Common Subtype Research Articles

Epidemiology, trends, and survival of ocular and orbital rhabdomyosarcoma: a nationwide study in the USA (1996-2018) : Ocular and orbital rhabdomyosarcoma in the USA.

Rhabdomyosarcoma (RMS) is a rare malignancy that affects both children and young adults. Therefore, the current incidence and mortality rates of ocular and orbital rhabdomyosarcoma (ORMS) need to be clarified. We aimed to explore the epidemiology, trends, and survival outcomes of ORMS in the United States population spanning over two decades, from 1996 to 2018. We retrospectively reviewed 92,633 patients with ocular and adnexal malignancies and identified 640 ORMS cases from the North American Association of National Cancer Registries. Demographics, tumor characteristics, treatment modalities, and survival outcomes were analyzed. Most ORMS cases (71.7%) were reported in children aged-0-9 years. The age-adjusted incidence of ORMS was 0.1 per million population (ppm), with males demonstrating a higher incidence (0.12 ppm) than females (0.09 ppm). Whites had the highest incidence rate (0.11 ppm). Embryonal ORMS is the most common histological subtype. The incidence trend over the 22-year study period revealed a decline in ORMS from 0.124 to 0.076, in contrast with the incidence of whole-body RMS, which showed an insignificant increase. The 5-year relative survival rates of patients with ORMS were 89.7%, whereas the 10-year relative survival rate was 87.2%. The 5-year relative survival trend for ORMS increased but was insignificant. ORMS primarily affects young children and males, with the embryonal subtype being the most common. Despite the declining incidence, survival rates have remained stable, underscoring the need for further research on the risk factors, diagnostics, and management strategies to improve patient outcomes. What is known Ocular and Orbital Rhabdomyosarcoma (ORMS) predominantly affects children, especially males, and is the most frequent primary tumor in the orbit during childhood. The embryonal subtype is the most common histological subtype of ORMS. What is new A significant decline in the incidence of ORMS was observed over the 22-yearstudy period, in contrast to the overall incidence of whole-body rhabdomyosarcoma. It has a characteristic bigeminal distribution with a peak at 3-4 and another at 6 years. Patients receiving combined treatment modalities showed improved survival rates, while those undergoing surgery alone had poorer outcomes. Despite advancements in treatment, there has been no significant increase in the 5-year relative survival trends for ORMS.

Management of Carcinoma of Esophagus in Old Patient with Panchagavya Therapy as a Palliative Care-A Case Report

ABSTRACT Esophageal cancer is a male-dominant, aggressive malignancy with a five-year survival rate of 15%-20%, predominantly affecting developed nations. Esophageal squamous cell carcinoma (ESCC) is the most common subtype. This case study involves a 70-year-old man with ESCC, who was suffering from difficulty swallowing, inability to burp, constant nausea, and occasional trouble swallowing water for two months. He was successfully treated with Panchagavya Chikitsa, which included Panchagavya Ghrita, Gomutra Arka, Kwath of Amla-Yashtimadhu-Shatpushpa, Haritaki Churna, Haridra Ghanvati, and Vibhitaki Avaleha, along with Nasya, Nabhipurana with Panchagavya Ghrita, and Matra Vasti with Tila Taila over six months. Significant symptom improvement was observed, attributed to the Rasayana (rejuvenative), Balya (strengthening), and Jeevaniya (vitality-enhancing) properties of the treatments. These properties inhibit cancer growth, nourish tissues, and restore balance due to their antioxidant effects. Panchagavya formulations showed promising results without adverse effects, highlighting their efficacy in improving the quality of life for this geriatric patient with ESCC.

Abstract A054: Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma

Abstract Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well- differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated biological functions of MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p- AKT, mTOR, p70S6K, MMP2 and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression. Citation Format: Fernanda Costas C. de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nippin Sp, Joal D Beane, Luciano Mazzoccoli, Matias Montes, Giovanni Nigita, Joe T Sharick, Jennifer L Leigth, Federica Calore, Dawn Chandler, Raphael E Pollock. Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A054.

Abstract B017: MicroRNA and proteomic analyses of plasma extracellular vesicles detect diffuse large B-cell lymphoma

Abstract Background: Liquid biopsy offers a non-invasive method for detection of non-Hodgkin lymphoma (NHL). Tissue biopsy, the standard method of NHL detection, causes patient discomfort and increases risk of infection. Extracellular vesicles (EVs) are secreted by cells as particles with cargos of nucleic acids and proteins enclosed in a lipid bilayer. The most common NHL subtype is diffuse large B-cell lymphoma (DLBCL). We analyzed plasma-derived EVs from DLBCL patients and matching healthy controls for microRNA (miRNA) and protein to identify potential liquid biopsy biomarkers. Approach: Plasma samples (1 mL) from DLBCL patients and healthy controls were eluted through Izon size-exclusion chromatography (SEC) to obtain EVs. The size distribution of EVs was characterized with nanoparticle tracking analysis. For miRNA analysis, SEC EVs from three DLBCL patients and three matching healthy controls underwent further selection by immunocapture and release according to NHL antigens CD19, CD20, CD22, and C37, with an EV microfluidic affinity purification (EV-MAP) chip. Western blot confirmed the presence of these NHL antigens in NHL cell lysate and NHL cell culture SEC EVs, with flow cytometry verifying expression on NHL cells. MiRNA from these immunocaptured EVs were then isolated and sequenced with Qiagen kits. MiRNA levels were assessed for fold change (FC) expression between cases and controls. Upregulated miRNAs from DLBCL patients were compiled with the miRNA Enrichment Analysis and Annotation Tool (miEAA). For proteomic analysis, SEC EVs from ten DLBCL patients and ten matching healthy controls were measured with label-free mass spectrometry and a custom peptide library. Protein levels were assessed for FC expression and compiled with the Mann-Whitney U test. Results: The size of EVs ranged from 50–300 nm. Exclusively different upregulated miRNAs (FC>2, p<0.05, FDR p<0.05) were found by selection with different antigens: None unique with CD19, one with CD20, eight with CD22, and one with CD37. MiR-320b was upregulated with CD20 (FC=52, p=0.0002, FDR p=0.02), and miR-3168 with CD37 (FC=906, p=0.0003, FDR p=0.02). With CD22, miR-190b-5p, let-7c-5p, miR-1-3p, miR-125b-5p, miR-133a-3p, miR-153-3p, miR- 184, and miR-206 were upregulated in DLBCL patients (FC>17, p<0.003, FDR p<0.05). The miEAA recognized all the upregulated CD22 miRNAs as overrepresented in B-cell lymphoma, except for miR-190b-5p. Proteomic analysis of EVs found 42 different exo-proteins with AUC>0.90 (p<0.05) and 12 different exo-proteins with AUC>0.95 (p<0.009) upregulated in DLBCL patients. Two upregulated exo-proteins (FC>2.81, p<0.0002, adjusted p<0.004), ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) and von Willebrand Factor (vWF), achieved a perfect AUC=1 (p=0.00001) for all DLBCL patients and healthy controls. Conclusions: These results support the hypothesis that liquid biopsy of plasma EVs detect DLBCL. Upregulated miRNA and proteomic signatures via EVs indicate the presence of DLBCL for non-invasive NHL detection. Citation Format: Arthur A. Lee, Sagar Rayamajhi, Mengjia Hu, Harsh Pathak, Rajni V. Puri, Kamilla Isakova, Mei Han, Claire S. Berquist, Samuel G. Mackintosh, Stephanie D. Byrum, Dennis W. Province, Mohammod M. Rahman, Foyez Ahmmed, Leonidas E. Bantis, Malgorzata A. Witek, Steven A. Soper, Andrew K. Godwin, Haitham Abdelhakim. MicroRNA and proteomic analyses of plasma extracellular vesicles detect diffuse large B-cell lymphoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B017.

Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

Abstract 4138483: Outcomes of Hypoplastic Left Heart Syndrome by Subtype and Presence of Ventriculocoronary Connections: A Fetal Heart Society Multi-Center Retrospective study

Background: Hypoplastic left heart syndrome (HLHS) is classified by subtype: mitral atresia and aortic atresia (MA-AA), mitral stenosis and aortic atresia (MS-AA), and mitral stenosis and aortic stenosis (MS-AS). It is controversial whether specific HLHS subtypes and presence of ventriculocoronary connections (VCC) are associated with transplant-free survival. We aimed to determine whether there is an increased risk of mortality associated with specific HLHS subtypes, whether this risk is stratified by the presence of VCC, and if a specific type of stage I palliation in patients with VCC improves survival. We also aimed to determine practice variation in the evaluation of HLHS patients with VCC. Methods: We performed a multicenter retrospective cohort study of fetuses and infants < 2 months of age with HLHS admitted between 1/2012-12/2016 to participating Fetal Heart Society institutions. Patients with HLHS variants were excluded. We collected patient specific data and surveyed participating centers for practice variation. Kaplan-Meier curves with log-rank test were used to assess transplant-free survival and cox proportional hazard analysis was performed with adjustment for center as a random intercept. Results: 341 patients from nine centers were included. MA-AA was the most common subtype (177, 52%), followed by MS-AA (102, 30%), and MS-AS (62, 18%). VCC were diagnosed or suspected in 65 patients (19%). A total of 287 patients were live born with intention to treat. HLHS subtype was not associated with transplant-free survival (Figure 1A). Presence of VCC was associated with a lower transplant-free survival (p=0.026, Figure 1B). In the subset of patients diagnosed with VCC, there was not a significant difference in survival based on type of stage I palliation (Figure 1C). Cox proportional hazard modeling adjusted for center demonstrates that presence of VCC has a hazard ratio of 1.74 (CI 1.02-2.98), p =0.04. Survey data regarding practice variation for patients with VCC (Figure 2) demonstrates 33% of centers modify the type of stage I palliation based on presence of VCC. Conclusions: In a multicenter cohort of HLHS patients, patients with VCC had lower transplant-free survival compared to those without VCC, while subtype and type of stage I palliation did not have a statistical difference. There is considerable practice variation in the management of HLHS patients with VCC that may warrant further investigation.

Intra-class switch among interleukin-17 inhibitors for the treatment of plaque psoriasis: a single-center experience

Psoriasis is a chronic immune-mediated disease primarily affecting the skin. The most common subtype is plaque psoriasis, which can affect any body area, with a predilection for the knees, elbows, scalp, lumbosacral region, and genitalia. The European guidelines adopted in Italy recommend systemic therapies for moderate-to-severe psoriasis, defined by a Psoriasis Area and Severity Index (PASI) ≥ 10, Dermatology Life Quality Index (DLQI) ≥ 10, and/or Body Surface Area (BSA) ≥ 10. Over the past two decades, the development of biological agents has revolutionized psoriasis management, targeting specific cytokines such as TNF-α, IL-23, and IL-17. Among these, ixekizumab, secukinumab, brodalumab, and bimekizumab are approved for the treatment of moderate-to-severe plaque psoriasis. However, some patients require switching therapy because of primary/secondary ineffectiveness or side effects. We retrospectively analyzed 20 patients who had switched from one anti-IL-17 drug to another, assessing both safety and effectiveness. 70% of patients was represented by males, with a median age of 49.5 years. The most frequent comorbidities were arterial hypertension and hypercholesterolemia. Effectiveness was evaluated in terms of a 90% (PASI90) and 100% (PASI100) reduction in PASI compared to baseline at 16 and 52 weeks. Before switching to the current IL-17 inhibitor, seven patients had failed at least two biologics. Thirteen patients experienced a loss of effectiveness after more than 6 months (secondary ineffectiveness), whereas the other seven never showed improvement with the previous drug (primary ineffectiveness). Fourteen patients completed at least one year of follow-up. Two patients were lost during the follow-up, while four more are currently still under treatment without having completed the established temporal cut-off. Two patients switched to bimekizumab, nine to brodalumab, and nine to ixekizumab. At baseline, the median PASI was 10 (IQR 4.5). After 16 weeks, the median PASI decreased to 2 (IQR 5.5), and after one year, it was 1 (IQR 2). Eight patients (40%) and six patients (30%) achieved PASI 90 and PASI 100 at 16 weeks, respectively. After one year, sustained effectiveness was observed with PASI 90 (57.1%), PASI 100 (35.7%), and PASI ≤ 2 (78.6%). No serious adverse events or discontinuations due to adverse events were observed during the study period. Our study confirms the safety and effectiveness of intraclass switching among IL-17 antagonists, highlighting that an inter-class switch can be a valid option when patients fail to respond or lose effectiveness with an IL-17 inhibitor. However, further larger and longer studies are needed for a deeper understanding.

Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction

Introduction: Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that LOY may be associated with lower survival rate of patients with STEMI. Aims: Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI. Methods: This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique. Results: During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15, P = 0.018), 2.11 (95% CI: 1.11–4.01, P = 0.024), and 1.88 (95% CI: 1.02–3.45, P = 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY < 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY < 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67; P = 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81; P = 0.035) increased risk of all-cause mortality than males with LOY < 18%, whereas the risk was similar to males with LOY ≥ 18%. Conclusion: LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.

EPCO-58. INTEGRATIVE PROTEOGENOMIC ANALYSES REVEAL INSIGHTS INTO SUBTYPE-SPECIFIC GLIOMA RISK

Abstract Gliomas are heterogeneous brain tumors with prognostically-significant subtypes and few risk factors. IDH-wildtype glioblastoma, the most common subtype, carries a dismal prognosis. Using the largest GWAS dataset with histological (11,304 cases, 304,523 controls) and molecular (3,418 cases, 8,156 controls) subtypes, we analyzed the plasma and brain proteome to uncover proteins associated with glioma susceptibility. Using protein quantitative trait loci (pQTL) for 1,776 proteins in brain tissue, we identified 21 candidate proteins, including 9 associations with high probability (>70%) of colocalization (shared causal genetic variants for glioma risk and protein abundance). We confirmed known risk genes such as EGFR (p=1.9×10-35) and D2HGDH (p=1.1×10-5). We also identified novel risk proteins, including ENPP6, a choline phosphodiesterase overexpressed in glioma, for IDH-wildtype glioblastoma (OR=0.62, p=7.6×10-5), and galectin-3, a lectin encoded by a tumor fitness gene in CRISPR screens of glioma proliferation and a clinical drug target, for glioma overall (OR=1.37, p=1.3×10-5). Analyses of the plasma proteome using pQTLs for 1,362 proteins from 3 cohorts (N=88,838) identified 9 colocalized associations in whole blood. Most risk signals were subtype-specific, such as CRELD1 (p=2.5×10-5) for triple-negative glioblastoma. We found three candidate risk proteins for IDH-mutant 1p19q-intact glioma: immunoglobulin glycoprotein BCAM (p=9.6×10-8), neurotrophin receptor SorCS2 (p=3.6×10-5) and immune checkpoint PD-1 (p=1.1×10-5). Interestingly, genetically-predicted PD-1 levels had a larger effect on IDH-mutant 1p19q-intact (OR=2.75, 95% CI=1.61-4.69) than IDH-wildtype (OR=0.73, 95% CI=0.51-1.05) tumors, suggesting germline differences in immune checkpoint mechanisms among subtypes. For all colocalized candidates, genetically-predicted protein abundance was correlated with cis-regulated transcriptional activity in brain tissue. For example, genetically-predicted SORCS2 gene expression in brain tissue was associated with plasma SorCS2 levels (Z=16.1, p=1.1×10-68). Our analysis identified candidate proteins involved in immune response and neuronal proliferation, which may enable prioritization of drug targets and provide insight into disease mechanisms for glioma.

Clinical features, treatment options and outcomes in primary cutaneous B-cell lymphomas: a real-world, multicenter, retrospective study.

Primary cutaneous B-cell lymphomas (PCBCLs) are rare cutaneous neoplasms with limited literature regarding treatment options and associated treatment outcomes. This study aimed to investigate and present real-world treatment outcomes in patients with PCBCLs. All patients with PCBCL who were treated in five major referral centers for cutaneous lymphoma in Greece over 10 years were retrospectively included with their baseline characteristics and treatment-associated outcomes collected and analyzed. In total, 235 PCBCL patients, of whom 125 (53.2%) were females, were included. The median age at diagnosis was 60 years (IQR 47-72), and the median follow-up duration was 3 years (IQR 1.3-6.4). The most common subtype was primary cutaneous marginal zone lymphoma (PCMZL) (52.3%), followed by primary cutaneous follicle center lymphoma (PCFCL) (40.9%), and primary cutaneous large B-cell lymphoma, leg type (PCDLBCL, LT) with 16 (6.8%) cases. Complete responses (CRs) were observed in 77.3% after first-line treatment. Both radiotherapy (RT) and surgical excision (SE) achieved superior outcomes, with 88.9% and 89% achieving CR, respectively. Relapses occurred in 22.6% of initial complete responders. The median time to the next treatment (TTNT) for the PCMZL and PCFCL was 349 days. RT and topical/intralesional steroids demonstrated longer TTNT compared to SE (445 and 359 vs. 154 days). For PCMZL and PCFCL, the 1-year progression-free survival (PFS) was 84.2% (75.7-89.9) and 85% (75.1-91.2), and the 5-year PFS was 66.5% (55.2-75.5) and 58.8% (44.4-70.7), respectively. PCBCLs have favorable outcomes. RT demonstrates significantly increased TTNT compared to SE, suggesting RT as the preferable option. After careful evaluation, "watch and wait" may be a reasonable option for asymptomatic patients.

Frequent Occurrence of High-Risk Basal Cell Carcinoma in Xeroderma Pigmentosum: A Histopathological Insight From an Indian Cohort.

Xeroderma pigmentosum (XP) is a genodermatosis, characterized both by premature aging and significantly increased risk of non-melanoma and melanoma skin cancers at an early age. However, limited literature is available on the common histopathological subtypes of basal cell carcinoma (BCC) in these patients. In this ambispective case series, we recruited patients of XP who had either a currently present skin tumor or previously excised one, provided their histopathological sections were available. Cytogenetic analysis was performed in all the patients. The histopathological findings were recorded by two trained dermatopathologists. Of 22 recruited patients with XP, 12 patients had 41 BCCs, and 23 (56.09%) of them showed a high-risk histopathological subtype. Basosquamous carcinoma (10, 24.39%) was the most frequent high-risk tumor followed by infiltrative variant (7, 17.07%). Mixed-histopathological subtypes were noted in six (14.63%) cases, and all of them had a high-risk component. The low-risk subtypes included nodular (n = 17, 41.46%) and superficial BCC (1, 2.43%). Though a deep dermal involvement was seen in 27 (65.85%) lesions, none showed a perineural invasion or necrosis. Three (7.31%) lesions showed ulceration, while 10 (24.39%) showed presence of pigmentation. A frequent occurrence of high-risk basal cell carcinoma was noted in patients with XP-mandating creation of appropriate treatment and follow-up strategies in these patients.

The relationship between seasonality and the diagnosis of acute leukaemia in central South Africa

Background: Leukaemias are haematological malignancies resulting from the abnormal clonal proliferation of haematopoietic precursors. Their incidence is influenced by various environmental and genetic factors.Aim: With this retrospective descriptive study, the authors aimed to explore the possible influence of seasonality on the type and number of acute leukaemia (AL) diagnoses made at the Universitas Academic Hospital (UAH) National Health Laboratory Service (NHLS) from 01 January 2018 to 31 December 2021.Setting: Universitas Academic Hospital, Bloemfontein, South Africa.Methods: Archived laboratory reports of all patients diagnosed with lymphoid and myeloid during the study period were included. Patients’ age, sex, ethnicity, final diagnosis and date of diagnosis were recorded. Information was pseudonymised to maintain confidentiality. A descriptive statistical analysis was performed to explore the possible influence of seasonality on the number of cases and type of leukaemia diagnosed.Results: In all, 249 patients were included. Acute myeloid leukaemia (AML) was the most common AL subtype (n = 117; 47.0%). Over the 4-year study period, all AL subtypes were more frequently diagnosed in summer (n = 131; 52.6%). However, the monthly number of AL diagnoses was relatively consistent over the 4 years for all subtypes (p = 0.7603), with consistent peaks of AML cases during January and February (summer) and May (autumn).Conclusion: No statistically significant association between the different seasons and AL diagnosis was noted.Contribution: Further studies using a larger study population and a wider geographical area, conducted over a more extended period, might affect the observations made in this study

Clinical characteristics and functional outcomes of pediatric Guillain-Barré syndrome admitted to the Neuro-intensive care unit: a decade-long retrospective observational study.

Guillain-Barré Syndrome (GBS) remains a significant contributor to acute flaccid paralysis in pediatric patients worldwide. Despite its impact, studies focusing on pediatric GBS requiring intensive care unit (ICU) management are limited. This study aimed to address this gap by exploring the clinical and outcome characteristics of pediatric GBS necessitating ICU care. This retrospective observational study, spanning a decade, analyzed the records of 75 pediatric GBS patients admitted to the Neuro-ICU of a tertiary care center in South India. Data included demographics, prodromal symptoms, clinical features, investigations, treatment modalities, and outcomes. The majority (55/75) of patients were male, with a median age of 12 years. The highest incidence of GBS requiring ICU admission was in the monsoon season. Prodromal symptoms were observed in 56%. Most patients (93.33%) presented with typical GBS symptoms, and 40% had respiratory distress on ICU admission. Acute motor axonal neuropathy (AMAN) was the most common subtype. Approximately 80% required mechanical ventilation, with a median duration of 22.5 days. No in-hospital mortality was recorded. At discharge, most patients had a GBS disability score of 4, improving to 2 at a median follow -up of 228 days. Pediatric GBS patients requiring ICU care exhibit distinctive characteristics, including a higher prevalence of AMAN subtype, seasonal clustering, and favorable outcomes with intensive treatment. The absence of in-hospital mortality underscores the effectiveness of prompt ICU admission and dedicated Neuro-intensive care.

Corynoxine suppresses lung adenocarcinoma proliferation and metastasis via inhibiting PI3K/AKT pathway and suppressing Cyclooxygenase-2 expression

BackgroundLung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer.MethodsThe impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice.ResultsIn this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstrated that treatment with Corynoxine resulted in the suppression of PI3K/AKT signaling and a consequent drop in cyclooxygenase-2 (COX-2) expression. These findings were further confirmed in vivo in mice harboring A549 tumor xenografts in which Corynoxine was able to interfere with the PI3K/AKT/COX-2 signaling axis.ConclusionThis study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

HPV infection status among women of all ages in Jinshan District, Shanghai.

We explored the prevalence of human papillomavirus (HPV) infection among women in Jinshan District, Shanghai. We analyzed all HPV testing samples sent from our unit between December 2023 and April 2024. We reported the HPV prevalence overall, by age, and by subtype. In total, 3788 women aged 16 to 90 years had HPV test results. The prevalence of infection with any HPV subtype was 17.9%. The HPV prevalence by age group was: ≤30 years, 15.4%; 31-40 years, 14.7%; 41-50 years, 17.0%; 51-60 years, 22.4%; >60 years, 31.0%. Among HPV-positive women, 80.6% had infection with one subtype, 16.4% had dual infection, and 3.1% had three or more subtypes detected. We found 640 cases (16.9%) of infection with high-risk HPV subtypes and 139 cases (5.04%) of infection with low-risk HPV subtypes. The most common high-risk subtypes were HPV 52, 53, 58, and 16; the most common low-risk subtypes were HPV 81, 70, and 42. We detected ≥1 HPV subtype among most women in our study. The prevalence of HPV was lowest in younger women and highest in women age >60 years. Tailored strategies for older women are needed to prevent HPV infection and cervical cancer.

Advanced Granulosa Cell Tumors of the Ovary: A Review with a Focus on Current and Novel Therapeutic Approaches.

Granulosa cell tumor (GCT) is the most common nonepithelial ovarian malignancy. Still, it is considered rare, with a paucity of high-level evidence guiding management, particularly in the metastatic setting. Advancements in molecular pathology allowed the identification of several targetable mutations that play an important role in GCT pathogenesis. Although current management approaches rely on guidelines extrapolated from the more common epithelial subtype, the unique histopathologic and molecular characteristics of GCTs entail a more focused approach. Systemic therapy remains the cornerstone treatment for advanced disease, and although chemotherapy has been the standard for decades, targeted treatments have gained considerable attention lately. Due to the rarity of this disease, validation of new therapies in large trials is the rate-limiting step for developing evidence-based recommendations. This review sheds light on pathogenesis, clinical and molecular characteristics, and prognostic factors, and discusses current treatment options including the role of novel therapies and immune checkpoint inhibitors in advanced GCT.

Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

MLLT3 knockdown suppresses proliferation and cell mobility in human lung adenocarcinoma.

Lung cancer is emerging as one of the most frequently encountered malignancies around the world that carries high morbidity and mortality. Lung adenocarcinoma (LUAD) has become the most common subtype of lung cancer. MLLT3 or named AF9 was first characterized in acute myeloid leukemia and can downregulate the expression of several critical genes. The aim of this study was to explore the function of MLLT3 in the progression of LUAD and related molecular mechanisms. Immunohistochemistry was employed to assess MLLT3 expression in LUAD tissues, while quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were utilized to detect MLLT3 expression levels in lung adenocarcinoma cell lines. These results revealed a significant overexpression of MLLT3 in LUAD cell lines and tissues. We further uncovered an association between MLLT3 expression profiles in LUAD tissues and metastasis, as well as TNM stage. Survival analysis showed that elevated MLLT3 correlated with a poorer survival rate. We also found that MLLT3 knockdown repressed LUAD cells invasion, migration, and proliferation in vitro, while inducing cell cycle arrest and apoptosis of LUAD cells. Moreover, knocking down MLLT3 inhibited tumor growth in vivo. Specific markers of apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and MLLT3-induced signaling were examined by Western blot. We demonstrated that MLLT3 knockdown inhibited the activity of the EGFR-MAPK/ERK signaling pathway, and MLLT3 might be a novel diagnostic biomarker and therapeutic target in lung adenocarcinomas.

Stromal tumor infiltrating lymphocytes in hormone receptor positive/HER2 negative metastatic breast cancer

The immune landscape of hormone receptor positive, HER2-negative metastatic breast cancer (HR+/HER2- mBC), the most common subtype of BC, remains understudied. This is mainly due to reduced sample acquisition opportunities from metastases as compared to primary tumors. In this study, we explored stromal tumor-infiltrating lymphocytes (sTIL) in metastatic samples collected through our post-mortem tissue donation program UPTIDER (NCT04531696). sTIL were scored as a continuous parameter according to international guidelines on 427 metastases and 38 primary untreated tumors acquired from 20 patients with HR+/HER2- mBC. ER-status was evaluated on 362 metastases with a cut-off for positivity set at 1% according to ASCO/CAP guidelines. Our analyses show that 54% and 15% of metastases had sTIL levels >1% and >5% respectively. sTIL levels tended to be lower in metastases as compared to their respective primary tumor (Estimate: -2.83, 95%CI: -5.77-0.11, p:0.07). sTIL levels were lower in metastases from invasive lobular carcinoma than in metastases from invasive breast carcinoma of no special type (Estimate: -1.67, 95%CI: -2.35--0.98, p:<0.001). A loss of ER expression was observed in 14% of all metastases, yet a negative ER-status was not significantly associated with increased sTIL levels. Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.