Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors.

This study aims to review the status of the clinical use of monoclonal antibodies (mAbs) that have completed or are in ongoing clinical trials for targeted fluorescence-guided surgery (T-FGS) for the intraoperative identification of the tumor margins of extra-hematological solid tumors. For each of them, the targeted antigen, the mAb generic/commercial name and format, and clinical indications are presented, together with utility, doses, and the timing of administration. Based on the current scientific evidence in humans, the top three mAbs that could be prepared in a GMP-compliant bank ready to be delivered for surgical purposes are proposed to speed up the translation to the operating room and produce a few readily available "off-the-shelf" injectable fluorescent probes for safer and more effective solid tumor resection.

Image-guided core-needle or surgical biopsy for neuroblastoma diagnosis in children: A systematic review and meta-analysis from the International Society of Pediatric Surgical Oncology (IPSO).

BACKGROUND: Image-guided core-needle biopsy (IGCNB) is a widely used and valuable clinical tool for tissue diagnosis of pediatric neuroblastoma. However, open surgical biopsy remains common practice even if children undergo more invasive and painful procedures. This review aims to determine the diagnostic accuracy and safety of IGCNBs in pediatric patients with neuroblastoma. METHODS: We conducted a systematic review of peer-reviewed original articles published between 1980 and 2023, by searching "pediatric oncology," "biopsy," "interventional radiology," and "neuroblastoma." Exclusion criteria were patients older than 18 years, studies concerning non-neurogenic tumors, case reports, and language other than English. Both the systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 533 abstracts articles were analyzed. Of these, eight retrospective studies met inclusion criteria (490 infants, 270 surgical biopsies [SB], 220 image-guided biopsies). Tissue adequacy for primary diagnosis (SB: n = 265, 98%; IGCNB: n = 199, 90%; p = .1) and biological characterization (SB: n = 186, 95%; IGCNB: n = 109, 89%; p = .15) was similar with both biopsy techniques, while intraoperative transfusion rate (SB: n = 51, 22%; IGCNB: n = 12, 6%; p = .0002) and complications (%) (SB: n = 58, 21%; IGCNB: n = 14, 6%; p = .005) were higher with surgical biopsy. Length of stay was similar in both groups; however, no additional data about concurrent diagnostic or treatment procedures were available in the analyzed studies. CONCLUSIONS: IGCNB is a safe and effective strategic approach for diagnostic workup of NB and should be considered in preferance to SB wherever possible.

Short and Medium Term Outcomes of Open and Laparoscopic Assisted Oesophageal Replacement Procedures.

AIM OF THE STUDY: We describe the short- and medium-term outcomes following open and laparoscopic assisted oesophageal replacement surgery in a single tertiary paediatric surgical centre. METHODS: A retrospective review (institutional audit approval no. 3213) on patients who underwent open or laparoscopic-assisted oesophageal replacement (OAR vs. LAR) at our centre between 2002 and 2021 was completed. Data collected (demographics, early complications, stricture formation, need for oesophageal dilatations, and mortality) were analysed using GraphPad Prism v 9.50 and are presented as median (IQR). RESULTS: 71 children (37 male) had oesophageal replacement surgery at a median age of 2.3 years (IQR 4.7 years). 51 were LAR (6 conversions). Replacement conduit was stomach (n = 67), colon (n = 3), or jejunum (n = 1). Most gastric transpositions had a pyloroplasty (46/67) or pyloromyotomy (14/67). Most common pathology was oesophageal atresia (n = 50 including 2 failed transpositions), caustic injury (n = 19 including 3 due to button battery), stricture of unknown cause (n = 1), and megaoesophagus (n = 1). There were 2 (2.8 %) early postoperative deaths at 2 days (major vessel thrombosis), 1 month (systemic sepsis), and one death at 5 years in the community. The rate of postoperative complications were comparable across LAR and OAR including anastomotic leak, pleural effusions, or early strictures. More patients with caustic pathology needed dilatations (60 % vs 30 % in OA, p = 0.05). CONCLUSIONS: Outcomes of open and laparoscopic-assisted oesophageal replacement procedures are comparable in the short and medium term. Anastomotic stricture is higher in those with caustic injury. LEVEL OF EVIDENCE: IV.

Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms.

Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]). In adults, the reticulin algorithm (RA) has proven inexpensive, reliable, predictive, and reproducible; however, it has been validated only recently in children in a limited number of cases. This study aims to assess the RA utility compared with other scoring systems in a series of 92 pediatric ACNs. All cases were individually scored, and mitotic rate cutoffs were recorded. Reticulin alterations were classified as quantitative and qualitative. Outcome data were available in 59/92. The median age was 5 years (0.1 to 18 y) with an M:F of 0.6. Clinical presentation included virilization (39%), Cushing syndrome (21%), other symptoms (4%), and asymptomatic (36%). The reticulin framework was intact in 27% and altered in 73% of cases, showing qualitative (22%), quantitative (73%), and both (5%) alterations. In patients with favorable outcomes, 59% showed either intact reticulin or qualitative alteration compared with the unfavorable outcome group, where 90% showed quantitative alterations. All scoring systems WC ( P < 0.0001), mWC ( P = 0.0003), and the adult/pediatric RA ( P < 0.0001) had predictive value. The RA is comparable to WC and mWC, easier to apply, and is the most sensitive histopathological approach to identifying aggressive behavior in pediatric ACN. Its integration into the WC might be helpful in ACN of uncertain malignant potential and deserves further investigation.

Laparoscopic inguinal hernia repair (LIHR): the benefit of the double stitch in the largest single-center experience.

AIM: To review our experience of laparoscopic inguinal hernia repair (LIHR) regarding complication rates, the practice of closing the asymptomatic patent processes vaginalis (PPV), and comparison of complication rates between pre-term (< 37 week gestation) and term infants. METHODS: Retrospective review of LIHR performed between 2009 and 2021. Repair was performed by intracorporal single or double purse string/purse string + Z-stitch using a non-absorbable suture. Data were analyzed using Chi-squared/Mann-Whitney and are quoted as median (range). RESULTS: 1855 inguinal rings were closed in 1195 patients (943 (79%) male). 1378 rings (74%) were symptomatic. 492 (41%) patients were pre-term. Corrected gestational age at surgery was 55 weeks (31 weeks-14.6 years) and weight 5.9 kg (1-65.5). Closure of contralateral PPV was higher in the premature group (210/397 [53%] vs. 265/613 [43%] p = 0.003). There were 23 recurrences in 20 patients, of whom 10 had been born prematurely. The only factor significantly associated with a lower recurrence was use of a second stitch (p = 0.011). CONCLUSION: This is the largest single-center reported series of LIHR. LIHR is safe at any age, the risk of recurrence is low, and can be corrected by re-laparoscopy. Use of a Z-stitch or second purse string is associated with a significantly lower rate of recurrence.

Identification of Pediatric Tumors Intraoperatively Using Indocyanine Green (ICG).

BACKGROUND: Fluorescence-guided surgery (FGS) with indocyanine green (ICG) is increasingly applied in pediatric surgical oncology. However, FGS has been mostly reported in case studies of liver or renal tumors. Applying novel technologies in pediatric surgical oncology is more challenging than in adult surgical oncology due to differences in tumor histology, biology, and fewer cases. No consensus exists on ICG-guided FGS for surgically managing pediatric solid tumors. Therefore, we reviewed the literature and discuss the limitations and prospects of FGS. METHODS: Using PRISMA guidelines, we analyzed articles on ICG-guided FGS for childhood solid tumors. Case reports, opinion articles, and narrative reviews were excluded. RESULTS: Of the 108 articles analyzed, 17 (14 retrospective and 3 prospective) met the inclusion criteria. Most (70.6%) studies used ICG to identify liver tumors, but the timing and dose of ICG administered varied. Intraoperative outcomes, sensitivity and specificity, were reported in 23.5% of studies. Fluorescence-guided liver resections resulted in negative margins in 90-100% of cases; lung metastasis was detected in 33% of the studies. In otolaryngologic malignancies, positive margins without fluorescence signal were reported in 25% of cases. Overall, ICG appeared effective and safe for lymph node sampling and nephron-sparing procedures. CONCLUSIONS: Despite promising results from FGS, ICG use varies across the international pediatric surgical oncology community. Underreported intraoperative imaging outcomes and the diversity and rarity of childhood solid tumors hinder conclusive scientific evidence supporting adoption of ICG in pediatric surgical oncology. Further international collaborations are needed to study the applications and limitations of ICG in pediatric surgical oncology.

Evaluating the Development Status of Fluorescence-Guided Surgery (FGS) in Pediatric Surgery Using the Idea, Development, Exploration, Assessment, and Long-Term Study (IDEAL) Framework.

Fluorescence-guided surgery (FGS) is used in many pediatric subspecialties but there are currently no standard guidelines or outcome data. We aimed to assess the current status of FGS in pediatrics using the Idea, Development, Exploration, Assessment, and Long-term study (IDEAL) framework. Clinical papers on FGS in children published from January 2000 to December 2022 were systematically reviewed. The stage of research development was measured considering seven fields of application: biliary tree imaging, vascular perfusion for gastrointestinal procedures, lymphatic flow imaging, tumor resection, urogenital surgery, plastic surgery, and miscellaneous procedures. Fifty-nine articles were selected. For each field of application, the overall IDEAL stage was determined to be 2a for biliary tree imaging (10 publications, 102 cases), 1 for vascular perfusion for gastrointestinal procedures (8 publications, 28 cases), 1 for lymphatic flow imaging (12 publications, 33 cases), 2a for tumor resection (20 publications, 238 cases), 2a for urogenital surgery (9 publications, 197 cases), and 1-2a for plastic surgery (4 publications, 26 cases). One report did not belong to any categories. FGS in children is still in an early phase of adoption and development. We recommend using the IDEAL framework as a guide and suggest developing multicenter studies to define the standard guidelines, effectiveness, and outcomes.

Ultrasonographic features associated with previous torsion and the impact of surgery in managing neonatal ovarian cysts: a 20-year single-centre retrospective study.

PURPOSE: To identify markers of previous ovarian torsion and outline the outcomes according to US appearance and operative management. METHODS: A retrospective single-centre review of neonatal ovarian cysts from January 2000 to January 2020. Data on postnatal cyst size and sonographic features and operative treatment were co-related with outcomes of ovarian loss and histology. RESULTS: 77 females were included with 22 simple and 56 complex cysts, one patient had bilateral cysts. 9/22 (41%) simple cysts regressed spontaneously in a median of 13 weeks (8-17). Complex cysts regressed spontaneously less frequently, 7/56(12%, P = 0.01), in 13 weeks (7-39). 38/56 (68%) complex and 12/22 (55%) simple cysts were treated operatively. 21/22 (95%) ovaries with initially simple cyst were salvaged compared to 20/56(36%) with initially complex cyst (P < 0.001). A fluid-debris level in 23/26 complex cysts was most associated with ovarian loss (P = 0.0006). Presence of viable ovarian stromal tissue was seen in 8/20 (40%) excised specimens during ovarian sparing procedures and in 5/30 (17%) oophorectomies for necrotic appearing ovaries. CONCLUSIONS: Fluid-debris level on US is significantly associated with ovarian loss likely due to previous torsion. Simple cysts are viable and often regress spontaneously. The finding of viable ovarian stromal tissue in resected specimens supports attempting ovarian preservation wherever possible.

Enhancing intraoperative tumor delineation with multispectral short-wave infrared fluorescence imaging and machine learning.

Significance: Fluorescence-guided surgery (FGS) provides specific real-time visualization of tumors, but intensity-based measurement of fluorescence is prone to errors. Multispectral imaging (MSI) in the short-wave infrared (SWIR) has the potential to improve tumor delineation by enabling machine-learning classification of pixels based on their spectral characteristics. Aim: Determine whether MSI can be applied to FGS and combined with machine learning to provide a robust method for tumor visualization. Approach: A multispectral SWIR fluorescence imaging device capable of collecting data from six spectral filters was constructed and deployed on neuroblastoma (NB) subcutaneous xenografts ( n = 6 ) after the injection of a NB-specific NIR-I fluorescent probe (Dinutuximab-IRDye800). We constructed image cubes representing fluorescence collected from ∼ 850 to 1450 nm and compared the performance of seven learning-based methods for pixel-by-pixel classification, including linear discriminant analysis, k -nearest neighbor classification, and a neural network. Results: The spectra of tumor and non-tumor tissue were subtly different and conserved between individuals. In classification, a combine principal component analysis and k -nearest-neighbor approach with area under curve normalization performed best, achieving 97.5% per-pixel classification accuracy (97.1%, 93.5%, and 99.2% for tumor, non-tumor tissue and background, respectively). Conclusions: The development of dozens of new imaging agents provides a timely opportunity for multispectral SWIR imaging to revolutionize next-generation FGS.

Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma.

Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Shortwave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) imaging with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW and IR12), with long tails emitting in the SWIR range, were conjugated with a clinical-grade anti-GD2 monoclonal antibody (dinutuximab-beta) to compare NIR-I and SWIR imaging for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR fluorescence imaging device was constructed to allow an objective comparison between the two imaging windows. Conjugates were first characterized in vitro. Tissue-mimicking phantoms, imaging specimens of known geometric and material composition, were used to assess the sensitivity and depth penetration of the NIR-I/SWIR device, showing a minimum detectable volume of ∼0.9 mm3 and depth penetration up to 3 mm. In vivo, fluorescence imaging using the NIR-I/SWIR device showed a high tumor-to-background ratio (TBR) for both dyes, with anti-GD2-IR800 being significantly brighter than anti-GD2-IR12. Crucially, the system enabled higher TBR at SWIR wavelengths than at NIR-I wavelengths, verifying SWIR imaging enables high-contrast delineation of tumor margins. This work demonstrates that by combining the high specificity of anti-GD2 antibodies with the availability and translatability of existing NIR-I dyes, along with the advantages of SWIR in terms of depth and tumor signal-to-background ratio, GD2-targeted NIR-I/SWIR-guided surgery could improve the treatment of patients with neuroblastoma, warranting investigation in future clinical trials. SIGNIFICANCE: Multispectral near-infrared I/shortwave infrared fluorescence imaging is a versatile system enabling high tumor-to-background signal for safer and more complete resection of pediatric tumors during surgery.

Spermine oxidase induces DNA damage and sensitizes fusion negative rhabdomyosarcoma cells to irradiation.

Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma that includes fusion-positive (FP) and fusion-negative (FN) molecular subtypes. FP-RMS expresses PAX3-FOXO1 fusion protein and often shows dismal prognosis. FN-RMS shows cytogenetic abnormalities and frequently harbors RAS pathway mutations. Despite the multimodal heavy chemo and radiation therapeutic regimens, high risk metastatic/recurrent FN-RMS shows a 5-year survival less than 30% due to poor sensitivity to chemo-radiotherapy. Therefore, the identification of novel targets is needed. Polyamines (PAs) such as putrescine (PUT), spermidine (SPD) and spermine (SPM) are low-molecular-mass highly charged molecules whose intracellular levels are strictly modulated by specific enzymes. Among the latter, spermine oxidase (SMOX) regulates polyamine catabolism oxidizing SPM to SPD, which impacts cellular processes such as apoptosis and DNA damage response. Here we report that low SMOX levels are associated with a worse outcome in FN-RMS, but not in FP-RMS, patients. Consistently, SMOX expression is downregulated in FN-RMS cell lines as compared to normal myoblasts. Moreover, SMOX transcript levels are reduced FN-RMS cells differentiation, being indirectly downregulated by the muscle transcription factor MYOD. Noteworthy, forced expression of SMOX in two cell lines derived from high-risk FN-RMS: 1) reduces SPM and upregulates SPD levels; 2) induces G0/G1 cell cycle arrest followed by apoptosis; 3) impairs anchorage-independent and tumor spheroids growth; 4) inhibits cell migration; 5) increases γH2AX levels and foci formation indicative of DNA damage. In addition, forced expression of SMOX and irradiation synergize at activating ATM and DNA-PKCs, and at inducing γH2AX expression and foci formation, which suggests an enhancement in DNA damage response. Irradiated SMOX-overexpressing FN-RMS cells also show significant decrease in both colony formation capacity and spheroids growth with respect to single approaches. Thus, our results unveil a role for SMOX as inhibitor of tumorigenicity of FN-RMS cells in vitro. In conclusion, our in vitro results suggest that SMOX induction could be a potential combinatorial approach to sensitize FN-RMS to ionizing radiation and deserve further in-depth studies.

Dynamic Changes in Microvascular Density Can Predict Viable and Non-Viable Areas in High-Risk Neuroblastoma.

Despite aggressive treatments, the prognosis of high-risk NB remains poor. Surgical oncology needs innovative intraoperative devices to help surgeons discriminate malignant tissue from necrotic and surrounding healthy tissues. Changes within the tumor vasculature could be used intraoperatively as a diagnostic tool to guide surgical resection. Here, we retrospectively analyzed the mean vascular density (MVD) of different NB subtypes at diagnosis and after induction chemotherapy using scanned histological samples. One patient was prospectively enrolled, and an ex vivo photoacoustic imaging (PAI) scan was performed on two representative sections to assess its capacity to discriminate different tumor regions. We found that post-chemotherapy, viable areas of differentiating NBs and ganglioneuroblastomas are associated with higher MVD compared to poorly differentiated NBs. Early necrotic regions showed higher MVD than late necrotic and viable regions. Finally, calcified areas showed significantly lower MVD than any other histological component. The acquired PAI images showed a good high-resolution ex vivo 3D delineation of NB margins. Overall, these results suggest that a high-definition preclinical imaging device such as PAI could potentially be exploited to guide surgical resection by identifying different vasculature signatures.

Minimal access surgery for congenital diaphragmatic hernia: surgical tricks to facilitate anchoring the patches to the ribs.

OBJECTIVE: Minimal Access Surgery (MAS) for Congenital Diaphragmatic Hernia (CDH) repair is well described, yet only a minority of surgeons report this as their preferred operative approach. Some surgeons find it particularly difficult to repair the defect using MAS and convert to laparotomy when a patch is required. We present in this study our institutional experience in using an easy and relatively cheap methodology to anchor the patch around the ribs using Endo Close™. This device has an application in MAS for tissue approximation using percutaneous suturing. METHODS AND TECHNIQUE: We retrospectively reviewed our database for patients undergoing MAS repair of CDH between 2009 and 2021. Outcome measures included length of surgery and recurrence rates after patch repair. Endo Close™ was used in all patients who required patch repair. We declare no conflict of interest and to not having received any funding from Medtronic (UK). The technique is as follows: (1) The edges of the diaphragm are delineated by dissection. When primary suture repair of the diaphragmatic hernia was unfeasible without tension, a patch was used. (2) The patch is anchored in place by two corner stitches at the medial and lateral borders. (3) The posterior border of the patch is fixed to the diaphragmatic edge by running or interrupted stitches. (4) For securing the anterior border, a non-absorbable suture is passed through the anterior chest wall and the patch border is taken with intracorporeal instruments. (5) Without making another stab incision, the Endo Close™ is tunnelled subcutaneously through the anterior chest wall. (6) The suture end is pulled through the Endo Close™ and the knot is tied around the rib. This procedure can be performed as many times as required to secure the patch. RESULTS: 58 patients underwent MAS surgery for repair of CDH between 2009 and 2021. 48 (82%) presented with a left defect. 34 (58%) had a patch repair. The length of patch repair surgery for CDH ranged from 100-343 min (median 197). There was only one patient (3%) in the patch repair cohort that had a recurrent hernia, diagnosed 12 months after the initial surgery. CONCLUSIONS: In our experience, MAS repair of CDH is feasible. We adopted a low threshold in using a patch to achieve a tension-free repair. We believe that the Endo Close™ is a cheap and safe method to help securing the patch around the ribs.

Thoracoscopic vs open repair of congenital diaphragmatic hernia after extracorporeal membrane oxygenation: a comparison of intra-operative data.

PURPOSE: ECMO is an escalation treatment for hypoxic respiratory failure in patients with CDH. Open repair has been advocated after ECMO indicating that physiological changes associated to thoracoscopic repair were not well tolerated. METHODS: We have performed a retrospective review of all patients who underwent ECMO prior CDH repair over a 7 year period (2015-2021). Outcome measures were intra-operative Ph, PCO2, PO2 and FiO2 at 30 min, 1 h 30 min, and 2 h 30 min of surgery, operative time and recurrence rate. Data are shown in median (range). RESULTS: Eleven patients required ECMO prior CDH repair. Six of eleven (55%) were done thoracoscopically (Group A) and five of eleven (45%) via laparotomy (Group B). Two of six (33%) patients (Group A) were converted to a laparotomy, one of six (16%) patient developed a recurrence, and there was no recurrence in Group B. Two of five (40%) patients died within the first 60 days of life, whilst there was no death in Group A. Intra-operative values are shown below. CONCLUSION: Whilst this is a preliminary report of a limited number of patients, there is no obvious difference of intra-operative blood gas parameters during surgical repair in patients after ECMO. Thoracoscopic CDH repair may be considered in patients after ECMO.

Indocyanine Green-Based Fluorescence-Guided Surgery in a Male Infant with Anorectal Malformation.

Reconstructive techniques for complex anorectal malformations (ARMs) require intestinal pull-through on vascular pedicles. Traditionally, the visual inspection of the intestinal perfusion is the sole modality adopted to assess tissue viability. In this article, we report the case of a child with a rectourethral prostatic fistula, who had a Peña's descending colostomy with distal mucous fistula in the neonatal period and a posterior sagittal anorectoplasty at 6 months of life. The ARM repair was guided by indocyanine green (ICG), which was intravenously administered to evaluate the blood flow of the intestinal pull-through using the EleVision IR system (Medtronic Ltd, U.K.). ICG-based fluorescence-guided surgery helped to define the proximal resection margin, impacting intraoperative decision making, and no postoperative complications occurred. We envisage that this technology will become part of the armory of pediatric surgeons soon, by reducing the risk of intra- and postoperative complications.

Fluorescence-Guided Surgery (FGS) during a Laparoscopic Redo Nissen Fundoplication: The First Case in Children.

We present the first case of fluorescence-guided surgery (FGS) using indocyanine green (ICG) in a pediatric redo-Nissen fundoplication. The patient is a 17-year-old male with recurrent gastroesophageal symptoms who underwent primary antireflux surgery at 10 months of age. During the redo fundoplication, ICG was intravenously administered to help the visualization during the adhesiolysis between liver, stomach and right crus of the diaphragm and to spare small oesophageal vessels and the left gastric artery. In this case, FGS made the surgery easier than usual and likely reduced the risk of intra-operative complications. Therefore, we believe that this new technology should be regularly used in these types of complex intra-abdominal redo operations.

Maintaining a minimally invasive surgical service during a pandemic.

PURPOSE: The safety of minimally invasive surgery (MIS) was questioned in the COVID-19 pandemic due to concern regarding disease spread. We continued MIS during the pandemic with appropriate protective measures. This study aims to assess the safety of MIS compared to Open Surgery (OS) in this setting. METHODS: Operations performed during 2020 lockdown were compared with operations from the same time-period in 2019 and 2021. Outcomes reviewed included all complications, respiratory complications, length of stay (LOS) and operating surgeon COVID-19 infections (OSI). RESULTS: In 2020, MIS comprised 52% of procedures. 29% of MIS 2020 had complications (2019: 24%, 2021: 15%; p = 0.08) vs 47% in OS 2020 (p = 0.04 vs MIS). 8.5% of MIS 2020 had respiratory complications (2019: 7.7%, 2021: 6.9%; p = 0.9) vs 10.5% in OS 2020 (p = 0.8 vs MIS). Median LOS[IQR] for MIS 2020 was 2.5[6] days vs 5[23] days in OS 2020 (p = 0.06). In 2020, 2 patients (1.2%) were COVID-19 positive (MIS: 1, OS: 1) and there were no OSI. CONCLUSION: Despite extensive use of MIS during the pandemic, there was no associated increase in respiratory or other complications, and no OSI. Our study suggests that, with appropriate protective measures, MIS can be performed safely despite high levels of COVID-19 in the population.

Long-term active problems in patients with cloacal exstrophy: A systematic review.

BACKGROUND: Cloacal exstrophy (CE) is the most severe end of the Exstrophy-Epispadias Complex malformations spectrum. Improvements in postnatal management and well-established operative techniques have resulted in survival rates approaching 100%. This systematic review aims to define the prevalence of long-term active medical problems affecting CE patients after the first decade of life. METHODS: PubMed/Medline, Embase, Scopus, and ISI Web of Knowledge databases were used for the literature search. Original articles related to medical, surgical, and psychosocial long-term problems in CE patients >10 years of age were included in the study. Quality assessment of the articles was performed through the Newcastle-Ottawa Scale. Prevalence estimates and 95% CI were assessed for each outcome. RESULTS: Twelve studies were included. The most common long-term active problems identified were: urinary incontinence with a prevalence ranging from 9.1% to 85%; sexual function issues related to vaginal anomalies with a prevalence ranging from 8.3% to 71.3%, and uterine anomalies, with a prevalence from 14.3% to 71%; gender identity issues in 46, XY patients raised female had a prevalence from 11.1% to 66.7%. There is no documented history of paternity. Impairment of ambulatory capacity was recorded in 13.8% of patients. Only one paper studied psychological well-being, reporting significantly higher levels of depression among gender reassigned patients. CONCLUSIONS: Teenagers and adults born with CE have well defined long-term problems compared to the general population. Recognition and expert management are crucial to improve care and quality of life during and after the transition into adulthood.