Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

The pathogenesis of neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) in the gastrointestinal tract remains poorly understood. This study aims to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared with a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn disease (9/18 vs 1/12; P = .024), occur in the rectum (9/18 vs 3/12) and small intestine (4/18 vs 0/12) (P < .01), be diagnosed on resection without a preceding biopsy (6/18 vs 0/12; P = .057), and have unidentifiable precursor lesions (10/18 vs 1/12; P = .018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs 4/12; P = .024), distant metastasis (8/18 vs 1/12; P = .049), mortality (8/18 vs 2/12; P = .058), and worse survival (Kaplan-Meier; P = .023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving TP53 (9/11; 82%), FBXW7 (4/11; 36%), and APC (3/11; 27%) genes, with the other genetic alterations randomly occurring in 1 or 2 cases. The neuroendocrine component, which shared similar molecular alterations as the nonneuroendocrine component, was subcategorized into intermediate (G3a) and high grade (G3b); the higher grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of gastrointestinal NEC/MiNEN may be refined for better clinical management.

Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.

Intraspecific cooperation allows the survival of Staphylococcus aureus staff: a novel strategy for disease relapse.

BACKGROUND: The contribution of interspecies interactions between coinfecting pathogens to chronic refractory infection by affecting pathogenicity is well established. However, little is known about the impact of intraspecific interactions on infection relapse, despite the cross-talk of different strains within one species is more common in clinical infection. We reported a case of chronic refractory pulmonary infection relapse, caused by two methicillin-sensitive S. aureus (MSSA) strains (SA01 and SA02) and revealed a novel strategy for relapse via intraspecific cooperation. METHODS: The hemolytic ability, growth curve, biofilm formation, virulence genes and response of G. mellonella larvae to S. aureus infection were analysed to confirm this hypothesis. RESULTS: SA02 hemolytic activity was inhibited by SA01, along with the expression of hemolysin genes and the virulence factor Hla. Additionally, SA01 significantly enhanced the biofilm formation of SA02. AIP-RNAIII may be a possible pathway for this interaction. Compared with mono-infection, a worse outcome (decreased larval survival and increased microbial burden) of the two MSSA strains coinfected with G. mellonella confirmed that intraspecific interactions indeed enhanced bacterial survival in vivo. CONCLUSION: The intraspecific interaction of S. aureus could lead to chronic refractory infection via pathogenicity changes.

Discharge within 24 h, transvaginal natural orifice transluminal endoscopic surgery- more suitable for ambulatory surgery in gynecology procedures: a retrospective study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is an achievement in the field of minimally invasive surgery. However, the vantage point of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecologicalprocedures remains unclear. The main purpose of this study was to compare vNOTES with laparo-endoscopic single-site surgery, and to determine which procedure is more suitable for ambulatory surgery in gynecologic procedures. METHODS: This retrospective observational study was conducted at the Department of Gynecology, Chengdu Women's and Children's Central Hospital. The 207 enrolled patients had accepted vNOTES and laparo-endoscopic single-site surgery in gynecology procedures from February 2021 to March 2022. Surgically relevant information regarding patients who underwent ambulatory surgery was collected, and 64 females underwent vNOTES. RESULTS: Multiple outcomes were analyzed in 207 patients. The Wilcoxon Rank-Sum test showed that there were statistically significant differences between the vNOTES and laparo-endoscopic single-site surgery groups in terms of postoperative pain score (0 vs. 1 scores, p = 0.026), duration of anesthesia (90 vs. 101 min, p = 0.025), surgery time (65 vs. 80 min, p = 0.015), estimated blood loss (20 vs. 40 mL, p < 0.001), and intestinal exhaustion time (12.20 vs. 17.14 h, p < 0.001). Treatment with vNOTES resulted in convenience, both with respect to time savings and hemorrhage volume in surgery and with respect to the quality of the prognosis. CONCLUSION: These comprehensive data reveal the capacity of vNOTES to increase surgical efficiency. vNOTES in gynecological procedures may demonstrate sufficient feasibility and provide a new medical strategy compared with laparo-endoscopic single-site surgery for ambulatory surgery in gynecological procedures.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Improving oral hygiene for better cognitive health: Interrelationships of oral hygiene habits, oral health status, and cognitive function in older adults.

OBJECTIVES: To explore the interrelationships between oral hygiene habits, oral health status and cognitive function in older adults. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 371 participants (age 76.79 [7.99] years) were enrolled from June 2020 to November 2021 in an aged care facility. METHODS: Cognitive function was screened using the mini-mental state examination (MMSE) with adjusted cut-off points for age and education. Periodontal status (Biofilm-Gingival Interface index based on periodontal probing depth and bleeding on probing), dental status (plaque, calculus, and caries), and tooth loss were assessed through full-mouth examination. Oral hygiene habits were based on self- or informant-reporting. RESULTS: Poor periodontal status was an associated factor for MCI (OR = 2.89, 95% CI = 1.20-6.95), while multiple tooth loss (OR = 4.90, 95% CI = 1.06 ~ 22.59), brushing teeth less than once a day (OR = 2.88, 95% CI = 1.12 ~ 7.45) and delayed dental visits (OR = 2.45, 95% CI = 1.05 ~ 5.68) were associated factors for cognitive impairment. An indirect effect of brushing teeth ≥2 daily on MMSE score through periodontal status was observed only in older adults without cognitive impairment (Bootstrap-corrected B = 0.17, 95%CI = 0.03 ~ 0.36, SE = 0.08, ß = 0.08). CONCLUSIONS AND IMPLICATIONS: Adequate toothbrushing might prevent cognitive decline indirectly by improving periodontal health only in older adults without cognitive impairment. Multiple tooth loss, infrequent toothbrushing, and delayed dental visits were associated factors for cognitive impairment. Nursing professionals and health care policymakers should advocate for the improvement of basic oral hygiene in older adults, and provide regular professional oral hygiene care for older adults with cognitive impairment. PATIENT OR PUBLIC CONTRIBUTION: The information on oral health habits of this study was based on an interview with the participants or their caregivers during the study period.

Clinicopathologic and Molecular Characterization of Anorectal Neuroendocrine Carcinomas Reveals Human Papillomavirus, p53, and c-Myc as Alternative Mechanisms of Carcinogenesis.

Poorly differentiated neuroendocrine carcinomas (NECs) are rare malignant neoplasms with aggressive behavior. The diagnosis remains challenging due to ever-changing terminologies and morphologic overlaps with other disease entities. Herein, we seek to better define anorectal NECs by high-risk human papillomavirus (HPV) status and molecular profiling. Fourteen cases, including 3 men and 11 women with a median age of 63 years, were included. High-risk HPV RNA in situ hybridization was diffusely positive (+) in 7 cases, focal rarely positive (+/-) in 2 cases, and completely negative (-) in 5 cases. By morphology, all HPV(-) NECs were large-cell type, 3 mixed with a tubular adenoma/dysplasia or invasive adenocarcinoma. HPV-related (+ or +/-) NECs were mostly small-cell type, 3 mixed with squamous dysplasia and/or squamous cell carcinoma. Immunohistochemically, all NECs were positive for at least 2 neuroendocrine markers. The HPV(-) NECs were also positive for CDX2, whereas all HPV-related NECs were negative or only focally positive for CDX2, p40, and p63. Overexpression of p53 was found in 3 HPV(-) and 2 HPV(+/-) NECs but not in any HPV(+) NECs. Molecular analysis revealed MYC gene amplification in 4 cases: 2 HPV(-), 1 HPV(+/-), and 1 HPV(+). This was confirmed by fluorescence in situ hybridization in all but 1 HPV(-) NEC, which showed polysomy 8 but no true MYC amplification. Interestingly, only 2 of the 4 MYC amplification-bearing cases, both p53 normal/wild-type, expressed c-Myc protein by immunohistochemistry. The other 2 cases, both p53 overexpressed, did not show c-Myc expression despite true MYC amplification. Our study demonstrates that anorectal NECs arise in HPV-dependent or -independent pathways, with heterogeneous expression of other lineage markers and different molecular signatures. Expressions of p53 and c-Myc proteins appear to be mutually exclusive regardless of HPV status, likely mediating alternative mechanisms of NEC carcinogenesis.

Postinfantile Giant Cell Hepatitis in Native and Allograft Livers: A Multi-Institutional Clinicopathologic Study of 70 Cases.

Postinfantile giant cell hepatitis (PIGCH) is a rare hepatitis pattern in adults with variable etiologies and clinical outcomes. We conducted a multi-institutional retrospective study to define the clinicopathologic characteristics of patients with PIGCH. A total of 70 PIGCH cases were identified and reviewed for pathological features, including fibrosis, cholestasis, inflammation, steatosis, necrosis, and apoptosis, as well as the distribution of giant cells and the maximum number of giant cells per high-power field. Demographic and clinical data, including age, sex, laboratory results, etiologies, and follow-up results, were recorded. Among the 70 cases, 40% (28/70) were associated with autoimmune liver diseases, followed by 9 (13%) with unknown etiology, 8 (11%) with viral infection, 5 (7%) with medications, 5 with combined etiologies, and 4 (6%) with malignancies (mostly chronic lymphocytic leukemia). Notably, another 16% were de novo PIGCH in liver allografts, most of which occurred after a rejection event. During follow-up, 26 (37%) patients died of the disease and 44 (63%) were alive. Deceased patients were characterized by older age (mean age, 54.9 vs 45.5 years; P = .02), higher alkaline phosphatase level (mean value, 253.3U/L vs 166.3 U/L; P = .03), higher fibrosis stage (stage 3-4 vs stage 0-2, 57.7% vs 29.6%; P = .03), being more likely to have de novo PIGCH after transplantation (23.1% vs 11.4%; P = .04), and being less likely to have primary autoimmune liver disease etiology (26.9% vs 47.7%; P = .04). These results indicate that PIGCH is a rare pattern of liver injury associated with different etiologies and variable clinical outcomes. Autoimmune liver disease with PIGCH is associated with better survival, whereas de novo PIGCH in allografts is associated with poorer survival. Older age, higher alkaline phosphatase level, and advanced fibrosis are adverse prognostic factors.

Non-conventional dysplasia is frequently associated with low-grade tubuloglandular and mucinous adenocarcinomas in inflammatory bowel disease.

There is limited information regarding the clinicopathological features of low-grade tubuloglandular (LGTGA) and mucinous (MAC) adenocarcinomas occurring in inflammatory bowel disease (IBD), especially with regard to their precursor lesions. METHODS AND RESULTS: Forty-six IBD colectomy specimens with LGTGA (n = 17) or MAC (n = 29) with adjacent precursor lesions were analysed. As controls, 12 IBD colectomy specimens with well- to moderately differentiated adenocarcinoma that lacked any mucinous, signet ring cell, low-grade tubuloglandular or serrated features were also analysed. Compared with MACs and controls, LGTGAs more often had a flat/invisible macroscopic appearance (LGTGAs = 88%, MACs = 34%, controls = 25%, P < 0.001). MACs were more likely to have high-grade differentiation (MACs = 31%, LGTGAs = 0%, controls = 0%, P = 0.002) and a higher pathological stage (pT3 and pT4 MACs = 76%, LGTGAs = 35%, controls = 33%, P = 0.007) than LGTGAs and controls. LGTGAs (70%) and MACs (53%) were more frequently associated with non-conventional dysplasia than controls (0%) (P < 0.001). Crypt cell (40%) and hypermucinous (34%) dysplasias were the most common non-conventional subtypes associated with LGTGAs and MACs, respectively. Synchronous dysplasia often demonstrated non-conventional features in the LGTGA (33%) and MAC (47%) groups (versus 0% for the control group, P = 0.074). Synchronous cancer frequently showed similar histological features as the main tumour (LGTGA group = 60%, MAC group = 38%, control group = 100%). CONCLUSIONS: Crypt cell and hypermucinous dysplasias are the most common precursor lesions associated with LGTGAs and MACs, respectively, and may serve as a marker of increased risk for these cancer subtypes.

Dual-Ligand-Functionalized Liposomes Based on Glycyrrhetinic Acid and cRGD for Hepatocellular Carcinoma Targeting and Therapy.

Hepatocellular carcinoma (HCC) is one of the most common cancers, with high mortality. Chemotherapy is one of the main treatment options for HCC. However, the high toxicity and poor specificity of chemotherapeutic drugs have limited their clinical application. In this study, dual-ligand liposomes modified with glycyrrhetinic acid (GA) and cyclic arginine-glycine-aspartic acid (cRGD) (GA/cRGD-LP) were designed to target the GA receptor and αvß3 integrin, respectively. The aim was to develop a highly selective targeted drug delivery system and further enhance the antitumor efficiency of drugs by targeting both hepatic tumor cells and vasculature. A novel lipid conjugate (mGA-DOPE) by coupling dioleoylphosphatidyl ethanolamine (DOPE) with methyl glycyrrhetinic acid (mGA) was synthesized, and its structure was confirmed. The targeting efficiency of GA/cRGD-LP by in vitro cellular uptake and ex vivo imaging was assessed. GA- and cRGD-modified doxorubicin-loaded liposomes (GA/cRGD-LP-DOX) were prepared, and their cytotoxicity in HepG2 and antitumor activity were evaluated. The results showed that the average particle size of the GA/cRGD-LP-DOX was 114 ± 4.3 nm, and the zeta potential was -32.9 ± 2.0 mV. The transmission electron microscopy images showed that the shapes of our liposomes were spherical. cGA/cRGD-LP-DOX displayed an excellent cellular uptake in both HepG2 and human umbilical vein endothelial cells. In the in vivo study, pharmacokinetic parameters indicated that cGA/cRGD-LP can prolong the circulation time of DOX in the blood. GA/cRGD-LP-DOX showed greater inhibition of tumor growth for HepG2-bearing mice than either the single-ligand-modified liposomes or nontargeted liposomes. GA/cRGD-LP-DOX displayed higher liver tumor localization than that of single-ligand-modified liposomes or free DOX. GA/cRGD-LP is a promising drug delivery system for liver cancer targeting and therapy and is worthy of further study.

Hysteropreservation versus hysterectomy in uterine prolapse surgery: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Hysteropreservation and hysterectomy for uterine prolapse have been compared in several randomized controlled trials (RCTs), as the best treatment has not been definitively determined. This study aimed to summarize the available evidence in RCTs of hysteropreservation versus hysterectomy. METHODS: We performed electronic searches in the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for eligible RCTs from inception to June 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated for categorical and continuous variables using random-effects models. RESULTS: Twelve RCTs involving 1177 patients were selected for meta-analysis. There were no significant differences between hysteropreservation and hysterectomy for the incidences of recurrence (RR, 0.55; 95% CI, 0.26-1.19; P = 0.130) and reoperation (RR, 1.15; 95% CI, 0.56-2.37; P = 0.705). Moreover, neither hysteropreservation nor hysterectomy had any significant effect on the risk of constipation (RR, 0.72; 95% CI, 0.15-3.46; P = 0.681), voiding dysfunction (RR, 0.99; 95% CI, 0.54-1.84; P = 0.981), intraoperative bleeding (RR, 0.35; 95% CI, 0.05-2.26; P = 0.271), upper leg dullness (RR, 0.70; 95% CI, 0.15-3.17; P = 0.643), dyspareunia (RR, 1.47; 95% CI, 0.69-3.13; P = 0.317), and wound infection (RR, 1.38; 95% CI, 0.24-7.80; P = 0.714). Furthermore, hysteropreservation was associated with less intraoperative blood loss (WMD, -25.68; 95% CI, -44.39 to -6.96; P = 0.007), shorter duration of surgery (WMD, -11.30; 95% CI, -19.04 to -3.55; P = 0.004), and shorter duration of hospitalization (WMD, -0.63; 95% CI, -1.10 to -0.16; P = 0.009) compared with hysterectomy. CONCLUSION: This study found that both hysteropreservation and hysterectomy have similar effects on recurrence and reoperation rates, while hysteropreservation was superior to hysterectomy in reducing intraoperative blood loss and shortening the duration of surgery and hospitalization.

The Therapy-Related Symptom Checklist for Children as a Method for Monitoring Symptoms in Chinese Children With Cancer: Linguistic Validation and Cross-Cultural Adaptation.

BACKGROUND: Children with cancer commonly experience severe symptoms. These may be managed by routine monitoring of their occurrence andseverity using a validated tool. AIM: This study aimed to translate and culturally validate a simplified Chinese version of the Therapy-Related Symptom Checklist for Children (TRSC-C). DESIGN: Qualitative method. PARTICIPANTS AND SETTING: We recruited children with cancer from a pediatric department of a tertiary hospital in Guangzhou, China. METHODS: We used forward and backward translation by bilingual translators and standardized cognitive interviewing for linguistic validation and to check cross-cultural adaptation. A panel of experts assessed content validity. RESULTS: Agreement was reached on cultural applicability, suitability for intended purpose, and clarification of the pre-test version. The content validity was good (indices ranged from 0.80-0.90). Fifteen Chinese children with cancer (aged 8-18 years) were included in cognitive interviews. The cognitive debriefing showed that the instrument was easy to understand and appropriate for monitoring symptoms in children with cancer. Some words were adjusted following participants' comments. CONCLUSIONS: The simplified Chinese version of the TRSC-C was semantically and conceptually equivalent to the original version. Children between 8-18 years old can use this instrument to report symptoms and share their experiences about their disease and treatment.

Psychometric validation of the simplified Chinese version of the therapy-related symptom checklist in children with cancer.

PURPOSE: To validate a simplified Chinese version of the therapy-related symptom checklist for children (TRSC-C) in children with cancer. METHODS: Reliability was assessed by internal consistency and test-retest coefficients. Dimensionality and construct validity were clarified using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Pearson's correlation coefficient was calculated between the TRSC-C and the PedsQL 3.0 cancer model (PedsQL 3.0) and the Lansky Play Performance Scale (LPPS) to test concurrent validity. A Student's t-test was used to compare the scores of the simplified Chinese version of the TRSC-C subscales by gender, age groups, and functional status to test sensitivity of the TRSC-C. RESULTS: A sample of 170 children with cancer was recruited (11.27 ± 2.31 years). Cronbach's alpha (0.89) and interclass correlation coefficient (0.98) were acceptable. Seven factors with eigenvalues >1 explained 56.86% of the total variances. CFA demonstrated an acceptable model (CFI = 0.93, RMSE = 0.04). Concurrent validity was supported by moderate to high correlations between the TRSC-C and both the PedsQL 3.0 (r = -0.71) and LPPS (r = -0.43). The TRSC-C scores significantly differed by age groups and functional status (effect size 0.40-0.93), indicating adequate sensitivity. CONCLUSION: The simplified Chinese version of the TRSC-C demonstrated acceptable reliability, validity, and sensitivity to support its use in clinical practice and future studies.

Assessing health-related quality of life in Chinese children and adolescents with cancer: validation of the DISABKIDS chronic generic module (DCGM-37).

BACKGROUND: With increasing cancer incidence and decreasing cancer mortality, there is a growing need for a valid and culturally adapted tool to measure health-related quality of life in children with cancer. This study validated the DISABKIDS Chronic Generic Module (DCGM-37) in Chinese children and adolescents with cancer. METHODS: The DCGM-37 was translated and adapted for use in China following the guidelines from its copyright holders. In total, 140 children and adolescents with cancer and their guardians were included in this cross-sectional study. Internal consistency and test-retest reliability were evaluated. Convergent validity was examined using Pearson correlation between the DCGM-37 and the PedsQL 4.0 Generic Core Scale. Dimensionality was clarified using exploratory factor analysis. Discriminant validity was evaluated by comparing DCGM-37 scores by sex, age, family income, and clinical characteristics. RESULTS: Internal consistency (Cronbach's alpha 0.91) and test-retest reliability were good (intraclass correlation coefficient 0.87, 95% confidence interval 0.73-0.94). Strong correlations between the DCGM-37 and the PedsQL 4.0 (r = 0.83) suggest good convergent validity. Six factors explained 51.94% of the total variance. Children with leukemia scored higher than those with sarcoma in all subscales (effect size ranged from 0.39 to 0.83), especially the "social exclusion" subscales (effect size 0.83). Small to moderate differences (effect size ranged from 0.38 to 0.58) were observed by sex, age, and family income. Neither floor nor ceiling effects were observed. CONCLUSION: The DCGM-37 is reliable and valid for measuring health-related quality of life in Chinese children and adolescents with cancer.

Conversion between Mini-Mental State Examination and Montreal Cognitive Assessment scores in older adults undergoing selective surgery using Rasch analysis.

AIMS: To develop and validate a conversion table between the MMSE and the MoCA using Rasch analysis in older adults undergoing selective surgery and examine its diagnostic accuracy in detecting cognitive impairment. DESIGN: Cross-sectional study. METHODS: Older patients [N = 129; age 66.0 (4.6) years, education 7.7 (3.5) years] undergoing elective surgery were recruited from December 2017 to June 2018. All participants completed the MMSE and MoCA and 113 of them completed a battery of neuropsychological tests. Common person linking based on Rasch analysis was performed to develop the conversion table. The conversions were validated by calculating the intraclass correlation coefficient (ICC), score differences between actual and converted scores, and root mean squared error of the difference (RMSE). The diagnostic accuracy of the conversions for detecting cognitive impairment was also tested. RESULTS: The MoCA [person measure: 1.3 (1.1) logits] was better targeted to the patients than the MMSE [person measure: 3.2 (1.3) logits]. Conversion from MoCA to MMSE scores (ICC 0.84, 95% CI 0.77-0.88; RMSE 1.36) was more precise than conversion from MMSE to MoCA (ICC 0.82, 95% CI 0.75-0.87; RMSE 2.56). Conversion from MoCA to MMSE demonstrated better diagnostic accuracy in detecting cognitive impairment than the actual MMSE, whereas conversion from MMSE to MoCA exhibited the opposite pattern. CONCLUSION: Conversion from MoCA to MMSE was more precise and had better diagnostic accuracy in detecting pre-operative cognitive impairment in older patients undergoing selective surgery than conversion from MMSE into MoCA. IMPACT: The finding is useful for interpreting, comparing, and integrating cognitive measurements in surgical settings and clinical research. Statistically sound conversion between MoCA and MMSE based on Rasch analysis is now possible for surgical setting and clinical research.

Validation of the Chinese version of the abnormal eating behavior questionnaire in people with dementia.

Abnormal eating behaviors are common in patients with dementia. To comprehensively assess and understand these issues, we validated the Chinese version of the Abnormal Eating Behaviour Questionnaire. Data for psychometric property evaluation were obtained from 129 patients with dementia. Internal consistency, test-retest reliability, dimensionality, and concurrent validity of the instrument were tested. The instrument showed acceptable internal consistency (Cronbach's alpha 0.73), time stability (Intra-class correlation coefficient 0.88, 95% CI: 0.77-0.94), and concurrent validity (ρ = 0.60, P < 0.001). Six factors (eigenvalues > 1, factor loading ≥ 0.3) explaining 55.1% of the variance were obtained through exploratory factor analysis. Overall, 86.8% of the participants showed at least one abnormal eating behavior. The instrument is reliable and valid for assessing abnormal eating behaviors in patients with dementia. Patients with dementia had a high prevalence of abnormal eating behaviors.

Mutation profile of high-grade appendiceal mucinous neoplasm.

AIMS: High-grade appendiceal mucinous neoplasm (HAMN) was recently proposed as a disease entity histologically analogous to low-grade appendiceal mucinous neoplasm (LAMN), but characterised by high-grade cytological atypia. The pathogenesis and clinical features of HAMN have not been fully elucidated. METHODS AND RESULTS: Nine cases of HAMN, eight LAMN, 10 appendiceal mucinous adenocarcinomas (MACA) and five appendiceal serrated polyps resected between 2008 and 2017 contributed by three medical centres underwent targeted next-generation sequencing of 50 cancer-related genes. The patients in each category had similar profiles with respect to gender, age, tumour stage and follow-up intervals. Both LAMN and HAMN harboured mutations of KRAS [nine of nine and eight of eight (100%), respectively] and GNAS [five of eight (63%) and five of nine (56%), respectively] in significantly higher proportions than MACA [KRAS, seven of 10 (70%, P = 0.04); GNAS: one of 10 (10%, P = 0.02)] and serrated polyps [KRAS, one of five (20%, P = 0.0007); GNAS: none of five (0%, P = 0.04)]. Four cases of HAMN, but none of LAMN, harboured mutations of TP53 [four of nine (44%)] and/or ATM [two of nine (22%)]. Three cases of HAMN (33%) showed extra-appendiceal spread with retention of the same mutational profiles in the intra- and extra-appendiceal components. The 10 cases of MACA harboured a similar prevalence of TP53 mutations (n = 5, 50%) as HAMN but, unlike LAMN and HAMN, some harboured mutations in PIK3CA, APC, FBXW7, PTEN and SMAD4. CONCLUSIONS: HAMN and LAMN share high rates of KRAS and GNAS co-mutations supporting a common histogenesis and distinguishing them from MACA. Acquisition of TP53 or ATM mutations by HAMN may drive its progression to a more advanced phenotype.

Colorectal carcinomas with mucinous differentiation are associated with high frequent mutation of KRAS or BRAF mutations, irrespective of quantity of mucinous component.

BACKGROUND: Mucinous adenocarcinoma (MAC) is a distinct type of colorectal cancer (CRC) associated with poor response to treatment and poorer prognosis. MAC is diagnosed by WHO definition when the extracellular mucin is more than 50% of the lesion. We aimed at assessing the gene expression profiles of the CRCs with any mucinous features (> 5%) in a retrospective study. METHODS: The data of a 50-gene next generation sequencing (NGS) panel of 166 CRCs was analyzed and the gene mutational profile with morphologic features was correlated. RESULTS: We identified the different genetic mutation profiles between CRCs with and without mucinous component, but noticed a similar genetic profile between MACs and CRCs with mucinous component, irrespective of the percentage (if mucinous component more than 5%). The different genetic mutation profile related to MSI status was also identified between two groups of tumors. The most frequent mutations in CRCs with mucinous component are KRAS (28/49, 57.1%) and BRAF (19/49, 38.7%), PIK3CA (16/49, 32.6%), followed by APC (12/49, 24.5%) and TP53 (11/49, 22.5%). The combined mutation frequency of the two key factors in the EGFR signaling pathway, KRAS and BRAF, in the CRCs with and without mucinous component is 95.9 and 52.1%, respectively. CONCLUSIONS: The dysregulation of EGFR pathway plays a critical role in the development of CRCs with mucinous component, irrespective of the percentage. The result suggested that the current cut off of 50% mucin component to define mucinous adenocarcinoma might be challengeable.

Impact of EUS-guided microforceps biopsy sampling and needle-based confocal laser endomicroscopy on the diagnostic yield and clinical management of pancreatic cystic lesions.

BACKGROUND AND AIMS: EUS-guided microforceps biopsy sampling (MFB) and needle-based confocal laser endomicroscopy (nCLE) are emerging diagnostic tools for pancreatic cystic lesions (PCLs). There is a paucity of data regarding their performance and impact. The aim of this study was to compare diagnostic outcomes and changes in clinical management resulting from MFB and nCLE use in PCLs. METHODS: This was a single-center retrospective study of patients with PCLs who underwent combined EUS-guided FNA, MFB, and nCLE. Primary outcomes included diagnostic yield (specific PCL type) and change in clinical management for each modality compared with the current "composite standard" (CS) obtained by combining clinical, morphologic, cyst fluid cytology, and chemical analysis. RESULTS: Forty-four cysts were studied in 44 patients. Technical success was 100% for EUS-FNA, 88.6% for MFB, and 97.7% for nCLE. Of 44 procedures, there was 1 adverse event (2.3%, an infected pseudocyst). Diagnostic yield for each individual modality was 34.1% for CS, 75.0% for MFB (P < .05 vs CS), and 84.1% for nCLE (P < .05 vs CS). Diagnostic yield for combined tests was 79.5% for CS/MFB, 88.6% for CS/nCLE, and 93.2% for CS/MFB/nCLE (P = not significant). Compared with the CS, the use of MFB, nCLE, and their combination led to overall change in clinical management in 38.6%, 43.2%, and 52.3% of cases, respectively. MFB and nCLE led to an overall increase in discontinuation of surveillance (MFB, 34.1% [P < .05]; nCLE, 31.8% [P < .05]), led by a reduction in the indication for follow-up radiologic or endoscopic studies (MFB, 34.1% [P < .05]; nCLE, 38.6% [P < .05]). Based on MFB and nCLE, 2 of 28 (7.1%) and 3 of 28 (10.7%) patients who would have undergone further surveillance were referred for surgery. CONCLUSIONS: In the evaluation of PCLs, the use of combined EUS-guided FNA, MFB, and nCLE is safe. MFB and nCLE led to significant improvements in specific PCL diagnosis, which in turn has major impacts in clinical management.

Malignant tumors in hernia sac: Clinicopathological and immunohistochemical studies of 21 cases at a single institution.

Malignant tumors presented in hernia sac are very rare and the clinicopathological features are not well studied. We retrospectively reviewed 21 patients with cancers identified in surgically resected hernia sac specimens at our institution, including 14 males and 7 females, with a median age of 65 years (range 35-93). Fourteen patients (66.7%) carried a synchronous or metachronous cancer diagnosis elsewhere and the tumors in hernia sac were proven to be metastasis. Of the remaining seven (33.3%) cases, hernia sac tumors were the initial presentation of malignancy, and a panel of immunohistochemistry markers were applied in combination with clinical information to identify tumor origin. The final classification of all 21 cases was as follows: 11 gastrointestinal tract tumors including 10 adenocarcinomas and 1 gastrointestinal stromal tumor, 5 pancreatobiliary adenocarcinomas and 5 gynecological serous carcinomas. Compared to other tumor types, pancreatobiliary adenocarcinomas were more likely to involve hernia sac as initial presentation before a primary site was identified (P = 0.0307) and had worse survival (P < 0.005). As the first and largest cohort of malignant tumors in hernia sac, our study provides critical data on frequency, distribution, clinicopathological features and applicability of immunohistochemical markers to determine tumor origin in cases with unknown primary.