Faculty of Medicine

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LAPAROSCOPIC VERSUS OPEN KASAI PORTOENTEROSTOMY FOR BILIARY ATRESIA: A SYSTEMATIC REVIEW AND META-ANALYSIS BY THE PEDIATRIC SURGERY META-ANALYSIS STUDY GROUP (PESMA)
(European Society of Paediatric Endoscopic Surgeons, 2025-10)
Duygu Gurel
;
Mustafa Azizoglu
;
Carlos Delgado Miguel
;
Federica Pederiva
;
Mehmet Hanifi Okur
Introduction: Biliary atresia (BA) is a rare but life-threatening neonatal liver disease requiring timely surgical intervention. The Kasai portoenterostomy (KPE) is the standard treatment, traditionally performed via laparotomy. Recently, laparoscopic approach has been introduced, but its efficacy remains debated. This systematic review and meta-analysis compared laparoscopic and open KPE in patients with BA. Methods: A comprehensive literature search of PubMed, Scopus, EMBASE, and Web of Science was conducted through April 2025. Primary outcomes were jaundice clearance, cholangitis, overall complications, 2-year native liver survival rate, and postoperative intestinal obstruction. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using Mantel–Haenszel methods under fixed- or random-effects models, based on heterogeneity (I²). We used RevMan 5.4 software meta-analysis statistic program. Results: A total of 26 studies were included. Jaundice clearance (17 studies; OR=1.10; 95%CI: 0.76–1.59; p=0.61; I²=42%) and cholangitis (15 studies; OR=1.17; 95%CI: 0.87– 1.59; p=0.30; I²=0%) rates showed no significant differences between laparoscopic and open groups. No significant differences were observed in overall complication rates (8 studies; OR=0.71; 95%CI: 0.24–2.09; p=0.54; I²=57%). Postoperative intestinal obstruction (7 studies) and 2-year native liver survival (8 studies) also showed comparable outcomes (OR=0.91; 95% CI: 0.36–2.27; p=0.83; I²=0% and OR=0.74; 95% CI: 0.49–1.10; p=0.13; I²=30% respectively). Conclusion: Laparoscopic KPE appears to be a safe and feasible alternative to the open approach, with comparable outcomes across major clinical parameters. While current evidence supports its feasibility, further high-quality prospective studies are needed to validate these findings and inform surgical practice.
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CAR T-cell therapy in pediatric oncology: From leukemia to emerging promise in Wilms tumor and solid malignancies
(Elsevier BV, 2025-08)
Mustafa Azizoglu
;
Asli Pinar
;
Ibrahim Baytar
;
Gonca Gercel
;
Ayten Ceren Bakir
CAR T cell therapy represents an advanced immunotherapeutic modality in pediatric oncology, involving genetic modification of a patient's own T cells to recognize and destroy cancer cells, offering highly targeted and personalized treatment. Originating from immunotherapy research in the 1980s, first-generation CARs were developed in 1989—1993, followed by second-generation CARs in the early 2000s with enhanced efficacy. FDA approval led to its first pediatric use in 2013, achieving complete remission in a child with acute lymphoblastic leukemia (ALL) [1—3]. Now approved for ALL and certain lymphomas, it provides hope for children with other cancers. Leukemia is a blood cancer that begins in the bone marrow, characterized by abnormal proliferation of blood cells, occurring in both children and adults, and can be controlled with early diagnosis and treatment. Recurrence of leukemia after chemotherapy remains challenging. CAR T-cell therapy, a breakthrough in hematologic cancers, enables engineered T cells to recognize and directly attack tumor antigens without MHC dependence, offering promising salvage treatment options [4]. A meta-analysis evaluated long-term outcomes and adverse effects of CAR T-cell therapy in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r BALL) using 10 clinical trials. Anti-CD19 CAR T-cell therapy achieved the highest minimal residual disease-negative complete remission (74.75 %), followed by anti-CD22 and CD19/CD22 combinations. The pooled remission rate was 70 %. Major adverse effects included cytokine release syndrome (81.8 %), hematologic toxicities (71.9 %), and neurotoxicity (33.2 %) [4]. Wilms tumor (nephroblastoma) is the most common pediatric kidney cancer, comprising over 90 % of childhood renal malignancies. Standard treatment―surgery, chemotherapy, and radiotherapy― achieves ~90 % 5-year survival in localized disease, but outcomes remain poor in high-risk or relapsed cases. CAR T-cell therapy offers a novel strategy, engineering patient T cells to target tumor-specific antigens. For Wilms tumor, promising targets include Wilms Tumor 1 (WT1), Glypican-3 (GPC3), and B7—H3 (CD276), all highly expressed in tumor tissue with limited presence in normal cells. Preclinical studies show these CAR T-cells can induce potent tumor cell killing. Challenges include antigen heterogeneity, the immunosuppressive tumor microenvironment, and limited CAR T-cell persistence. Strategies under investigation involve multi-antigen targeting, microenvironment modulation, and genetic enhancements (e.g., cytokine signaling domains) to improve durability. Several clinical trials are evaluating WT1-, GPC3-, and B7—H3-directed CAR T-cell therapies in pediatric solid tumors, including Wilms tumor. While still early in development, this approach holds promise for improving survival in high-risk and recurrent disease, potentially reducing the need for more toxic conventional therapies [5,6]. CAR T-cell therapy, while highly successful in hematologic cancers, faces significant challenges in pediatric solid tumors such as rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, medulloblastoma, and gliomas. These challenges include tumor heterogeneity, a suppressive microenvironment, and difficulty identifying safe, consistently expressed antigens. Promising targets under investigation include B7—H3, GD2, and HER2, each evaluated in ongoing clinical trials for tumors like osteosarcoma and rhabdomyosarcoma [7—9]. CAR T-cell therapy has revolutionized treatment for pediatric hematologic malignancies and shows emerging potential in Wilms tumor through novel antigen targets like WT1, GPC3, and B7—H3. While significant challenges remain in solid tumors, ongoing innovations and clinical trials may expand its curative potential for high-risk and relapsed pediatric cancers.
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Generative Artificial Intelligence Accuracy in Interpreting Forest Plots in Pediatric Surgery Meta-analyses: A Perspective From Pediatric Surgery Meta-analysis Study Group (PESMA)
(Elsevier BV, 2025-04)
Mustafa Azizoglu
;
Maria Escolino
;
Tahsin Onat Kamci
;
Sergey Klyuev
;
Sonia Perez Bertolez
Pediatric surgery is a relatively newer specialty compared to fields such as orthopedics, internal medicine, and pediatrics. The number of pediatric surgeons worldwide is significantly lower than in many other medical disciplines. Consequently, this has resulted in a lower cumulative volume of academic research in pediatric surgery, including a smaller number of meta-analyses. However, in recent years, there has been a noticeable increase in the number of meta-analyses within this field and dedicated pediatric surgery meta-analysis study groups such as PESMA have emerged. Despite this progress, there remains a considerable need for further research in this area.
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Comparing Loop and Divided Colostomy for Anorectal Malformation: A Systematic Review and Meta-Analysis
(Elsevier, 2025-01)
Gonca Gerçela
;
Mustafa Azizoglu
;
Esra Karakas
;
;
Maria Escolino
Introduction: The optimal type of colostomy for patients with anorectal malformations (ARM) remains unclear. We conducted a systematic review and meta-analysis to compare the clinical outcomes of loop colostomies (LC) versus divided colostomies (DC) in patients with ARM. Methods: After review registration (PROSPERO: CRD42024513335), we searched multiple databases for comparative studies on LCs and DCs in patients with ARMs. Gray literature was sought. The complications examined included stoma prolapse, urinary tract infection (UTI), skin excoriation, stoma retraction, parastomal hernia, wound infection rate, and stoma stricture. Three reviewers independently assessed the eligibility and quality of the included studies. Meta-analysis of selected complications was performed using Revman 5.4, with p < 0.05 considered significant. Results: Eleven studies were included in the analysis, incorporating a total of 2550 neonates with ARMs, of which 1147 underwent LCs and 1403 underwent DCs. The meta-analysis revealed no significant differences between the two groups in the incidence of stoma prolapse (OR: 1.55, 95 % CI: 0.63 to 3.79; p = 0.34), UTIs (OR: 1.78, 95 % CI: 0.50 to 6.36; p = 0.38), skin excoriation (OR: 1.26, 95 % CI: 0.68 to 2.34; p = 0.46), stoma retraction (OR: 0.79, 95 % CI: 0.09 to 6.64; p = 0.83), parastomal hernia (OR: 0.99, 95 % CI: 0.22 to 4.48; p = 0.99), wound infection (OR: 0.35, 95 % CI: 0.10 to 1.20; p = 0.10), and stoma stricture (OR: 0.70, 95 % CI: 0.22 to 2.18; p = 0.53). Conclusions: The findings suggest that LCs and DCs are viable options for fecal diversion, presenting similar risks and benefits. The choice between these techniques should consider individual patient characteristics and surgical expertise.

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