Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Patient Characteristics, Treatment, and Outcome-A Systematic Review.

BACKGROUND: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome. METHODS: A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan-Meier's methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures. RESULTS: Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1-60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis. CONCLUSIONS: SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.

Reconstructive Strategies in Pediatric Patients after Oncological Chest Wall Resection: A Systematic Review.

An appropriate reconstruction strategy after surgical resection of chest wall tumors in children is important to optimize outcomes, but there is no consensus on the ideal approach. The aim of this study was to provide an up-to-date systematic review of the literature for different reconstruction strategies for chest wall defects in patients less than 18 years old. A systematic literature search of the complete available literature was performed and results were analyzed. A total of 22 articles were included in the analysis, which described a total of 130 chest wall reconstructions. All were retrospective analyses, including eight case reports. Reconstructive options were divided into primary closure (n = 21 [16.2%]), use of nonautologous materials (n = 83 [63.8%]), autologous tissue repair (n = 2 [1.5%]), or a combination of the latter two (n = 24 [18.5%]). Quality of evidence was poor, and the results mostly heterogeneous. Reconstruction of chest wall defects can be divided into four major categories, with each category including its own advantages and disadvantages. There is a need for higher quality evidence and guidelines, to be able to report uniformly on treatment outcomes and assess the appropriate reconstruction strategy.

The results of concentration of care: Surgical outcomes of neuroblastoma in the Netherlands.

INTRODUCTION: In the Netherlands pediatric oncological care for solid tumours is concentrated in one centre since November 2014. One of the most frequently diagnosed solid non-brain tumours in children is the neuroblastoma. Results of surgical treatment of neuroblastoma since the start of this centralization are presented and compared to a historic cohort. METHODS: The new national cohort of neuroblastoma (n = 111) consists of all consecutive patients treated between January 1st, 2015 and April 1st, 2021. The historic neuroblastoma cohort consists of all operated neuroblastoma patients in the Netherlands between 1998 and 2014 (n = 244). Intra-operative complications and surgical outcome were registered. Post-operative complications were divided in short (<30 days after surgery) and long term (>30 days). The severity of complications was graded using the Clavien Dindo Classification (CDC) system. RESULTS: Intraoperative outcomes showed significant differences in favour of the new cohort with less blood loss (p < 0.001), fewer vascular complications (p < 0.001) and shorter duration of surgery (p < 0.001). Short term complications were comparable in numbers, but significantly more patients had CDC grade 3/4/5 complications in the historic cohort (p = 0.005). Long term complications did not differ. Estimated overall survival showed a better survival in the new cohort (log rank 0.022). CONCLUSION: Centralization of care for neuroblastoma patients has led to a significant improvement of both intraoperative outcomes and short term complications.

Recurrence of a Mediastinal Germ-Cell Tumor as a Somatic-Type Malignancy: A Complex Case Report.

Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies.

Treatment and Survival of Malignant Extracranial Germ Cell Tumours in the Paediatric Population: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis was performed to explore overall survival (OS) and event free survival (EFS) rates internationally over the past two decades and to define specific subgroups with inferior outcomes which may demand different treatment strategies. METHODS: The search focused on malignant extracranial germ cell tumours (GCTs) in the paediatric population. The initial database search identified 12,556 articles; 32 articles were finally included in this review, comprising a total of 5095 patients. RESULTS: The studies were heterogeneous, varying from single institution reports to large prospective trials. Older studies, describing eras where non-platinum-based chemotherapy regimens were used, showed clearly worse outcomes. Survival for stage I-II gonadal disease is excellent. On the other hand, patients with an initial alpha-fetoprotein (AFP) > 10,000 ng/mL or kU/L, age > 11 years and stage IV disease confer a survival disadvantage. For testicular disease in particular, lymphovascular invasion and certain histopathological subtypes, such as embryonal carcinoma (EC) and mixed malignant GCTs, survival is poorer. Survival data for sacrococcygeal and mediastinal GCTs show a heterogeneous distribution across studies in this review, independent of year of publication. Patients > 12 years presenting with a mediastinal GCT pose a subpopulation which fares worse than GCTs in other locations or age groups. This is independent of AFP levels, stage of disease or treatment protocol, and these patients may demand a different treatment strategy. CONCLUSIONS: This review describes the heterogeneous nature of GCTs in different anatomical locations, impacting on stage at presentation, treatment modalities used and survival data. Despite this heterogeneity, in line with the current developmental biology-based classification system, subpopulations can be defined which have an inferior EFS and OS and where future research and more individualised treatment would help to improve survival.

Loss of H3K27me3 occurs in a large subset of embryonal rhabdomyosarcomas: Immunohistochemical and molecular analysis of 25 cases.

Loss of histone 3 lysine 27 trimethylation (H3K27me3) has been described as a diagnostic marker for malignant peripheral nerve sheath tumor (MPNST), also discriminating MPNST with rhabdomyoblastic differentiation (malignant Triton tumor) from rhabdomyosarcoma (RMS). We studied the immunohistochemical expression of H3K27me3 in embryonal RMSs (ERMSs), performed methylation profiling in order to support the diagnosis and RNA-sequencing for comparison of the transcriptome of H3K27me3-positive and -negative cases. Of the 25 ERMS patients, 17 were males and 8 were females with an age range from 1 to 67 years (median, 6 years). None were known with neurofibromatosis type 1. One patient had Li-Fraumeni syndrome. Tumor localization included paratesticular (n = 9), genitourinary (n = 6), head/neck (n = 5), retroperitoneal (n = 4) and lower arm (n = 1). Five MPNSTs served as reference group. All ERMS had classical features including a variable spindle cell component. Immunohistochemical loss (partial or complete) of H3K27me3 was detected in 18/25 cases (72%). Based on methylation profiling, 22/22 cases were classified as ERMS. Using RNA sequencing, the ERMS group (n = 14) had a distinct gene expression profile in contrast to MPNSTs, confirming that the H3K27me3 negative ERMS cases do not represent malignant Triton tumors. When comparing H3K27me3-negative and -positive ERMSs, gene set enrichment analysis revealed differential expression of genes related to histone acetylation and normal muscle function with H3K27me3 negative ERMSs being associated with acetylation. Conclusion: Loss of H3K27me3 frequently occurs in ERMSs and correlates with H3K27 acetylation. H3K27me3 is not a suitable marker to differentiate ERMS (with spindle cell features) from malignant Triton tumor.

The diagnostic value of magnetic resonance imaging in differentiating benign and malignant pediatric ovarian tumors.

BACKGROUND: The diagnostic workup of ovarian tumors in children and adolescents is challenging because preserving fertility, in addition to oncological safety, is of particular importance in this population. Therefore, a thorough preoperative assessment of ovarian tumors is required. OBJECTIVE: To investigate the diagnostic value of MR imaging in differentiating benign from malignant ovarian tumors in children and adolescents. MATERIALS AND METHODS: We conducted a retrospective study of all children and adolescents age <18 years who underwent MR imaging of ovarian tumors during 2014-2019 at a pediatric specialty center. Two radiologists reviewed all MR imaging. We used pathology reports to define the histological diagnosis. RESULTS: We included 30 girls who underwent MR imaging for an ovarian tumor. Signs indicative for malignancy were tumors with a diameter ≥8 cm, with areas of contrast enhancement, irregular margins, extracapsular tumor growth, and ascites. All benign and malignant ovarian tumors were correctly identified by the radiologists. CONCLUSION: The diagnostic utility of MR imaging in classifying ovarian tumors in children and adolescents as benign or malignant is promising and might aid in defining the indication for ovarian-sparing versus non-ovarian-sparing surgery. We recommend evaluating these tumors with MR imaging prior to deciding on surgical treatment.

Testis Sparing Surgery in Pediatric Testicular Tumors.

OBJECTIVE: The purpose of this review is to evaluate the outcomes of testis sparing surgery (TSS) and to investigate under which circumstances TSS can be considered a safe treatment option in pediatric patients with testicular tumors. METHODS: A database search was performed in Cochrane, Pubmed, and Embase for studies that focused on TSS as treatment for testicular tumors in the pediatric population, excluding reviews and single case reports. RESULTS: Twenty studies, describing the surgical treatment of 777 patients with testicular tumors, were included in the analysis. The majority of pediatric patients with benign germ cell tumors (GCTs) (mean age: 3.7 years) and sex cord-stromal tumors (SCSTs) (mean age: 6.6 years) were treated with TSS, 61.9% and 61.2%, respectively. No cases of testicular atrophy occurred. Four of the benign GCTs, i.e., three teratomas and one epidermoid cyst, recurred. No cases of recurrence were reported in patients with SCSTs. Of the 243 malignant GCTs (mean age: 4.2 years), only one patient had TSS (0.4%). CONCLUSION: TSS is a safe treatment option for prepubertal patients less than 12 years of age with benign GCTs and low grade SCSTs.

MR imaging in discriminating between benign and malignant paediatric ovarian masses: a systematic review.

OBJECTIVES: The use of magnetic resonance (MR) imaging in differentiation between benign and malignant adnexal masses in children and adolescents might be of great value in the diagnostic workup of sonographically indeterminate masses, since preserving fertility is of particular importance in this population. This systematic review evaluates the diagnostic value of MR imaging in children with an ovarian mass. METHODS: The review was made according to the PRISMA Statement. PubMed and EMBASE were systematically searched for studies on the use of MR imaging in differential diagnosis of ovarian masses in both adult women and children from 2008 to 2018. RESULTS: Sixteen paediatric and 18 adult studies were included. In the included studies, MR imaging has shown good diagnostic performance in differentiating between benign and malignant ovarian masses. MR imaging techniques including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging seem to further improve the diagnostic performance. CONCLUSION: The addition of DWI with apparent diffusion coefficient (ADC) values measured in enhancing components of solid lesions and DCE imaging may further increase the good diagnostic performance of MR imaging in the pre-operative differentiation between benign and malignant ovarian masses by increasing specificity. Prospective age-specific studies are needed to confirm the high diagnostic performance of MR imaging in children and adolescents with a sonographically indeterminate ovarian mass. KEY POINTS: • MR imaging, based on several morphological features, is of good diagnostic performance in differentiating between benign and malignant ovarian masses. Sensitivity and specificity varied between 84.8 to 100% and 20.0 to 98.4%, respectively. • MR imaging techniques like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging seem to improve the diagnostic performance. • Specific studies in children and adolescents with ovarian masses are required to confirm the suggested increased diagnostic performance of DWI and DCE in this population.

Does Mechanical Bowel Preparation Reduce the Risk of Developing Infectious Complications in Pediatric Colorectal Surgery? A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate whether the application of mechanical bowel preparation (MBP) before colorectal surgery reduces the risk of developing infectious complications in children. STUDY DESIGN: In this systematic review and meta-analysis, PubMed, Embase, and the Cochrane Library were systematically searched to identify all articles comparing pediatric patients receiving MBP with pediatric patients not receiving MBP before colorectal surgery. Results are presented with weighted risk differences based on the number of events and sample size per study. RESULTS: Six original studies were included comparing MBP (n = 810) and no MBP (n = 1167). The overall risk of developing infectious complications was 10.1% in patients with MBP, compared with 9.1% in patients without MBP, resulting in a nonsignificant risk difference of -0.03% (95% CI, -0.09% to 0.03%). Concerning the number of wound infections and anastomotic leaks, we found nonsignificant risk differences of -0.03% (95% CI, -0.08% to 0.02%) and 0.01% (95% CI, -0.01% to 0.02%), respectively. CONCLUSION: Based on the current literature, there is insufficient evidence to indicate that the use of MBP leads to a significant difference in the risk of developing infectious complications in pediatric colorectal surgery.

Esophageal Atresia and Upper Airway Pathology.

Esophageal atresia is an anomaly with frequently occurring sequelae requiring lifelong management and follow-up. Because of the complex issues that can be encountered, patients with esophageal atresia preferably should be managed in centers of expertise that have the ability to deal with all types of anomalies and sequelae and can perform rigorous lifelong follow-up. Tracheomalacia is an often-occurring concurrent anomaly that may cause acute life-threatening events and may warrant immediate management. In the past, major thoracotomies were necessary to carry out the aortopexy. Nowadays, aortopexy and posterior tracheopexy can both be performed thoracoscopically with quick recovery.

Effects of esketamine sedation compared to morphine analgesia on hydrostatic reduction of intussusception: A case-cohort comparison study.

BACKGROUND: Hydrostatic or pneumatic reduction of intussusception is an invasive procedure that is stressful and may be painful for a child. Resistance of the child may increase the duration of the procedure and decrease success rate of reduction. Analgesia can help to reduce pain, but not necessarily resistance. General anesthesia increases success rate of reduction. However, it requires the presence of an anesthesiologist, and may lead to anesthesia-related complications. Procedural sedation with esketamine could be a safe alternative. AIM: The aim of this study was to compare hydrostatic reduction using morphine analgesia compared to procedural sedation with esketamine in terms of success rate, adverse events, and duration of reduction. METHODS: A retrospective case-cohort comparison study was performed with two groups of patients who had undergone hydrostatic reduction for ileocolic intussusception and received morphine analgesia (n = 37) or esketamine sedation (n = 20). Until July 2013, reduction was performed after intravenously administered morphine. Hereafter, a new protocol for procedural sedation was implemented and reduction was performed after administration of esketamine. Cases were matched for age and duration of symptoms. RESULTS: No adverse events requiring intervention other than administration of oxygen were reported for either group. Success rate of reduction using esketamine sedation was 90% vs 70% using morphine analgesia, risk ratio (RR) 1.29, 95% CI[0.93-1.77]. Recurrence rate using esketamine sedation was 10% vs 15% using morphine analgesia, RR 0.67, 95% CI[0.12-3.57]. Reduction time was shorter using esketamine sedation (Median 5 minutes, IQR 9 minutes) vs morphine analgesia (Median 8 minutes, IQR 16 minutes, P = .04, Median difference 3, 95% CI[-1.50-8.75]). Median hospital stay in the esketamine group was 1.5 days (IQR 1.8) vs 2 days (IQR 5.3) in the morphine group. CONCLUSION: No serious adverse events were recorded. In comparison to morphine analgesia, with esketamine there was weak evidence for a higher success rate, lower recurrence rate, shorter duration, and shorter length of hospital stay.

A scoring system to predict the severity of appendicitis in children.

BACKGROUND: It appears that two forms of appendicitis exist. Preoperative distinction between the two is essential to optimize treatment outcome. This study aimed to develop a scoring system to accurately determine the severity of appendicitis in children. MATERIALS AND METHODS: Historical cohort study of pediatric patients (aged 0-17 y old) with appendicitis treated between January 2010 and December 2012. Division into simple, complex appendicitis, or another condition based on preset criteria. Multiple logistic regression analysis was used to build the prediction model with subsequent validation. RESULTS: There were 64 patients with simple and 66 with complex appendicitis. Five variables explained 64% of the variation. Independent validation of the derived prediction model in a second cohort (55 simple and 10 complex appendicitis patients) demonstrated 90% sensitivity (54-99), 91% specificity (79-97), a positive predictive value of 64% (36-86), and an negative predictive value of 98% (88-100). The likelihood ratio+ was 10 (4.19-23.42), and likelihood ratio- was 0.11 (0.02-0.71). Diagnostic accuracy was 91% (84-98). CONCLUSIONS: Our scoring system consisting of five variables can be used to exclude complex appendicitis in clinical practice if the score is <4.

[Malrotation with or without volvulus]. / Malrotatie met en zonder volvulus.

Malrotation occurs when there is a failure in the intestinal rotation leading to abnormal fixation to the abdominal wall and a mesentery with a short root. Volvulus is a life-threatening complication of malrotation. It can lead to irreversible intestinal necrosis and requires immediate attention. Early recognition of malrotation and surgical correction could prevent the onset of volvulus. We describe 3 cases of children with a malrotation. Case A involves a 2-year-old boy who suffered from repeated episodes of vomiting. Case B, a 1-month-old female, was taken to the general practitioner after acute onset of crying and flexing of the legs. Case C, a 5-year-old-boy with no medical history, had started vomiting hourly. In presenting these 3 cases, we highlight the dangers of untreated malrotation and make recommendations on how to manage a patient suspected of having this congenital abnormality.

Efficacy and adverse events of laparoscopic gastrostomy placement in children: results of a large cohort study.

INTRODUCTION: A gastrostomy placement is frequently performed in pediatric patients who require long-term enteral tube feeding. However, data on efficacy, perioperative complications and postoperative gastroesophageal reflux (GER) after laparoscopic gastrostomy (LAG) placement is limited. The aim of this study is to evaluate long-term efficacy and adverse events after LAG in a large cohort and determine whether routine preoperative 24-h pH monitoring should be used to predict postoperative GER. METHOD: A retrospective observational cohort study was performed including 300 patients (75 % neurologically impaired) that underwent LAG. RESULTS: After a median follow-up of 2.63 years, feeding was successful in 95.9 % of patients. Weight-for-length z-scores significantly increased (p < 0.0005). Major complications were seen in only 6 patients (2.0 %), but minor complications occurred frequently (73.6 %). Overall incidence of GER remained unchanged after LAG. Sensitivity and specificity of preoperative pH monitoring were 17.5 and 76.9 %, respectively. CONCLUSION: LAG placement in pediatric patients leads to successful feeding in 96 % of patients and serious adverse events are rare. However, the minor complication rate is high. Overall incidence of GER does not increase after LAG. Preoperative 24-h pH monitoring is not a reliable tool to predict postoperative GER. This invasive investigation technique should therefore not be routinely performed.

[An inflammatory pseudotumor of the liver]. / Een inflammatoire pseudotumor in de lever.

BACKGROUND: Inflammatory pseudotumours are rare benign tumours that can present as solid and potentially malignant tumours on diagnostic images. CASE DESCRIPTION: A 59-year-old male presented at the emergency department with continuous pain in his right upper abdomen, attacks of colic and intermittent fever. CT scans of the abdomen revealed a solid lesion in the liver. Histopathological analysis of a biopsy showed an inflammatory pseudotumour. Since the pain persisted and a malignancy could not be excluded with certainty, surgical resection of the tumour was performed. The specimen showed an inflammatory pseudotumour with an increase in IgG4 positive plasma cells as well as a purulent infection around aggregates of Actinomyces. CONCLUSION: It is important to realise that a pseudotumour caused by an inflammatory reaction can mimic a malignancy.

Evidence-based treatment of open ankle fractures.

Fractures of the ankle are fairly common injuries. Open ankle fractures are much less common and associated with severe injuries to surrounding tissues. We have performed a systematic review of the literature concerning the clinical results and complication rates in the treatment of open ankle fractures. We conducted a search limited to the following databases: Pubmed/Medline, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register and Embase. These were searched from 1968 to April 2010 to identify studies relating to the treatment of open ankle fractures. Fifteen articles concerning 498 patients with treatment of an open ankle fracture were identified. The number of included patients varied from 11 to 64. There were 2 prospective and 13 retrospective studies. All articles were case series and classified as Level IV evidence. In 373 cases, open ankle fractures were treated by immediate internal fixation. In 125 cases, a conservative treatment or delayed/other fixation treatment was followed. Of those patients treated by immediate internal fixation, 81% had satisfactory result. Poor results (15%) were most commonly due to non-anatomic reductions, articular surface damage or deep infection. When conservative treatment was followed, 76% had satisfactory results. The most reported complications after immediate internal fixation were deep infection (8%) and skin necrosis (14%). There is a lack of high quality literature concerning the (operative) treatment of patients with open ankle fractures. Remarkable is that most authors reported satisfactory results after performance of their treatment protocol. Based on the available literature, we formulated guidelines regarding: timing of operative treatment, wound irrigation, the role of internal fixation, wound coverage and closure, the use of antibiotics and additional therapies.