Research Models to Mimic Necrotizing Enterocolitis and Inflammatory Bowel Diseases: Focus on Extracellular Vesicles Action.

This review focuses on the crucial role of the intestinal epithelium in maintaining intestinal homeostasis and its significance in the pathogenesis of necrotizing enterocolitis (NEC) and inflammatory bowel diseases (IBD). NEC is a devastating neonatal disease, while IBD represents a global healthcare problem with increasing incidence. The breakdown of the intestinal barrier in neonates is considered pivotal in the development and progression of both disorders. This review provides an overview of the current state of in vitro, ex vivo, and animal models to study epithelial injury in NEC and IBD, addressing pertinent questions that engage clinicians and researchers alike. Despite significant advancements in early recognition and aggressive treatment, no single therapy has been conclusively proven effective in reducing the severity of these disorders. Although early interventions have improved clinical outcomes, NEC and IBD continue to impose substantial morbidity, mortality, and economic burdens on affected individuals and society. Consequently, exploring alternative therapeutic options capable of preventing and treating the sequelae of NEC and IBD has become a pressing necessity. In recent decades, extracellular vehicles (EVs) have emerged as a potential solution to modulate the pathogenic mechanism in these multifactorial and complex disorders. Despite the diverse array of proposed models, a comprehensive model to investigate and decelerate the progression of NEC and IBD remains to be established. To bridge the translational gap between preclinical studies and clinical applications, enhancements in the technical development of gut-on-a-chip models and EVs hold considerable promise.

Pediatric kidney transplantation: is it safe to perform during night-time or day-off?

PURPOSE: To investigate the impact of after-hours surgery on the outcomes of pediatric kidney transplantation (KT). METHODS: Medical records of pediatric KTs performed at a single institution between 2013 and 2021 were retrospectively reviewed. The population was split into three groups according to the incision time and calendar: ordinary day (8.00 AM - 6.30 PM), day-off, and night-time (6.30 PM - 8.00 AM). The following endpoints were compared: ischemia times, length of surgery, complications, delayed graft function (DGF), primary graft non-function (PGNF), and eGFR at three-month follow-up. RESULTS: Ninety-six non-living donor KTs were performed, median age 11 (IQR 4.3-14) years and median body weight 26 (IQR 13-50) kg. Forty-one (43%) were performed during night-time and 28 (29%) during day-off. Ischemia times were similar (p = 0.769, p = 0.536). Day-off KTs presented an extended length of surgery (p = 0.011). Thirty-two complications were reported in 31 KTs. No difference in the overall rate of complications, DGF, PNGF, and three-month eGFR was found (p = 0.669, p = 0.383, p = 0.949, p = 0.093). Post-operative bleedings were more common in days-off (p = 0.003). CONCLUSION: The number of pediatric KTs performed during after-hours was considerable. Even though similar outcomes were reported, more caution should be focused on the KTs performed in days-off to avoid severe complications.

Aesthetic transaxillary subpectoral placement of vagus nerve stimulator in children and young adults: A technical note.

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement. MATERIALS AND METHODS: From May 2021 to May 2023, 10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up. RESULTS: In this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up. CONCLUSION: The transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults.

Enhancing diagnosis of Hirschsprung's disease using deep learning from histological sections of post pull-through specimens: preliminary results.

PURPOSE: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology. METHODS: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves. RESULTS: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%. CONCLUSION: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists.

Can real-time near-infrared spectroscopy monitoring detect graft venous thrombosis after pediatric kidney transplantation?

BACKGROUND: A prompt detection of graft venous thrombosis might preserve the transplanted organ. A real-time near-infrared spectroscopy (NIRS) monitoring of the allograft perfusion could fulfill this goal. The aim of this work was to report the trend of allograft perfusion (rSO2) after pediatric kidney transplantation (KT) complicated by graft venous thrombosis. CASE PRESENTATION: An infant, affected by end-stage kidney disease due to posterior urethral valves, underwent non-living donor KT. The allograft presented both arterial and venous variants and required a complex bench surgery reconstruction. The perfusion of the allograft was monitored by real-time transcutaneous NIRS. The early post-operative was conditioned by worsening clinical conditions, and a graft venous thrombosis was detected after four hours since the transplantation. NIRS monitoring lasted for 348 minutes. Median lower pole rSO2-value was 65% (IQR 62-66%), while the median upper pole rSO2-value was 70% (IQR 70-71%). These data reflected the congestion of the lower pole, observed at the end of the transplantation. The lower pole showed inferior rSO2 values (p<0.0001). At the end of the monitoring, the decrease in peripheral rSO2, measured in left lower limb as a benchmark, was consistent with the ongoing hypovolemic shock and severe acute anemia. CONCLUSION: Transcutaneous NIRS might be a reliable device for monitoring allograft and peripheric perfusion after pediatric KT. The modifications of rSO2 values helped the clinicians manage the patients in the post-operative and early detect acute complications.

Extraperitoneal kidney transplantation: a comparison between children weighting ≤15 kg and >15 kg. Experience of a single institution.

Extraperitoneal approach is sometimes recommended for kidney transplantation (KT) in children weighting <15 kg. We hypothesized that this approach might be as successful as in patients with normal weight. Data of all consecutive KTs performed between 2013 and 2019 were retrospectively reviewed. Early outcomes and surgical complications were compared between children weighing ≤15 kg (low-weight (LW) group) and those weighing >15 kg (Normal-weight (NW) group). All the 108 KTs were performed through an extraperitoneal approach. The LW group included 31 patients (mean age 3.5 ± 1.4 years), whose mean weight was 11.1 ± 2.0 kg. In the LW group,-a primary graft nonfunction (PNGF) occurred in one patient (3.2%), surgical complications occurred in nine (29%), with four venous thrombosis. In the NW group, PNGF occurred in one case (1.3%), delayed graft function (DGF) in eight (10%), surgical complications in 11 (14%) with only one case of venous thrombosis. In both groups, no need for patch during wound closure and no wound dehiscence were reported. The extraperitoneal approach can be effectively used in LW children. No differences were observed in the overall complication rate (P = 0.10), except for the occurrence of venous thrombosis (P = 0.02). This might be related to patients' characteristics of the LW group.

Congenital Pouch Colon: Case Series and Review of Evidences for Resection.

BACKGROUND: Congenital pouch colon (CPC) is a rare variant of anorectal malformations (ARM) with its highest reported incidence in India. We aimed to describe five patients affected by CPC, in which the tissue from the terminal dilated colon has been successfully used and to discuss our results on the light of an extended revision of the literature. MATERIALS AND METHODS: The clinical details of five cases treated for CPC in two Italian Centers were retrospectively reviewed assessing the fate of the terminal dilated colon. RESULTS: In all cases, the tissue from dilated colon has been used. The double vascular system of the dilated pouch allowed increasing bladder capacity (case 4), reconstruction of the vagina (case 3, 5), and lengthening of the colon (case 1, 2, 5).In our series, 3/5 have a good bowel control with daily bowel management after ARM correction. In literature, there are not differences in terms of dependence from bowel management in patients with pouch resected and in patients with pouch saved (P = 0.16). CONCLUSIONS: We acknowledge that the analysis of the available literature is limited by the absence of studies with high level of evidence and the removal or the preservation of the abnormal colon tissue seems to follow the surgeon preferences.

Neonatal independent predictors of severe NEC.

PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal disease. The present study aimed to identify factors predisposing the development of severe forms of NEC. METHODS: This retrospective study examined NEC patients in a single centre between 2002 and 2015. Data concerning clinical characteristics, therapeutic management as well as short-term outcomes were collected. We compared the patients receiving successful medical treatment and those requiring surgical intervention. Patients who underwent surgery were distinguished in three subcategories. Bivariate and multivariate analyses were used for the statistical analysis. RESULTS: We identified 155 patients in the study period. 102 were treated conservatively and 53 required surgery. 8 received a primary peritoneal drainage, 31 received a drainage and a subsequent laparotomy and 14 received a laparotomy. Multivariate regression analysis identified a lower risk for surgery with a later onset and higher serum pH values, whereas an increased risk with higher C reactive Protein (CRP) levels at the onset. Pneumatosis intestinalis was identified as a protective factor. Overall mortality was 6.4%, with higher percentage in surgical NEC. CONCLUSION: This study suggests that a later onset is a protective sign for the progression to surgery, whereas lower pH values and higher CRP levels are prognostic factors associated with the need for surgery. The line of treatment involving explorative laparotomy in case of perforation seems to be rewarded by low morbidity and mortality rate.

Minimally invasive resection of adrenal masses in infants and children: results of a European multi-center survey.

BACKGROUND: Minimal access adrenal surgery (MAAS) for adrenal pathologies is the standard for many pediatric surgical centers. However, the literature offers few reports and minimal evidence from small case series. The aim of this study was to evaluate the outcomes of pediatric MAAS through a multi-center data analysis. METHOD: Pediatric patients who underwent MAAS between January 2002 and December 2013 were retrospectively included. Data analysis was conducted using Spss software (Welch's t-test, X-square, Fisher tests, multiple regression model). RESULTS: Six European centers participated, 68 patients were included with mean age of 5.2 years (2 months-16 years). Lesion volume was of 18.1 cc (0.78-145.6), with a mean diameter of 2.8 cm (1.1-6.5). Localization was 50% left-sided masses, 45.6% right-side masses, and 4.4% bilateral. Histological examination revealed 36 neuroblastomas, 15 adenomas, nine pheochromocytomas, three ganglioneuromas, two ganglioneuroblastomas, one bilateral hyperplasia, one adrenocortical carcinoma, an alveolar sarcoma, and a calcification. Surgical access was transperitoneal in 63 (92.6%) and retroperitoneal in 5 (7.4%). Mean operative time was 170 ± 87 min (285 ± 30 min for bilateral lesions). Mean hospital stay was 4.2 ± 2.5 days. Complications included blood loss requiring transfusion in five patients (7.4%) and a diaphragmatic tear. Infiltration of surrounding structures correlated with intraoperative complication rate (p = 0.027) and operative time (p < 0.01). No mass rupture, conversion, or post-operative complications were observed. Median follow-up was 52 months (1-161). Two recurrences occurred in patients with pheochromocytoma. Age, weight, symptoms, characteristics at imaging, chemistry, volume, or histology, did not influence operative time, hospital stays, or complication rate. CONCLUSIONS: Pediatric MAAS was safe adopted for masses up to 145.6 cc, with a very low rate of complication. Conversion to open is not necessary even in the presence of infiltrations. MAAS should represent the first-line treatment for selected cases in centers experienced in laparoscopy.

Neonatal Appendicitis and Incarcerated Inguinal Hernia: Case Report and Review of the Literature.

Neonatal appendicitis carries a high mortality rate. We describe a peculiar case presented after an incarcerated hernia manually reduced in a 4-week-old male neonate with ipsilateral undescended testis. Laparoscopy allowed a prompt recognition of an unexpected intra-abdominal life-threatening condition. Pathogenesis, treatment, and outcome are discussed on the light of a comprehensive literature review.

Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism.

OBJECTIVE: Necrotising enterocolitis (NEC) remains one of the primary causes of morbidity and mortality in neonates and alternative strategies are needed. Stem cells have become a therapeutic option for other intestinal diseases, which share some features with NEC. We tested the hypothesis that amniotic fluid stem (AFS) cells exerted a beneficial effect in a neonatal rat model of NEC. DESIGN: Rats intraperitoneally injected with AFS cells and their controls (bone marrow mesenchymal stem cells, myoblast) were analysed for survival, behaviour, bowel imaging (MRI scan), histology, bowel absorption and motility, immunofluorescence for AFS cell detection, degree of gut inflammation (myeloperoxidase and malondialdehyde), and enterocyte apoptosis and proliferation. RESULTS: AFS cells integrated in the bowel wall and improved rat survival and clinical conditions, decreased NEC incidence and macroscopic gut damage, improved intestinal function, decreased bowel inflammation, increased enterocyte proliferation and reduced apoptosis. The beneficial effect was achieved via modulation of stromal cells expressing cyclooxygenase 2 in the lamina propria, as shown by survival studies using selective and non-selective cyclooxygenase 2 inhibitors. Interestingly, AFS cells differentially expressed genes of the Wnt/ß-catenin pathway, which regulate intestinal epithelial stem cell function and cell migration and growth factors known to maintain gut epithelial integrity and reduce mucosal injury. CONCLUSIONS: We demonstrated here for the first time that AFS cells injected in an established model of NEC improve survival, clinical status, gut structure and function. Understanding the mechanism of this effect may help us to develop new cellular or pharmacological therapies for infants with NEC.

Pneumatic pyloric dilatation for the treatment of gastric outlet obstruction in a child.

Acquired causes of gastric outlet obstruction (GOO) are rarely encountered in infancy, having an approximate incidence of 1 per 100,000 live births. Reports of short-term exposure to non-steroidal anti-inflammatory drugs having adverse events are few. We present the case of a previously healthy 3-year-old boy who developed severe chronic gastric outlet obstruction and antral stenosis after a short-term ingestion of liquid ibuprofen at a dosage not thought to be associated with unfavorable effects. Even though the optimal management of these cases remains to be determined, we report on a prompt and successful endoscopic treatment for this condition.

Laparoscopic Heller-Dor Is a Persistently Effective Treatment for Achalasia Even in Pediatric Patients: A 25-Year Experience at a Single Tertiary Center.

BACKGROUND: Esophageal achalasia (EA) is a rare primary motility disorder in any age group, and particularly rare in the pediatric population, with a reported incidence of 0.18 per 100,000 children a year. EA in pediatric age is currently treated in the same way as in adults, but this approach is based on only a few studies on small case series. The aim of this retrospective study was to assess the long-term outcome of the laparoscopic Heller-Dor (LHD) procedure when performed in pediatric patients with EA at our university hospital. MATERIALS AND METHODS: We considered children and adolescents younger than 16 years old diagnosed with EA and treated with LHD between 1996 and 2022. Clinical data were prospectively collected in an ongoing database. Symptoms were recorded and their severity was calculated using the Eckardt score. Barium swallow, esophageal manometry (conventional or high-resolution), and endoscopy were performed before and after the surgical procedure. RESULTS: During the study period, 40 children with a median age of 14 years (interquartile range [IQR]: 11-15) underwent LHD. At a median follow-up of 10.5 years (IQR: 4.5-13.9), a good outcome was achieved in 36/40 patients (90%). Two of the four patients whose surgical procedure failed underwent complementary pneumatic dilations successfully, thus increasing the overall success rate to 95%. A previous endoscopic treatment (in five patients) did not affect the final outcome (p = 0.49). An intraoperative mucosal lesion was detected in only one patient (2.5%) and was repaired at the time without further consequences. During the follow-up, 22 patients underwent endoscopy, and 17 had pH monitoring as well: only 2 of these patients showed reflux esophagitis at endoscopy (one of them with abnormal findings on pH monitoring), amounting to a 9.1% rate of instrumentally confirmed postoperative reflux. CONCLUSION: LHD is a safe and persistently effective treatment for EA in pediatric age, with a success rate comparable with what is usually obtained in adults, and better than what has been reported to date in the pediatric literature. Adding a fundoplication certainly helps ensure an optimal long-term control of any gastroesophageal reflux induced by the myotomy.

Postoperative Hirschsprung's associated enterocolitis (HAEC): transition zone as putative histopathological predictive factor.

AIMS: Hirschsprung's-associated enterocolitis (HAEC) is the most severe complication of Hirschsprung disease (HD), and its pathogenesis is still unknown. Length of transition zone (TZ) interposed between aganglionic and normal bowel has been poorly explored as predictor for postoperative HAEC (post-HAEC). This study aimed to identify potential predictive factors for post-HAEC, with a particular focus on histopathological findings. METHODS: Data from Hirschsprung patients treated in a single Italian centre between 2010 and 2022 with a follow-up >6 months were collected. Thorough histopathological examination of the resected bowel was conducted, focusing on length of TZ and aganglionic bowel.The degree of inflammatory changes in ganglionic resected bowel was further obtained. Ultra-long HD, total colonic aganglionosis and ultra-short HD were excluded. Bivariate and multivariate regression analysis were performed. RESULTS: Thirty-one patients were included; 5 experienced preoperative HAEC (pre-HAEC) and later post-HAEC (16.1%), further 10 patients developed post-HAEC (total post-HAEC 48.38%). Pre-HAEC-history and a TZ<2.25 cm correlated with an early development of post-HAEC. Multivariate analysis identified a TZ<2.25 cm as an independent post-HAEC predictive factor (p=0.0096). Inflammation within the ganglionic zone and a TZ<2.25 cm correlated with higher risk of post-HAEC (p=0.0074, 0.001, respectively). Severe post-HAEC more frequently occurred in patients with pre-HAEC (p=0.011), histological inflammation (p=0.0009) and short TZ (p=0.0015). CONCLUSIONS: This study suggests that TZ<2.25 cm predicts the risk of post-HAEC. Preoperative clinical and histopathology inflammation may predispose to worst post-HAEC. Readily available histopathological findings might help identifying patients at higher risk for HAEC and implementing prevention strategies.

Complex Bench Surgery Does Not Increase the Risk of Vascular Complications after Pediatric Kidney Transplantation.

INTRODUCTION: Vascular complications are severe complications of pediatric kidney transplantation (KT). We aimed to investigate whether a complex bench surgery (BS) affects the outcomes. METHODS: All pediatric KT performed at the University Hospital of Padua from 2015 to 2019 were analyzed, comparing those in which a standard BS was possible to those that necessitated a complex BS. The rates of vascular complications, patients' outcome, and graft survival were compared in the two groups. RESULTS: Eighty KTs were performed in 78 patients with a median age of 11 years (interquartile range [IQR] 4.3-14) and a median body weight of 24 kg (IQR 13-37). Thirty-nine donor kidneys (49%) needed a complex BS due to anomalies of renal veins in 12 (31%) and renal arteries in 16 (41%). The remaining 11 grafts (28%) underwent an elongation of the vein. There was no difference in the rate of primary graft non function (p = 0.97), delayed graft function (p = 0.72), and overall survival (p = 0.27). The rates of vascular complications, bleedings, and venous graft thrombosis were similar (p = 0.51, p = 0.59, p = 0.78, respectively). No arterial thrombosis or stenosis was reported. CONCLUSION: Complex BS did not compromise survival of the graft and did not put the allograft at risk of vascular complications, such as bleedings or thrombosis.

Robot-Assisted Versus Laparoscopic Approach for Splenectomy in Children: Systematic Review and Meta-Analysis.

Aim: To compare the outcomes of pediatric splenectomies for hematologic diseases performed by robot-assisted laparoscopic surgery (RALS) and laparoscopic approach. Materials and Methods: Web of Science, Scopus, and PubMed databases were systematically searched for publications in English language from January 2000 to March 2020. All the studies dealing with pediatric elective splenectomies performed by RALS were included. The primary outcomes were the rate of postoperative complications and conversion. The secondary outcomes were the length of hospital stay and the operative time. Results: The search yielded 969 articles. Ten articles were included in the systematic review. Eighty patients underwent RALS splenectomy. Thirteen postoperative complications (16%) were reported and RALS was converted to open surgery in five cases (6.3%). Five of the included articles, three retrospective studies and two case series, were considered relevant for the meta-analysis and dealt with 130 patients. Of them, 71 children (55%) underwent RALS. No difference in the rate of complications was found between the two approaches (P = .235). RALS presented a similar rate of conversion to open surgery (P = .301). The mean operative times and length of hospital stays for RALS, reported in three different studies, were 107.5, 159.6, 140.5 minutes and 4.2, 3.93, 2.1 days, respectively. Conclusion: Even if few studies were included in the review, this meta-analysis reported similar rates of complication and conversion for RALS when compared with laparoscopy. Further studies are required to prove that this innovative technique was as safe and feasible as the current gold standard technique.

Urological Impact of Epididymo-orchitis in Patients with Anorectal Malformation: An ARM-Net Consortium Study.

INTRODUCTION: To investigate the current experience of the ARM-Net Consortium in the management of epididymo-orchitis (EO) in patients with anorectal malformations (ARMs), and to identify specific risk factors and the need for urological care involvement. MATERIALS AND METHODS: We retrospectively collected data of EO in patients with ARM between 2015 and 2019. Data on urological aspects, ARM type, surgical approach, associated anomalies, diagnosis, and treatment of EO were collected and analyzed. RESULTS: Twenty-nine patients were reported by 12 centers. Twenty-six patients with EO (90%) had ARM with a rectourinary fistula. Median age at first EO was 2 years (range: 15 days-27 years). Twenty patients (69%) experienced multiple EO, and 60% of recurrences were ipsilateral. Associated urological anomalies included vesicoureteral reflux (48%), urethral anomalies (41%), neurogenic bladder (41%), and ectopic vas (10%). A positive urine culture during EO was present in 69%. EO was treated with antibiotics (90%), limiting surgical exploration to 14%. Prevention of recurrences included surgery (bulking agents 15%, vasectomy 15%, and orchiectomy 5%) and antibiotic prophylaxis (20%). CONCLUSION: Urologists may encounter patients with EO in ARM patients, frequently with positive urine culture. An appropriate urologic work-up for most ARM patients is necessary to identify and treat underlying risk factors. A practical scheme for the work-up is suggested for a close collaboration between pediatric surgeons and urologists.

Anesthesia for fetal operative procedures: A systematic review.

Objective: The anesthetic management of fetal operative procedures (FOP) is a highly debated topic. Literature on fetal pain perception and response to external stimuli is rapidly expanding. Nonetheless, there is no consensus on the fetal consciousness nor on the instruments to measure pain levels. As a result, no guidelines or clinical recommendations on anesthesia modality during FOP are available. This systematic literature review aimed to collect the available knowledge on the most common fetal interventions, and summarize the reported outcomes for each anesthetic approach. Additional aim was to provide an overall evaluation of the most commonly used anesthetic agents. Methods: Two systematic literature searches were performed in Embase, Medline, Web of Science Core Collection and Cochrane Central Register of Controlled Trials up to December 2021. To best cover the available evidence, one literature search was mostly focused on fetal surgical procedures; while anesthesia during FOP was the main target for the second search. The following fetal procedures were included: fetal transfusion, laser ablation of placental anastomosis, twin-reversed arterial perfusion treatment, fetoscopic endoluminal tracheal occlusion, thoraco-amniotic shunt, vesico-amniotic shunt, myelomeningocele repair, resection of sacrococcygeal teratoma, ligation of amniotic bands, balloon valvuloplasty/septoplasty, ex-utero intrapartum treatment, and ovarian cyst resection/aspiration. Yielded articles were screened against the same inclusion criteria. Studies reporting anesthesia details and procedures' outcomes were considered. Descriptive statistical analysis was performed and findings were reported in a narrative manner. Results: The literature searches yielded 1,679 articles, with 429 being selected for full-text evaluation. A total of 168 articles were included. Overall, no significant differences were found among procedures performed under maternal anesthesia or maternal-fetal anesthesia. Procedures requiring invasive fetal manipulation resulted to be more effective when performed under maternal anesthesia only. Based on the available data, a wide range of anesthetic agents are currently deployed and no consistency has been found neither between centers nor procedures. Conclusions: This systematic review shows great variance in the anesthetic management during FOP. Further studies, systematically reporting intraoperative fetal monitoring and fetal hormonal responses to external stimuli, are necessary to identify the best anesthetic approach. Additional investigations on pain pathways and fetal pain perception are advisable.