far behind high-income countries (HIC). We explored the impact of central nervous system (CNS) involvement on outcome of pediatric patients with ALL in Tanzania. PROCEDURE: Comprehensive chart review was performed to characterize CNS involvement, treatment, and outcomes of pediatric patients with ALL at Muhimbili National Hospital in Dar es Salaam, Tanzania between January 1, 2011 and December 31, 2013. RESULTS: One hundred fifty-six patients with confirmed ALL had accessible data, and 128 initiated therapy. Sixteen percent of 156 patients had a documented cerebral spinal fluid analysis by cytospin. Seventy patients (45%) had a documented lumbar puncture with intrathecal (IT) therapy within 1 week of diagnosis. Thirteen patients presented with CNS involvement at diagnosis based on cytospin and/or unequivocal symptoms. Twenty-one patients (16%) experienced CNS relapse, three of whom had CNS disease at diagnosis. Median event-free survival (EFS) for all patients was 7.9 months and estimated EFS at 24 months was 31%. For the patients with CNS involvement at diagnosis, the estimated EFS at 24 months was 45%. Only three of 21 patients with CNS relapse were still alive with a median follow up of 3 months. CONCLUSIONS: The rate of CNS disease in patients with ALL in Dar es Salaam at diagnosis and relapse was higher than that reported in HIC, and overall survival was lower. Improving outcomes will require further advances including consistent CNS prophylaxis and may include targeting high-risk patients with additional IT treatments.

Current treatment and outcome for childhood acute leukemia in Tanzania.

BACKGROUND: In order to understand the disparity in childhood leukemia survival in low-income countries (LICs) compared to high-income countries (HICs), we evaluated the resources available at Tanzania's national pediatric oncology ward, and clinical characteristics, disease course and outcomes of children diagnosed with acute leukemia from 2008 through 2010. PROCEDURES: A chart review and assessment of services was performed to assess childhood leukemia diagnoses, treatment, and outcomes in Tanzania at the Ocean Road Cancer Institute (ORCI) from January 1, 2008 to December 31, 2010. Results were compared to those from a 2005 evaluation that showed only one of 20 children with leukemia surviving at 1 year. RESULTS: During the study period, 106 patients presented with leukemia, including 81 patients with acute lymphoblastic leukemia (ALL) and 25 with acute myeloid leukemia (AML). Forty-nine of 58 (84%) patients with ALL, and six of 17 (35%) with AML who received therapy and had complete data, achieved complete remission. Estimated 2-year event-free survival for all patients with ALL was 33%; for AML it was 0%. Ten patients died prior to initiation of therapy, 19 died of toxicity, and eight abandoned therapy. CONCLUSIONS: Though leukemia survival in Tanzania remains far below that in HICs, survival rates for ALL have significantly improved in recent years due to standardization of treatment regimens and better staff, though AML outcome remains dismal. Ongoing improvements in pediatric leukemia outcomes will require strategies to improve awareness and early access to treatment coupled with improvements in diagnostic capabilities, supportive care, and training.

Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease.

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.

First-year experience of chemotherapy for advanced retinoblastoma in Tanzania: disease profile, outcomes, and challenges in 2008.

PURPOSE: To examine the profile of retinoblastoma in a national tertiary referral center in Tanzania and to report first-year outcomes of its treatment using chemotherapy. METHODS: All patients with retinoblastoma referred in 2008 were included. Disease was classified on clinical grounds as ocular, orbital, or metastatic. Those with ocular and orbital disease received chemotherapy. Remission was the main outcome measure and defined as absence of disease at the end of treatment. RESULTS: In 2008, 37 patients (20 males and 17 females) with retinoblastoma were referred to Ocean Road Cancer Institute. The mean delay from the first sign of disease to presentation at hospital was 10.4 ± 8.7 months. Disease was ocular in 32% (12 of 37), orbital in 57% (21 of 37), and metastatic in 11% (4 of 37). Of those with ocular disease, 67% (8 of 12) completed chemotherapy and all (8 of 8) achieved remission. In contrast, 48% (10 of 21) with orbital disease completed chemotherapy and only 50% (5 of 10) achieved remission. The difference in outcome between the groups was statistically significant (P = .001, Fisher exact test). CONCLUSION: The profile of retinoblastoma in Tanzania is skewed toward severe invasive disease. Despite the introduction of chemotherapy, further improvements in mortality and morbidity can only be achieved through emphasis on early detection.