Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey.

Introduction: Alongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors' quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors. Methods: A single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head & Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN-C), and a question extracted from the Cancer Survivors' Unmet Needs Measure (CaSUN). Results: Two hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 - 1.914, p < 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 - 1.604, p < 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p < 0.001). Conclusion: Virtually all NPC survivors suffer from late toxicities, which interplay with survivors' perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted.

Enhancing neonatal thoracoscopic surgical training with rabbit model.

Background: Thoracoscopy, which has an increasing role in the treatment of indexed neonatal surgical conditions, requires adequate training. To support this, the current study aimed to evaluate the feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons. Methods: Following didactic lectures and demonstrations, the participants were given hands-on opportunities to perform thoracoscopic procedures. The feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons were evaluated with pre-/post-course procedural confidence scores and a questionnaire. Results: This study included 13 paediatric surgeons-2 (15 %) males and 11 (85 %) females-who were evenly distributed. There were four basic surgical trainees, five higher surgical trainees and four fellows in paediatric surgery (mean surgical practice experience: 4.5 ± 3.7 years). Most had experience assisting paediatric (70 %) and neonatal (62 %) thoracoscopic surgery. Only 30 % had experience as the chief surgeon of paediatric thoracoscopic surgery, with none on neonates. Significant improvement was seen in procedural confidence as the assistant and chief surgeon of all procedures post-workshop. The surgeons rated the model positively. Conclusion: The procedural confidence level of paediatric surgeons improved significantly after workshop participation. This realistic and easily reproducible model can help perfect thoracoscopic skills. Therefore, its integration into paediatric surgical training would promote surgical skill proficiency and could improve surgeons' confidence in neonate operations.

Major surgical conditions of childhood and their lifelong implications: comprehensive review.

BACKGROUND: In recent decades, the survival of children with congenital anomalies and paediatric cancer has improved dramatically such that there has been a steady shift towards understanding their lifelong health outcomes. Paediatric surgeons will actively manage such conditions in childhood and adolescence, however, adult surgeons must later care for these 'grown-ups' in adulthood. This article aims to highlight some of those rare disorders encountered by paediatric surgeons requiring long-term follow-up, their management in childhood and their survivorship impact, in order that the adult specialist may be better equipped with skills and knowledge to manage these patients into adulthood. METHODS: A comprehensive literature review was performed to identify relevant publications. Research studies, review articles and guidelines were sought, focusing on the paediatric management and long-term outcomes of surgical conditions of childhood. The article has been written for adult surgeon readership. RESULTS: This article describes the aforementioned conditions, their management in childhood and their lifelong implications, including: oesophageal atresia, tracheo-oesophageal fistula, malrotation, short bowel syndrome, duodenal atresia, gastroschisis, exomphalos, choledochal malformations, biliary atresia, Hirschsprung disease, anorectal malformations, congenital diaphragmatic hernia, congenital lung lesions and paediatric cancer. CONCLUSION: The increasing survivorship of children affected by surgical conditions will translate into a growing population of adults with lifelong conditions and specialist healthcare needs. The importance of transition from childhood to adulthood is becoming realized. It is hoped that this timely review will enthuse the readership to offer care for such vulnerable patients, and to collaborate with paediatric surgeons in providing successful and seamless transitional care.

Patient Preference of Apalutamide Versus Enzalutamide for Recurrent or Metastatic Hormone-sensitive Prostate Cancer: An Open-label, Randomized, Crossover Trial.

BACKGROUND AND OBJECTIVE: Treatment preference regarding apalutamide versus enzalutamide in prostate cancer (PCa) and the factors influencing decisions are largely unknown. Our aim was to investigate the preference for apalutamide versus enzalutamide among prostate cancer patients and their physicians and caregivers, and factors influencing their decision. METHODS: This was a prospective, open-label, randomized, crossover trial. Patients with recurrence of localized PCa or with metastatic disease not considered as high-risk or high-volume and on continued androgen deprivation therapy were recruited. All subjects received a trial of two agents, apalutamide (A) and enzalutamide (E), for 12 wk each, with a 5-wk washout period in between. The sequencing of the drugs was randomized. The primary outcome was patient preference for one the drugs, assessed at the end of the study. Other outcomes included factors influencing patient preference, a comparison of side-effect profiles, and patients' quality of life (QoL). Physician and caregiver preferences for the drugs and factors affecting their choice were also assessed. KEY FINDINGS AND LIMITATIONS: A total of 74 patients met the eligibility criteria and were randomized to the A â†’ E or E â†’ A arm. Of these, 66 patients (89.1%; 32 A â†’ E, 34 E â†’ A) completed the study. Baseline characteristics were comparable between the two groups, and ∼90% of the patients had low-volume metastatic disease. After completion of both treatments for 12 wk each, the difference in preference for A over E was 17.8%, with similar trends for preference of A over E among physicians (18.2%) and caregivers (22.4%). Fewer side effect was the most critical factor influencing the preference of patients. Among the side effects, less fatigue was the benefit of A over E most frequently reported. No notable difference in QoL was observed between the two drugs. However, the study was terminated on interim analysis and the results might not be conclusive. CONCLUSIONS: There was a trend for preference of A over E among patients with predominantly low-volume recurrent or metastatic PCa and their physicians and caregivers. Fewer side effects was the most critical factor influencing their choice. PATIENT SUMMARY: Patients with low-volume recurrent or metastatic prostate cancer tended to prefer treatment with apalutamide over enzalutamide. Side effects were the most critical factor influencing treatment preference.

Prophylactic anti-reflux procedure for children undergoing laparoscopic gastrostomy: Rethinking of the routine practice.

AIM: Laparoscopic gastrostomy is a frequently performed procedure in children requiring long-term enteral nutrition. The role of prophylactic anti-reflux surgery during gastrostomy placements is controversial. The current study aims to evaluate the role of prophylactic anti-reflux procedures during gastrostomy placement. METHODS: A retrospective single-center analysis of all children without reflux receiving laparoscopic gastrostomy from January 2005 through December 2021 was performed. Demographics and clinical outcomes were compared between patients receiving gastrostomy placement alone and patients receiving gastrostomy with prophylactic anti-reflux surgery. RESULTS: A total of 79 patients had a confirmed absence of reflux by a 24-h pH/impedance study before operation. Thirty-six of these patients underwent prophylactic anti-reflux surgery (PAR) while 43 received gastrostomy (PG) alone. The operative time and conversion rate were significantly higher in the PAR group (140.5 ± 67.5 vs. 80.2 ± 66.8 min, p = 0.0001 and 8.3% vs. 0%, p = 0.04). There were no major complications in either group. De novo reflux was detected in five patients (11.6%) in the PG group. None of these patients progressed to require anti-reflux surgery. CONCLUSION: The occurrence of de novo reflux after laparoscopic gastrostomy was low and could be managed without anti-reflux surgery. A routine pre-operative pH study is helpful for appropriate patient selection to avoid unnecessary anti-reflux surgery, which lengthens operative time and increases the conversion rate.

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors.

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods: A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results: A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions: GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

Background: Androgen deprivation therapy (ADT) is the foundational treatment for metastatic prostate cancer (PCa). Androgen receptor (AR) axis-targeted therapies are a new standard of care for advanced PCa. Although these agents have significantly improved patient survival, the suppression of testosterone is associated with an increased risk of cardiometabolic syndrome. This highlights the urgency of multidisciplinary efforts to address the cardiometabolic risk of anticancer treatment in men with PCa. Methods: Two professional organizations invited five urologists, five clinical oncologists, and two cardiologists to form a consensus panel. They reviewed the relevant literature obtained by searching PubMed for the publication period from April 2013 to April 2023, to address three discussion areas: (i) baseline assessment and screening for risk factors in PCa patients before the initiation of ADT and AR axis-targeted therapies; (ii) follow-up and management of cardiometabolic complications; and (iii) selection of ADT agents among high-risk patients. The panel convened four meetings to discuss and draft consensus statements using a modified Delphi method. Each drafted statement was anonymously voted on by every panelist. Results: The panel reached a consensus on 18 statements based on recent evidence and expert insights. Conclusion: These consensus statements serve as a practical recommendation for clinicians in Hong Kong, and possibly the Asia-Pacific region, in the management of cardiometabolic toxicities of ADT or AR axis-targeted therapies in men with PCa.

Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy.

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

Internet Health Resources on Nocturnal Enuresis: A Readability, Quality, and Accuracy Analysis.

INTRODUCTION: Nocturnal enuresis is a common yet quality-of-life-limiting pediatric condition. There is an increasing trend for parents to obtain information on the disease's nature and treatment options via the internet. However, the quality of health-related information on the internet varies greatly and is largely uncontrolled and unregulated. With this study, a readability, quality, and accuracy evaluation of the health information regarding nocturnal enuresis is carried out. MATERIALS AND METHODS: A questionnaire was administered to parents and patients with nocturnal enuresis to determine their use of the internet to research their condition. The most common search terms were determined, and the first 30 websites returned by the most popular search engines were used to assess the quality of information about nocturnal enuresis. Each site was categorized by type and assessed for readability using the Gunning fog score, Simple Measure of Gobbledygook (SMOG) index, and Dale-Chall score; for quality using the DISCERN score; and for accuracy by comparison to the International Children's Continence Society guidelines by three experienced pediatric urologists and nephrologists. RESULTS: A total of 30 websites were assessed and classified into five categories: professional (n = 13), nonprofit (n = 8), commercial (n = 4), government (n = 3), and other (n = 2). The information was considered difficult for the public to comprehend, with mean Gunning fog, SMOG index, and Dale-Chall scores of 12.1 ± 4.3, 14.1 ± 4.3, and 8.1 ± 1.3, respectively. The mean summed DISCERN score was 41 ± 11.6 out of 75. Only seven (23%) websites were considered of good quality (DISCERN score > 50). The mean accuracy score of the websites was 3.2 ± 0.6 out of 5. Commercial websites were of the poorest quality and accuracy. Websites generally scored well in providing their aims and identifying treatment benefits and options, while they lacked references and information regarding treatment risks and mechanisms. CONCLUSION: Online information about nocturnal enuresis exists for parents; however, most websites are of suboptimal quality, readability, and accuracy. Pediatric surgeons should be aware of parents' health-information-seeking behavior and be proactive in guiding parents to identify high-quality resources.

Does Chewing Gum Lead to Earlier Postoperative Gastrointestinal Recovery in Children? A Systematic Review and Meta-analysis.

INTRODUCTION: Postoperative ileus is a common occurrence among children undergoing major operations, including gastrointestinal and spinal surgeries. Preliminary evidence in adults suggests that chewing gum plays a role in accelerating the return of postoperative gastrointestinal function. However, evidence is scarce in the paediatric population. The aim of this study was to investigate whether chewing gum has benefits for children. METHODS: We searched PubMed, Medline, Embase, and Cochrane Trials databases for randomised controlled trials that compare gum chewing with standard care after elective surgery in children from 1st Jan 2005 to 31st July 2021. We assessed the identified trials for quality and performed a systematic review and meta-analysis in accordance with PRISMA and registered in PROSPERO (CRD42022358801). The main outcome measures examined were time to flatus and stool postoperatively, time to tolerate oral intake, and length of hospital stay, which were analysed using fixed effects models. We also examined clinical complication rates and postoperative pain control. RESULTS: We included six eligible trials, with a total of 357 enrolled patients. The intervention was well tolerated without complications. There was no significant difference in time to flatus (-2.86 h; 95 % CI: -6.2 to 0.47 h, p = 0.09), time to stool (-6.39 h; 95 % CI: -13.9 to 1.2 h, p = 0.1), time to tolerate oral intake (-0.03 days; 95 % CI: -0.15 to 0.1 days, p = 0.68), and length of hospital stay (0.08 days; 95 % CI: -0.07 to 0.22 days, p = 0.29). Postoperative pain control (opioid consumption, pain score, nausea score) was similar in both groups (p > 0.05). CONCLUSION: Current evidence demonstrates that gum chewing is not associated with earlier postoperative gastrointestinal recovery in children. Future adequately powered and well-designed trials are necessary to evaluate any clinical benefit of chewing gum for children and whether it could result differences in healthcare satisfaction. LEVEL OF EVIDENCE: I.

Open Versus Thoracoscopic Repair of Congenital Diaphragmatic Hernia: A 19-Year Review in a Tertiary Referral Centre in Hong Kong.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a developmental defect that causes herniation of abdominal organs into the thoracic cavity with significant morbidity. Thoracoscopic repair of CDH is an increasingly prevalent yet controversial surgical technique, with limited long-term outcome data in the Asian region. The aim of this study was to compare open laparotomy versus thoracoscopic repair of CDH in paediatric patients in a major tertiary referral centre in Asia. METHODS: We performed a retrospective analysis of neonatal patients who had open laparotomy or thoracoscopic repair for CDH in our institution between July 2002 and November 2021. Demographic data, perioperative parameters, recurrence rates and surgical complications were analysed. RESULTS: 64 patients were identified, with 54 left sided CDH cases. 33 patients had a prenatal diagnosis and 35 patients received minimally invasive surgical repair. There was no significant difference between open and minimally invasive repair in recurrence rate (13 % vs 17 %, P = 0.713), time to recurrence (184 ± 449 days vs 81 ± 383 days, P = 0.502), or median length of ICU stay (11 ± 14 days vs 13 ± 15 days, P = 0.343), respectively. Gastrointestinal complications occurred in 7 % of neonates in the open group and none in the thoracoscopic group. Median follow-up time was 9.5 years. CONCLUSIONS: This study is a large congenital diaphragmatic hernia series in Asia, with long term follow-up demonstrating no significant difference in recurrence rate, time to recurrence or median length of ICU stay between open and minimally invasive repair, suggesting thoracoscopic approach is a non-inferior surgical option with avoidance of gastrointestinal complications compared to open repair. TYPE OF STUDY: Retrospective Cohort Study.

Quality of Life in Long-Term Survivors of Surgical Necrotizing Enterocolitis.

OBJECTIVE: This study evaluated the quality of life (QoL) in patients who have recovered from surgical necrotizing enterocolitis (NEC). METHODS: This is a cross-sectional study conducted in a tertiary centre and patients who have received surgery for NEC between 2000 and 2014 were invited to participate. The Pediatric Quality of Life Inventory Generic (PedsQL™) Core Scale Version 4.0 was used as the assessment tool. Values were reported as median (interquartile rage) and compared with age-matched controls. RESULTS: During the study period, 90 patients were eligible for the study and 29 patients have completed the survey. There was no gender difference and the median age was 10 years (9-13 years). Nine patients have suffered from short bowel syndrome (SBS) as a result of the surgery. For the QoL assessment, 17 participants have completed both parent proxy and child-rated survey; 11 completed the parent-rated survey and 1 completed child-rated survey only. The scores for parent-rated survey were - overall: 86.4 (70.7-92.7); physical: 95.3 (83.6-100) and psychosocial: 82.5 (66.3-90.4). The scores for child-rated survey were - overall: 82.1 (73.4-96.2); physical: 96.9 (90.6-99.2) and psychosocial: 81.7 (64.2-95.8). Regarding the impact of previous SBS on the QoL, there were no significant difference in the overall score for both parent proxy and child-rated survey (SBS-ve vs + ve) (parent-rated: 87.5 vs 85.3, p = 0.849; child-rated: 81.0 vs 88.0, p = 0.503). There were also no differences in physical and psychosocial assessments (parent-rated: [physical] 95.3 vs 95.3, p = 0.267; [psychosocial] 84.2 vs 80.0, p = 0.274; child-rated: [physical] 95.3 vs 96.9, p = 0.395; [psychosocial] 79.2 vs 87.5, p = 0.611). CONCLUSION: The QoL in long-term survivors of surgical NEC without major medical illnesses is comparable to normal population. However, they may have a lower psychosocial well-being that should be addressed. Previous history of SBS does not have a significant impact on the future QoL. LEVEL OF EVIDENCE: III.

Wide Resection for Pediatric Extremity Vascular Malformation-A Tertiary Hospital's Experience.

BACKGROUND: Vascular malformations of the extremities (VM) are common benign lesions that tend to grow throughout the patient's lifetime. They can cause various issues like pain, swelling, and even limb length discrepancies. Sclerotherapy was the preferred treatment choice in previous studies. However, sclerotherapy and many other treatments have the potential to result in higher recurrence rates. Surgical treatment has been shown to be effective and safe in many cases. Hence, this study aims to evaluate the suitability of wide resection surgery for VM to reduce recurrence. METHODS: Fort-seven VM cases that underwent wide resection were identified retrospectively in the institution of study. Demographics, depth of malformation, whether malformations were local or diffuse, location and size of malformations, and histology records were taken note of. Records of recurrence and postoperative function were also gathered. We utilized self-reported questionnaires, QuickDASH and Lower Extremity Functional Scale, to determine patients' postsurgical physical function. RESULTS: Out of 47 cases that underwent wide resection, we found a recurrence rate of 2.1%. No patients sustained any loss of function postsurgery, with few patients experiencing minor complications like tenderness, hypertrophic scars/keloids, as well as numbness. Good functionality posttreatment was also seen through self-reported questionnaires, with an average score of 2.12 for QuickDASH and 99.96% for LEFS. CONCLUSION: Where margins can be obtained without functional impairment, surgical-wide resection for VM is a viable treatment option to minimize recurrence. LEVEL OF EVIDENCE: Level-IV.

The Pediatric Proton and Photon Therapy Comparison Cohort: Study Design for a Multicenter Retrospective Cohort to Investigate Subsequent Cancers After Pediatric Radiation Therapy.

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially. Direct studies of the potential risks and benefits are needed in children, who have the highest risk of radiation-related subsequent cancers. The Pediatric Proton and Photon Therapy Comparison Cohort aims to meet this need. Methods and Materials: We are developing a record-linkage cohort of 10,000 proton and 10,000 photon therapy patients treated from 2007 to 2022 in the United States and Canada for pediatric central nervous system tumors, sarcomas, Hodgkin lymphoma, or neuroblastoma, the pediatric tumors most frequently treated with protons. Exposure assessment will be based on state-of-the-art dosimetry facilitated by collection of electronic radiation records for all eligible patients. Subsequent cancers and mortality will be ascertained by linkage to state and provincial cancer registries in the United States and Canada, respectively. The primary analysis will examine subsequent cancer risk after proton therapy compared with photon therapy, adjusting for potential confounders and accounting for competing risks. Results: For the primary aim comparing overall subsequent cancer rates between proton and photon therapy, we estimated that with 10,000 patients in each treatment group there would be 80% power to detect a relative risk of 0.8 assuming a cumulative incidence of subsequent cancers of 2.5% by 15 years after diagnosis. To date, 9 institutions have joined the cohort and initiated data collection; additional centers will be added in the coming year(s). Conclusions: Our findings will affect clinical practice for pediatric patients with cancer by providing the first large-scale systematic comparison of the risk of subsequent cancers from proton compared with photon therapy.

Congenital lung malformations.

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.

Analysing Factors Prolonging Hospital Stay After Excision of Choledochal Cyst-A Pathway Towards Enhanced Recovery After Surgery.

BACKGROUND: To evaluate factors affecting length of stay (LOS) after choledochal cyst resection in paediatric patients. METHODS: This was a retrospective study on patients operated between 2004 and 2021. Associations between clinical factors and LOS were evaluated by bivariate analysis, multiple regression, and equivalence test. RESULTS: Sixty-two patients were included. Twenty-four underwent hepaticoduodenostomy as biliary reconstruction. Five suffered from major complications. The median (25th-75th percentile) operation time was 279 (182-378) min. Median LOS, time to enteral feeding, and time to abdominal drain removal were 8(6-10), 2(1-3), and 5(4-7) days, respectively. Seven factors were found significantly associated with a shorter LOS in bivariate analysis and were included in multiple regression. It revealed that early abdominal drain removal (p < 0.001), early enteral feeding (p = 0.042), and the absence of major complications (p < 0.001) were significantly associated with shorter LOS. Equivalence test suggested that age and preoperative cholangitis had no practical effect on LOS. CONCLUSIONS: Early enteral feeding, early drain removal, and avoidance of major complications are associated with a shorter LOS.

The AMPK-like protein kinases Sik2 and Sik3 interact with Hipk and induce synergistic tumorigenesis in a Drosophila cancer model.

Homeodomain-interacting protein kinases (Hipks) regulate cell proliferation, apoptosis, and tissue development. Overexpression of Hipk in Drosophila causes tumorigenic phenotypes in larval imaginal discs. We find that depletion of Salt-inducible kinases Sik2 or Sik3 can suppress Hipk-induced overgrowth. Furthermore, co-expression of constitutively active forms of Sik2 or Sik3 with Hipk caused significant tissue hyperplasia and tissue distortion, indicating that both Sik2 and Sik3 can synergize with Hipk to promote tumorous phenotypes, accompanied by elevated dMyc, Armadillo/ß-catenin, and the Yorkie target gene expanded. Larvae expressing these hyperplastic growths also display an extended larval phase, characteristic of other Drosophila tumour models. Examination of total protein levels from fly tissues showed that Hipk proteins were reduced when Siks were depleted through RNAi, suggesting that Siks may regulate Hipk protein stability and/or activity. Conversely, expression of constitutively active Siks with Hipk leads to increased Hipk protein levels. Furthermore, Hipk can interact with Sik2 and Sik3 by co-immunoprecipitation. Co-expression of both proteins leads to a mobility shift of Hipk protein, suggesting it is post-translationally modified. In summary, our research demonstrates a novel function of Siks in synergizing with Hipk to promote tumour growth.

The impact of pre-operative cholecystostomy on laparoscopic excision of choledochal cyst in paediatric patients.

PURPOSE: This aim of this study was to identify the pre-operative risk factors for conversion during laparoscopic excision of choledochal cyst in paediatric patients. METHODS: A retrospective single-centre study was carried out. All paediatric patients (< 18 years) who had undergone laparoscopic excision of choledochal cyst between 2004 and 2021 were reviewed. The outcome was conversion to open surgery and pre-operative factors that affected the conversion rate were analyzed. RESULTS: Sixty-one patients were included. Conversion was required in 24 cases (39.3%). There was no difference in the conversion rate between the first (before 2012, n = 30) and second (after 2012, n = 31) half of the series (36.7% vs. 42.0%, p = 0.674). Majority was type 1 cyst (86.8%) and the median cyst size was 4.6 cm (IQR: 2.2-6.4 cm). Antenatal diagnosis was available in 18 patients (29.5%). The median age at operation was 23.0 months (IQR: 8.0-72.0 months). Pre-operatively, 19 patients (31.1%) suffered from cholangitis and 5 (8.2%) of them required cholecystostomy. Comparing patients with successful laparoscopic surgery (L) and converted cases (C), there were no differences in the age at operation (p = 0.74), cyst size (p = 0.35), availability of antenatal diagnosis (p = 0.23) and cholangitic episodes (p = 0.40). However, a higher percentage of patients required cholecystostomy in the converted group (L vs. C = 2.7% vs. 16.7%, p = 0.05). Using logistic regression analysis, it was also a risk factor for conversion (OR = 3.5 [1.37-5.21], p = 0.05). CONCLUSION: Pre-operative cholecystostomy is a potential risk factor for conversion during laparoscopic excision of choledochal cyst in children.

C-reactive protein of ≥ 20 mg/L and ultrasound finding of an effusion ≥ 7 mm has a high specificity and sensitivity in diagnosing paediatric hip septic arthritis.

PURPOSE: Differentiating septic arthritis (SA) from transient synovitis (TS) in children remains a diagnostic challenge. Several algorithms have been developed to diagnose SA including Kocher's criteria and its subsequent modifications, but reports show variable efficacy. This study aims to examine the diagnostic utility of a novel method only using C-reactive protein (CRP) and ultrasound (US) findings of effusion in differentiating SA from TS, determine the optimal values for these predictors and validate this method against existing clinical predictors. METHODS: A 5-year retrospective study was performed including all paediatric patients with acute, non-traumatic hip pain with a suspicion of SA. All patients were evaluated using Kocher's criteria, Caird's criteria, and the novel method. Multivariate logistic regression was performed to identify independent clinical predictors of SA. The degree of agreement between the various methods were assessed using Cohen's kappa (k). Receiver operating characteristics (ROC) curves were used to examine the diagnostic accuracy of this novel method as well as to determine optimal cut-offs for US effusion and CRP in diagnosing SA. RESULTS: Hundred and one patients were recruited. CRP and effusion on US were found to be independent predictors of SA. Both Kocher's and Caird's method showed good specificity (98.9%) but extremely poor sensitivity for SA (0%). When Kocher's four clinical predictors were present, probability of SA was only 59.16%. The k for both Kocher's and Caird's methods, was -0.017 indicating poor agreement. However the k in the novel method was 0.641, indicating good agreement. CONCLUSION: Our study showed that the novel method using CRP (≥ 20 mg/L) and US finding of effusion (≥ 7 mm) has a high specificity (97%) and sensitivity (71%) in diagnosing SA.