[A Uncommon Case: Kasabach-Merritt syndrome with VACTERL Association]. / Ein seltener Fall: Kasabach-Merrit-Syndrom bei VACTERL-Assoziation.

The Kasabach-Merrit syndrome is characterized as the association of a vascular tumor, typically a caposiform hemangioendothelioma and rarely a tufted hemangioma, and a severe consumptive coagulopathy with potentially life-threatening thrombocytopenia. The severe coagulopathy with increased bleeding tendency must be considered before invasive procedures and often requires repeated platelet concentrate substitutions. We present a case of a mature male neonate with Kasabach-Merritt- Syndrome as well as VACTERL association. The VACTERL association describes a group of malformations. Our patient presented with anal atresia combined with tethered cord, and left renal agenesis. The VACTERL association as well as Kasabach-Merritt syndrome were found to be independent pathologies within this patient. A common occurrence or an association with each other has not been described in the literature so far. The challenging coagulation setting due to severe thrombocytopenia complicated the surgical management so far. Finally, mTOR-inhibitor sirolimus was successful in terms of tumor reduction and especially reduction of platelet consumption.

Stereological Lung Parameters After Fetoscopic Abdominal Decompression of Congenital Diaphragmatic Hernia in an Ovine Model: A Pilot Study.

Background: Fetoscopic endoluminal tracheal occlusion (FETO) improves lung maturation in severe cases of congenital diaphragmatic hernia (CDH) but it does not ameliorate lung compression by herniated abdominal organs. Surgically opening the fetal abdomen (abdominal decompression [AD]) reduces the intrathoracic pressure by diverting the abdominal organs into the amniotic cavity-a probable causal therapy for lung hypoplasia and pulmonary hypertension in CDH. Open surgical abdominal decompression has been reported: we describe a minimally invasive approach in an ovine model of CDH as a probable fetoscopic intervention. Materials and Methods: Eight fetuses were included, 2 were kept as HEALTHY controls. A CDH (left side, liver down) was created by open fetal surgery at midgestation in 6 fetuses, 2 were taken as CDH controls. Fetoscopic abdominal decompression (fAD) was performed 21 days later in 4 animals. The fetuses were retrieved at the end of gestation and evaluated by lung stereology. Results: fAD led to a near total evacuation of the thoracic cavity in 2 of the 4 animals. Fetuses with CDH had a lower total volume and fraction of alveolar air space, a lower volume fraction of the parenchyma, and an increase of the volume fraction of the alveolar septa and atelectasis, as well as an increased mean thickness of alveolar septa compared with HEALTHY fetuses. Fetuses treated with abdominal decompression showed an improvement of stereological parameters. Conclusions: In spite of relevant limitations (pilot study, small groups, spontaneous closure of the abdominal incision) we were able to demonstrate that abdominal decompression for CDH can be performed by fetoscopy. Our results support the hypothesis of causally improving lung development by abdominal decompression, thus implying increased survival in extreme cases of CDH. A refinement of the fetoscopic techniques and direct comparison to FETO appears warranted.

Fetoscopic techniques for prenatal covering of gastroschisis in an ovine model are technically demanding and do not lead to permanent anchoring on the fetus until the end of gestation.

INTRODUCTION: This is the cumulative technical report on the operative procedures and limitations of fetoscopic bag insertion, intestinal bag placement, and bag fixation to the fetus in a series of pilot studies in an ovine model for prenatal treatment of gastroschisis. MATERIAL AND METHODS: In 24 German blackhead sheep, a surgically created gastroschisis was managed by fetoscopic placement of the extruded intestines into a bag. The bag was then fastened onto the fetal abdominal wall. Different materials (sterile gloves, latex condoms, laparosopic retrieval bags) and different fixation techniques (laparoscopic staplers, interrupted and continuous sutures) have been examined. The fetuses were retrieved and evaluated at the end of gestation. RESULTS: Uterine bag insertion was successful in 15 of 24 (62.5%) and intestinal bag placement in 10 of 15 available fetuses (66.6%). The main factor limiting fetoscopic procedures was chorioamniotic separation (CAS). Sterilized condoms provided the most appropriate type of bags and the V-Loc™ running suture, the most expedient type of fixation, which was achieved in 9 of the 10 fetuses (complete = 2, partially = 7) by using a three port access (5 mm and 2 × 3 mm). All bags were encountered completely or partially dislocated from the fetus at the end of gestation. CONCLUSIONS: Fetoscopic intestinal bag placement and fixation in gastroschisis technically demanding. None of the evaluated techniques led to permanent anchorage of the bag to the fetus. The development of specially designed instruments, bags and fixation methods is required to optimize this approach.

Regenerative capacity of the enteric nervous system: is immaturity defining the point of no return?

BACKGROUND: Intestinal obstruction in newborns is associated with intestinal motility disorders after surgery. Alterations in the enteric nervous system (ENS) might cause abnormal peristalsis, which may then result in intestinal motility disorders. We aimed to quantify alterations in the myenteric plexus after a ligation and to test if these alterations were reversible. METHODS: Small intestines of chicken embryos were ligated in ovo at embryonic day (ED) 11 for either 4 d (ED 11-15) or 8 d (ED 11-19). Both treated groups and control group were sacrificed and intestinal segments examined by means of both light and electron microscopy. RESULTS: The number of proximal myenteric ganglia increased (ED 19, 30.7 ± 3.16 versus 23.1 ± 2.03; P < 0.001) in the 8-d ligature group but had values similar to the control group in the 4-d ligature group. The size distribution was skewed toward small ganglia in the 8-d ligature group (ED 19, 83.71 ± 11.60% versus 3.88 ± 4.74% in the control group; P < 0.001) but comparable with the control group in the 4-d ligature group. Subcellular alterations in the 4-d ligature group were reversible. CONCLUSIONS: The pathologic alterations in the ENS were fully reversible in the 4-d ligature group. This reversibility might be linked to the degree of immaturity of the ENS.

Reversible small bowel obstruction in the chicken foetus.

BACKGROUND: Ligation of the embryonic gut is an established technique to induce intestinal obstruction and subsequently intestinal atresia in chicken embryos. In this study, we modified this established chicken model of prenatal intestinal obstruction to describe (1) the kinetics of morphological changes, (2) to test if removal of the ligature in ovo is possible in later embryonic development and (3) to describe morphological adaptations following removal of the ligature. MATERIALS AND METHODS: On embryonic day (ED) 11, small intestines of chick embryos were ligated micro surgically in ovo. In Group 1 (n = 80) gut was harvested proximal and distal to the ligation on ED 12-19. In Group 2 (n = 20) the induced obstruction was released on day 15 and gut was harvested on ED 16-19. Acetyl choline esterase staining was used as to assess resulting morphological changes. RESULTS: A marked intestinal dilatation of the proximal segment can be seen 4 days after the operation (ED 15). The dilatation increased in severity until ED 19 and intestinal atresia could be observed after ED 16. In the dilated proximal segments, signs of disturbed enteric nervous system morphology were obvious. In contrast to this, release of the obstruction on ED 15 in Group 2 resulted in almost normal gut morphology at ED 19. CONCLUSION: Our model not only allows the description of morphological changes caused by an induced obstruction on ED 11 but also-more important - of morphological signs of adaptation following the release of the obstruction on ED 15.

Midterm outcome of transumbilically laparoscopic-assisted versus laparoscopic and open appendectomy in children--a matched prospective study.

BACKGROUND: Prospective data of transumbilically laparoscopic-assisted appendectomies (TULAA) is absent in the pediatric population. We therefore compared the midterm outcome of TULAA with open (OA) and laparoscopic (LA) appendectomies in children with appendicitis in a matched prospective study. METHODS: A total of 20 patients operated with TULAA were matched to 20 cases operated by LA and OA, respectively, according to sex, age, and histology of the resected appendix. All 60 children were evaluated during a 3-month follow-up visit. RESULTS: The subjective pain level after discharge, the rate of complications, and persistent painful wound as well as the duration of days refraining from school or kindergarten were similar in all three groups. The wound satisfaction was significantly higher in TULAA and LA. Children operated with TULAA had a faster return to full physical activity compared with OA. CONCLUSION: Our data suggest that TULAA, LA, and OA have a similar outcome 3 months after surgery apart from cosmetic appearance of the wound and return to full physical activity in pediatric patients. Whether parental bias or the increased wound satisfaction act as confounders for early return to full physical activity should be evaluated in larger prospective randomized trials.

Complex gastroschisis is a different entity to simple gastroschisis affecting morbidity and mortality-a systematic review and meta-analysis.

BACKGROUND: Comparison of the outcome of newborns with simple (sGS) and complex gastroschisis (cGS: gastroschisis with atresia, necrosis, perforation or volvulus). MATERIALS AND METHODS: We conducted a systematic database search, quality assessment and meta-analyzed relevant articles which evaluated the mortality and morbidity of newborns with cGS versus sGS. Risk ratios (RR) with 95% confidence interval (CI) were reported for categorical data, and the mean difference (MD) was calculated for continuous data. Pooled estimates of RR and MD were computed using generic inverse variance and a random-effects model. RESULTS: Of 19 identified reports, 13 eligible studies were included. The mortality of infants with cGS (16.67%) was significantly higher than sGS (2.18%, RR: 5.39 [2.42, 12.01], p<0.0001). Significantly different outcome was found for the following parameters: Infants with cGS are started on enteral feedings later and they take longer to full enteral feedings with a subsequent longer duration of parenteral nutrition. Their risk of sepsis, short bowel syndrome and necrotizing enterocolitis is higher. They stay longer in hospital and are more likely to be sent home with enteral tube feedings and parenteral nutrition. DISCUSSION: Occurring in 17% of infants born with gastroschisis, complex gastroschisis is associated with a significantly increased morbidity and mortality. More research should be focused on this special subgroup of patients, not only on postnatal management, but additionally directing efforts to improve diagnosing and predicting complex gastroschisis prenatally as well as implement any probable fetal intervention to alleviate its disastrous outcome.

Transumbilical laparoscopic-assisted versus 3-port laparoscopic and open appendectomy: a case-control study in children.

INTRODUCTION: Aim of this study was to compare the short-term outcome of transumbilical laparoscopic-assisted (TULAA) with laparoscopic (LA) and open appendectomy (OA) in a case-control study. MATERIALS AND METHODS: Our first 20 consecutive children with appendicitis treated with TULAA were matched to 20 patients treated with LA and OA, respectively. Matching criteria were age, sex, and the histology of appendicitis. The children were retrospectively evaluated for outcome, efficacy, and complications. RESULTS: No significant differences between the groups were found, except that children operated by OA required less analgesics than children operated by LA and TULAA. DISCUSSION: TULAA appears to be a safe procedure with no disadvantage except for postoperative pain, which needed a longer course of analgesics compared to OA. Whether TULAA has advantages over LA and OA has to be evaluated in larger prospective series.

Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis.

BACKGROUND: The pathogenesis of intestinal dysmotility in gastroschisis is not completely understood. Peel formation and disorganization of interstitial Cajal cells (ICC) have been proposed in humans. The aim of this study was to evaluate the impact of prenatal coverage of gastroschisis on gut inflammation and expression of ICC in a fetal lamb model. METHODS: Twenty-one German blackhead sheep with an abdominal wall defect that was created fetoscopically on day 77 of 145 days gestation were used in this study. Intrauterine surgery with the aim to cover the defect was performed 3 weeks later; two fetuses were covered completely, 5 partially and 11 remained uncovered. Three fetuses without gastroschisis were used as controls. All fetuses were retrieved by cesarean section at day 135. Samples of the small intestine were stained with hematoxylin and eosin for histologic analysis of peel formation and serosal and muscular thickness. For ICC detection, immunohistochemistry using anti-CD117 (c-Kit) antibody was used. RESULTS: In all samples with exposure to amniotic fluid, peel formation and significantly decreased ICC were found. Complete coverage reduced peel formation and disorganization of ICC compared to uncovered animals almost to the level of controls. CONCLUSIONS: Peel formation and ICC derangement were significantly reduced by prenatal coverage of gastroschisis. Moreover, this animal model mimics the histopathological bowel changes as seen in human gastroschisis and may, therefore, be used for further research on the pathophysiology and fetal therapy of this malformation.

PGK1 as predictor of CXCR4 expression, bone marrow metastases and survival in neuroblastoma.

BACKGROUND AND AIM: A close relationship between phosphoglycerate kinase 1 (PGK1) and the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) has been shown for several cancers. However, the role of PGK1 has not been investigated for neuroblastoma, and PGK1 might be a therapeutic target for this tumor entity. The aim of the current study was to evaluate the role of PGK1 expression in neuroblastoma patients, to determine the impact of PGK1 expression levels on survival, and to correlate PGK1 expression with CXCR4 expression and bone marrow dissemination. MATERIALS AND METHODS: Samples from 22 patients with neuroblastoma that were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated for expression of PGK1 and CXCR4 using immunohistochemistry. Results were correlated with clinical parameters, metastases and outcome of patients. Immunocytochemistry, proliferation and expression analysis of CXCR4 and PGK1 were performed in neuroblastoma cell lines. RESULTS: PGK1 is expressed in neuroblastoma cells. PGK1 expression is significantly positively correlated with CXCR4 expression and tumor dissemination to the bone marrow. Moreover the expression of PGK1 is significantly associated with a negative impact on survival in patients with neuroblastoma. PGK1 is downregulated by inhibition of CXCR4 in neuroblastoma cells. CONCLUSION: PGK1 appears to play an important role for neuroblastoma, predicting survival and tumor dissemination. Further in vivo studies outstanding, it is a candidate target for novel therapeutic strategies.

Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis.

INTRODUCTION: The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC). MATERIAL AND METHODS: Newborn Sprague-Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression. RESULTS: The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p<0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1. DISCUSSION: Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.

Clinical and sonographic features predict testicular torsion in children: a prospective study.

OBJECTIVE: To test the clinical and sonographic predictors of testicular torsion (TT) with the aim of reducing negative exploration rates. PATIENTS AND METHODS: We performed a prospective study of all boys treated for 'acute scrotum' at our institute between January 2001 and April 2012 and clinical findings were documented. If available, ultrasonography (US) was added to the diagnostic evaluation. A prediction of the diagnosis was based on clinical and sonographic features, and was followed by surgical exploration in all patients. RESULTS: A total of 104 patients were included in the 16-month period of the study. No single finding excluded TT. The clinical features (pain <24 h, nausea/vomiting, abnormal cremasteric reflex, high position of the testis) appeared predictive (100% sensitivity) and the clinical scoring system was proven to be reliable, reducing the negative exploration rate by >55%. Ultrasound predictors alone were not able to identify all boys with TT. CONCLUSIONS: It is safe to refrain from routine surgical exploration in every child with acute scrotum if the clinical score is applied, which results in a marked reduction of negative explorations. A reliable diagnosis could not be obtained based on US alone. As scrotal US is unpleasant for the child, we propose to refrain from this if the clinical score is positive. Patients with a negative clinical score are suitable candidates for US to establish and secure diagnosis.

Differentiation of epididymitis and appendix testis torsion by clinical and ultrasound signs in children.

OBJECTIVE: To identify the signs that can help to differentiate torsion of the appendix testis (AT) and epididymitis and to establish the incidence of the various pathologic entities in boys with an acute scrotum. MATERIALS AND METHODS: A retrospective study was performed of the data from all boys treated at our institute from January 2008 to January 2012 for the diagnosis of an "acute scrotum." The clinical and, if available, ultrasound findings were documented. Differences between groups were calculated using a chi-square test or analysis of variance and classification and regression tree analysis. RESULTS: A total of 241 boys with acute scrotal pain were included and underwent surgical exploration. Of the 241 boys, 163 (70%) had AT, 44 (18.5%) had epididymitis, 31 (13.3%) had testicular torsion, and 3 (1.3%) had idiopathic scrotal edema. The incidence of AT was significantly increased in the colder months (P = .01). We found that AT and epididymitis shared several aspects but differed regarding dysuria (epididymitis, P ≤.001), a painful epididymis on palpation (epididymitis, P = .028), increased epididymal echogenicity (epididymitis, P = .043), augmented peritesticular perfusion (epididymitis, P = .05), and a positive blue dot sign (AT, P <.001). The classification and regression tree analysis showed that the presence of dysuria, a positive blue dot sign, and a painful epididymis are the best factors for distinguishing AT and epididymitis. CONCLUSION: Most children with an acute scrotum will have AT or epididymitis. It will be possible to differentiate most cases using the clinical and ultrasound findings. In our study, the best predictors were dysuria, a painful epididymis on palpation, and altered epididymal echogenicity and increased peritesticular perfusion found on ultrasound studies for epididymitis and a positive blue dot sign for AT.

Rectum perforation after broomstick impalement in a 17-year-old: case report and review.

Impalement injuries are uncommon, especially in the pediatric population. Because of the rarity of these injuries, physicians may have difficulty recognizing and treating impalement injuries appropriately. Clinical findings are sometimes innocuous, but can be life threatening. Therefore, evaluation of suspected impalement injury should involve careful history and thorough physical examination, even if there is no evidence of trauma to the perineum. We report a very rare case of rectum perforation after transanal introduction of a broomstick with almost no clinical findings. Impalement injuries are difficult to recognize, and severity may not be reflected by their external appearance. To diagnose these injuries in time, it is important to use a well-organized workup.

Abdominal wall incision with or without exteriorization of bowel: results from a fetal lamb model for the embryogenesis of gastroschisis.

INTRODUCTION: The embryogenesis of gastroschisis is not completely understood. The aim of our study was to evaluate the impact of a simple abdominal wall defect versus a defect including eviscerated intestine or omentum for the development of gastroschisis in a fetal lamb model. MATERIAL AND METHODS: At mid-gestation (day 77) an abdominal wall defect was fetoscopically created with three different approaches in 19 German blackhead sheep. The intestine was eviscerated in 7 fetuses (group 1). The peritoneum was incised and a patch of the omentum pulled through the incision in 5 fetuses (group 2). In 7 fetuses (group 3) the skin and rectus muscle were incised until the peritoneum was visible. In this group, no abdominal contents were exteriorized and the peritoneum was left intact. A second fetoscopic procedure was performed 21 days later, assessing the condition and extension of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. RESULTS: The second fetoscopy acting as a control for the creation of gastroschisis demonstrated eviscerated and inflamed intestine in all 3 groups. The amount of eviscerated intestine did not appear to depend on the size of the defect nor on its duration. DISCUSSION: It appears that a simple incision of the abdominal wall with intact peritoneum is sufficient for the development of gastroschisis in a fetal sheep model. This finding may improve the understanding of the etiology of gastroschisis.

Clinical predictors of testicular torsion in children.

OBJECTIVE: To distinguish the prognostic factors that decrease the probability of a negative exploration for "acute scrotum." In some institutes, patients with "acute scrotum" undergo immediate exploration after clinical evaluation. Because testicular torsion (TT) accounts only for a fraction of these cases, most infants can be treated conservatively. METHODS: We performed a retrospective study of all patients treated at our institute from January 2008 to December 2009 for the diagnosis of "acute scrotum." Differences between groups were calculated using the chi-square test or analysis of variance and Mann-Whitney-Wilcoxon test for univariate or multivariate analysis, expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The data from 138 patients were analyzed. The mean age was 9 years, 8 months. Of the 138 patients, 19 (13.8%) had TT. This group was compared with the boys without TT at exploration. The patients with TT were older on average (11 years, 1 month vs 9 years, 1 month, p = .035). Pain for <24 hours (OR 4.2, 95% CI 1.3-13.4), nausea and/or vomiting (OR 21.6, 95% CI 4.9-93.4), abnormal cremasteric reflex (OR 4.8 95% CI 0.7-35.2), and a high position of the testis (OR 18.0 95% CI 1.8-177.1) were associated with an increased likelihood of torsion. In the group of boys with ≥ 2 of these findings present, 100% had TT at exploration, with 0% false-positive results. CONCLUSION: TT is uncommon among the group of boys treated for "acute scrotum." In particular, a pain duration <24 hours, nausea or vomiting, a high position of the testis, and an abnormal cremasteric reflex had a positive prognostic value for TT. A clinical score might help to avoid unnecessary explorations. In the future, we intend to test the diagnostic set described combined with ultrasonography.

Fetoscopic management of gastroschisis in a lamb model.

BACKGROUND: Gastroschisis is a malformation consisting of an abdominal wall defect with eviscerated bowel. Its standard treatment is postnatal repositioning or temporary prosthetic bag placement. The aim of our study is to evaluate the feasibility of its fetoscopic management in a lamb model. METHODS: At mid-gestation (day 75), gastroschisis was created in eight German blackhead sheep. A second fetoscopic procedure was performed on day 105, assessing the viability, extension, and potential for repositioning of eviscerated bowel. The fetus was retrieved by Cesarean section on day 132 and evaluated. RESULTS: In six fetuses gastroschisis could be successfully created and assessed with fetoscopy. Two fetuses were lost due to technical complications. Primary repair by repositioning the intestine into the abdomen was not possible because it grew into an inflammatory conglomerate too large for the small fetal abdominal cavity. CONCLUSIONS: Although technically demanding, we were able to produce and reassess six cases of gastroschisis by fetoscopy. As primary repositioning appears unfavorable, fetoscopic prosthetic bag placement may become an alternative.

Differential diagnosis of tendon tumors: xanthomas caused by hyperlipidemia in children.

Tumors of tendons and tendon sheaths causing pain and mechanical problems are often because of overstraining, and in most cases the resulting common ganglia can be easily removed. We describe an 8-year-old child in whom the tumor's origin had remained undetected and was related to a homozygous familial hypercholesterolemia, which can be associated with multiple xanthomas of the skin and tendons. After a thorough investigation and therapy, a program to prevent arteriosclerosis and myocardial infarct in this patient was initiated.

Hemorrhagic necrotizing pancreatitis with a huge pseudocyst in a child with Crohn's disease.

Pancreatitis has been described occasionally in association with Crohn's disease in adults before, but it is uncommon in children. It may be caused by multiple etiologies, and there exist a few reports of pancreatitis in pediatric patients with inflammatory bowel disease because of biliary obstruction or drug induced. We report a rare case of a 14-year-old girl with Crohn's disease and hypoparathyroidism who suffered from hemorrhagic necrotizing pancreatitis with development of huge psyeudocysts, a life-threatening complication that required surgical treatment.