Grade Group Research Articles

Sub-region based histogram analysis of amide proton transfer-weighted MRI for predicting tumor budding grade in rectal adenocarcinoma: a prospective study.

To explore the sub-regional histogram features of amide proton transfer-weighted (APTw) MRI, compared with those of diffusion-weighted imaging (DWI), in predicting the tumor budding (TB) grade of rectal cancer (RC). This study prospectively enrolled 74 patients with pathologically confirmed RC, who underwent APTw MRI before surgery from July 2022 to March 2023. Hematoxylin-eosin staining was used for TB scoring. K-means clustering (K = 4-6) was applied to obtain multiple sub-regions (n = 3-5), and corresponding histogram features (including mean, standard deviation, minimum, maximum, and 10th, 25th, 50th, 75th, and 90th quantile) of APT and apparent diffusion coefficient (ADC) maps were extracted and filtered using stepwise regression. When K = 5, the K-means clustering is four sub-regions, showing the best prediction for TB grade compared to K = 4 or 6. When K = 5, there were significantly higher histogram features of the APT map in sub-regions 3 and 4 in the high TB grade group compared to the low-intermediate TB grade group. Receiver operating characteristic (ROC) curve and internal validation suggested that the predictive efficiency of the model was highest when K = 5, with AUC, sensitivity, specificity, accuracy, and kappa values of 0.92, 93%, 71%, 87%, and 0.65, respectively. There were no significant differences in the histogram features of each sub-region in the ADC map (p > 0.05). The sub-regional histogram features of APTw images can help to distinguish the heterogeneous regions of RC, which can be used to predict the TB grade of RC. Question Can the sub-regional histogram features of APTw MRI predict the tumor budding (TB) grade of rectal cancer (RC)? Findings Differences exist in histogram features of APT map subregions between high and low-intermediate TB grade groups; subregions of the APT map have different predictive abilities. Clinical relevance APT-weighted imaging might outperform DWI in predicting TB grade in RC.

Detecting Clinically Significant Prostate Cancer in PI-RADS 3 Lesions Using T2w-Derived Radiomics Feature Maps in 3T Prostate MRI

Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) category 3 lesions are a challenge in the clinical workflow. A better detection of the infrequently occurring clinically significant prostate cancer (csPCa) in PI-RADS 3 lesions is an important objective. The purpose of this study was to evaluate if feature maps calculated from T2-weighted (T2w) 3 Tesla (3T) MRI can help detect csPCa in PI-RADS category 3 lesions. In-house biparametric 3T prostate MRI examinations acquired between January 2019 and June 2023 because of elevated prostate-specific antigen (PSA) levels were retrospectively screened. Inclusion criteria were a PI-RADS 3 lesion and available results of an ultrasound-guided targeted and systematic biopsy. Exclusion criteria were a simultaneous PI-RADS category 4 or 5 lesion and hip replacement. Target lesions with the International Society of Urological Pathology (ISUP) grade group 1 were rated clinically insignificant PCa (ciPCa) and ≥2 csPCa. This resulted in 52 patients being included in the final analysis, of whom 11 (21.1%), 8 (15.4%), and 33 (63.5%) patients had csPCa, ciPCa, and no PCa, respectively, with the latter two groups being combined as non-csPCa. Eight of the csPCas were located in the peripheral zone (PZ) and three in the transition zone (TZ). In the non-csPCa group, 29 were located in the PZ and 12 in the TZ. Target lesions were marked with volumes of interest (VOIs) on axial T2w images. Axial T2w images were then converted to 93 feature maps. VOIs were copied into the maps, and feature quantity was retrieved directly. Features were tested for significant differences with the Mann–Whitney U-test. Univariate models for single feature performance and bivariate models implementing PSA density (PSAD) were calculated. Ten map-derived features differed significantly between the csPCa and non-csPCa groups (AUCs: 0.70–0.84). The diagnostic performance for TZ lesions (AUC: 0.83–1.00) was superior to PZ lesions (AUC: 0.74–0.85). In the bivariate models, performance in the PZ improved with AUCs >0.90 throughout. Parametric feature maps alone and as bivariate models with PSAD can (?) noninvasively identify csPCa in PI-RADS 3 lesions and could serve as a quantitative tool reducing ambiguity in PI-RADS 3 lesions.

Role of Apparent Diffusion Coefficient Value and Apparent Diffusion Coefficient Ratio as Prognostic Factors for Prostate Cancer Aggressiveness

Background: Prostate cancer is one of the most prevalent cancers in the male population. To determine the aggressiveness of suspected lesions precisely, predictive models are increasingly being developed using quantitative MRI measurements, and particularly the ADC value. This study aimed to determine whether ADC values could be used to establish the aggressiveness of prostate cancer. Methods: A retrospective single-center study included 398 patients with prostate cancer who underwent a multiparametric MRI prior to radical prostatectomy. DWI ADC values were measured (µm2/s) using b values of 50 and 1000. The dominant lesion best visualized on MRI was analyzed. The ADC values of the index lesion and reference tissue were compared to tumor aggressivity according to the Gleason grade groups based on radical prostatectomy results. Statistical analysis was performed using the Mann–Whitney U test, Kruskal–Wallis H test, Spearman’s rank correlation, and ROC curves. Results: A very strong negative correlation (rs = −0.846, p < 0.001) between ADC and GS was found. ROC analysis revealed an AUC of 0.958 and an ADC threshold value of 758 µm2/s in clinically significant prostate cancer diagnoses using the absolute ADC value, with no advantage of using the ADC ratio over the absolute ADC value being identified. Conclusion: DWI ADC values and the calculated ADC ratio have a significant inverse correlation with GS. The findings indicate a strong capability in determining prostate cancer aggressiveness, as well as the possibility of assisting with assigning PI-RADS categories using ADC as quantitative metrics.

Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI.

Multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are complementary imaging modalities used in the presurgical evaluation of patients with prostate cancer (PCa). The purpose of this study was to characterize clinically significant PCa (csPCa) detected and not detected by PSMA PET/CT and mpMRI, focusing on tumors detected solely by PSMA PET/CT and overlooked by mpMRI. Methods: We conducted a single-center, retrospective analysis of patients who underwent both PSMA PET/CT and mpMRI within 3 mo of each other and before radical prostatectomy. Two nuclear medicine physicians and 2 radiologists, in a masked manner, independently contoured PCa lesions on PSMA PET/CT and mpMRI, respectively. A consensus read was done with a third reader for each modality, and a majority rule was applied (2:1). After centralized imaging, a pathologic review was done by a genitourinary pathologist. We assessed agreement between imaging modalities and correlation with pathology. Logistic regression models explored associations between clinicopathologic variables and tumor detection on imaging. Results: In total, 132 csPCa tumors from 100 patients were identified on surgical pathology. PSMA PET/CT showed higher lesion-level (87% vs. 80%) and patient-level (98% vs. 94%) sensitivity than mpMRI. Tumors detected on both imaging modalities were larger and had higher grade groups than those not detected by one or both imaging modalities. On multivariable analysis, csPCa tumors undetected by mpMRI but detected by PSMA PET/CT were smaller than those detected by both modalities. Most tumors showing aggressive pathologic features, such as the large cribriform pattern (94.7%) and the intraductal carcinoma (96%), were correctly detected by both imaging modalities. Limitations included selection bias in a surgical cohort. Conclusion: PSMA PET/CT tends to detect smaller csPCa not detected by mpMRI. Larger tumors on pathology with higher grade groups are more likely to be correctly detected by both imaging modalities. These findings provide insights for refining presurgical evaluation strategies in PCa.

Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance

Background and Aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC. Materials and Methods: Men with PC and a BMI > 25 kg/m2 undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro–Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively. Results: Ten AS patients aged 62.1(±5.4) years were enrolled with an average BMI of 31.7 kg/m2 (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline. Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

PSMA PET/CT Accuracy in Diagnosing Prostate Cancer Nodes Metastases.

This study aimed to evaluate the diagnostic accuracy of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) in pelvic nodal staging, using postoperative histopathology data as the reference standard. From January 2020 to June 2024, 78 patients with clinically significant prostate cancer (PCa) (ISUP Grade Group 2) underwent radical prostatectomy plus extended pelvic lymph node dissection (ePLND): 60 (77%) vs. 18 (23%) men had an intermediate vs. high risk PCa. All the patients underwent PSMA PET/TC before surgery for clinical staging and nodes focal uptake (standardized uptake value "SUVmax) was evaluated to rule out the presence of metastases. PSMA PET/CT was suspicious for nodes metastases in 16/78 (20.5%) men (median SUVmax 26.2), conversely, histology demonstrated nodes metastases in 18/78 (23.1%). PSMA PET/CT was negative for nodal involvement in all Grade Group 2 (GG2) PCa, positive in 4/4 (100%) GG3 PCa, and in 10/14 (71.4%) GG5 PCa. In detail, PSMA PET/CT was false negative in 2/4 PCa, characterized by GG5 plus ductal adenocarcinoma. Overall, PSMA PET/CT sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy in diagnosing nodal metastases were equal to 87.5, 96.8, 87.5 96.7, and 92.3%, respectively. PSMA PET/CT demonstrated an overall diagnostic accuracy of 92.3% in nodal staging (100% in GG2 PCa), which decreased to 63.6% in GG5 PCa. In high-risk patients or in case of ductal adenocarcinoma, a negative PSMA PET/CT does not rule out the need for ePLND.

Measuring health-related quality of life in a Chinese Mainland adolescent population: psychometric properties of the Mandarin Chinese self-reported KIDSCREEN-27 and KIDSCREEN-10 index

BackgroundThe self-reported KIDSCREEN questionnaires are ideal for capturing children’s and adolescents’ health-related quality of life (HRQoL) and have gained worldwide popularity. Responding to demands for the concise nature of KIDSCREEN among Chinese Mainland researchers and practitioners, this study aimed to evaluate the psychometric properties of the Mandarin Chinese self-reported KIDSCREEN-27 (KS-27) and KIDSCREEN-10 index (KS-10), which are short versions of the self-reported KIDSCREEN-52 (KS-52).MethodsThis study reanalyzed the validation dataset of the Mandarin Chinese self-reported KS-52. The dataset originated from a cross-sectional survey conducted in Weifang City, the Chinese Mainland, from October to November 2016. Adolescents aged 11–17 years (N = 4385) were surveyed, and sub-samples (N = 841) were retested. Statistical analyses were conducted on the feasibility, item and dimension properties, reliability, and validity of the Mandarin Chinese self-reported KS-27 and KS-10.ResultsIndirect evidence from the Small Group Pilot Survey indicated that the Mandarin Chinese self-reported KS-27 and KS-10 can be completed on average in less than 12.33 mins. Their response rate exceeded 90% regardless of the unit- and item (dimension)-level. The psychometric properties of items and dimensions were likewise found to be satisfactory. Internal consistency was robust with inter-item and item-total correlations (0.173–0.873, 0.422–0.786), Cronbach’s alpha (0.786–0.881), Guttman’s lambda-2 and - 6 (0.807–0.889, 0.829–0.896), and McDonald’s omega (0.725–0.886). Test–retest reliability at both item- and dimension-level was excellent, with intraclass correlation coefficients (ICCs) of (0.590–0.696, 0.785–0.842); standard error of measurements (SEMs) of (0.352–0.635, 0.949–1.949). Confirmatory factor analysis (CFA) confirmed their five- and one-dimensional structures, albeit with slight modifications. Moreover, the multi-group confirmatory factor analysis (MG-CFA) substantiated their configural and metric invariance across gender and grade groups. Convergent validity was robust, with stronger correlations observed with comparable dimensions of the Mandarin Chinese self-reported PedsQL™ 4.0, while discriminant validity was evident with low correlations observed with less comparable dimensions. The known-group validity was mainly supported by medium to large effect sizes concerning differences in socioeconomic status (η2 = 0.07–0.17, Cohen’s d = 0.55–1.03) and mental health status (η2 = 0.09–0.40, Cohen’s d = 0.73–1.83). The Mandarin Chinese self-reported KS-52 served as the criterion; the ICCs between the Mandarin Chinese self-reported KS-27 and KS-10 and their comparable dimensions were stronger, indicating robust criterion validity.ConclusionsThe Mandarin Chinese self-reported KS-27 and KS-10 demonstrated excellent psychometric properties, indicating their good potential for measuring HRQoL for children and adolescents in the Chinese Mainland.

The Association Between Lymphovascular or Perineural Invasion in Radical Prostatectomy Specimen and Biochemical Recurrence

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.

HOXA9 and CD163 potentiate pancreatic ductal adenocarcinoma progression

BackgroundThe role of HOXA9 requires investigations in pancreatic ductal adenocarcinoma (PDAC) as HOXA9 inhibitors are being developed. HOXA9 might attract CD163 expressed tumor associated macrophages (TAM) and could affect PDAC prognosis. This work aims to study the expression and relevance of HOXA9 and CD163 in PDAC progression.Materials and methodsSelected 98 PDAC and 98 adjacent non tumor tissues as a control group were immunostained with HOXA9 and CD163 antibodies.ResultsPDAC displayed highly significant higher HOXA9 staining intensity, percent and H score values than control group. HOXA9 staining of PDAC cases showed significant associations with poor prognostic indicators including larger tumor size, higher grade and advanced stage. PDAC showed highly significant differences regarding CD163 macrophage-specific staining intensity, percent and H score values than control group. CD163 showed significant higher expressions with larger tumor size, higher histological grade and advanced stage group. HOXA9 staining in PDAC showed highly significant direct correlations with CD163 positive macrophages. Follow up of PDAC cases revealed that high median H score of HOXA9 and CD163 were significantly associated with worse overall survival. CD163 was an independent prognostic marker of worse survival.ConclusionsIn conclusion, HOXA9 could potentiate PDAC progression by stimulating CD163 expressed TAM attraction in tumors. HOXA9 and CD163 could participate in PDAC therapy. HOXA9 and CD163 could be predictors of worse prognosis and shorter survival in PDAC.

Triple-console robotic telesurgery: first impressions and future impact.

Telesurgery has been recently gaining momentum as a natural evolution of robotic surgery. Besides providing expert surgical care to patients who cannot geographically access it, telesurgery can also facilitate surgical collaboration between surgeons who might need urgent assistance or coaching experts. The idea of having two consoles, with one remote and one local, has been the ideal setup for such ecosystems. However collaborations can take on many forms and might require more than one remote surgeon, depending on procedure complexity and surgeon availability. The objective of the study was to describe our perspectives and experience performing telesurgery on one patient, using three surgeon consoles for three surgeons, operating from three separate cities. In November 2023, a triple-console, robot-assisted radical prostatectomy (RARP) was performed in a collaborative effort among three surgeons in three separate locations employing telesurgery using the Kangduo Endosopic Surgical Robot (KD-SR-01, Sagebot Medical). The furthest distance between participants was approximately 2600km between Beijing and Hainan. We described and illustrated the applications and outcomes of this procedure to treat a single patient with prostate cancer. The local surgeon, along with the operating room team, and the patient were in Hainan, while the other two surgeons were in Beijing and Hunan Telesurgery command centers. The procedure lasted approximately 120min and there were no intra- or postoperative complications. Estimated blood loss was 100ml. The patient was ambulating 4h after surgery and remained in the hospital for 2days secondary to the postoperative care protocol followed by the local team taking care of the patient. The Foley catheter was removed on postoperative day 7 without complication. The final pathology was ISUP Grade Group 4 (Gleason score 4 + 4 = 8) T2cN0 with negative surgical margins. Our experience shows that telesurgery involving multiple surgeons at multiple remote locations is possible and can be completed safely with low-latency connections via available telecommunication networks.

The Role of Digital Rectal Examination for Early Detection of Significant Prostate Cancer in the Era of Magnetic Resonance Imaging

The role of digital rectal examination (DRE) in the early detection of significant prostate cancer (PCa) is being questioned in the era of magnetic resonance imaging (MRI). However, some men with suspected PCa may still be identified solely through DRE, even with low serum prostate-specific antigen (PSA) levels. Additionally, most predictive models designed to improve significant PCa diagnostic pathways incorporate DRE findings. We assessed the role of DRE among 5005 men with serum PSA levels > 3.0 ng/mL and/or suspicious DRE findings, who underwent pre-biopsy MRI and targeted and/or systematic biopsies, as part of the significant PCa opportunistic screening program in Catalonia (Spain) between 2016 and 2023. Significant PCa, defined as grade group > 2, was detected in 2097 men (41.9%). Suspicion of PCa was based solely on DRE in 206 cases (4.1%) with significant PCa detected in 50 of them (2.4%). Two pathways using the Barcelona predictive models, before and after MRI, with and without DRE findings showed specificities of 52.8 and 38.7%, respectively (p < 0.001), after fixing sensitivity at 90%. Prostate biopsy was avoided in 35.1 and 26.7%, respectively (p < 0.001), while its efficacy increased from 52.8 to 58%. We conclude that DRE improved the effectiveness of an opportunistic significant PCa-screening program.

Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: lessons from the French POLA cohort.

In POLA cohort, three pathological groups of CNS WHO grade 3 oligodendroglioma IDH-mutant and 1p/19q co-deleted have been described: group 1 (high mitotic count only), group 2 (microvascular proliferation MVP and no necrosis), and group 3 (MVP and necrosis). 494 patients from the POLA cohort, with a median follow up of 96 months were included. To identify the impact of the pathological groups and contrast enhancement in group 1 on overall survival (OS) or progression free survival (PFS), survival curves were obtained (Kaplan-Meier method) and compared (log-rank test). Prognostic value of clinical factors and CDKN2A homozygous deletion HD were also tested. Multivariate analysis was performed. Survival analysis demonstrated that the pathological groups were associated with both progression-free survival (PFS P=0.01) and overall survival (OS P=0.001). In group 1, patients with contrast enhancement (1CE+) had a poorer prognosis compared to those without (OS P=0.028, PFS P=0.006). Further stratification into group 1CE-, group 1CE+, group 2, and group 3 provided clearer prognostic distinctions (OS P=0.002, PFS P<0.0001). Other prognostic factors included age (OS P<0.0001, PFS P=0.002), extent of surgical resection (OS P=0.001, PFS P=0.003), KPS (OS P<0.0001, PFS P=0.002), postoperative treatment (OS P=0.007, PFS P<0.0001), and CDKN2A HD (OS and PFS P<0.0001). The pathological groups remained of prognostic significance for PFS in multivariate analysis. Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH mutant and 1p/19q co-deleted. Besides, in group 1 patients, lack of contrast enhancement is a factor of better prognosis.

Prospective evaluation of PI-RADSv2.1 using multiparametric and biparametric MRI for detecting clinically significant prostate cancer based on MRI/US fusion-guided biopsy.

To evaluate the cancer detection rates for each category of Prostate Imaging-Reporting and Data System version 2.1 (PI-RADSv2.1) using multiparametric magnetic resonance imaging (mpMRI) and biparametric MRI (bpMRI) based on MRI/ultrasound (US)-fusion biopsy. This prospective study included participants who underwent mpMRI or bpMRI with a PI-RADSv2.1 interpretation and subsequently received MRI/US-fusion biopsy between August 2022 and December 2023. The lesion-based detection rates of clinically significant prostate cancer (csPCa) in each PI-RADSv2.1 category and the correlation between PI-RADSv2.1 categories and International Society of Urological Pathology (ISUP) grade groups were analyzed. The diagnostic performance of PI-RADSv2.1 in predicting csPCa was evaluated, and diagnostic performance of mpMRI and bpMRI was compared using cut-offs, with PI-RADSv2.1 categories ≥ 3 or ≥ 4 defined as positive. A total of 247 lesions from 216 participants were included in this study. A total of 157 patients underwent mpMRI and the remaining 59 underwent bpMRI. The csPCa detection rates for each PI-RADSv2.1 category of mpMRI and bpMRI were as follows: category 1, 0% (0/11); 2, 13% (3/23); 3, 16% (5/31); 4, 60% (43/72); 5, 65% (26/40), in mpMRI; category 1, 0% (0/4); 2, 33% (1/3); 3, 25% (3/12); 4, 61% (19/31); 5, 75% (15/20) in bpMRI. PI-RADSv2.1 categories were significantly positively associated with csPCa detection rates in both mpMRI and bpMRI (p < 0.0001 and p = 0.00048, respectively). PI-RADSv2.1 categories correlated with ISUP grade groups for mpMRI and bpMRI (p < 0.0001 for both). There were no significant differences in the detection rates between mpMRI and bpMRI for PI-RADS v2.1 positive and negative lesions. PI-RADSv2.1 using mpMRI and bpMRI could stratify the risk of csPCa, and the csPCa detection rate of bpMRI was compatible with that of mpMRI using cut-offs of PI-RADSv2.1 categories ≥ 3 or ≥ 4.

The efficacy of wrapping with polyglycolic acid mesh and fibrin glue in preventing clinically relevant pancreatic fistula after minimally invasive distal pancreatectomy (WRAP Study): study protocol for a multicenter randomized controlled trial in Japan

BackgroundPostoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP.MethodsThis multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C).DiscussionThe WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety.Trial registrationThis trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors

Abstract Introduction/Objective Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality. Methods/Case Report 50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally. Results (if a Case Study enter NA) Grade Group 1 (Gleason score: 3 + 3): 2.35 percentage point increase in the risk of metastasis within 10 years. 3.51 percentage point increase in the risk of mortality within 15 years. Grade Group 2 Base level for comparison with other grade groups. Grade Group 3 (Gleason score: 4 + 3): No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2. Grade Group 4 (Gleason score: 4 + 4): 10.07 percentage point increase in the risk of metastasis within 5 years. 17.27 percentage point increase in the risk of metastasis within 10 years. 18.48 percentage point increase in the risk of mortality within 15 years. Conclusion The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality. However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.

2022 개정 특수교육 기본 교육과정 수학과 성취기준 분석: Bloom의 신교육목표분류학에 기초하여

Objectives This study aims to provide implications for the achievement standards of the basic curriculum for mathematics in the 2022 Revised Special Education Basic Curriculum by analyzing them based on Bloom's revised taxonomy of educational objectives. Methods To this end, a total of 182 mathematics achievement standards of the revised 2022 special education basic curriculum were analyzed for five grade groups and five mathematics areas based on Bloom's new taxonomy of educational objectives. Results First, the achievement standards for each grade were analyzed. As a result, among Bloom's knowledge dimensions in all grade groups, ‘factual knowledge’ was the highest with 104 (57.1%), and among the cognitive process dimensions, ‘Understanding’ was the highest with 89 (48.9%). A binary classification analysis of knowledge and cognitive process levels, the achievement standards for remembering factual knowledge were found in 55 achievement standards(30.2%). There were no achievement standards for ‘Meta-cognitive knowledge’, ‘Evaluation’, and ‘Create’. Second, as a result of analyzing the achievement standards by mathematics area, ‘Factual knowledge’ was the highest in the knowledge dimension with 45 achievement standards (48.9%) for numbers and operations, 28 (87.5%) for shapes, and 24 (92.2%) for measurement. ‘Conceptual knowledge’ was the highest with 12 (70.5%) in the regularity area and 9 (60%) in the data and probability area. In the cognitive process, ‘Remember’ was the highest with 29 (31.5%) in the number and calculation areas and 18 (56.3%) in the measurement areas was the highest with 17 achievement standards (65.3%), the regularity area with 7 achievement standards (41.1%), and the data and probability area with 9 achievement standards(60.0%). There were no achievement standards for ‘Meta-cognitive knowledge’, ‘Evaluation’, and ‘Create’. Conclusions Based on the results of this study, implications for the development of mathematics achievement standards of the basic curriculum for special education and suggestions for future research were made.

2022 개정 특수교육 기본교육과정 사회과 내 인권교육 관련 성취기준 분석

Objectives The purpose of this study is to analyze the social studies achievement standards of the 2022 revised basic curriculum of special education by content elements of human rights education to check the current status of each school level and human rights education area, and to suggest the direction of human rights education in special education. Methods In this study, the social studies achievement standards of the 2022 special education basic curriculum were analyzed using the analysis framework of previous studies related to human rights education. In addition, in order to confirm the reliability and validity of the analysis results, the reliability between analysts and the validity of the expert content were implemented. Results Elementary school showed the highest frequency, and middle and high school showed the highest frequency of I. respect for human rights in the major area, and I-3. Human rights values and attitudes in the sub-area showed a very high percentage. The analysis results of human rights education by grade group showed that in all grade groups, I. respect for human rights showed the highest frequency, and in the sub-area, I-3. Human rights values and attitudes and II-1. Freedom rights showed the highest frequency, while middle and high school levels showed the highest frequency of human rights values and attitudes. Conclusions The conclusions according to the analysis contents are as follows. First, special teachers need to construct a holistic human rights education through curriculum restructuring. Second, the content elements of human rights education need to be sequenced and connected by grade group of the curriculum.

Using a novel PSMA-PET and PSA-based model to enhance the diagnostic accuracy for clinically significant prostate cancer and avoid unnecessary biopsy in men with PI-RADS ≤ 3 MRI.

The diagnostic evaluation of men with suspected prostate cancer (PCa) yet inconclusive MRI (PI-RADS ≤ 3) presents a common clinical challenge. [68Ga]Ga-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has shown promise in identifying clinically significant PCa (csPCa). We aim to establish a diagnostic model incorporating PSMA-PET to enhance the diagnostic process of csPCa in PI-RADS ≤ 3 men. This study retrospective included 151 men with clinical suspicion of PCa and PI-RADS ≤ 3 MRI. All men underwent [68Ga]Ga-PSMA PET/CT scans and ultrasound/MRI/PET fusion-guided biopsies. csPCa was defined as Grade Group ≥ 2. PRIMARY-scores from PSMA-PET scans were evaluated. A diagnostic model incorporating PSMA-PET and prostate-specific antigen (PSA)-derived parameters was developed. The discriminative performance and clinical utility were compared with conventional methods. Internal validation was conducted using a fivefold cross-validation with 1000 iterations. In this PI-RADS ≤ 3 cohort, areas-under-the-curve (AUCs) for detecting csPCa were 0.796 (95%CI, 0.738-0.853), 0.851 (95%CI, 0.783-0.918) and 0.806 (95%CI, 0.742-0.870) for PRIMARY-score, SUVmax and routine clinical PSMA-PET assessment, respectively. The diagnostic model comprising PRIMARY-score, SUVmax and serum free PSA/total PSA (fPSA/tPSA) achieved a significantly higher AUC of 0.906 (95%CI, 0.851-0.961) compared to strategies based on PRIMARY-score or SUVmax (P < 0.05) and markedly superior to conventional strategies typically based on PSA density (P < 0.001). The average fivefold cross-validated AUC with 1000 iterations was 0.878 (95%CI, 0.820-0.954). Theoretically, using a threshold of 21.6%, the model could have prevented 78% of unnecessary biopsies while missing only 7.8% of csPCa cases in this cohort. A novel diagnostic model incorporating PSMA-PET derived metrics-PRIMARY-score and SUVmax-along with serum fPSA/tPSA, has been developed and validated. The integrated model may assist clinical decision-making with enhanced diagnostic accuracy over the individual conventional metrics. It has great potential to reduce unnecessary biopsies for men with PI-RADS ≤ 3 MRI results and warrants further prospective and external evaluations.

Solitary Loss of PMS2 in a patient with Colon carcinoma

Abstract Introduction/Objective In the United States, there are about 150,000 new cases of Colorectal cancer (CRC) and about 50,000 CRC related deaths each year. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) accounts for 2% - 4% of CRC. It is characterized by germline mutations in mismatch repair (MMR) genes - MLH1, MSH2, MSH6 and PMS2. Patients with Lynch syndrome have up to an 80% lifetime risk (LTR) of CRC and up to 60% LTR of endometrial cancer. Lynch syndrome patients also have an associated LTR of ovarian cancer (38%), upper urologic tract cancer (18%), gastric cancer (13%), small bowel cancer (6%), hepatobiliary tract cancer (4%), and brain tumors (3% - usually glioblastoma). Methods/Case Report A 76-year-old man with history of moderately differentiated colorectal adenosarcoma involving the transverse colon and a recently diagnosed grade group 5 (Gleason 4 + 5) prostate adenocarcinoma, currently being managed at an outside hospital. The case was sent to UAB for DNA MMR/microsatellite instability (MSI) status evaluation testing. Immunostaining showed loss of PMS2 and intact expression of MLH1, MSH2 and MSH6. These results were confirmed by the IdyIIa MSI assay which detected microsatellite instability in 5 of 7 markers and negative for BRAF V600E variant confirming microsatellite instable tumor. Results (if a Case Study enter NA) NA Conclusion Solitary loss of PMS2 in colonic adenocarcinoma is uncommon and may be caused by an underlying germline mutation of MLH-1 or PMS2, thus could represent Lynch Syndrome. Our patient’s age doesn’t favor Lynch syndrome. Next step would be to perform MLH-1 promoter methylation to confirm sporadic nature of carcinoma. Somatic methylation of the MLH1 promoter occurs in approximately 80% of CRC with defective MMR. Prostate cancer is not currently considered a part of Lynch syndrome.

Association between beta‐blocker atenolol use and prostate cancer upgrading in active surveillance1

AbstractObjectivesThe objective of this study is to investigate the association between the use of beta‐adrenergic antagonist atenolol and risk of pathologic upgrade in patients on active surveillance, considering growing literature implicating adrenergic innervation with disease progression mediated through beta‐adrenergic signalling.Patients and MethodsMen with low‐risk or favourable intermediate‐risk prostate cancer who were placed on an active surveillance protocol between 2006 and 2020 across three diverse urban hospitals were included. Exposure was duration of atenolol use, and outcome was pathologic grade group upgrading (to GG ≥ 3) on final prostate biopsy. Cox proportional hazard regression models were used to determine the associations between atenolol use and risk of upgrading with time, on a per‐examination basis.ResultsA total of 467 men with initial GG ≤ 2 were included. Postdiagnosis atenolol use was associated with a decreased risk of pathologic upgrade to GG ≥ 3 on final repeat biopsy (HR 0.81, 95% CI 0.39–0.98). Longer duration of postdiagnosis atenolol use (&gt;2 years) and greater cumulative atenolol dose (&gt;730 defined daily doses) were associated with a more pronounced decreased risk of upgrade to GG ≥ 3 (HR 0.41, 95% CI 0.05–0.88, and HR 0.32, 95% CI 0.15–0.99, respectively). Initiation of atenolol use prior to prostate cancer diagnosis had a slightly greater protective effect than drug initiation postdiagnosis (HR 0.79, 95% CI 0.43–0.98, and HR 0.83, 95% CI 0.30–0.99, respectively).ConclusionsBeta‐adrenergic blockade with atenolol use in men on active surveillance is associated with a reduced risk for clinically significant grade group pathologic upgrade.