Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach.

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN.

A rapid action plan to improve diagnosis and management of lipodystrophy syndromes.

Introduction: Lipodystrophy syndromes are rare diseases that can present with a broad range of symptoms. Delays in diagnosis are common, which in turn, may predispose to the development of severe metabolic complications and end-organ damage. Many patients with lipodystrophy syndromes are only diagnosed after significant metabolic abnormalities arise. Prompt action by clinical teams may improve disease outcomes in lipodystrophy syndromes. The aim of the Rapid Action Plan is to serve as a set of recommendations from experts that can support clinicians with limited experience in lipodystrophy syndromes. Methods: The Rapid Action Plan was developed using insights gathered through a series of advisory meetings with clinical experts in lipodystrophy syndromes. A skeleton template was used to facilitate interviews. A consensus document was developed, reviewed, and approved by all experts. Results: Lipodystrophy is a clinical diagnosis. The Rapid Action Plan discusses tools that can help diagnose lipodystrophy syndromes. The roles of clinical and family history, physical exam, patient and family member photos, routine blood tests, leptin levels, skinfold measurements, imaging studies, and genetic testing are explored. Additional topics such as communicating the diagnosis to the patients/families and patient referrals are covered. A set of recommendations regarding screening and monitoring for metabolic diseases and end-organ abnormalities is presented. Finally, the treatment of lipodystrophy syndromes is reviewed. Discussion: The Rapid Action Plan may assist clinical teams with the prompt diagnosis and holistic work-up and management of patients with lipodystrophy syndromes, which may improve outcomes for patients with this rare disease.

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance.

With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic ß-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin ß-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

Management strategy for children with ovarian immature teratoma: results from a tertiary pediatric oncology center.

OBJECTIVES: We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection. METHODS: A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children's Oncology Group (COG), grading based on the Norris system, management, and outcomes. RESULTS: Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively. CONCLUSIONS: Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size.

Epiretinal membranes in patients with uveitis: an update on the current state of management.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of uveitic epiretinal membranes (ERM). METHODS: A thorough investigation of the literature was conducted using the PubMed database. Additionally, a complementary search was carried out on Google Scholar to ensure the inclusion of all relevant items in the collection. RESULTS: ERM is an abnormal layer at the vitreoretinal interface, resulting from myofibroblastic cell proliferation along the inner surface of the central retina, causing visual impairment. Known by various names, ERM has diverse causes, including idiopathic or secondary factors, with ophthalmic imaging techniques like OCT improving detection. In uveitis, ERM occurrence is common, and surgical intervention involves pars plana vitrectomy with ERM peeling, although debates persist on optimal approaches. CONCLUSIONS: Histopathological studies and OCT advancements improved ERM understanding, revealing a diverse group of diseases without a unified model. Consensus supports surgery for uveitic ERM in progressive cases, but variability requires careful consideration and effective inflammation management. OCT biomarkers, deep learning, and surgical advances may enhance outcomes, and medical interventions and robotics show promise for early ERM intervention.

Bibliometric and visual analyses of advancements in chronic kidney disease management.

Chronic kidney disease (CKD) is characterized by high incidence, prolonged course, significant health damage, and a heavy societal burden. Understanding the history and content of CKD research is crucial to further its recognition and management, in addition to reducing its individual and societal burdens. This study aimed to assess the management history of CKD to provide a foundation for clinical medical staff to systematically understand its evolution. The Web of Science Core Collection database was screened for CKD management studies published between January 1, 1948, and December 31, 2021. From the search results, we performed statistical descriptions of the publication date, volume, and type. Using VOS-viewer 1.6.19, variables from the included articles were obtained for keyword co-occurrence clustering and sequence analyses to determine research themes, segment phases based on publication volumes over varied timeframes, assess the dynamic progression of CKD management, and anticipate future research trends. In total, 26,133 articles met the inclusion criteria. The analysis revealed 3 stages of CKD management research: the slow development stage (1948-1998), which was initiated by epidemiological studies without ideal clustering; the steady growth stage (1999-2010), which was focused on CKD complication management and quality-of-life research; and the rapid development stage (2011-2022), which was dominated by 7 major clusters, mainly regarding the treatment and management of severe conditions and management patterns. The CKD research journey is comprised of 3 stages, the contents of which form an interconnected research model. Future research should focus on the establishment of management models and the application of intelligent management tools. Furthermore, this work can serve as a reference for the further expansion of research in this field and in improving its management.

Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis.

Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based on their origin, macrophages can be divided into monocyte-derived macrophages (MoMacs) and tissue-resident macrophages (TrMacs). During nephritis, TrMacs develop a hybrid pro-inflammatory and anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration of these mixed-phenotype macrophages is related to the continuous damage caused by immune complexes and exposure to circulating inflammatory mediators, which is an indication of the failure to resolve inflammation. On the other hand, MoMacs differentiate into M1 or M2 cells under cytokine stimulation. M1 macrophages are pro-inflammatory and secrete pro-inflammatory cytokines, while the M2 main phenotype is essentially anti-inflammatory and promotes tissue repair. Conversely, MoMacs undergo differentiation into M1 or M2 cells in response to cytokine stimulation. M1 macrophages are considered pro-inflammatory cells and secrete pro-inflammatory mediators, whereas the M2 main phenotype is primarily anti-inflammatory and promotes tissue repair. Moreover, based on cytokine expression, M2 macrophages can be further divided into M2a, M2b, and M2c phenotypes. M2a and M2c have anti-inflammatory effects and participate in tissue repair, while M2b cells have immunoregulatory and pro-inflammatory properties. Further, memory macrophages also have a role in the advancement of LN. Studies have demonstrated that the polarization of macrophages is controlled by multiple metabolic pathways, such as glycolysis, the pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, the tricarboxylic acid cycle, and arginine metabolism. The changes in these metabolic pathways can be regulated by substances such as fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, and salbutamol, which inhibit M1 polarization of macrophages and promote M2 polarization, thereby alleviating LN.

Clinical presentation and management of atypical hemolytic uremic syndrome in Latin America: a narrative review of the literature.

INTRODUCTION: Comprehensive information about atypical hemolytic uremic syndrome (aHUS) is relatively scarce outside of Europe and North America. This narrative review assembles available published data about the clinical presentation and management of aHUS in Latin America. AREAS COVERED: A search conducted in February 2023 of the MEDLINE (from inception), Embase (from inception), and LILACS/IBECS (1950 to 2023) databases using search terms 'atypical hemolytic uremic syndrome' and 'Latin America' and their variations retrieved 51 records (full papers and conference abstracts) published in English, Spanish, or Portuguese. After de-duplication, manual screening of titles/abstracts and addition of author-known articles, 25 articles were included of which 17 (68%) are full papers. All articles were published during the years 2013-2022. Articles include cohort studies, a registry analysis, and case reports from Argentina, Brazil, Chile and Columbia. Overall, Latin American patients with aHUS present the classic epidemiological, clinical, and genetic characteristics associated with this condition as described in other world regions. Depending on the country and time of reporting, aHUS in Latin America was treated mainly with plasma therapy and/or eculizumab. Where reported, eculizumab substantially improved aHUS-related outcomes in almost all adult and pediatric patients. EXPERT OPINION: Eculizumab has dramatically altered the natural course of aHUS, improving prognosis and patient outcomes. Addressing economic challenges and investing in healthcare infrastructure will be essential to implement strategies for timely detection and early treatment of aHUS in Latin America.

Outcome measures in hemophilia: current and future perspectives.

INTRODUCTION: Hemophilia can detrimentally affect patients' quality of life and likelihood of survival. In the evolving landscape of therapies, the therapeutic gain of each treatment must be understood to accurately position it in the therapeutic armamentarium. Accordingly, appropriate outcomes must be measured with appropriate tools. AREAS COVERED: Our narrative review (PubMed search for 'hemophilia AND outcome' until June 2023), provides a compendium of outcome measures used in hemophilia clinical research. To define each outcome measure's relative value and applicability, several characteristics are critically discussed. EXPERT OPINION: Bleeding assessment, first annual/annualized bleeding rate, remains central in evaluating the efficacy and safety of hemophilia treatments. As modern therapies improve clinical outcomes toward zero bleeding events, this endpoint may become less sensitive to detect differences between therapeutic approaches. Technological advancements necessitate the adaptation of outcome measures to address infrequent bleeding events, age-related comorbidities, and laboratory parameters with limited comparability after different treatments. Considerable effort has been dedicated to the development of tools that comprehensively assess coagulation, such as thrombin generation assays. Patient-reported outcome measures are gaining importance although limited by their subjectivity. A definitive set of research outcome measures remains elusive. Outcomes may need to be tailored to different therapeutic interventions.

Iodine Plaque Brachytherapy a Customized Conservative Approach to the Management of Medium/Large-sized Uveal Melanoma.

BACKGROUND/AIM: The objective of this study was to assess the role of iodine (125I) plaque brachytherapy in the management of uveal melanoma. PATIENTS AND METHODS: This is a retrospective study of 50 patients (median age 67 years; range=33-86 years) with uveal melanoma, treated with 125I plaque brachytherapy at the University Hospital of Pisa. Uveal melanoma was diagnosed with A-scan and B-scan standardized echography, fluorescein angiography, indocyanine green-angiography, optical coherence tomography, and/or magnetic resonance imaging. The primary outcomes assessed were local control, overall survival, disease progression, globe preservation, and metastases. Secondary outcomes were acute and late radiation adverse effects. RESULTS: Inclusion criteria comprised Eastern Cooperative Oncology Group performance status ≤2, life expectancy >6 months, and tumor thickness ≤10 mm and\or diameter ≤20 mm. All the patients were treated with 125I plaque brachytherapy, with a prescription dose of 85 Gy to the tumor apex. The 5-year rate of local control, progression-free survival, metastasis-free survival, enucleation-free survival, and overall survival were 83.0%, 81.4%, 90.3%, 83.1%, and 92.1% respectively. Twenty-four patients (48.0%) had one or more acute and late toxicities. The most common acute adverse events (CTCAE vs. 5.0) grade 1-3 were conjunctivitis and eye pain (6.0%). Regarding late events, radiation retinopathy grade 1-3 occurred in 18.0% of cases, while grade 1-3 vitreous hemorrhage in 2.5%. CONCLUSION: 125I plaque brachytherapy offers an effective and safe approach for selected cases of uveal melanoma, due to the reported satisfactory results in terms of local control, eye conservation and survival.

The Definition, Classification, and History of Urticaria.

The term "urticaria" was first introduced by William Cullen in the eighteenth century. Urticaria is a common mast cell-mediated cutaneous disease presenting with pruritic wheals, angioedema, or both. It is classified as acute (≤6 weeks) or chronic (>6 weeks) and as spontaneous (no definite triggers) or inducible (definite and subtype-specific triggers). The international urticaria guideline on the definition, classification, diagnosis, and management of urticaria is revised every 4 years. The global network of Urticaria Centers of Reference and Excellence, the biggest and most active consortium of urticaria specialists, offers physicians and patients several research, educational, and digital care initiatives.

Empowering pharmacists working in primary care through a cardiovascular disease clinical management course: Impact on practice.

INTRODUCTION: Cardiovascular disease (CVD) is currently the leading cause of mortality and morbidity worldwide. A competent healthcare workforce working in primary care delivering disease management services efficiently is the cornerstone of well performing health systems, impacting patient outcomes positively. The aim of this study was to evaluate the effectiveness of a training course to support pharmacists working in General Practitioner (GP) practices; and to evaluate its impact on practice. METHODS: A before and after evaluation model was employed to assess the effectiveness of training resorting to a survey exploring self-confidence and knowledge on clinical management of three CVD topics: Atrial Fibrillation (AF), Hypertension and hyperlipidaemia. Before and after training data (immediate and retained after 6 months) were analysed at the Primary Care Network (PCN) and GP Practice level of the pharmacists who took part in the training sessions. Data were analysed in IBM SPSS v.29 resorting to paired samples t-test and Cohen's d for estimation of the effect size. Independent samples t-tests were performed for a sample group of PCNs and GP practices with and without training (comparator group). RESULTS: An improvement with large effect size was observed in pharmacists' self-confidence and knowledge related to the hypertension topic, suggesting potential practical benefit. For the topics of AF and hyperlipidaemia, pharmacists' confidence also increased with a large effect size, but for knowledge, the effect size of the increase was medium or small. Data suggests that pharmacists' practice has improved in both groups after 6 months, which suggests that it was not a sole result of the training. CONCLUSIONS: This study provide evidence that the course improved pharmacists' knowledge and self-confidence, likely to contribute to performance in their clinical practice. Patients' clinical benefit is expected from pharmacists' improved capacity to effectively engage in medicines optimisation.

Knowledge, attitudes, and practices among patients with anemia towards disease management.

Objective: This study aimed to assess the knowledge, attitudes and practices among anemia patients toward disease management. Methods: This web-based cross-sectional study was conducted between September and December 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine). A self-designed questionnaire was developed to collect demographic information of anemia patients, and assess their knowledge, attitudes and practices (KAP) toward disease management. Results: A total of 396 valid questionnaires were collected. The mean age of the participants was 57.44 ± 16.80 years, and 52.02% were female. The mean knowledge, attitudes, and practices scores were 11.47 ± 1.73 (possible range: 0-14), 27.32 ± 2.96 (possible range: 7-35), and 40.49 ± 6.06 (possible range: 10-50), respectively. Multivariate analysis showed that bachelor's degree or above was independently associated with sufficient knowledge (OR = 2.372, 95%CI: 1.160-4.853, p = 0.018). Knowledge (OR = 1.350, 95%CI: 1.166-1.563, p < 0.001) and hemoglobin within 60-90 g/L (OR = 1.782, 95%CI: 1.090-2.912, p = 0.021) were independently associated with positive attitudes. Moreover, attitudes (OR = 1.618, 95%CI: 1.454-1.799, p < 0.001) and diagnosis ≥1 year (OR = 1.949, 95%CI: 1.171-3.243, p = 0.010) were independently associated with proactive practices. The path analysis demonstrated that knowledge was directly and positively correlated with attitudes (ß = 0.484, 95% CI: 0.363-0.647, p = 0.008), and attitudes was directly and positively correlated with practices (ß = 1.195, 95% CI: 1.062-1.332, p = 0.007). Moreover, knowledge was indirectly and positively correlated with practice (ß = 0.579, 95% CI: 0.434-0.805, p = 0.004). Conclusion: Anemia patients have sufficient knowledge, negative attitudes, but proactive practices toward the toward disease management Comprehensive training programs are needed to improve anemia patients practices in this area.

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

The Role of Echocardiography for the Clinical Diagnosis, Risk Stratification, and Management of Cardiac Amyloidosis.

Amyloidosis is a rare, heterogeneous group of diseases characterized by extracellular infiltration and deposition of misfolded fibrils in different organs and tissues. A timely diagnosis is important as it can improve outcome. Echocardiography has emerged as a powerful tool to prompt suspicion and refer patients to second-level evaluation to reach a definitive diagnosis. In this scenario, new echo techniques offer new insight into the cardiac amyloidosis (CA) pathophysiology and clinical course. The present review aims to describe the developments in echocardiographic assessment of patients with suspected CA and it summarizes new available echocardiographic scores able to guide a definite diagnosis.

Using a Cohort-Based Quality Improvement Coaching Model to Optimize Chronic Disease Management for Federally Qualified Health Center Patients.

CONTEXT: In fall 2020, Community Clinic Association of Los Angeles County, in collaboration with the Los Angeles County Department of Public Health, launched a 3-year, cohort-based quality improvement (QI) coaching program to assist Federally Qualified Health Centers (FQHCs) in improving their clinical management of hypertension, high blood cholesterol, diabetes, and chronic kidney disease. PROGRAM: The QI program utilized a cohort-based coaching model in which 5 FQHCs were each assigned a practice transformation coach who provided them with guidance and support to monitor clinical quality measures. These measures were then used to facilitate changes and improvements in clinical workflows and approaches to patient care. To encourage peer learning and promote inter-organizational collaboration, the coaching team hosted quarterly cohort check-ins and an online group messaging board where the participating FQHCs could share lessons learned. Throughout the program, the FQHCs were provided trainings and resources to advance their clinical quality measures of choice. IMPLEMENTATION: To implement the program, each FQHC selected 2 clinical quality measures to focus on, completing a minimum of 1 Plan-Do-Study-Act cycle per year for each measure. Throughout, the coaches met regularly with FQHC staff to discuss progress, strategize on how best to address challenges encountered, and identify training or resource needs for their clinic sites. EVALUATION: To drive implementation of QI interventions and monitor overall progress, the FQHCs reported quarterly on the clinical quality measures being addressed. By program's end, all 5 FQHCs reached their 10% improvement goals. DISCUSSION: This QI coaching program allowed participating FQHCs to build new competencies and achieve measurable improvements in how they managed their patients' chronic diseases. This model of practice serves as a promising approach for achieving sustainable clinical improvements in these FQHCs.

Testing an Innovative Approach to Improve Hypertension Management at a Federally Qualified Health Center.

Despite the availability of effective treatments, hypertension control rates remain inadequate in the United States and locally in Los Angeles County. To address this health condition, QueensCare Health Centers developed and launched a team-based hypertension management program that was led by clinical pharmacists and designed to mitigate treatment barriers encountered at the system, provider, and patient levels. System- and provider-focused strategies included incorporating self-monitored blood pressure values into the electronic health record and retraining clinicians to regularly review these values; adding a community health worker to the disease management team; and utilizing clinical pharmacists to assess and titrate medications. Patient-focused strategies included tailoring education materials to reduce literacy and linguistic barriers; providing tailored one-on-one education and support; and providing blood pressure cuffs and pedometers. This multilevel intervention serves as a practical example of how team-based care can be optimized at a Federally Qualified Health Center.

Current Advances in the Management of Nonurothelial Subtypes of Bladder Cancer.

Urothelial cancer (UC) is the most common histology seen in bladder tumors. The 2022 WHO classification of urinary tract tumors includes a list of less common subtypes (formerly known as variants) for invasive UC which are considered high-grade tumors. This review summarizes the most recent advances in the management of selected nonurothelial subtypes of bladder cancer: squamous cell carcinoma, small cell carcinoma, sarcomatoid urothelial carcinoma, micropapillary carcinoma, plasmacytoid carcinoma, adenocarcinoma, and urachal carcinoma. The role of neoadjuvant and adjuvant chemotherapy has not been well characterized for most of these histologies, and prospective data are extremely limited. Participation in clinical trials is recommended in advanced disease.