The potential of rectal swabs to differentiate simple and complex appendicitis in children with a microbiota-based test.

Currently, accurate biomarkers differentiating simple (phlegmonous) from complex (gangrenous and/or perforated) appendicitis in children are lacking. However, both types may potentially require different treatment strategies, and the search for diagnostic modalities remains warranted. Previously, we demonstrated a distinct microbiota (both an increased bacterial diversity and abundance) in the appendix of children with complex compared to simple appendicitis. From the same cohort of patients we have collected 35 rectal swabs under general anesthesia prior to appendectomy and microbiota analysis was performed by IS-pro, a 16S-23S rDNA-based clinical microbiota profiling technique. Using the obtained IS-profiles, we performed cluster analyses (UPGMA), comparison of diversity (Shannon Diversity Index) and intensity (abundance in relative fluorescence units) on phylum level, and comparison on species level of bacteria between simple and complex appendicitis. Regarding these analyses, we observed no clear differences between simple and complex appendicitis. However, increased similarity of the microbial composition of the appendix and rectal swab was found within children with complex compared to simple appendicitis. Furthermore, PLS-DA regression analysis provided clear visual differentiation between simple and complex appendicitis, but the diagnostic power was low (highest AUC 0.65).   Conclusion: Microbiota analysis of rectal swabs may be viable to differentiate between simple and complex appendicitis prior to surgery as a supervised classification model allowed for discrimination of both types. However, the current diagnostic power was low and further validation studies are needed to assess the value of this method. What is Known: • Simple and complex appendicitis in children may require different treatment strategies, but accurate preoperative biomarkers are lacking. • Clear differentiation can be made between both types in children based upon the microbial composition in the appendix. What is New: • Increased similarity was found between the microbial composition of the appendix and rectal swab within children with complex compared to simple appendicitis. • Using a supervised classification model rectal swabs may be viable to discriminate between simple and complex appendicitis, but the diagnostic power was low.

Clinical recovery in children with uncomplicated appendicitis undergoing non-operative treatment: secondary analysis of a prospective cohort study.

Non-operative treatment of uncomplicated appendicitis in children is gaining ground. Pending definitive evidence regarding its effectiveness, there is a call to evaluate clinical recovery after non-operative treatment. In this study, we analyzed data collected during initial admission of a multicenter prospective cohort in which children, 7-17 year, were treated non-operatively for uncomplicated appendicitis. During admission clinical parameters (pain and gastro-intestinal symptoms), inflammation parameters and sequential abdominal ultrasound were recorded. In total, 45 children were included, 42(93%) were discharged without the need for appendectomy; median [IQR] pain scores on admission were 5 [4-7], decreasing to 2 [0-3] after 1 day of treatment. Initially, 28/42 (67%) reported nausea and 19/42 (45%) vomiting; after 1 day, this was 3/42 (7%) and 1/42 (2%), respectively. White blood cell count declined from a median [IQR] of 12.9 [10.7-16.7] 10E9/L on admission to 7.0 [5.8-9.9] 10E9/L on day 1. Median [IQR] C-reactive protein levels increased from 27.5 [9-69] mg/L on admission to 48 [22-80] mg/L on day 1, declining to 21.5 [11-42] mg/L on day 2. Follow-up ultrasound showed no signs of complicated appendicitis in any of the patients.Conclusion: Clinical symptoms resolved in most children after 1 day of non-operative treatment. This suggests that non-operative treatment is a viable alternative to appendectomy regarding clinical recovery.Trail registration: NCT01356641 What is Known: • Non-operative treatment of uncomplicated appendicitis in children is safe and its use around the world is gaining ground, however high quality evidence from adequately designed randomized trials is still lacking. • Concerns have been raised regarding the potentially prolonged clinical recovery associated with non-operative treatment. What is New: • Most clinical symptoms resolve after 1 day of non-operative treatment in the majority of children.

Composition of the cellular infiltrate in patients with simple and complex appendicitis.

BACKGROUND: It is now well established that there are two types of appendicitis: simple (nonperforating) and complex (perforating). This study evaluates differences in the composition of the immune cellular infiltrate in children with simple and complex appendicitis. MATERIALS AND METHODS: A total of 47 consecutive children undergoing appendectomy for acute appendicitis between January 2011 and December 2012 were included. Intraoperative criteria were used to identify patients with either simple or complex appendicitis and were confirmed histopathologically. Immune histochemical techniques were used to identify immune cell markers in the appendiceal specimens. Digital imaging analysis was performed using Image J. RESULTS: In the specimens of patients with complex appendicitis, significantly more myeloperoxidase positive cells (neutrophils) (8.7% versus 1.2%, P < 0.001) were detected compared to patients with a simple appendicitis. In contrast, fewer CD8+ T cells (0.4% versus 1.3%, P = 0.016), CD20 + cells (2.9% versus 9.0%, P = 0.027), and CD21 + cells (0.2% versus 0.6%, P = 0.028) were present in tissue from patients with complex compared to simple appendicitis. CONCLUSIONS: The increase in proinflammatory innate cells and decrease of adaptive cells in patients with complex appendicitis suggest potential aggravating processes in complex appendicitis. Further research into the underlying mechanisms may identify novel biomarkers to be able to differentiate simple and complex appendicitis.

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990-2013).

BACKGROUND: Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival. METHOD: Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013. RESULTS: A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation. CONCLUSIONS: Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to survival.

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.

Patient-Reported Defecation and Micturition Problems Among Adults Treated for Sacrococcygeal Teratoma During Childhood--The Need for New Surveillance Strategies.

BACKGROUND: To evaluate defecation and micturition complaints in adults treated for sacrococcygeal teratoma (SCT) during childhood and to identify risk factors for soiling, urinary incontinence, and constipation beyond childhood. PROCEDURE: Records of patients aged ≥18 treated for SCT during infancy in the Netherlands were retrospectively reviewed. Frequency and severity of soiling, constipation, and urinary incontinence were evaluated using questionnaires designed in line with the Krickenbeck classification. Problems during childhood were compared to outcomes at adult age in part of the cohort. Associations between patient- and disease-related factors with complaints beyond childhood were analyzed with the chi-square test or Fisher's exact test, when appropriate. RESULTS: Of 47 included patients (mean age 26.2 years, SD ±6.5), 49% reported at least one defecation or micturition complaint. Urinary incontinence was present in 30% and had a greater negative impact than soiling (24%). Ten patients (21%) reported constipation; five found this severely bothering. Three patients reported social restrictions due to defecation or micturition complaints (6.4%). While sex and tumor histology were not identified as risk factors, a tumor diameter of >10 cm and Altman type I or type II SCT were associated with constipation during adulthood. CONCLUSIONS: One-third of the patients treated for SCT during childhood reported urinary and defecation problems beyond childhood. In only a minority of cases, these led to social restrictions. A greater tumor diameter was associated with a higher risk of constipation during adulthood. Prolonged surveillance strategies are advised for all patients with SCT.

Prevalence of Symptomatic and Asymptomatic Thrombosis in Pediatric Oncology Patients With Tunneled Central Venous Catheters.

BACKGROUND: Pediatric oncology patients with tunneled central venous catheters (CVCs) are at increased risk to develop venous thromboembolic events (VTEs), but the true prevalence of (a)symptomatic VTE is unknown. Aim of this study was to evaluate the prevalence of (a)symptomatic VTE in pediatric oncology patients with tunneled CVCs. PROCEDURE: All patients were included in the Aristocaths study: a randomized controlled multicenter trial investigating the prophylactic effect of 70% ethanol locks on CVC-associated bloodstream infections (CABSIs) were eligible for this study. We assessed the following outcomes: (i) symptomatic VTE and (ii) asymptomatic CVC-related VTE (using ultrasound [US]). Follow-up was 6 months, unless patients developed one of the following events: VTE, CABSI, CVC removal, or death. RESULTS: We included 305 patients (hematologic malignancy, n = 148; solid tumor, n = 157), median age 9 years (range, 1-18 years). Symptomatic VTE was detected in 8 of 305 patients (2.6%; 95% confidence interval [CI]: 1.1-5.1%), which was related to the CVC in three patients. Patients (185/305) were evaluated with US: 11 of 185 (5.9%; 95% CI: 3.0-10.4%) patients had asymptomatic CVC-related VTE. CONCLUSIONS: Prevalence of both symptomatic VTE and asymptomatic CVC-related VTE was low compared to other studies, which may be explained by the inclusion of patients with solid tumors, reduction of CABSI by ethanol, use of tunneled CVCs, and use of US.

Intervention not always necessary in post-appendectomy abscesses in children; clinical experience in a tertiary surgical centre and an overview of the literature.

UNLABELLED: This study aims to provide an overview of both our own experience and the available literature on the treatment of post-appendectomy abscess (PAA) in children. We performed a historical cohort study encompassing all children aged 0-17 years old treated for a radiologically confirmed PAA between 2007 and 2013. Their medical charts were reviewed and descriptive analyses were performed. A literature search on the treatment of PAA in children was performed. In our cohort, 25 out of 372 (7 %) children developed a PAA. Thirteen were treated with a noninvasive strategy and 12 with an invasive strategy (percutaneous or surgical drainage). The immediate success rate was 9/13 (69 %) and 8/12 (67 %) for the noninvasive and invasive strategy, respectively. In both groups, four children (31 and 33 % resp.) required delayed interventions after their initial treatment. In the literature review, six studies were included which reported a median (range) frequency of persistent or recurrent abscess of 9 % (0-30 %), 50 % (0-100 %) and 24 % (0-33 %) for the antibiotic (noninvasive), percutaneous drainage (invasive) and surgical drainage strategies, respectively. CONCLUSION: Although confounding by indication cannot be excluded, we recommend noninvasive treatment as a safe strategy for PAA in children with stable condition. WHAT IS KNOWN: • Post-appendectomy abscess is a well-known and feared complication, occurring in up to 24 % of the children treated surgically for appendicitis. • Several strategies are available to treat this condition, all with advantages and disadvantages. What is new: • Noninvasive strategy is a safe strategy for children with a PAA in a stable condition. • An overview of the literature (the first to our knowledge) supports the above-mentioned statement.

Evaluation of chemotherapeutic sequelae and quality of life in survivors of malignant sacrococcygeal teratoma.

PURPOSE: The impact of chemotherapeutic sequelae on long-term quality of life (QoL) for survivors of malignant sacrococcygeal teratoma (SCT) is unknown. The incidence of chemotherapeutic toxicity in patients treated for malignant SCT and possible effects on the QoL were analyzed. METHODS: Retrospective chart review of patients ≥18 years treated for SCT in the Netherlands was performed. Present QoL was evaluated using the SF-36 questionnaire. The results of survivors of malignant SCT were compared to those of patients treated for benign SCT. RESULTS: Fifty-one of 76 traceable patients consented to participate. The results of 47 (92.2 %), 9 men and 38 women (median age 25.4 years, range 18.3-41.2), were analyzed. Eleven had been treated for malignancy; 63.6 % suffered from at least one chemotherapeutic sequel with hearing loss as the most common one. Results for both groups were similar on all but one SF-36 subcategory; those treated for malignant tumor scored significantly lower on the subcategory physical functioning (p = 0.02). CONCLUSION: Despite the high incidence of chemotherapeutic sequelae among survivors of malignant SCT, their QoL does not differ from that of those treated for benign SCT. Even though their physical functioning is restricted, daily activities and psychosocial functioning of survivors of malignant SCT are not restricted.

Intestinal lengthening and reversed segment in a piglet short bowel syndrome model.

BACKGROUND: Treatment of short bowel syndrome (SBS) remains difficult, entailing severe morbidity and mortality. Accepted surgical treatment modalities for SBS are the Bianchi intestinal lengthening procedure and reversed-segment procedure. We seek to investigate the short-term effects regarding growth, nutrition, and microscopic and functional adaptation after the intestinal lengthening and RS procedures in a piglet SBS-model. MATERIAL AND METHODS: Twenty-four piglets (Sus scrofa, ±30 kg) were divided into four groups (n = 6 each) as follows: sham, SBS, Bianchi lengthening procedure (BIA), and reversed-segment (RS). At day one either sham laparotomy (sham) or 75% small bowel resection (SBS, BIA, and RS) was performed. After 2 wk sham laparotomy (sham and SBS), BIA, or RS procedure was performed. After 8 wk all animals were terminated. During the experimental time course, the following parameters were assessed: body weight, intestinal length, diameter, and weight, fat absorption, and biochemical parameters from serum and urine. Citrulline was used as a marker of absorptive enteral mass to demonstrate massive functional bowel loss. Intestinal biopsies were obtained for histologic analysis and electrophysiological measurements to analyze glucose absorptive capacity. RESULTS: Eight weeks after bowel resection, piglet growth was reduced in SBS, BIA, and RS piglets as demonstrated by reduced weight (51 ± 4 kg, 47 ± 2 kg, and 53 ± 1 kg, respectively) compared with sham (69 ± 3 kg; P < 0.01), with no demonstrable difference between SBS and treatment groups. Malabsorption and malnutrition occurred in SBS, BIA, and RS piglets reflected by increased fecal fat loss per 24 h (35 ± 4%, 30 ± 2%, and 32 ± 4%, respectively versus 18 ± 1% in sham; P < 0.01) and reduced serum albumin levels (24 ± 1 g/L, 22 ± 1 g/L, and 24 ± 1 g/L, respectively versus sham 33 ± 1 g/L; P < 0.01), but there was no significant difference between SBS and treatment groups. Serum citrulline levels reflected massive functional bowel loss (SBS 36 ± 7 µmol/L, BIA 23 ± 1 µmol/L, and RS 24 ± 2 µmol/L) compared with sham (64 ± 5 µmol/L; P < 0.01). Electrophysiological measurements demonstrated reduced glucose absorption after intestinal resection, which did not return to base levels within the experimental time course. However, the intestine of BIA and RS piglets adapted more profoundly than SBS piglets, as reflected by a greater crypt depth (490 ± 25 µm and 492 ± 21 µm versus 388 ± 20 µm; P < 0.01); and BIA piglets showed greater villus length (884 ± 58 µm) than RS or SBS piglets (715 ± 30 µm and 737 ± 64 µm, respectively; P < 0.01) after 8 wk. CONCLUSIONS: Despite increased histologic intestinal adaptation, neither intestinal lengthening nor RS procedure demonstrated significantly improved absorption, nutrition, or weight gain for the treatment of SBS during the study period. Reduced glucose uptake on electrophysiology measurements and persistent low levels of citrulline may indicate reduced small bowel enterocyte functioning during the initial phase of intestinal adaptation.

Children With Anorectal Malformations, Hirschsprung Disease, and Their Siblings: Proxy Reports and Self-Reports.

OBJECTIVES: The aim of the present study was to compare parent proxy reports with that of self-reports of children with anorectal malformations (ARMs) or Hirschsprung disease (HD) and healthy siblings and thereafter was examine whether these comparisons differed between patients and their siblings. METHODS: Parents (n = 98) of either children with ARM (n = 44) or HD (n = 54) and a healthy sibling (n = 98) recruited from the 6 Dutch pediatric surgical centers and from the ARM and HD patient societies were included in this cross-sectional multilevel study. Agreement between child self-reports and parent proxy reports was compared through mean differences and through (intraclass) correlations. We conducted multilevel analyses to take dependencies between assessments within families into account. RESULTS: All of the children (children with ARM or HD and their siblings) reported more pain and symptoms than their parents reported. We also found that only children with ARM or HD reported less positive emotions than their parents. Furthermore, higher correlations were found between parent proxy reports and patient-self reports than between parent proxy reports and sibling self-reports on cognitive functioning and social interaction. CONCLUSIONS: Parents tend to overestimate the physical functioning of both their ill and healthy children, and overestimate the emotional functioning of only their children with ARM or HD. Furthermore, children with ARM or HD and parents agree more on health-related quality of life domains than healthy children and parents.

Predicting posttraumatic stress disorder in children and parents following accidental child injury: evaluation of the Screening Tool for Early Predictors of Posttraumatic Stress Disorder (STEPP).

BACKGROUND: Children and their parents are at risk of posttraumatic stress disorder (PTSD) following injury due to pediatric accidental trauma. Screening could help predict those at greatest risk and provide an opportunity for monitoring so that early intervention may be provided. The purpose of this study was to evaluate the Screening Tool for Early Predictors of Posttraumatic Stress Disorder (STEPP) in a mixed-trauma sample in a non-English speaking country (the Netherlands). METHODS: Children aged 8-18 and one of their parents were recruited in two academic level I trauma centers. The STEPP was assessed in 161 children (mean age 13.9 years) and 156 parents within one week of the accident. Three months later, clinical diagnoses and symptoms of PTSD were assessed in 147 children and 135 parents. We used the Anxiety Disorders Interview Schedule for DSM-IV - Child and Parent version, the Children's Revised Impact of Event Scale and the Impact of Event Scale-Revised. Receiver Operating Characteristic analyses were performed to estimate the Areas Under the Curve as a measure of performance and to determine the optimal cut-off score in our sample. Sensitivity, specificity, positive and negative predictive values were calculated. The aim was to maximize both sensitivity and negative predictive values. RESULTS: PTSD was diagnosed in 12% of the children; 10% of their parents scored above the cut-off point for PTSD. At the originally recommended cut-off scores (4 for children, 3 for parents), the sensitivity in our sample was 41% for children and 54% for parents. Negative predictive values were 92% for both groups. Adjusting the cut-off scores to 2 improved sensitivity to 82% for children and 92% for parents, with negative predictive values of 92% and 96%, respectively. CONCLUSIONS: With adjusted cut-off scores, the STEPP performed well: 82% of the children and 92% of the parents with a subsequent positive diagnosis were identified correctly. Special attention in the screening procedure is required because of a high rate of false positives. The STEPP appears to be a valid and useful instrument that can be used in the Netherlands as a first screening method in stepped psychotrauma care following accidents.

Evaluation of pregnancy and delivery in 13 women who underwent resection of a sacrococcygeal teratoma during early childhood.

BACKGROUND: Sacrococcygeal teratoma resection often brings changes in pelvic anatomy and physiology with possible consequences for defecation, micturition and sexual function. It is unknown, whether these changes have any gynecological and obstetric sequelae. Until now four pregnancies after sacrococcygeal teratoma resection have been described and cesarean section has been suggested to be the method of choice for delivery. We evaluated the pregnancy course and mode of delivery in women previously treated for a sacrococcygeal teratoma. METHODS: The records of all patients who underwent sacrococcygeal teratoma resection after 1970 in one of the six pediatric surgical centers in the Netherlands were reviewed retrospectively. Women aged 18 years and older were eligible for participation. Patient characteristics, details about the performed operation and tumor histology were retrieved from the records. Consenting participants completed a questionnaire addressing fertility, pregnancy and delivery details. RESULTS: Eighty-nine women were eligible for participation; 20 could not be traced. Informed consent was received from 41, of whom 38 returned the completed questionnaire (92.7%). Thirteen of these 38 women conceived, all but one spontaneously. In total 20 infants were born, 17 by vaginal delivery and 3 by cesarean section, in one necessitated by previous intra-abdominal surgery as a consequence of sacrococcygeal teratoma resection. Conversion to a cesarean section was never necessary. None of the 25 women without offspring reported involuntary childlessness. CONCLUSIONS: There are no indications that resection of a sacrococcygeal teratoma in female patients is associated with reduced fertility: spontaneous pregnancy is possible and vaginal delivery is safe for mother and child, irrespective of the sacrococcygeal teratoma classification or tumor histology.

The role of 131I-metaiodobenzylguanidine (MIBG) therapy in unresectable and compromising localised neuroblastoma.

PURPOSE: In patients with localised neuroblastoma without adverse genetic aberrations, observational treatment is justified. Therapy is required when organ or respiratory functions have become compromised. As the outcome is good, side effects of treatment should be prevented. The aim of this retrospective study was to evaluate response and outcome in patients treated with (131)I-metaiodobenzylguanidine (MIBG) for unresectable localised neuroblastoma, with compromised organ functions. METHODS: Patients with localised neuroblastoma [median age 1.6 years (0-5.5 years)] diagnosed between 1989 and 2008 were included in this retrospective study (n = 21). Primary tumours were unresectable and there was a compromised organ or respiratory function. Diagnosis and staging were performed according to the International Neuroblastoma Staging System. Fixed doses of (131)I-MIBG therapy (50-200 mCi) were given. The median number of infusions was two (range one to seven). Response was graded according to the International Neuroblastoma Response Criteria. RESULTS: Of the 21 patients, 14 did not need any chemotherapy. Patients were treated with (131)I-MIBG therapy and, in most cases, with additional surgery and/or chemotherapy. Sixteen achieved complete response (CR), three very good partial response (VGPR), one partial response (PR) and one progressive disease (PD). Two patients died of PD after having achieved CR initially and due to surgical complications a few months after resection. Ten-year overall survival and event-free survival were 90.5 %. The median follow-up was 8.5 years (range 0.4-19.6 years). CONCLUSION: (131)I-MIBG therapy is an effective treatment modality for unresectable localised neuroblastoma with compromised organ functions. However, this was a small and heterogeneous cohort and further studies are needed.

Totally implantable venous access device in children with cancer lead to disfiguring scar.

BACKGROUND: In pediatric cancer patients scars of totally implantable venous access devices (TIVAD) are often widened and hypertrophic. This study report on the prevalence and deviation of abnormal scarring in children with a TIVAD and to describe the influencing factors for this abnormal scarring. METHODS: In a cross-sectional study scars of 122 childhood cancer patients (age 1-21 years) were evaluated; 72 patients had a TIVAD in-situ and in 50 the TIVAD had been removed. Outcome parameters were hypertrophy (modified Vancouver Scar Scale (mVSS), scar surface area, pain, and itching. Scar abnormality was defined as mVSS of >2, or scar width >3 mm. RESULTS: Abnormal TIVAD scars were found in 107 participants. The mVSS score was higher in patients ≤45 months after removal and the widest >45 months after TIVAD removal. Multivariable analyses showed that the mVSS score was positively related with scar width (mm) and children being ≤45 months after TIVAD removal. Furthermore, TIVAD scar width was positively related with age at last TIVAD surgery, and associated with suture material. In conclusion, there was a high incidence of abnormal TIVAD scars with some pain and itching complaints. However, no typical cancer related influencing factors were associated with increasing abnormalities.

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

Introduction: Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known. Methods: To characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient. Results: Appendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4+ T cells and to a lesser extent by CD8+ T cells. Frequencies of phenotypic tissue-resident memory CD69+CD4+ T cells and CD69+CD8+ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4+ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A+ CD4+ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis. Conclusion: In conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.

Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. The prevalence and risk factors of pulmonary function impairment were investigated in a large cohort of CCSs treated with potentially pulmotoxic therapy with a minimal follow-up of 5 years after diagnosis. METHODS: The study cohort consisted of all adult 5-year CCSs who were treated with bleomycin, pulmonary radiotherapy and/or pulmonary surgery in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996. Pulmonary function tests were performed to diagnose obstructive and restrictive pulmonary function impairment, and diffusion capacity impairment. RESULTS: The study population consisted of 220 out of 248 eligible CCSs, of whom 193 (87.7%) had performed a pulmonary function test at a median follow-up of 18 years after diagnosis. 85 (44.0%) out of 193 CCSs developed a pulmonary function impairment. Pulmonary function impairments occurred in all treatment groups. Most prevalent were restrictive pulmonary function impairment (17.6%) and a decreased carbon monoxide diffusion capacity (39.9%). Multivariate logistic regression models showed that, compared with bleomycin treatment only, treatment with radiotherapy, radiotherapy combined with bleomycin and radiotherapy combined with surgery were associated with the highest risk of pulmonary function impairment. CONCLUSIONS: The prevalence of pulmonary function impairment in long-term adult CCSs who received potentially pulmotoxic therapy is high. Bleomycin, pulmonary radiotherapy and pulmonary surgery are all associated with pulmonary function impairment. Pulmonary radiotherapy, especially in combination with bleomycin or surgery, is the most important risk factor. This emphasises the need for adequate counselling and follow-up for this patient population.

Long-term outcome of bilateral Wilms tumors (BWT).

BACKGROUND: Modern WT management consist of ample chemotherapy, nephron-sparing surgery, and, when indicated, radiotherapy. Survivors may develop renal failure or secondary tumors due to anticancer treatment. We analyzed long-term outcome (follow-up >5 years) after bilateral Wilms tumor (BWT) treatment with respect to survival, renal function, and secondary malignancies. METHODS: From 41 patients (23 females, 28 synchronous tumors) diagnosed with BWT between 1967 and 2007, 25 (18 females, 14 synchronous) with a follow-up >5 years could be included. Of this subgroup, median age at diagnosis was 1.64 years (range 0.27-5.35), and at maximum follow-up 14.99 years (range 5.40-33.99). Data were retrospectively collected and analyzed. RESULTS: One patient (4%) died 17.75 years after diagnosis, five (20%) had renal transplants: 3/5 after bilateral nephrectomy for Denys-Drash syndrome (DDS), and 2/5 for ESRD after an interval of 7 and 18 years, respectively. All transplanted patients remained in CR. Another three patients developed mild renal insufficiency (creatinine levels 1.3, 1.8, and 2.8 mg/100 ml, respectively; N = 0.5-1.2), combined with hypertension in 1; neither of them was transplanted. Sixteen (64%) had normal renal function and were in CR. Long-term renal function appeared significantly better after bilateral nephron sparing surgery (NSS) then after other surgical procedures (P < 0.0001). Seven secondary tumors were found in five (20%) patients, one of whom had a DDS. CONCLUSION: Long-term 10-year overall survival was 78%. There was significant morbidity (13/25, 52%), in terms of renal failure (8/25, 32%) including renal transplantation (5/25, 20%), and secondary tumors (5/25). These findings necessitate long-term follow-up beyond childhood. Future work should be directed at reducing the harmful effects of treatment, including the increased use of NSS.

A Role of brachytherapy in bilateral Wilms tumors: A long-term follow-up of three highly selected cases and literature review.

PURPOSE: To describe experience with partial nephrectomy combined with brachytherapy as part of the local management of bilateral Wilms tumor (WT) including a review of the available literature. RESULTS (METHODS AND CASE DESCRIPTION): Between 2011 and 2014, three highly selected patients (age nine months, 16 months, and 4 years) with bilateral WT (two synchronous and one metachronous) underwent enucleation and perioperative brachytherapy to the tumor bed. With a minimum follow-up of 5 years, all three patients are in continuous complete remission with preserved kidney function. CONCLUSIONS: Although nephron sparing surgery aiming at tumor free-margins remains the gold standard for bilateral WT, tumor enucleation followed by brachytherapy may be considered in carefully selected patients at high risk for end-stage kidney failure. Given the rarity and complexity of the procedure, concentration of care of such patients is mandatory.

Congenital diaphragmatic hernia: long-term risk of gastroesophageal reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is a well-recognized consequence of congenital diaphragmatic hernia (CDH). Results of studies examining predictive factors for early and late GERD are inconclusive. The aim of this study was to assess the incidence of early (<2 years) and late GERD (≥6 years) following CDH repair and to identify predictive variables. PATIENTS AND METHODS: Of 183 patients born with high-risk CDH, 107 survived and 38 were excluded. Perinatal and postnatal data of 69 eligible patients were analysed to identify variables predictive for early GERD. For the follow-up study, 58 patients (84%) (ages 12.1 ± 3.4 years; range 6-17) completed a standardised questionnaire. Results were compared with those from a healthy control group (n = 83). Patients who had a score indicating increased risk of GERD underwent further diagnostic assessment. Predictive factors for early and late GERD were identified using multivariate regression analysis. RESULTS: Early GERD was demonstrated in 27 patients (39%). Patch closure and intrathoracic position of the stomach were independent predictive variables for early GERD. At the time of follow-up, 9 of 58 patients (16%) had symptoms suggestive of GERD. In 7 patients (12%), late GERD was confirmed. For late GERD, however, no perinatal or postnatal risk factors were identified. CONCLUSIONS: Early GERD is more common in CDH patients with patch closure or intrathoracic position of the stomach. Predictive factors for late GERD could not be identified and screening for early GERD does not protect for future GERD; therefore, long-term follow-up for GERD in CDH survivors is mandatory.