Optimal timing of re-planning for head and neck adaptive radiotherapy.

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) relies on re-planning to correct treatment variations, but the optimal timing of re-planning to account for dose changes in head and neck organs at risk (OARs) is still under investigation. We aimed to find out the optimal timing of re-planning in head and neck ART. MATERIALS AND METHODS: A total of 110 head and neck cancer patients were retrospectively enrolled. A semi auto-segmentation method was applied to obtain the weekly mean dose (Dmean) to OARs. The K-nearest-neighbour method was used for missing data imputation of weekly Dmean. A dose deviation map was built using the planning Dmean and weekly Dmean values and then used to simulate different ART scenarios consisting of 1 to 6 re-plannings. The difference between accumulated Dmean and planning Dmean before re-planning (ΔDmean_acc_noART) and after re-planning (ΔDmean_acc_ART) were evaluated and compared. RESULTS: Among all the OARs, supraglottic showed the largest ΔDmean_acc_noART (1.23 ± 3.13 Gy) and most cases of ΔDmean_acc_noART > 3 Gy (26 patients). The 3rd week is suggested in the optimal timing of re-planning for 10 OARs. For all the organs except arytenoid, 2 re-plannings were able to guarantee the ΔDmean_acc_ART below 3 Gy while the average |ΔDmean_acc_ART| was below 1 Gy. ART scenarios of 2_4, 3_4, 3_5 (week of re-planning separated with "_") were able to guarantee ΔDmean_acc_ART of 99 % of patients below 3 Gy simultaneously for 19 OARs. CONCLUSIONS: The optimal timing of re-planning was suggested for different organs at risk in head and neck adaptive radiotherapy. Generic scenarios of timing and frequency for re-planning can be applied to guarantee the increase of accumulated mean dose within 3 Gy simultaneously for multiple organs.

Single-Port Laparoscopic Extraperitoneal Repair of Pediatric Inguinal Hernias and Hydroceles by Using Hernia Crochet Needle With a Cannula.

PURPOSE: Numerous modifications laparoscopic techniques have mushroomed in recent years. Here we describe a modified technique of extracorporeal ligation of processus vaginalis in children using a hernia crochet needle with a cannula. METHODS: Processus vaginalis repair was carried out on patients diagnosed with inguinal hernia or hydroceles using this novel technique between June 2021 and June 2022. The processus vaginalis was closed extracorporeally using a hernia crochet needle with a cannula. In the presence of patent processus vaginalis, the same procedure would be performed on the contralateral side. The primary outcomes was the safety and efficiency of this modified procedure, and the secondary outcomes was the post operative complications. RESULTS: A total of 212 (165 inguinal hernia and 47 hydroceles) children were corrected by this novel technique. The mean operation time was 27.49 min for unilateral inguinal hernia cases and 36.55 min for bilateral cases. The unilateral hydrocele median operation time was 27.83 min and that for the bilateral cases was 37.30 min. During the mean of 10.92 months of follow-up, there was only a boy subject to a metachronous contralateral occurrence of hernia 10 months after surgery, and no other complications (knot reactions, testicular atrophy, postoperative hydrocele or iatrogenic) have been observed yet. CONCLUSION: This study shown a unique procedure with using a hernia crochet needle with a cannula to be simple, safe, and effective in managing inguinal hernias and hydroceles in the pediatric population.

A contrast-enhanced CT radiomics-based model to identify candidates for deintensified chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma patients.

OBJECTIVES: To develop a contrast-enhanced CT (CECT) radiomics-based model to identify locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients who would benefit from deintensified chemoradiotherapy. METHODS: LA-NPC patients who received low-dose concurrent cisplatin therapy (cumulative: 150 mg/m2), were randomly divided into training and validation groups. 107 radiomics features based on the primary nasopharyngeal tumor were extracted from each pre-treatment CECT scan. Through Cox regression analysis, a radiomics model and patients' corresponding radiomics scores were created with predictive independent radiomics features. T stage (T) and radiomics score (R) were compared as predictive factors. Combining the N stage (N), a clinical model (T + N), and a substitution model (R + N) were constructed. RESULTS: Training and validation groups consisted of 66 and 33 patients, respectively. Three significant independent radiomics features (flatness, mean, and gray level non-uniformity in gray level dependence matrix (GLDM-GLN)) were found. The radiomics score showed better predictive ability than the T stage (concordance index (C-index): 0.67 vs. 0.61, AUC: 0.75 vs. 0.60). The R + N model had better predictive performance and more effective risk stratification than the T + N model (C-index: 0.77 vs. 0.68, AUC: 0.80 vs. 0.70). The R + N model identified a low-risk group as deintensified chemoradiotherapy candidates in which no patient developed progression within 3 years, with 5-year progression-free survival (PFS) and overall survival (OS) both 90.7% (hazard ratio (HR) = 4.132, p = 0.018). CONCLUSION: Our radiomics-based model combining radiomics score and N stage can identify specific LA-NPC candidates for whom de-escalation therapy can be performed without compromising therapeutic efficacy. CLINICAL RELEVANCE STATEMENT: Our study shows that the radiomics-based model (R + N) can accurately stratify patients into different risk groups, with satisfactory prognosis in the low-risk group when treated with low-dose concurrent chemotherapy, providing new options for individualized de-escalation strategies. KEY POINTS: • A radiomics score, consisting of 3 predictive radiomics features (flatness, mean, and GLDM-GLN) integrated with the N stage, can identify specific LA-NPC populations for deintensified treatment. • In the selection of LA-NPC candidates for de-intensified treatment, radiomics score extracted from primary nasopharyngeal tumors based on CECT can be superior to traditional T stage classification as a predictor.

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies. METHODS: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively. RESULTS: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/ß-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). CONCLUSIONS: ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Structure-Based Ligand Discovery Targeting the Transmembrane Domain of Frizzled Receptor FZD7.

Despite the essential roles of Frizzled receptors (FZDs) in mediating Wnt signaling in embryonic development and tissue homeostasis, ligands targeting FZDs are rare. A few antibodies and peptide modulators have been developed that mainly bind to the family-conserved extracellular cysteine-rich domain of FZDs, while the canonical binding sites in the transmembrane domain (TMD) are far from sufficiently addressed. Based on the recent structures of FZDs, we explored small-molecule ligand discovery by targeting TMD. From the ChemDiv library with ∼1.6 million compounds, we identified compound F7H as an antagonist of FZD7 with an IC50 at 1.25 ± 0.38 µM. Focusing on this hit, the structural dissection study, together with computing studies such as molecular docking, molecular dynamics simulation, and free energy perturbation calculations, defined the binding pocket with key residue recognition. Our results revealed the structural basis of ligand recognition and demonstrated the feasibility of structure-guided ligand discovery for FZD7-TMD.

CPVL suppresses metastasis of nasopharyngeal carcinoma through inhibiting epithelial-mesenchymal transition.

PURPOSE: Distant metastasis is the main obstacle to treating nasopharyngeal carcinoma (NPC). Tumor distance metastasis is a complex process involving the jointly participation of multiple oncogenes, tumor suppressor genes, and metastasis-associated genes. Enough accurate prognostic genes for evaluating metastasis risk are lacking. We aimed to identify more precise biomarkers for NPC metastasis. METHODS: We performed weighted gene co-expression network analysis, differentially expressed gene analysis, univariate and multivariate stepwise Cox regression, and Kaplan-Meier (K-M) survival analyses, on data obtained from RNA sequencing of 10 NPC samples and the public database, to identify key genes correlated with NPC metastasis. Wound healing assays, transwell assays, and immunohistochemistry were conducted to validate our bioinformatic conclusions. Western blotting was performed to evaluate and quantify the effect of identified EMT genes on epithelial-mesenchymal transition (EMT) of NPC. RESULTS: Combined our own RNA sequencing data and public data, we determined carboxypeptidase vitellogenic-like protein (CPVL) as a tumor suppressor for NPC. Pathway enrichment analyses indicated that genes associated with CPVL are involved in EMT. NPC with low CPVL expression had high tumor purity and low levels of immune cells. Experimental results showed that CPVL protein predominantly expressed in cytoplasmic and membranous and it exhibited higher expression levels in NPC tissues without distant metastasis than those with distant metastasis. CPVL inhibits the migration and invasive capability of NPC cells. Overexpression of CPVL upregulates E-cadherin and ZO-1, whereas it downregulates vimentin, suggesting that CPVL suppresses tumor metastasis by inhibiting EMT. CONCLUSION: CPVL inhibits migration and invasion of NPC cells and is associated with tumor metastasis suppression through upregulating epithelial marker and inhibiting mesenchymal marker expression and could be a prognostic biomarker for metastasis risk evaluation in NPC.

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Background: Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study. Methods: Genotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR. Results: Based on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137. Conclusion: The plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis.

BACKGROUND: The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease. AIM: To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC. METHODS: We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish. RESULTS: After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1ß and IL-8. CONCLUSION: GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1ß and IL-8 in zebrafish, and is important for prevention and control of HAEC.

An investigation into the risk of population bias in deep learning autocontouring.

BACKGROUND AND PURPOSE: To date, data used in the development of Deep Learning-based automatic contouring (DLC) algorithms have been largely sourced from single geographic populations. This study aimed to evaluate the risk of population-based bias by determining whether the performance of an autocontouring system is impacted by geographic population. MATERIALS AND METHODS: 80 Head Neck CT deidentified scans were collected from four clinics in Europe (n = 2) and Asia (n = 2). A single observer manually delineated 16 organs-at-risk in each. Subsequently, the data was contoured using a DLC solution, and trained using single institution (European) data. Autocontours were compared to manual delineations using quantitative measures. A Kruskal-Wallis test was used to test for any difference between populations. Clinical acceptability of automatic and manual contours to observers from each participating institution was assessed using a blinded subjective evaluation. RESULTS: Seven organs showed a significant difference in volume between groups. Four organs showed statistical differences in quantitative similarity measures. The qualitative test showed greater variation in acceptance of contouring between observers than between data from different origins, with greater acceptance by the South Korean observers. CONCLUSION: Much of the statistical difference in quantitative performance could be explained by the difference in organ volume impacting the contour similarity measures and the small sample size. However, the qualitative assessment suggests that observer perception bias has a greater impact on the apparent clinical acceptability than quantitatively observed differences. This investigation of potential geographic bias should extend to more patients, populations, and anatomical regions in the future.

An efficient strategy to select head and neck cancer patients for adaptive radiotherapy.

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) is workload intensive but only benefits a subgroup of patients. We aimed to develop an efficient strategy to select candidates for ART in the first two weeks of head and neck cancer (HNC) radiotherapy. MATERIALS AND METHODS: This study retrospectively enrolled 110 HNC patients who underwent modern photon radiotherapy with at least 5 weekly in-treatment re-scan CTs. A semi auto-segmentation method was applied to obtain the weekly mean dose (Dmean) to OARs. A comprehensive NTCP-profile was applied to obtain NTCP's. The difference between planning and actual values of Dmean (ΔDmean) and dichotomized difference of clinical relevance (BIOΔNTCP) were used for modelling to determine the cut-off maximum ΔDmean of OARs in week 1 and 2 (maxΔDmean_1 and maxΔDmean_2). Four strategies to select candidates for ART, using cut-off maxΔDmean were compared. RESULTS: The Spearman's rank correlation test showed significant positive correlation between maxΔDmean and BIOΔNTCP (p-value <0.001). For major BIOΔNTCP (>5%) of acute and late toxicity, 10.9% and 4.5% of the patients were true candidates for ART. Strategy C using both cut-off maxΔDmean_1 (3.01 and 5.14 Gy) and cut-off maxΔDmean_2 (3.41 and 5.30 Gy) showed the best sensitivity, specificity, positive and negative predictive values (0.92, 0.82, 0.38, 0.99 for acute toxicity and 1.00, 0.92, 0.38, 1.00 for late toxicity, respectively). CONCLUSIONS: We propose an efficient selection strategy for ART that is able to classify the subgroup of patients with >5% BIOΔNTCP for late toxicity using imaging in the first two treatment weeks.

Expression of S100A9 in adamantinomatous craniopharyngioma and its association with wet keratin formation.

Wet keratin is a hallmark of adamantinomatous craniopharyngioma (ACP), which is frequently infiltrated by inflammatory cells. S100 calcium-binding protein A9 (S100A9) has been confirmed to play a decisive role in the development of inflammation. However, the relationship between wet keratin (keratin nodules) and S100A9 in ACP is poorly understood. The objective of the present study was to explore the expression of S100A9 in ACP and its association with wet keratin formation. Immunohistochemistry and immunofluorescence were used to detect the expression of S100A9, ß-catenin and Ki67 in 46 cases of ACP. A total of three online databases were used to analyze S100A9 gene expression and protein data. The results revealed that S100A9 was primarily expressed in wet keratin and some intratumoral and peritumoral cells, and its expression in wet keratin was upregulated in the high inflammation group (P=1.800x10-3). In addition, S100A9 was correlated with the degree of inflammation (r=0.6; P=7.412x10-3) and the percentage of Ki67-positive cells (r=0.37; P=1.000x10-2). In addition, a significant correlation was noted between the area of wet keratin and the degree of inflammation (r=0.51; P=2.500x10-4). In conclusion, the present study showed that S100A9 was upregulated in ACP and may be closely associated with wet keratin formation and the infiltration of inflammatory cells in ACP.

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309).

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo-chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumab-chemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot" tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment. VIDEO ABSTRACT.

An overall survival predictive nomogram to identify high-risk patients among locoregionally advanced nasopharyngeal carcinoma: Developed based on the SEER database and validated institutionally.

Objective: Locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients. Materials and methods: Histologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan-Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored. Results: Our nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p<0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients. Conclusions: Our OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.

A composite score based on immune-related gene prognostic index and m6A risk score of head and neck squamous cell carcinoma.

Background: Immunotherapy has been demonstrated favorable in head and neck squamous cell carcinoma (HNSCC). Studies indicated that immune-related gene prognostic index (IRGPI) was a robust signature, and N6-methyladenosine (m6A) methylation had a significant impact on the tumor immune microenvironment (TIME) and immunotherapy of head and neck squamous cell carcinoma. Thus, combining indicated that immune-related gene prognostic index with m6A status should offer a better predictive power for immune responses. Methods: Head and neck squamous cell carcinoma samples from the cancer genome atlas (TCGA, n = 498) and gene expression omnibus database (GSE65858, n = 270) were used in this study. Cox regression analysis was used to construct the indicated that immune-related gene prognostic index through immune-related hub genes which were identified by weighted gene co-expression network analysis (WGCNA). The m6A risk score was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. Principal component analysis was used to construct a composite score, and systematically correlate subgroups according to tumor immune microenvironment cell-infiltrating characteristics. Results: A composite score was determined based on indicated that immune-related gene prognostic index and m6A risk score. Head and neck squamous cell carcinoma patients in the cancer genome atlas were divided into four subgroups: A (IRGPI-High&m6A-risk-High, n = 127), B (IRGPI-High&m6A-risk-Low, n = 99), C (IRGPI-Low&m6A-risk-High, n = 99), and D (IRGPI-Low&m6A-risk-Low, n = 128), and overall survival (OS) was significantly different between subgroups (p < 0.001). The characteristics of tumor immune microenvironment cell infiltration in the four subgroups were significantly different in subgroups (p < 0.05). The receiver operating characteristic (ROC) curves show the predictive value of composite score for overall survival was superior to other scores. Conclusion: The composite score is a promising prognostic signature which might distinguish immune and molecular characteristics, predict prognosis, and guide more effective immunotherapeutic strategies for head and neck squamous cell carcinoma.

Molecular biological features of cyst wall of adamantinomatous craniopharyngioma.

The molecular biological differences between cyst walls and those in solid bodies are the foundation of the outcomes. In this study, the CTNNB1 mutations were confirmed by DNAsequencing; CTNNB1 expression levels were detected by PCR; the differences between solid bodies and cyst walls in proliferative capacity and tumor stem cell niches were assessed by immunohistochemistry; the effect of the residual cyst wall on recurrence was assessed by follow-up. Mutations in the CTNNB1 in the cyst wall and the solid body were identical in each case. No differences were found in the transcriptional level of CTNNB1 between the cyst walls and the solid bodies (P = 0.7619). The cyst wall showed a pathological structure similar to the solid body. Proliferative capacity of cyst walls was stronger than that of solid body (P = 0.0021), and ß-catenin nuclear positive cells (cell clusters) in cyst walls were more than that in solid tumor (P = 0.0002). The retrospective 45 ACPs showed residual cyst wall was significantly associated with tumor recurrence or regrowth (P = 0.0176). Kaplan-Meier analysis showed there was a significant difference in the prognosis between GTR and STR (P < 0.0001).The cyst wall of ACP contained more tumor stem cell niches which could lead to the recurrence. According to the above-mentioned, a special attention to the management of the cyst wall should be paid.

Effect of modified transanal Soave assisted by laparoscopy in the treatment of Hirschsprung's disease in children and its influencing factors.

OBJECTIVE: To investigate the effect of modified transanal Soave assisted by laparoscopy in children with Hirschsprung's disease (HD). METHODS: The clinical data of 120 children with Hirschsprung's disease admitted to Fujian Children's Hospital from January 2018 to November 2021 were retrospectively analyzed. Based on the surgical methods, 58 children treated with modified transanal Soave were regarded as the modified group and 62 children treated with modified transanal Soave assisted by laparoscopy were divided into the laparoscopic group. The operative indexes, anal function, quality of life and perianal pressure 6 months after surgery, complications within 1 month after surgery, and recovery within 6 months after surgery of the two groups were compared. The risk factors influencing the postoperative recovery of hirschsprung's disease in children were analyzed by univariate and logistic regression analysis. RESULTS: The operation time, intraoperative blood loss, length of hospital stay and gastrointestinal recovery time in the laparoscopic group were lower than those in modified group (P < 0.05). The excellent and good rate of postoperative anal function in laparoscopic group was 87.10%, which was higher than that in modified group (68.97%) (P < 0.05). The proportion of patients with good quality of life in laparoscopic group (90.32%) was higher than that in modified group (74.14%) (P < 0.05). The anal resting pressure and systolic pressure in laparoscopic group were lower than those in modified group (all P < 0.05). The total complication rate of laparoscopic group (6.45%) was lower than that of modified group (22.41%) (P < 0.05). After 6 months, 64 cases (53.33%) were cured and 56 cases (46.67%) were not. After univariate analysis, there were statistically significant differences in enteritis, abdominal distension, and anastomotic stenosis between cured children and uncured children (all P < 0.05). There was no significant difference in other factors (P > 0.05). Logistic regression analysis showed that enteritis, abdominal distension and anastomotic stenosis were the risk factors affecting the recovery of hirschsprung's disease in children (all P < 0.05). CONCLUSIONS: Modified transanal Soave assisted by laparoscopy can improve anal function and quality of life, relieve anal pressure, and have a low complication rate. Enteritis, abdominal distension, and anastomotic stenosis are the factors affecting the recovery of Hirschsprung's disease in children.

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series.

BACKGROUND: Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. METHODS: Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. RESULTS: A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. CONCLUSION: Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

Diagnosis and Management of Pediatric Papillary Craniopharyngiomas.

OBJECTIVE: Papillary craniopharyngioma (PCP) was previously believed to occur only in adults. Sporadic pediatric PCP (PPCP) confirmed by detection of BRAF V600E mutation has been reported since 2018, but is often misdiagnosed before being diagnosed definitively. We aimed to evaluate PPCP characteristics and propose diagnostic criteria for prompt diagnosis, seeking to reduce patient morbidity and mortality and reduce costs linked to misdiagnosis. METHODS: This study included 5 patients with PPCPs whose data were retrieved retrospectively from among 1032 patients with craniopharyngiomas admitted to Sanbo Brain Hospital Management Group from March 2017 to May 2021. Patients' demographics, clinical presentation, tumor imaging characteristics, histopathologic results, surgical approaches, and postoperative outcomes were analyzed. RESULTS: PPCP was misdiagnosed intraoperatively as sellar abscess (n = 4) or Rathke cleft cyst (n = 1). Preoperative magnetic resonance imaging showed that all tumors were under the saddle diaphragm, and the cyst wall was enhanced (n = 5). Computed tomography scans showed scattered high-density signs (n = 4). No recurrence was noted after complete resection. Postoperative hypothalamic dysfunction was mild. BRAF V600E mutation was confirmed in all cases by sequencing and immunohistochemistry. Immunohistochemistry showed granulation and inflammation and MPO, CD3, CD20, CD38, CD68, and CD163 were positively expressed. CONCLUSIONS: Misdiagnosis of PPCP is responsible for failed surgical treatment. We propose that prompt diagnosis of PPCP can be achieved if preoperative magnetic resonance images show the tumor under saddle diaphragm with tumor wall enhancement and computed tomography scans show high-density signs scattered in the tumor, which leads to safe, effective tumor resection. Our proposed diagnosis and treatment strategy for PPCP reduces morbidity and mortality.

Comparative Analysis of Phytochemical Profiles and Antioxidant Activities between Sweet and Sour Wampee (Clausena lansium) Fruits.

As a local medicine and food, wampee fruit, with abundant bioactive compounds, is loved by local residents in Southern China. Titratable acid (TA), total sugar (TS), and total phenolic and flavonoid contents were detected, and phytochemical profiles and cellular antioxidant activities were analyzed by the HPLC and CAA (cellular antioxidant activity) assay in five sweet wampee varieties and five sour wampee varieties. Results showed that the average TS/TA ratio of sweet wampee varieties was 29 times higher than sour wampee varieties, while TA content was 19 times lower than sour wampee varieties. There were much lower levels of total phenolics, flavonoids, and antioxidant activities in sweet wampee varieties than those in sour wampee varieties. Eight phytochemicals were detected in sour wampee varieties, including syringin, rutin, benzoic acid, 2-methoxycinnamic acid, kaempferol, hesperetin, nobiletin, and tangeretin, while just four of them were detected in sweet wampee varieties. Syringin was the only one that was detected in all the sour wampee varieties and was not detected in all sweet wampee varieties. Correlation analysis showed significant positive correlations between TA with phenolics, flavonoids, and total and cellular (PBS wash) antioxidant activities, while there were significant negative correlations between TS/TA with phenolic and cellular (no PBS wash) antioxidant activities. This suggested that the content of titratable acid in wampee fruit might have some relationship with the contents of phenolics and flavonoids. Sour wampee varieties should be paid much attention by breeders for their high phytochemical contents and antioxidant activities for cultivating germplasms with high health care efficacy.

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p.

BACKGROUND: Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression. METHODS: PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession. RESULTS: PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10. CONCLUSION: PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.