The epidemiology, genetics, and thrombosis risk of MPNs among Arabs are largely unknown. This may be attributed to scarce epidemiological data, particularly from our region. Our study included 381 Kuwaiti nationals with Ph-negative MPNs and a confirmed driver mutation involving JAK2 (exon 12 14), CALR, or MPL. This first regional study examines the demographics, clinical parameters, and thrombosis-related attributes of the participants. This study reported a median age of 58 years, with females and males representing 54.9% and 45.1%, respectively. ET was the most frequent subtype of Ph-negative MPNs in our population, accounting for 52.0% of the cases, followed by PV, found in 34.6% of the participants, and PMF, found in 8.4% of participants. The crude annual cumulative incidence of Ph-negative MPNs in Kuwait ranged from 0.674 to 3.177 per 100,000 population across the study period. The most common driver mutation was JAK2V617F, with a frequency of 89.5%. At diagnosis, 19.2% of the patients presented with unexplained thrombosis, and almost half were of arterial origins. Males were more likely to present with arterial thrombosis than females (61.5% vs. 35.3%), whereas venous thrombotic events were more common in females than in males (47.1% vs. 17.9%; p-value = 0.025). Ph-negative MPNs in Kuwait are rare; however, thrombosis is a frequent complication, being documented in up to 19.2% of cases at presentation, more commonly at arterial sites. These findings call for thorough evaluation of patients with unexplained derangements in their hematological parameters during follow-ups.

Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing.

MPLW515K or W515L mutation plays an important role in the pathogenesis of myeloproliferative neoplasms (MPNs) through signaling molecules of the cytokine receptor axis. Besides MPLW515K or W515L, more than 30 atypical MPL mutations have been reported in patients who are negative for JAK2V617F, MPLW515K/L, and CALR mutations. Here, we aimed to identify the disease-causing mutations in the triple-negative case of ET. We described two MPL mutations in patients diagnosed with ET by target sequencing the hotspot mutation region of MPL gene. The MPLA497-L498ins4 is an insertion mutation detected recurrently in ET patients, and the MPLW515RQ516E is a novel double-point mutation found in an ET patient. Functional studies of MPLA497-L498ins4 and MPLW515RQ516E revealed that they are gain-of-function mutations. Mutants of MPLA497-L498ins4 and MPLW515RQ516E promoted autonomous proliferation on Ba/F3 cells in the absence of IL-3. Autonomous activation of TPO-R without ligand TPO was observed in MPLA497-L498ins4 and MPLW515RQ516E mutants. Lower percentage of cells in G1 phase and higher percentage of cells in S phase of two atypical MPL mutants were detected after culturing without any cytokines. These two atypical MPL mutations also presented increase in phosphorylation of signaling proteins including JAK2/STAT, PI3K/AKT, and MAPK/RAS. In summary, the MPLA497-L498ins4 and MPLW515RQ516E are gain-of-function mutations which may be novel driving factors participating in the pathogenesis of triple-negative MPN.

The clinical characteristics and survival of patients with myeloproliferative neoplasms (MPNs) with secondary cancer were analyzed to explore the possible risk factors for secondary cancer in MPN patients.

Gastroesophageal Junction neuroendocrine neoplasms (GEJ-NENs) are rare and heterogeneous tumors. We aim to analyze the clinicopathlogical features and prognostic factors of GEJ-NENs and to compare the outcome of GEJ-NENs with other gastric NENs.

Percutaneous thermal ablation has become the preferred therapeutic treatment option for liver cancers that cannot be resected. Since ablative zone tissue changes over time, it becomes challenging to determine therapy effectiveness over an extended period. Thus, an immediate post-procedural evaluation of the ablation zone is crucial, as it could influence the need for a second-look treatment or follow-up plan. Assessing treatment response immediately after ablation is essential to attain favorable outcomes. This study examines the efficacy of image fusion strategies immediately post-ablation in liver neoplasms to determine therapeutic response.

The 8th tumor-node-metastasis (TNM) classification of the American Joint Committee on Cancer (AJCC) can be used to estimate the prognosis of gastric neuroendocrine tumor (gNET) and gastric neuroendocrine carcinoma (gNEC) patients but not gastric neuroendocrine neoplasms (gNENs).

Cyclin D2/D3 (CCND2/3) are core components of the machinery that drives cell cycle progression and therefore, are associated with tumorigenesis. Currently, there are contradictory evidences on the function of CCND2/3 in tumorigenesis. Thus, we conducted a comprehensive meta-analysis to derive a precise predictive value of CCND2/3 in various tumors. We searched PubMed, EMBASE, Web of Science for eligible studies up to October 8, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated using Forest plot analysis to demonstrate their associations. A total of 14 studies were ultimately included in this meta-analysis. Our results indicated CCND2/3 played an oncogenic role in all of the cancer patients (CCND2: pooled HR = 2.21, 95% CI: 1.67-2.93; CCND3: pooled HR = 2.29, 95% CI: 1.05-5.03). In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66-2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12-0.64). In addition, CCND3 was correlated to reduced OS in breast cancer patients (HR = 1.64, 95% CI: 1.07-2.52) and shorter DFS/PFS/RFS in bladder cancer patients (HR = 4.60, 95% CI: 1.89-12.57). Taken together, CCND2/3 could be the promising biomarkers for predicting the prognosis of patients with malignant neoplasms.

To explore the risk factors of thrombosis in patients with JAK2V617F -mutated myeloproliferative neoplasms (MPNs), a cohort of 1537 Chinese patients with JAK2V617F -mutated MPN was retrospectively analyzed. The Kaplan-Meier method and multivariate Cox analysis were used to study the risk factors of thrombosis in patients with JAK2V617F -mutated MPN. Among the 1537 MPN patients, 931, 468, and 138 had polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), respectively. The median follow-up time was 7 years (range 1-47), and 12.8% of patients (197/1537) died during this period. A total of 16.8% (259/1399) of PV and ET patients had secondary myelofibrosis, and 2.5% (38/1537) of patients developed acute myeloid leukemia (AML). Thrombotic events occurred in 43.9% (675/1537) of patients, among which 91.4% (617/675) were arterial thrombosis and 16.6% (112/675) were venous thrombosis. The number of thrombotic events in PV, ET, and PMF patients was 439 (47.2%), 197 (42.1%) and 39 (28.2%), respectively. The multivariate analysis indicated that age ≥60 years old, HCT ≥48%, at least one cardiovascular risk factor, a history of thrombosis, and JAK2V617F allele burden (V617F%) ≥50% are risk factors for thrombosis in JAK2V617F -mutated MPN. According to the results of the multivariate analysis, a risk model of thrombosis was established and comprised low-risk (0 points), intermediate-risk (1 points) and high-risk (≥2 points) groups, among which the incidence of thrombosis was 9.1%, 33.7% and 72.9%. For elderly patients with JAK2V617F -mutated MPN and a history of thrombosis, reducing the V617F%, controlling HCT and preventing cardiovascular risk factors are necessary measures to prevent thrombosis.

Treatment with PEGylated interferon-alpha2 (IFN) of patients with essential thrombocythemia and polycythemia vera induces major molecular remissions with a reduction in the JAK2V617F allele burden to undetectable levels in a subset of patients. A favorable response to IFN has been argued to depend upon the tumor burden, implying that institution of treatment with IFN should be as early as possible after the diagnosis. However, evidence for this statement is not available. We present a thorough analysis of unique serial JAK2V617F measurements in 66 IFN-treated patients and in 6 untreated patients. Without IFN treatment, the JAK2V617F allele burden increased exponentially with a period of doubling of 1.4 year. During monotherapy with IFN, the JAK2V617F allele burden decreased mono- or bi-exponentially for 33 responders of which 28 patients satisfied both descriptions. Bi-exponential description improved the fits in 19 cases being associated with late JAK2V617F responses. The decay of the JAK2V617F allele burden during IFN treatment was estimated to have half-lives of 1.6 year for the monoexponential response and 1.0 year in the long term for the bi-exponential response. In conclusion, through data-driven analysis of the JAK2V617F allele burden, we provide novel information regarding the JAK2V617F kinetics during IFN-treatment, arguing for early intervention.

Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal myeloid proliferative disorders characterized by sustained systemic inflammation. Despite its renowned importance, the knowledge concerning the inflammatory pathophysiology of these conditions is currently limited to studies on serum cytokines, while cellular immunity has rarely been investigated.

The detection of low-level persistent or relapsed B-cell neoplasms, particularly post-therapy, can be challenging, often requiring multiple testing modalities.

The study aims to evaluate the performance of three advanced machine learning algorithms and a traditional Cox proportional hazard (CoxPH) model in predicting the overall survival (OS) of patients with pancreatic neuroendocrine neoplasms (PNENs).

Patients who suffer from gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) often present with liver metastatic disease. The efficacy of primary tumor resection (PTR) for these patients remains controversial due to the relatively heterogeneous behavior of the primary tumor and the lack of clinical evidence. In this series, GEP-NEN patients with liver metastases (LM) were selected from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. A logistic regression model was used to analyze variables that were associated with PTR. A Cox proportional hazards model was used to identify independent prognostic risk factors. In total, 1547 patients were enrolled in our study, including 897 patients who underwent PTR. Resection of the primary tumor was associated with prolonged survival in all patients (5-year overall survival (OS) rates: 57.0% vs 15.4%, P < .001), and improved 5-year OS rates were observed in patients with gastric, small intestinal, colorectal, and pancreatic subtypes (39.7%, 73.3%, 24.6%, and 59.7%, respectively). On the multivariate analysis, PTR was an independent prognostic factor of prolonged OS (HR = 0.48, 95% CI: 0.39-0.59, P < .001). Patients with a young age (≤60 years), small intestinal or colorectal NENs, a large primary tumor, lymph node (LN) metastases, and high tumor differentiation were more likely to undergo PTR. However, patients with colorectal NENs or a large primary tumor (≥4 cm) were at an increased risk of death independently in the PTR subgroup. The risk factors for OS also included old age, gastric tumor location, and poor differentiation. In conclusion, although PTR prolonged OS in all GEP-NEN patients presenting with LM, surgical recipients should be considered carefully. Age, primary tumor site, size, and differentiation might help surgeons identify patients who could benefit from PTR.

This study aimed to investigate the characteristics of colonic neuroendocrine neoplasms (NENs) and to validate the prognostic value of the European Neuroendocrine Tumor Society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems.

To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes.

Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk-to-benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer.

Kidney renal clear cell carcinoma (KIRC), as a common case in renal cell carcinoma (RCC), has the risk of postoperative recurrence, thus its prognosis is poor and its prognostic markers are usually based on imaging methods, which have the problem of low specificity. In addition, cuproptosis, as a novel mode of cell death, has been used as a biomarker to predict disease in many cancers in recent years, which also provides an important basis for prognostic prediction in KIRC. For postoperative patients with KIRC, an important means of preventing disease recurrence is pharmacological treatment, and thus matching the appropriate drug to the specific patient's target is also particularly important. With the development of neural networks, their predictive performance in the field of medical big data has surpassed that of traditional methods, and this also applies to the field of prognosis prediction and drug-target prediction.

Tumor characteristics can be prognostically relevant in patients with high-grade serous ovarian carcinoma (HGSOC). This study aimed to determine whether different subtypes of HGSOC, especially the mesenchymal subtype, are associated with overall survival (OS) or progression-free survival (PFS) in patients with HGSOC.

Immune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from different studies were controversial.