Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.

Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.

Breast implant surface topography triggers a chronic-like inflammatory response.

Breast implants are extensively employed for both reconstructive and esthetic purposes. However, the safety of breast implants with textured surfaces has been questioned, owing to a potential correlation with anaplastic large-cell lymphoma and the recurrence of breast cancer. This study investigates the immune response elicited by different prosthetic surfaces, focusing on the comparison between macrotextured and microtextured breast implants. Through the analysis of intraoperatively harvested periprosthetic fluids and cell culture experiments on surface replicas, we demonstrate that macrotextured surfaces elicit a more pronounced chronic-like activation of leucocytes and an increased release of inflammatory cytokines, in contrast to microtextured surfaces. In addition, in vitro fluorescent imaging of leucocytes revealed an accumulation of lymphocytes within the cavities of the macrotextured surfaces, indicating that the physical entrapment of these cells may contribute to their activation. These findings suggest that the topography of implant surfaces plays a significant role in promoting a chronic-like inflammatory environment, which could be a contributing factor in the development of lymphomas associated with a wide range of implantable devices.

Congenital Internal Jugular Phlebectasia: An Anomaly Still Poorly Recognized.

Congenital internal jugular phlebectasia (CIJP) is a rare condition characterized by congenital dilatation of the vein without tortuosity that becomes more evident during straining as a lateral neck mass. CIJP often remains undiagnosed from a few months to several years after the onset of the swelling. It is frequently asymptomatic although symptomatic cases have been occasionally reported. We present the case of a healthy 7-year-old boy with a lateral neck mass, triggered by the Valsalva maneuver. Neck ultrasound (US) showed right internal jugular axial ectasia, increasing during the Valsalva maneuver; contrast computed tomography (CT) scan confirmed a fusiform dilatation of the right internal jugular vein. Due to the lack of symptoms, we treated our patient conservatively. At 5 years of follow-up, the patient is still asymptomatic, with no evidence of complications or thrombosis. Due to its self-limiting nature, treatment for asymptomatic cases of CIJP should be conservative, providing a follow-up with both clinical and US annual evaluations.

Endoscopic Treatment for Nonhypertrophic Idiopathic Pyloric Stenosis in an Adolescent Patient.

Nonhypertrophic idiopathic pyloric stenosis (NHIPS) is a rare occurrence in children. It could be related to peptic ulcers, but a definitive cause is yet to be found. Treatment is a matter of debate, ranging from medical to surgical. We report the case of a 15-year-old boy suffering postprandial vomiting and weight loss in the previous 3 months. NHIPS was diagnosed and successfully treated with several sessions of endoscopic pyloric dilation and jejunal feeding. In association with a multidisciplinary approach, endoscopic dilation should be considered as a first-line treatment to avoid surgery.

Meta-Analysis on Long-Term Outcomes of Pediatric Renal Cancer Survivors Following COG and SIOP Protocols.

BACKGROUND: Pediatric renal cancer survivors have higher rate of chronic renal disease and hypertension. These patients have similar survival rates when treated according to either Children's Oncology Group (COG) or International Society of Pediatric Oncology (SIOP) protocols. We aimed to compare the late outcome of these two approaches. METHODS: We performed a meta-analysis of all studies from 2000 to 2021; database search using keywords: long-term outcomes OR late effects, nephrectomy, pediatric renal cancer. For each protocol, data were collected, and the "pooled" outcomes were compared. Continuous and dichotomous variables were obtained with a 95% odds ratio. RESULTS: Sixteen studies with a total of 715 pediatric renal cancer survivors were analyzed. The mean follow-up time was 17.4 (standard deviation 5.6) years. Reduced renal function and hypertension were the most encountered long-term complications. The mean estimated glomerular filtration rate was similar in both protocols (101.62 vs. 101.70 mL/min/1.73 m2), while the prevalence of hypertension was 23% in COG and 10% in SIOP. The prevalence of secondary malignancy was 1.1% in COG and 6.7% in SIOP (1.1% vs. 6.7%, p ≤ 0.001). Chronic kidney disease was similar in both groups. CONCLUSION: A high prevalence of hypertension was observed among pediatric renal cancer survivors, as well as an increased risk of a secondary tumor. These results emphasize the importance of long-term follow-up into adulthood, to promptly diagnose any long-term side effects of the treatment. Thanks to the increased overall survival, future protocols will pay attention to the reduction of long-term sequelae.

Pediatric Surgical Care During the COVID-19 Lockdown: What Has Changed and Future Perspectives for Restarting in Italy. The Point of View of the Italian Society of Pediatric Surgery.

Background: The coronavirus disease 2019 (COVID-19) time exacerbated some of the conditions already considered critical in pediatric health assistance before the pandemic. A new form of pediatric social abandonment has arisen leading to diagnostic delays in surgical disorders and a lack of support for the chronic ones. Health services were interrupted and ministerial appointments for pediatric surgical healthcare reprogramming were postponed. As a result, any determination to regulate the term "pediatric" specificity was lost. The aim is, while facing the critical issues exacerbated by the COVID-19 pandemic, to rebuild future perspectives of pediatric surgical care in Italy. Methods: Each Pediatric Society, including the Italian Society of Pediatric Surgery (SICP), was asked by the Italian Federation of Pediatric Associations and Scientific Societies to fill a questionnaire, including the following the main issues: evaluation of pre-pandemic criticalities, pediatric care during the pandemic and recovery, and current criticalities. The future care model of our specialty was analyzed in the second part of the questionnaire. Results: Children are seriously penalized both for surgical treatment as well as for the diagnostic component. In most centers, the pediatric surgical teams have been integrated with the adult ones and the specificity of training the pediatric operating nursing is in danger of survival. "Emotional" management of the child is not considered by the general management and the child has become again an adults patient of reduced size. Conclusion: A new functional pediatric surgical model needs to be established in general hospitals, including activities for day surgery and outpatient surgery. To support the care of the fragile child, a national health plan for the pediatric surgery is required.

The Role of Video-Assisted Thoracoscopic Surgery in Pediatric Oncology: Single-Center Experience and Review of the Literature.

Aim: Video-assisted thoracoscopic surgery (VATS) has been widely used in the last decades. Nevertheless, the pros and cons of thoracoscopy vs. open surgery in pediatric oncology are still under debate. In literature, VATS has been applied for both diagnostic and ablative surgery to treat neurogenic tumors, thymic neoplasms, lung tumors and metastases, germ cell tumors, lymphoproliferative diseases, and other rare tumors. Recent reviews described excellent outcomes in pediatric oncology as well as in the treatment of adult lung cancer, with a significantly higher rate of mortality and complication in thoracotomy compared to VATS. We reviewed our experience on thoracoscopy in pediatric malignancy and compared it to the literature. Materials and Methods: This was a retrospective cohort-study of pediatric oncological patients who underwent VATS at our institution from 2007 to 2020, and a review of the recent literature on the topic. Results: A total of 43 procedures were performed on 38 oncological patients (18 males, 20 females). Median age was years 7.72 (0.35-18.6). Diagnosis: 10 neurogenic tumors, nine hematological diseases, five metastases, four lypoblastomas, three thymic pathologies, three germ cell tumors, two pleuropneumoblastomas, two myofibroblastic tumors, one myoepithelial carcinoma, one liposarcoma, and three suspected oncological mass. In three cases, a 3D model was elaborated to better plan the surgical approach. Diagnostic biopsies were 22 (51.1%), and ablative surgeries, 21 (48.9%). One neurogenic tumor was resected with the Da Vinci Robot. Median operative time was 120 min (30-420). A drain was left in place in 20 (46.5%) for a median of 4 days. Median length of hospitalization was 5 days (1-18). One case (2.3%) was converted (intraoperative bleeding). There were three post-operative complications (7.0%): one pneumonia, one pleural effusion, and one diaphragmatic paralysis (need for plication). Results were compared to recent literature, and morbidity and conversion rate were comparable to reviewed publications. Conclusion: VATS represents a valuable tool for diagnostic and therapeutic procedures in pediatric oncology. Nonetheless, it is a challenging technique that should be performed by expert surgeons on oncological and mini-invasive surgery. Three-dimensional reconstruction can optimize the pre-operative planning and guarantee a safer and more targeted treatment. Finally, the advent of robotics-assisted surgery represents a new challenge that may further implement the advantages of VATS.

The Effectiveness of Abdominal Lymphangioma Laparoscopic Removal in Children: A Single Center Experience.

Background: Lymphangiomas represent 5% of all benign pediatric tumors. Abdominal lymphangiomas (ALs) are extremely rare. Therapy includes surgery, sclerotherapy, or pharmacological treatment. Laparoscopic resection (LR) has been already described, but mainly as case reports. The aim of this study is to present our series of ALs LR. Materials and Methods: From 2007 to 2020, 10 cases of ALs were electively treated by LR. Patients' age ranged from 4 months to 14 years. Preoperative diagnosis was achieved by ultrasonography and magnetic resonance images. In all cases LR was performed with four trocars: a 10 mm transumbilical trocar for camera and extraction and three 3-5 mm operative trocars. Results: Lymphangiomas arise from mesocolon in 5 giant cases, ileal mesentery in 3 and right adrenal gland in 2. LR was achieved without intraoperative complications and need of conversion in all cases. Two giant cases needed a percutaneous puncture under laparoscopic view to gain working space. A minimal ileal resection by video-assisted procedure was carried out in 2. Median hospital length was 4 days; no recurrence of disease at serial ultrasound examinations was seen at median follow-up of 5.9 years. Discussion: Several approaches have been proposed for AL treatment. The main challenges are the huge dimensions, the difficulty to achieve a complete resection, and the risk of recurrence. In this series, elective LR of ALs resulted as feasible and effective, and we consider it the standard surgical therapy.

Effectiveness of Articulating Linear Stapler for Total and Partial Laparoscopic Splenectomy in Children.

Purpose: We performed a retrospective study to determine the effectiveness and feasibility of articulating linear stapler in laparoscopic total splenectomy (LTS) and laparoscopic partial splenectomy (LPS), focusing on technical laparoscopic skills that could help pediatric surgeons to avoid intra- and postoperative complications. Methods: Retrospective cohort study of children younger than 18 years who underwent laparoscopic spleen surgery between January 2008 and March 2020. Age, sex, indication for surgery, operative time (OT), intra- and postoperative complications, and postoperative length of hospital stay (LHS) were analyzed. Data from parenchymal resection and vessels sealing techniques were obtained. Results: Thirty patients, 19 LTS and 11 LPS, were included. The mean age of the patients was 10.9 years, and 16 patients were male and 14 were female. For hematologic diseases, LTS was the elective surgery, associated with cholecystectomy in 5 cases. LPS was the common procedure for splenic cysts. The stapler was used in LTS to close the hilum vessels and in LPS for parenchymal resection. No statistically significant differences in OT were observed comparing LTS and LPS. Two conversions occurred in LTS; none in LPS. The mean LHS was 6 days in both groups. No recurrence or major complications appeared in both groups at 1-12 years of follow-up. In particular for LPS, there are no relapse of cyst neither reduction in splenic function. Conclusions: This study shows the effectiveness, feasibility, and safety of mechanic stapler in splenic surgery both for hilum vessels sealing and for parenchymal resection. The use of this device can reduce risk of hemorrhagic recurrences or major surgical complications improving the safety of the operation.

Eosinophilic colitis in children: a new and elusive enemy?

PURPOSE: Eosinophilic gastrointestinal disorders are rare in children and present with a broad spectrum of non-specific symptoms. To date, no guidelines for diagnosis, therapy and follow-up are validated. Aim of our study is to focus on eosinophilic colitis (EC), to determine a possible correlation between associated disorders, macroscopic findings and treatment/follow up. METHODS: Retrospective study from 2015 to 2019 including all colonoscopies performed at our Institution. Eosinophilic colitis was defined according to the threshold identified by Collins: > 100 Eo/Hpf: right colon, > 84 Eo/Hpf transverse and left colon, > 64 Eo/Hpf sigma and rectum. We excluded colonoscopy in patients with IBD or other diseases causing hypereosinophilia (i.e., parasite infection, GVHD). RESULTS: Among 399 colonoscopies performed in 355 patients, we made 50 diagnosis of EC, 36 males, 14 females, median age 8.5 (3-17). Symptoms leading to endoscopy were recurrent abdominal pain (66%), chronic diarrhea (64%), and chronic constipation (8%). Two patients presented with GI bleeding and one with weight loss. Macroscopic findings were mostly normal or lymphoid nodular hypertrophy presenting different endoscopic features. In seven children (14%) we found history of allergy and atopy. 22 children present a diagnosis of autistic spectrum disorder (ASD) with a prevalence higher than in the overall population (44% vs 28.5%, p = 0.03). According to symptoms, treatment consist variably of steroids, six food elimination diet, mesalamine. For patients with available follow-up, we found histological persistence of Eosinophils in 75%, even in patients with symptoms relief. CONCLUSION: This study focus attention on EC as a new challenging pathology. Multicentric randomized clinical trials are needed to understand physiopathological mechanisms to validate a possible endoscopic score and related histological threshold, and to standardize therapy according to clinical features and instrumental findings. The high prevalence of EC in ASD need further specific research.

Intracavitary electrocardiography-guided positioning of central vascular access device can spare unnecessary ionizing radiation exposure in pediatric patients.

BACKGROUND: Most hospital protocols-including those of our own institute-require the use of radiography to validate tip position in every central vascular access device placement. This study evaluated whether unnecessary ionizing radiation exposure could be spared in the pediatric population when intracavitary electrocardiography is used to guide catheter placement. MATERIAL AND METHODS: Retrospective study of intracavitary electrocardiography-guided central vascular access device placements in our pediatric surgery department between 2013 and 2018. We evaluated the operating time, success in positioning the catheter, and accuracy of final tip position. We also assayed the effects of catheter type and of catheter access point on operating time, success, accuracy, and complications. We applied the chi-square test for statistical analysis. RESULTS: In total, 622 interventions of central vascular access device placements were evaluated; 340 intracavitary electrocardiography-guided central vascular access device placements were included in the study. The electrocardiography method successfully positioned the tip of the catheter in 316/340 (92.94%) of placements. Where intracavitary electrocardiography placement was successful, radiography confirmed accuracy of tip position in 314/316 (99.41%) of placements. CONCLUSION: When electrocardiography-guided positioning is uneventful and a valid P-Wave pattern is seen, postprocedure radiograph imaging for verification is unnecessary. Any effort should be made to upgrade hospital policies according to evidences and newest guidelines to spare pediatric patients harmful exposure to radiation by limiting the use of radiography only to selected cases.

Robotics-Assisted Pediatric Oncology Surgery-A Preliminary Single-Center Report and a Systematic Review of Published Studies.

AIM: The use of robotics-assisted surgery in oncology has been proved effective and safe in adults. Despite these results, the use of robotics has been rarely reported for pediatric oncology. Our review aims to evaluate the safety and feasibility of robotics-assisted surgery in this field, analyzing our experience and performing a systematic review of the most recent studies. METHODS: We reviewed all patients affected by an oncological disease who underwent a robotics-assisted procedure at our institute. We performed a systematic review of the literature from 2012 to 2021 on the subjects. FINDINGS: A total of 14 patients underwent robotics-assisted tumor resection. Eleven procedures (median age 13.2-years old) were carried out in children with adnexal lesions (seven tumor excision and four ovariectomies). Histological diagnosis was mature teratoma (six), serous papillary cystadenofibromas of the fallopian tube (two), ovarian serous cystadenoma (one), ovarian mucinous cystadenoma (one), and ovarian seromucinous cystadenoma. The median length of stay was 2 days. No recurrences or complications at a median follow-up of 2.1-years were observed. A 5-year-old girl underwent a complete posterior resection of a type 3 sacrococcygeal tumor with a robotics-assisted approach for the dissection of a possible intraabdominal residual component of the lesion. No intra- and postoperative complications were recorded. Complete excision of a recurrent differentiating neuroblastoma of the left para-renal region was performed on a 9-year-old girl. An idiopathic anaphylactic shock occurred 1 day after the procedure. At 9 months' follow-up, no local recurrences of the lesion were observed. Overall, we reported no conversion to open surgery. Lastly, a robotic excision of a growing left superior mediastinal intermixed ganglioneuroblastoma was performed on an 8-year-old girl with no postoperative complications. Follow-up was uneventful (7 months). In the literature, the rate of complications ranges from 0 to 28%, mainly related to difficult dissection and impaired anatomy. Conversion is reported in 5% of all oncological procedures, due to more invading tumors and altered anatomical features. No robotics-related complications were reported. CONCLUSION: Robotics-assisted surgery in pediatric oncology has proven to be feasible. Nevertheless, its use should be limited to selected cases and performed by highly trained oncological surgeons. Preparation and patient positioning, alongside a correct port placement, are crucial to carrying out these procedures. Further innovations in robotics may allow a wider application of this technology in pediatric oncology.

Juvenile Granulosa Cell Tumor of the Testis: Prenatal Diagnosis and Management.

Prepubertal primary testicular tumors account for ∼1% of all pediatric solid tumors. We report a new case of prenatal diagnosis of juvenile-type granulosa cell tumor (JGCT). A fetal ultrasound performed at the 38th week of gestation for suspected nonvertex presentation identified a left multilocular septated cystic testicular mass, suggestive for JGCT. At birth, a painless left scrotal mass was detected. Ultrasound re-evaluation excluded torsion of the testis. Tumor markers and abdominal ultrasound were normal for age. Inguinal exploration revealed a cystic mass beneath the tunica albuginea that had replaced all the normal parenchyma. Since organ-sparing surgery was thus not feasible, an orchiectomy was performed and diagnosis of JGCT was confirmed. At 7-year follow-up, the child presented an uneventful outcome. Our case shows that neonatal JGCT, which has an intrauterine genesis, can be diagnosed prenatally by ultrasound in the last weeks of pregnancy.

Juxta-articular Myxoma of the Hip: A Rare Pediatric Tumor.

Juxta-articular myxoma (JAM) is a very rare myxoid tumor in pediatric age. JAM is frequently located at large joints, particularly in the knee, and most lesions present as palpable swelling sometimes associated with pain or tenderness. Only three cases of pediatric JAM have been reported in the literature to date. We describe a case of JAM in a 12-year-old boy, characterized by several unique aspects related to age, site of onset, size, and associated symptoms.

Intestinal Duplication and Hirschsprung's Disease: An Extremely Rare and Misleading Combination.

Hirschsprung's disease and, more rarely, intestinal duplication can both cause intestinal obstruction in neonates. The simultaneous occurrence of these two diseases is reported in only two studies, and in both cases, intestinal duplication was an incidental finding, as it had not determined clinical intestinal occlusion. This paper reports a unique case of coexistence of the two conditions, with both causing intestinal obstruction, delayed appropriate, and definitive surgical treatment.

Robotic-assisted surgery for excision of an enlarged prostatic utricle.

INTRODUCTION: Prostatic utricle is a rare malformation arising from incomplete regression of the Müllerian ducts. Diagnosis is easily made but management may be challenging. The minimally invasive approach has so far been considered the gold standard for surgical treatment. Many endoscopic and surgical procedures have been described for removal, but to date only few cases of robot-assisted procedures have been mentioned in the literature and there are no reports of redos. PRESENTATION OF THE CASE: We report the case of a giant prostatic utricle cyst successfully treated with robotic-assisted surgery two years after an unsuccessful first attempt at laparoscopic excision. No relapse was found at one year follow up. DISCUSSION: We were able to excise a retro-vescical structure in spite of adhesions caused by the previous surgery and the very large size of the diverticulum thanks to the high magnification and 3-D visualization available in robotic assisted laparoscopy. CONCLUSION: Robot assisted laparoscopy should be considered an advantageous technique for the treatment of prostatic utricle.

Five millimetre-instruments in paediatric robotic surgery: Advantages and shortcomings.

PURPOSE: The study was designed to assess the utility and controversies surrounding the usage of 5-mm instruments in paediatric robotic surgery. Adequate, delicate instruments for surgery in very narrow spaces are still lacking. MATERIAL AND METHODS: Thirty children underwent elective abdominal robotic surgery. Working sites, assembly and operative time, hospital stay, advantages, complications and shortcomings are reported. RESULTS: Interventions were performed in the following anatomical sites: 11 upper abdominal, nine pelvic, ten renal procedures. The majority of procedures required two operative trocars. A 2-3 mm accessory port was necessary for operations in the renal area and upper abdomen. The ports had to be placed at least 3 cm from the costal margins and superior iliac spines and at an angle of at least 130° with respect to the camera trocar. This configuration allowed intra-corporal knotting, vessel ligation and dissection with instruments in the inverted position. Operative times and hospital stays were similar to those reported for 8 mm-instruments. CONCLUSION: The use of 5-mm instruments was advantageous in renal and pelvic sites. The benefits in upper abdominal surgery need further evaluation, particularly in patients weighing <10 kg. Smaller sized instruments with high endowrist dexterity would resolve the problems encountered in paediatric robotic-assisted surgery using 5-mm instruments.

Robotic-assisted surgery approach in a biliary rhabdomyosarcoma misdiagnosed as choledochal cyst.

Rhabdomyosarcoma is a soft tissue malignant tumor affecting 1% of children from 0 to 14 years. Preoperative imaging may not always be diagnostic for hepatobiliary rhabdomyosarcoma and differential diagnosis with choledochal cyst (CC) could be difficult. We report a case of 2-years-old girl with a strange CC pattern of presentation. A grapelike lesion involving the choledochal and biliary ducts was easily and completely resected by robotic assisted surgery. Since no previous reports were available about oncologic safety of robotic approach, the porto-enterostomy was performed in open surgery. On histologic examination, the specimen revealed a botryoidembryonal rhabdomyosarcoma affecting both the common bile duct and the common hepatic duct. One year postoperatively the child is safe of tumor relapse. Robotic approach seems to be safe and advantageous to obtain a radical excision of the tumor at the porta hepatis, even in case of misdiagnosed malignant lesion mimicking a CC.

Pediatric robotic pyeloplasty in patients weighing less than 10 kg initial experience.

AIM: To report the feasibility and safety of a robotic-assisted laparoscopic pyeloplasty (RALP) in patients weighing <10 kg. MATERIALS AND METHODS: Three patients weighing between 5 and 8 kg who were affected by severe congenital ureteropelvic junction obstruction, including a child with solitary kidney, were subjected to RALP. Three trocars were placed; sutures and pyeloplasty remodeling were performed with interrupted stitches. A double J stent was inserted through a 2-mm transparietal angiocatheter to protect the pyelic suture. RESULTS: The procedures were all completed within 90 minutes, the "docking" time requiring 20 minutes. The patients were discharged on postoperative day 2, without any complications. CONCLUSIONS: Comprehensive assessment of pyelic suture in a very narrow field with 2 operative instruments is feasible and safe. Robotic pyeloplasty provides all the advantages of mini-invasive surgery with the added advantage of higher magnification and excellent surgical navigation in very small spaces and on fragile infant tissues.