Diagnosis and Management of Congenital H-Type Tracheoesophageal Fistula: Results of a National Survey.

BACKGROUND: Congenital h-type tracheoesophageal fistula (H-TEF) without esophageal atresia (EA) represents about 4% of congenital esophageal anomalies. The diagnosis is challenging, and surgery is considered curative. The aim was to report a national survey on the diagnosis, management, and outcome of patients with congenital H-TEF. METHODS: Following approval of the Italian Society of Pediatric Surgery, a survey was sent to all Pediatric Surgery Units to retrospectively collect H-TEF treated in the period 2010-2022. Descriptive analysis was performed, and results are given as prevalence, mean ± standard deviation (SD), or median and interquartile range (IQR). RESULTS: The survey was sent to 65 units. Seventeen responded with one or more cases; 78 patients were diagnosed with H-TEF during the study period. Associated malformations were present in 43%, mostly cardiac (31%). The most frequent symptoms were cough (36%), bronchopneumonia (24%), and dysphagia (19%). H-TEF was detected by tracheobronchoscopy (90%), and/or upper GI (58%), and/or esophagoscopy (32%). The median age at diagnosis was 23 days (1 day-18 years). The most common approach was cervicotomy (76%), followed by thoracoscopy (14%) and thoracotomy (9%). The fistula underwent ligation and section of the fistula in 90% of the patients and clip closure and section in 9%. In one patient, the fistula was cauterized endoscopically. H-TEF preoperative cannulation was performed in 68% of cases, and a drain was placed in 26%. One month after surgery, 13% of the patients had mild persisting symptoms, mainly hypophonia. Recurrence occurred in 5%, and a second recurrence occurred in 1%. CONCLUSIONS: H-TEF prevalence was six cases/year, consistent with the expected rate of five cases/year in our country. The diagnosis was challenging, sometimes delayed, and, in most patients, required multiple examinations. Fistula ligation and section through cervicotomy were the most frequent treatment. Long-term outcomes are good, and recurrence is a rare event.

Congenital lung malformations: a nationwide survey on management aspects by the Italian Society of Pediatric Surgery.

INTRODUCTION: Over the years, congenital lung malformations (CLM) management remains a controversial topic in pediatric thoracic surgery. The Italian Society of Pediatric Surgery performed a national survey to study the current management variability among centers, trying to define national guidelines and a standardized approach of children with congenital lung malformations. METHODS: Following a National Society approval, an electronic survey including 35 items on post-natal management was designed, focusing on surgical, anesthesiology, radiology and pneumology aspects. The survey was conducted contacting all pediatric surgical units performing thoracic surgery. RESULTS: 39 pediatric surgery units (97.5%) participated in the study. 13 centers (33.3%) were classified as high-volume (Group A), while 26 centers (66.7%) were low volume (Group B). Variances in diagnostic imaging protocols were observed, with Group A performing fewer CT scans compared to Group B (p = 0.012). Surgical indications favored operative approaches for asymptomatic CLM and pulmonary sequestrations in both groups, while a wait-and-see approach was common for congenital lobar emphysema. Surgical timing for asymptomatic CLM differed significantly, with most high-volume centers operating on patients younger than 12 months (p = 0.02). Thoracoscopy was the preferred approach for asymptomatic CLM in most of centers, while postoperative long-term follow-up was not performed in most of the centers. CONCLUSION: Thoracoscopic approach seems uniform in asymptomatic CLM patients and variable in symptomatic children. Lack of uniformity in surgical timing and preoperative imaging assessment has been identified as key areas to establish a common national pattern of care for CLM.

Current Status of Pediatric Robot-Assisted Surgery in Italy: Epidemiologic National Survey and Future Directions.

Background: Pediatric robot-assisted surgery (RAS) is gaining increasing acceptance. We aimed to assess the diffusion of pediatric RAS in Italy, the training period, indications, preliminary outcomes, and limitations. Materials and Methods: An online questionnaire-based survey was performed. The data about robotic activity of 9 Italian Pediatric Surgery units were collected and analyzed. Results: Most of the participating centers (7/9, 77.8%) started RAS less than 5 years ago with only 2 centers (22.2%) performing RAS since 2010. The training included dry-lab in 5/9 centers (55.5%), wet-lab in 5/9 centers (55.5%), and robot simulator in 7/9 centers (77.8%), followed by an exam to obtain a certificate. The average duration of training was 23.7 hours (range 5-50). A total of 209 robotic procedures was performed in all centers during the period 2010-2018 and included 119 urological (56.9%), 31 gynecological (14.8%), 41 gastrointestinal (19.6%), 12 oncological (5.7%), and 6 other (2.8%) procedures. The docking time significantly fell down after 18 robotic procedures (P = .001). Intraoperative complications were recorded in 4 cases (1.9%). Conversion to laparoscopy was needed in 4 cases (1.9%) whereas conversion to open was required in 6 cases (2.8%). Postoperative complications occurred in 17/209 cases (8.1%) and were graded Clavien I-II in 14 cases (6.7%) and Clavien IIIb in only 4 cases (1.9%). Conclusions: Our study confirmed that RAS has still a limited diffusion in Italy for pediatric patients. Before starting robotic activity, pediatric surgeons have to obtain a certificate after a virtual and experimental training period. A mentorship clinical period of 10 cases under supervision of a proctor is also needed. The main indications in children remain reconstructive urological procedures. RAS is safe in children but its applications are currently limited to patients older than 2 years and with a weight >15 kg, due to the size of robotic ports.

WT1 and Cyclin D1 Immunohistochemistry: A Useful Adjunct for Diagnosis of Pediatric Small Round Blue Cell Tumors on Small Biopsies.

Pediatric small round blue cell tumors (SRBCTs) are a heterogeneous group of neoplasms with overlapping morphological appearance. Accordingly, their diagnosis is one of the most difficult in the field of surgical pathology. The most common tumors include rhabdomyosarcoma, Ewing's sarcoma, neuroblastoma, lymphoblastic lymphoma and Wilms' tumor (the blastemal component). Over time their diagnosis has become more difficult due to the increasing use of small biopsies. However, the advent of immunohistochemistry has improved the quality of diagnosis in most cases by the application of an adequate panel of immunomarkers. Recently, WT1 and Cyclin D1 have been shown to be useful in the differential diagnosis of SRBCTs on surgically-resected specimens, showing a diffuse cytoplasmic positivity of the former in all RMSs and a diffuse nuclear staining of the latter in both EWS and NB. The aim of the present study was to investigate the expression of WT1 and Cyclin D1 on small biopsies from a series of 105 pediatric SRBCTs to evaluate their diagnostic utility. Both immunomarkers were differentially expressed, with a diffuse and strong cytoplasmic staining for WT1 limited to all cases of RMS, and a diffuse nuclear staining for cyclin D1 restricted to all cases of EWS and NB. Notably, the expression of WT1 and cyclin D1 was also retained in those cases in which the conventional tumor markers (myogenin, desmin and MyoD1 for RMS; CD99 for EWS; NB84 for NB) were focally expressed or more rarely absent. The present study shows that WT1 and Cyclin D1 are helpful immunomarkers exploitable in the differential diagnosis of pediatric SRBCTs on small biopsies, suggesting their applicability in routine practice.

Desmoplastic Small Round Cell Tumor with "Pure" Spindle Cell Morphology and Novel EWS-WT1 Fusion Transcript: Expanding the Morphological and Molecular Spectrum of This Rare Entity.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare pediatric soft tissue neoplasm composed of small round tumor cells with prominent stromal desmoplasia, polyphenotypic differentiation and EWSR1-WT1 gene fusion. We, herein, present a unique case of DSRCT, exhibiting a pure spindle cell morphology, absence of desmoplastic stroma and showing a novel EWS-WT1 fusion transcript. METHODS: A 12-year-old boy presented multiple intra-abdominal, confluent and mass-forming nodules that affected the entire abdominal and pelvic cavities. RESULTS: Histologically, the nodules were composed of spindle cells with scant cytoplasm and oval nuclei arranged into short, intersecting fascicles and set in a scant, non-desmoplastic, stroma. Immunohistochemically, neoplastic cells were stained with vimentin, desmin, WT-1 (C-terminus antibodies) and EMA. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed the presence of an unusual chimeric transcript, composed of an in-frame junction of exon 9 of EWS to exon 7 of WT1, confirming the histological diagnosis of DSRCT. CONCLUSIONS: The present case contributes to widen the morphological spectrum of this entity; notably, the additional presence of a novel chimeric fusion transcript contributes to making the present case even more unique. Whether the detection of the above-mentioned fusion transcripts could explain the unusual morphology of the tumor remains to be established.

Guidelines of the Italian Society of Videosurgery in Infancy (SIVI) for the minimally invasive treatment of fetal and neonatal ovarian cysts.

In the last three decades, fetal ovarian cysts were diagnosed more frequently, due to technological improvement and the increasing use of prenatal screening ultrasound. Nonetheless, treatment uncertainties are still present, either prenatally or postnatally. Recently, significant innovations on diagnosis and treatment have been proposed and a more conservative, minimally invasive approach may be offered to the Pediatrician or the Surgeon who face with this condition during prenatal or neonatal age. (...).

Guidelines of the Italian Society of Videosurgery (SIVI) in Infancy for the minimally invasive treatment of Hypertrophic Pyloric Stenosis in neonates and infants.

The most appropriate treatment for the infantile Hypertrophic Pyloric Stenosis (HPS) is still debated. The non-surgical conservative treatment with oral or intravenous administration of atropine does not enjoy a widespread appreciation for several factors (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia.

Esophageal Atresia (EA) is defined as an interruption in esophageal continuity that results in a proximal tract that ends in a blind pouch in 98% of cases, and a distal tract that in 87% of cases arises via a Fistula from the Trachea (TEF). (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of pediatric nephrectomy and partial nephrectomy.

Throughout history, the pediatric laparoscopic nephrectomy was first described at the beginning of the Nineties by Erlich and colleagues in a child and by Koyle and colleagues in an unweaned patient. (...).

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the ureteropelvic-junction obstruction.

The hydronephrosis, characterized by the dilation of the renal pelvicalyceal system with possible functional damage to the renal parenchyma, is the most common congenital abnormality of the urinary system detected in utero through the prenatal ultrasound screening. (...).

Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells.

BACKGROUND: It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. METHODS: Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. inhibition of phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cytotoxic function, was examined. Gene expression profiles, known to be related to tumor cell stemness, Wnt pathway activation, epithelial-mesenchymal transition (EMT) and tumor metastasis were also evaluated. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls. RESULTS: NB-MSCs presented the typical MSC morphology and phenotype. They showed a proliferative capacity superimposable to BM-MSCs. Stemness marker expression (Sox2, Nanog, Oct3/4) was comparable to BM-MSCs. NB-MSC in vitro osteogenic and chondrogenic differentiation was similar to BM-MSCs, but NB-MSCs lacked adipogenic differentiation capacity. NB-MSCs reached senescence phases at a median passage of P7 (range, P5-P13). NB-MSCs exhibited greater immunosuppressive capacity on activated T lymphocytes at a 1:2 (MSC: PBMC) ratio compared with BM-MSCs (p = 0.018). NK cytotoxic activity was not influenced by co-culture, either with BM-MSCs or NB-MSCs. Flow-cytometry cell cycle analysis showed that NB-MSCs had an increased number of cells in the G0-G1 phase compared to BM-MSCs. Transcriptomic profiling results indicated that NB-MSCs were enriched with EMT genes compared to BM-MSCs. CONCLUSIONS: We characterized the biological features, the immunomodulatory capacity and the gene expression profile of NB-MSCs. The NB-MSC gene expression profile and their functional properties suggest a potential role in promoting tumor escape, invasiveness and metastatic traits of NB cancer cells. A better understanding of the complex mechanisms underlying the interactions between NB cells and NB-derived MSCs should shed new light on potential novel therapeutic approaches.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the esophageal atresia.

Not available.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of the ureteropelvic-junction obstruction.

Not available.

Guidelines of the Italian Society of Videosurgery in Infancy for the minimally invasive treatment of pediatric nephrectomy and partial nephrectomy.

Not available.

Severe disease in Cystic Fibrosis and fecal calprotectin levels.

Fecal calprotectin (FC) is used to asses the presence of intestinal inflammation also in patients with Cystic Fibrosis (CF) and recent studies showed a correlation between bowel and lung disease in these patients. The aim of this study was to analyze the levels of FC in CF and correlate them with different phenotypes of disease. We enrolled a cohort of 54 CF patients and 50 healthy controls. In these patients, calprotectin has been assayed on a stools sample using an ELISA kit. In all patients we analyzed, FC levels were elevated above the cut-off value and significantly higher than in healthy controls. Among CF patients, FC was significantly higher in patients older than 18 years, with pancreatic insufficiency, underweight status, Pseudomonas Aeruginosa airways colonization, CF-related diabetes mellitus, reduced lung function, or high number of pulmonary exacerbations. These results suggest that in patients with CF, FC levels are not only influenced by the CF enteropathy but also by the severity of the genetic disease. Since we found higher FC levels in patients with a severe phenotype (P. Aeruginosa airways colonization, FEV1<50% of predicted, pancreatic insufficiency, underweight status,) we suggest that this marker could be useful to monitor longitudinally a clinical worsening.

Bilateral adrenal neuroblastoma in the infant: Is it an image-defined risk factor?

The treatment of neuroblastoma is based on the International Neuroblastoma Risk Group stratification considering life-threatening symptoms, image-defined risk factors (IDRFs), presence and site of metastases, biology, and histopathology. The authors present an infant with bilateral nonmetastatic adrenal neuroblastoma with favorable biology. Both tumors were resectable and without IDRFs, but bilateral resection was considered mutilating, so it was decided to operate one side only. The authors suggest considering bilaterality among IDRFs.

A difficult diagnosis of Hodgkin lymphoma due to immune thrombocytopenia.

We report a rare clinical presentation of childhood Hodgkin lymphoma with immune thrombocytopenia. Diagnostic biopsy of the abdominal mass was performed after administration of intravenous immunoglobulins, steroids, and platelet transfusion. Concomitant thrombocytopenia complicated the whole diagnosis work up and the initial management of neoplasia.

European Society of Pediatric Endoscopic Surgeons (ESPES) guidelines for training program in pediatric minimally invasive surgery.

PURPOSE: The aim of this paper was to propose structured guidelines for a European pediatric MIS training program created by ESPES. METHODS: A questionnaire, focused on how the pediatric training program in MIS has to be structured, was proposed to all participants at the ESPES Congress in Marseille in 2013. RESULTS: We received 178 questionnaires but only 139 questionnaires were fully completed and analyzed. All respondents agree that the training program has to be divided into 4 steps: (1) theoretical part: 2 theoretical courses in laparoscopy (101/139 respondents, 72.7 %), 1 theoretical course in retroperitoneoscopy (99/139 respondents, 71.2 %) and 1 in thoracoscopy (91/139 respondents, 65.5 %); (2) experimental part: 10-20 h of training on pelvic trainer (103/139 respondents, 74.1 %) and 10 h of training on animal models (91/139 respondents, 65.5 %); (3) stages in European centers of reference for MIS: a 1-3 months stage (96/139 respondents, 69.1 %); (4) personal experience: 30 procedures as cameraman (98/139 respondents, 70.5 %) and >50 basic MIS procedures as main surgeon under supervision (114/139 respondents, 82 %). CONCLUSIONS: On the basis of our survey ESPES MIS training curriculum for pediatric surgeons must contain the following educational components: (1) theoretical knowledge; (2) practice-based learning and improvement in experimental setting; (3) stages in European centers of reference for MIS; (4) personal operative experience. At the end of the training program, ESPES will analyze the candidate training booklet and release for each applicant an ESPES certification after an exam.

Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.