Artificial intelligence model for enhancing the accuracy of transvaginal ultrasound in detecting endometrial cancer and endometrial atypical hyperplasia.

OBJECTIVES: Transvaginal ultrasound is typically the initial diagnostic approach in patients with postmenopausal bleeding for detecting endometrial atypical hyperplasia/cancer. Although transvaginal ultrasound demonstrates notable sensitivity, its specificity remains limited. The objective of this study was to enhance the diagnostic accuracy of transvaginal ultrasound through the integration of artificial intelligence. By using transvaginal ultrasound images, we aimed to develop an artificial intelligence based automated segmentation model and an artificial intelligence based classifier model. METHODS: Patients with postmenopausal bleeding undergoing transvaginal ultrasound and endometrial sampling at Mayo Clinic between 2016 and 2021 were retrospectively included. Manual segmentation of images was performed by four physicians (readers). Patients were classified into cohort A (atypical hyperplasia/cancer) and cohort B (benign) based on the pathologic report of endometrial sampling. A fully automated segmentation model was developed, and the performance of the model in correctly identifying the endometrium was compared with physician made segmentation using similarity metrics. To develop the classifier model, radiomic features were calculated from the manually segmented regions-of-interest. These features were used to train a wide range of machine learning based classifiers. The top performing machine learning classifier was evaluated using a threefold approach, and diagnostic accuracy was assessed through the F1 score and area under the receiver operating characteristic curve (AUC-ROC). RESULTS: 302 patients were included. Automated segmentation-reader agreement was 0.79±0.21 using the Dice coefficient. For the classification task, 92 radiomic features related to pixel texture/shape/intensity were found to be significantly different between cohort A and B. The threefold evaluation of the top performing classifier model showed an AUC-ROC of 0.90 (range 0.88-0.92) on the validation set and 0.88 (range 0.86-0.91) on the hold-out test set. Sensitivity and specificity were 0.87 (range 0.77-0.94) and 0.86 (range 0.81-0.94), respectively. CONCLUSIONS: We trained an artificial intelligence based algorithm to differentiate endometrial atypical hyperplasia/cancer from benign conditions on transvaginal ultrasound images in a population of patients with postmenopausal bleeding.

RECIST 1.1, mRECIST, and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab.

OBJECTIVES: We aimed to compare the early responder rates, defined as complete or partial responders, using response evaluation criteria in solid tumors (RECIST) 1.1, modified RECIST (mRECIST), and Choi criteria in advanced HCC patients treated with atezolizumab-bevacizumab (atezo-bev), and to correlate them with progression-free survival (PFS) and overall survival (OS). METHODS: This retrospective study included advanced HCC patients treated with ≥ 3 cycles of atezo-bev. Two reviewers assessed responses using RECIST 1.1, mRECIST, and Choi criteria at 1st follow-up imaging. Kaplan-Meier curves with log-rank tests evaluated and compared PFS and OS. Cox proportional hazard models identified survival outcome predictors. Kappa statistics assessed inter-reader agreement. RESULTS: We evaluated 77 patients (65 men; mean age, 62.8 ± 12.3 years). Choi's criteria revealed the highest early responders rate (53.2%), exceeding mRECIST (32.5-33.8%) and RECIST 1.1 (24.7-26.0%), with an excellent agreement in all criteria (κ, 0.85-0.95). Across criteria, a consistent number of patients progressed (23-26) and was associated with significantly poor OS (ps ≤ 0.049). Responders by any criteria showed longer PFS (ps ≤ 0.009), and 1-year OS (ps ≤ 0.01). Choi criteria linked to significantly better OS without landmark (p = 0.003), with 1-year OS rates at 76.9% for responders vs 38.1% for non-responders. Cox analysis identified responders by Choi criteria as a significant OS predictor. CONCLUSION: Choi criteria identified more early responders than RECIST 1.1 and mRECIST, significantly correlating with improved OS. Choi criteria could be considered as a formal response assessment criterion for the emerging atezo-bev systemic treatment. CLINICAL RELEVANCE STATEMENT: For atezo-bev treatment of advanced HCC, more comprehensive response criteria, such as Choi criteria, could be effective in identifying early responders and predicting survival outcomes along with RECIST 1.1 and mRECIST. KEY POINTS: Choi criteria identified a higher rate of early responders compared to mRECIST and RECIST1.1 following atezo-bev treatment. Responders by all criteria had longer PFS and 1-year OS, and only those by Choi criteria experienced longer OS without landmark time. Choi criteria, with RECIST 1.1 and mRECIST, is an effective response assessment tool for atezo-bev treatment.

Prognostic Factors of Pulmonary Metastasectomy for Oligometastatic Hepatocellular Carcinoma Spread to the Lungs.

Background/Objectives: Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods: Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results: Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions: PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy.

A preoperative scoring system for predicting the extraprostatic extension of prostate cancer following radical prostatectomy using magnetic resonance imaging and clinical factors.

PURPOSE: We aimed to develop a preoperative prediction model for extraprostatic extension (EPE) in prostate cancer (PCa) patients following radical prostatectomy (RP) using MRI and clinical factors. METHODS: This retrospective study enrolled 266 consecutive patients who underwent RP for PCa in 2022. These patients were divided into a training set (n = 187) and a test set (n = 79) through random assignment. The evaluated variables included age, prostate-specific antigen (PSA) level, prostate volume, PSA density (PSAD), index tumor length on MRI, Prostate Imaging-Reporting and Data System (PI-RADS) category, and EPE-related MRI features as defined by PI-RADS v2.1. A predictive model was constructed through multivariable logistic regression and subsequently translated into a scoring system. The performance of this scoring system in terms of prediction and calibration was assessed using C statistics and the Hosmer‒Lemeshow test. RESULTS: Among patients in the training and test cohorts, 74 (39.6%) and 25 (31.6%), respectively, exhibited EPE after RP. The formulated scoring system incorporated the following factors: PSAD, index tumor length, bulging prostatic contour, and tumor-capsule interface > 10 mm as identified on MRI. This scoring system demonstrated strong prediction performance for EPE in both the training (C statistic, 0.87 [95% confidence interval, 0.86-0.87]) and test cohorts (C statistic, 0.85 [0.83-0.89]). Furthermore, the scoring system exhibited good calibration in both cohorts (P = 0.988 and 0.402, respectively). CONCLUSION: Our scoring system, built upon MRI features defined by the PI-RADS, offers valuable assistance in assessing the likelihood of EPE after RP.

Reliability of the DI-60 Digital Image Analyzer for Detecting Platelet Clumping and Obtaining Accurate Platelet Counts.

Pseudothrombocytopenia caused by platelet clumping (PC) can lead to unnecessary platelet transfusions or underdiagnosis of hematologic neoplasms. To overcome these limitations, we assessed the capacity of the Sysmex DI-60 digital morphology analyzer (Sysmex, Kobe, Japan) for detecting PC and determining an accurate platelet count in the presence of PC. For this purpose, 135 samples with or without PC (groups Y and N, respectively) were processed by an examiner (a hematologic specialist) using both the Sysmex XN-9000 and DI-60 analyzers. Although the platelet aggregate (PA) and giant platelet (GP) counts reported by the DI-60 and the examiner exhibited strong correlations, they proved inadequate as effective indicators for screening samples containing PC. Between the PA and GP counts and four platelet indices (the platelet distribution width [PDW], mean platelet volume [MPV], platelet large cell ratio [P_LCR], and plateletcrit [PCT]) reported by the XN-9000, we observed statistically significant correlations (both overall and with group Y), but they were relatively weak. The platelet counts determined using the DI-60 and light microscopy in group Y showed substantial variations. Although the performance of the DI-60 was reliable for detecting PA and GP in smear images, such fixed areas are not representative of whole samples. Further, in the presence of PC, the resulting platelet counts determined using the DI-60 were not sufficiently accurate to be accepted as the final count.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Interpretation of Complete Tumor Response on MRI Following Chemoradiotherapy of Rectal Cancer: Inter-Reader Agreement and Associated Factors in Multi-Center Clinical Practice.

OBJECTIVE: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCRT2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. RESULTS: The mrCRT2W and mrCRoverall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCRT2W to non-mrCRoverall. The kappa values for mrTRG, mrCRT2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). CONCLUSION: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

Papillary renal neoplasm with reverse polarity: a clinicopathologic study of 43 cases with a focus on the expression of KRAS signaling pathway downstream effectors.

Papillary renal neoplasm with reverse polarity (PRNRP) is a renal tumor with frequent KRAS mutations. In this study, we aimed to report the clinical, histological, and immunohistochemical characteristics of PRNRP and the protein expression of various KRAS signaling pathway downstream effectors in PRNRP. PRNRP samples from patients who underwent surgical resection at Seoul National University Hospital over an 11-year period (January 2011 to December 2021) were analyzed. We identified 43 PRNRPs, defined as papillary renal tumors with a thin papillary architecture, eosinophilic finely granular cytoplasm, and apical nuclear position. Immunohistochemistry revealed typical characteristics of PRNRP, including exclusively positive GATA3 (43/43); highly positive L1CAM (43/43), PAX8 (43/43), and EMA (43/43); and low positive AMACR (4/43), RCC (1/43), and vimentin (1/43). KRAS signaling pathway effectors, such as p-ERK, RalA, and RalB, were highly expressed in PRNRP compared to papillary renal cell carcinoma (pRCC) with low or high nuclear grade (P < .001, all). Compared to pRCC with high nuclear grade, patients with PRNRP exhibited significantly longer progression-free survival (P < .001). PRNRP showed the best clinical outcome, with no disease progression in any of the cases. Our study analyzed the largest number of PRNRP cases and is the first to analyze the association between PRNRP and the KRAS downstream signaling pathway. PRNRP was found at a high frequency among all papillary renal tumors (43/207) and demonstrated a very good prognosis. PRNRP showed high GATA3, L1CAM, PAX8, and EMA protein expression as well as high p-ERK, RalA, and RalB protein expression.

Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study.

BACKGROUND: Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. METHODS: We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. RESULTS: High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. CONCLUSIONS: Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology.

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy.

The prognostic role of soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in patients with gastric cancer (GC) receiving systemic chemotherapy remains unelucidated. Thus, we examined their prognostic significance in patients with advanced GC. Blood samples were obtained from 99 patients with advanced GC receiving first-line chemotherapy. Serum-derived exosomes were isolated by centrifugation and polymer precipitation. The correlation between serum-derived exoPD-L1, plasma sPD-L1, immune-related markers, and circulating immune cells was evaluated. Patients were divided into two groups according to pretreatment sPD-L1 and exoPD-L1 levels: low sPD-L1 and high sPD-L1 groups, low exoPD-L1 and high exoPD-L1 groups. Patients with low sPD-L1 level before treatment (< 9.32 pg/mL) showed significantly better overall survival (OS) and progression-free survival (PFS) than those with high sPD-L1 level (≥ 9.32 pg/mL). The low exoPD-L1 group (< 10.21 pg/mL) showed a tendency of longer PFS than the high exoPD-L1 group (≥ 10.21 pg/mL). Pretreatment sPD-L1 was an independent prognostic factor for OS in multivariate analysis. exoPD-L1 was associated with systemic inflammation markers, immunomodulatory cytokines, and T cells, while sPD-L1 was associated with tumor markers. Pretreatment plasma-derived sPD-L1 level could be used as a prognostic marker for patients receiving cytotoxic chemotherapy. Serum-derived exoPD-L1 may reflect the immunosuppressive state of patients with advanced GC.

Clinical application of the anti-human telomerase reverse transcriptase (hTERT) antibody (SCD-A7) immunocytochemistry in liquid-based urine cytology: A prospective, single institute study.

OBJECTIVES: Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. METHODS: A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid-based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD-A7) ICC. RESULTS: From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow-up histology. The hTERT ICC-positive rate was 95.9% (n = 208/217), 96% (n = 24/25), and 100% (n = 4/4) in cytology samples with high-grade urothelial carcinoma, carcinoma in situ, and low-grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% (n = 59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC-negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow-up were hTERT-negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC = 0.963; 95% CI = 0.960-0.967). CONCLUSIONS: The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid-based urine cytology.

Estimating postsurgical outcomes of patients with a single hepatocellular carcinoma using gadoxetic acid-enhanced MRI: risk scoring system development and validation.

OBJECTIVES: To develop and validate risk scoring systems using gadoxetic acid-enhanced liver MRI features and clinical factors that predict recurrence-free survival (RFS) of a single hepatocellular carcinoma (HCC). METHODS: Consecutive 295 patients with treatment-naïve single HCC who underwent curative surgery were retrospectively enrolled from two centers. Cox proportional hazard models developed risk scoring systems whose discriminatory powers were validated using external data and compared to the Barcelona Clinic Liver Cancer (BCLC) or American Joint Committee on Cancer (AJCC) staging systems using Harrell's C-index. RESULTS: Independent variables-tumor size (per cm; hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.02-1.13; p = 0.005), targetoid appearance (HR, 1.74; 95% CI: 1.07-2.83; p = 0.025), radiologic tumor in vein or tumor vascular invasion (HR, 2.59; 95% CI: 1.69-3.97; p < 0.001), the presence of a nonhypervascular hypointense nodule on the hepatobiliary phase (HR, 4.65; 95% CI: 3.03-7.14; p < 0.001), and pathologic macrovascular invasion (HR, 2.60; 95% CI: 1.51-4.48; p = 0.001)-with tumor markers (AFP ≥ 206 ng/mL or PIVKA-II ≥ 419 mAU/mL) derived pre- and postoperative risk scoring systems. The risk scores showed comparably good discriminatory powers in the validation set (C-index, 0.75-0.82) and outperformed the BCLC (C-index, 0.61) and AJCC staging systems (C-index, 0.58; ps < 0.05). The preoperative scoring system stratified the patients into low-, intermediate-, and high-risk for recurrence, whose 2-year recurrence rate was 3.3%, 31.8%, and 85.7%, respectively. CONCLUSION: The developed and validated pre- and postoperative risk scoring systems can estimate RFS after surgery for a single HCC. KEY POINTS: • The risk scoring systems predicted RFS better than the BCLC and AJCC staging systems (C-index, 0.75-0.82 vs. 0.58-0.61; ps < 0.05). • Five variables-tumor size, targetoid appearance, radiologic tumor in vein or vascular invasion, the presence of a nonhypervascular hypointense nodule on the hepatobiliary phase, and pathologic macrovascular invasion-combined with tumor markers derived risk scoring systems predicting postsurgical RFS for a single HCC. • In the risk scoring system using preoperatively-available factors, patients were classified into three distinct risk groups, with 2-year recurrence rates in the low-, intermediate-, and high-risk groups being 3.3%, 31.8%, and 85.7% in the validation set.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.

Targetoid Primary Liver Malignancy in Chronic Liver Disease: Prediction of Postoperative Survival Using Preoperative MRI Findings and Clinical Factors.

OBJECTIVE: We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. MATERIALS AND METHODS: This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan-Meier curves were used to estimate RFS and OS for the different risk-score groups. RESULTS: In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2-5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62-0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). CONCLUSION: Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer.

Muscle-invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high-throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in-house patient-derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform-based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype (TUBB6 migration, P = .0509 and P < .0001; invasion, P = .0002 and P = .0044; TGFBI migration, P = .0214 and P = .0026; invasion, P < .0001 and P = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein-based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P < .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.

Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.