Benign Disease Research Articles

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

ObjectiveElucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.DesignWe performed single-cell transcriptome analysis on 230...

Risk factors for postoperative urinary retention in patients underwent surgery for benign anorectal diseases: a nested case–control study

BackgroundPostoperative urinary retention (POUR) is a common complication of anorectal surgery. This study was to determine the incidence of POUR in anorectal surgery for benign anorectal diseases, identify its risk factors, and establish a nomogram for prediction of POUR.MethodsA nested case–control study was conducted. The clinical data of patients were collected, and the incidence of POUR was analyzed. Univariate analysis was used to identify the risk factors associated with POUR, and multivariate logistic regression analysis was used to determine independent risk factors for POUR. A nomogram for the preoperative prediction of POUR using a logistic regression model was developed (n = 609).ResultsThe incidence of POUR after anorectal surgery for benign anorectal diseases was 19.05%. The independent risk factors for POUR were: female (P = 0.007); male with benign prostatic hyperplasia (BPH) (P = 0.001); postoperative visual analogue scale (VAS) score > 6 (P = 0.002); patient-controlled epidural analgesia (PCEA) (P = 0.016); and a surgery time > 30 min (P = 0.039). In the nomogram, BPH is the most important factor affecting the occurrence of POUR, followed by a postoperative VAS score > 6, PCEA, surgery time > 30 min, and sex has the least influence.ConclusionFor patients undergoing anorectal surgery for benign anorectal diseases, preventive measures can be taken to reduce the risk of POUR, taking into account the following risk factors: female or male with BPH, severe postoperative pain, PCEA, and surgery time > 30 min. Furthermore, we developed and validated an easy-to-use nomogram for preoperative prediction of POUR in anorectal surgery for benign anorectal diseases.Trial registrationChina Clinical Trial Registry: ChiCTR2000039684, 05/11/2020.

Effect of A118G (rs1799971) single-nucleotide polymorphism of the μ-opioid receptor OPRM1 gene on intraoperative remifentanil requirements in Japanese women undergoing laparoscopic gynecological surgery.

Abundant data are available on the effect of the A118G (rs1799971) single-nucleotide polymorphism (SNP) of the μ-opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements. We investigated 333 Japanese women, aged 21-69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann-Whitney U test. The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039). The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.

Brief Pain Inventory (BPI) Pain Survey Versus Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs). Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively. Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa. This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction.

Cost-effectiveness and safety of mediastinal transbronchial cryobiopsy guided by endobronchial ultrasonography (CRYO-EBUS) in 110 cases

IntroductionTransbronchial needle aspiration guided by endobronchial ultrasonography (EBUSTBNA) has the disadvantage of sometimes offering samples of an unsuitable size for an accurate histo-molecular diagnosis. Transbronchial mediastinal cryobiopsy (CRYOEBUS) is a very novel and additional technique to EBUS-TBNA that allows us to obtain larger and quality samples, improving diagnostic performance. Material and methodsDescriptive study of 110 patients with lesions and/or mediastinal lymphadenopathy who underwent EBUS-TBNA and CRYO-EBUS in a single procedure. Our objective was to analyze the diagnostic profitability and safety of the technique. ResultsCRYO-EBUS obtained samples of 0.42 cm on average compared to 0.14 cm obtained by EBUS-TBNA. The overall diagnostic performance of the techniques was 60% for EBUS-TBNA and 94.5% for CRYO-EBUS. Furthermore, the latter was more sensitive for the diagnosis of both malignant and benign diseases. With a very high security profile. ConclusionsThe CRYO-EBUS technique is cost-effective and safe, and is superior to EBUS-TBNA. Future studies may confirm our findings.

Development of a fit-for-purpose multi-marker panel for early diagnosis of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

The Application of Artificial Intelligence in Thyroid Nodules: A Systematic Review Based on Bibliometric Analysis.

Thyroid nodules are common lesions in benign and malignant thyroid diseases. More and more studies have been conducted on the feasibility of artificial intelligence (AI) in the detection, diagnosis, and evaluation of thyroid nodules. The aim of this study was to use bibliometric methods to analyze and predict the hot spots and frontiers of AI in thyroid nodules. Articles on the application of artificial intelligence in thyroid nodules were retrieved from the Web of Science core collection database. A website (https://bibliometric.com/), VOSviewer and CiteSpace software were used for bibliometric analyses. The collaboration maps of countries and institutions were analyzed. The cluster and timeline view based on cocitation references and keywords citation bursts visualization map were generated. The study included 601 papers about AI in thyroid nodules. China contributed to more than half (52.41%) of these publications. The cluster view and timeline view of co-citation references were assembled into 9 clusters, "AI", "deep learning", "papillary thyroid carcinoma", "radiomics", "ultrasound image", "biomarkers", "medical image segmentation", "central lymph node metastasis (CLNM)", and "self-organizing auto-encoder". The "AI", "radiomics", "medical image segmentation", "deep learning," and "CLNM", emerging in the last 10 years and continuing until recent years, were included. An increasing number of scholars were devoted to this field. The potential future research hotspots include risk factor assessment and CLNM prediction of thyroid carcinoma based on radiomics and deep learning, automatic segmentation based on medical images (especially ultrasound images).

Effect of laparoscopic cholecystectomy on 25-hydroxyvitamin D levels and bone mineral density in post menopausal women

Background Laparoscopic cholecystectomy (LC) is the gold standard management for benign gallbladder diseases. It has been observed that there is alteration in vitamin D levels and bone mineral density after cholecystectomy due to altered enterohepatic circulation. With increase in average age expectancy of the population, low levels of vitamin D levels and osteoporosis after cholecystectomies might cause increased health care burden. Methods A prospective observational study was planned between 1 January 2022 and 30 June 2023 in the Department of General Surgery at PGIMER Chandigarh, a tertiary care hospital in north India. One hundred and three post-menopausal women who underwent LC and met the inclusion and exclusion criteria were included in the study. All participants underwent estimation of vitamin D and bone mineral density preoperatively and third-post operative month (POM). Results The mean age of the patients was 58.46 ± 7.44. Pain abdomen was present in 68(66%) patients, 18 had epigastric discomfort and 17 had dyspepsia. The mean levels of vitamin D decreased from 21.92 at the baseline to 20.12 at third POM (p < .001). There was a significant change in t score Femoral Neck (−1.12 vs −1.15, p < .001) and Lumbar spine L1–L4 − 1.98 vs −1.98 (p = .033). z-scores of the femoral neck were −0.34 vs −0.54 (p < .001) and of lumbar spine L1–L4 were −0.95 vs 1.02 (p < .001). The decrease in fracture risk for the femoral neck (p = .344) and the lumbar spine (p = .223) was not statistically significant. Conclusion There is a significant decrease in vitamin D and BMD levels after LC in post-menopausal females.

Circulating adipose-tissue miRNAs in gastrointestinal cancer patients and their association with the level and type of adiposity at body composition analysis

BackgroundAdipose tissue (AT) wasting in cancer is an early catabolic event with negative impact on outcomes. Circulating miRNAs may promote body weight loss and cachexia. We measured circulating miRNAs linked to AT alterations and compared their levels between i) gastrointestinal (GI) cancer patients and controls, ii) cachectic and non-cachectic cancer patients, and iii) according to adiposity level and its distribution.MethodsPatients with GI cancer and subjects with benign diseases as controls were considered. Cachexia was assessed and adiposity evaluated by CT-scan for subcutaneous AT area (SAT), visceral AT area and the total AT area (TAT). MiRNAs involved were measured in plasma by RT-qPCR.Results37 naïve GI cancer patients and 14 controls were enrolled. Patients with cachexia presented with lower SAT compared to non-cachectic (p &amp;lt; 0.05). In cancer patients, we found higher levels of miR-26a, miR-128, miR-155 and miR-181a vs. controls (p &amp;lt; 0.05). Cancer patients with BMI &lt; 25 kg/m2 showed higher levels of miR-26a vs. those with BMI ≥ 25 (p = 0.035). MiR-26a and miR-181a were higher in cachectic and non-cachectic vs. controls (p &amp;lt; 0.05). Differences between cachectic and controls were confirmed for miR-155 (p &amp;lt; 0.001) but not between non-cachectic vs. control (p = 0.072). MiR-155 was higher in cachectic patients with low TAT vs. those without cachexia and high TAT (p = 0.036).ConclusionOur data confirm a modulation of specific and different miRNAs involved in AT metabolism in cancer and cachexia. MiR-155 levels were higher in patients presenting with cachexia and low adiposity with implications in the pathogenic mechanisms and clinical consequences of GI cancer patients.

Invasive group A Streptococcus infection (Streptococcus pyogenes): Current situation in Spain.

Group A ß-hemolytic Streptococcus (S. pyogenes), also known as GAS, is a Gram-positive bacterium. It can be easily identified in the microbiology laboratory by its ability to hemolyse blood in culture media. This bacterium is highly virulent due to its production of enzymes and toxins, and its ability to cause immunologically mediated diseases such as rheumatic fever and post-streptococcal glomerulonephritis. GAS is the primary cause of bacterial pharyngotonsillitis, although it is typically a benign and non-invasive disease. However, it also has the potential to cause severe skin and soft tissue infections, necrotising fasciitis, bacteraemia and endocarditis, pneumonia and empyema, and streptococcal toxic shock syndrome, without any age or predisposition limits. The term invasive GAS disease (iGAS) is used to refer to this group of conditions. In more developed countries, iGAS disease has declined thanks to improved hygiene and the availability of antibiotics. For example, rheumatic fever has practically disappeared in countries such as Spain. However, recent data suggests a potential increase in some iGAS diseases, although the accuracy of this data is not consistent. Because of this, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has posed several questions about invasive GAS infection, especially its current situation in Spain. The committee has enlisted the help of several experts in the field to answer these questions. The following lines contain the answers that we have collaboratively produced, aiming to assist not only the members of ICOMEM but also anyone interested in this topic.

Clinical effectiveness of transaxillary single-port endoscopic surgery in the treatment of breast benign tumor.

Benign breast lumps affect 10% of women in their lifetimes. Endoscopic surgery could be an alternative surgical technique for benign breast tumors because it is performed through small wounds hidden in inconspicuous areas. The aim of this study was to explore the safety and esthetic effects of endoscopic surgery in the treatment of benign breast disease. This retrospective cohort study analyzed 363 patients with benign breast tumors from August 2021 to December 2023 in the Sixth Affiliated Hospital of Sun Yat-Sen University, of whom 118 underwent transaxillary single-port endoscopic surgery and 245 underwent traditional open surgery. Clinicopathologic characteristics, surgery type, hospital stay, and complications were analyzed to assess the effectiveness of the procedure for benign breast tumors. Breast tumor resection was successfully performed in 363 patients by endoscopic surgery or traditional open surgery. Endoscopic procedures demonstrated longer durations of surgery (98.54±35.17min vs. 70.28±26.06min, p<0.01) and postoperative drainage (64.30±34.92mL vs.18.49±19.86mL, p<0.01), but there was less blood loss. The nipple-areolar complex of the patients who underwent endoscopic resection was significantly more sensitive than the traditional open surgery group. Patients in the endoscopic group reported higher satisfaction with surgical outcome (13.10±1.97 vs. 12.63±1.90, p<0.01). And there was a significant difference in the wound scar and cosmetic outcome total score between the two groups. Transaxillary single-port endoscopic surgery is effective and safe and improves postoperative nipple-areolar sensation and cosmetic outcome, as compared to the conventional technique.

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls

BackgroundAdenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles.ResultsDifferences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse.ConclusionsThe vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Approaches for hysterectomy and implementation of robot-assisted surgery in benign gynaecological disease: A cost analysis study in a large university hospital

BackgroundAs a minimally invasive technique, robot-assisted hysterectomy (RAH) offers surgical advantages and significant reduction in morbidity compared to open surgery. Despite the increasing use of RAH in benign gynaecology, there is limited data on its cost-effectiveness, especially in a European context. Our goal is to assess the costs of the different hysterectomy approaches, to describe their clinical outcomes, and to evaluate the impact of introduction of RAH on the rates of different types of hysterectomy. MethodsA retrospective single-centre cost-analysis was performed for patients undergoing a hysterectomy for benign indications. Abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), laparoscopically assisted vaginal hysterectomy (LAVH) and RAH were included. We considered the costs of operating room and hospital stay for the different hysterectomy techniques using the “Activity Centre–Care program model”. We report on intra- and postoperative complications for the different approaches as well as their cost relationship. ResultsBetween January 2014 and December 2021, 830 patients were operated; 67 underwent VH (8%), 108 LAVH (13%), 351 LH (42%), 148 RAH (18%) and 156 AH (19%).After the implementation and learning curve of a dedicated program for RAH in 2018, AH declined from 27.3% in 2014–2017, to 22.1% in 2018 and 6.9 % in 2019–2021.The reintervention rate was 3–4% for all surgical techniques. Pharmacological interventions and blood transfusions were performed after AH in 28%, and in 17–22% of the other approaches.AH had the highest hospital stay cost with an average of €2236.40. Mean cost of the hospital stay ranged from €1136.77-€1560.66 for minimally invasive techniques.The average total costs for RAH were €6528.10 compared to €4400.95 for AH. ConclusionImplementation of RAH resulted in a substantial decrease of open surgery rate. However, RAH remains the most expensive technique in our cohort, mainly due to high material and depreciation costs. Therefore, RAH should not be considered for every patient, but for those who would otherwise need more invasive surgery, with higher risk of complications. Future prospective studies should focus on the societal costs and patient reported outcomes, in order to do cost-benefit analysis and further evaluate the exact value of RAH in the current healthcare setting.

Minimally invasive versus open pancreatoduodenectomy in benign, premalignant, and malignant disease.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease.

MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study.

Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer. The MIRABILE study aimed to identify miRNAs in bile that can differentiate malignant from benign pancreaticobiliary disease. There were 111 patients recruited prospectively at endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) for obstructive jaundice, and bile was aspirated for cell-free RNA (cfRNA) extraction and analysis. In a discovery cohort of 78 patients (27 with pancreatic ductal adenocarcinoma (PDAC), 14 cholangiocarcinoma (CCA), 37 benign disease), cfRNA was subjected to small-RNA sequencing. LASSO regression was used to define bile miRNA signatures, and NormFinder to identify endogenous controls. In a second cohort of 87 patients (34 PDAC, 14 CCA, 39 benign disease), RT-qPCR was used for validation. LASSO regression identified 14 differentially-expressed bile miRNAs of which 6 were selected for validation. When comparing malignant and benign pancreaticobiliary disease, bile miR-340 and miR-182 were validated and significantly differentially expressed (P<0.05 and P<0.001, respectively). This generated an AUC of 0.79 (95%CI 0.70-0.88, sensitivity 65%; specificity 82%) in predicting malignant disease. Bile collected during biliary drainage contains miRNAs able to differentiate benign from malignant pancreaticobiliary diseases in patients with obstructive jaundice. These bile miRNAs have the potential to increase diagnostic accuracy.

Predicting the Diagnosis of Prostate Cancer with a Novel Blood-Based Biomarker: Comparison of Its Performance with Prostate-Specific Antigen

The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48–97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa. The normal men displayed a mean NEM plasma level of 0.948 ± 0.051 ng/mL, which increased to 1.813 ± 0.315 ng/mL in men with BPH, 86.49 ± 15.51 ng/mL in men with PCa, and 10.47 ± 1.029 ng/mL in men with other Ca. The corresponding concentrations of prostate-specific antigen (PSA) in these subjects were 1.787 ± 0.135, 5.405 ± 0.699, 35.77 ± 11.48 ng/mL, and 8.036 ± 0.518, respectively. Receiver operating characteristic (ROC) curve analysis was performed to compare NEM and PSA performance, and the Jouden Index for each biomarker was calculated to determine cut-off points for each biomarker. The area under the ROC curve to predict PCa was 0.99 for NEM and 0.81 for PSA (p &lt; 0.0001). The cut-off for NEM was at 1.9 ng/mL, with sensitivity of 98% and specificity of 97%. The corresponding PSA values were 4.4 ng/mL, with sensitivity of 76% and specificity of 95%. The predictive value of each biomarker in a patient was matched with his pathologic data to determine the accuracy of each biomarker. NEM was more accurate than PSA in differentiating cancer from benign conditions, such as BPH or prostatitis. In conclusion, NEM was a better predictor of PCa than PSA in patients visiting urology clinics. NEM tests, either alone or in conjunction with other biomarkers, provide a reliable, non-invasive, and inexpensive test to remarkably reduce false positives and thereby reduce the number of diagnostic biopsies and associated painful procedures and the loss of quality of life.

The impact of COVID-19 on colorectal cancer in regional Northern Australia and changes to treatment related to distance to care: A retrospective cohort study

Background: The COVID-19 pandemic has created challenges in the diagnosis and management of colorectal cancer (CRC). It was proposed in regional Northern Australia that the distance to services could further impact cancer outcomes, leading to delayed diagnosis. We compared the outcomes of patients prior and during the pandemic; with a focus on whether patients were presenting in the emergency setting with more advanced disease. The distance to treatment was also analysed to see if there was any impact to the management of patients with colorectal cancer. Methods: A retrospective analysis of 444 patients that underwent treatment for colorectal cancer over 2 time periods were examined. Time period 1 (prior to COVID-19); March 2017-July 2019 and time period 2 (during COVID-19); March 2020-July 2022. Only patients with colorectal adenocarcinoma were included if they were primarily treated at a hospital in northern Australia; those with benign pathologies or recurrent disease were also excluded. Data was collected in terms of treatment and outcomes and compared between the two groups. A separate analysis of whether locality affected outcomes and referral times was also performed. Results: In the time period prior to COVID-19 174 patients’ required invasive management, while in the second time period during COVID-19 there were 188 patients managed surgically or endoscopically. Of the patients managed prior to COVID-19 17/174 (9.8%) patients required emergency interventions, during COVID-19 this number increased to 37/188 (19.7%). This difference was deemed to be statistically significant (P =0.008). No substantial difference in cancer staging at presentation was found between the two groups. There was an increase in complication rate found during COVID-19 34.6% vs 25.5% prior to COVID-19 (P =0.046). During COVID-19 the median time between General Practitioner (primary care physician) referral and colonoscopy was actually lower than prior to covid 26.5 vs 36 days (P=0.047). When comparing local to distant patients we found locally based patients had lower rates of neoadjuvant treatment 18.9% vs 30.4% (P=0.018) and higher rates of open surgery 39.1% vs 26.5%, P =0.012. An increase in time between colonoscopy and outpatient department review (OPD) was seen in patients not from the local area 13 vs 18 days (P =0.006). Conclusion: We found during the COVID-19 pandemic a greater proportion of patients were presenting with colorectal cancer that required emergency intervention. This may be due to decreased presentations to general practitioners due to lockdown causing potential delays in diagnosis. We did not see more advanced disease in these patients presenting emergently, between the two groups. Further assessment of local patients’ vs patients from distant sites, showed difference in how patients were managed but similar outcomes. Our large catchment area with distance to treatment in Northern Australia may further impact the management of colorectal cancer in the future.

Osteopoikilia in the practice of a rheumatologist

Osteopoikilia (OPC) is a rare, benign autosomal dominant disease characterized by sclerotic bone lesions, which usually proceeds asymptomatically. It is usually diagnosed by accident with conventional radiography. In most patients, the disease is asymptomatic, but some may complain of mild joint pain and swelling. Differential diagnoses of the disease include osteoblastic metastases, primary bone tumor, mastocytosis, tuberous sclerosis, synovial chondromatosis and melanostasis. In the literature, we have found reports of the coexistence of OPC with rheumatological diseases such as fibromyalgia, reactive arthritis, familial Mediterranean fever, psoriatic arthritis, rheumatoid arthritis, seronegative spondyloarthritis. Thus, the clinical case we observed is interesting not only from the standpoint of the importance of establishing a clinical diagnosis, but also the timeliness of starting treatment, which affects the prognosis of the disease.

Enhancing Men's Awareness of Testicular Diseases (E-MAT) using virtual reality: A randomised pilot feasibility study and mixed method process evaluation.

Testicular cancer is among the most common malignancies in men under the age of 50 years. Most testicular symptoms are linked to benign diseases. Men's awareness of testicular diseases and testicular self-examination behaviours are suboptimal. In this pilot feasibility study and process evaluation we examine the feasibility of conducting a future definitive randomised controlled trial (RCT) to test the effect of the Enhancing Men's Awareness of Testicular Diseases using Virtual Reality intervention (E-MATVR) compared to the Enhancing Men's Awareness of Testicular Diseases using Electric information control (E-MATE). The study protocol is registered on ClinicalTrials.gov (NCT05146466). Male athletes, engaged in Gaelic games, and aged 18 to 50 years were included. Recruitment was via FacebookTM, XTM (formerly TwitterTM), and posters. Participants were individually randomised to either E-MATVR or E-MATE. Data were collected at baseline (T0), immediately post-test (T1), and three months post-test (T2) using surveys. Qualitative interviews were conducted with participants and researchers. Data were collected from 74 participants. Of those, 66 were retained. All E-MATVR participants and most E-MATE participants (n = 33, 89.2%) agreed/strongly agreed that the device was easy to use and that they were engaged to learn by the device. Most E-MATVR participants (n = 34, 91.9%) and all E-MATE participants agreed/strongly agreed that the time it took them to complete the intervention was reasonable. All 74 participants were extremely satisfied/somewhat satisfied with their overall participation in the study. E-MATVR was described as interactive, easy, fun, and close to real life. Initial difficulty using VR equipment, nausea, and technical issues were identified as challenges to engaging with E-MATVR. Recommendations were made to make VR more accessible, shorten the survey, and incorporate more interactivity. Across all participants, mean testicular knowledge scores (range 0-1) increased from 0.4 (SD 0.2) at T0 to 0.8 (SD 0.2) at T1. At T2, overall mean scores for participants were 0.7 (SD 0.2). Mean knowledge scores did not differ by trial arm at any timepoint. At T2, all E-MATVR participants and 29/32 E-MATE participants (90.6%) reported purposefully examining their testes within the past three months. Findings are promising, highlighting the feasibility of using VR to promote young athletes' awareness of testicular diseases. Considering the strengths, limitations, and lessons learned from this study, some modifications are required prior to conducing an RCT. These include but are not limited to shortening survey questions, incorporating more interactivity and visual content, and targeting more heterogenous male-dominated environments.

A Large-Scale Proteomics Resource of Circulating Extracellular Vesicles for Biomarker Discovery in Pancreatic Cancer.

Pancreatic cancer has the worst prognosis of all common tumors. Earlier cancer diagnosis could increase survival rates and better assessment of metastatic disease could improve patient care. As such, there is an urgent need to develop biomarkers to diagnose this deadly malignancy. Analyzing circulating extracellular vesicles (cEVs) using 'liquid biopsies' offers an attractive approach to diagnose and monitor disease status. However, it is important to differentiate EV-associated proteins enriched in patients with pancreatic ductal adenocarcinoma (PDAC) from those with benign pancreatic diseases such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). To meet this need, we combined the novel EVtrap method for highly efficient isolation of EVs from plasma and conducted proteomics analysis of samples from 124 individuals, including patients with PDAC, benign pancreatic diseases and controls. On average, 912 EV proteins were identified per 100µL of plasma. EVs containing high levels of PDCD6IP, SERPINA12 and RUVBL2 were associated with PDAC compared to the benign diseases in both discovery and validation cohorts. EVs with PSMB4, RUVBL2 and ANKAR were associated with metastasis, and those with CRP, RALB and CD55 correlated with poor clinical prognosis. Finally, we validated a 7-EV protein PDAC signature against a background of benign pancreatic diseases that yielded an 89% prediction accuracy for the diagnosis of PDAC. To our knowledge, our study represents the largest proteomics profiling of circulating EVs ever conducted in pancreatic cancer and provides a valuable open-source atlas to the scientific community with a comprehensive catalogue of novel cEVs that may assist in the development of biomarkers and improve the outcomes of patients with PDAC.