Successful treatment of a solitary skull metastasis in a child with Wilms' Tumor

This report presents the successful treatment of a child with a solitary metastatic lesion to the calvarium following treatment for Stage III anaplastic Wilms’ Tumor

Physical Examination is the Best Predictor of the Need for Abdominal Surgery in Children Following Motor Vehicle Collision

BACKGROUND: Exploratory laparotomy in children after motor vehicle collision (MVC) is rare. In the absence of definitive hemorrhage or free abdominal air on radiographic imaging, predictors for operative exploration are conflicting. OBJECTIVE: The purpose of this study was to explore objective findings that may aid in determining which children require operative abdominal exploration after MVC. METHODS: Data from 2010-2014 at an American College of Surgeons-certified level 1 pediatric trauma center were retrospectively reviewed. Demographics, vital signs, laboratory data, radiologic studies, operative records, associated injuries, and outcomes were analyzed and p < 0.05 was considered statistically significant. RESULTS: Eight hundred sixty-two patients 0-18 years of age presented to the hospital after an MVC during the study period. Seventeen patients (2.0%) required abdominal exploration and all were found to have intraabdominal injuries. Respiratory rate was the only vital sign that was significantly altered (p = 0.04) in those who required abdominal surgery compared with those who did not. Physical examination findings, such as the seat belt sign, abdominal bruising, abdominal wound, and abdominal tenderness, were present significantly more frequently in those requiring abdominal surgery (p < 0.0001). Each finding had a negative predictive value for the need for operative exploration of at least 0.98. There were no significant differences in trauma laboratory values or radiographic findings between the 2 groups. CONCLUSION: Data from this study solidify the relationship between specific physical examination findings and the need for abdominal exploration after MVC in children. In addition, these data suggest that a lack of the seat belt sign, abdominal bruising, abdominal wounds, or abdominal tenderness are individually predictive of patients who will not require surgical intervention

Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)

INTRODUCTION: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC. METHODS: One hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at \u3c40 or breast cancer \u3c50 years of age). RESULTS: Frequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants. CONCLUSION: Type and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies

Identification of Neoantigen-Reactive Tumor-Infiltrating Lymphocytes in Primary Bladder Cancer

Immune checkpoint inhibitors (ICIs) are effective in treating a variety of malignancies, including metastatic bladder cancer. A generally accepted hypothesis suggests that ICIs induce tumor regressions by reactivating a population of endogenous tumor-infiltrating lymphocytes (TILs) that recognize cancer neoantigens. Although previous studies have identified neoantigen-reactive TILs from several types of cancer, no study to date has shown whether or not neoantigen-reactive TILs can be found in bladder tumors. To address this, we generated TIL cultures from patients with primary bladder cancer and tested their ability to recognize tumor-specific mutations. We found that CD4+ TILs from one patient recognized mutated C-terminal binding protein 1 (CTBP1Q277R) in an MHC class II-restricted manner. This finding suggests that neoantigen-reactive TILs reside in bladder cancer, which may help explain the effectiveness of immune checkpoint blockade in this disease, and also provides a rationale for the future use of adoptive T-cell therapy targeting neoantigens in bladder cancer

Ovarian fibrothecoma in an adolescent: A case report

Introduction: Ovarian fibrothecoma is a rare subtype of ovarian sex-chord stromal tumor canonically described in peri-menopausal and post-menopausal women. There have been some cases reported in young adults; however, there have not been any cases documented in the adolescent patient population. Case report: We present the youngest recorded case of an ovarian fibrothecoma. A 13 year old female presented with pelvic pain and non-specific symptoms. Diagnostic workup showed a mixed-density ovarian mass and tumor markers within normal limits. A right ovarian mass was resected without complication. The final pathology revealed a fibrothecoma. Conclusion: This case identifies a new type of ovarian mass that can present in adolescents and should be considered during the workup for adolescents with ovarian masses