Increase In Splenic Volume Research Articles

The Fetal Spleen in Low-Risk Pregnancies and prior to Preterm Birth: Observational Study of the Role of Anatomical and Functional Magnetic Resonance Imaging

Introduction: Spontaneous preterm birth complicates ∼7% of pregnancies and causes morbidity and mortality. Although infection is a common etiology, our understanding of the fetal immune system in vivo is limited. This study aimed to utilize T2-weighted imaging and T2* relaxometry (which is a proxy of tissue oxygenation) of the fetal spleen in uncomplicated pregnancies and in fetuses that were subsequently delivered spontaneously prior to 32 weeks. Methods: Women underwent imaging including T2-weighted fetal body images and multi-eco gradient echo single-shot echo planar sequences on a Phillips Achieva 3T system. Previously described postprocessing techniques were applied to obtain T2- and T2*-weighted imaging of the fetal spleen and T2-weighted fetal body volumes. Results: Among 55 women with uncomplicated pregnancies, an increase in fetal splenic volume, splenic:body volume, and a decrease in splenic T2* signal intensity was demonstrated across gestation. Compared to controls, fetuses who were subsequently delivered prior to 32 weeks’ gestation (n = 19) had a larger spleen when controlled for the overall size of the fetus (p = 0.027), but T2* was consistent (p = 0.76). Conclusion: These findings provide evidence of a replicable method of studying the fetal immune system and give novel results on the impact of impending preterm birth on the spleen. While T2* decreases prior to preterm birth in other organs, preservation demonstrated here suggests preferential sparing of the spleen.

Computed Tomography Assessment of Linear Splenic Dimensions and their Correlation with Anthropometric Measurements in Nepalese Population

Background: Geographical locations and ethnicity may influence variations in normal spleen dimensions, potentially leading to errors in assessment. This study aimed to correlate splenic dimensions with anthropometry and predict their variation with age and body surface area.
 Materials and Methods: Subjects (n=384) undergoing abdominal computed tomography were selected by random sampling. Splenic volume was calculated using the standard prolate ellipsoid equation. Correlation of splenic volume with body surface area and body mass index was done with Pearson’s correlation analysis. A multiple regression was run to predict splenic volume from age, height, and body surface area.
 Results: The mean age was 45±18 (range, 18-90 years). The mean splenic length, width, thickness, and volume were 7.6 ± 1.7 cm, 8.8 ± 1.5cm, 3.8 ± 0.9 cm, and 139 ± 58.2 cm3, respectively. The splenic width and splenic volume were significantly lower at extremes of age. A significant (P<0.05) correlation was seen between splenic volume, body surface area(r=0.393) and body mass index (r=0.126); a negative correlation was observed between splenic volume and age (r=-0.180). Splenic dimensions were significantly larger in males. Multiple regression revealed that an increase in body surface area (by 10 cm2), predicted increased splenic volume was 4.3 cm3. An increase in age (by 1-year), predicted decrease in splenic volume was 8.3 cm3. For 10 cm increase in height, predicted increase in splenic volume was 1.7cm3.
 Conclusion: The study showed a positive correlation between splenic volume and body surface area, as well as body mass index and provides a crucial normative data for assessing splenic enlargement in Nepalese population.

The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma

IntroductionResistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients.MethodsWe analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients’ body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis.ResultsMedian splenic volume change was 10% (ranging from − 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1–4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1–6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly.ConclusionOur findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy

The aim of our study was to evaluate the association between increased splenic volume (SV) and liver fibrosis indices in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Patients who received adjuvant oxaliplatin-based regimens with the diagnosis of stage II and III colon cancer were evaluated. Splenic volume measurements, liver function tests, platelet count, and non-invasive liver fibrosis indices [NAFLD fibrosis score (NFS), AST to platelet ratio (APRI), and Fibrosis-4 (FIB-4)] were measured before and after treatment. A 30% increase in SV after chemotherapy compared to baseline was considered increased SV. The rate of increase in SV was 57.7% in the whole group. An increase in SV was shown at a higher rate in patients treated with capecitabine and oxaliplatin (CAPOX) than those treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (66.3% vs. 36.8%, p = 0.002). Furthermore, the CAPOX regimen (OR: 2.831, 95% CI: 1.125-7.121; p = 0.027), and higher post-treatment FIB-4 score (OR: 3.779; 95% CI:1.537- 9.294, p = 0.004) were determined as independent risk factors for the increased SV. Our study revealed that increased SV had a significant association with higher FIB-4 score in patients treated with oxaliplatin-based chemotherapy.

Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome

BackgroundSinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early.MethodsIn this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT.ResultsOf the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32–0.41). The change in rate of LSM by SWE was correlated with an SV increase ≥ 30% (r = 0.40).ConclusionsThe usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.

Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy.

Simple SummarySplenic volume (SV) has been identified as a highly predictive parameter for prognosis in patients with hepatocellular carcinoma (HCC). Moreover, an association between immunotherapy and an increase in SV has been described for various types of cancer. In our cohort of patients with HCC under immunotherapy, SV was a highly predictive factor for overall survival at baseline and initial follow-up. Although a large proportion of patients (76%) showed an SV increase after the initiation of immunotherapy, this additional immuno-modulated SV change was negligible compared to long-standing changes in the splanchnic circulation in our patient cohort.Background: An association between immunotherapy and an increase in splenic volume (SV) has been described for various types of cancer. SV is also highly predictive of overall survival (OS) in patients with hepatocellular carcinoma (HCC). We evaluated SV and its changes with regard to their prognostic influence in patients with HCC undergoing immunotherapy. Methods: All patients with HCC who received immunotherapy in first or subsequent lines at our tertiary care center between 2016 and 2021 were screened for eligibility. SV was assessed at baseline and follow-up using an AI-based tool for spleen segmentation. Patients were dichotomized into high and low SV based on the median value. Results: Fifty patients were included in the analysis. The median SV prior to treatment was 532 mL. The median OS of patients with high and low SV was 5.1 months and 18.1 months, respectively (p = 0.01). An increase in SV between treatment initiation and the first follow-up was observed in 28/37 (75.7%) patients with follow-up imaging available. This increase in itself was not prognostic for median OS (7.0 vs. 8.5 months, p = 0.73). However, patients with high absolute SV at the first follow-up continued to have impaired survival (4.0 months vs. 30.7 months, p = 0.004). Conclusion: High SV prior to and during treatment was a significant prognostic factor for impaired outcome. Although a large proportion of patients showed an SV increase after the initiation of immunotherapy, this additional immuno-modulated SV change was negligible compared to long-standing changes in the splanchnic circulation in patients with HCC.

Splenic volume as a predictor of treatment response in patients with non-small cell lung cancer receiving immunotherapy.

IntroductionThe spleen is a lymphoid organ and we hypothesize that clinical benefit to immunotherapy may present with an increase in splenic volume during treatment. The purpose of this study was to investigate whether changes in splenic volume could be observed in those showing clinical benefit versus those not showing clinical benefit to pembrolizumab treatment in non-small cell lung cancer (NSCLC) patients.Materials and methodsIn this study, 70 patients with locally advanced or metastatic NSCLC treated with pembrolizumab; and who underwent baseline CT scan within 2 weeks before treatment and follow-up CT within 3 months after commencing immunotherapy were retrospectively evaluated. The splenic volume on each CT was segmented manually by outlining the splenic contour on every image and the total volume summated. We compared the splenic volume in those achieving a clinical benefit and those not achieving clinical benefit, using non-parametric Wilcoxon signed-rank test. Clinical benefit was defined as stable disease or partial response lasting for greater than 24 weeks. A p-value of <0.05 was considered statistically significant.ResultsThere were 23 responders and 47 non-responders based on iRECIST criteria and 35 patients with clinical benefit and 35 without clinical benefit. There was no significant difference in the median pre-treatment volume (175 vs 187 cm3, p = 0.34), post-treatment volume (168 vs 167 cm3, p = 0.39) or change in splenic volume (-0.002 vs 0.0002 cm3, p = 0.97) between the two groups. No significant differences were also found between the splenic volume of patients with partial response, stable disease or progressive disease (p>0.017). Moreover, there was no statistically significant difference between progression-free survival and time to disease progression when the splenic volume was categorized as smaller or larger than the median pre-treatment or post-treatment volume (p>0.05).ConclusionNo significant differences were observed in the splenic volume of those showing clinical benefit versus those without clinical benefit to pembrolizumab treatment in NSCLC patients. CT splenic volume cannot be used as a potentially simple biomarker of response to immunotherapy.

Hyaluronic Acid May Be a Predictive Biomarker for Thrombocytopenia and Liver Dysfunction After Oxaliplatin-based Chemotherapy.

Following oxaliplatin-based chemotherapy, approximately half of all colorectal cancer patients develop sinusoidal obstruction syndrome (SOS). SOS can be monitored by measuring splenic volume; however, obtaining this measurement is not a simple process. In this study, we evaluated changes in hyaluronic acid (HA) concentrations as a simpler marker of SOS. We measured splenic volume and laboratory data, including hyaluronic acid concentration, liver enzymes, and platelet counts, in 34 patients with colorectal cancer who underwent radical resection and who received capecitabine plus oxaliplatin (CapeOx) chemotherapy. A strong correlation was identified between ≥30% increase in splenic volume and significantly elevated HA concentrations. Affected patients also had persistent thrombocytopenia and liver dysfunction compared to patients without elevated HA concentration. HA concentration may predict SOS in patients who receive CapeOx adjuvant chemotherapy.

Comparison of Methods to Estimate Splenic Volume in Myelofibrosis Trials

▪Primary myelofibrosis (PM) is a chronic blood cancer which increases burden on the spleen to produce blood cells and results in palpable splenomegaly. In the clinic, splenomegaly is classified based on the distance between the spleen's lowest point and the left costal margin, however, this method is highly subjective and depends on the subject's position and respiration. Imaging techniques have the potential to provide accurate, reliable, and reproducible measurements of splenic volume (SV). In clinical trials assessing therapy response, an accepted imaging-based endpoint is ≥35% reduction in SV at week 24 from baseline as measured by Magnetic Resonance Imaging (MRI) or Computer Tomography (CT). A ≥25% increase in SV is typically considered progression. The most accurate method for volume assessment is manual segmentation, since the entire spleen boundary can be utilized for the volume calculation. This study compared two other volume estimation methods: ellipsoid method and a model proposed by Bezerra et al (AJR Am J Roentgenol. 2005). We compared the methods' performance in assessing treatment response or progression based on SV change from baseline to week 24.Imaging data from 30 participants were used in this study, predominantly acquired using MRI modality; CT was used as an alternative, when MRI was contraindicated. Scans from two timepoints per participant were used: baseline and 24 weeks after start of treatment. For the manual segmentation method, preliminary regions of interest were manually outlined on every imaging slice by an experienced imaging analyst and then reviewed by a trained radiologist. SV was derived by multiplying the number of voxels contained in the spleen outlined by the voxel size of the scan. For the ellipsoid method, maximum width (W) and orthogonal thickness (T) were measured on the axial images. Length (L) was measured by multiplying the number of slices containing spleen by the slice interval. Ellipsoid volume was calculated as follows:V = W * T * L * π / 6For the length-estimated SV based on the Bezerra et al model, spleen length was utilized as shown:V = (L - 5.8006) / 0.0126For each of the three methods, percent change in SV was calculated from baseline to week 24. Pearson's correlation coefficient and Bland Altman analysis were implemented for comparison of methods to manual segmentation. Sensitivity and specificity analysis was performed to determine the accuracy of each method to predict response or progression.The manual segmentation volume was significantly correlated with both the ellipsoid method (r(58) = 0.94, p < 0.0001) and the length-estimated method (r(58) = 0.89, p < 0.0001). When assessing percent changes from baseline to week 24 using manual segmentation, 4 of the participants achieved splenic response and 4 progressed with 25% increase in SV. However, analysis using ellipsoid method yielded 3 responding and 2 progressing participants. Finally, analysis with length-estimated volume yielded no responding or progressing participants. This data is also illustrated in Table 1, which shows the sensitivity and specificity results. Figure 1 illustrates Bland-Altman plots, suggesting that ellipsoid method provides a more accurate estimation of the change in SV compared to length-estimated volume. Furthermore, we found that the inaccuracy with length-estimated volume increases with larger spleens (not shown).Change in spleen volume contributes to the primary/ secondary endpoints in large multi-center clinical trials for myelofibrosis, so it is imperative that the methods used to measure SV are consistent across imaging sites. The current standard for assessing SV is the manual segmentation method because it provides the most comprehensive measurement of spleen size however, this process is burdensome, time consuming, and requires specific training. The ellipsoid and length-estimated methods were strongly correlated with the manual segmentation method; however, they were not as sensitive when determining treatment response or progression. The length-estimated method had the least level of agreement with manual segmentation. The ellipsoid method may be a better alternative; however, it is important to use one method consistently across all visits for a study participant. Additional work is required to test performance of methods on a larger cohort, as well as assess automated segmentation algorithms that may reduce the burden of manual tracing. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary Splenic Pleomorphic Liposarcoma in a Bitch

Background: Liposarcoma is a malignant neoplasm of lipoblasts with low incidence in dogs, representing 1.7% of neoplasms diagnosed in the spleen. In veterinary medicine, this neoplasm is classified morphologically into the myxoid, well-differentiated, undifferentiated and pleomorphic subtypes, the latter being one of the most aggressive forms, mainly in cavity organs. This study reports a case of primary splenic pleomorphic liposarcoma in a female dog, addressing anatomopathological and immunohistochemical aspects.Case: A 14-year-old, 35 kg female mongrel canine with a history of absence of defecation, progressive weight loss, difficulty walking, sensitivity to abdominal palpation, prostration, pale mucous membranes, tachypnea and abdominal distention. The condition evolved to death and, on necroscopy, there was an increase in splenic volume with neoformation of whitish and reddish color, measuring 32 × 27 cm in its largest axes and weighing 8.9 kg. The neoformation exhibited areas of firm and soft consistency, and sectioning revealed the existence of focal areas of extensive necrosis and cavity collections of different diameters that allowed the flow of liquid serous contents with a brownish red color. Microscopy showed cells of neoplastic morphology infiltrating the splenic parenchyma, mostly with slightly acidophilic cytoplasm and few intracytoplasmic lipid vacuoles, which varied in size and distribution. The nuclei of the cells were large, eccentric and irregular, with round to oval morphology, grossly lacy chromatin and single or multiple evident nucleoli. These cells exhibited marked anisocytosis, anisokaryosis and pleomorphism, with more than one mitotic figure per high magnification field visible. Moderately inflammatory infiltrate, predominantly lymphocytic, permeated the neoplastic cells, and marked depletion of lymphoid follicles and atrophy of the red pulp were found in the remaining splenic parenchyma. Immunohistochemical tests revealed marked and discrete immunostaining for anti-vimentin and anti-S100 antibodies, respectively. No staining was observed for anti-pan cytokeratin, anti-desmin, anti-alpha smooth muscle actin or anti-CD20 antibodies. Based on anatomopathological and immunohistochemical aspects, it was concluded to be a splenic pleomorphic liposarcoma of primary origin.Discussion: the spleen is not a common anatomical site for the development of liposarcoma, a neoplasm whose origin remains unclear. Similar to what occurs in humans, liposarcoma is believed to develop from the adipose tissue of the splenic hilum. Thus, it should be considered as a differential diagnosis of invasive abdominal tumors. For the identification and classification of liposarcoma as a pleomorphic subtype, we considered mainly histological findings such as marked cell atypia and intracytoplasmic lipid vacuoles, which may or may not be present in neoplastic cells. Immunohistochemical examination favored the diagnosis of liposarcoma, regardless of the subtype, due to the marked immunostaining for the anti-vimentin antibody, unlike immunostaining for the anti-S100 antibody, for which it was variable. This fact is related to adipocyte differentiation, where lower amounts of intracytoplasmic lipids translate into lower immunostaining intensity for anti-S100. Histological and immunostaining aspects should be regarded with caution in the diagnosis of pleomorphic liposarcoma, as it is a distinct neoplastic entity, with a complex karyotype and without correlation with the other subtypes.

Baseline Splenic Volume as a Prognostic Biomarker of FOLFIRI Efficacy and a Surrogate Marker of MDSC Accumulation in Metastatic Colorectal Carcinoma.

Background: Predictive biomarkers of response to chemotherapy plus antiangiogenic for metastatic colorectal cancer (mCRC) are lacking. The objective of this study was to test the prognostic role of splenomegaly on baseline CT scan. Methods: This study is a sub-study of PRODIGE-9 study, which included 488 mCRC patients treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab in first line. The association between splenic volume, and PFS and OS was evaluated by univariate and multivariable Cox analyses. The relation between circulating monocytic Myeloid derived suppressor cells (mMDSC) and splenomegaly was also determined. Results: Baseline splenic volume > 180 mL was associated with poor PFS (median PFS = 9.2 versus 11.1 months; log-rank p = 0.0125), but was not statistically associated with OS (median OS = 22.6 versus 28.5 months; log-rank p = 0.1643). The increase in splenic volume at 3 months had no impact on PFS (HR 0.928; log-rank p = 0.56) or on OS (HR 0.843; log-rank p = 0.21). Baseline splenic volume was positively correlated with the level of baseline circulating mMDSC (r = 0.48, p-value = 0.031). Conclusion: Baseline splenomegaly is a prognostic biomarker in patients with mCRC treated with FOLFIRI and bevacizumab, and a surrogate marker of MDSC accumulation.

Postprandial dynamics of splenic volume in healthy volunteers.

Throughout the history of medicine, many functions have been attributed to the spleen and numerous researchers have focused on a postulated digestive function. Beginning in 1825, systematic animal studies showed evidence for a postprandial increase in splenic volume (SV) with a peak 30 min to five hours after food intake. Since the introduction of imaging techniques, two studies have been conducted on humans, revealing a decrease in SV 30 to 45 min postprandially. The aim of this study was to examine possible postprandial changes in SV over a period of seven hours. The ethics‐approved, randomized crossover study included 10 healthy volunteers, who received a standardized meal (3,600 kJ) on one study day and fasted on the other. Sonographic measurements were obtained at six measurement points on each day. Thirty minutes after the meal, SV increased significantly by 38.2 ± 51.2 cm3 (17.3%; p = .04) compared to the baseline measurement and decreased gradually afterward. In males, SV 30 min after the meal was 70.2 ± 21.6 cm3 higher (p = .002) compared to the fasting condition and 60 min later it was still significantly increased. The apparent SV increase after food intake is discussed in relation to hemodynamic changes in the splanchnic region. It seems plausible that the spleen has a rhythmic and regulative function within the portal system, something which warrants further research and should be taken more into account in nutritional physiology.

Splenic NKG2D confers resilience versus susceptibility in mice after chronic social defeat stress: beneficial effects of (R)-ketamine

The spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of (R)-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of (R)-ketamine. Thus, the brain–spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.

Correlation of postoperative splenic volume increase with prognosis of hepatocellular carcinoma after curative hepatectomy

Previous studies have reported a close connection between the spleen and hepatic tumours. We investigated the prognostic value of postoperative splenic volume increase (PSVI) in patients with hepatocellular carcinoma after curative hepatectomy. This was a retrospective study of adult patients with hepatocellular carcinoma who underwent hepatectomy between January 2007 and May 2013. We categorized patients into 2 groups according to the cut-off value of the receiver operating characteristic curve: group A (PSVI < 19.0%) and group B (PSVI ≥ 19.0%). We compared the clinicopathological data, overall survival and disease-free survival between the 2 groups. We performed univariate and multivariate analyses to identify factors associated with disease-free and overall survival. There were 275 patients in group A and 196 patients in group B. The 1-, 3- and 5-year overall survival rates were 98.9%, 74.9% and 63.6%, respectively, for patients in group A, and 97.4%, 65.3% and 49.8%, respectively, for patients in group B (p = 0.004). The corresponding disease-free survival rates were 69.5%, 48.0% and 40.3%, and 58.1%, 36.5%, and 29.8% (p = 0.01). On multivariate analysis, PSVI was an independent predictor of overall (p = 0.01) and disease-free (p = 0.03) survival. Postoperative splenic volume increase correlates with poor prognosis of patients with hepatocellular carcinoma after curative hepatectomy.

Splenic volume as a biomarker of hepatic damage after chemotherapy in patients with resected colorectal liver metastases (CRLM).

Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6months after resection. A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.

Occurrence of irreversible sinusoidal obstruction syndrome during adjuvant chemotherapy for colorectal cancer using oxaliplatin: A multi-center study.

546 Background: Oxaliplatin reduces the recurrence rate after curative surgery for stage III colorectal cancer. However, it can cause hepatic sinusoidal obstruction syndrome (SOS), an adverse effect that creates morbidity after liver resection for recurrence. SOS has conventionally been diagnosed by liver biopsy, which is invasive. We have reported that a 10% increase in splenic volume (SV) indicates SOS (J Surg Oncol 2017). In this multi-center study, we measured SV to evaluate SOS caused by adjuvant chemotherapy. Methods: This multi-center study included the participants of the FACOS study, which included patients with Stage III colon cancer. Participants received 12 cycles of mFOLFOX6 or eight cycles of XELOX as adjuvant chemotherapy. We used multi-detector raw CT to measure SV three times; before surgery, on completion of adjuvant chemotherapy, and 1-year after completing adjuvant chemotherapy. CT images were taken in 5-mm slices. SV was calculated by using a volume calculator SYNAPSE VINCENT v3.0(Fujifilm, Japan). Results: The FACOS study included 130 patients, 16.9% of whom discontinued treatment. The mean relative dose intensity (RDI) of oxaliplatin was 80.3%. Grade 3 neutropenia, thrombocytopenia, and neuropathy were observed in 28.5%, 6.2%, and 4.6% of patients, respectively. The 3 year DFS was 82.2%. We analyzed data of 75 patients (57.7%) for whom the three CT studies were available. SV on completing chemotherapy (median 181 cm3) and SV 1-year after completing chemotherapy (141 cm3) were significantly higher than that before surgery (128 cm3) (P &lt; 0.001). SV increased by more than 10% after chemotherapy in 72% and was still increased 1 year after chemotherapy in 51% of patients. Conclusions: In our previous single center study, SV had increased in 84% on completing chemotherapy and was still increased in 47% 1 year after completing chemotherapy. Adjuvant chemotherapy without oxaliplatin induced SV increases in only 20% of patients on completing chemotherapy. Thus, these results are reproducible and show the potential of oxaliplatin to induce SOS. Oxaliplatin frequently induces SOS and this SOS persists for over 1 year in half of affected patients. Clinical trial information: UMIN000005427.

Noninvasive Monitoring of Liver Disease Regression after Hepatitis C Eradication Using Gadoxetic Acid-Enhanced MRI.

We evaluated changes in relative liver enhancement (RLE) obtained by gadoxetic acid-enhanced MRI (GA-MRI) in the hepatobiliary phase and changes in splenic volume (SV) after hepatitis C virus (HCV) eradication as well as their predictive value for the development of (further) hepatic decompensation during follow-up. This retrospective study comprised 31 consecutive patients with HCV-induced advanced chronic liver disease who underwent GA-MRI before and after successful interferon-free treatment, as well as a cohort of 14 untreated chronic HCV-patients with paired GA-MRI. RLE increased by 66% (20%–94%; P < 0.001) from pre- to posttreatment, while SV decreased by −16% (−28% to −8%; P < 0.001). However, SV increased in 16% (5/31) of patients, the identical subjects who showed a decrease in RLE (GA-MRI-nonresponse). We observed an inverse correlation between the changes in RLE and SV (ρ=−0.608; P < 0.001). In the untreated patients, there was a decrease in RLE by −11% (−25% to −3%; P=0.019) and an increase in SV by 23% (7%–43%; P=0.004) (both P < 0.001 versus treated patients). Interestingly, GA-MRI-nonresponse was associated with a substantially increased risk of (further) hepatic decompensation 2 years after the end of treatment: 80% versus 8%; P < 0.001. GA-MRI might distinguish between individuals at low and high risk of (further) hepatic decompensation (GA-MRI-nonresponse) after HCV eradication. This could allow for individualized surveillance strategies.

Diagnosis of diffuse spleen involvement in haematological malignancies using a spleen-to-liver attenuation ratio on contrast-enhanced CT images.

We aimed to test the hypothesis that the spleen-to-liver-attenuation ratio on portal-venous enhancement phase CT images can identify diffuse splenic infiltration in subjects with lymphoma. A database search yielded 70 subjects with malignant haematological diseases who underwent contrast-enhanced CT (CECT) between December 2010 and March 2018. Additionally, consecutive control subjects were evaluated. We compared the splenic volume, splenic attenuation, spleen-to-liver, spleen-to-aorta and spleen-to-musculature ratios on portal-venous phase CECT images, pre- to post-treatment and between the different lymphoma entities. The standard of reference for splenic involvement was normalisation of the spleen volume following chemotherapy or normalisation of FDG-uptake. In subjects with diffuse splenic involvement, the spleen attenuation was significantly lower before treatment (93.48 HU) compared to controls (112.39 HU; p < .01) and after successful treatment (113.39 HU; p < .01). The spleen-to-liver attenuation ratio significantly increased after treatment (p < .001) and proved significantly lower at baseline when compared to control subjects (p < .01). The spleen volume significantly decreased after successful treatment (from 586.14.87 cm3 to 284.90 cm3; p < .001). Spleen-to-liver ratio significantly increased in lymphoma patients after therapy, inversely correlating with the decline in FDG-uptake (n=10) even in patients with normal-sized spleens (2/10), staying unchanged at follow-up. The outcome variables were not significantly different between the lymphoma subtypes. We suggest the additional use of spleen-to-liver attenuation ratio to splenic volume alone for detection of diffuse splenic infiltration in subjects with lymphoma. The course of spleen-to-liver attenuation ratio inversely correlated with that of FDG-uptake in a subgroup of patients working accurately in normal-sized diffusely involved spleens. • Involvement of the spleen is frequent in haematological malignancies and is important for staging and appropriate treatment. • Diffuse splenic infiltration often results in only homogeneous splenomegaly without a focal lesion, but even no or only minimal increase in splenic volume is possible. In these cases diagnosis of spleen involvement is a challenge for the radiologist. • Our data support the use of the spleen-to-liver attenuation ratio in addition to size measurements for the detection of diffuse splenic infiltration in subjects with lymphoma.

Surgical Strategy Based on Indocyanine Green Test for Chemotherapy-Associated Liver Injury and Long-Term Outcome in Colorectal Liver Metastases

BackgroundIt remains unclear whether the presence of chemotherapy-induced liver injury (CALI) or impaired liver functional reserve affects the long-term outcome. This study assessed the applicability and long-term effects of using criteria based on the indocyanine green (ICG) test results in selecting the operative procedure among patients with colorectal liver metastases (CRLM) who had a risk of CALI. Study DesignCRLM patients who received preoperative chemotherapy including oxaliplatin and/or irinotecan prior to a curative hepatectomy between 2007 and 2017 were included. For each case, the minimum required future remnant liver volume and operative procedure were decided based on the ICG retention rate at 15 min (ICG R15). Patients with an ICG R15 >10% and who had undergone a major hepatectomy were categorized in a marginal liver functional reserve (MHML) group. ResultsOverall, 161 patients were included; 77 of them had an ICG R15 >10%, and 57 had pathological liver injury (PLI). After the median follow-up time of 30.9 months, the 5-year overall survival rate was 36.1%. The presence of an impaired ICG test result or CALI did not negatively impact the overall and recurrence-free survival outcomes. A multivariate analysis revealed that the presence of four or more nodules of liver metastases was the only independent predictor of a poor overall survival. A significantly larger proportion of patients in the MHML group (n=37) had a 25% or larger increase in splenic volume (30 vs. 13%; P=0.024). ConclusionThe presence of an impaired ICG test result or PLI did not affect the long-term outcome after individually selected operative procedure. However, patients undergoing MHML had a higher possibility of developing a >25% splenic volume increase after hepatectomy.

Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX.

Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy-related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy. We enrolled 103 consecutive patients with stage III and high-risk stage II colorectal cancer treated with mFOLFOX6 (n = 37) or oral fluorouracil and leucovorin (n = 66) after curative surgery. SV was measured three times; pre-operatively, after chemotherapy, and 1 year after chemotherapy. SV was higher after mFOLFOX6 (median 135.89 mL) than pre-operatively (105.75 mL) (P < 0.001); SV at 1-year after finishing mFOLFOX6 (114.16 mL) returned to the same level as before surgery (P = 0.0015). SV increased in 28 patients (75.7%) treated with mFOLFOX6 (95%CI, 61.8-89.5), but had not recovered in 12 of these cases (42.9%) 1 year after finishing treatment (95%CI, 17.3-47.5). In contrast, oral fluorouracil and leucovorin did not change SV. SV increased after adjuvant mFOLFOX6, and had not recovered in almost half of cases 1-year after finishing chemotherapy. This increase may indicate continuous SOS, which can adversely affect treatment after recurrence.