Potential Risk Of Progression Research Articles

Abstract IA22: Myeloproliferative neoplasms: Inflammation and treatment

Abstract Myeloproliferative neoplasms have a prevalence of around 350,000 in the USA and include the diagnoses of essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). These clonal neoplasms share core set of acquired driver mutations in JAK2, calreticulin (CALR), and MPL which all lead to constitutive activation of the JAK-STAT pathway. Additionally, a range of somatic mutations may occur which impact disease phenotype as risk of progression (such as ASXL1, IDH 1 & 2, EZH2 2 etc). The burden of these illnesses include a predisposition to thrombosis or bleeding, a range of challenging symptoms (from spleen pain, to hypermetabolic symptoms, pruritus, fatigue, bone pain), splenomegaly, cytopenias, and potential progression to acute myeloid leukemia. Although the origin of these diseases are anchored in a clonal neoplastic process, inflammation potentially plays a role in the risk of thrombosis, the origin of many of the difficult symptoms, potential contribution to cytopenias, and the potential risk of progression from ET/PV to MF, or from MF to AML. A spectrum of cytokines have been found to be elevated in MPNs (especially in MF), with elevation of certain ones negatively impacting prognosis including IL-8, IL-2R, IL-12, IL-15. Therapy of MPNs now includes non-specific cytoreduction (i.e. hydroxyurea for ET-PV), long acting interferons (i.e. ropegylated interferon a2b for polycythemia vera), and JAK inhibition with ruxolitinib (inhibits JAK1 and JAK2), fedratinib (JAK2 and FLT3), pacritinib (inhibits JAK2, FLT3, IRAK1, and ACVR1), and momelotinib (inhibits JAK1, JAK2, ACVR1). The JAK inhibitors have made a significant impact on decreasing the burden MPN patients face by decreasing splenomegaly (and its associated symptom burden), by decreasing MPN associated symptoms, and by improving survival. The mechanism of improved survival is not fully understood but may include a decrease in marrow inflammation and perhaps decreasing the mutagenic pressure that leads to additional somatic mutations such as ASXL1 that leads to AML. Hepcidin associated with inflammation is dually being investigated as means to decrease erythrocytosis in PV with hepcidin mimetics (i.e. rusferatide), and to improve MF associated anemia by inhibiting hepcidin (momelotinib or pacritinib by ACVR1 inhibition). Inflammation as both a driver of disease burden and progression, as well as a viable therapeutic target remains an important focus of investigation and interventional trials. Citation Format: Ruben Mesa. Myeloproliferative neoplasms: Inflammation and treatment [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr IA22.

Management of tympanic retraction pockets: case of Mali

Background: This study aims to study the epidemiological and therapeutic aspects of tympanic retraction pockets in the ENT-CCF department of the CHU GT. Method: This was a descriptive prospective study. Results: A total of 9400 patients consulted during the study period. A retraction pocket was diagnosed in 70 patients, i.e., 0.74% of all consultations. The most represented age group was that of [25-39 years]. The average age was 45.71 years. The extremes of ages were 10 years and 81 years. The female gender was the most represented, i.e., 60% with a sex ratio꞊0.67. CT of the petrous bone was performed in two patients. Medical treatment based on systemic corticosteroids and nasal decongestant was initiated in all our patients associated with quarterly monitoring for stage I charachon. The placement of a tympanostomy tube was performed in 8 patients classified (stage II of charachon). Cartilaginous tympanoplasty was performed in one patient, antroatticotomy associated with reinforcement tympanoplasty was performed in one patient (1.43%). Conclusions: The pockets of tympanic retraction constitute a particular nosological entity which deserves rigorous monitoring. The ENT surgeon will be faced with two major challenges: the erosion of the ossicular chain and their potential risk of progression towards cholesteatoma. The diversity of therapeutic options represents an issue that makes this entity a hot topic.

Can Real-time Computer-Aided Detection Systems Diminish the Risk of Postcolonoscopy Colorectal Cancer?

The adenoma detection rate is the constant subject of research and the main marker of quality in bowel cancer screening. However, by improving the quality of endoscopy via artificial intelligence methods, all polyps, including those with the potential for malignancy, can be removed, thereby reducing interval colorectal cancer rates. As such, the removal of all polyps may become the best marker of endoscopy quality. Thus, we present a viewpoint on integrating the computer-aided detection (CADe) of polyps with high-accuracy, real-time colonoscopy to challenge quality improvements in the performance of colonoscopy. Colonoscopy for bowel cancer screening involving the integration of a deep learning methodology (ie, integrating artificial intelligence with CADe systems) has been assessed in an effort to increase the adenoma detection rate. In this viewpoint, a few studies are described, and their results show that CADe systems are able to increase screening sensitivity. The detection of adenomatous polyps, which are associated with a potential risk of progression to colorectal cancer, and their removal are expected to reduce cancer incidence and mortality rates. However, so far, artificial intelligence methods do not increase the detection of cancer or large adenomatous polyps but contribute to the detection of small precancerous polyps.

Essential thrombocythemia in children and adolescents — analysis of 31 cases

Introduction. Essential thrombocythemia is an extremely rare disorder in childhood. This disease is characterized by a persistent increase in the peripheral blood platelet count, associated with a proliferation of atypical megakaryocytes in the bone marrow.Aim — to analyze the clinical features of the course of essential thrombocythemia (ET) and the response to therapy in pediatric and adolescent patientsMaterials and methods. Thirty-one patients with ET under the age of 21 years were analyzed. All patients were diagnosed with ET in accordance with WHO criteria on the basis of an examination, including assessment of clinical data, laboratory tests (general clinical tests; morphological, genetic, and histological examinations of bone marrow), instrumental studies, and an assessment of response to treatment.Results. The average age of disease onset was 9 years 9 months, with a median of 9 years 6 months. Organomegaly was recorded in 16 (52 %) patients, of whom 6 (37.5 %) had isolated splenomegaly and 6 (37.5 %) had hepatosplenomegaly. Bleeding was noted in 6 (19.4 %) patients with a deep decrease in vWF:RCo (no more than 15 %) and an extreme increase in platelets (PLT) (more than 2000 × 109 /L). Twelve (38.7 %) patients suffered from microcirculation disorders (headaches, dizziness, melalgia), half of them had a platelet count of 1000–2000 × 109 /L, which is comparable to asymptomatic patients. No thrombosis was registered in our group. The JAK2V617F mutation was detected in 3 (9.7 %) patients, a mutation in the CALR gene was found in 9 (29.0 %) of patients, there was a mutation in the MPL gene in one (3.2 %) patient, and in the remaining cases (18 (58.1 %) patients), there was no damage to typical driver genes. Translocation t(12;12) was revealed in 1 (3.2 %) patient. The response to one-component cytoreductive therapy (CR+PR) was found to be quite high in young patients and constituted about 70–80 %. The complete response rate (CR) was as follows, respectively: 42.9 % (3) — to anagrelide therapy (ANA), 47.4 % (9) — to interferon therapy (INF), and 0 % — to hydroxycarbamide (HU). However, HU was not used in the fi rst line of therapy for the children in our group.Conclusion. In the pediatric population, ET patients are dominated by the group of “triple-negative” disease, which somewhat complicates the differential diagnosis with secondary thrombocytosis. Compared to the adult population, the risk of bleeding is higher for pediatric patients, which is associated with the large number of patients with extremely high levels of platelets. In the case of hemorrhagic syndrome development or microcirculatory disorders that cannot be stopped by taking antiplatelet agents, we recommend giving preference to INF and HU as fi rst-line therapy, due to the peculiarities of pharmacokinetics and the potential risk of progression of myelofi brosis during ANA therapy.

Predictive Role of the p16 Immunostaining Pattern in Atypical Cervical Biopsies with Less Common High Risk HPV Genotypes.

P16 immunostaining is considered a useful surrogate of transcriptionally active high-risk (hr) HPV infection. Only strong and widespread “block-like” immunoreactivity is considered specific, whereas weak/focal p16 positive immunostaining is considered not specific, and follow-up and HPV molecular detection is not indicated. The aim of the study was to evaluate the presence of HPV DNA and Ki67 immunostaining in 40 cervical atypical biopsies (CALs) with mild and focal histological features suggestive of HPV infection—20 cases with weak/focal p16 positive immunoreactivity and 20 cases negative for p16 expression. In 16/20 weak/focal p16 positive CALs (80%), the INNO-LiPA HPV genotyping detected hrHPV genotypes (HPV 31, 51, 56, 59, 26, 53, 66, 73, and 82). Co-infection of two or more hrHPV genotypes was often evidenced. HPV16 and 18 genotypes were never detected. Ki67 immunostaining was increased in 10/20 cases (50%). In 19/20 p16 negative CALs, hrHPV infection was absent and Ki67 was not increased. These results suggest that weak/focal p16 immunostaining represents the early stage of transcriptionally active infection, strongly related to the presence of less common hrHPV genotypes, probably with a slower transforming power, but with a potential risk of progression if the infection persists. HPV DNA genotyping and follow-up could be useful in these cases to verify if they are able to evolve into overt dysplastic changes and to improve knowledge of less common hrHPV genotypes.

Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance is a premalignant, plasma cell disorder. Due to the potential risk of progression to multiple myeloma or a plasma cell-related disorder, it is important for GPs to recognise and manage patients in this cohort appropriately. This article aims to improve understanding, recognition and management of these patients in primary care.

Traumatic esophageal laceration presenting as a tongue laceration

Esophageal injuries may occur spontaneously because of iatrogenic instrumental injury, foreign body impaction, or external trauma. Traumatic esophageal laceration is rare and can lead to significant morbidity such as perforation, mediastinitis, retropharyngeal abscess, or deep neck infection. Early detection of esophageal injury improves patient outcome and survival compared with a diagnosis that is delayed by more than 24 hours after rupture. We describe the case of a 45-year-old man with esophageal laceration after facial contusion and tongue laceration. Upper airway compromise is the major concern for emergency physicians. In a nonsurgical approach, close observation is needed because there is a potential risk of progression to delayed esophageal rupture. If there is clinical deterioration, repeat endoscopy or surgical intervention should be considered. Early detection of esophageal rupture in patients with minor head injuries can reduce mortality and morbidity and avoid major surgery and, in most cases, allows the esophagus to heal normally.