Rationale and Objectives
The aim of this study was to assess splenic perfusion in patients with spleen involvement in malignant hematologic diseases and liver cirrhosis and in controls without hepatosplenic disease using volume perfusion computed tomography.
Materials and Methods
Between October 2009 and December 2011, 14 hematologic patients with known spleen involvement were recruited. An additional 17 consecutive patients without known splenic or liver disease were enrolled as controls, as well as 29 patients with liver cirrhosis and portal hypertension. A 40-second volume perfusion computed tomographic scan of the upper abdomen was performed. Analysis included measurement of splenic volume, blood flow (BF), blood volume (BV), K trans , and mean transit time (MTT).
Results
In lymphoma patients, mean splenic volume and perfusion parameters were as follows: splenic volume, 1125.34 mL; BF, 61.24 mL/100 mL/min; BV, 16.53 mL/100 mL; K trans , 37.00 mL/100 mL/min; and MTT, 12.42 seconds. All perfusion values of patients with lymphoma and cirrhosis differed significantly, except for BV, compared to controls. For patients with lymphoma, significant correlations were found between splenic volume and BF ( r = −0.683, P = .000), splenic volume and BV ( r = −0.525, P = .002), and splenic volume and MTT ( r = 0.543, P = .001). During treatment, significant correlations between the diameters of nodular lymphoma target lesions, splenic volume, and the perfusion parameters were present for splenic volume ( r = 0.601, P = .002), BF ( r = −0.777, P = .000) and BV ( r = −0.500, P = .011).
Conclusions
Volume perfusion computed tomography represents a novel tool for the assessment of splenic perfusion. Preliminary results in patients with spleen involvement reveal lower perfusion values compared to controls or patients with cirrhosis. Therefore, this technique might provide additional information in clinical routine.
As a result of rare primary splenic diseases , the spleen is often considered “silent and forgotten” . On the other hand, secondary manifestations of hematologic, immunologic, oncologic, infectious, vascular, and systemic disorders are frequently found in the spleen . Forty-four percent of patients with lymphoma have splenic involvement . Splenomegaly is a common but unspecific finding, as enlarged spleens do not necessarily indicate lymphoma infiltration , and only 1% to 2% of all patients with non-Hodgkin’s lymphoma present with such splenic enlargement . Spleen involvement is common in mantle cell lymphoma and follicular lymphoma , as well as chronic lymphatic leukemia . Accurate staging with assessment of splenic disease is essential for clinical management and follow-up . However, a study by Munker et al revealed a low accuracy of only 15% to 37% for computed tomography (CT) and a disappointing correlation with histologic state. Nevertheless, CT is the most frequently used staging modality. Especially for diffuse involvements, positron emission tomography (PET) using [ 18 F]-fluorodeoxyglucose (FDG) seems to be superior to CT . Secondary portal hypertension due to either direct lymphoma infiltration of the liver or mediastinal compression of the superior vena cava may additionally alter splenic perfusion. In a similar scenario, portal hypertension in liver cirrhosis can prolong blood transit time because of splenic venous congestion and decreased splenic perfusion . Various imaging techniques such as isotope scintigraphy and [ 15 O]-labeled water PET have been applied for the assessment of hepatic and splenic perfusion. These techniques are complex and are available only at specialized imaging sites. Functional CT, based on the exchange of iodinated contrast material between the intravascular space and the extravascular interstitial space, is an interesting approach that can be integrated in the clinical routine with manageable effort . This method evolved from single-location dynamic sequences toward multi–detector row computed tomographic perfusion . Recently, Goetti et al applied four-dimensional spiral-mode for computed tomographic liver perfusion with 128-row CT and coverage of up to 14.8 cm.
The aim of our study was to assess and compare the ranges of splenic perfusion using this new method. In the first step, a group of hematologic patients with spleen involvement was analyzed. Elderly patients in particular require special attention, because in this group, liver cirrhosis is frequently (23.7%) undiagnosed . Therefore, we additionally analyzed splenic perfusion in a population with proven liver cirrhosis, portal hypertension and hepatocellular carcinoma (HCC) who had undergone liver perfusion CT prior to transarterial chemoembolization. Finally, a group of patients who had undergone tumor perfusion CT for other purposes but presented with neither splenic diseases nor portal hypertension were included as normal controls.
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Materials and methods
Study Population
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Computed Tomographic Protocol
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Quantitative Perfusion Analysis
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Statistical Analyses
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Results
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Spleen Involvement
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Table 1
Splenic Volumes and Perfusion Parameters for All Groups
Variable Malignant Hematologic Diseases_P_ ∗ Control Group_P_ † Entire Cirrhotic HCC Group Cirrhotic HCC Child Class A Group Cirrhotic HCC Child Class B Group Splenic volume (mL) 1125.34 ± 784.24 <.001 253.79 ± 75.28 <.001 639.09 ± 355.22 594.56 ± 375.96 779.05 ± 253.04 Blood flow (mL/100 mL/min) 61.24 ± 22.80 <.001 95.66 ± 25.25 .002 72.38 ± 21.00 74.51 ± 22.93 65.67 ± 12.24 Blood volume (mL/100 mL) 16.53 ± 14.32 .095 16.39 ± 4.64 .089 13.91 ± 6.46 13.39 ± 6.58 15.54 ± 6.27 K trans (mL/100 mL/min) 37.00 ± 12.97 .011 49.12 ± 15.58 .036 52.21 ± 10.43 51.84 ± 11.19 53.38 ± 8.22 Mean transit time (seconds) 12.42 ± 2.66 .023 10.67 ± 2.05 <.001 13.77 ± 3.57 13.56 ± 3.91 14.46 ± 2.32
HCC, hepatocellular carcinoma.
Data are expressed as mean ± standard deviation.
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Table 2
Patients with Malignant Hematologic Diseases and Spleen Involvement
Patient Age (y) Sex Diagnosis First Diagnosis Treatment Study Date Splenic Volume BF BV K trans MTT Baseline 1 58.6 M Low-grade B-NHL 02.2007 No 10.2010 1826.31 59.35 6.51 52.46 14.29 2 72.7 M Relapse PTCL-NOS 03.2011 6 × CHOP (5/06 to 8/06) 01.2011 560.21 87.69 13.97 47.60 10.54 3 68.6 F SMZL 12.2010 No 03.2010 1878.34 55.82 7.45 43.36 15.13 4 65.7 M B-CLL 07.2005 15 × KNOSPE (5/07 to 12/07)
1 × rituximab (6/08)
5 × R-bendamustine (6/08 to 10/08)
5 × fludarabine/cyclophosphamide (9/09 to 1/10) 04.2011 648.92 46.76 8.37 30.78 12.16 5 76.8 M B-CLL 01.1998 5 × KNOSPE (12/01 to 3/02)
6 × KNOSPE (7/03 to 10/03)
4 × R-bendamustine (10/09 to 2/10) 06.2010 2057.63 51.62 14.09 55.17 16.86 Baseline and follow-up 6 49.5 M B-CLL 10.2005 No 01.2011 503.45 64.88 13.20 22.09 10.11 6 × R-FC (3/11 to 8/11) 09.2011 320.55 117.95 55.67 202.42 11.97 7 63.6 F Relapse low-grade B-NHL 08.2010 6 × VACOP-B (2/95)
6 × R-bendamustine (8/07 to 2/08) 01.2011 922.71 25.40 3.56 28.36 13.66 2 × R-VIPE (1/11) 02.2011 457.40 73.98 15.42 40.21 11.29 8 56.6 M Low-grade B-NHL 10.2008 6 × R-CHOP + 2 × rituximab (10/08 to 3/09) 05.2010 1187.25 45.53 17.43 24.15 19.00 1 × R-VIPE (10/10) 08.2010 1748.80 37.51 4.93 36.07 16.01 2 × R-VIPE (11/10) 11.2010 1168.38 43.23 6.83 39.53 13.28 No 12.2010 1168.83 45.08 6.53 41.28 12.44 4 × R-bendamustine (11/10 to 6/11) 03.2011 1116.84 37.83 5.50 29.26 12.76 9 56.6 F DLBCL 07.2010 No 07.2010 1886.14 13.00 3.13 12.46 8.79 4 × R-CHOP (7/10 to 9/10) 09.2010 448.37 60.91 9.72 37.55 11.61 2 × R-CHOP + 2 × rituximab (10/10 to 12/10) 01.2011 329.28 65.88 9.89 47.66 9.72 No 06.2011 320.18 94.16 41.47 33.84 10.90 10 67.7 M Relapse DLBCL 12.2010 6 × CHOP-21 (7/02 to 11/02) 02.2011 513.55 48.09 7.62 35.62 13.64 1 × R-VIPE (2/11) 03.2011 275.24 99.54 17.33 37.40 8.30 2 × R-VIPE (3/11) 04.2011 279.67 79.95 14.80 36.09 7.71 1 × HD + PBSCT (4/11) 08.2011 260.00 69.21 10.50 37.63 9.16 11 51.5 M PTCL-NOS 05.2010 2 × CHOP + 2 × VIPE (5/10 to 8/10) 08.2010 1856.29 49.86 15.43 47.25 14.30 HD + PBSCT (10/10) 12.2010 2982.11 32.37 4.20 36.13 12.12 12 50.5 F PTCL-NOS 02.2003 No 04.2010 1862.25 50.93 6.66 46.75 14.98 3 × CHOP + 2 × VIPE + 2 × DHAP + HD-BEAM (4/10 to 2/11) 03.2011 1241.66 60.56 32.04 29.77 12.26 1 × cladribine (5/11) 06.2011 1017.42 83.80 48.92 4.73 15.15 13 56.6 M MCL 11.2010 2 × R-CHOP; 1 × R-DHAP 12.2010 560.85 85.30 39.98 25.89 11.98 1 × R-DHAP 01.2011 407.80 95.46 50.64 14.11 12.76 1 × HD + PBSCT (4/11) 05.2011 323.11 86.82 18.76 44.48 10.84 14 60.6 M MCL 03.2010 No 03.2010 2908.62 48.95 6.18 40.93 10.26 3 × R-CHOP + 2 × R-DHAP (4/10 to 7/10) 06.2010 1069.75 88.09 39.88 67.18 10.34
B-CLL, B-cell chronic lymphocytic leukemia; BF, blood flow; B-NHL, B-cell non-Hodgkin’s lymphoma; BV, blood volume; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HD, high-dose chemotherapy; KNOSPE, chlorambucil, prednisolone; MCL, mantle cell lymphoma; MTT, mean transit time; PBSCT, peripheral blood stem cell transplantation; PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone; R-DHAP, rituximab, dexamethasone, cytarabine, cisplatin; R-FC, rituximab, fludarabine, cyclophosphamide; R-VIPE, rituximab, mesna, cisplatin, etoposide; SMZL, splenic marginal zone lymphoma; T-NHL, T-cell non-Hodgkin’s lymphoma; VACOP-B, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin.
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![Figure 1, (a) Blood flow map of a patient with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) with splenic involvement. The black stars indicate an area with low blood flow. (b) Corresponding [ 18 F]-fluorodeoxyglucose positron emission tomographic image of the patient with PTCL-NOS showing increased FDG uptake. (c) Blood volume map of the patient with PTCL-NOS. Fast and slow enhancing compartments of the spleen cause the heterogeneous patterns. (d) K trans map of the patient with PTCL-NOS. Fast and slow enhancing compartments of the spleen cause the heterogeneous patterns. (e) Mean transit time map of the patient with PTCL-NOS. Fast and slow enhancing compartments of the spleen cause the heterogeneous patterns. (f) Hematoxylin and eosin (H&E) staining of a spleen specimen from a patient with PTCL-NOS (magnification, 5×). The black stars indicate a fine nodular infiltrate and surrounding diffuse infiltrations. (g) H&E staining of a spleen specimen from a patient with PTCL-NOS (magnification, 5×). The black star shows lymphomatous invasion into a trabecular artery.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/AssessmentofSplenicPerfusioninPatientswithMalignantHematologicDiseasesandSpleenInvolvementLiverCirrhosisandControlsUsingVolumePerfusionCTVPCT/0_1s20S1076633212000426.jpg)
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Patients with Nonhepatosplenic Disease and Liver Cirrhosis
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Discussion
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Conclusions
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Acknowledgments
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