Ahmed Samir Alfaar

BACKGROUND Marital status influences the presentation and outcome of various cancers. We explored the relationship between marital status and survival of uveal melanoma (UM) and factors influencing this relationship. METHODS We conducted a retrospective cohort study on patients diagnosed with UM and registered in the Surveillance Epidemiology and End Results program between 1973 and 2017. Cox regression model was conducted to calculate the hazard ratio of overall and cancer-specific survival rate and delineate the effect of each confounder. RESULTS The study involved 10,557 patients with a male-to-female ratio of 1:1.1. Most of the diagnosed patients were aged between 40 and 79 years (81%). Married patients (62%) represented the majority, followed by singles (12%), widowed (11%), and then divorced patients (7%). Single patients were the youngest group (mean age of 59.3 years) while widowed patients were the oldest (mean age of 75.8 years). In the Cox regression model for overall survival, married and single patients exhibited the best overall survival (no significant difference in between them), both surpassing divorced and widowed patients. Married patients were at a significantly lower risk to die from UM than divorced patients. Female patients and younger age groups showed the best overall and cancer-specific survival. CONCLUSION Maintained marriages improved the survival of UM patients. Widowed and divorced patients should be included in specially designed support programs during their cancer management.

Registries resemble a systematic way of collecting data for a specific theme or a population. As well-built registries represent a wealth of information for scientists, huge investments are paid to ensure their quality. The quality of the data gathered depends on a rigorous process of data validation and updating and, the comprehensiveness of the sources providing the data. Therefore, the data release may take years after the data collection. The advancement in information and computer technologies has helped in the progress of building better disease registries. In the process of learning from experiences in building registries, we aim in this presentation at discussing the lessons learned from building cancer (and other diseases) registries in different setups to facilitate building better ophthalmological registries. Moreover, to discuss the most common mistakes that lead to delayed collection and publishing of the data.

Fragestellung: Endophthalmitis ist eine seltene, aber sehbedrohende Erkrankung. Die Ursache der Krankheit kann entweder exogen, nach den ophthalmologischen Eingriffen oder Augenverletzungen, oder endogen sein. In letzter Zeit wurden mehrere Studien veröffentlicht, die über einen Anstieg der Endopthtalmitis-Inzidenz in der Zeit der Covid-Pandemie berichteten und als eine von möglichen Ursachen das Tragen des Nasen Mund-Schutzes bei den Patienten nach den intraokularen Eingriffen angeben. Methodik: In dieser Studie werden die Daten aus Jahren 2019 (vor der Pandemie) und 2020 (während der Pandemie) analysiert, die von der DRG (Disease-Related Groups) unter den Codierung H44.0 und H44.1 für alle in Deutschland stationär behandelten Patienten gemeldet wurden. Hiernach wird bei den jeweiligen Daten zwischen purulenter und sonstiger Endophthalmitis unterschieden. Folgende Daten wurden aus dem Register abgefragt und evaluiert: Gesamtzahl der Fälle, Verweildauer, Komorbiditäten (Patient Comorbidity Score) und die Altersstruktur der Patienten. Begleitend wurden Nebendiagnosen und Prozeduren aufgeführt. Ergebnisse: Die Gesamtzahl der im DRG- Register erfassten Endophthalmitis- Fälle im Jahr 2019 betrug 2539 und ging im Jahr 2020 auf 2405 Fälle zurück. Auch bei der Anzahl der als „purulente Endophthalmitis“ erfassten Fälle zeigte sich zwischen Jahr 2019 und 2020 ein leichter Rückgang von 965 auf 881 Fälle. Der Anteil der Frauen zeigte zwischen den beiden Jahren keine signifikanten Unterschiede (53 % der erfassten Fälle), allerdings stieg der Anteil der Patienten mit einem Alter > 80 Jahre von 31,8 % im Jahr 2019 auf 35,3 % im Jahr 2020. In beiden Jahren hatten 71 % der Patienten einen Patient Comorbidity Score von 0. Schlussfolgerung: Der Vergleich der gemeldeten Endophthalmitis-Fälle zeigte, dass die Anzahl der erfassten Fälle im Covid-Jahr 2020 gegenüber zum Jahr 2019 (vor der Pandemie) um 9 % zurückging. Da keine exakten Angaben zur Gesamtzahl der intraokularen Eingriffe in diesen Zeiträumen vorliegen, kann die Inzidenz der Endophthalmitis vor und während der Pandemie nicht zuverlässig ermittelt werden. Aus den vorliegenden Daten ist jedoch ersichtlich, dass der Anteil der älteren Patienten (>80 Jahre) im Jahr 2020 zunahm, was die Alterszunahme der versorgten Patienten in der Augenheilkunde wiederspiegelt.

Fragestellung: Bisher wurde noch keine Studie zur Häufigkeit von okulären Traumata in Deutschland verfasst. Ziel dieser Studie ist es die Prävalenz okulärer Traumata in Deutschland zu erfassen und den Effekt, den die Covid-19 Pandemie, darauf hatte. Methodik: Die gewonnenen Daten basieren auf dem DRG- System (Diagnosis Related Group) mit dem ICD- 10 Code S05.0-9 und schließen alle stationär behandelten Patienten vom 01.01.2019 bis 31.12.2020 ein. Eine weitere Analyse bezüglich Alter, Geschlecht, Dauer der Hospitalisierung, PCCL (Patient Clinical Complexity Level) und Ursache des Traumas wird noch erfolgen. Es liegen bereits erste Auswertungen zur Traumaursache vor. Ergebnisse: Im Jahr 2019 ereigneten sich in ganz Deutschland 4636 Traumata im Bereich der Orbita und des Auges. Dieser Wert sank im darauffolgenden Jahr 2020 auf 3943 ab. Dies entspricht einer Abnahme von 14,9 %. Dabei machten Männer einen Anteil von 74 % der Fälle aus. Die durchschnittliche Verweildauer im Krankenhaus betrug 4,1 Tage, sowohl im Jahr 2019 als auch 2020. 80 % dieser Patienten hatten einen PCCL von 0. Die Streuung des Alters zeigte eine zweigipflige Verteilung. Der eine Gipfel lag im Alter von 18 bis 29 Jahren, der andere bei 80 Jahren. Am häufigsten führten die Verletzungsmechanismen zu einer Contusio bulbi. Die Häufigkeit dieser Prellungen sank bemerkenswerterweise von 1597 im Jahr 2019 auf 1185 im Jahr 2020 ab. Dies entspricht einer Abnahme von 26 %. Des Weiteren nahmen Rissverletzungen und Rupturen des Auges mit Prolaps oder Verlust von intraokulärem Gewebe um 11 % ab. Interessanterweise stieg dagegen die Zahl der penetrierenden Verletzungen der Orbita mit Fremdkörpern um 10 %. Schlussfolgerungen: Die Häufigkeit von okulären Traumata in Deutschland wurde signifikant von der Covid-19 Pandemie beeinflusst. Dies zeigte sich in erster Linie durch eine Abnahme der Gesamtzahl der Verletzungen. Interessanterweise nahmen jedoch die penetrierenden Augenverletzungen zu. Weitere Studien müssen durchgeführt werden, um die Ursache dafür zu finden.

Fragestellung: Bestimmung der Enukleationsrate in Deutschland und der Auswirkungen, die die Covid-19-Pandemie auf Ihr gehabt haben könnte. Methodik: Die Enukleationsraten in Deutschland in den Jahren 2019 und 2020 wurden aus dem Diagnosis Related Group (DRG) Register unter die Operationen- und Prozedurenschlüssel 5-163.0 bis 5-163.23 und 5-163.x extrahiert. Die Daten wurden statistisch ausgewertet. Ergebnisse: Die Anzahl der Enukleationen zeigte eine Verringerung um 16,6 % von 1295 Fällen im Jahr 2019 im Vergleich zu 1080 Fällen im Jahr 2020 (p = 0,17). In beiden Jahren waren durchschnittlich 54,1 % der Fälle Männer. Patienten, die älter als 65 Jahre sind, machten 53 % bzw. 56 % der Fälle in den Jahren 2019 und 2020 aus. Die häufigste Indikation zur Enukleation war in beiden Jahren Phthisis bulbi (n = 373 bzw. n = 307) mit 29,7 % der Fälle, gefolgt von Malignomen der Aderhaut (24 %). Die Enukleation mit gleichzeitigem Einbringen eines alloplastischen Augenhöhlenimplantats in die Tenonkapsel stellte das häufigste Verfahren dar (38,7 % kombinierter Zweijahresdurchschnitt), gefolgt von einer umhüllten Variante (26,6 %) und einem bulbären Implantat aus nicht resorbierbaren mikroporösen Materialien (16,8 %), ohne signifikante Veränderung zwischen den Jahren. Enukleationen ohne Implantation stiegen von 7,8 % im Jahr 2019 auf 11,1 % im Jahr 2020 (p = 0,006). Der Anteil der Patienten, die sich einer Re-Operation unterziehen, stieg leicht von 5,6 % auf 8 % (p = 0,018). Die meisten Eingriffe (65,6 %) wurden in großen öffentlichen Krankenhäusern (≥1000 Betten) durchgeführt. Schlussfolgerungen: Trotz des Rückgangs der Gesamtzahl der durchgeführten Eingriffe wurde die Enukleationsrate in Deutschland durch die Covid- 19-Pandemie nicht signifikant verändert. Die Enukleationsrate ohne Implantate und Reoperationen nahm signifikant zu.

Aim: Retinal detachment (RD) is an ophthalmic emergency. Few studies addressed its incidence in the whole world. A recent study from Germany tried to estimate its incidence in a group of patients between 35 and 74 years of age in the city of Mainz. In our study, we aim to present the incidence of RD in the whole population in Germany, studying the trends and incidence per different age groups. Methods: We have analyzed the DRG records made by the institute for the hospital remuneration system and provided by the German federal statistics office. The data were collected using ICD- 10 H33.0, H33.2, and H33.4 for rhegmatogenous, serous, and tractional RD respectively. The files spanned the period between 2005 and 2019. We have calculated the crude and age-standardized incidence rates per 100,000 persons. We have analyzed the age and sex distributions, length of stay, patient comorbidity score, and geographical distribution. Results: We have analyzed the files of 389,138 admissions due to RD between 2005 to 2019. The number of admissions with all types of RD together increased from 20,457 in 2005, to 31,522 in 2019. This represented an increase in the crude incidence rate of RD from 25.1 to 37.7 per 100,000 respectively. The fraction of rhegmatogenous RD increased from 68% in 2005 to 76% in 2019. In General, the Age group of 70 to 74 showed the highest age-standardized incidence rate, however, this pattern was not the same for the whole study period. Interestingly, our study discovered a shift in the peak case numbers from the age group of the late sixties in 2005 to the late fifties/early sixties in 2019. The fraction of men diagnosed with rhegmatogenous RD increased from 59.15% in 2005 to 64.3% in 2019. The tractional type of RD showed a similar pattern. Apart from Bremen, all the federal stats showed an increase in the incidence rates over the study period. The duration of admission decreased from around 6 days in 2005 to 3.4 in 2019. In 2019, the reoperation rate was 12.2 % in rhegmatogenous RD, compared to 14.14 % in serous, and 21.2 % in tractional RD. Patients’ comorbidity conditions were favorable in rhegmatogenous RD, while they were least favorable in tractional disease. Conclusion: The incidence of RD increased in Germany over the study period. The incidence rates also increased with age until the age group of the late sixties then declined again. The regulations enforced by the remuneration system resulted in decreasing the admission duration.

PURPOSE To calculate the overall incidence of uveal melanoma in Germany and to compare incidences in different German states. In addition, we computed the overall and cancer-specific survival rates nationwide. METHODS Incidence data for the period between 2009 and 2015, covering the entire German population, was collected through the German Center for Cancer Registry. ICD-O-3 topography codes C69.3-C69.4 and histology codes for melanoma subtypes were used to collect the incidence data. Confidence Intervals with a level of 95% (95% CI) were calculated for rates. Survival was calculated using the Kaplan-Meier. The log-rank test was used for survival comparisons. RESULTS This study comprised 3654 patients with uveal melanomas, including 467 (12.8%) with iridial and ciliary body tumors. The overall age-standardized incidence rate (ASIR) was 6.41 person per million. Generally, the ASIR was higher in males than females (6.67 (95% CI 6.37-6.98) vs. 6.16 (95% CI 5.88-6.45 per million). Higher crude incidence rates were noted in the northeastern states (12.5 per million (95% CI 10.5-14.7) in Mecklenburg-Vorpommern) compared with the southwestern states (2.1 per million (95% CI 1.7-2.6) in Hessen). The 5-year overall survival stood at 47%, while the cancer-specific survival stood at 84%. Multivariate analysis showed that women, younger patients, and patients living in Berlin achieved significantly higher overall survival. CONCLUSION Overall ASIR of uveal melanoma in Germany indicates that the disease is more common in males and that it follows the same geographical distribution previously noted in central European countries, with the highest incidence in northern parts of Germany.

PURPOSE The eye and its adnexal structures can give rise to first or consecutive primary malignancies or to encounter metastasis. Our aim was to define the characteristics of the second primary neoplasms affecting the eye and its adnexa and find the risk modifying factors for them after malignancies elsewhere in the body. METHODS We have queried the Surveillance, Epidemiology and End-Results "SEER"-9 program of the National Cancer Institute for the malignancies of the eye and its adnexa that occurred between 1973 and 2015. The malignancies were ordered chronologically according to their incidence: first or second primary malignancies. The tumors were classified according to ICD-O-3 classification. Standardized incidence ratios (SIR) and survival probabilities were calculated for subgroups. RESULTS Among 3,578,950 cancer patients, 1203 experienced a second malignancies of the eye and its adnexa. The first malignancy was diagnosed between 50 and 69 years of age in 58.94% of them. The eyelid showed 280 events, while 50 in lacrimal gland, 181 in the orbit, 21 in the overlapping lesions, 15 in optic nerve, 148 in the conjunctiva, 9 in the cornea, 6 in the Retina, 379 in the choroid, and 93 in the ciliary body. The SIR of a second malignancy after a prior non-Hodgkin lymphoma was 2.42, and in case of previous skin carcinomas it was 3.02, melanoma of skin, and 2.13 and 1.58 in oral cavity/pharynx malignancies. The second ocular and adnexal neoplasms increased steadily over the 5-year periods on contrary to first primary neoplasms. The survival of patients affected with first ocular and adnexal neoplasms was significantly higher than those with second ocular and adnexal neoplasms. On the other side, second primary ocular and adnexal tumors showed a better survival than second primary malignancies elsewhere. CONCLUSIONS The epidemiological differences between first and second ocular and adnexal primaries suggest different underlying mechanisms. Careful ocular examination should be integrated in the long-term follow-up plan of cancer patients. Special attention should be given to patients with non-Hodgkin's lymphoma and melanoma as first primary.

BACKGROUND Uveal melanoma (UM) is the most common primary ocular malignancy of adults. A small group of patients was found to express familial predisposition. Moreover, it may be preceded or followed by other malignancies elsewhere in the body. We aim to compare the incidence of UM and other associated cancers and study the factors that may influence each condition. PATIENTS AND METHODS We have collected the data from the Surveillance, Epidemiology and End Results database of nine US cancer registries for UM patients between 1973 and 2015. We calculated the standardised incidence ratios for single primary UM, first primary and second primary UM, and compared the groups for multiple factors. RESULTS A total of 4946 patients were included in the study; 3863 with single primary UM, 646 developed a second primary malignancy following UM, and 437 patients developed second primary UM following a previous primary malignancy. The risk of developing UM increased after leukaemia, melanoma of the skin and prostate. On the other side, the risk of developing melanoma of the skin, thyroid, renal and other eye and orbit malignancies has increased significantly after initial UM. This risk was more evident in the age group between 50 and 70 years old. Cancer-specific survival was significantly higher in UM associated with other malignancies group compared with single primary UM. CONCLUSION Our study showed a different behaviour of the UM when associated with other tumours that exceed the known spectrum of hereditary UM. Further studies are required to dissect the genetic background of this behaviour.

This cohort study examines outcomes of patients with brain cancer to provide demographic details on the increase in suicide rate after brain cancer diagnosis.

Adrenocortical carcinoma (ACC) is a rare, aggressive endocrine neoplasm. Complete surgical resection is the single most important treatment. Most available information has been learned from experience with its more frequent adult counterpart. In this study, we assessed the features and survival outcome of patients with ACC at Children's Cancer Hospital Egypt (CCHE). Patients diagnosed at CCHE between July 2007 and November 2016 were followed up on until November 2018. Patients with stages I and II were operated upon, while stages III and IV had received combinations of doxorubicin, etoposide, platinol, and mitotane (DEPM) beside the attempt to conduct surgery when feasible. Data belonging to 18 patients (7 men and 11 women) were analyzed; median age at diagnosis was 48.5 months. Sixteen patients had presented with secreting tumors. Six patients were diagnosed with stage I disease; four with stage II; three with stage III; and five with stage IV carcinoma. By the end of this study, 10 patients have survived; five-year overall survival of 66.3%. Surviving patients were all of stage I or II diseases and were all in remission. Seven patients who did not survive died due to tumor progression, while one patient died after chemotherapy. The prognosis of ACC is essentially dependent on a successful complete resection of the tumor and thus on the initial tumor stage. The mitotane and DEP protocols may help control tumor growth in the advanced stages for only short periods. Key pointsInitial stage and resectability are the main indicators of outcomes in adrenocortical carcinoma.Chemotherapeutic agents used in developed countries did not achieve the same outcomes.Further molecular-pharmacology differentiation is needed for various ethnic populations.

The BEST1 gene product bestrophin-1, a Ca2+ -dependent anion channel, interacts with CaV 1.3 Ca2+ channels in the retinal pigment epithelium (RPE). BEST1 mutations lead to Best vitelliform macular dystrophy. A common functional defect of these mutations is reduced trafficking of bestrophin-1 into the plasma membrane. We hypothesized that this defect affects the interaction partner CaV 1.3 channel affecting Ca2+ signaling and altered RPE function. Thus, we investigated the protein interaction between CaV 1.3 channels and bestrophin-1 by immunoprecipitation, CaV 1.3 activity in the presence of mutant bestrophin-1 and intracellular trafficking of the interaction partners in confluent RPE monolayers. We selected four BEST1 mutations, each representing one mutational hotspot of the disease: T6P, F80L, R218C, and F305S. Heterologously expressed L-type channels and mutant bestrophin-1 showed reduced interaction, reduced CaV 1.3 channel activity, and changes in surface expression. Transfection of polarized RPE (porcine primary cells, iPSC-RPE) that endogenously express CaV 1.3 and wild-type bestrophin-1, with mutant bestrophin-1 confirmed reduction of CaV 1.3 surface expression. For the four selected BEST1 mutations, presence of mutant bestrophin-1 led to reduced CaV 1.3 activity by modulating pore-function or decreasing surface expression. Reduced CaV 1.3 activity might open new ways to understand symptoms of Best vitelliform macular dystrophy such as reduced electro-oculogram, lipofuscin accumulation, and vision impairment.

Changes in cell function occur by specific patterns of intracellular Ca2+, activating Ca2+-sensitive proteins. The anoctamin (TMEM16) protein family has Ca2+-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca2+-dependent phosphatidyl-scramblase activity. Using amino acid sequence analysis combined with measurements of ion channel function, we clarified the so far unknown Ano4 function as Ca2+-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca2+ activated conductance with weak selectivity of K+ > Na+ > Li+ . Endogenously expressed Ca2+-dependent cation channels in the retinal pigment epithelium were identified as Ano4 by KO mouse-derived primary RPE cells and siRNA against Ano4. Exchanging a negatively charged amino acid in the putative pore region (AA702-855) into a positive one (E775K) turns Ano4-elicited currents into Cl– currents evidencing its importance for ion selectivity. The molecular identification of Ano4 as a Ca2+-activated cation channel advances the understanding of its role in Ca2+ signaling.

BACKGROUND Glioblastoma multiforme (GBM) patients with a prior malignancy are usually excluded from clinical trials on GBM based on the assumption that this history will affect their survival outcomes. This practice may affect clinical trial accrual and limit the gathering of knowledge essential to the formulation of therapeutic options for this patient population. However, not much is known about the real impact of these prior malignancies on the survival of patients with subsequent GBM. We aimed to investigate the degree of such an impact. PATIENTS AND METHODS We used the Surveillance, Epidemiology, and End Results (SEER) Program to analyze data of GBM patients diagnosed between 1973 and 2014. We calculated the overall and GBM-specific survival of these patients using the unadjusted Kaplan-Meier test and the multivariable covariate-adjusted Cox models. RESULTS Of 51,158 GBM patients, 3,076 had a prior malignancy. The unadjusted Kaplan-Meier test showed worse overall and GBM-specific survivals for patients who had a prior history of cancer. However, after adjusting for age at diagnosis of GBM, sex, race, marital status, and the conduction of surgery as treatment for GBM, no significant difference was found between both overall and GBM-specific survivals of patients without and without a prior history of cancer (HR =1.025, 95% CI =.986-1.066, P=.213 and HR =1.005, 95% CI =.963 - 1.049, P=.810, respectively). CONCLUSIONS Our findings suggest that the broad practice of excluding patients with a prior history of cancer should be reconsidered as it may adversely affect accrual, trial completion rates, and generalizability of the results.

BACKGROUND The suicide risk after a new cancer diagnosis remains a controversial issue. This study examines the suicide risk within the year after a cancer diagnosis. This is the largest study to assess recent trends in suicide risk after a cancer diagnosis. METHODS Data were obtained from the Surveillance, Epidemiology, and End Results Program. All patients diagnosed with cancer between 2000 and 2014 were selected. The event was defined as death due to suicide within the first year after a cancer diagnosis, and patients who experienced the event after their diagnosis were observed. The observed/expected (O/E) ratio was assessed as well as the excess risk per 10,000 person-years to determine the suicide risk change after the diagnosis in comparison with the general population. RESULTS A total of 4,671,989 patients with cancer were included; 1585 committed suicide within 1 year of their diagnosis. The risk of suicide increased significantly with an O/E ratio of 2.52 and with an excess risk of 2.51 per 10,000 person-years. When the risk of suicide was studied according to the cancer site, the highest increases in the O/E ratio came after diagnoses of pancreatic cancer (8.01) and lung cancer (6.05). The risk of suicide also increased significantly after a diagnosis of colorectal cancer with an O/E ratio of 2.08. However, the risk of suicidal death did not increase significantly after breast and prostate cancer diagnoses. CONCLUSIONS The risk of suicide increases significantly in the first year after a diagnosis of cancer in comparison with the general population, and this increase varies with the type and prognosis of cancer. Close observation and referral to mental health services, when indicated, are important for mitigating such risk.

PURPOSE Advances in cancer treatment achieved during the past decades have resulted in increased survival of most pediatric and adult patients that suffered from different adrenal tumor types. This article reviews the incidence and survival of adrenal gland tumors as second primary tumors, according to data from the Surveillance, Epidemiology, and End Results (SEER) database. METHOD The SEER 13 Registries Database from 1992 to 2013 was used. All primary cancer sites were selected using the Multiple Primary Standardized Incidence Ratios (MP-SIR) session. RESULTS Data for a total of 2,887,468 persons with cancer were reviewed. 117 of whom had suffered second primary adrenal tumors. The overall standardized incidence ratio (SIR) of adrenal gland tumor as a second primary was 1.49. A high incidence ratio of the event was also detected in specific primary tumor sites: hypopharynx (Observed/Expected(O/E) = 44.59); other endocrine tissue (including the thymus) (O/E=38.27); chronic myeloid leukemia (O/E=11.15); small intestine (O/E=8.86); liver (O/E=8.74); stomach (O/E=4.95); nodal NHL (O/E=3.79); kidney and renal pelvis (O/E=3.19); and breast (O/E=1.78). CONCLUSION The underlying shared mechanisms should be investigated between adrenal tumors and hypopharyngeal, endocrine and other tumors. Racial disparity is an important challenge in cancer treatment at US and should be taken into consideration in the design of cancer prevention programs. This could be achieved through follow-up programs at specialized national cancer networks, especially for rare tumors like adrenal gland.

BACKGROUND Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5-3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors. METHODS The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier. RESULTS Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR = 1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR = 33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR = 24.53)*** and the kidneys (SIR = 5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR = 4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%). CONCLUSIONS Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

PURPOSE Incidence of BS primitive neuroectodermal tumors (BS-PNET) in children is not reported to date. Our main objectives were to estimate the incidence and report the outcome of BS-PNET in children. METHODS Data were collected using the Surveillance Epidemiology and End Results cancer registry. RESULTS From 1973 to 2013, we identified 83 pediatric patients (aged 0-21 years). Patients were divided into two age groups (0-3 years and 4-21 years). Median overall survival was 53 months. Patients in the older age group had a significant survival advantage (P < 0.001), as did those who received three modalities of therapy (surgery, chemotherapy, and radiation therapy) (P < 0.001) and patients with gross or subtotal tumor resection (P < 0.001). CONCLUSIONS This study presents the first estimate of incidence and the largest cohort of pediatric BS-PNETs to date. A high index of suspicion of BS-PNET in similar cases is crucial for diagnosis, treatment, and outcome.

Clinical research is an integrated part of medical education. There is a noticeable decrease in the number of physician-scientists in developing countries, which is reflected by a decrease in research output and publications from these countries. We conducted a survey aiming to identify the gaps in clinical research training from the perspective of medical students. The results can be used to customize future clinical research trainings. The survey tool was divided into six modules which represent the cornerstones of clinical research based on similar surveys done for the same purpose. For each module, questions covered the perceived knowledge of its aspects and how much relevant the responder thought it was to clinical research. Five hundred one candidates have filled the survey. Evidence-based medicine (EBM) had the highest knowledge score of 2.20/4, while "clinical trials execution" knowledge got the lowest score of 1.64/4. Responders perceived EBM as the most relevant aspect of clinical research (3.39/4), while research ethics received the lowest score 3.18/4. "Clinical trials execution" had the largest gap of a difference calculated as 1.60, while EBM had the lowest gap of 1.20. More attention must be paid to clinical research training for medical students in developing countries. These trainings have to be customized to focus on clinical trial execution, research methodology, and biostatistics. In parallel, awareness campaigns targeted toward the medical community emphasizing the importance of the ethics as an aspect of clinical research should be established.

BACKGROUND Retinoblastoma poses a substantial burden in developing countries. We conducted this study to assess the effect of implementing a multidisciplinary approach and standardized protocols for treating pediatric patients with retinoblastoma at the Children's Cancer Hospital Egypt (CCHE). MATERIALS AND METHODS In January 2011, the CCHE implemented standardized protocols for the diagnosis, treatment, and reporting of retinoblastoma cases. The hospital also introduced a new retinoblastoma management algorithm and data analysis system. In this study, we compared the pathologic features, tumor invasiveness, reporting, and survival of 276 pediatric patients who underwent enucleations of 290 eyes before or after the implementation of the retinoblastoma protocols. RESULTS Time to enucleation (indicating time needed for decision taking) decreased significantly within the neoadjuvant chemotherapy group for intraocular disease after January 2011 (68.7 ± 48 weeks vs. 47.3 ± 28.3 weeks; p < 0.05). Mean optic nerve stump length increased from 5.6 mm in the earlier period to 7.2 mm in the later period (p = 0.004). The overall quality of pathology reporting also improved during the later period. The probability of 3-year survival was significantly higher for patients during the later period (94.2% vs. 79.2%; p = 0.018). CONCLUSIONS The implementation of standardized protocols and a multidisciplinary approach improved reporting; discrepancies in disease classification and the amount of missing data were reduced; and quality measures and prognostic capabilities of the team were substantially improved. Such established data-driven practice supports faster decision making to enucleate diseased eyes and save patients' lives through providing measurable indicators.

Neonatal tumors are rare with no standard treatment approaches to these diseases, and the patients experience poor outcomes. Our aim was to determine the distribution of cancers affecting neonates and compare survival between these cancers and older children. We analyzed SEER data (1973-2007) from patients who were younger than 2 years at diagnosis of malignancy. Special permission was granted to access the detailed (i.e., age in months) data of those patients. The Chi-square Log-rank test was used to compare survival between neonates (aged <1 month) and older children (>1 month to <2 years). We identified 615 neonatal cancers (454 solid tumors, 93 leukemia/lymphoma, and 68 CNS neoplasms). Neuroblastoma was the most common neonatal tumor followed by Germ cell tumors. The 5-year overall survival (OS) for all neonates was 60.3% (95% CI, 56.2-64.4). Neonates with solid tumors had the highest 5-year OS (71.2%; 95% CI, 66.9-75.5), followed by those with leukemia (39.1%; 95% CI, 28.3-49.9) or CNS tumors (15%; 95% CI, 5.4-24.6). Except for neuroblastoma, all neonatal tumors showed inferior outcomes compared to that in the older group. The proportion of neonates who died from causes other than cancer was significantly higher than that of the older children (37.9% vs. 16.4%; P < 0.0005). In general, the outcome of neonatal cancers has not improved over the last 34 years. The distribution of neonatal cancer is different than other pediatric age groups. Although the progress in neonatal and cancer care over the last 30 years, only death from noncancer causes showed improvement. Studying neonatal tumors as part of national studies is essential to understand their etiology, determine the best treatment approaches, and improve survival and quality of life for those patients.

Childhood adrenocortical carcinoma (ACC) is a rare tumor and its association with acute lymphoblastic leukemia (ALL) is even rarer. One such case is discussed in this case report. A 3-year-old patient was concomitantly diagnosed with ALL and an initially nonmetastatic ACC. Management started by following the Total XV protocol without a window phase. Left adrenalectomy was conducted after the consolidation phase. Recurrence of a mass at the tumor bed was discovered at week 33 of the continuation phase. Reexcision was conducted, followed by the administration of an ACC protocol including cisplatin, etoposide, and doxirubicin. Mitotane was added when a pulmonary metastasis was discovered and then stopped after the patient suffered from an arachnoid cyst and speech difficulties. The ALL protocol was resumed from week 34 of the continuation phase. Progression of pulmonary nodules was noted after week 45. A pulmonary metastectomy was performed. The ALL protocol was resumed up to week 51 with a good response as proven by assessment of minimal residual disease. A further recurrence was diagnosed at the abdominal tumor bed with a paravertebral mass and a pulmonary nodule. The patient was assigned to palliative treatment and died after a 32-month survival. Such rare associations need more extensive discussions of the best possible management in scientific literature.

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients' awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.