Percutaneous kidney biopsies in children: a 24-year review in a tertiary center in northern Portugal / Biópsias renais percutâneas em crianças: uma revisão de 24 anos em um centro terciário no norte de Portugal

Introduction: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. Methods: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). Results: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. Conclusions: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.

RESUMO Introdução: A biópsia renal (BR) percutânea é fundamental para diagnóstico e manejo de diversas patologias renais. Dados nacionais sobre BR nativa em pacientes pediátricos são escassos. Nosso objetivo foi revisar características demográficas, clínicas e padrões histopatológicos em crianças submetidas a BR percutânea nativa ao longo de 24 anos. Métodos: Estudo observacional retrospectivo de pacientes submetidos a BR percutâneas nativas em unidade de nefrologia pediátrica entre 1998 e 2021, comparando três períodos: período 1 (1998-2005), período 2 (2006-2013), período 3 (2014-2021). Resultados: Constatamos que foram realizadas 228 BR, 78 (34,2%) no período 1, 91 (39,9%) no período 2, 59 (25,9%) no período 3. A idade mediana na BR foi 11 (7-14) anos. As principais indicações para BR foram síndrome nefrótica (SN) (42,9%), hematúria e/ou proteinúria não nefrótica (35,5%), lesão renal aguda (13,2%). Glomerulopatias primárias foram mais frequentes (67,1%), principalmente doença de lesão mínima (DLM) (25,4%), nefropatia por IgA (12,7%), glomerulonefrite mesangioproliferativa (GN) (8,8%). Das glomerulopatias secundárias, nefrite lúpica (NL) foi a mais prevalente (11,8%). No grupo 1, hematúria e/ou a proteinúria não nefrótica foram os principais motivos para BR, ao contrário da SN nos grupos 2 e 3 (p < 0,01). A NL apresentou tendência crescente (período 1-3: 2,6%-5,3%) e a glomeruloesclerose segmentar focal (GESF) apresentou leve tendência decrescente (período 1-3: 3,1%-1,8%), sem significância estatística. Conclusões: A principal indicação para BR foi SN, que aumentou ao longo do tempo, justificando o achado de DLM como principal diagnóstico histológico. A NL apresentou aumento na incidência ao longo do tempo, enquanto os casos de GESF não aumentaram.

To scan or not to scan? A retrospective cohort study analysing the efficacy of routine post-operative CT after brain biopsy.

PURPOSE: Postoperative management following elective cranial surgery, particularly after biopsy procedures, varies significantly across neurosurgical centres. Routine postoperative head CT scans, traditionally performed to detect complications such as intracranial bleeding or cerebral oedema, lack substantial evidence supporting their necessity. METHODS: This study is a retrospective cohort analysis conducted at a regional neurosurgical department of 236 patients who underwent brain biopsies between 2018 and 2022. Patient data, including demographics, surgical details, and postoperative outcomes, were collected and analysed. The outcomes investigated were the incidence and impact of postoperative CT scans on time to discharge, management changes, and the influence of preoperative anticoagulation. RESULTS: Out of 236 patients, 205 (86.86%) underwent postoperative CT scans. There was no significant relationship between postoperative hematoma, as detected on a CT scan, and neurological deficit (p = 0.443), or between preoperative anticoagulation and postoperative bleeding on CT scans (p = 0.464). Patients who had postoperative CT scans had a significantly longer length of stay (LOS) compared to those who did not (p < 0.001). Intraoperative bleeding was a predictor of hematoma on postoperative CT (p = 0.017) but not of postoperative neurological deficit. The routine postoperative CT scan showed limited predictive value for symptomatic deficits, with a positive predictive value of 6.67% and a negative predictive value of 96.88%. CONCLUSIONS: Routine postoperative CT scans after brain biopsies do not significantly impact management or improve patient outcomes but are associated with longer hospital stays. CT scans should be reserved for patients showing clinical signs of complications rather than used as a routine procedure after a brain biopsy.

Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

PURPOSE: To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. METHODS: This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. RESULTS: This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9 years and age range = 22-61 years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5 ml/min and normal graft was 64 ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. CONCLUSION: IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Targeted biopsy of the prostate.

Diagnostic multiparametric MRI of the prostate has steadily evolved over the last three decades and can now reliably depict the dominant tumor in most men with prostate cancer. In response, several methods of targeted biopsy to direct tissue sampling of suspected tumor foci seen at multiparametric MRI have been developed and successfully tested in recent years, including software-assisted MRI-ultrasound (US) fusion biopsy and direct MRI-guided in-bore biopsy. These advances are leading to a sea change in the approach to prostate cancer diagnosis, with the traditional approach of blind systematic biopsy increasingly being replaced by MRI directed targeted biopsy. This review aims to describe the current status of targeted biopsy, with an emphasis on the relative accuracy of different techniques. The results of several critical large multicenter trials are presented, while unanswered questions that require more research are highlighted.

Novel liquid biopsy CNV biomarkers in malignant melanoma.

Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.

Safety and efficacy of tract embolization using gelatin sponge particles in reducing pneumothorax after CT-guided percutaneous lung biopsy in patients with emphysema.

BACKGROUND: The incidence of pneumothorax is higher in patients with emphysema who undergo percutaneous lung biopsy. Needle embolization has been shown to reduce the incidence of pneumothorax in patients with emphysema. Existing studies have reported small sample sizes of patients with emphysema, or the degree of emphysema has not been graded. Therefore, the efficacy of biopsy embolization in the prevention of pneumothorax induced by percutaneous pulmonary biopsy in patients with emphysema remains to be determined. METHODS: In this retrospective, controlled study, patients with emphysema who underwent CT-guided PTLB were divided into two groups: group A (n = 523), without tract embolization, and Group B (n = 504), with tract embolization. Clinical and imaging features were collected from electronic medical records and Picture Archiving and Communication Systems. Univariate and multivariate analyses were performed to identify risk factors for pneumothorax and chest tube placement. RESULTS: The two groups did not differ significantly in terms of demographic characteristics and complications other than pneumothorax. The incidence of pneumothorax and chest tube placement in group B was significantly lower than in group A (20.36% vs. 46.12%, p < 0.001; 3.95% vs. 9.18%, p < 0.001, respectively). In logistic regression analyses, variables affecting the incidence of pneumothorax and chest tube placement were the length of puncture of the lung parenchyma (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.30, p = 0.001; OR = 1.55, 95% CI: 1.30-1.85, p < 0.001, respectively), tract embolization (OR = 0.31, 95% CI: 0.24-0.41, p < 0.001; OR = 0.39, 95% CI: 0.22-0.69, p = 0.001, respectively), and grade of emphysema. CONCLUSIONS: Tract embolization with gelatin sponge particles after CT-guided PTLB significantly reduced the incidence of pneumothorax and chest tube placement in patients with emphysema. Tract embolization, length of puncture of the lung parenchyma, and grade of emphysema were independent risk factors for pneumothorax and chest tube placement. TRIAL REGISTRATION: Retrospectively registered.

Diagnostic utility of adding needle aspiration (using PeriView FLEX needle) to radial endobronchial ultrasound guide sheath transbronchial lung biopsy: a single center retrospective study.

Background: Radial endobronchial ultrasound (rEBUS) guide sheath (GS) transbronchial lung biopsy (TBLB) improves the diagnostic yield of peripheral lung lesions (PLL). However, its diagnostic yield is approximately 60%. We aimed to evaluate the diagnostic utility of adding rEBUS GS transbronchial needle aspiration (TBNA) using PeriView FLEX needle (Olympus, Tokyo, Japan) to rEBUS GS TBLB. Methods: In this retrospective study, we initially screened 124 PLLs in 123 patients who underwent rEBUS GS procedures for PLLs from December 2020 to August 2021. The analysis was performed on 74 PLLs in 73 patients who underwent both rEBUS GS TBLB and TBNA. Results: PLLs showed the following characteristics: lesion size [mean ± standard deviation (SD)], 24±12 mm; nature (solid vs. subsolid), 59 (79.7%) vs. 15 (20.3%); distance from the pleura (mean ± SD), 14±14 mm; rEBUS visualization type (probe within PLL vs. probe adjacent to PLL), 56 (75.7%) vs. 18 (24.3%). Among 74 PLLs, 47 (63.5%) were successfully diagnosed by rEBUS GS TBLB. In 27 PLLs not diagnosed by rEBUS GS TBLB, 5 (18.5%) were further diagnosed by rEBUS GS TBNA [overall diagnostic yield: 70.3% (52/74)]. EBUS visualization type of "probe adjacent to PLL" was a significant factor associated with the diagnostic yield of additional rEBUS GS TBNA. Conclusions: In rEBUS GS procedures for PLLs, the diagnostic yield might be improved by implementing TBNA in addition to TBLB. In particular, additional TBNA is preferable if the probe is adjacent to the lesion rather than within the lesion on rEBUS.

Long-term clinicopathological characteristics of TAFRO syndrome and its relapse: a case series study.

Introduction: This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission. Methods: This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization. Results: Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment. Conclusions: This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors.

Revisiting the standards of cancer detection and therapy alongside their comparison to modern methods.

In accordance with the World Health Organization data, cancer remains at the forefront of fatal diseases. An upward trend in cancer incidence and mortality has been observed globally, emphasizing that efforts in developing detection and treatment methods should continue. The diagnostic path typically begins with learning the medical history of a patient; this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy. Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization. Thus, there is a need for novel cancer detection methods such as liquid biopsy, elastography, synthetic biosensors, fluorescence imaging, and reflectance confocal microscopy. Conventional therapeutic methods, although still common in clinical practice, pose many limitations and are unsatisfactory. Nowadays, there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy, exosome-based therapy, nanotechnology, dendritic cells, chimeric antigen receptors, immune checkpoint inhibitors, natural product-based therapy, tumor-treating fields, and photodynamic therapy. The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions. As evidenced, modern methods are not without drawbacks; there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity, specificity, safety, and efficacy. Nevertheless, an appropriate route has been taken, as confirmed by the approval of some modern methods by the Food and Drug Administration.

Colorectal cancer screening: Modalities and adherence.

In the last decade, several studies have explored various modalities and strategies for colorectal cancer (CRC) screening, taking into account epidemiological data, individual characteristics, and socioeconomic factors. In this editorial, we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology. Our focus is on screening trends, particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide, aiming to enhance early diagnosis rates of CRC. There is a need to raise awareness through health edu-cation programs and to consider the use of readily available, non-invasive screening methods. These strategies are crucial for attracting screen-eligible populations to participate in first-line screening, especially those in high- or average-risk groups and in regions with limited resources. Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis; however, their clinical relevance has yet to be standardized.

A Young Female with a Hepatic Epithelioid Hemangioendothelioma.

Background: Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumour of vascular origin with an incidence of <0.1 cases per 100,000 people worldwide. Case description: A 29-year-old female with the history of epigastric pain and unintentional weight loss (3 kg over six months) was referred for upper endoscopy. The examination was without visual pathological findings, but a rapid urease test was positive. First-line treatment with clarithromycin-containing triple therapy for Helicobacter pylori infection was given. After completion of eradication therapy, diffuse abdominal pain developed. An abdominal computed tomography (CT) showed multiple liver nodules. Three consecutive core liver biopsies were performed and were inconclusive. A subsequent surgical liver nodule resection was performed. Histopathology of the specimen revealed grade 2 hepatocellular carcinoma; bone scintigraphy was negative for metastasis. A multidisciplinary team (MDT) recommended giving the patient sorafenib, which was poorly tolerated. The histology was reviewed using immunohistochemistry staining at the request of the oncologist, which showed expression of CD31 and CD34. Based on clinical, morphological and immunohistochemistry findings, a diagnosis of hepatic epithelioid hemangioendothelioma was made. Based on the multidisciplinary team's findings, liver transplantation was indicated as the only curative treatment. Conclusion: Because of the rarity of this disease, combining clinical, radiological and histopathological methods as well as an MDT approach can help to reach the correct final diagnosis. As demonstrated in this clinical case, it is crucial to perform immunohistochemistry of a liver biopsy to confirm a HEHE diagnosis. LEARNING POINTS: Hepatic epithelioid hemangioendothelioma is a rare vascular tumour that is often misdiagnosed and mismanaged.This case emphasises the critical importance of interdisciplinary teamwork and the use of non-invasive and invasive techniques to achieve a definitive diagnosis.

Actinic Granuloma Complicated by Secondary Syphilis: A Case Report.

Introduction: Actinic granuloma (AG) is a rare skin eruption thought to result from a sun-induced inflammatory response attracting giant cells, which are large, multinucleated, and inflammatory, to form granulomas and degrade surrounding elastic material. Clinically, lesions begin on sun-exposed skin as pink papules and nodules that coalesce into demarcated annular plaques with a hypopigmented center. Histologically, actinic elastosis surrounds the outer annulus ring, with histiocytes and giant cells within the raised border, and the innermost central zone is filled with minimal to absent elastic fibers. Case Presentation: We present a middle-aged female with a pruritic eruption of diffuse erythematous macules and papules coalescing into plaques with mild scale involving the scalp, face, neck, torso, and upper and lower extremities, including the palms and soles, but sparing the ears, bilateral axillae, elbows, and knees. Skin biopsies revealed solar elastosis and abundant multinucleated foreign body giant cells with ingested elastic fibers. The patient's clinical presentation and histopathology were consistent with a diagnosis of AG. Furthermore, spirochete immunostaining of the specimens revealed multiple Treponema pallidum spirochetes throughout the epidermis and dermis. Secondary syphilis with primary chancre was added to the diagnosis. Treatment included oral and topical steroids followed by intravenous penicillin G. After 1 month, all lesions had resolved with post-inflammatory erythema. Conclusion: Our patient differs from the typical presentation in describing intense pruritus with her eruption. This interesting collision reminds clinicians to retain a high index of suspicion for multiple diagnoses in a single patient.

Enhancing prostate cancer diagnosis and reducing unnecessary biopsies with [18F]DCFPyL PET/CT imaging in PI-RADS 3/4 patients.

For patients presenting with prostate imaging reporting and data system (PI-RADS) 3/4 findings on magnetic resonance imaging (MRI) examinations, the standard recommendation typically involves undergoing a biopsy for pathological assessment to ascertain the nature of the lesion. This course of action, though essential for accurate diagnosis, invariably amplifies the psychological distress experienced by patients and introduces a host of potential complications associated with the biopsy procedure. However, [18F]DCFPyL PET/CT imaging emerges as a promising alternative, demonstrating considerable diagnostic efficacy in discerning benign prostate lesions from malignant ones. This study aims to explore the diagnostic value of [18F]DCFPyL PET/CT imaging for prostate cancer in patients with PI-RADS 3/4 lesions, assisting in clinical decision-making to avoid unnecessary biopsies. 30 patients diagnosed with PI-RADS 3/4 lesions through mpMRI underwent [18F]DCFPyL PET/CT imaging, with final biopsy pathology results as the "reference standard". Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, evaluating the diagnostic efficacy of molecular imaging PSMA (miPSMA) visual analysis and semi-quantitative analysis in [18F]DCFPyL PET/CT imaging. Lesions were assigned miPSMA scores according to the prostate cancer molecular imaging standardized evaluation criteria. Among the 30 patients, 13 were pathologically confirmed to have prostate cancer. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis in [18F]DCFPyL PET/CT imaging for diagnosing PI-RADS 3/4 lesions were 61.5%, 88.2%, 80.0%, 75.0%, and 76.5%, respectively. Using SUVmax 4.17 as the optimal threshold, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis were 92.3%, 88.2%, 85.7%, 93.8%, and 90.0%, respectively. The area under the ROC curve (AUC) for semi-quantitative analysis was 0.94, significantly higher than visual analysis at 0.80. [18F]DCFPyL PET/CT imaging accurately diagnosed benign lesions in 15 (50%) of the PI-RADS 3/4 patients. For patients with PI-RADS 4 lesions, the positive predictive value of [18F]DCFPyL PET/CT imaging reached 100%. [18F]DCFPyL PET/CT imaging provides potential preoperative prediction of lesion nature in mpMRI PI-RADS 3/4 patients, which may aid in treatment decision-making and reducing unnecessary biopsies.

Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid.

Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Effect of freeze-thawing, cell collection, and laser irradiation cycles on mosaicism occurrence in preimplantation genetic testing for aneuploidy.

OBJECTIVE: In preimplantation genetic testing for aneuploidy, opinions regarding the handling of mosaic embryos vary. In this study, we aimed to investigate the effects of freeze-thawing, the number of cells obtained, and the number of laser irradiation cycles on the degree of embryonic mosaicism. STUDY DESIGN: This study was conducted in three parts. First, we classified specimens into the normal biopsy (control) (119 patients, 304 blastocysts) and thawed-biopsy (TB group) (26 patients, 72 blastocysts)) groups. The control and TB groups were then classified into three categories (euploidy, mosaic and aneuploidy) according to next-generation sequencing (NGS) results, and the number of cells collected and laser irradiation cycles were compared for each category. Subsequently, the effects of differences in the number of cells collected and laser irradiation cycles on NGS results were investigated in the control and TB groups. Finally, data on cell collection and laser irradiation cycles and NGS analysis results for the groups were compared. RESULTS: The TB group had a significantly higher incidence of chromosomal mosaicism than the control group. Neither the number of cells collected nor the laser irradiation cycles affected the percentage of chromosomal mosaicism. However, the freeze-thaw process increased the occurrence of mosaicism. CONCLUSIONS: This study showed that repeated freeze-thaw cycles increase the incidence of mosaicism, but the embryos are not aneuploid and are therefore suitable for transfer.

Additional yield of random biopsy in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: There is limited clinical data regarding the additional yields of random biopsies during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for IBD patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis, and 16.20% in per-lesion analysis. The detection rate were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full HD equipment should consider incorporating RB in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.

Assessing the Correlation between Allostatic Load and False-Positive Image-Guided Breast Biopsies.

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Any advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer. METHODS: A combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed. RESULTS: Overall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046). CONCLUSIONS: TAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Repeat Prostate-specific Antigen Testing Improves Risk-based Selection of Men for Prostate Biopsy After Magnetic Resonance Imaging.

Background and objective: The aim of our study was to investigate whether repeat prostate-specific antigen (PSA) testing as currently recommended improves risk stratification for men undergoing magnetic resonance imaging (MRI) and targeted biopsy for suspected prostate cancer (PCa). Methods: Consecutive men undergoing MRI and prostate biopsy who had at least two PSA tests before prostate biopsy were retrospectively registered and assigned to a development cohort (n = 427) or a validation (n = 174) cohort. Change in PSA level was assessed as a predictor of clinically significant PCa (csPCa; Gleason score ≥3 + 4, grade group ≥2) by multivariable logistic regression analysis. We developed a multivariable prediction model (MRI-RC) and a dichotomous biopsy decision strategy incorporating the PSA change. The performance of the MRI-RC model and dichotomous decision strategy was assessed in the validation cohort and compared to prediction models and decision strategies not including PSA change in terms of discriminative ability and decision curve analysis. Results: Men who had a decrease on repeat PSA testing had significantly lower risk of csPCa than men without a decrease (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.16-0.54; p < 0.001). Men with an increased repeat PSA had a significantly higher risk of csPCa than men without an increase (OR 2.97, 95% CI 1.62-5.45; p < 0.001). Risk stratification using both the MRI-RC model and the dichotomous decision strategy was improved by incorporating change in PSA as a parameter. Conclusions and clinical implications: Repeat PSA testing gives predictive information regarding men undergoing MRI and targeted prostate biopsy. Inclusion of PSA change as a parameter in an MRI-RC model and a dichotomous biopsy decision strategy improves their predictive performance and clinical utility without requiring additional investigations. Patient summary: For men with a suspicion of prostate cancer, repeat PSA (prostate-specific antigen) testing after an MRI (magnetic resonance imaging) scan can help in identifying patients who can safely avoid prostate biopsy.