Follow-up Regimen Research Articles

Recommendations for Research to Develop a Patient-Centered Clinical Follow-Up Protocol for Oral Epithelial Dysplasia.

Oral epithelial dysplasia (OED) is the primary histological marker for assessing the progression of oral potentially malignant disorders (OPMDs) to cancer. Despite challenges in grading and low inter-pathologist reproducibility, OED severity remains the key predictor of malignant transformation. However, globally accepted guidelines for OED monitoring are lacking, despite calls for individualized management based on host and lesion characteristics. The proposed research protocol involves acquiring high-quality intraoral images, assessing oral hygiene and periodontal status, eliminating chronic mechanical irritation and Candida infections, and applying adjunctive diagnostic methods like toluidine blue staining, optical evaluation, and brush cytology. Tailored follow-up regimens based on individual risk assessments are emphasized, with frequent monitoring for high-grade dysplasia or patients at higher risk of progression. Therefore, effective OED management should consider the patient's immune status, dietary habits, and oral microbiota, aiming to develop personalized treatment strategies that optimize patient-centered care.

Gold standard nephroureterectomy, chemoprophylaxis and surveillance in upper tract urothelial carcinoma.

The purpose of this review is to summarize the most recent evidence on surgical management, strategies to reduce tumor recurrence, and surveillance regimens in patients diagnosed with upper tract urothelial carcinoma (UTUC) and elected for radical treatment. Minimally invasive surgery is gaining momentum in the surgical management of UTUC. Chemoprophylaxis is still the gold standard to reduce intravesical recurrence after radical nephroureterectomy (RNU). Novel surveillance strategies have been proposed to adapt follow-up regimens to patients' characteristics. Minimally invasive surgery has been associated with comparable oncological outcomes to the open approach while improving postoperative morbidity. In these cases, bladder cuff excision (BCE) is mostly performed by an extravesical approach, that demonstrates a noninferiority compared to the intravesical one in terms of oncological outcomes. Although lymphadenectomy is recommended in patients with high-risk tumors, its benefits are still unclear. Currently, there is a lack of recent prospective trials on chemoprophylaxis to reduce intravesical recurrence post RNU, making single-dose postoperative chemotherapy instillation the standard treatment. Although novel risk stratification models were released by international urological guidelines, their validity is mainly nonevidence-based. Risk-adapted follow-up strategies incorporating cystoscopy and cross-sectional imaging accounting for individual patient factors should be implemented.

Early detection of liver fibrosis in patients with Fontan circulation using multiparametric magnetic resonance imaging

Abstract Introduction Fontan procedure (FP), serving as the palliative intervention for complex congenital heart diseases characterized by single-ventricle physiology, precipitates a spectrum of late-stage complications. Fontan-associated liver disease (FALD) encompassing liver fibrosis (LF) which may progress to liver cirrhosis (LC) and thereby hepatocellular carcinoma (HCC) is among the most serious. Despite its importance, optimal surveillance of FALD remains undefined. Multiparametric Liver Multiscan (LMS) with corrected T1 (cT1) value emerges as a novel magnetic resonance (MRI) based non-invasive quantitative tool for liver inflammation and fibrosis evaluation. Aim of this study was to ascertain prevalence and severity of LF utilizing LMS, alongside identifying contributory risk factors for LF in adults post-FP. Material and methods Our cohort included 29 adult patients after FP who underwent LMS. Median age was 25y (20-43y) 54% were females. Liver morphology was assessed by ultrasound (USG) and MRI-based LMS protocol. Hepatic scoring systems, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) Index, and Model for End-Stage Liver Disease (MELD), were computed. Additionally, presence of fenestrations in the Fontan circulation, hemoglobin levels (Hb), and blood oxygen saturation both at rest and during exercise (SatO2%) were evaluated. Results Median cT1 was 914 (±207) ms, in 87% exceeding normal threshold . In those with elevated cT1, LF was undetected by USG in 38%. LC was identified in 27% of the cohort by USG. LC group exhibited significantly higher cT1 values (P<0.001) compared to non-LC group. cT1 value >933ms was associated with a sensitivity of 89% and a specificity of 80% for diagnosing LC (AUC 0.92). Significant correlation was found between cT1 values and Hb (P=0.01) and desaturation (SatO2 <90%/ interventional closure of fenestration, P=0.004). Conventional liver tests and hepatic scoring systems (APRI/FIB-4/MELD) did not predict cT1 nor LC. Conclusion Our study confirmed that LF is almost widely prevalentamong adult patients with single-chamber circulation. Risk factors for LF are systemic desaturation (SatO2 <90% or interventional closure of fenestration) and polyglobulia. However, reliable FALD surveillance remains challenging. Conventional liver assessments and scoring algorithms fall short in delineating the full scope of LF or LC. Consequently, the integration of non-invasive LMS into routine follow-up regimens is advocated, given its pronounced sensitivity for detecting subclinical FALD manifestations and predicting LC. The LMS-derived cT1 value >933ms is a critical predictor for LC, underscoring its importance in guiding further patient monitoring, treatment, and facilitating early HCC detection.

Deciphering the molecular heterogeneity of intermediate- and (very-)high-risk non-muscle-invasive bladder cancer using multi-layered -omics studies.

Bladder cancer (BC) is the most common malignancy of the urinary tract. About 75% of all BC patients present with non-muscle-invasive BC (NMIBC), of which up to 70% will recur, and 15% will progress in stage and grade. As the recurrence and progression rates of NMIBC are strongly associated with some clinical and pathological factors, several risk stratification models have been developed to individually predict the short- and long-term risks of disease recurrence and progression. The NMIBC patients are stratified into four risk groups as low-, intermediate-, high-risk, and very high-risk by the European Association of Urology (EAU). Significant heterogeneity in terms of oncological outcomes and prognosis has been observed among NMIBC patients within the same EAU risk group, which has been partly attributed to the intrinsic heterogeneity of BC at the molecular level. Currently, we have a poor understanding of how to distinguish intermediate- and (very-)high-risk NMIBC with poor outcomes from those with a more benign disease course and lack predictive/prognostic tools that can specifically stratify them according to their pathologic and molecular properties. There is an unmet need for developing a more accurate scoring system that considers the treatment they receive after TURBT to enable their better stratification for further follow-up regimens and treatment selection, based also on a better response prediction to the treatment. Based on these facts, by employing a multi-layered -omics (namely, genomics, epigenetics, transcriptomics, proteomics, lipidomics, metabolomics) and immunohistopathology approach, we hypothesize to decipher molecular heterogeneity of intermediate- and (very-)high-risk NMIBC and to better stratify the patients with this disease. A combination of different -omics will provide a more detailed and multi-dimensional characterization of the tumor and represent the broad spectrum of NMIBC phenotypes, which will help to decipher the molecular heterogeneity of intermediate- and (very-)high-risk NMIBC. We think that this combinatorial multi-omics approach has the potential to improve the prediction of recurrence and progression with higher precision and to develop a molecular feature-based algorithm for stratifying the patients properly and guiding their therapeutic interventions in a personalized manner.

Uveal melanoma: molecular-genetic mechanisms of arising and the therapeutic approaches

Uveal melanoma (UM) is a tumor of neuroectodermal origin, which results from malignant transformation of melanocytes of the eye vasculature: iris, ciliary body and chorioidea. UM represents up to 5% of all melanoma cases, but it is extremely aggressive, since half of patients with UM develop metastases within the first 1‒2 years after the tumor appearance. Molecular mechanisms of uveal melanoma carcinogenesis are poorly understood, and have already been shown to be different from those of skin melanoma. Activating mutations in the GNAQ and GNA11 genes, encoding the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The main signaling cascade leading to the transformation of melanocytes of the uveal tract is the signaling pathway Gaq/PKC/MAPK, and the major regulators of this cascade are targets for the development of drugs. The development of the metastatic form of UM is most often associated with mutations in the genes BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, has been shown to be highly effective prognostic signature in prediction the risk of metastases. The risk of metastases determines the choice of therapy and patient follow-up regimen. At the same time, no systemic therapy for the treatment of metastatic UM has been developed to date; new drugs undergoing clinical trials mostly refer to either targeted therapy aimed at inhibiting the protein products of mutant genes, or immunotherapy designed to stimulate an immune response against specific antigens. In addition to these approaches, the review also considers potential therapeutic targets of epigenetic regulation of UM development.

Preserflo MicroShunt versus Trabeculectomy: Efficacy and Surgical Success within a Heterogenous Patient Cohort.

To compare success rates of trabeculectomy (TE) and Preserflo MicroShunt (PMS) in heterogenous glaucoma cohorts with regards to different pre- and postoperative therapeutic regimens. Data of 187 glaucoma patients who either received TE (73 eyes) or PMS implantation (114 eyes) between January 2018 and December 2022 were retrospectively evaluated. Surgical success and failure rates were analyzed within six months of follow-up. Intraocular pressure (IOP) development over the course of follow-up was compared between both groups. Tertiary outcome measures were best-corrected visual acuity (BCVA), number and type of medications, frequency of postoperative complications and revision surgeries. Outcome measures underwent additional assessment based on subgroup categorizations, and failure time hazard ratios were computed. The success rates were comparable between both procedures (TE: 54.1%, PMS: 60.0%; p = 0.17). Both procedures showed significant IOP reduction (p < 0.01); however, overall IOP reduction was greater in the TE group than in the PMS group (TE: Reduction by 12 mmHg (188.9%), PMS: Reduction by 7 mmHg (51.3%); p = 0.01). The number of topical medications decreased significantly in both groups over the course of follow-up (TE: 4 to 0, PMS: 3 to 0; p < 0.01). While the number of complications and revision surgeries were similar in both groups, the time interval until the first revision surgery within the TE group was significantly shorter (TE: 13.5 d, PMS: 163 d; p = 0.01) than within the PMS group. No difference could be detected between TE and PMS with regard to the follow-up regimen. In particular, there was no significant difference in the need for 5-floururacil injections postoperatively (p = 0.29). Less invasive glaucoma surgery with the PMS appeared comparable to the TE within a heterogenous glaucoma cohort with regards to IOP development and freedom from medication.

Lymphocytic Variant of Triple-Negative Breast Cancer Carcinoma Erysipeloides: A Rare Case of Carcinoma Erysipeloides Following TNBC Mastectomy

Background: Carcinoma erysipeloides (CE) is a rare but significant cutaneous manifestation of metastatic breast cancer, often misdiagnosed due to its rarity and nonspecific presentation. This is particularly true in patients with triple-negative breast cancer (TNBC), where the disease may progress undetected by conventional imaging modalities. This manuscript aims to elucidate the challenges and implications of diagnosing CE in breast cancer survivors, emphasizing the insufficiency of PET scans in detecting such cutaneous metastases and the potential for mismanagement due to diagnostic oversight. Case Presentation: We present a detailed case study of a 43-year-old female with a history of metastatic TNBC, who developed suspicious skin lesions post-treatment. Despite initial negative PET scan results, further investigations revealed CE through histopathological examination of skin biopsies. The case highlights the critical need for biopsy in the presence of new skin lesions in breast cancer survivors, irrespective of imaging results. It also underscores the possibility of lymphatic spread of CE, which could lead to life-threatening complications if not properly managed. Conclusion: The diagnosis of carcinoma erysipeloides must be considered in patients with breast cancer presenting with unusual skin lesions. Increased vigilance and dermatological assessment should be integral to the post-cancer follow-up regimen. The findings advocate for revising current treatment protocols and guidelines to better manage and potentially prevent the complications associated with this diagnosis. Enhanced surveillance for dermatological changes and a more aggressive approach to the biopsy of new skin lesions in cancer patients are recommended to improve outcomes and prevent the misdiagnosis of CE.

Intramedullary pediatric low-grade glioma of the spine.

Pediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis. The first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors. Ultimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.

Association between p16/Ki-67 dual stain cytology results prior to and 6months after LLETZ treatment for CIN and the follow-up regimen three years after treatment: a retrospective cohort study.

Investigate the association between p16/Ki-67 dual stain cytology test (DST) results, obtained prior to- and 6months after LLETZ surgery for treatment of CIN, and the follow-up regimen three years after treatment. Secondary analysis of a prospective cohort study. Cervical cytology samples were obtained just prior to- and 6months after LLETZ and underwent conventional liquid-based cytology (LBC) and p16/Ki-67 dual staining, as well as high-riskHPV genotyping. Clinical management after the LLETZ was according to Belgian national guidelines, with clinicians being blinded to DST results at both time points. Case records were reviewed in 01/2023 to document the follow-up regimen on average three years afterwards: women had either been advised to return to routine screening (i.e., three-annual LBC testing according tothe Belgian guideline at that time), or were still subject to more frequent posttreatment surveillance (i.e., more frequent visitsbecause of persistent hrHPV infection orabsence of cytological regression). The follow-up regimen was recorded in 79/110 women originally recruited (72%). The need for continued intense posttreatment surveillance was associated with hrHPV infection 6months after treatment (79.3% vs. 18.0%, p < 0.001), a positive DST result at baseline and follow-up (41.4% vs. 84.0%, p < 0.001-55.2% vs. 16.0%, p < 0.001), and persistent cytological anomalies at 6months (at an ASCUS or worse threshold, 37.9% vs. 16.0%, p = 0.028). In multivariable logistic regression analysis, a positive DST at baseline (aOR 20.1, 95%CI 2.03-199.1) was independently associated with the need for intense post-treatment surveillance multiple years after treatment. This exploratory study suggests a possible role of dual-stain cytology in predicting treatment outcome multiple years after LLETZ surgery.

Real-World Treatment Patterns Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

The treatment landscape for type 2 diabetes mellitus (T2DM) is complex and constantly evolving, and real-world evidence of prescribing patterns is limited. The objectives of this study were to characterize lines of therapy (LOTs), calculate the length of time spent on each LOT, and identify the reasons for the LOT end among patients who initiated oral semaglutide for T2DM. This retrospective, claims-based study included commercial and Medicare Advantage adults with T2DM. Data from November 1, 2019, and June 30, 2020, were obtained from Optum Research Database. Patients with ≥ 1 claim for oral semaglutide and continuous health plan enrollment for ≥ 12months prior to (baseline period) and ≥ 6months following (follow-up period) the date of the first oral semaglutide claim were included. LOT 1 began on the date of the first oral semaglutide claim. The start date of any subsequent LOTs was the date of the first claim for an additional non-insulin anti-diabetic drug class or a reduction in drug class with use of commitment medications. The LOT ended at the first instance of medication class discontinuation, change in regimen or end of follow-up. Of the 1937 patients who initiated oral semaglutide, 950 (49.0%) remained on their initial regimen over the 6-month follow-up period, 844 (43.6%) had at least one subsequent LOT, and 89 (4.6%) had at least two subsequent LOTs. Among patients with more than one LOT, approximately 20%-25% used oral semaglutide as monotherapy or combination therapy during LOTs 2 and 3. Metformin was frequently used during treatment across all LOTs. This study provides insight for physicians and payers into the real-world prescribing practices within the first 6months following oral semaglutide initiation and fills the gap in understanding the frequency of regimen changes in the constantly evolving and complex environment of T2DM care.

Is Perineural Invasion an Independent Prognostic Factor for Local Recurrence in Oral Squamous Cell Carcinoma?

The purpose of this study was to analyse the independent prognostic significance of perineural invasion (PNI) on local recurrence (LR) in patients with oral squamous cell carcinoma (OSCC) managed primarily with surgery. Clinical and histopathological data of 195 patients with OSCC were analysed retrospectively to identify risk factors associated with PNI and to evaluate its significant correlation with local recurrence, overall survival (OS) and recurrence free survival (RFS). Patients were followed for a mean period of 39.5 ± 1.376months and median 35months. PNI was found in 57 patients (29.2%). PNI correlated with tongue subsite (p = 0.001), nodal metastasis (p < 0.000), depth of invasion (DOI) (p = 0.002), stage (p = 0.013) and adjuvant therapy (p < 0.001). Mean time to recurrence with PNI was significantly shorter (p = 0.002).Multivariate analysis did not establish significant relationship between PNI and LR. Kaplan-Meier curve did not show statistical significance with OS (p = 0.085) or RFS (p = 0.110). PNI remains an aggressive factor for nodal metastasis mandating neck management for regional control. Though PNI showed no statistical significance with LR, time to recurrence in PNI positive patients were significantly shorter. Hence, close follow-up regimen becomes necessary.

Telemedicine in diabetic eye care: A meta-analysis of its effectiveness in underserved populations

Telemedicine has emerged as a promising tool in diabetic eye care, particularly for underserved populations facing barriers to accessing traditional healthcare services. This meta-analysis aims to evaluate the effectiveness of telemedicine interventions in managing diabetic eye conditions within underserved communities. Through a systematic review of existing literature, encompassing diverse telemedicine approaches such as remote screening, teleconsultation, and telemonitoring. These studies were conducted across various regions with underserved populations, including rural areas, low-income urban neighborhoods, and underserved ethnic groups. The meta-analysis revealed significant improvements in several key outcome measures. Firstly, telemedicine interventions led to increased rates of early detection of diabetic retinopathy and other diabetic eye complications, facilitating timely intervention and preventing progression to more severe stages of the disease. Secondly, telemedicine facilitated better access to specialist care, overcoming geographical barriers and reducing the burden of travel for patients. Thirdly, telemedicine interventions were associated with improved patient compliance with follow-up appointments and treatment regimens, leading to better long-term management of diabetic eye conditions. Moreover, subgroup analyses revealed that telemedicine was particularly effective in reaching vulnerable populations such as elderly individuals, those with limited mobility, and ethnic minorities, thereby addressing disparities in healthcare access. Telemedicine holds great promise as an effective tool for diabetic eye care in underserved populations, offering a scalable and cost-effective approach to improving access to timely screening, diagnosis, and management of diabetic eye conditions. Further research and implementation efforts are warranted to optimize telemedicine interventions and ensure equitable access to quality eye care for all.

Long-term treatment outcomes and natural course of low-grade intracranial dural arteriovenous fistulas.

In contrast to high-grade dural arteriovenous fistula (dAVF), low-grade dAVF is mainly associated with tinnitus and carries a low risk of morbidity and mortality. It remains unclear whether the benefits of active interventions outweigh the associated risk of complications in low-grade dAVF. The authors conducted a retrospective single-center study that included all consecutive patients diagnosed with an intracranial low-grade dAVF (Cognard type I and IIa) during 2012-2022 with DSA. The authors analyzed symptom relief, symptomatic angiographic cure, treatment-related complications, risk for intracerebral hemorrhage (ICH), and mortality. All patients were followed up until the end of 2022. A total of 81 patients were diagnosed with a low-grade dAVF. Of these, 48 patients (59%) underwent treatment (all primary endovascular treatments), and 33 patients (41%) did not undergo treatment. Nine patients (19%) underwent retreatments. Angiographic follow-up was performed after median (IQR) 7.7 (6.1-24.1) months by means of DSA (mean 15.0, median 6.4 months, range 4.5-83.4 months) or MRA (mean 29.3, median 24.7 months, range 5.9-62.1 months). Symptom control was achieved in 98% of treated patients after final treatment. On final angiographic follow-up, 73% of patients had a completely occluded dAVF. There were 2 treatment-related complications resulting in 1 transient (2%) and 1 permanent (2%) neurological complication. One patient showed recurrence and progression of a completely occluded low-grade dAVF to an asymptomatic high-grade dAVF. No cases of ICH- or dAVF-related mortality were found in either treated patients (median [IQR] follow-up 5.1 [2.0-6.8] years) or untreated patients (median [IQR] follow-up 5.7 [3.2-9.0] years). Treatment of low-grade dAVF provides a high rate of symptom relief with small risks for complications with neurological sequela. The risks of ICH and mortality in patients with untreated low-grade dAVF are minimal. Symptoms may not reveal high-grade recurrence, and radiological follow-up may be warranted in selected patients with treated low-grade dAVF. An optimal radiographic follow-up regimen should be developed by a future prospective multicenter registry.

National Survey of Current Follow-up Protocols for Patients Treated for Endometrial Cancer in the UK

AimsThe aim of this study was to establish a baseline of national practice for follow-up after treatment for endometrial cancer in the UK. Materials and methodsAn online cross-sectional survey was developed and distributed through the Royal College of Radiologists via an email link to the audit leads of radiotherapy centres in the UK. The survey was conducted from November 2021 to 5 January 2022. The main themes assessed in the survey were the form, frequency and duration of follow-up practices. ResultsThere were a total of 43/61 (70%) complete responses. 93% of centres had a standard follow-up protocol and 7% who did not have a follow-up protocol discharged patients after the post-operative review. Five centres (13%) used molecular profiling to inform follow-up practices.Patient-initiated follow-up was mainly used in the cohort of patients who had surgery alone with no adjuvant treatment (68%, (19/28)). In the cohort who had face-to-face follow-up, the majority had pelvic examinations as part of their review and total follow-up for five years.93% of respondents are interested in a national follow-up protocol. ConclusionOur data shows that there is national variation in practise with regard to follow-up of women treated for endometrial cancer. Many of the follow-up practises are based on conventional follow-up regimens and these may fail to address the more holistic needs of cancer survivors. Recent publication of updated guidance from the British Gynaecological Cancer Society may help standardise practise and provide a more relevant approach to follow-up for women treated for endometrial cancer.

Papillary Thyroid Microcarcinoma: Differences between Lesions in Incidental and Nonincidental Settings-Considerations on These Clinical Entities and Personal Experience.

Papillary thyroid microcarcinoma (PTMC) represents 35-40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis (p < 0.001); a lower male/female ratio (p < 0.01); a larger mean nodule diameter (p < 0.001); and a higher rate of aggressive pathological findings, such as multifocality, capsular invasion and/or lymphovascular invasion (p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy (p < 0.05), while disease-free long-term survival did not differ between subgroups (p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence.

Uveal Melanoma: Molecular and Genetic Mechanisms of Development and Therapeutic Approaches

Uveal melanoma (UM) is a neuroectodermal tumor that results from malignant transformation of melanocytes in the eye uvea, including the iris, the ciliary body, and the choroid. UM accounts for 5% of all melanoma cases and is extremely aggressive with half of the UM patients developing metastases within the first 1-2 years after tumor development. Molecular mechanisms of UM carcinogenesis are poorly understood, but are known to differ from those of skin melanoma. Activating mutations of the GNAQ and GNA11 genes, which code for the large G protein subunits Gq and G11, respectively, are found in 90% of UM patients. The Gaq/PKC/MAPK signaling pathway is a main signaling cascade that leads to the transformation of melanocytes of the uveal tract, and major regulators of the cascade provide targets for the development of drugs. Metastatic UM (MUM) is most often associated with mutations of BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. A combination of a commercial expression test panel of 15 genes and a mutation panel of 7 genes, supplemented with data on the size of the primary tumor, is highly efficient in predicting the risk of metastasis. The risk of metastasis determines the choice of therapy and the patient follow-up regimen. However, no systemic therapy for MUM has been developed to date. New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.

P913 Intestinal Ultrasound in paediatric Crohn’s disease reduces the need for subsequent ileocolonoscopy

Abstract Background Approximately 20% of patients with Crohn's disease (CD) are diagnosed during childhood (pCD). At diagnosis, the vast majority (87%) of patients with pCD demonstrate severe disease activity.(1) Severe disease activity necessitates intensive treatment followed by frequent blood tests, faecal calprotectin tests, and endoscopic procedures. Ileocolonoscopy is burdensome for the patient, as bowel preparation and general anaesthesia are needed, and furthermore, the procedure is costly. In recent European guidelines for pCD management, Intestinal Ultrasound (IUS) is recommended for clinical follow-up. Our objective was to investigate the extent to which patients with pCD underwent subsequent endoscopy after having IUS performed during their follow-up regimen. Methods We conducted a retrospective descriptive cohort study, encompassing all patients with pCD at a referral center (Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital, Amager and Hvidovre) who had undergone a minimum of one ultrasound examination over a 2.5-year period (May 1, 2021, to November 1, 2023). Results A total of 29 patients with pCD were enrolled in the study. Demographic data can be found in Table 1. The median follow-up since time of diagnosis was 40 months (interquartile range (IQR) 30-57). Time to the first IUS examination after diagnosis was median 28 months (IQR 13-49). The indications for IUS were as follows: Clinical suspicion of disease activity and/or elevated faecal calprotectin levels (66% of cases), evaluation of disease activity after initiating biologic therapy (10%), assessment of disease activity status (14%), suspicion of treatment failure (7%) and other indications (3%). Following the IUS procedure, 10% of patients subsequently underwent ileocolonoscopy, which was performed within 11, 14, or 53 days after IUS. Among the remaining 90% of patients, 14% underwent ileocolonoscopy 8-16 months after the IUS procedure, while 76% never had a repeat ileocolonoscopy performed after a median follow-up of 342 days (IQR 247-441) after IUS. Conclusion In 90% of patients with pCD IUS can be used to evaluate disease activity without the necessity for an ileocolonscopy in the subsequent 12 moths of follow up.

Appendiceal Neuroendocrine Neoplasms: an Update for 2023.

To summarize the literature from the last 5years on treatment of appendiceal neuroendocrine neoplasms (aNEN). Furthermore, to evaluate the prognostic significance of lymph node metastases, indications for adjuvant treatment, and challenges of the current follow-up regimen. Simple appendectomy is sufficient in tumors < 1cm while extended surgery is indicated in tumors > 2cm. In a multicenter study of aNENs measuring 1-2cm, extended surgery offered no significant prognostic advantage and is now limited to incomplete tumor resection or high-grade G2 or G3 aNEN. Follow-up remains debatable, as the use of imaging and biomarkers lacks validation. While surgical procedure is well established in aNEN tumors < 1cm and > 2cm, the need for extended surgery in aNEN tumors 1-2cm is questionable. Future studies should address the prognostic impact of lymph node metastases and the optimal design and duration of follow-up.

Personalized Treatment Strategy in "Low-Risk Prostate Cancer Active Surveillance Candidates" Using Irreversible Electroporation: Prospective Evaluation of Feasibility, Morbidity, Functional and Oncological Outcomes.

To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in "active surveillance (AS)" candidates refusing standard treatment options. IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

The rollout of paediatric dolutegravir and virological outcomes among children living with HIV in Mozambique.

In 2022, Mozambique introduced Dolutegravir 10mg (pDTG), as part of paediatric antiretroviral therapy for children weighing < 20 kg. Understanding real-world challenges during national rollout can strengthen health systems in resource-limited settings. We described the transition rate to, and new initiation of, pDTG, viral load suppression (VLS) post-pDTG, and factors associated with VLS among children living with HIV. We conducted a retrospective cohort study involving children aged < 9 years and abstracted data from clinical sources. We used logistic regression to assess VLS and pDTG initiation predictors. Of 1353 children, 1146 initiated pDTG; 196 (14.5%) had no recorded weight. Post-pDTG switch, 98.9% (950/961) of children maintained the same nucleoside reverse transcriptase inhibitor backbone. After initiating Abacavir/Lamivudine+pDTG, 834 (72.8%) children remained on the regimen, 156 (13.6%) switched off (majority to Dolutegravir 50mg), 22 (1.9%) had ≥ 2 anchor drug switches; 134 (11.7%) had no documented follow-up regimen. Factors associated with pDTG initiation or switch were younger age (adjusted odds ratio [AOR] = 0.71 [0.63-0.80]) and a recorded weight (AOR = 55.58 [33.88-91.18]). VLS among the 294 children with a viral load (VL) test after ≥ 5 months post-pDTG was 75.5% (n = 222/294). Pre-pDTG VLS rate among treatment-experienced children was 56.5% (n = 130/230). Factors associated with VLS were older age (AOR = 1.18 [1.03-1.34]) and previous VLS (AOR = 2.27 [1.27-4.06]). Most eligible children initiated pDTG per guidelines, improving post-pDTG VLS. Challenges included unexplained switches off pDTG after initiation, low VL coverage and inadequate documentation in clinic records.