Expression of Cytochrome P450 Enzymes in Pediatric Non-Rhabdomyosarcoma Soft Tissue Sarcomas: Possible Role in Carcinogenesis and Treatment Response.

The 5-year relative survival rate estimate of treated patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is ∼50% since they generally present with tumor progression, relapse, metastasis, and/or chemoresistance. The expression of cytochrome P450 (CYP) enzymes in malignancies can affect the pharmacology of drugs commonly used in chemotherapy or confer susceptibility to development of chemical carcinogenesis; in addition, their specific tumor expression can be used as a therapeutic target. Using qPCR and Western blot assays, the expression of CYP1B1, CYP2E1, CYP3A4, and CYP3A5 were analyzed in a cohort of tumor tissue paired with non-malignant adjacent tissue of patients with NRSTS. The mRNA and protein expression of CYP1B1, CYP2E1, and CYP3A4 were significantly increased in tumor tissue. We propose that the expression of these isoforms is related to carcinogenesis and chemoresistance frequently observed in these neoplasms.

Academic paediatric surgery and work-life balance: Insights from Mexico.

Academic pediatric surgery in Mexico has many challenges and opportunities. Work life balance, health service delivery and committements to our many students and residents must be tailored to goals and aspirations respecting talent at every opportunity when we encounter it. This article offers a perspective on the landscape and how we can shape the future in our nation to embrace new leadership in academic pediatric surgery.

Delivery of Pediatric Cancer Care in Mexico: A National Survey.

Purpose Limited data describe the delivery of pediatric cancer care in Mexico. We report a nationwide survey of pediatric cancer units. Methods An electronic survey was distributed to 74 pediatric cancer units in Mexico to describe case volumes; organization of care; and availability of medical/surgical specialists, supportive care, complex therapies, and diagnostic services. Centers were classified as low (< 30 new patients/year), medium (30 to 59/year) and high (≥ 60/year). Results Sixty-two centers completed the survey (response rate, 84%). The median annual new case volume per center was 50 (interquartile range [IQR], 23 to 81). Thirty-four percent (n = 21), 26% (n = 16), and 40% (n = 25) of units were low-, medium-, and high-volume centers, respectively. Treatment units reported a median of two pediatric oncologists (IQR, 2) and one pediatric hematologist (IQR, 1 to 2). Availability of medical and surgical subspecialists varied by center size, with substantially more specialist support at higher-volume centers ( P < .01). Multidisciplinary tumor boards are available at 29% (six of 21), 56% (nine of 16), and 76% (19 of 25) of low- to high-volume centers, respectively ( P = .005). Radiation and palliative care services are available at 42% (n = 26) and 63% (n = 36) of all centers, which did not vary by center volume. Educational support for hospitalized children and school reintegration programs are available at 56% (n = 36) and 58% (n = 36) of centers, respectively. One third (38% [n = 23]) of centers reported that at least one half of patients were lost to follow-up during the transition from pediatric to adult programs. Conclusion A large variation exists in annual case volumes across Mexican pediatric cancer centers. Additional efforts to increase access to multidisciplinary, supportive, and palliative care across all pediatric cancer units in Mexico are required.

MDR1 not CYP3A4 gene expression is the predominant mechanism of innate drug resistance in pediatric soft tissue sarcoma patients.

BACKGROUND: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) prior to drug treatment and their role in innate resistance remain unclear. OBJECTIVE: The aim of this study was characterize MDR1 and CYP3A4 expression pattern before to chemotherapy and its clinical implication in pediatric STS. METHODS: In this prospective study we analyzed MDR1 and CYP3A4 mRNA expression in both normal and tumor tissues from 28 newly diagnosed STS pediatric and then compared with patients' clinical-pathological data, including chemotherapy response. RESULTS: Our data showed that the expression of the MDR1 gene was significantly higher in malignant tissue than in the normal tissues of patients with STS. In addition, high MDR1 expression was significantly associated with local advances, as well as poor response to treatment. In contrast, CYP3A4 expression level was negligible in both tumoral and non-tumoral tissues. CONCLUSIONS: These results suggest that a significant mRNA level of MDR1 gene was intrinsically present in STS before exposure to chemotherapeutic drugs, suggesting that MDR1 may be important contributors of innate chemoresistance of this tumor type.

The burden of childhood cancer in Mexico: Implications for low- and middle-income countries.

In Mexico, childhood cancer incidence and mortality have increased in the last decade. Through government actions since 2005, the Popular Medical Insurance (PMI) program for childhood cancer was created. The objective of PMI was to offer early cancer diagnosis, standardized treatment regimens, and numerous pediatric oncology residency programs. It has also accredited 55 national hospitals for the care of these children. Current problems still present under the PMI include shortage of pediatric oncologists and nurses and high rate of abandonment of treatment. Our aim is to describe the current scenario of childhood cancer care in Mexico, especially from the perspective of the PMI and how it has impacted human resources, infrastructure, and medical education.

Descriptive Epidemiology in Mexican children with cancer under an open national public health insurance program.

BACKGROUND: All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide. METHODS: In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate. RESULTS: A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6. CONCLUSIONS: The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.

Hemoperitoneum: an unusual presentation of chronic granulocytic leukemia in a pediatric patient.

Chronic granulocytic leukemia (CGL) is a rare hematologic disease in pediatric patients. It usually presents with insidious symptoms. However, some cases may have an atypical presentation. We report herein the case of a 13-year-old female admitted to the emergency department with acute abdomen. She had hyperleukocytosis of 500.0 × 1000 cells/mm suggestive of CGL. A paracentesis was performed due to abdominal compartment syndrome that demonstrated hemoperitoneum. At laparotomy, a ruptured ovarian mass was found with multiple tumor implants in the serosal surface. Pathology revealed a CGL-infiltrated ovary. The patient is currently stable, has finished adjuvant chemotherapy, and is at 24 months of follow-up. To our knowledge, this is the first report of such a case.

Teratoma bilateral metacrónico. Salvamento de tejido ovárico: reporte de dos casos y revisión de la literatura / Metachronous bilateral teratoma: Ovarian tissue rescue two cases report and literature. Review

Los tumores de células germinales pertenecen al conjunto de neoplasias de origen no epitelial y que pueden presentar localización gonadal o extragonadal. Los teratomas son tumores compuestos por elementos derivados de dos o más capas embrionarias. Por lo común, su presentación es unilateral, aunque la presentación bilateral puede ser de hasta el 10% de los casos. La preservación ovárica es una técnica factible y útil, que permite tener una funcionalidad hormonal adecuada en pacientes en edad pediátrica que los presentan bilateralmente. Informamos dos casos clínicos en pacientes, una de 12 y la otra de 15 años de edad, con teratoma ovárico bilateral metacrónico, en las cuales se realizó salvamento del tejido ovárico. En la actualidad presentan niveles normales de producción hormonal, y para el futuro se espera la posibilidad de que sean fértiles gracias al tejido ovárico residual.

The germinal tumors belong to a group of non epithelial neoplasias which can have a gonadal or extragonadal localization. Teratomas are tumors which can have two or more embrionary layers its presentation is unilateral, but in 10% of the cases are bilateral. Ovary rescue is a feasible and useful technique in pediatric patients who present the bilateral form of the disease. In this paper we report two cases of pediatric patients, who developed a methacronic bilateral teratomas, one case of a 12 years old patient and the second one of a 15 years old girl, in both cases we performed ovarian tissue rescue. At the present time they have normal hormonal levels, and in the future they can probably be fertile thanks to the residual ovary tissue.

Hepatoblastoma. Clinical experience at a single institution using the Siopel staging system.

BACKGROUND: Staging in Hepatoblastoma has recently become controversial. In developing countries diagnosis occurs mostly in advanced stages under these circumstances, we propose another option that can be considered of prognostic value. METHOD: A retrospective analysis of cases diagnosed with Hepatoblastoma (HB), treated in a single Institution, in nine years was conducted. Chemotherapeutic regimens were analyzed, as well as the number of courses administered and response to treatment. RESULTS: Thirty-two patients were studied. Patients had symptoms from 1 to 25 weeks before diagnosis. SIOP stratification was used, finding 12 cases in PRETEXT II, 6 cases in PRETEXT III, and 14 cases in PRETEXT IV. No single case was identified in PRETEXT I. CONCLUSIONS: When comparing survival using the PRETEXT system, SIOP and our study showed marked differences. These results may not be comparable due to differences in tumor volume among the same PRETEXT stratification. We believe that tumor volume is related to prognosis.