Diagnostic Performance of Magnetic Resonance Imaging for Pediatric Ovarian Neoplasms: A Multi-Institutional Review.

STUDY OBJECTIVE: To assess the diagnostic performance of MRI to predict ovarian malignancy alone and compared with other diagnostic studies. METHODS: A retrospective analysis was conducted of patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals. Sociodemographic information, clinical and imaging findings, tumor markers, and operative and pathology details were collected. Diagnostic performance for detecting malignancy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for MRI with other diagnostic modalities. RESULTS: One thousand and fifty-three patients, with a median age of 14.6 years, underwent resection of an ovarian mass; 10% (110/1053) had malignant disease on pathology, and 13% (136/1053) underwent preoperative MRI. MRI sensitivity, specificity, PPV, and NPV were 60%, 94%, 60%, and 94%. Ultrasound sensitivity, specificity, PPV, and NPV were 31%, 99%, 73%, and 95%. Tumor marker sensitivity, specificity, PPV, and NPV were 90%, 46%, 22%, and 96%. MRI and ultrasound concordance was 88%, with sensitivity, specificity, PPV, and NPV of 33%, 99%, 75%, and 94%. MRI sensitivity in ultrasound-discordant cases was 100%. MRI and tumor marker concordance was 88% with sensitivity, specificity, PPV, and NPV of 100%, 86%, 64%, and 100%. MRI specificity in tumor marker-discordant cases was 100%. CONCLUSION: Diagnostic modalities used to assess ovarian neoplasms in pediatric patients typically agree. In cases of disagreement, MRI is more sensitive for malignancy than ultrasound and more specific than tumor markers. Selective use of MRI with preoperative ultrasound and tumor markers may be beneficial when the risk of malignancy is uncertain. CONCISE ABSTRACT: This retrospective review of 1053 patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals found that ultrasound, tumor markers, and MRI tend to agree on benign vs malignant, but in cases of disagreement, MRI is more sensitive for malignancy than ultrasound.

Use and Accuracy of Intraoperative Frozen Section Analysis for Ovarian Masses in Children and Adolescents.

STUDY OBJECTIVE: Describe the current practice patterns and diagnostic accuracy of frozen section (FS) pathology for children and adolescents with ovarian masses DESIGN: Prospective cohort study from 2018 to 2021 SETTING: Eleven children's hospitals PARTICIPANTS: Females age 6-21 years undergoing surgical management of an ovarian mass INTERVENTIONS: Obtaining intraoperative FS pathology MAIN OUTCOME MEASURE: Diagnostic accuracy of FS pathology RESULTS: Of 691 patients who underwent surgical management of an ovarian mass, FS was performed in 27 (3.9%), of which 9 (33.3%) had a final malignant pathology. Among FS patients, 12 of 27 (44.4%) underwent ovary-sparing surgery, and 15 of 27 (55.5%) underwent oophorectomy with or without other procedures. FS results were disparate from final pathology in 7 of 27 (25.9%) cases. FS had a sensitivity of 44.4% and specificity of 94.4% for identifying malignancy, with a c-statistic of 0.69. Malignant diagnoses missed on FS included serous borderline tumor (n = 1), mucinous borderline tumor (n = 2), mucinous carcinoma (n = 1), and immature teratoma (n = 1). FS did not guide intervention in 10 of 27 (37.0%) patients: 9 with benign FS underwent oophorectomy, and 1 with malignant FS did not undergo oophorectomy. Of the 9 patients who underwent oophorectomy with benign FS, 5 (55.6%) had benign and 4 (44.4%) had malignant final pathology. CONCLUSIONS: FSs are infrequently utilized for pediatric and adolescent ovarian masses and could be inaccurate for predicting malignancy and guiding operative decision-making. We recommend continued assessment and refinement of guidance before any standardization of use of FS to assist with intraoperative decision-making for surgical resection and staging in children and adolescents with ovarian masses.

Global Pediatric Surgery in the Era of COVID-19.

There is a tremendous unmet need regarding the surgical care of children in low- and middle-income countries. The rapid spread of coronavirus disease 2019 (COVID-19), and the resultant redistribution of health care resources required to combat it, has created even more unique difficulties in the provision of safe, timely, and affordable surgical care of children globally. The downstream effects of potential diminished surgical capacity may even more significantly affect the morbidity and mortality of children. The full effects of these changes are yet to be seen. The COVID-19 pandemic has also created unique opportunities that can be built on moving forward. It is critical that the focus on global surgical needs, particularly for children, continues to be a priority to mitigate the challenges caused by the COVID-19 pandemic. [Pediatr Ann. 2022;51(8):e316-e318.].

Laparoscopy versus laparotomy for pediatric ovarian dermoids.

BACKGROUND: With increased surgeon comfort using laparoscopy, we hypothesized resection of pediatric ovarian dermoids using laparoscopy would yield a shorter length of stay and no increase in morbidity or recurrence compared to laparotomy. METHODS: A retrospective review was performed amongst eleven pediatric hospitals. Patients aged 2 to 21 who underwent resection of an ovarian dermoid from 2010 to 2020 were included. Patient characteristics, operative details, and outcomes by approach were evaluated using Chi-squared and Wilcoxon-Mann tests. RESULTS: 466 patients were included, with a median age of 14.4 and median follow-up of 4.0 months. 279 patients underwent laparoscopy (60%), 139 laparotomy (30%), and 48 laparoscopy converted to laparotomy (10%). There were no differences in rates of tumor spillage by approach (p = 0.15). 65% underwent ovarian-sparing surgery and 35% underwent oophorectomy. Length of stay was significantly shorter amongst patients who underwent laparoscopy (1 day versus 2 days for laparotomy and converted, p<0.0001). There were no differences in rates of suspected recurrence or reoperation (p = 0.19 and p = 0.57, respectively). CONCLUSION: Patients who underwent laparoscopy experienced no differences in the rates of tumor spillage, recurrence, or reoperation and had a shorter length of stay compared to laparotomy. Laparoscopy is an acceptable approach for resection of pediatric ovarian dermoids.

Multi-Institutional Review of the Preoperative Diagnostic Accuracy for Pediatric Ovarian Mature Cystic Teratomas.

STUDY OBJECTIVE: To assess the preoperative imaging impression and surgeon diagnostic accuracy for pediatric ovarian mature cystic teratomas (MCTs) DESIGN: Retrospective review SETTING: Eleven pediatric hospitals PARTICIPANTS: Patients ages 2 to 21 who underwent surgical management of an ovarian neoplasm or adnexal torsion with an associated ovarian lesion INTERVENTION: None MAIN OUTCOME MEASURES: Preoperative imaging impression, surgeon diagnosis, tumor markers, and pathology RESULTS: Our cohort included 946 females. Final pathology identified 422 (45%) MCTs, 405 (43%) other benign pathologies, and 119 (12%) malignancies. Preoperative imaging impression for MCTs had a 70% sensitivity, 92% specificity, 88% positive predictive value (PPV), and 79% negative predictive value (NPV). For the preoperative surgeon diagnosis, sensitivity was 59%, specificity 96%, PPV 92%, and NPV 74%. Some measures of diagnostic accuracy were affected by the presence of torsion, size of the lesion on imaging, imaging modality, and surgeon specialty. Of the 352 masses preoperatively thought to be MCTs, 14 were malignancies (4%). Eleven patients with inaccurately diagnosed malignancies had tumor markers evaluated and 82% had at least 1 elevated tumor marker, compared with 49% of those with MCTs. CONCLUSIONS: Diagnostic accuracy for the preoperative imaging impression and surgeon diagnosis is lower than expected for pediatric ovarian MCTs. For all ovarian neoplasms, preoperative risk assessment including a panel of tumor markers and a multidisciplinary review is recommended. This process could minimize the risk of misdiagnosis and improve operative planning to maximize the use of ovarian-sparing surgery for benign lesions and allow for appropriate resection and staging for lesions suspected to be malignant.

Factors Associated with Torsion in Pediatric Patients with Ovarian Masses.

BACKGROUND: Management of ovarian torsion has evolved toward ovarian preservation regardless of ovarian appearance during surgery. However, patients with torsion and an ovarian neoplasm undergo a disproportionately high rate of oophorectomy. Our objectives were to identify factors associated with ovarian torsion among females with an ovarian mass and to determine if torsion is associated with malignancy. METHODS: A retrospective review of females aged 2-21 y who underwent an operation for an ovarian cyst or neoplasm between 2010 and 2016 at 10 children's hospitals was performed. Multivariate logistic regression was used to assess factors associated with torsion. Imaging data were assessed for sensitivity, specificity, and predictive value in identifying ovarian torsion. RESULTS: Of 814 girls with an ovarian neoplasm, 180 (22%) had torsion. In risk-adjusted analyses, patients with a younger age, mass size >5 cm, abdominal pain, and vomiting had an increased likelihood of torsion (P < 0.01 for all). Patients with a mass >5 cm had two times the odds of torsion (odds ratio: 2.1; confidence interval: 1.2, 3.6). Imaging was not reliable at identifying torsion (sensitivity 34%, positive predictive value 49%) or excluding torsion (specificity 72%, negative predictive value 87%). The rates of malignancy were lower in those with an ovarian mass and torsion than those without torsion (10% versus 17%, P = 0.01). Among the 180 girls with torsion and a mass, 48% underwent oophorectomy of which 14% (n = 12) had a malignancy. CONCLUSIONS: In females with an ovarian neoplasm, torsion is not associated with an increased risk of malignancy and ovarian preservation should be considered.

Understanding the Value of Tumor Markers in Pediatric Ovarian Neoplasms.

PURPOSE: The purpose of this study was to determine the diagnostic accuracy of tumor markers for malignancy in girls with ovarian neoplasms. METHODS: A retrospective review of girls 2-21 years who presented for surgical management of an ovarian neoplasm across 10 children's hospitals between 2010 and 2016 was performed. Patients who had at least one concerning feature on imaging and had tumor marker testing were included in the study. Sensitivity, specificity, and negative and positive predictive values (PPV) of tumor markers were calculated. RESULTS: Our cohort included 401 patients; 22.4% had a malignancy. Testing for tumor markers was inconsistent. AFP had high specificity (98%) and low sensitivity (42%) with a PPV of 86%. The sensitivity, specificity, and PPV of beta-hCG was 44%, 76%, and 32%, respectively. LDH had high sensitivity (95%) and Inhibin A and Inhibin B had high specificity (97% and 92%, respectively). CONCLUSIONS: Tumor marker testing is helpful in preoperative risk stratification of ovarian neoplasms for malignancy. Given the variety of potential tumor types, no single marker provides enough reliability, and therefore a panel of tumor marker testing is recommended if there is concern for malignancy. Prospective studies may help further elucidate the predictive value of tumor markers in a pediatric ovarian neoplasm population. TYPE OF STUDY: Retrospective Cohort Review. LEVEL OF EVIDENCE: Level III.

An Unusual Lung Mass of Heterotopic Pancreatic Tissue in a Neonate With an Elevated Immunoreactive Trypsinogen on Newborn Screen.

We present a case of a neonate with tracheoesophageal fistula and esophageal atresia along with a suspicious lung mass who had a false-positive newborn screen for cystic fibrosis due to an elevated serum immunoreactive trypsinogen with an additionally elevated serum lipase. The infant's lung mass was found to contain heterotopic pancreatic tissue consisting of acini, ducts, and islet cells, without an associated gastrointestinal duplication cyst. This constellation of congenital abnormalities has not been described in previous literature. Also, this is the first reported case of a neonate with elevated serum pancreatic enzymes in which the underlying etiology was discovered to be heterotopic pancreas.

Evaluation of a water-soluble contrast protocol for nonoperative management of pediatric adhesive small bowel obstruction.

BACKGROUND/PURPOSE: We examined outcomes before and after implementing an enteral water-soluble contrast protocol for management of pediatric adhesive small bowel obstruction (ASBO). METHODS: Medical records were reviewed retrospectively for all children admitted with ASBO between November 2010 and June 2017. Those admitted between November 2010 and October 2013 received nasogastric decompression with decision for surgery determined by surgeon judgment (preprotocol). Patients admitted after October 2013 (postprotocol) received water-soluble contrast early after admission, were monitored with serial examinations and radiographs, and underwent surgery if contrast was not visualized in the cecum by 24 h. Group outcomes were compared. RESULTS: Twenty-six patients experienced 29 admissions preprotocol, and 11 patients experienced 12 admissions postprotocol. Thirteen (45%) patients admitted preprotocol underwent surgery, versus 2 (17%) postprotocol patients (p = 0.04). Contrast study diagnostic sensitivity as a predictor for ASBO resolution was 100%, with 90% specificity. Median overall hospital LOS trended shorter in the postprotocol group, though was not statistically significant (6.2 days (preprotocol) vs 3.6 days (postprotocol) p = 0.12). Pre- vs. postprotocol net operating cost per admission yielded a savings of $8885.42. CONCLUSIONS: Administration of water-soluble contrast after hospitalization for pediatric ASBO may play a dual diagnostic and therapeutic role in management with decreases in surgical intervention, LOS, and cost. TYPE OF STUDY: Retrospective comparative study. LEVEL OF EVIDENCE: Level III.

A divergent variant of the eleventh human polyomavirus species, saint louis polyomavirus.

Saint Louis polyomavirus (STLPyV) was recently discovered in human feces. Using random-primed rolling circle amplification combined with deep sequencing, we have found a divergent variant of STLPyV in a sanitized human skin wart specimen. The result strongly suggests that STLPyV directly infects humans and is not simply a dietary contaminant.

Colorectal cancer biomarkers and the potential role of cancer stem cells.

Over 50% of patients with colorectal cancer (CRC) will progress and/or develop metastases. Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells are thought to be responsible for tumor initiation, dissemination and treatment failure. Therefore, we hypothesized that CRC stem cell markers (CRCSC) can identify a group of patients whom are at increased risk for recurrence or progression of disease. If proven correct, these CRCSC biomarkers may herald a paradigm shift in the treatment of this deadly disease. This manuscript reviews current CRC evidence based screening modalities, patient stratification, and summarizes the current state of biomarkers and discusses the novel concept of putative CRCSC's as prognostic biomarkers.

Complete genome sequence of a tenth human polyomavirus.

Nine polyomavirus (PyV) species are known to productively infect humans. The circular DNA genomes of PyVs are readily detectable using rolling circle amplification (RCA). RCA-based analysis of condyloma specimens from a patient with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome demonstrated the presence of a tenth apparently human-tropic polyomavirus species, which we name HPyV10.

A Pilot Study Assessing the Potential Role of non-CD133 Colorectal Cancer Stem Cells as Biomarkers.

INTRODUCTION: Over 50% of patients with colorectal cancer (CRC) will progress and/or develop metastases. Biomarkers capable of predicting progression, risk stratification and therapeutic benefit are needed. Cancer stem cells are thought to be responsible for tumor initiation, dissemination and treatment failure. Therefore, we hypothesized that CRC cancer stem cell markers (CRCSC) will identify a group of patients at high risk for progression. METHODS: Paraffin-embedded tissue cores of normal (n=8), and histopathologically well-defined primary (n= 30) and metastatic (n=10) CRC were arrayed in duplicate on tissue microarrays (TMAs). Expression profiles of non-CD133 CRCSC (CD29, CD44, ALDH1A1, ALDH1B1, EpCam, and CD166) were detected by immunohistochemistry and the association with clinicopathological data and patient outcomes was determined using standard statistical methodology. An independent pathologist, blinded to the clinical data scored the samples. Scoring included percent positive cells (0 to 4, 0 = <10%, 1 = 10 - 24%, 2 = 25 - 49%, 3 = 50 - 74%, 4 = 75 - 100%), and the intensity of positively stained cells (0 to 4; 0 = no staining, 1 = diminutive intensity, 2 = low intensity, 3 = intermediate intensity, 4 = high intensity). The pathologic score represents the sum of these two values, reported in this paper as a combined IHC staining score (CSS). RESULTS: Of 30 patients 7 were AJCC stage IIA, 10 stage IIIB, 7 stage IIIC and 6 stage IV. Median follow-up was 113 months. DFI was 17 months. Median overall survival (OS) was not reached. Stage-specific OS was: II - not reached; III - not reached; IV - 11 months. In a univariate analysis, poor OS was associated with loss of CD29 expression; median OS, 32 months vs. not reached for CSS 3-7 vs. >7.5, respectively; p=0.052 comparing entire curves, after adjustment. In a Cox model analysis, loss of CD29 exhibited a trend toward association with survival (p=0.098) after adjusting for the effect of stage (p=0.0076). Greater expression of ALDH1A1 was associated with increasing stage (p=0.042 over stages 2, 3b, 3c, and 4) while loss of CD29 expression exhibited a trend toward being associated with stages 3 and 4 (p=0.08). Compared to normal colon tissue, primary tumors were associated with increased expression of ALDH1B1 (p=0.008). ALD1H1B1 expression level differed according to whether the tumor was moderately or poorly differentiated, well differentiated, or mucinous; the highest expression levels were associated with moderately or poorly differentiated tumors (p=0.011). Lymph node metastases were associated with a trend toward decreased expression of EpCAM (p = 0.06) when comparing 0 vs. 1 vs. 2+ positive lymph nodes, as was CD29 (p = 0.08) when comparing 0 vs. any positive lymph nodes. Compared to normal colon tissue metastatic colon cancers from different patients were associated with increased ALDH1B1 expression (p=0.001) whereas CD29 expression was higher in normal colonic tissue (p=0.014). CONCLUSION: CD29 may be associated with survival as well as clinical stage and number of lymph nodes. ALDH1B1 expression was associated with differentiation as well as type of tissue evaluated. ALDH1A1 was associated with clinical stage, and decreased EpCAM expression was found in patients with advanced lymph node stage. CRCSCs may be useful biomarkers to risk stratify, and estimate outcomes in CRC. Larger prospective studies are required to validate the current findings.

Evaluation and management of intestinal obstruction.

Acute intestinal obstruction occurs when there is an interruption in the forward flow of intestinal contents. This interruption can occur at any point along the length of the gastrointestinal tract, and clinical symptoms often vary based on the level of obstruction. Intestinal obstruction is most commonly caused by intra-abdominal adhesions, malignancy, or intestinal herniation. The clinical presentation generally includes nausea and emesis, colicky abdominal pain, and a failure to pass flatus or bowel movements. The classic physical examination findings of abdominal distension, tympany to percussion, and high-pitched bowel sounds suggest the diagnosis. Radiologic imaging can confirm the diagnosis, and can also serve as useful adjunctive investigations when the diagnosis is less certain. Although radiography is often the initial study, non-contrast computed tomography is recommended if the index of suspicion is high or if suspicion persists despite negative radiography. Management of uncomplicated obstructions includes fluid resuscitation with correction of metabolic derangements, intestinal decompression, and bowel rest. Evidence of vascular compromise or perforation, or failure to resolve with adequate bowel decompression is an indication for surgical intervention.