Rare case of mantle cell lymphoma of the lacrimal sac

ABSTRACT Mantle cell lymphoma of the ocular and periorbital regions is extremely rare but should be considered in the differential diagnosis of lesions affecting the periorbital tissues. In this study, we present a rare case of mantle cell lymphoma of the lacrimal sac in a 65-year-old male presenting with a mass in the lacrimal sac region and epiphora. After clinical examinations and imaging studies, the mucocele was misdiagnosed. Considering the unexpected findings during external dacryocystorhinostomy, a frozen biopsy was performed, which confirmed the diagnosis of lymphoma.

Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

The influence of color vision deficiency on vessel visibility during colorectal endoscopic submucosal dissection and the potential advantage of red dichromatic imaging to achieve color vision barrier-free.

Objectives: Although color information is important in gastrointestinal endoscopy, there are limited studies on how endoscopic images are viewed by people with color vision deficiency. We aimed to investigate the differences in the visibility of blood vessels during endoscopic submucosal dissection (ESD) among people with different color vision characteristics and to examine the effect of red dichromatic imaging (RDI) on blood vessel visibility. Methods: Seventy-seven pairs of endoscopic images of white light imaging (WLI) and RDI of the same site were obtained during colorectal ESD. The original images were set as type C (WLI-C and RDI-C), a common color vision. These images were computationally converted to simulate images perceived by people with color vision deficiency protanope (Type P) or deutanope (Type D) and denoted as WLI-P and RDI-P or WLI-D and RDI-D. Blood vessels and background submucosa that needed to be identified during ESD were selected in each image, and the color differences between these two objects were measured using the color difference (ΔE 00) to assess the visibility of blood vessels. Results: ΔE 00 between a blood vessel and the submucosa was greater under RDI (RDI-C/P/D: 24.05 ± 0.64/22.85 ± 0.66/22.61 ± 0.64) than under WLI (WLI-C/P/D: 22.26 ± 0.60/5.19 ± 0.30/8.62 ± 0.42), regardless of color vision characteristics. This improvement was more pronounced in Type P and Type D and approached Type C in RDI. Conclusions: Color vision characteristics affect the visibility of blood vessels during ESD, and RDI improves blood vessel visibility regardless of color vision characteristics.

Current status of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms.

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

Gel immersion endoscopic mucosal resection for small gastric neoplastic lesions: A pilot study.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Outcomes of patients with active cancer after transcatheter aortic valve replacement: an updated meta-analysis.

BACKGROUND: Patients with active cancer and aortic stenosis may be under-referred for valve interventions due to concerns over a prohibitive risk. However, whether active cancer impacts outcomes after transcatheter aortic valve replacement (TAVR) remains unknown. METHODS: We searched PubMed, Embase, and Cochrane Library in December 2023 for studies comparing the post-TAVR outcomes of patients with versus without active cancer. We pooled odds ratios (OR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) applying a random-effects model. Statistical analyses were performed in R version 4.3.2. RESULTS: We included nine observational studies analyzing 133,906 patients, of whom 9,792 (7.3%) had active cancer. Compared with patients without cancer, patients with active cancer had higher short- (OR 1.33; 95% CI 1.15-1.55; p < 0.001) and long-term mortality (OR 2.29; 95% CI 1.80-2.91; p < 0.001) rates, not driven by cardiovascular mortality (OR 1.30; 95% CI 0.70-2.40; p = 0.40), and higher major bleeding rates (OR 1.66; 95% CI 1.15-2.42; p = 0.008). The higher mortality rate was sustained in an adjusted analysis (aHR 1.77; 95% CI 1.34-2.35; p < 0.001). There was no significant difference in cardiac, renal, and cerebral complications at a follow-up ranging from 180 days to 10 years. CONCLUSION: Patients with active cancer undergoing TAVR had higher non-cardiovascular mortality and bleeding rates, with comparable incidences of other complications. This highlights the need for a shared decision and appropriate patient selection considering cancer type, staging, bleeding risk, and optimal timing for intervention.

Development of a prognostic nomogram for esophageal squamous cell carcinoma patients received radiotherapy based on clinical risk factors.

Purpose: The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT). Methods: In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA). Results: T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, Δ computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003). Conclusions: For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS.

Symptom experiences and self-management strategies of patients with haematological malignancy undergoing chemotherapy: A qualitative study.

Objective: To explore symptom experiences and self-management strategies from the haematological malignancy patient's perspective. Methods: A qualitative descriptive approach was used to provide a direct and comprehensive understanding of the symptoms experienced and self-management strategies during treatment among patients with haematological malignancy. Fourteen patients with haematologic malignancies who received chemotherapy at a Chinese tertiary hospital were selected using purposeful sampling. Data were collected via semi-structured interviews and one-on-one patient sessions. The collected data were analysed using the content analysis methods. Reporting adhered to the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines. Results: The data from this study were categorized into four themes and eight subthemes: (1) the dynamics and complexity of symptom experience (nonlinear, and overloaded symptom burden); (2) strategies for coping with symptomatic change (actively responding to challenges, and facing symptoms negatively); (3) symptom affects interaction (symptoms affect family interactions, and symptoms affect social interactions); and (4) benefit from symptom management (promoting family relationships, and regaining a new role in society). Conclusions: Patients with haematological malignancy undergoing chemotherapy still face complex and variable symptoms, and there are still considerable challenges in symptom management. The findings underscore that health care providers should provide the necessary symptom assessment to enhance the well-being of patients based on the characteristics of the patient's symptom experience and symptom management needs at different stages of the disease.

Cancer Burden and Attributable Risk Factors of Cancers in China: Epidemiological Insights and Comparisons With India.

BACKGROUND: Cancer is a major health concern in China. Understanding the epidemiology of cancer can guide the development of effective prevention and control strategies. This study aimed to comprehensively analyze the cancer burden, time trends, and attributable risk factors of cancers in China and compare them with those in India. METHODS: We utilized the GLOBOCAN database for 2022, Cancer Incidence in Five Continents (C15 plus) series, and Global Burden of Disease (GBD) 2021 to extract data on cancer incidence, mortality, disability-adjusted life years (DALYs), and risk factors. Time-trend analysis was performed using a join-point regression model. Correlations between cancer DALY rates and risk factors were analyzed using linear regression. RESULTS: In 2022, China experienced 4,824,703 new cancer cases and 2,574,176 cancer-related deaths. Cancers also caused approximately 71.2 million DALYs in China in 2021. Compared with India, China has higher incidence, mortality, and DALY rates for various cancers. Breast and thyroid cancers in China have shown a rapid increase in the age-standardized incidence rate (ASIR), along with a substantial burden of lung, stomach, esophageal, and colorectal cancer. However, stomach and liver cancers in China showed a downward trend in ASIR. In 2021, diet low in milk was a major risk factor among females for colorectal cancer DALYs in China (23% of age-standardized DALYs) and India (22.9%). In China, smoking has been associated with increased DALYs due to lung cancer. CONCLUSIONS: China has a heavier cancer burden than India. The heavy burden of lung, stomach, esophageal, and colorectal cancers, combined with the rising incidence of breast and thyroid cancers, pose a critical challenge to public health in China. Cancer burden may be reduced through public health initiatives that prioritize primary prevention, prompt identification, and therapeutic intervention.

Burden of major cancer types in Almaty, Kazakhstan.

Globally, cancer is the second leading cause of death, with a growing burden also observed in Kazakhstan. This study evaluates the burden of common cancers in Almaty, Kazakhstan's major city, from 2017 to 2021, utilizing data from the Information System of the Ministry of Health. In Kazakhstan, most common cancers among men include lung, stomach, and prostate cancer, while breast, cervical, and colorectal cancers are predominant among women. Employing measures like disability-adjusted life years (DALYs), we found that selected cancer types accounted for a total DALY burden of 25,016.60 in 2021, with mortality contributing more than disability (95.2% vs. 4.7%) with the ratio of non-fatal to fatal outcomes being 1.4 times higher in women than in men. The share of non-fatal burden (YLD) proportion within DALYs increased for almost all selected cancer types, except stomach and cervical cancer over the observed period in Almaty. Despite the overall increase in cancer burden observed during the time period, a downward trend in specific cancers suggests the efficacy of implemented cancer control strategies. Comparison with global trends highlights the significance of targeted interventions. This analysis underscores the need for continuous comprehensive cancer control strategies in Almaty and Kazakhstan, including vaccination against human papillomavirus, stomach cancer screening programs, and increased cancer awareness initiatives.

Clinicohistopathological Correlation and Prognostic Significance of Molecular Biomarkers in Urinary Bladder Neoplasms: A Comprehensive Analysis.

BACKGROUND: Urinary bladder neoplasms constitute a heterogeneous group of tumors with diverse clinical behaviors and outcomes. Understanding the correlation between clinicopathological characteristics and the prognostic significance of molecular biomarkers in bladder cancer is vital for personalized treatment strategies and improved patient outcomes. OBJECTIVE: This prospective observational study aimed to comprehensively investigate the clinicopathological correlations and prognostic significance of molecular biomarkers in urinary bladder neoplasms. METHODS: A cohort of 174 patients diagnosed with urinary bladder neoplasm participated in this study. Clinicopathological data, including demographic information, medical history, imaging findings, and histopathological reports, were collected from the patient records. Tissue samples obtained from transurethral resection or biopsy were subjected to molecular biomarker analysis using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular profiling techniques. Longitudinal follow-up assessments were conducted to monitor disease progression, recurrence, and overall survival. RESULT: Out of 174 patients diagnosed with bladder neoplasms, the mean age of the patients was 62.4 years (±8.7), indicating that the study cohort primarily comprised elderly individuals. The majority of patients were male (126, 72.4%), reflecting the higher prevalence of bladder cancer among men compared to women. Preliminary analysis revealed significant associations between clinicopathological parameters, molecular biomarker expression profiles, and clinical outcomes in patients with urinary bladder neoplasms. Elevated expression levels of specific biomarkers such as tumor protein p53 (p53), Ki-67, and estimated glomerular filtration rate (EGFR) were observed in advanced tumor stages (p < 0.001) and higher histological grades (p < 0.05), indicating their potential prognostic significance. Furthermore, genetic alterations detected using molecular profiling techniques, including chromosomal gains and losses, were significantly correlated with aggressive disease phenotypes and increased recurrence risk (p < 0.01). Longitudinal follow-up data demonstrated that patients with elevated biomarker expression levels or genetic alterations had poorer treatment responses and shorter overall survival durations than those with lower biomarker expression levels. CONCLUSION: This study highlights the importance of integrating clinicopathological parameters and molecular biomarker data for the risk stratification, treatment selection, and prognostic assessment of urinary bladder neoplasms.

Identification of lateral pelvic nodes without metastasis in patients with rectal cancer treated with preoperative chemoradiotherapy or chemotherapy based on magnetic resonance imaging.

Background: Intensive localized therapy is promising for the treatment of rectal cancer. In Japan, chemoradiotherapy (CRT) and neoadjuvant chemotherapy (NAC) are used as preoperative treatments for this disease. Magnetic resonance imaging (MRI) is used to diagnose lateral pelvic node (LPN) metastases, but the changes in LPN findings on MRI following preoperative treatment are unclear. Furthermore, there may be patients in whom LPN dissection can be omitted after CRT/NAC. Methods: Patients who underwent total mesorectal excision with LPN dissection after CRT/NAC at 13 Japanese Society for Cancer of the Colon and Rectum member institutions between 2017 and 2019 were included. Changes in the short diameter of the LPNs after CRT/NAC and the reduction rate were examined. Results: A total of 101 LPNs were examined in 28 patients who received CRT and 228 in 47 patients who received NAC. Comparison of LPNs before and after CRT/NAC showed that most LPNs shrank after CRT but that the size reduction was variable after NAC. Although some LPNs with a short diameter of <5 mm showed residual metastasis, no metastases were observed in LPNs that were <5 mm in short diameter before and after CRT/NAC and did not shrink after treatment. Conclusion: Although the short diameter of LPNs was significantly reduced by both CRT and NAC, even LPNs with a short diameter of <5 mm could have residual metastases. However, dissection may be omitted for LPNs <5 mm in short diameter that do not shrink after preoperative CRT or NAC.

[Budd-Chiari syndrome and JAK2 gene mutation].

Budd-Chiari syndrome (BCS) is a rare vascular disorder characterized by obstruction of hepatic venous outflow, culminating in elevated hepatic and portal venous pressure. BCS is associated with myeloproliferative neoplasms (MPN) in 40% of cases, which is significantly higher than the rate observed in other venous thrombotic conditions, and suggests that MPN may contribute to the etiology of BCS. In particular, the JAK2 V617F mutation has recently attracted substantial attention, given its profound association with thrombogenesis, mechanically implicated through endothelial damage, increased blood cell adhesion, and facilitation of neutrophil extracellular trap formation. A common treatment approach consists of anticoagulation for prevention and treatment of thrombosis, and cytoreductive therapy targeting MPN. However, as no definitive evidence exists for this approach, a bespoke therapeutic strategy tailored to individual patient profiles is required.

Can Patients With Urogenital Cancer Rely on Artificial Intelligence Chatbots for Treatment Decisions?

OBJECTIVES: In the era of artificial intelligence, almost half of the patients use the internet to get information about their diseases. Our study aims to demonstrate the reliability of the information provided by artificial intelligence chatbots (AICs) about urogenital cancer treatments. METHODS: The most frequently searched keyword about prostate, bladder, kidney, and testicular cancer treatment via Google Trends was asked to 3 different AICs (ChatGPT, Gemini, Copilot). The answers were evaluated by 5 different examiners in terms of readability, understandability, actionability, reliability, and transparency. RESULTS: The DISCERN score evaluation indicates that ChatGPT and Gemini provided moderate quality information, while Copilot's quality was low. (Total DISCERN scores; 41, 42, 35, respectively). PEMAT-P Understandability scores were low (40%) and PEMAT-P Actionability scores were moderate only for Gemini (60%) and low for the others (40%). Their readability according to the Coleman-Liau index was above the college level (16.9, 17.2, 16, respectively). CONCLUSIONS: In the era of artificial intelligence, patients will inevitably use AICs due to their easy and fast accessibility. However, patients need to recognize that AICs do not provide stage-specific treatment options, but only moderate-quality, low-reliability information about the disease, as well as information that is very difficult to read.

Association of Shorter Time to Recurrence and Recurrence-free Survival with Transthoracic Lung Biopsy in Stage I Lung Cancer.

Purpose: We aim to determine whether preoperative percutaneous needle aspiration or biopsy (PCNA/Bx) increases recurrence risk and reduces survival in stage I lung cancer patients, using a nationwide lung cancer registry. Materials and Methods: We retrospectively included 3,452 patients diagnosed with stage I lung cancer who underwent curative surgery between 2014 and 2019, as recorded in the Korean Association of Lung Cancer Registry. To balance the characteristics of patients with and without PCNA/Bx, we applied inverse probability of treatment weighting. We used cumulative incidence plots and a weighted subdistribution hazard model to analyze time to recurrence. Recurrence-free survival and overall survival were analyzed using Kaplan-Meier curves and weighted Cox proportional hazard ratio models. Results: In patients with adenocarcinoma, the use of PCNA/Bx was associated with a 1.9-fold increase (95% CI, 1.5-2.4) in the risk of recurrence and a 1.7-fold decrease (95% CI, 1.3-2.2) in recurrence-free survival. Subgroup analysis based on pathologic pleural invasion revealed that the risk of recurrence increased when PCNA/Bx was performed, with 2.1-fold (95% CI, 1.5-2.8) in patients without pleural invasion and 1.6-fold (95% CI, 1.0-2.4) in those with pleural invasion. No association was found between the use of PCNA/Bx and overall survival. Conclusion: Preoperative PCNA/Bx was associated with increased recurrence risks in stage I adenocarcinoma, regardless of pathologic pleural invasion status. In early lung cancer cases where adenocarcinoma is strongly suspected and curative surgery is feasible, the use of transthoracic biopsy should be approached with caution.

Involvement of CREB3L1 in erythropoiesis induced by JAK2 exon 12 mutation.

CREB3L1, a gene encoding the endoplasmic reticulum stress transducer, is specifically overexpressed in platelet RNA from patients with myeloproliferative neoplasms (MPNs). However, the pathophysiological roles of CREB3L1 overexpression remain unclear. In the present study, we aimed to study CREB3L1 mRNA expression in the red blood cells (RBCs) of patients with MPN and its role in erythrocytosis. Elevated expression of CREB3L1 was exclusively observed in the RBCs of patients with polycythemia vera (PV) harboring JAK2 exon 12 mutations, but not in those harboring JAK2 V617F mutation or control subjects. In erythropoiesis, CREB3L1 expression was sharply induced in erythroblasts of bone marrow cells collected from patients with JAK2 exon 12 mutation. This was also evident when erythropoiesis was induced in vitro using hematopoietic stem and progenitor cells (HSPCs) with JAK2 exon 12 mutation. Interestingly, overexpression of CREB3L1 in RBCs was observed in patients with reactive erythrocytosis whose serum erythropoietin (EPO) levels exceeded 100 mIU/mL. Elevated CREB3L1 expression was also observed in the erythroblasts of a patient with acute erythroid leukemia. EPO-dependent induction of CREB3L1 was evident in erythroblasts differentiated from HSPCs in vitro, regardless of driver mutation status or MPN pathogenesis. These data strongly suggest that CREB3L1 overexpression in RBCs is associated with hyperactivation of the EPO receptor and its downstream molecule, JAK2. shRNA knockdown of CREB3L1 expression in HSPCs blocked erythroblast formation in vitro. These results suggest that CREB3L1 is required for erythropoiesis in the presence of JAK2 exon 12 mutation or high level of EPO, possibly by antagonizing cellular stress.

Link between isolated para-aortic lymph node metastasis and intrauterine cancer site in early stage endometrial cancer.

OBJECTIVE: Missing occult para-aortic lymph node metastasis is one of the primary concerns of sentinel lymph node biopsy in endometrial cancer. Our study aimed to evaluate the relationship between intrauterine cancer site and isolated para-aortic lymph node metastasis to tailor treatment and reduce the false negative rate of the sentinel lymph node procedure. METHODS: A retrospective, multicenter, case control study was performed in four international centers. All patients with positive lymph nodes who had complete surgical staging with pelvic and para-aortic lymphadenectomy, between January 2013 and December 2023, were included. Detailed descriptions of the cancer location within the uterine cavity on the cranio-caudal plane and the myometrial wall involvement on the cranio-caudal and ventro-dorsal planes were collected, as were clinical data and cancer histological features. Patients with isolated para-aortic lymph node metastasis were allocated to group 1; patients with pelvic lymph node metastasis and those with both pelvic and para-aortic lymph node metastasis were allocated to group 2. The groups were compared according to the variables collected. RESULTS: 200 preoperative early stage endometrial cancer patients with postoperative International Federation of Gynecology and Obstetrics 2009/2023 stage IIIC1/IIIC2 were included in our study: 42 patients (21%) with isolated para-aortic lymph node metastasis were allocated to group 1 and the remaining patients to group 2. The two groups had comparable clinical and pathological characteristics (p>0.05): mean age was 66.5±10.3 (group 1) and 63.5±11.9 (group 2); endometrioid histotype was the predominant one for both groups (50%); most patients had myometrial infiltration >50% (80.9% and 79.7%), grade 3 (61.9% and 63.9%), and lymph vascular space invasion (78.5% and 82.2%). Cancers involving the fundal uterine cavity, the fundal myometrial wall, or the anterior myometrial wall were 3.11 (1.04-9.27), 3.03 (1.12-8.21), and 2.12 (0.77-5.80) times more likely to metastasize only to para-aortic lymph nodes compared with cancers located in other uterine sites. CONCLUSIONS: In this study, the intrauterine location of the cancer determined the site of lymph node metastasis. When the tumor involved the fundus (cavity or wall) and infiltrated exclusively the anterior wall, the baseline risk of spreading only into the para-aortic area increased significantly in selected patients at risk of nodal disease.

Impact of gated FDG PET/CT on the staging of patients with suspected or proven newly diagnosed advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer: results from a non-randomized, phase II clinical trial.

OBJECTIVE: Imaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT. METHODS: The IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques. RESULTS: A total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients. CONCLUSIONS: Gated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients. TRIAL REGISTRATION NUMBER: NCT02258165.