Spleen Diameter Research Articles

ICG-r15 predicts esophageal varices in compensated liver cirrhosis: a noninvasive approach

ObjectiveThe aim of our study was to evaluate the indocyanine green (ICG) retention test as a noninvasive marker of esophageal varices(EV).MethodsThe clinical data of patients diagnosed with compensated liver cirrhosis in Tianjin Second People’s Hospital between January 2018 and January 2021 were analysed with SPSS 23.0.ResultA total of 144 patients (88 M/56 F, 51.7 ± 11.06 years) were enrolled. The ICG retention at 15 min(ICG-r15), PVD, TBIL, Cholinesterase(CHE), AST to ALT ratio(ARR), APRI, splenic area, Lok index, Park index and liver stiffness measurement in the absent or small EV group were lower than those in the medium or large EV group, while the ICG disappareance rate(ICG-K), Effective hepatic blood flow(EHBF), ALB, PLT, and Platelet to Spleen Diameter Ratio(PSDR) were higher, and the differences were significant (P < 0.05). ICG-r15, splenic area, APRI and PLT were independent predictors for medium or large esophageal varices (OR = 1.115, 1.025, 0.281, and 0.987, respectively,P < 0.05). The predictive value of ICG-r15 for medium or large varices was 17.95%, the specificity was 0.849, and the sensitivity was 0.662, the AUROC was 0.815. The cut-off value of PLT for M/L EV was 113.5, and the specificity and sensitivity were 0.616 and 0.887, the AUROC was 0.759. The AUROC of ICG-r15 combined with PLT was 0.866, which was more superior than others.ConclusionAlthough we are far from the replacement of endoscopy, ICG-r15 combined with PLT seems to be able to identify patients with medium or large EV in patients with compensated liver cirrhosis.

The Interplay between Severe Cirrhosis and Heart: A Focus on Diastolic Dysfunction.

Background/Objectives: Cardiovascular involvement in severe cirrhosis presents diagnostic challenges and carries significant prognostic implications. This study aims to evaluate the relationship between liver disease severity and portal hypertension with the burden of diastolic dysfunction. Methods: We prospectively enrolled patients with hepatic cirrhosis, classified according to the Child-Pugh criteria. Of the 102 patients included, 65 were classified as Group A (non-severe cirrhosis: Child-Pugh Classes A and B) and 37 as Group B (severe cirrhosis: Child-Pugh Class C). Portal vein and spleen diameters were assessed using abdominal ultrasound. All patients underwent echocardiographic evaluation. LV systolic function was assessed by measuring ejection fraction, while diastolic function was evaluated using three parameters: E/Em ratio, E/Vp ratio, and indexed left atrial volume. Results: We observed a significantly greater burden of diastolic dysfunction in Group B compared to Group A. Specifically, the E/Vp ratio was 2.2 ± 0.4 in Group B versus 1.9 ± 0.3 in Group A (p < 0.001); the indexed LA volume was 34.5 ± 3.2 mL/m2 in Group B versus 30.1 ± 2.9 mL/m2 in Group A (p < 0.001); and the E/Em ratio was 17.0 ± 3.0 in Group B versus 11.5 ± 2.8 in Group A (p < 0.001). Additionally, the mean diameters of the portal vein and spleen were larger in Group B, with measurements of 14.3 ± 2.1 mm versus 11.5 ± 1.6 mm for the portal vein and 15.0 ± 1.2 mm versus 11.7 ± 1.5 mm for the spleen (p < 0.001), which correlated with the extent of diastolic dysfunction. Conclusions: Diastolic dysfunction was prevalent in 55% of patients with liver cirrhosis. The burden of diastolic dysfunction was higher in patients with severe hepatic cirrhosis compared to those with milder forms, and it correlated with the severity of portal hypertension, as assessed by measuring portal vein diameter and spleen diameter.

Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI

Introduction and objectivesIn this study, we aim to develop a model for predicting Gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Materials and methodsThis study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. ResultsA total of 40 CHB patients were enrolled and categorized into the high-risk group (n=15) and the non-high-risk group (n=25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. ConclusionThe prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Assessment of Sensitivity of Fib-4, Lok Score and Platelet Count / Spleen Diameter Ratio as Non-Invasive Indicator of Esophageal Varices in Egyptian Patients with Chronic Hepatitis C virus (HCV) Infection

Abstract Background The development of esophageal varices is one of the major complications of portal hypertension, which is considered a main complication of liver cirrhosis.Variceal bleeding occurs in 20–40% of cirrhotic patients with esophageal varices and The use of endoscopic prophylactic band ligation and non-selective beta blockers can decrease the risk of esophageal bleeding by 50%, so the current guidelines recommend screening all liver cirrhosis patients by endoscopy. Aim of the Work Assessment of sensitivity of fib-4, lok score and platelet count / spleen diameter ratio as non-invasive indicator of oesphageal varices in egyptian patients with chronic hepatitis c virus (hcv) infection. Patients and Methods This study will include 100 egyptian patients selected from internal medicine and hepatology outpatient clinics and inpatient wards at matria teaching hospital. Results Plt count/spleen diameter ratio, plt count and spleen diameter demonstrated a high statistically significant correlation with the presence and grade of esophageal varices. as according to sensitivity and specificity test the most accurate screening test for diagnosis of esophageal varicose is PLT/SD ratio as AUC (87.4%), also it is a good negative test as specificity (86.7%) with cutoff value (1026.7), but for suspect a case most sensitive test is PLT count as sensitivity (93.3%) with cutoff value (120.5). these tests followed by spleen diameter with accuracy (78.2%), and the least test is right lobe/ albumin ratio which cannot depend on it in diagnosis of esophageal varices as its accuracy is (52.2%),sensitivity 66.7% and specificity 48.3%. Conclusion The use of plt count/spleen diameter ratio, plt count and spleen diameter, especially the platelet count/spleen diameter ratio, can help physicians as noninvasive predictors of esophageal varices to restrict the use of endoscopic screening only to patients presenting a high probability of esophageal varices. This is especially useful in clinical settings where resources are limited and endoscopic facilities are not present in all areas.While rt liver lobe/albumin ratio can not be used as a non invasive predictor of esophageal varices.

Point Shear Wave Elastography for Splenic Assessment: A Comparative Study of Splenomegaly and Normal Spleens.

Background The spleen, a key immunological organ, plays a crucial role in filtering aged or damaged red blood cells. Splenomegaly, an enlargement of the spleen, can arise from a variety of physiological and pathological conditions, including hematological disorders, hepatic diseases, and infections. Accurate diagnosis and evaluation of splenomegaly are essential for effective treatment. Objectives The objective of this study was to evaluate splenic stiffness in patients with splenomegaly using point shear wave elastography (pSWE) and compare the findings with those of individuals with normal spleen. Materials and methods This hospital-based observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, from October 2022 to December 2023. The study included 56 participants, divided into two groups: 28 patients with splenomegaly and 28 healthy controls. Spleen stiffness was measured using a Samsung HS70A ultrasound machine (Samsung Electronics Pvt. Ltd., Seoul, South Korea), and pSWE was performed with a curvilinear probe. Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), and the significance of differences was assessed using an independent t-test with a p-value of <0.05, considered statistically significant. Results The mean spleen stiffness, measured in kilopascals (kPa), was significantly higher in individuals with splenomegaly (32.05 ± 12.54 kPa) compared to controls (22.9 ± 9.49 kPa) (p = 0.003). A positive correlation (rho = 0.482, p < 0.001) was observed between spleen diameter and spleen stiffness. Conclusion This study demonstrates that pSWE is an effective, non-invasive tool for assessing spleen stiffness. The higher spleen stiffness in splenomegaly patients underscores pSWE's diagnostic utility, with a positive correlation between spleen diameter and stiffness. Further multi-center studies are recommended to validate these findings, highlighting pSWE's promise in evaluating and monitoring splenic disorders.

Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure

Background and aimsOxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. MethodsWe made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. Results41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48–133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71–23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. ConclusionThe increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Use of non-invasive scales for detecting esophageal varices in paediatric patients with portal vein thrombosis

IntroductionPortal vein thrombosis (PVT) is the most frequent cause of portal hypertension in paediatric population. Baveno VI Consensus considers endoscopic variceal ligation (EVL) as the second therapeutic option after Meso-Rex bypass (surgical shunt). AimAnalyse the diagnostic profitability of non-invasive scales in order to predict the risk of esophageal varices (OV) in children with PVT. Materials and methodsDescriptive retrospective study where every upper gastrointestinal endoscopy (UGE) carried on patients <15 years old with non-cirrhotic PVT were included. There were divided according to the presence of OV and sex, cause, age, previous gastrointestinal bleeding or treatments, results of UGE and scales (Clinical Prediction Rule-CPR), Varices Prediction Rule-VPR), King’s Variceal Prediction Score-K-VaPS) and Platelet count / Spleen diameter Ratio-PSR). Qualitative variables were expressed as absolute frequency and percentage, and quantitative variables as median and intercuartilic range. U Mann–Whitney and Hanley–McNeil tests were used for comparisons. Results45 UGE were analysed. 80% (n = 36) presented OV: median of 3(2–3) and 33,3%(n = 12) required EVL. Statistical differences were demonstrated between both groups: CPR (142,39 (132,22–166,53) vs. 122,75 (115,24–133,15); p = 0,003), VPR (9,91 (9,36 – 11,75) vs. 5,6 (3,34–8,39) p = 0,001), K-VaPS (117,86 (99,66–126,58) vs. 99,64 (94,88–110,18) p = 0,019), PSR (2384,62 (1902,22–3201,63) vs. 1252,5 (579,6–2144,42) p = 0,05), with and area under the curve AUROC > 75%, without statistical differences between scales. ConclusionsIn paediatric patients with non-cirrotic PVT non-invasive scales can be used as a tool to predict the presence of OV and raise the indication of UGE.

Spleen Stiffness-Based Algorithms Are Superior to Baveno VI Criteria to Rule Out Varices Needing Treatment in Patients With Advanced Chronic Liver Disease.

The Baveno VI criteria have set the stage for noninvasive assessment of compensated advanced chronic liver disease (ACLD). The algorithm combining liver stiffness measurement (LSM, <20 kPa) and platelet count (>150,000/μL) safely avoids screening endoscopy for varices needing treatment (VNT) but identifies only a relatively low number of patients. We aimed to evaluate the value of spleen stiffness measurement (SSM) using spleen-dedicated elastography in ruling out VNT. In this real-life multicenter retrospective derivation-validation cohort, all consecutive patients with ACLD (defined by LSM ≥10 kPa) with available upper endoscopy, laboratory results, spleen diameter, LSM, and SSM measured with spleen-dedicated transient elastography were included. VNT were defined as medium-to-large varices or small varices with red spots. In the derivation cohort (n = 201, 11.9% VNT), SSM demonstrated excellent capability at identifying VNT (area under the receiver operating characteristic curve [AUROC] 0.88), outperforming LSM (AUROC 0.77, P = 0.03) and platelets (AUROC 0.73, P = 0.002). In comparison with Baveno VI criteria (33.8% spared endoscopies), the sequential Baveno VI plus SSM and a novel spleen size and stiffness model were able to increase the number of patients avoiding endoscopy (66.2% and 71.1%, respectively) without missing more than 5% of VNT. These findings were confirmed in an external validation cohort of patients with more advanced liver disease (n = 176, 34.7% VNT) in which the number of spared endoscopies tripled (27.3% and 31.3% for SSM-based algorithms) compared with Baveno VI criteria (8.5%). Spleen stiffness-based algorithms are superior to Baveno VI criteria in ruling out VNT in patients with ACLD and double the number of patients avoiding screening endoscopy.

Combining Spleen Diameter and the Baveno VI Criteria Assessed by 2-Dimensional Shear Wave Elastography to Rule Out High-Risk Varices.

Patients with compensated advanced chronic liver disease (cACLD) can safely spared screening esophagogastroduodenoscopy (EGD) when they meet the Baveno VI criteria as assessed by transient elastography. Recently, the cutoff values of the Baveno VI criteria assessed by 2-dimensional shear wave elastography (2D-SWE) were proposed. We aimed to validate it to rule out high-risk varices (HRVs) in cACLD patients; combine spleen diameter (SPD) with the Baveno VI criteria and assess whether it can spare more screening EGD. A total of 173 cACLD patients with successful liver stiffness (LS) measurements and EGD examinations were included. We analyzed the risk factors that predicted HRVs and compared the performances of different models for ruling out HRVs. The platelet count, LS, and SPD were independent predictors of HRVs. The AUCs of platelet count, LS, spleen stiffness and SPD for diagnosing HRVs were 0.797, 0.757, 0.834, and 0.804, respectively. The Baveno VI criteria assessed by 2D-SWE spared 25.4% of EGD screenings and missed 2.4% of the HRV patients. Combining SPD ≤11.1 cm with the Baveno VI criteria could spare more EGD screenings than just applying the Baveno VI criteria (45.1% vs 25.4%, P < 0.001), and missed 4.9% of the HRV patients. The Baveno VI criteria assessed by 2D-SWE could be safely applied in cACLD patients to rule out HRV patients. The combined model Baveno VI/SPD could safely and significantly increase the rate of spared EGD.

Evaluation of Noninvasive Tools for Predicting Esophageal Varices in Patients With Cirrhosis at Tygerberg Hospital, Cape Town.

Background: In patients with cirrhosis, esophageal variceal hemorrhage (EVH) is a devastating consequence of portal hypertension (PH). Upper endoscopy is considered the gold standard for the detection and diagnosis of esophageal varices (EVs), despite being invasive and costly. This study was aimed at identifying and evaluating the diagnostic accuracy of noninvasive tools in predicting EVs in patients with compensated cirrhosis. Methods: This cross-sectional study included 50 patients with compensated cirrhosis at the Tygerberg Hospital Gastroenterology Clinic in Cape Town between November 2022 and May 2023. We collected clinical, anthropometric, and laboratory data from patients' physical and electronic charts. All patients underwent an abdominal ultrasound, vibration-controlled transient elastography (VCTE) to assess liver and splenic stiffness, and upper endoscopy. In this comparative study, we evaluated the diagnostic accuracy of different noninvasive tools in detecting EVs in patients with compensated cirrhosis. Results: Of the 50 patients included in the study, 30 (60%) were female and 20 (40%) were male. The patients' age ranged from 18 to 83, with a mean age of 46.6 years. Cirrhosis was mainly due to alcohol use (n = 11, 22%), hepatitis B virus (HBV) infection (n = 11, 22%), and autoimmune hepatitis (n = 10, 20%). The patients included in the study were divided into two subgroups: with (n = 34, 68%) or without (n = 16, 32%) EVs. Statistically significant differences were detected between groups in platelet count (PC), liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter (PVD), bipolar spleen diameter (SBD), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), platelet/bipolar spleen diameter ratio (PSR), liver stiffness-spleen size-platelet ratio (LSPS), liver stiffness-spleen stiffness-platelet ratio score (LS3PS), and spleen stiffness-spleen size-platelet ratio score (SSPS) (p < 0.001). The highest diagnostic precision was observed with SSM (96%), SSPS (96%), LS3PS (94%), LSPS (94%), PSR (94%), and PC (92%). SBD (88%), LSM (86%), APRI (82%), and FIB-4 (82%) had the lowest diagnostic accuracy. Conclusion: SSM and SSPS have the highest diagnostic accuracy for predicting the presence of EVs in patients with compensated cirrhosis. LSPS, LS3PS, and PSR come second at 94%. We recommend SSM and SSPS in institutions with transient elastography equipped with the software necessary to measure splenic stiffness. We introduce and propose LS3PS as a novel composite score for predicting the presence of EVs in patients with compensated cirrhosis. Large-sample-size studies are needed to validate these prediction scores and to allow direct comparison with Baveno VII. These prediction tools can help clinicians avoid unnecessary endoscopic procedures in patients with compensated cirrhosis, especially in developing countries with limited resources such as South Africa.

Accuracy of non-invasive diagnosis of esophageal varices among cirrhotic patients in a low-income setting

Cirrhosis is a chronic liver disease that is frequently complicated by increased portal venous pressure and the formation of EV. The most common clinical manifestation of portal hypertension is esophageal varices, and ruptured varices are the most fatal complication of portal hypertension. The diagnosis and follow-up of esophageal varices is done by Esophagogastroduodenoscopy, but in most developing countries, the follow-up of cirrhotic patients by gastrointestinal endoscopy remains a challenge. ObjectiveAssessment of diagnostic accuracy of noninvasive tests as predictors of esophageal varices among cirrhotic patients at University of Gondar comprehensive Hospital. MethodInstitution based cross-sectional study was conducted among cirrhotic patients from March 2022–October 2022. All study participants underwent screening for Esophageal Varices, Spleen Diameter, Platelet count and Platelet count/spleen diameter ratio. Data were analyzed using SPSS version 26. ROC curves were plotted for Spleen Diameter, Platelet count and Platelet count/spleen diameter ratio with specific cutoffs determined. Diagnostic performance was assessed using ROC curve. The diagnostic thresholds were specified with their sensitivity, specificity, positive predictive value, negative predictive value positive and negative likelihood ratios. ResultA total of 206 patients were included. The mean age was 41.84 year and SD of (41.84 ± 12.398). About 79.4 % percent were males. Endoscopy confirmed esophageal varices were present in 176(85.4 %) cases. Sixty-seven percent of cases had decompensated cirrhosis (Child-Pugh class B&C). The platelet count to spleen diameter ratio less than 818 had a PPV of 94.7 % (AUROC = 0.835), while spleen diameter greater than 145 mm had 93.7 % PPV (AUROC = 0.783). At a platelet count cutoff <121,000/mm3, the PPV was 95.1 % (AUROC = 0.818). ConclusionIn this study, platelet count, spleen diameter, and PC/SD all performed well for EV diagnostics, with PC/SD outperforming the others. This finding supports the use of these noninvasive indicators for the diagnosis and implementation of prophylactic treatment foe esophageal varices in health institutions where gastrointestinal endoscopy is unavailable.

Clinical and Immunological Factors Associated with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis Patients

Allogeneic hematopoietic stem cell transplantation (HSCT) is widely recognized as the sole curative treatment for myelofibrosis (MF). However, patients with MF often experience graft function impairment despite successful engraftment and absence of relapse signs. Although it has been reported that poor graft function can have a negative impact on the outcomes of patients with MF after HSCT, the specific factors that can influence poor graft function are not yet clearly understood. In this background, we analyzed various clinical and immunological factors that may contribute to poor graft function after transplantation. The study included 93 patients who underwent HSCT for the treatment of MF at Seoul St. Mary's Hospital between the years 2000 and 2022. By cumulative incidence analysis of poor graft function (death, relapse, graft failure, and loss of chimerism as competing risks), we evaluated which pre-HSCT factors has significant impact on poor graft function after HSCT. The definition of poor graft function and graft failure in this study followed the criteria set by the European Society for Blood and Marrow Transplantation (EBMT). We measured the longitudinal diameter of spleen up to 2 months prior to HSCT, and classified the patients into pre-HSCT splenomegaly (≥ 14cm) or not. Next, we investigated the association of immune-related gene expression signature in bone marrow immune-microenvironment with the occurrence of poor graft function, by performing targeted gene expression profiling and gene set enrichment analysis using a custom NanoString panel composed of 579 immune-related genes in pre- and post-HSCT BM samples from patients with poor graft function and good graft function (total 24 samples). A median age of 93 patients was 57 years, and 55.9% were male. Secondary MF was observed in 30.1% of the cases. Fifty-three (57.0%) received graft from a matched sibling donor graft and 40 (43.0%) from a matched unrelated donor. Sixty-three (67.7%) patients were classified to the pre-HSCT splenomegaly group. In terms of ABO match, 45 (48.4%) patients were matched, 10 (10.8%) had bi-directional mismatch, 17 (18.3%) had major mismatch, and 19 (20.4%) had minor mismatch. The median infused CD34 (+) cell dose was 6.4 x 10^6/kg (Interquartile range 5.3 x 10^6/kg-8.3 x 10^6/kg). In our patients, cumulative incidence of poor graft function after 5 years from HSCT was 32.0% (95% CI: 23.4-42.7). Infused CD34 (+) cell dose, the presence of splenomegaly before HSCT were revealed to have an impact on the occurrence of poor graft function after HSCT. The other significant factor associated with poor graft function was ABO mismatch, in particular, with a substantial difference between matched patients and patients with bi-directional ABO mismatch. (Figure A). In NanoString panel analysis, although the expression of immune-related genes mostly upregulated after HSCT, genes related to processes such as complement system, inflammasomes, phagocytosis and degradation, and MHC class II antigen presentation pathways were significantly downregulated in PGF. Whereas, oxidative stress, inflammasomes, and autophagy pathways were downregulated in GGF (Figure B). In this study, we could observe that a significant proportion of MF patients undergoing HSCT experienced poor graft function. Factors that significantly associated with the occurrence of poor graft function included the CD34 (+) cell dose at the time of HSCT, the presence of splenomegaly before HSCT, and ABO mismatch. Interestingly, distinct gene expression signatures present in IME between pre- and post-SCT in both PGF and GGF. Further research is warranted to investigate the impact of poor graft function caused by these factors on outcomes such as transfusion requirements and quality of life.

Importance of FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) in Staging and Response Assessment of Hairy Cell Leukemia (HCL)

Alessandro Mancini and Luca De Carolis are Co-first authors. Nicodemo Baffa, Brunangelo Falini and Enrico Tiacci are Co-last authors. INTRODUCTION HCL is an indolent BRAF-mutated leukemia usually presenting with cytopenias, splenomegaly, little or no lymphadenopathy, heavy bone marrow (BM) infiltration and few circulating leukemic cells. Imaging exams for staging include abdominal echography and computed tomography (CT), while the role of PET is largely unknown. METHODS 84 patients (pts) with relapsed/refractory HCL participating to our clinical trials of BRAF inhibitor-based therapies prospectively underwent PET/CT pre- and post-treatment, in addition to usual examinations for response assessment. Since FDG uptake is normally higher in liver than spleen, BM and lymph nodes, uptake in the latter tissues was considered abnormal if equal to or higher than the liver. Splenomegaly was defined by a longest spleen diameter &amp;gt;13 cm on PET/CT. The standard definition of complete remission (CR) in HCL just requires no palpable splenomegaly on physical examination, in addition to resolution of cytopenias as well as no hairy cells visible in the blood smear and the BM biopsy by non-immunological stains. RESULTS Pre-therapy, 58/77 (75%) non-splenectomized pts showed abnormal splenic FDG uptake (maximal standardized uptake value/SUVmax: median 4.8, vs 3.9 for the liver), which was always diffuse without focal lesions. Conversely, focal splenic uptake is not infrequent in splenic marginal zone lymphoma (18%, 7/39 pts - Abdom Radiol 2018;43:2721; vs of 0/58 HCL pts, p=0.0003), which may aid in the differential diagnosis with this HCL-mimicker. Moreover, 14/58 (24%) HCL pts. with a PET+ spleen did not have splenomegaly, and splenic uptake returned to normal in 10/11 evaluable cases (91%) achieving at least a partial response post-therapy, which suggests leukemic spleen involvement even without splenomegaly. Abnormal diffuse BM uptake was observed in 41/82 evaluable pts (50%; median SUVmax 5, vs 3.4 for the liver). In these cases, leukemic involvement in the BM biopsy was greater (median 80%) than in the other 41 pts (median 65%; p-value &amp;lt;0.01), pointing to HCL infiltration as the cause of abnormal BM uptake rather than to reactive hyperplasia of non-involved BM. Post-therapy, pathologic spleen uptake normalized in 46/51 evaluable pts (90%), and their CR rate was higher (32/46 pts, 70%) than in the other 5 pts remaining PET+ (1/5, 20%; p=0.047). Among the 46 PET- cases, 31 (67%) were not splenomegalic while 15 (33%) had residual splenomegaly (up to 17 cm; Fig. 1A); interestingly, within PET- cases relapse-free survival (RFS) was similar not only in conventionally defined CR cases with (n=8) vs without (n=24) residual non-palpable splenomegaly (p=0.84 after a median follow-up of 19 months), but also when the 6 cases meeting all conventional CR criteria except for still palpable splenomegaly were added to the 8 CR pts with residual non-palpable splenomegaly (p=0.7 after a median follow-up of 20.5 months - Fig. 1B). These findings suggest that metabolic status reflects splenic HCL involvement more reliably than spleen size or palpability, a concept that could improve the current definition of CR in HCL. Abnormal BM uptake resolved after treatment in 34/37 evaluable pts (92%), and their CR rate was again higher (23/34, 68%) than in the other 3 pts remaining PET+ (0/3; p=0.047). Leukemic infiltration of the BM biopsy was lower in the 34 PET- vs the 3 PET+ pts (median 5% vs 70%-80%, respectively; p=0.0004), indicating that BM abnormal uptake reflects HCL infiltration load rather than reactive BM hyperplasia post-therapy. Finally, abnormal lymph node uptake was observed pre-therapy in 9/84 (11%) pts (median SUVmax 7.1, vs 3.4 for the liver) and normalized after treatment in 7/8 evaluable pts (88%), including one case with residual lymph node enlargement (2.2 cm); all these 7 pts had achieved a CR while the remaining pt had no response to therapy. CONCLUSIONS PET is potentially useful in the differential diagnosis with splenic marginal zone lymphoma and may aid in the clinical management of HCL pts by detecting metabolic involvement of the main disease sites even in the absence of organomegaly. Importantly, PET signal tracks with response to therapy even in case of persistent organomegaly, which may lead to refine the definition of CR in HCL.

Efficacy and Safety of Obinutuzumab in Relapsed or Refractory Hairy Cell Leukemia (R/R HCL): An Italian Multicenter Phase-2 Academic Trial (HCL-PG04)

INTRODUCTION About 50% of HCL patients (pts) relapse after chemotherapy with purine analogs (PA). After identifying the BRAF-V600E mutation as the genetic cause of HCL (Tiacci et al. NEJM 2011), we documented a high efficacy of the BRAF inhibitor vemurafenib in R/R pts (Tiacci, Park et al. NEJM 2015), especially when added to rituximab (Tiacci et al. NEJM 2021). HCL expresses bright CD20 and obinutuzumab (OBI) is a more effective anti-CD20 agent than rituximab (RTX) in other indolent B-cell neoplasms such as chronic lymphocytic leukemia and follicular lymphoma. RTX produces ~20% complete remissions (CR) in R/R HCL (Kreitman, ASH Educ Program 2012), while OBI activity in this setting is unknown. METHODS In the ongoing academic, phase-2, multi-center trial HCL-PG04, R/R HCL pts needing treatment due to cytopenia(s) received OBI 1000 mg intravenously on days 1-8-15 of cycle 1 and on day 1 of cycles 2-6 (1 cycle = 28 days). CR required resolution of cytopenias (platelets ≥ 100,000/mmc; neutrophils ≥ 1500/mmc; hemoglobin ≥ 11 g/dl), no palpable splenomegaly and no leukemic cells on morphologic analysis of the bone marrow biopsy, as assessed one month after the last OBI dose. Minimal residual disease (MRD) was analyzed by BRAF-V600E specific PCR in the bone marrow aspirate (sensitivity: 0.05% mutant alleles). RESULTS We enrolled 26 pts (M/F 24/2; median age 62 years, range 39-80) with a median of 2 prior therapies (range 1-7), including 7 refractory to PA (26%) and 2 to RTX (8%). Median values of disease burden parameters at baseline were: 70% BM HCL infiltration, 830 neutrophils/mmc, 62000 platelets/mmc, 14 g/dl hemoglobin, and 16 cm of longest spleen diameter (in 16/26 splenomegalic patients; 1 pts. had been splenectomized and 9 were not splenomegalic at baseline). Toxicity was as expected, largely of grade (G) 1-2, always reversible and mainly consisting in: infusion reactions (G1-2 92%; G3 4%, in a single pt allergic to previous RTX who discontinued OBI); asymptomatic increase of liver enzymes (G1-2 19%; G3 GGT 15%; G3 ALT 4%); transient worsening of baseline G1-G3 thrombocytopenia to G3 (23%) or G4 (35%), with only 1 minor bleeding (4%, G1 epistaxis); transient neutropenia (G2 4%; G3 15%; G4 15%); and rare infections (G1-2 herpes labialis 8%; G3 pneumonia 4%). CR was reached in 12/25 evaluable pts (48%), including 2 pts with incomplete platelet recovery (~70000-90000/mmc) and 2 pts with delayed resolution of palpable splenomegaly. Notably, CR was achieved in 5/7 pts refractory to PA and 1/2 pts refractory to RTX. Furthermore, CR was negative for MRD in 9/12 pts (75%, including 3 pts with delayed MRD clearance), something never observed with vemurafenib. However, the kinetics of cytopenia resolution was slower compared to our previous vemurafenib trial, in that in pts obtaining CR with OBI neutrophil recovered to ≥1500/mmc after a median of 7 weeks (vs 4 weeks with vemurafenib) and platelets recovered to ≥100000/mmc after a median of 8 weeks (vs 2 weeks with vemurafenib). Prior exposure to RTX (n=12 pts) did not compromise OBI efficacy (5 CR, all MRD-negative, in 11 evaluable pts). In pts achieving CR with OBI, progression-free and MRD-free survival were both 100% at 56 months (range 20-66) and 48 months (range 6.5-60) of median follow-up, respectively (Fig.1). The 13 non-CR pts (minor response 7; no response 3; progression 3) were effectively salvaged with another course of OBI combined with vemurafenib, which will be presented at the meeting. CONCLUSIONS OBI frequently produced deep and durable responses in R/R HCL, to an extent apparently greater than RTX, thus qualifying as an active and safe chemotherapy-free strategy in this setting.

Porto-spleno-mesenteric venous thrombosis after elective splenectomy: a retrospective cohort study

BackgroundElective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe complications of this procedure. The aim of this study was to evaluate risk factors associated with development of porto-spleno-mesenteric venous thrombosis after elective splenectomy.MethodsAll cases of elective splenectomy carried out from April 1st 2017 to January 31st 2023 were included in this single centre retrospective cohort study. Patients’ demographics and perioperative data were analysed and correlated with the incidence of postoperative thrombosis. All patients underwent postoperative doppler ultrasound screening for thrombosis. Analysis was performed using SPSS 28, with p-value &amp;lt; 0.05 considered significant.ResultsTwenty-two patients (10 women, 12 men) underwent splenectomy during the study period. Indications were: immune thrombocytopenia (n: 6), myeloproliferative disorder (n: 6), hereditary spherocytosis (n: 4), thalassemia (n: 1), lymphoma (n: 1), leukaemia (n: 1), other malignancies (n: 3). Six patients developed porto-spleno-mesenteric venous thrombosis and only 2 of them were symptomatic. Patients were treated with anticoagulation therapy with complete resolution. Analysis identified three main factors associated with thrombosis: spleen diameter (p = 0.03), myeloproliferative disorder (p = 0.02), intraoperative platelet transfusion (p = 0.002) and intraoperative red blood cells transfusion (p = 0.009).ConclusionStandardized postoperative screening allows prompt diagnosis and treatment of porto-spleno-mesenteric venous thrombosis even in asymptomatic cases. Patient with splenomegaly and affected by myeloproliferative disorder have a greater risk to develop this complication.

Gallbladder Wall Thickening as a Non-Invasive Screening Parameter for Esophageal Varices Compared to Upper GI Endoscopy

Abstract Background Variceal hemorrhage is considered a life threatening complication of esophageal varices (EV).The main cause of esophageal varices is liver Cirrhosis and subsequent Portal hypertension. Current Guidelines recommend screening via Upper GI Endoscopy which is an invasive procedure which has its own hazards, complications and disadvantages. Gallbladder wall thickening is an early finding in patients with liver cirrhosis that occurs even before other manifestations of portal hypertension. In this study, the utility and efficiency of sonographic measurement of gallbladder wall thickness will be analyzed as a non-invasive screening alternative for upper endoscopy for assessment of EV. Objective To assess possibility of using the Gallbladder wall thickness as a non invasive screening parameter for esophageal varices in cirrhotic patients. Patients and Methods 150 patients were enrolled in this study. The laboratory tests, sonographic and endoscopy findings of 150 CLD patients to assess their correlation to esophageal varices. The Patients were classified into two groups according to the presence of varices and ascites into EV Group of 75 cirrhotic patients with esophageal varices regardless of ascites, and Non EV: Group of 75 patients with chronic liver disease and no ascites on sonography as a control group. The esophageal varices group were further subclassified into 3 groups according to the grade of varices present. Patients with grade I varices were assigned to Group (EV 1). Patients with grade II varices (EV 2). Patients with grade III varices were included in (EV 3) group. Results On Comparison of the lab finding, Sonography, and Child score of the EV and Non EV group, it was found a statistical significance in most variables. On using the multi variate assessment, the following parameters were significant as independent predictors for varices being, platelet count, AFP, Liver Span, and GBWT. The platelet levels seem to be of statistical significance with a mean of 109 with an interquartile range of 79 to 146 in the EV group. while the Non EV group, the median is 195 with IQR from 178 to 234. Alpha feto protein shows statistical significance with a median of 4.5 with IQR of 2.7 to 6.7 in the EV group, and median of 2.1 with an IQR of 1.5 to 4.9 in the Non EV group. The mean liver span in the EV group is 127.56 ± 16.19 with values ranging from 84 to 175. While the mean liver span in the Non EV group in 146.88 ± 14.47 with values ranging from 114 to 184.The mean spleen diameter in the EV group was 161.18±20.73 with values ranging from 118 to 213. The mean splenic diameter in the Non EV group is 141.84±12.34 with measurements ranging from 114 to 167. AUROC curve was drawn with a best cutoff value at 3.8 mm with AUC of 0.810 showing a sensitivity of 76%, specificity at 76 %, PPV at 76 % and NPV of 76%. At a cut off value of 4 mm sensitivity was at 62% specificity 81.3%, PPV 77% and a NPV 68%. PC/ SD was assessed with AUROC with a cutoff of 1006.29 with AUC of 0.879 with a sensitivity of 76%, specificity of 96 %, PPV of 95% and NPV of 80%.Noteworthy that GBWT showed statistical significance between grades of varices with a P-value of 0.003 and mean thickness in EV1, EV2, and EV 3 as follows 4.04 ± 0.8, 4.46 ± 0.68, and 5.27 ± 1.75. Conclusion GBWT seems to be a good predictor of varices which could be used as a screening modality for varices.

Assessment of Right Lobe Size/Serum Albumin Ratio as a Non-Invasive Marker for EsophagealVarices in HCV Patients

Abstract Background Oesophageal varices are the most critical porto-systemic shunts that develop secondary to portal hypertension, which is considered the main complication of liver cirrhosis. Many studies recommend the screening of all cirrhotic patients by endoscopy, but repeated endoscopic examinations are unpleasant for patients and have a high- cost impact and burden on endoscopic units. Aim and of the work To investigate the value of measurement of (Rt. lobe diameter/ serum albumin ratio) in the prediction of esophageal varices. Subjects and Methods This was Case- control study, was carried out at outpatient clinics of Hepatology and inpatient department of Gastroenterology at Ain Shams University Hospital on 100 patients divided into 3 groups: (Group 1): 30 patients with Child-Pugh A, (Group 2): 30 patients with Child-Pugh, (Group 3): 40 patients with Child-Pugh C, during a period of 6 months. Result There were highly significant difference between both groups as regard Platelet count /spleen diameter ratio and Right liver lobe size/Serum Albumin ratio. Conclusion The use of Right liver lobe/serum albumin ratio can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of esophageal varices. This is especially useful in clinical settings where resources are limited, and endoscopic facilities are not present in all areas.

Transsplenic tract closure after transsplenic portalvenous access using gelfoam-based tract plugging

BackgroundTo assess the feasibility and safety of a gelfoam torpedo plugging technique for embolization of the transsplenic access channel in adult patients following transvenous portal vein interventions.Materials and methodsBetween 09/2016 and 08/2021, an ultrasound guided transsplenic portalvenous access (TSPVA) was established in twenty-four adult patients with a 21-G needle and 4-F microsheath under ultrasound guidance. Afterwards, sheaths ranging from 4-F to 8-F were inserted as needed for the procedure. Following portal vein intervention, the splenic access tract was embolized with a gelfoam-based tract plugging (GFTP) technique. TSPVA and GFTP were performed twice in two patients. Patients’ pre-interventional and procedural characteristics were analyzed to assess the feasibility and safety of the plugging technique according Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system. Values are given as median (minimum;maximum). Subgroup analysis of intercostal vs. subcostal puncture site for TSPVA was performed using the two-sided Mann–Whitney-U test or Student’s t-test and Fisher’s exact test. Level of significance was p < 0.05.ResultsThe study population’s age was 56 (29;71) years and 54% were female patients. Primary liver disease was predominantly liver cirrhosis with 62% of the patients. Pre-interventional model for end-stage liver disease score was 9 (6;25), international normalized ratio was 1.15 (0.86;1.51), activated partial thromboplastin time was 33s (26s;52s) and platelet count was 88.000/µL (31.000;273.000/µL). Ascites was present in 76% of the cases. Craniocaudal spleen diameter was 17cm (10cm;25cm). Indication for TSPVA was assisted transjugular intrahepatic portosystemic shunt placement in 16 cases and revision in two cases, portal vein stent placement in five cases and variceal embolization in three cases. TSPVA was successfully established in all interventions; interventional success rate was 85% (22/26). The splenic access time was 33min (10min;133min) and the total procedure time was 208min (110min;429min). Splenic access was performed with a subcostal route in 11 interventions and with an intercostal route in 15 interventions. Final sheath size was 4-F in 17 cases, 5-F in three cases, 6-F in five cases, 7-F in two cases and 8-F in one case. A median of two gelfoam cubes was used for GFTP. TSPVA- and GFTP-related complications occurred in 4 of 26 interventions (15%) with a subcapsular hematoma of the spleen in two patients (CIRSE grade 1), access-related infection in one patient (CIRSE grade 3) and both in one patient (CIRSE grade 3). In detail, one access-related complication occurred in a patient with subcostal TSPVA (CIRSE grade 1 complication) and the other three complications occurred in patients with intercostal TSPVA (one CIRSE grade 1 complication and two CIRSE grade 3 complication) (p = 0.614). No patient required interventional or surgical treatment due to puncture tract bleeding.ConclusionGelfoam-based plugging of the puncture tract was feasible and safe for transsplenic access in adult patients undergoing percutaneous portal vein interventions. The lack of major bleeding complications and complete absorption of the gelatine sponge make it a safe alternative to transjugular and transhepatic access and re-interventions via the splenic route.

#6841 IS NEPHRECTOMY ALWAYS USEFUL IN ADPKD? A CASE REPORT OF HEPATIC FIBROSIS WITH SPLENOMEGALY AND PANCYTOPENIA AS LATE CONSEQUENCE

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. Its main feature is the progressive enlargement of both kidneys with progressive loss of kidney function. ADPKD is the 4th leading cause of dialysis in the world. The disease has systemic involvement. Liver cysts are the most common extrarenal manifestations of ADPKD and are often incidental findings. However the liver can reach considerable size but its function is always preserved. Cysts lead to structural changes of the biliary tree and determine discomfort related to mass effect when significant liver enlargement occurs. Few cases of Budd Chiari syndrome (BCS) or of hepatic fibrosis have been reported in ADPKD patients after nephrectomy. Probably the removal of the kidneys can lead to obstruction of inferior vena cava by liver cysts. Method We report a case of hepatic fibrosis with splenomegaly and severe pancytopenia as a tardive complication after bilateral nephrectomy. Case report A 47 years old man was admitted c/o Division of Nephrology of San Raffaele Hospital in August 2018 because of a high-grade fever, general malaise, nausea and abdominal pain. The patient had a previous diagnosis of ADPKD. Genetic test indicative of PKD1 truncating mutation. He was chronically attended in the outpatient clinic of the same Division. On admission in hospital his renal function was severely impaired (crea 10 mg/dl; urea 213 mg/dl). No abnormalities at the blood count. Reactive C protein was elevated (156 mg/l nv 0-6). Urine culture was found negative. Abdominal NMR showed an important volumetric increase (compared with a NMR performed in 2014) of both kidneys with diameters of about 30 cm, several cysts with hemorrhagic and infective features and numerical and dimensional increase of the hepatic cysts; spleen was reported with normal diameters. Multiple antibiotic treatments were performed unfortunately without benefit. Therefore considering the state of end stage renal disease, the persistent infection and the severe symptoms, in September 2018 the patient underwent bilateral nephrectomy and hemodialysis was started. During the following years imaging studies aimed at the preparation for transplantation were performed. In November 2020 an abdominal NMR showed for the first time splenomegaly with a bipolar diameter of 14 cm. A NMR follow up was started. In January 2021 a further increase was reported as spleen diameter resulted of 14.5 cm and a volumetric increase of hepatic cysts was shown. In September 2022 spleen reached to a diameter of 17 cm. Contextually in November 2020 patient started to present pancytopenia that had progressively been worsening with many concomitant infective and bleeding episodes. All hematologic causes were excluded. Just to explain the genesis of the splenomegaly in September 2022 a fibroscan was performed and a pathological liverstiffness was found. All hepatitis markers were negative and immunologic ones as well. Splenectomy was assumed, but patient clinical conditions so far do not allow it. Transplantation is currently contraindicated Conclusion These evidences underline the necessity of scrupolous evaluation of polycystic kidneys and their anatomic relationship with the liver before nephrectomy. Nephrectomy is frequently considered in the preparation for renal transplantation. In light of these possible complications, maybe removal of kidneys should be considered carefully in ADPKD patients with large involvement of the liver by cysts.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.