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Purpose: Over the last 15 years thoracoscopic lobectomy for congenital and acquired lesions has become an accepted modality in pediatric thoracic surgery. There is still debate about the need to perform a complete lobectomy for some of these lesions, and some advocate observation rather then resection, despite possible longterm complications of untreated lesions. High-resolution computed tomography (CT) scans and physical findings at the time of surgery, along with new advanced techniques, now allow for discrete partial anatomic resections, which may preserve normal lung. This study evaluates the feasibility and early results using these techniques in selected cases. Patients and Methods: With institutional review board approval, the records of all patients undergoing thoracoscopic lung resection were reviewed. From January 2006 to December 2012, 23 patients, ranging from 1 month to 16 years of age and weighing 3.8-42 kg, underwent thoracoscopy for planned resection. Pathology was congenital cystic lung disease in 19 patients, bronchiectasis in 3 patients, and arteriovenous malformation in 1 patient. In each case findings on CT scan and at the time of surgery warranted consideration of lung-preserving surgery. Procedures were performed through three ports using single lung ventilation and CO2 insufflation to achieve lung collapse. The LigaSure device (Covidien, Norwalk, CT) was the primary instrument used to seal and divide the lung parenchyma and seal vessels. Results: All procedures were completed successfully thoracoscopically. An anatomic segmental resection was achieved in 22 of 23 cases. Operative time ranged from 30 to 300 minutes (mean, 120 minutes). Segmental resections included the left upper lobe apical/posterior (n = 4), lingula (n = 3), left lower lobe superior (n = 5), medial or posterior basal (n = 3), right middle lobe medial (n = 1), right upper lobe apical (n = 1), right lower lobe superior (n = 4), and posterior basal (n = 2). Two patients had more than one segment excised. Chest tubes were left in for 24 hours in 16 cases, 48 hours in 4 cases, and 5 days in 1 case. Hospital stay ranged from 1 to 6 days (mean, 2 days). Follow-up CT scans obtained at 1-6 years (mean, 28 months) show no residual disease in 20 of 21 patients. One patient underwent a nonanatomic resection and had evidence of recurrent congenital pulmonary airway malformation at the 4-year follow-up. This patient underwent a secondary thoracoscopic resection. Conclusions: Thoracoscopic lung-conserving therapy is technically feasible and safe in infants and children. The magnification provided by a thoracoscopic approach makes identification of segmental anatomic planes easier, aiding in safe dissection and resection. Anatomic resection appears to be associated with a low morbidity. It may be appropriate in the case of bilateral or extensive disease or in cases where the diseased tissue is clearly limited to an anatomic segment. Continued long-term follow-up is needed. [ABSTRACT FROM AUTHOR]

Purpose: Most functional intestinal obstruction in childhood is due to defects in the enteric innervation. Functional intestinal obstruction due to smooth muscle disorders is rare. The aim of this study was to describe four patients with functional intestinal obstruction where the only histopathological abnormality was deficient, alpha-smooth muscle actin (alpha-SMA) in the circular muscle of their small bowel.Materials and Methods: Resected intestinal segments from four children with functional intestinal obstruction were either snap frozen or embedded in paraffin wax, and transversely sectioned. Sections were examined by routine H&E staining, AChE and NADPH-diaphorase histochemistry, and immunohistochemistry using PGP9.5 and alpha-SMA antibodies. Normal age-matched tissue was used as controls.Results: All four patients demonstrated normal innervation in the small and large bowel. We observed striking differences in the expression of alpha-SMA within the intestinal muscle layers in all four patients. There was a markedly decreased level of alpha-SMA in the smooth muscle compared to the longitudinal muscle in the small bowel in each patient. All other regions of the intestine examined showed normal levels of alpha-SMA, with similar levels expressed in both the circular and longitudinal muscles.Conclusion: The decreased level of alpha-SMA in the smooth muscle of these patients causes a serious mechanical defect, thus interfering with normal intestine motility. These findings suggest that patients with functional intestinal obstruction should have a comprehensive investigation of the intestinal smooth muscle in addition to the assessment of the enteric nervous system. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatoblastoma is the most common malignant liver tumor in children. Small cell undifferentiated histology and low alpha-fetoprotein have been previously reported as factors associated with poor prognosis. It is important to exclude rhabdoid tumors (a rare pediatric liver tumor that is difficult to cure) in patients diagnosed with hepatoblastoma with alpha-fetoprotein levels less than 100 ng/mL and in patients with hepatoblastoma with small cell undifferentiated histology since the treatment for these patients is very different. When rhabdoid tumors are correctly diagnosed with testing for loss of SMARCB1, neither hepatoblastoma with small cell undifferentiated component nor alpha-fetoprotein less than 100 ng/mL confer poor prognosis. Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid tumors (n = 11), HB with SCU component (n = 41), and HB with low AFP (n = 14). Seven were excluded for erroneously low AFP levels. Overall survival was 0% for patients with rhabdoid tumors, 76% for patients with HB with SCU component, and 64% for patients with HB with AFP less than 100 ng/mL. Patients with HB with SCU component or low AFP should be assessed for SMARCB1 mutations and, if confirmed, treated as rhabdoid tumors. When rhabdoid tumors are excluded, the presence of SCU component and low AFP at diagnosis were not associated with poor prognosis in patients diagnosed with HB. [ABSTRACT FROM AUTHOR]

The European Union of Medical Specialists (UEMS) Section and Board of Pediatric surgery was founded more than 40 years ago. Since then major activities have been related to the improvement of quality of care of pediatric surgery in Europe. Remarkable success was achieved in the development of pediatric surgery as an independent specialty all over Europe. Other major successful activities of the UEMS Section and Board of Pediatric Surgery consisted of the development of a high-quality European examination and delineating a minimal common standard in pediatric surgery training in the form of European training requirements. Recommendations drawn from examination experience support that candidates who achieve weaker passes in part 1 may wish to consider more practice before attempting part 2 due to the weak correlation between the two scores. It may be helpful for candidates to consider having some experience working in an English-speaking clinical setting, if not truly fluent in English, to improve their chances of being successful in the part 2 examination. Other achievements of the Section were accreditation of the training centers in Europe and European Census in pediatric surgery project. All the aforementioned activities led to standardization and harmonization of pediatric surgery, as well as contributed to increasing quality of pediatric surgical service throughout Europe. [ABSTRACT FROM AUTHOR]

Surgical interventions in patients with peritoneal metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic treatment are becoming more common and, when applied to selected patient groups, they reach 5-year survival rates of 32–52%. Good clinical outcomes require experienced and well-equipped healthcare centers, experienced surgical team and adequate patient qualification process. As a result of the discussion on the need for evaluation of quality of care and treatment outcomes and at the request of the Peritoneal Cancer Section of the Polish Society of Surgical Oncology, accreditation standards have been developed and the Accreditation Committee has been established for healthcare centers providing cytoreductive surgery and HIPEC for the management of primary and secondary peritoneal cancers. [ABSTRACT FROM AUTHOR]

Surgical treatment of patients with peritoneal metastases in combination with Hyperthermic intraperitoneal Chemotherapy (HIPEC) and systemic treatments is applied with increasing frequency and, with correct patient qualification, allows for obtaining 5-year survival at a level of 32-52%. The conditions necessary for positive results of such treatment include the high experience of a given centre, its appropriate infrastructure, and appropriate patient qualification for the procedure. As a result of the debate connected with the need to evaluate treatment quality and results, at the request of the Peritoneal Cancer Section of the Polish Society of Oncological Surgery, the conditions for quality assurance were worked out and a Quality Assurance Commission was set up for the centres performing cytoreductive procedures and HIPEC procedures in the treatment of primary and secondary peritoneal tumours. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate single-port laparoscopic appendectomy (SPLA) in comparison with three-port laparoscopic appendectomy (3PLA) in children about the extent of surgical trauma after SPLA and 3PLA measured by serum interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations. Materials and Methods: A total of 50 patients with a median age of 11.5 were randomized to two groups. Experts in both methods performed the surgeries. The decision on the type of planned surgery was randomly determined. Serum IL-6 and CRP levels were measured using an enzyme-linked immunosorbent assay before, and at 12 and 36 hours after surgery. Furthermore, we compared operating time, hospital stay, postoperative pain, and complication rates. Results: The operative time in the 3PLA group was shorter than that in the SPLA group (P < .05). Preoperative IL-6 levels were not different between the two groups, but the rise (pre- versus postoperative) of IL-6 in the SPLA group was remarkably higher when compared with the 3PLA group (P < .05). Similar results were obtained for CRP; basal serum CRP levels were not different between the two groups, but the rise of CRP in the 3PLA group was significantly lower compared with that in the SPLA group. During the first 12 hours postoperative, the SPLA patients reported more severe postoperative pain and longer inpatient opiate usage was noted that after 3-PLA. Only one SPLA case was converted to 3PLA. There were no conversions to open surgery. The length of hospital stay and complication rate were not different between the two groups. Conclusions: SPLA in children is associated with longer operative times, increased pain level, and more severe surgical trauma as measured by postoperative CRP and IL-6 levels in comparison with a 3PLA. The two approaches were comparable regarding the length of hospital stay and complication rate. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the impact of a microscopically positive resection margin (microPRM) on the outcome of hepatoblastoma patients pretreated with chemotherapy. Methods Local recurrence and survival rates of 431 children treated in the SIOPEL 2 and 3 trials were analysed comparing 58 patients with microPRM with 371 who had a complete resection (CR) and who were then stratified by risk category. The tumour was standard-risk in 312 patients and high-risk (PRETEXT IV and/or extrahepatic disease and/or α-fetoprotein [AFP]<100 ng/ml) in 117 patients. All received cisplatinum-based neoadjuvant and postoperative chemotherapy as per protocol. Apart from one microPRM patient who went on to transplant, none received any additional local treatment. Results With a median follow-up of 67 months, local relapse occurred in 3/58 patients with microPRM (5%) and in 23/371 (6%) patients with CR. The 5-year overall survival (OS) was 91% (95% confidence interval [CI] 80%–96%) for the microPRM and 92% (95% CI 89%–95%) for the CR group. The 5-year event-free survival (EFS) was 86% (95% CI 74%–93%) for the microPRM and 86% (95% CI 82%–89%) for the CR group. Neither OS nor EFS was statistically significantly different between the two groups, neither overall nor when risk group stratified. Conclusions In the context of cisplatin-based chemotherapy, the presence of microPRM did not influence the outcome even without additional local treatment. Although CR remains the aim, microPRM does not necessitate mandatory second look surgery. A 'wait and see policy' is warranted if postoperative chemotherapy is administered and AFP levels and imaging become normal. Highlights • A R1 Hepatoblastoma resection does not necessitate mandatory second look surgery, provided postoperative chemotherapy is administered and alpha-fetoprotein levels and imaging become normal. • Nevertheless, complete resection remains the aim of surgery. [ABSTRACT FROM AUTHOR]

Imaging is crucial in the assessment of children with a primary hepatic malignancy. Since its inception in 1992, the PRETEXT (PRE-Treatment EXTent of tumor) system has become the primary method of risk stratification for hepatoblastoma and pediatric hepatocellular carcinoma in numerous cooperative group trials across the world. The PRETEXT system is made of two components: the PRETEXT group and the annotation factors. The PRETEXT group describes the extent of tumor within the liver while the annotation factors help to describe associated features such as vascular involvement (either portal vein or hepatic vein/inferior vena cava), extrahepatic disease, multifocality, tumor rupture and metastatic disease (to both the lungs and lymph nodes). This manuscript is written by members of the Children's Oncology Group (COG) in North America, the International Childhood Liver Tumors Strategy Group (SIOPEL) in Europe, and the Japanese Study Group for Pediatric Liver Tumor (JPLT; now part of the Japan Children's Cancer Group) and represents an international consensus update to the 2005 PRETEXT definitions. These definitions will be used in the forthcoming Trial to Pediatric Hepatic International Tumor Trial (PHITT). [ABSTRACT FROM AUTHOR]

European ReferenceNetworks (ERNs) are virtual networks that involve healthcare providers across Europe. The aim of ERNs is to tackle complex or rare diseases and conditions that necessitate highly specialized treatment, knowledge and resources. This article summarizes the concept of European Reference Networks in the EuropeanUnion, legislation and policy behind ERNs from the standpoint of pediatric surgical specialty. There are seven ERNs in which pediatric surgeons are involved, four of which are being discussed, namely ERN PaedCan, eUROGEN ERN, ERN RARE-LIVER and ERNICA. ERNs program is a step towards improving health care quality, reducing access inequalities, and increasing overall medical experience and knowledge but its final impact is yet to be determined. [ABSTRACT FROM AUTHOR]

We present a case of a girl with an extremely rare, posterior type of persistent cloaca, which was associated with other abnormalities, including an undeveloped vulva and vagina, agenesis of the right kidney, secondary obstructive megaureter, unicornate uterus, persisted tailgut, sacral bone hypoplasia, and pubic symphysis hypertrophy. An operative approach was as follows: (i) colostomy and ureterocutaneostomy; (ii) creation of an ileal conduit with antirefluxing uretero-ileal anastomosis, and then creation of a continent catheterizable ileal reservoir; (iii) anastomosis of sigmoid colon to rectal stump; and (iv) vaginal and external genital reconstruction. Because of abnormal anatomical conditions where the uterus was situated adjacent to the open, incompetent bladder neck, we decided to create a vagina using the bladder wall instead of the bowel segment. [ABSTRACT FROM AUTHOR]

Objectives To present versatile surgical reconstructive techniques and their outcomes in pediatric patients with genitourinary rhabdomyosarcoma. Methods We retrospectively analyzed the oncological and urological outcomes of seven patients treated between 1992 and 2014 according to the Cooperative Weichteilsarkom Studiengruppe protocols. Intergroup Rhabdomyosarcoma Study staging: local, six patients; and IV, one patient. Histology: embryonal, five patients; unclassified, one patient; triton tumor one patient. Surgical treatment included: cystectomy, uterectomy and partial vaginectomy, one patient; radical cystectomy, two patients; cystectomy, one patient; cystectomy with partial prostatectomy, one patient; partial cystectomy, one patient; and partial prostatectomy, one patient. Results All patients were alive in complete remission at last follow up. In four cases, ileal conduit with ureteral reimplantation with serous-lined extramural tunnel (Abol-Enein technique) was carried out, which was followed by conversion into ileal continent bladder with continent appendiceal stoma for clean intermittent catheterization in three patients. In one boy, partial cystectomy and continent reconstruction was carried out during a single surgical procedure. One child with incontinent urinary diversion is still awaiting a continence solution. One child after partial prostatectomy is continent without any voiding disturbances. Conclusions The timing and extent of radical surgery for treatment of genitourinary rhabdomyosarcoma depend on the local anatomical conditions, and the response to previous chemo- and radiotherapy. Cystectomy followed by various reconstructive techniques still remains an important option in the local treatment. [ABSTRACT FROM AUTHOR]

The treatment outcomes in children with bladder/prostate rhabdomyosarcoma (B/P RMS) have considerably improved in the past few decades. Current protocols incorporate chemotherapy, radiotherapy, and surgery (radical or organ sparing). Using this multimodal and multidisciplinary approach, the cure rates for nonmetastatic RMS have gradually increased from 25% in the 1970s, and 70% in the 1990s, to over 80% in the 2000s. Surgery plays a role not only in the diagnosis andmanagement of all stages of B/P RMS, but also in the urinary reconstruction and long-term follow-up. Furthermore, the tendency to avoid mutilating surgery and to preserve functional genitourinary tract has been noticeable. Authors describe the current status and future surgical treatment approaches and possibilities for patients with B/P RMS and how reconstructive urologic surgery in B/P RMS continues to evolve. [ABSTRACT FROM AUTHOR]

Purpose: Surgeons are at risk for developing work-related musculoskeletal symptoms (WMS). The present study aims to compare laparoscopy and SILS ergonomy among pediatric surgeons. Methods: A questionnaire formed by 17 questions was mailed to 14 pediatric surgeons, seven with a large experience in laparoscopy and seven in SILS. All surgeons completed the survey. The questionnaires were focused on the type of laparoscopic or SILS activity, location and type of pain, need for drugs and its physical consequences. Results were analyzed using χ test. Results: Results indicated a similar incidence of WMS with shoulder symptoms (>75 %) in both groups. In laparoscopic group this pain is evident only after a long lasting procedure, while in SILS group the pain is present after each procedure performed. SILS surgeons used painkillers and other therapies statistically more frequently than laparoscopic group ( χ = 0.001). Conclusions: This study confirms there is a strong association between WMS and MIS surgery. The incidence of pain is similar in both groups. Pain was present only after long lasting procedures in laparoscopic group, while SILS surgeons have pain after each procedure performed. In addition SILS surgeons use more frequently painkillers and other therapies compared to laparoscopic surgeons. In conclusion, it seems that SILS has a worse ergonomy compared to laparoscopy. [ABSTRACT FROM AUTHOR]

Summary: Background: The objective of this study was to establish the efficacy and safety of a new treatment regimen consisting of dose-dense cisplatin-based chemotherapy and radical surgery in children with high-risk hepatoblastoma. Methods: SIOPEL-4 was a prospective single-arm feasibility study. Patients aged 18 years or younger with newly diagnosed hepatoblastoma with either metastatic disease, tumour in all liver segments, abdominal extrahepatic disease, major vascular invasion, low α fetoprotein, or tumour rupture were eligible. Treatment consisted of preoperative chemotherapy (cycles A1–A3: cisplatin 80 mg/m2 per day intravenous in 24 h on day 1; cisplatin 70 mg/m2 per day intravenous in 24 h on days 8, 15, 29, 36, 43, 57, and 64; and doxorubicin 30 mg/m2 per day intravenous in 24 h on days 8, 9, 36, 37, 57, and 58) followed by surgical removal of all remaining tumour lesions if feasible (including liver transplantation and metastasectomy, if needed). Patients whose tumour remained unresectable received additional preoperative chemotherapy (cycle B: doxorubicin 25 mg/m2 per day in 24 h on days 1–3 and 22–24, and carboplatin area under the curve [AUC] 10·6 mg/mL per min per day intravenous in 1 h on days 1 and 22) before surgery was attempted. After surgery, postoperative chemotherapy was given (cycle C: doxorubicin 20 mg/m2 per day in 24 h on days 1, 2, 22, 23, 43, and 44, and carboplatin AUC 6·6 mg/mL per min per day in 1 h on days 1, 22, and 43) to patients who did not receive cycle B. The primary endpoint was the proportion of patients with complete remission at the end of treatment. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00077389. Findings: We report the final analysis of the trial. 62 eligible patients (39 with lung metastases) were included and analysed. 60 (98%, 95% CI 91–100) of 61 evaluable patients (one child underwent primary hepatectomy) had a partial response to preoperative chemotherapy. Complete resection of all tumour lesions was achieved in 46 patients (74%). At the end of therapy, 49 (79%, 95% CI 67–88) of 62 patients were in complete remission. With a median follow-up of 52 months, 3-year event-free survival was 76% (95% CI 65–87) and 3-year overall survival was 83% (73–93). 60 (97%) patients had grade 3–4 haematological toxicity (anaemia, neutropenia, or thrombocytopenia) and 44 (71%) had at least one episode of febrile neutropenia. Other main grade 3 or 4 toxicities were documented infections (17 patients, 27%), anorexia (22, 35%), and mucositis (seven, 11%). One child died of fungal infection in neutropenia. Moderate-to-severe ototoxicity was documented in 31 (50%) patients. 18 serious adverse events (including two deaths) reflecting the observed side-effects were reported in the trial (the most common was ototoxicity in five patients). Interpretation: The SIOPEL-4 treatment regimen is feasible and efficacious for complete remission at the end of treatment for patients with high-risk hepatoblastoma. Funding: Cancer Research UK and Cancer Research Switzerland/Oncosuisse. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To identify factors relevant to long-term outcome in newly diagnosed hepatoblastoma, and define subgroups for clinical research on tailoring treatment to the individual patient. Patients and methods: Between 1995 and 2006 the SIOPEL group conducted two clinical trials which established risk-adapted therapy for hepatoblastoma patients. Patients were stratified into high-risk (AFP<100ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease (V+/P+/E+) and/or metastases) and standard-risk (all others). The hierarchy of these factors plus multifocality, PRETEXT III, AFP>1,200,000ng/mL, patient age, platelet count and histology were further explored. The outcome measure was event-free survival (EFS). Results: In 541 patients, reduced EFS correlated significantly with AFP<100ng/ml (hazard ratio [HR] 4.09, 95% confidence interval 2.16–7.75), AFP⩾1.2×106 ng/mL (2.48, 1.47–4.17), metastatic disease (3.02, 2.05–4.44), PRETEXT IV (2.15, 1.19–3.87), multifocality (1.59, 1.01–2.50), age>5years (2.76, 1.68–4.53); borderline with small cell undifferentiated (SCU) histology (2.29, 95% confidence interval 0.91–5.77); but not with PRETEXT III, age 30–60months, platelet count or V+/P+/E+. By using the significant factors and SCU to stratify the population, we have identified three distinct prognostic groups: PRETEXT I/II/III, and no other factors, have 3year EFS of 90%, PRETEXT IV and/or multifocal tumour and/or age>5years and/or AFP>1.2×106 have 3year EFS of 71% and SCU and/or AFP<100ng/mL and/or metastatic have a 3year EFS of 49%. Conclusion: Prognostic stratification for clinical research on newly diagnosed hepatoblastoma should take into consideration PRETEXT, metastatic disease, AFP, multifocality, age and SCU histology. [Copyright &y& Elsevier]

Background: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). Methods: Children with standard-risk hepatoblastoma who were younger than 16 years of age were eligible for inclusion in the study. After they received one cycle of cisplatin (80 mg per square meter of body-surface area per 24 hours), we randomly assigned patients to receive cisplatin (every 14 days) or cisplatin plus doxorubicin administered in three preoperative cycles and two postoperative cycles. The primary outcome was the rate of complete resection, and the trial was powered to test the noninferiority of cisplatin alone (<10% difference in the rate of complete resection). Results: Between June 1998 and December 2006, 126 patients were randomly assigned to receive cisplatin and 129 were randomly assigned to receive cisplatin plus doxorubicin. The rate of complete resection was 95% in the cisplatin-alone group and 93% in the cisplatin–doxorubicin group in the intention-to-treat analysis (difference, 1.4%; 95% confidence interval [CI], –4.1 to 7.0); these rates were 99% and 95%, respectively, in the per-protocol analysis. Three-year event-free survival and overall survival were, respectively, 83% (95% CI, 77 to 90) and 95% (95% CI, 91 to 99) in the cisplatin group, and 85% (95% CI, 79 to 92) and 93% (95% CI, 88 to 98) in the cisplatin–doxorubicin group (median follow-up, 46 months). Acute grade 3 or 4 adverse events were more frequent with combination therapy (74.4% vs. 20.6%). Conclusions: As compared with cisplatin plus doxorubicin, cisplatin monotherapy achieved similar rates of complete resection and survival among children with standard-risk hepatoblastoma. Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma. (ClinicalTrials.gov number, NCT00003912.) N Engl J Med 2009;361:1662-70. [ABSTRACT FROM AUTHOR]

Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system. [ABSTRACT FROM AUTHOR]

The authors discuss an early hybrid cardiovascular intervention in a neonate with left-sided congenital diaphragmatic hernia and significant left heart hypoplasia. The operation included persistent ductus arteriosus stenting and right pulmonary artery calibrated banding (3.5 mm) to increase blood flow in the aorta and to decrease right ventricle overload and decrease blood pressure and overflow in pulmonary circulation. The operation improved the child's general condition and gained time for left ventricle growth and restoration of its function. [ABSTRACT FROM PUBLISHER]

Background: In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Children's Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and 2010., Methods: Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models., Findings: Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) ( P  < 0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% ( P  = 0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999 ng/mL) or older age at diagnosis (≥3 years old) were significantly worse than others., Interpretation: The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000 ng/mL) or older age (≥3 years old) showed better outcomes in the UF group and might be considered for initial resection., Funding: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Children's Oncology Group Cure Search grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research and Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

Background and Aims: Hepatoblastoma (HB) is the predominant form of pediatric liver cancer, though it remains exceptionally rare. While treatment outcomes for children with HB have improved, patients with advanced tumors face limited therapeutic choices. Additionally, survivors often suffer from long-term adverse effects due to treatment, including ototoxicity, cardiotoxicity, delayed growth, and secondary tumors. Consequently, there is a pressing need to identify new and effective therapeutic strategies for patients with HB. Computational methods to predict drug sensitivity from a tumor's transcriptome have been successfully applied for some common adult malignancies, but specific efforts in pediatric cancers are lacking because of the paucity of data., Approach and Results: In this study, we used DrugSense to assess drug efficacy in patients with HB, particularly those with the aggressive C2 subtype associated with poor clinical outcomes. Our method relied on publicly available collections of pan-cancer transcriptional profiles and drug responses across 36 tumor types and 495 compounds. The drugs predicted to be most effective were experimentally validated using patient-derived xenograft models of HB grown in vitro and in vivo. We thus identified 2 cyclin-dependent kinase 9 inhibitors, alvocidib and dinaciclib as potent HB growth inhibitors for the high-risk C2 molecular subtype. We also found that in a cohort of 46 patients with HB, high cyclin-dependent kinase 9 tumor expression was significantly associated with poor prognosis., Conclusions: Our work proves the usefulness of computational methods trained on pan-cancer data sets to reposition drugs in rare pediatric cancers such as HB, and to help clinicians in choosing the best treatment options for their patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects, including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Thirty-eight patients were identified. The median age at diagnosis of HB was 16 months (range: 3 to 168 mo). All patients had received a platinum agent, and almost all had anthracycline exposure. The SMNs reported were hematopoietic malignancies (n=19), solid tumors (n=12), and post-transplant lymphoproliferative disorder (n=7). Of the 36 patients with outcome data, 19 survived. SMNs following HB treatment were primarily seen in patients with chemotherapy exposure, a history of liver transplantation, hereditary tumor predisposition syndromes, and/or a history of radiation treatment. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data through a companion late effects study or international registry could be used to further evaluate the rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To present a single-centre experience in bi- and uni-segmentectomies for primary liver tumours in children., Methods: This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours (hepatoblastoma-13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour., Results: The median tumour diameter was 52 mm (range 15-170 mm). Bisegmentectomy 2-3 was most frequently performed (seven patients), followed by bisegmentectomy 5-6 (four patients). The median operative time was 225 min (range 95-643 min). Intraoperative complications occurred in two patients-small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1-15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12-144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease., Conclusions: From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset.

Background: Liver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials. The current study is the validation of this initial classification and first large-scale application by international expert reviewers., Procedure: The CHIC initiative includes data from 1605 children treated on eight multicenter hepatoblastoma (HB) trials. Review of 605 available tumors was performed by seven expert pathologists from three consortia (US, EU, Japan). Cases with discordant diagnoses were collectively reviewed to reach a final consensus diagnosis., Results: Of 599 cases with sufficient material for review, 570 (95.2%) were classified as HB by all consortia, and 29 (4.8%) as non-HB, which included "hepatocellular neoplasm, NOS" and malignant rhabdoid tumors. 453 of 570 HBs were classified as epithelial by final consensus. Some patterns (i.e., small cell undifferentiated, macrotrabecular, cholangioblastic) were selectively identified by reviewers from different consortia. All consortia identified a similar number of mixed epithelial-mesenchymal HB., Conclusions: This study represents the first large-scale application and validation of the pediatric malignant hepatocellular tumors consensus classification. It is a valuable resource to train future generations of investigators on accurate diagnosis of these rare tumors and provides a framework for further international collaborative studies and refinement of the current classification of pediatric liver tumors., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction: The place of laparoscopy in the resection of Wilms' tumors has remained debatable, but evidence that neoadjuvant chemotherapy causes tumor shrinkage has made laparoscopic nephrectomy (LN) a feasible option. Laparoscopic nephron-sparing surgery (NSS) is technically very demanding and seems to be feasible and effective only when performed by a very experienced surgeon., Aim: We report 7 cases of laparoscopic nephrectomy and 1 case of laparoscopic heminephrectomy for Wilms' tumor., Material and Methods: Forty-two consecutive children with primary renal tumor underwent nephrectomy between 2013 and 2020; 11 had an LN. Among them there were 8 children with Wilms' tumor, with age between 13 months and 7 years. All patients received neoadjuvant chemotherapy according to the current SIOP protocol. The mean tumor volume before and after chemotherapy was 174.4 ml (range: 14.7-501) and 32.8 ml (range: 4.3-68) respectively., Results: Seven laparoscopic nephrectomies and one heminephrectomy were performed. No patient had an intraoperative tumor rupture. All children had an attempt of lymph node sampling (their number per pathology assessment was in the range 0-5). There were no intraoperative events. One complication after heminephrectomy occurred, which was urine leak. Five patients had stage I tumor and 3 had stage II. Seven patients had an intermediate-risk and one had a high-risk tumor. There were no local or distant relapses. All patients remained disease-free at a median follow-up of 71 months (range: 16-94)., Conclusions: This report demonstrates the feasibility of LN in children with Wilms' tumors. The patients should be carefully selected and specific training in laparoscopy is necessary, particularly with regard to laparoscopic heminephrectomy., Competing Interests: The authors declare no conflict of interest, (Copyright © 2023 Sekcja Wideochirurgii TChP.)

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression., (©2023 American Association for Cancer Research.)

Hepatoblastoma is the most common primary malignant paediatric liver tumour and surgery remains the cornerstone of its management. The aim of this article is to present the principles of surgical treatment of hepatoblastoma. All aspects of surgery in hepatoblastoma are discussed, from biopsy, through conventional and laparoscopic liver resections, to extreme resection with adjacent structures, staged hepatectomy and transplantation., (© 2023. The Author(s).)

According to a recent national audit, the cost of treating patients in geriatric wards is 20-30% less compared to those treated in internal medicine wards. Yet, geriatric care remains largely underdeveloped in Poland, with few human, material, and financial resources. Despite numerous attempts to raise the profile of geriatrics over the years, little progress has been achieved. In 2019, experts under the President of Poland proposed the creation of a network of Health Centres 75+ as the first pillar of geriatric care. These are meant to provide ambulatory services for older people and coordinate provision of other health and social care services at the county level. The goal is to create a community model of care, whereby older people would receive needed services close to their place of residence, allowing them to live independently for as long as possible. Although the proposal has been welcomed by the geriatric community and the patients, the acute shortages of human, physical, and financial resources raise concerns about its feasibility. However, the new strategic plans for the health system propose solutions that appear to be supportive of the new proposal, and the Office of the President is discussing joining forces with the Ministry of Health to improve its chances of implementation. Given the increasing pace of population ageing and underdeveloped provision of geriatric services, these efforts are very much needed.

Background/purpose: Neuroblastic tumors are the most common pediatric extracranial solid tumors in infants and very young children. Although, especially in newborns, there is an increasing number of situations in which observation alone is used, surgery remains an important step in the treatment of neuroblastoma but can be complicated by arterial vasospasm in the surgical field. The aim of this two-center retrospective study was to analyze the occurrence of arterial constriction as a complication of neuroblastic tumors resection., Methods: Medical records of patients who were treated surgically for neuroblastic tumors in the years 2012-2019 were reviewed., Results: For 8 years, 113 children were treated for neuroblastic tumors. The treatment included both primary and delayed surgery after initial chemotherapy carried out according to SIOPEN protocols. In 11 out of 113 cases (9.7%) local arterial constriction was observed. In 6 out of 11 cases an attempt was made to save the organ, however, two patients suffered from kidney atrophy, two other partial kidney infarctions, one child suffered from partial limb paresis, and another from brain ischemia and death., Conclusions: Local arterial constriction constitutes a relatively common (10% of cases) and severe complication of neuroblastic tumors resection. Efficacy of local application of papaverine based on our experience remains unproven hence further research is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gastrointestinal stromal tumors and neuroendocrine tumors in adult and pediatric populations differ immensely. Despite these established differences, the extreme rarity of gastrointestinal stromal tumors and neuroendocrine tumors in the pediatric population has resulted in the lack of consensus management guidelines, making optimal surgical approaches unclear. Comprehensive management principles to guide surgical approaches in adult literature are extensive. However, these are still lacking for pediatric patients. International cooperation to develop standardized pediatric-specific guidelines is urgently warranted in the future. This article highlights the vast differences between adult and pediatric parameters and provides recommendations on optimal and novel surgical approaches in children., Competing Interests: Disclosure The authors declare no commercial or financial conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The most recent advance in the care of children diagnosed with hepatoblastoma and hepatocellular carcinoma is the Pediatric Hepatic International Tumor Trial, which opened to international enrollment in 2018. It is being conducted as a collaborative effort by the pediatric multicenter trial groups in North America, Europe, and the Far East. This international effort was catalyzed by a new unified global risk stratification system for hepatoblastoma, an international histopathologic consensus classification for pediatric liver tumors, and a revised 2017 collaborative update of the PRE-Treatment EXTent of disease radiographic based staging system., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Laparoscopy for the resection of liver tumors in children has remained undeveloped in comparison to adults. Most of the indications for pediatric laparoscopic hepatic surgery have been limited to diagnostic laparoscopy (biopsy). Over the past ten years, however, laparoscopic liver resections for pediatric hepatic diseases have been performed successfully, and many case reports have been published., Methods: The authors report 6 cases of laparoscopic hepatic resection of benign tumors in children. The most important aspects of surgical technique are presented. There were 3 boys and 3 girls, with age between 4 months and 16 years. The lesions were located in the following segments: II and III (4 patients), I (1), V (1). The maximum tumor size was 7 cm., Results: One anatomical (left bisegmentectomy) and 5 nonanatomical resections were performed. Conversion to laparotomy was necessary in 1 patient owing to bleeding from the posterior branch of the right hepatic artery. There were no postoperative complications and patients were discharged on postoperative day 4, 5, 5, 5, 7 and 3 accordingly. The postoperative pathology of the specimens confirmed their benign nature: infantile hemangioendothelioma (1), nested stromal epithelial tumor (1), focal nodular hyperplasia (3), mixed benign tumor (hamartoma + vascular malformation) (1)., Conclusions: This report demonstrates the feasibility of a laparoscopic hepatic resection in children. On the other hand, laparoscopic liver resection is challenging and teamwork and specific training are necessary., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Undifferentiated embryonal sarcomas of the liver (UESL) are extremely rare and continue to pose a diagnostic and therapeutic challenge. The aim of the study was to present a multicenter experience of the German CWS and Polish PPSTG groups in the treatment of UESL in children., Procedure: Twenty-five patients were treated according to the CWS-96, CWS-2002, and CYVADIC protocols. Distant metastases were observed in four cases (16%). In four cases, an initial disease presentation mimicked other entities. A pure cystic appearance of liver mass led to misdiagnosis of hydatid cyst in three cases. In one case, laparotomy was performed due to the signs of appendicitis, and bleeding from ruptured liver tumor was found. All these patients were finally diagnosed as UESL., Results: Thirteen patients received preoperative chemotherapy. Partial response was observed in 10 cases. Tumor resection was performed in 20 patients (primary resections, 12; delayed resections-, 8). In five patients, the primary tumor never became operable. The macroscopically complete resection rate was 95% (19/20). Postoperative chemotherapy was given to 20 children. Local radiotherapy was used in three children. After a median follow-up time of 136 months, 17 patients (68%) were alive with no evidence of disease. All children with unresectable tumor and three out of four patients with distant metastases died. The five-year overall survival (OS) rate was 72%., Conclusions: In summary, a complete tumor excision plays the central role in the treatment of UESL. A cystic presentation of the liver lesion on imaging does not exclude the diagnosis of malignant tumor., (© 2020 Wiley Periodicals LLC.)

Purpose: Treatment outcomes for hepatoblastoma have improved markedly in the contemporary treatment era, principally due to therapy intensification, with overall survival increasing from 35% in the 1970s to 90% at present. Unfortunately, these advancements are accompanied by an increased incidence of toxicities. A detailed analysis of age as a prognostic factor may support individualized risk-based therapy stratification., Methods: We evaluated 1605 patients with hepatoblastoma included in the CHIC database to assess the relationship between event-free survival (EFS) and age at diagnosis. Further analysis included the age distribution of additional risk factors and the interaction of age with other known prognostic factors., Results: Risk for an event increases progressively with increasing age at diagnosis. This pattern could not be attributed to the differential distribution of other known risk factors across age. Newborns and infants are not at increased risk of treatment failure. The interaction between age and other adverse risk factors demonstrates an attenuation of prognostic relevance with increasing age in the following categories: metastatic disease, AFP < 100 ng/mL, and tumor rupture., Conclusion: Risk for an event increased with advancing age at diagnosis. Increased age attenuates the prognostic influence of metastatic disease, low AFP, and tumor rupture. Age could be used to modify recommended chemotherapy intensity., (© 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.)

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB., Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies., Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth., Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB., Lay Summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer., Competing Interests: Conflict of interest Prof. Josep M. Llovet is receiving research support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb and Ipsen, and consulting fees from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Eisai Inc, Celsion Corporation, Eli Lilly, Exelixis, Merck, Ipsen, Glycotest, Navigant, Leerink Swann LLC, Midatech Ltd, Fortress Biotech, Sprink Pharmaceuticals and Nucleix and CANFITE. CA has a research contract with CHIOME Biosciences Inc. The other authors report no conflicts of interest in this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Surgical interventions in patients with peritoneal metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic treatment are becoming more common and, when applied to selected patient groups, they reach 5-year survival rates of 32-52%. Good clinical outcomes require experienced and well-equipped healthcare centers, experienced surgical team and adequate patient qualification process. As a result of the discussion on the need for evaluation of quality of care and treatment outcomes and at the request of the Peritoneal Cancer Section of the Polish Society of Surgical Oncology, accreditation standards have been developed and the Accreditation Committee has been established for healthcare centers providing cytoreductive surgery and HIPEC for the management of primary and secondary peritoneal cancers.

The wide scope of neuropathology is also connected to different systemic pathology findings. Neuroectodermal-type female genital tract lesions are not frequent. This article presents a short review of such entities in gynecological pathology and reports on two rare cases. The first described lesion is an endometrial glial polyp in a young woman. The second is a mature cystic teratoma accompanied by a peritoneal gliomatosis in an adolescent girl. Both presented entities posed diagnostic difficulties from the clinical and pathological perspective. They demanded careful sampling, immunophenotyping, as well as neuropathological consultation.