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The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes ( NR5A2 , MED1 , NCOA2 and RUNX1 ) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10 −5 ) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.

Introduction: Cardiac rhabdomyomas represent a frequent manifestation of tuberous sclerosis. Tumor growth, mainly prenatally, can result in intrauterine fetal or neonatal deaths in almost 10% of patients. Case Report: We treated 3 consecutive infants aged less than 12 months with sirolimus, an oral mTOR inhibitor. All patients achieved significant reductions in cardiac rhabdomyomas. A complete response was documented in 2 patients, while a partial response with tumor debulking greater than 50% was seen in the other one. The median time to best cardiac response was 1.9 months in all patients, and 3.3 months in those with complete response. The side effects profile was acceptable. Conclusion: Sirolimus may have a significant role in promoting natural regression of cardiac rhabdomyomas. Prospective clinical trials are needed.

Background The incidence of gemcitabine-induced hemolytic uremic syndrome has already been described in adults. Several approaches have been employed in the treatment of gemcitabine-induced hemolytic uremic syndrome with different outcomes. One of the most promising agents is eculizumab, which is a monoclonal antibody directed against C5 complement protein. Case presentation We reported the case of a 3-year-old white boy with medulloblastoma who underwent high-dose chemotherapy and craniospinal irradiation. Afterwards he started maintenance chemotherapy with gemcitabine and oxaliplatin. After five courses he presented a progressive clinical worsening, which resulted in a systemic thrombotic microangiopathy. Initially he was treated with rituximab without clinical improvement. Therefore he started therapy with repeated cycles of eculizumab. After seven infusions he showed a gradual improvement and finally a complete remission of gemcitabine-induced hemolytic uremic syndrome. Conclusions Eculizumab prevents serious complement-mediated vascular damage for chemotherapy-induced thrombotic microangiopathy in pediatric cases.

Modern immunotherapy with checkpoint inhibitors has changed clinical practice of adult patients with advanced cancer. Blockade of CTLA-4 and PD-1 pathways have shown survival benefits in different diseases. In children, combination of surgery, radiotherapy and chemotherapy have improved survival rates of solid tumors. However, the outcomes for subsets of patients such as those with high-grade, refractory, or metastatic disease remain extremely poor. Currently, the treatment of these patients is almost exclusively based on standard chemotherapy. The significant proportion of pediatric cancers with high number of mutations and subsequent high expression of neoantigens, together with the potential prognostic role of the immunosuppressive checkpoint molecules (CTLA-4, PD-L1) can represent a promising rationale that support the use of checkpoint inhibitors. We made a revision about emerging data regarding safety and activity of checkpoint inhibitors in children with solid tumors.

Despite some advances, the search for effective treatment modalities for advanced gastric and gastro-esophageal junction cancer (GEJC) is far from over. However, using biologic agents to target key molecular pathways, such as those regulated by human epidermal growth factor receptor (HER) family members, may be an effective approach. This Review briefly describes HER biology, summarizes available data regarding the clinical activity of anti-HER agents and their use in gastric cancer and GEJC, and provides insight into treatment personalization strategies. Despite some advances in the past few years, the search for effective treatment modalities for advanced gastric and gastro-esophageal junction cancer is far from over. Available data clearly demonstrate that the development of new drugs will have little, if any, chance of success if it is not guided by in-depth knowledge of disease biology. However, using biologic agents to target key molecular pathways, such as those regulated by human epidermal growth factor receptor (HER) family members, may be effective. Indeed, the positive results achieved by the anti-HER2 agent trastuzumab in a phase III trial in HER2-positive patients support this approach. Many new anti-HER molecules are now under evaluation for the treatment of gastric and gastro-esophageal junction cancer, but so far attempts to identify reliable predictive factors from phase I and II trials have produced inconclusive results. In addition, large phase III trials are still being conducted in molecularly unselected populations. Refining patient selection is essential to maximize the benefit of targeted agents, to avoid significant toxicities and for the development of alternative therapeutic approaches in patients who have nonresponsive disease. Key Points Human epidermal growth factor receptor (HER) family members are the target of multiple biologic agents currently under investigation for the treatment of gastric and gastro-esophageal junction cancer The combination of trastuzumab and chemotherapy has demonstrated improved efficacy compared with chemotherapy alone, paving the way for new treatment modalities in subsets of patients with gastric cancer Evaluation of HER2 status by immunohistochemistry or fluorescent in situ hybridization does not represent a definitive selection parameter for treatment, as not all HER2-positive patients respond to treatment Additional potential biomarkers for anti-HER2 therapies are still to be defined and may represent promising targets for novel therapeutics Many anti-EGFR (epidermal growth factor receptor) agents are at advanced stages of clinical development, but attempts to identify responsive patients on the basis of molecular parameters have been disappointing The development of biologic agents for use in highly selected patient subsets should represent a new paradigm for the treatment of gastric and gastro-esophageal junction cancer

Purpose In infants aged less than 12 months, there are few data on pharmacokinetics of high-dose methotrexate (MTX) for brain tumors at the dose of 8 g/m 2 . Consolidated knowledges are present only with the dose of 5 g/m 2 in acute lymphoblastic leukemia. Methods We collected data on 8 infants at the time of their first treatment with high-dose MTX, 8 g/m 2 , to evaluate the pharmacokinetic profile. All children had a dose adjustment with a weight-based prescription (1 m 2  = 30 kg). Results The median age was 4.5 months (range 0–9). The median weight was 5.63 kg (range 3.12–9.0). The median steady-state MTX concentration at the end of 6-hr infusion was 486 µM/L (range 227–790). The median systemic MTX clearance was 4.14 L/h/m 2 (range 1.98–9.35). The median MTX concentration after 24 h from the beginning of infusion was 3.29 µM/L (range 1.14–100.44). Three (37.5 %) patients had a delayed elimination of MTX (delayed early, delayed late, or total delayed: one for each). These altered elimination occurred principally in children weighing less than 4 kg ( p : 0.0179). Moreover, a systemic MTX clearance at the end of infusion minor than 3 L/h/m 2 can predict a delayed elimination ( p : 0.0179). Patients with altered elimination underwent rescue measures (leucovorin supplement and/or exchange transfusion). Conclusions Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg.

Background Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. Case presentation We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Conclusions Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

Despite the prevalence of pain among patients with cancer and the availability of pertinent guidelines, the clinical management of oncological pain is decisively insufficient. To address this issue, we evaluated current trends in clinical practice and subsequently generated a list of ten corrective actions-five things to do and five things not to do-for the diagnosis, management, and monitoring of cancer pain. The survey included 18 questions about clinical practice surrounding background pain and breakthrough cancer pain (BTcP). Survey questions were developed by a scientific board of 10 physician experts and communicated via email to an expanded panel of physicians in Italy. Responses were tabulated descriptively for analysis. Of 51 invited physicians, 32 (63%) provided complete survey responses. The responses revealed several incongruencies with current guideline recommendations: physicians did not always diagnose or monitor pain using diagnostically validated or disease-specific instruments; frequently based clinical decision-making on time availability or convenience; and pharmacological therapy was often inappropriate (eg, prescribing NSAIDs or corticosteroids for BTcP). The list of corrective actions generated by the scientific board favored a guideline-oriented approach that systematically characterizes oncological pain and implements treatment based on pain characteristics (eg, fast-acting transmucosal opioids for BTcP) and evidence-based recommendations. Oncologists require better education and training about the diagnosis, treatment, and monitoring of oncological pain. Physicians should be aware of current guideline recommendations as well as available pharmacological tools for BTcP.

According to the Chompret criteria, around 25% of families show a Li-Fraumeni-like syndrome (LFL) which includes the following: high-risk sarcoma, brain tumor, breast cancer and ACC before 36 years of age and cancer under the age 46 years in first- or second-degree relatives or multiple primary tumors, including two of the previous tumors or ACC at any age. There is a high prevalence of this tumor in the carriers of Brazil founder mutation TP53 R337H, which is present in 78-97% of children with ACC (10). [...]a more recent study demonstrated that the R337H mutation can be detected in families with a broad spectrum of LFS-associated cancers. Cerebrospinal fluid cytology was negative. [...]the patient underwent radiotherapy for a total dose of 59.4 Gy (1.8 Gy/fraction, five fractions per week) to the operative bed plus 2 cm margin. A better knowledge of the tumors associated with LFS could help to identify individuals who should be tested for the presence of germline TP53 mutation. [...]the characterization of germline TP53 mutation in a family may consent an early identification of high-risk subjects and provide the basis for a correct surveillance with an appropriate long-life monitoring clinical and psychosocial program.