Multidisciplinary Treatment Strategies for Wilms Tumor: Recent Advances, Technical Innovations and Future Directions.

Significant progress has been made in the management of Wilms tumor (WT) in recent years, mostly as a result of collaborative efforts and the implementation of protocol-driven, multimodal therapy. This article offers a comprehensive overview of current multidisciplinary treatment strategies for WT, whilst also addressing recent technical innovations including nephron-sparing surgery (NSS) and minimally invasive approaches. In addition, surgical concepts for the treatment of metastatic disease, advances in tumor imaging technology and potentially prognostic biomarkers will be discussed. Current evidence suggests that, in experienced hands and selected cases, laparoscopic radical nephrectomy and laparoscopic-assisted partial nephrectomy for WT may offer the same outcome as the traditional open approach. While NSS is the standard procedure for bilateral WT, NSS has evolved as an alternative technique in patients with smaller unilateral WT and in cases with imminent renal failure. Metastatic disease of the lung or liver that is associated with WT is preferably treated with a three-drug chemotherapy and local radiation therapy. However, surgical sampling of lung nodules may be advisable in persistent nodules before whole lung irradiation is commenced. Several tumor markers such as loss of heterozygosity of chromosomes 1p/16q, 11p15 and gain of function at 1q are associated with an increased risk of recurrence or a decreased risk of overall survival in patients with WT. In summary, complete resection with tumor-free margins remains the primary surgical aim in WT, while NSS and minimally invasive approaches are only suitable in a subset of patients with smaller WT and low-risk disease. In the future, advances in tumor imaging technology may assist the surgeon in defining surgical resection margins and additional biomarkers may emerge as targets for development of new diagnostic tests and potential therapies.

Hepatoblastoma Cancer Stem Cells Express PD-L1, Reveal Plasticity and Can Emerge upon Chemotherapy.

The biology of cancer stem cells (CSCs) of pediatric cancers, such as hepatoblastoma, is sparsely explored. This is mainly due to the very immature nature of these tumors, which complicates the distinction of CSCs from the other tumor cells. Previously, we identified a CSC population in hepatoblastoma cell lines expressing the CSC markers CD34 and CD90, cell surface Vimentin (csVimentin) and binding of OV-6. In this study, we detected the co-expression of the immune escape factor PD-L1 in the CSC population, whereas the other tumor cells remained negative. FACS data revealed that non-CSCs give rise to CSCs, reflecting plasticity of CSCs and non-CSCs in hepatoblastoma as seen in other tumors. When we treated cells with cisplatin and decitabine, a new CD34+/lowOV-6lowCD90+ population emerged that lacked csVimentin and PD-L1 expression. Expression analyses showed that this new CSC subset shared similar pluripotency and EMT features with the already-known CSCs. FACS results further revealed that this subset is also generated from non-CSCs. In conclusion, we showed that hepatoblastoma CSCs express PD-L1 and that the biology of hepatoblastoma CSCs is of a plastic nature. Chemotherapeutic treatment leads to another CSC subset, which is highly chemoresistant and could be responsible for a poor prognosis after postoperative chemotherapy.

Ovarian lesions and tumors in infants and older children.

Objectives: Ovarian lesions are rare but frequent in children. Patients could present with abdominal pain, but ovarian lesions could also be incidentally found on ultrasound. Awareness is required in cases with acute, severe lower abdominal pain, as ovarian torsion could be the cause. Other lesions can be cysts or benign or malignant ovarian tumors. Thus, the aim of this paper is to review typical ovarian lesions according to age, imaging and laboratory findings, and surgical management. Methods: We retrospectively analysed the patient charts of 39 patients aged 10.4 ± 6.1 years (from 3 months to 18 years) with ovarian lesions treated in our institution between 01/2009 and 08/2020. All clinical and pathological findings of infants and children operated on for ovarian lesions were included. Results: Ovarian lesions in children younger than 2 years of age were typically ovarian cysts, and ovarian tumors were not observed in this age group. In older children over 10 years of age, tumors were more common - with mostly teratoma or other germ cell tumors, followed by epithelial tumors. Moreover, acute or chronic ovarian torsion was observed in all age groups. In general, ovarian tumors were much larger in size than ovarian cysts or twisted ovaries and eventually showed tumor marker expression of AFP or ß-HCG. Simple ovarian cysts or twisted ovaries were smaller in size. Surgery for all ovarian lesions should aim to preserve healthy ovarian tissue by performing partial ovariectomy. Conclusions: In adolescent girls with acute abdominal pain, immediate laparoscopy should be performed to rule out ovarian torsion. Careful imaging evaluation and the assessment of tumor markers should be performed in painless ovarian lesions to indicate an adequate surgical ovarian-sparing approach.

Comparison of perioperative outcomes between laparoscopic and open partial splenectomy in children and adolescents.

BACKGROUND: In order to avoid consequences of total splenectomy, partial splenectomy (PS) is increasingly reported. The purpose of this study was to compare perioperative outcomes of laparoscopic PS (LPS) and open PS (OPS) in children and adolescents. AIM: To compare perioperative outcomes of patients with LPS and OPS. METHODS: After institutional review board approval, a total of 26 patients that underwent LPS or OPS between January 2008 and July 2018 were identified from the database of our tertiary referral center. In total, 10 patients had LPS, and 16 patients underwent OPS. Blood loss was calculated by Mercuriali's formula. Pain scores, analgesic requirements and complications were assessed. The Wilcoxon rank sum test was used for comparison. To compare categorical variables, Fisher's exact test was applied. RESULTS: LPS was performed in 10 patients; 16 patients had OPS. Demographics (except for body mass index and duration of follow-up), indicating primary disease, preoperative spleen size and postoperative spleen volume, perioperative hematological parameters, postoperative pain scores, analgesic requirements, adverse events according to the Clavien-Dindo classification and the comprehensive complication index, median time from operation to initiation of feeds, median time from operation to full feeds, median time from operation to mobilization and median length of hospital stay did not differ between LPS and OPS. Median (range) operative time (min) was longer in LPS compared to the OPS group [185 (135-298) vs 144 (112-270), respectively; P = 0.048]. Calculated perioperative blood loss (mL of red blood cell count) was higher in the LPS group compared to OPS [87 (-45-777) vs -37 (-114-553), respectively; P = 0.039]. CONCLUSION: This is the first study that compared outcomes of LPS and OPS. Both operative approaches had comparable perioperative outcomes. LPS appears to be a viable alternative to OPS.

Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG.

Cancer stem cells (CSCs) are nowadays one of the major focuses in tumor research since this subpopulation was revealed to be a great obstacle for successful treatment. The identification of CSCs in pediatric solid tumors harbors major challenges because of the immature character of these tumors. Here, we present CD34, CD90, OV-6 and cell-surface vimentin (csVimentin) as reliable markers to identify CSCs in hepatoblastoma cell lines. We were able to identify CSC characteristics for the subset of CD34+CD90+OV-6+csVimentin+-co-expressing cells, such as pluripotency, self-renewal, increased expression of EMT markers and migration. Treatment with Cisplatin as the standard chemotherapeutic drug in hepatoblastoma therapy further revealed the chemo-resistance of this subset, which is a main characteristic of CSCs. When we treated the cells with the Hsp90 inhibitor 17-AAG, we observed a significant reduction in the CSC subset. With our study, we identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. This set of markers could be helpful to estimate the success of novel therapeutic approaches, as resistant CSCs are responsible for tumor relapses.

The testicular descent in the rat: a scanning electron microscopic study.

PURPOSE: Numerous researchers studied the morphology of testicular descent including the possible function of gubernaculum. However, a clear illustration of this process is still missing. The aim of this study was to illustrate testicular descent using scanning electron microscopy (SEM) in a rat model. METHODS: The abdomen of rat fetuses between gestational day (E) 15 and E 22 and newborns at postnatal day (D) 0 and D 1.5 was opened by microsurgery. Standard preparation for SEM was carried out. The position of the testis and gubernaculum testis was documented. RESULTS: The gubernaculum was obvious in male rat embryos at E 17.5. In a first phase (E 16-E 21) the testis moved from cranio-lateral and dorsal to caudo-medial and ventral, while clear signs of an active role of the gubernaculum were missing. In a second phase (E 22-D 1.5) the processus vaginalis peritonei (PVP) developed, while the conus of the gubernaculum disappeared, after which, the testis moved out of the abdominal cavity and entered the PVP. CONCLUSION: In our study, we could not specify the role of gubernaculum for testicular descent. However, our data showed that the testis lay intraperitoneal throughout the descensus testis.

Comparison of outcomes between complete and incomplete congenital duodenal obstruction.

BACKGROUND: Congenital duodenal obstruction (CDO) can be complete (CCDO) or incomplete (ICDO). To date there is no outcome analysis available that compares both subtypes. AIM: To quantify and compare the association between CCDO and ICDO with outcome parameters. METHODS: We retrospectively reviewed all patients who underwent operative repair of CCDO or ICDO in our tertiary care institution between January 2004 and January 2017. The demographics, clinical presentation, preoperative diagnostics and postoperative outcomes of 50 patients were compared between CCDO (n = 27; atresia type 1-3, annular pancreas) and ICDO (n = 23; annular pancreas, web, Ladd´s bands). RESULTS: In total, 50 patients who underwent CDO repair were enrolled and followed for a median of 5.2 and 3.9 years (CCDO and ICDO, resp.). CCDO was associated with a significantly higher prenatal ultrasonographic detection rate (88% versus 4%; CCDO vs ICDO, P < 0.01), lower gestational age at birth, lower age and weight at operation, higher rate of associated congenital heart disease (CHD), more extensive preoperative radiologic diagnostics, higher morbidity according to Clavien-Dindo classification and comprehensive complication index (all P ≤ 0.01). The subgroup analysis of patients without CHD and prematurity showed a longer time from operation to the initiation of enteral feeds in the CCDO group (P < 0.01). CONCLUSION: CCDO and ICDO differ with regard to prenatal detection rate, gestational age, age and weight at operation, rate of associated CHD, preoperative diagnostics and morbidity. The degree of CDO in mature patients without CHD influences the postoperative initiation of enteral feeding.

C-kit receptor in the human vas deferens: distinction of mast cells, interstitial cells and interepithelial cells.

The molecular mechanisms underlying the regulation of vas deferens (VD) motility and semen emission are still poorly understood. Interstitial cells of Cajal (ICC), which harbour the c-kit receptor (CD117), provide the basis of coordinated gut motility. We investigated whether c-kit receptor-positive cells also exist in the normal human VD. Enzyme and fluorescence immunohistochemical techniques were applied on serial sections of human proximal, middle, and distal VD segments (n=49) employing 13 different monoclonal and polyclonal antibodies recognizing the c-kit receptor. The c-kit receptor was detected in either round- or spindle-shaped cells. On account of their antigenic profile, the round- and oval-shaped c-kit receptor-positive cells were identified as mast cells (MC) occurring in all layers of the VD except the epithelium. In contrast, two distinct populations of exclusively c-kit receptor-positive spindle-shaped cells were found within the lamina propria and, rarely, in the inner and outer smooth muscle layers, as well as within the epithelium. Different shaped c-kit receptor-positive MC and IC were present in all layers of the human VD. Our findings demonstrate the presence of different c-kit receptor-positive cells also in the human VD. Their rather ubiquitous distribution within the lamina propria and muscle layers suggests that IC and MC may modulate the neuromuscular transmission and the propagation of electrical signals in multiple systems involved in the draining of fluids. The importance of the c-kit receptor-positive interepithelial cells remains unclear.

L1 is associated with favorable outcome in neuroblastomas in contrast to adult tumors.

BACKGROUND: Neuroblastoma is the most common solid tumor in childhood with unconventional clinical behavior. L1, a neuronal cell adhesion molecule, is associated with poor survival in malignant adult tumors. The aim of the current study was to determine expression of L1 in pediatric neuroblastoma. METHODS: L1 expression was assessed on a tissue microarray with 66 surgically resected neuroblastoma samples by immunohistochemistry with a monoclonal antibody and peroxidase method. Additionally, mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction with L1-specific primers. Data were correlated survival data by log rank test and Cox regression multivariate analysis. RESULTS: L1 was detected in 57 (86%) of 66 neuroblastomas, whereas 9 (14%) were L1 negative. Median survival of all children was 72 months. Analysis with Kaplan-Meier method revealed a surprising and contrary finding to adult tumor entities: an association of L1 positivity with better event-free and overall survival (P < .001 and P < .01 by log rank test). Multivariate Cox regression analysis showed an independent prognostic impact of L1 negativity for event-free and overall survival of the children (P < .05). CONCLUSIONS: In contrast to adult tumor entities, where L1 is associated with aggressive clinical behavior, our data show that L1 predicts good outcome in children with neuroblastoma. This novel finding suggests an inverse role of L1 in neuroblastoma. Future studies might focus on the molecular basis of the varying effect of L1 in different tumors.

Thy-1 as a potential novel diagnostic marker for gastrointestinal stromal tumors.

PURPOSE: Only few immunohistochemical markers besides c-kit exist for gastrointestinal stromal tumors (GISTs). Thy-1, a cell-surface glycoprotein, is a marker for several types of stem cells and particularly for neuronal precursor cells. The aim of this study was to determine Thy-1 expression in GISTs. MATERIALS AND METHODS: Fifty-seven surgically resected and paraffin-embedded GIST samples were analyzed by immunohistochemistry with peroxidase method for Thy-1 molecule. RESULTS: Thy-1 was detected in the majority of 57 GIST samples (54 out of 57 patients, 95%). All samples were c-kit positive and 90% were CD34 positive. All three Thy-1 negative samples were CD34 positive, had a low proliferative index (Ki-67

Midkine as a prognostic marker for gastrointestinal stromal tumors.

PURPOSE: Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The outcome of patients with gastrointestinal stromal tumors (GISTs) is correlated with tumor size and mitotic count. The aim of this study was to determine MK expression in GISTs. METHODS: Midkine was detected in 31 (55%) of 57 surgically resected GISTs by immunohistochemistry with a rabbit antibody against MK and peroxidase method. RESULTS: A significant worse outcome of MK-positive patients was found (P < 0.05; log rank test). Multivariate Cox regression analysis showed an independent prognostic impact (relative risk for overall survival 3.64; P < 0.05). Interestingly, MK expression was significantly associated with mitotic rate (P < 0.05; Chi-squared test), but not with tumor size (P = 0.97). CONCLUSIONS: Taken together, MK is a prognostic marker for GIST patients. MK might also be a useful peripheral tumor marker since it can be detected in peripheral serum. Future studies should involve higher GIST patient numbers including tumor and serum samples for detection of MK.

Cell growth and differentiation of different hepatic cells isolated from fetal rat liver in vitro.

Stem cells are interesting candidates as a new source for cell/organ culture or cell transplantation concepts. So far it is believed that the hepatoblast is the common progenitor cell during fetal liver development. In previous studies two distinct fractions of liver cells were found during development: cells co-expressing Thy1 and CK-18 (cytokeratin-18) and cells expressing CK-18 only. In this study we cultured Thy1-positive and Thy1-negative hepatic progenitors isolated from collagenase digested fetal rat livers after depletion of OX43/OX44-positive hematopoietic cells. The cells were cultured on a collagen-I matrix in a medium containing epidermal growth factor, insulin, and fetal calf serum. Thy1-positive cells isolated from ED16, ED18, or ED20 livers showed significantly enhanced cell growth compared with Thy1-negative cells during the culture period. Both cell types showed expression of the liver-specific genes CK-18, albumin and alpha-feto-protein at the beginning of the culture period, as assessed by reverse-transcription polymerase chain reaction and immunocytochemistry. The growth of Thy1-positive cells was significantly higher when compared with Thy1-negative cells and declined with maturation of the liver. The data suggest a stem cell-like growth potential of Thy1-positive fetal hepatic cells. Thus, these cells might be useful for concepts of cell-based therapies. However, further efforts must be undertaken to define the biological, ethical, and legal aspects of using fetal cells.

Hepatocytic differentiation of mesenchymal stem cells in cocultures with fetal liver cells.

AIM: To investigate the hepatocytic differentiation of mesenchymal stem cells (MSCs) in co-cultures with fetal liver cells (FLC) and the possibility to expand differentiated hepatocytic cells. METHODS: MSCs were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSCs were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with stem cell factor (SCF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and fibroblast growth factor 4 (FGF-4) alone, or in presence of freshly isolated FLC. Cells in co-cultures were harvested, and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. Reverse transcription-polymerase chain reaction (RT-PCR) for the liver specific markers cytokeratin-18 (CK-18), albumin, and alpha-fetoprotein (AFP) was performed in different cell populations. RESULTS: Under the specified culture conditions, rat MSCs co-cultured with FLC expressed albumin, CK-18, and AFP-RNA over two weeks. At wk 3, MSCs lost hepatocytic gene expression, probably due to overgrowth of the cocultured FLC. FLC also showed a stable liver specific gene expression in the co-cultures and a very high growth potential. CONCLUSION: The rat MSCs from bone marrow can differentiate hepatocytic cells in the presence of FLC in vitro and the presence of MSCs in co-cultures also provides a beneficial environment for expansion and differentiation of FLC.

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma.

AIM: To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS: We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody UJ127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendocrine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS: L1 was detected in 5 (7.9%) of 63 pancreatic neuroendocrine tumors. Four (44.4%) of 9 poorly-differentiated carcinomas expressed L1. In contrast, only 1 (1.9%) of 54 well-differentiated tumors or carcinomas was positive for L1. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas (P<0.01). CONCLUSION: L1 is specifically expressed in poorly-differentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.

Injectable liver: a novel approach using fibrin gel as a matrix for culture and intrahepatic transplantation of hepatocytes.

Cell transplantation and tissue engineering with liver cells are currently under investigation as experimental therapies for certain liver diseases. In this study we evaluated a fibrin-based gel matrix as carrier for hepatocytes in culture. Furthermore, a novel technique for direct intrahepatic injection of fibrin gel-immobilized hepatocytes was developed and evaluated in a rat model. Hepatocytes were harvested from rats. Fibrin matrix was generated with modified fibrin sealant. Cells, in medium containing epidermal growth factor and insulin, were seeded in a drop of fibrin matrix onto plastic culture dishes. Cell numbers were assessed by DNA content. Hepatocyte differentiation was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistology (IH) for cytokeratin (CK)-18 and albumin. PKH26-labeled fibrin gel-immobilized hepatocytes were transplanted into liver by direct injection underneath the capsule. Fluorescence microscopy of explanted liver was performed to identify PKH26+ donor cells. Neotissue was characterized by IH for the markers CK-18, ED1, and desmin. Culture in a fibrin matrix allowed stable cell numbers and three-dimensional neotissue formation. RT-PCR and IH showed preservation of liver-specific markers CK-18 and albumin in vitro. Transplanted cells were identified by fluorescence microscopy after 2 and 7 days. CK-18 and desmin staining showed integration of hepatocytes and hepatic stellate cells into the host liver. Fibrin matrix is an appropriate environment for hepatocytes in culture. Direct intrahepatic injection of fibrin gel-immobilized hepatocytes is technically feasible. We conclude that fibrin gel immobilization is an attractive tool for the development of tissue engineering-based liver support systems.

Liver-specific gene expression in mesenchymal stem cells is induced by liver cells.

AIM: The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stem cell cultures. We investigated the potential of rat mesenchymal stem cells (MSC) from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore, we assessed the influence of cocultured liver cells on induction of liver-specific gene expression. METHODS: Mesenchymal stem cells were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF, EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thy1 and the hepatocytic markers CK-18, albumin, CK-19, and AFP was performed in the different cell populations. RESULTS: Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18, CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression. CONCLUSION: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

Stem-like cells in human hepatoblastoma.

Hepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma.

Influence of flow conditions and matrix coatings on growth and differentiation of three-dimensionally cultured rat hepatocytes.

Maintenance of liver-specific function of hepatocytes in culture is still difficult. Improved culture conditions may enhance the cell growth and function of cultured cells. We investigated the effect of three-dimensional culture under flow conditions, and the influence of surface modifications in hepatocyte cultures. Hepatocytes were harvested from Lewis rats. Cells were cultured on three-dimensional polymeric poly-lactic-co-glycolic acid (PLGA) matrices in static culture, or in a pulsatile flow-bioreactor system. Different surface modifications of matrices were investigated: coating with collagen I, collagen IV, laminin, or fibronectin; or uncoated matrix. Hepatocyte numbers, DNA content, and albumin secretion rate were assessed over the observation period. Culture under flow condition significantly enhanced cell numbers. An additional improvement of this effect was observed, when matrix coating was used. Cellular function also showed a significant increase (4- to 5-fold) under flow conditions when compared with static culture. Our data showed that culture under flow conditions improves cell number, and strongly enhances cellular function. Matrix modification by coating with extracellular matrix showed overall an additive stimulatory effect. Our conclusion is that combining three-dimensional culture under flow conditions and using matrix modification significantly improves culture conditions and is therefore attractive for the development of successful culture systems for hepatocytes.

Adenomyoma of the small intestine a rare pathological lead point for intussusception in an infant.

INTRODUCTION: Intussusception is a typical abdominal emergency in early childhood. CASE DESCRIPTION: We report a case of an infant in the typically affected age group with an intussusception triggered by a rare benign intramural intestinal adenomyoma as a pathological lead point. The infant had the typical symptoms of a recurrent idiopathic ileocolic intussusception. DISCUSSION AND EVALUATION: Idiopathic intussusception is frequent in the infant age group. Contrary to that, reports on pathological lead points for intussusceptions are sparse in the toddler age. CONCLUSIONS: That case illustrates that even in intussusceptions in the typically affected age group, it is important to be aware of pathological lead points, especially if the intussusceptions are recurrent.