A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Location, Patients, and Study Design
2.2. Statistics
3. Results
3.1. Comparison of Superficial LN and Splenic Palpation between MD1 and MD2
3.2. Comparison of Superficial LN and Spleen Assessment Using Two Different US Sonographers
3.3. Comparison between Palpation and US
3.3.1. Detection of Pathological SupLN and Splenomegaly by US over Palpation
3.3.2. Dimensional Assessment of Pathological SupLNs and Splenomegaly Detected by US Missed by Palpation
3.3.3. Impact of BMI and Age on Discordance between Palpation and US
3.4. Ultrasound Echostructure of CLL SupLNs and Splenic Involvement Pattern
3.4.1. Ultrasound Echostructure of CLL SupLNs
3.4.2. Ultrasound Patterns of Splenic CLL Involvement
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Hallek, M.; Cheson, B.D.; Catovsky, D.; Caligaris-Cappio, F.; Dighiero, G.; Dohner, H.; Hillmen, P.; Keating, M.; Montserrat, E.; Chiorazzi, N.; et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018, 131, 2745–2760. [Google Scholar] [CrossRef] [Green Version]
- Marchal, G.; Oyen, R.; Verschakelen, J.; Gelin, J.; Baert, A.L.; Stessens, R.C. Sonographic appearance of normal lymph nodes. J. Ultrasound Med. 1985, 4, 417–419. [Google Scholar] [CrossRef]
- Vassallo, P.; Wernecke, K.; Roos, N.; Peters, P.E. Differentiation of benign from malignant superficial lymphadenopathy: The role of high-resolution US. Radiology 1992, 183, 215–220. [Google Scholar] [CrossRef]
- Weskott, H.-P.; Ioanitescu, E.S. Diagnostic approach to lymph node disease in ultrasound. In EFSUMB Course Book on Ultrasound; Central Ultrasound Department: Hannover, Germany, 2012. [Google Scholar]
- Eichhorst, B.; Robak, T.; Montserrat, E.; Ghia, P.; Niemann, C.U.; Kater, A.P.; Gregor, M.; Cymbalista, F.; Buske, C.; Hillmen, P.; et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2021, 32, 23–33. [Google Scholar] [CrossRef]
- Zhou, H.; Hu, P.; Yan, X.; Zhang, Y.; Shi, W. Ibrutinib in Chronic Lymphocytic Leukemia: Clinical Applications, Drug Resistance, and Prospects. OncoTargets Targets Ther. 2020, 13, 4877–4892. [Google Scholar] [CrossRef] [PubMed]
- Woyach, J.A.; Ruppert, A.S.; Heerema, N.A.; Zhao, W.; Booth, A.M.; Ding, W.; Bartlett, N.L.; Brander, D.M.; Barr, P.M.; Rogers, K.A.; et al. Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N. Engl. J. Med. 2018, 379, 2517–2528. [Google Scholar] [CrossRef] [PubMed]
- Gribben, J.G.; Bosch, F.; Cymbalista, F.; Geisler, C.H.; Ghia, P.; Hillmen, P.; Moreno, C.; Stilgenbauer, S. Optimising outcomes for patients with chronic lymphocytic leukaemia on ibrutinib therapy: European recommendations for clinical practice. Br. J. Haematol. 2018, 180, 666–679. [Google Scholar] [CrossRef] [Green Version]
- Wierda, W.G.; Tambaro, F.P. How I manage CLL with venetoclax-based treatments. Blood 2020, 135, 1421–1427. [Google Scholar] [CrossRef]
- O’Brien, S.; Furman, R.R.; Coutre, S.; Flinn, I.W.; Burger, J.A.; Blum, K.; Sharman, J.; Wierda, W.; Jones, J.; Zhao, W.; et al. Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: A 5-year experience. Blood 2018, 131, 1910–1919. [Google Scholar] [CrossRef] [PubMed]
- Benedetti, E.; Baratè, C.; Bruno, B.; Bramanti, E.; Ghia, P.; Scarfò, L.; Morganti, R.; Ricchiuto, V.; Galimberti, S. Response assessment to venetoclax in relapsed/refractory chronic lymphocytic leukemia by ultrasonography. Leuk. Res. 2021, 100, 106488. [Google Scholar] [CrossRef]
- Ioanitescu, S.; Iliescu, L.; Harza, M.; Ismail, G.; Copaci, I. Ultrasound of the spleen. In EFSUMB Course Book, 2nd ed.; Tuma, J., Badea, R., Dietrich, C.F., Eds.; e-book; EFSUMB: London, UK, 2015. [Google Scholar]
- Benedetti, E.; Tavarozzi, R.; Morganti, R.; Bruno, B.; Bramanti, E.; Barate, C.; Balducci, S.; Iovino, L.; Ricci, F.; Ricchiuto, V.; et al. Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms. J. Clin. Med. 2020, 9, 2149. [Google Scholar] [CrossRef]
- Benedetti, E.; Bruno, B.; Martini, F.; Morganti, R.; Bramanti, E.; Caracciolo, F.; Galimberti, S.; Lippolis, P.; Neri, E.; Arena, C.; et al. Early Diagnosis of Neutropenic Enterocolitis by Bedside Ultrasound in Hematological Malignancies: A Prospective Study. J. Clin. Med. 2021, 10, 4277. [Google Scholar] [CrossRef]
- Benedetti, E.; Proietti, A.; Miccoli, P.; Basolo, F.; Ciancia, E.; Erba, P.A.; Galimberti, S.; Orsitto, E.; Petrini, M. Contrast-enhanced ultrasonography in nodular splenomegaly associated with type B Niemann-Pick disease: An atypical hemangioma enhancement pattern. J. Ultrasound 2009, 12, 85–92. [Google Scholar] [CrossRef] [Green Version]
- Benedetti, E.; Bruno, B.; McDonald, G.B.; Paolicchi, A.; Caracciolo, F.; Papineschi, F.; Pelosini, M.; Campani, D.; Galimberti, S.; Petrini, M. Prospective qualitative and quantitative non-invasive evaluation of intestinal acute GVHD by contrast-enhanced ultrasound sonography. Bone Marrow Transplant. 2013, 48, 1421–1428. [Google Scholar] [CrossRef]
- Benedetti, E.; Lippolis, P.V.; Caracciolo, F.; Galimberti, S.; Papineschi, F.; Pelosini, M.; Focosi, D.; Stella, S.M.; Neri, E.; Seccia, M.; et al. Ultrasound findings guided a successful hemicolectomy in a leukemic patient with neutropenic enterocolitis. J. Ultrasound 2008, 11, 97–101. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Benedetti, E.; Mavilia, F.; Baratè, C.; Bramanti, E.; Morganti, R.; Bruno, B.; Pelosini, M.; Capochiani, E.; Stella, M.S.; Galimberti, S. Prospective Cross-Sectional Study for the Comparison Between Palpation and Ultrasound of Lymph Node and Splenic Assessment in Chronic Lymphocytic Leukemia Patients. J. Ultrasound 2022. submitted. [Google Scholar]
- Hallek, M.; Cheson, B.D.; Catovsky, D.; Caligaris-Cappio, F.; Dighiero, G.; Döhner, H.; Hillmen, P.; Keating, M.J.; Montserrat, E.; Rai, K.R.; et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines. Blood 2008, 111, 5446–5456. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dudea, S.M.; Lenghel, M.; Vasilescu, D.; Duma, M.M. Ultrasonography of superficial lymph nodes: Benign vs. malignant. Med. Ultrason. 2012, 14, 294–306. [Google Scholar]
- Dudea, S.M.; Botar-Jid, C.; Dumitriu, D.; Vasilescu, D.; Manole, S.; Lenghel, M.L. Differentiating benign from malignant superficial lymph nodes with sonoelastography. Med. Ultrason. 2013, 15, 132–139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ying, M.; Bhatia, K.S.S.; Lee, Y.P.; Yuen, H.Y.; Ahuja, A.T. Review of ultrasonography of malignant neck nodes: Greyscale, Doppler, contrast enhancement and elastography. Cancer Imaging 2014, 13, 658–669. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Berzigotti, A.; Piscaglia, F. Ultrasound in portal hypertension—Part 2—and EFSUMB recommendations for the performance and reporting of ultrasound examinations in portal hypertension. Ultraschall Med. 2012, 33, 8–31. [Google Scholar] [CrossRef]
- Wolfel, D.A.; Smalley, R.H. “Lipoplastic” lymphadenopathy. Am. J. Roentgenol. Radium Ther. Nucl. Med. 1971, 112, 610–612. [Google Scholar] [CrossRef] [PubMed]
- Parsons, C.A.; King, D.M. Disseminated lipoplastic lymphadenopathy. Br. J. Radiol. 1982, 55, 535–536. [Google Scholar] [CrossRef] [PubMed]
- Giovagnorio, F.; Drudi, F.M.; Fanelli, G.; Flecca, D.; Francioso, A. Fatty changes as a misleading factor in the evaluation with ultrasound of superficial lymph nodes. Ultrasound Med. Biol. 2005, 31, 1017–1022. [Google Scholar] [CrossRef]
- Whitman, G.J.; Lu, T.J.; Adejolu, M.; Krishnamurthy, S.; Sheppard, D. Lymph Node Sonography. Ultrasound Clin. 2011, 6, 369–380. [Google Scholar] [CrossRef]
- Quaia, E. Contrast Media in Ultrasonography. In Medical Radiology; Springer: Berlin/Heidelberg, Germany, 2005; pp. 315–322. ISBN 3-540-40740-5. [Google Scholar]
- Saiag, P.; Bernard, M.; Beauchet, A.; Bafounta, M.-L.; Bourgault-Villada, I.; Chagnon, S. Ultrasonography using simple diagnostic criteria vs palpation for the detection of regional lymph node metastases of melanoma. Arch. Dermatol. 2005, 141, 183–189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Prayer, L.; Winkelbauer, H.; Gritzmann, N.; Winkelbauer, F.; Helmer, M.; Pehamberger, H. Sonography versus palpation in the detection of regional lymph-node metastases in patients with malignant melanoma. Eur. J. Cancer Clin. Oncol. 1990, 26, 827–830. [Google Scholar] [CrossRef]
Superficial LN Region | Cohen’s Kappa |
---|---|
Inguinal R | 0.425 |
Inguinal L | 0.754 |
Axillary R | 0.324 |
Axillary L | 0.663 |
Laterocervical R | 0.649 |
Laterocarvical L | 0.660 |
Mean Comparison (mm) | Correlation Analysis | |||||
---|---|---|---|---|---|---|
Superficial LN Region | N | Mean (mm) | SD (mm) | p-Value | Pearson’s r | p-Value |
Inguinal MD1 | 89 | 9 | 7 | 0.005 | 0.446 | <0.001 |
Inguinal MD2 | 89 | 7 | 5 | |||
Axillary MD1 | 38 | 7 | 6 | 0.017 | 0.248 | 0.133 |
Axillary MD2 | 38 | 4 | 4 | |||
Laterocervical MD1 | 69 | 8 | 5 | <0.001 | 0.486 | <0.001 |
Laterocervical MD2 | 69 | 5 | 5 |
Mean Comparison (mm) | Correlation Analysis | |||||
---|---|---|---|---|---|---|
Superficial LN Dimensions | N | Mean (mm) | SD (mm) | p-Value | Pearson’s r | p-Value |
US1_Subclavicular_R | 37 | 11.03 | 4.45 | 0.480 | 0.992 | <0.001 |
US2_ Subclavicular_R | 37 | 11.19 | 4.18 | |||
US1_ Subclavicular_L | 46 | 9.47 | 2.83 | 0.259 | 0.993 | <0.001 |
US2_ Subclavicular_L | 46 | 9.30 | 2.66 | |||
US1_Sovraclavicular_R | 14 | 9.67 | 2.75 | 1.000 | 0.996 | <0.001 |
US2_Sovraclavicular_R | 14 | 9.67 | 2.58 | |||
US1_Sovraclavicular_L | 9 | 9.03 | 3.69 | 0.307 | 0.994 | <0.001 |
US2_Sovraclavicular_L | 9 | 9.24 | 3.35 | |||
Spleen dimension | Mean (mm) | SD (mm) | p-value | r | p-value | |
US1_splenic_Longdiam | 75 | 13.66 | 2.79 | 0.276 | 0.981 | <0.001 |
US2_splenic_Longdiam | 75 | 13.46 | 2.83 | |||
US1_splenic_CSarea | 75 | 67.30 | 31.56 | 0.381 | 0.967 | <0.001 |
US2_splenic_CSarea | 75 | 64.47 | 25.12 |
Normal | Pathological | Cohen’s Kappa | ||
---|---|---|---|---|
Spleen (Palpation) | ||||
Spleen US | Normal | 14 | 0 | 0.063 |
Pathological | 51 | 10 | ||
R-Ing_palpation | ||||
R-Ing. US | Normal | 19 | 1 | 0.031 |
Pathological | 101 | 18 | ||
L-Ing_palpations | ||||
L-Ing. US | Normal | 17 | 3 | 0.001 |
Pathological | 100 | 21 | ||
R-Ax-palpation | ||||
R-Ax-US | Normal | 10 | 0 | 0.001 |
Path | 160 | 8 | ||
L-Ax-palpation | ||||
L-Ax-US | Normal | 3 | 0 | 0.001 |
Pathological | 168 | 5 | ||
R-Lcv-palpation | ||||
R-Lcv-US | Normal | 8 | 1 | 0.005 |
Pathological | 149 | 16 | ||
L-Lcv-palpation | ||||
L-Lcv-US | Norm | 8 | 0 | 0.001 |
Pathological | 170 | 10 |
SupLNs | Median (Range) (mm) |
---|---|
Right inguinal | 18.6 (5.5–45) |
Left inguinal | 18 (3.0–43.5) |
Right axillary | 17 (5–54) |
Left axillary | 18.6 (6–54) |
Right sub-clavicular | 10 (4.3–31) |
Left sub-clavicular | 9 (6.0–20) |
Right supraclavicular | 9.5 (7.7–30.6) |
Left supraclavicular | 14 (6–21) |
Right laterocervical | 13.5 (4–34.5) |
Left laterocervical | 12.1 (4–33) |
Spleen | Median (range) |
Longitudinal diameter (cm) | 13.8 (12.5–18.4) |
Area (in cm2) | 69 (47–135) |
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Benedetti, E.; Mavilia, F.; Baratè, C.; Bramanti, E.; Morganti, R.; Cervetti, G.; Capochiani, E.; Bruno, B.; Pelosini, M.; Stella, S.M.; et al. A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy. J. Clin. Med. 2022, 11, 3206. https://doi.org/10.3390/jcm11113206
Benedetti E, Mavilia F, Baratè C, Bramanti E, Morganti R, Cervetti G, Capochiani E, Bruno B, Pelosini M, Stella SM, et al. A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy. Journal of Clinical Medicine. 2022; 11(11):3206. https://doi.org/10.3390/jcm11113206
Chicago/Turabian StyleBenedetti, Edoardo, Fabrizio Mavilia, Claudia Baratè, Emilia Bramanti, Riccardo Morganti, Giulia Cervetti, Enrico Capochiani, Benedetto Bruno, Matteo Pelosini, Salvatore Massimo Stella, and et al. 2022. "A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy" Journal of Clinical Medicine 11, no. 11: 3206. https://doi.org/10.3390/jcm11113206
APA StyleBenedetti, E., Mavilia, F., Baratè, C., Bramanti, E., Morganti, R., Cervetti, G., Capochiani, E., Bruno, B., Pelosini, M., Stella, S. M., & Galimberti, S. (2022). A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy. Journal of Clinical Medicine, 11(11), 3206. https://doi.org/10.3390/jcm11113206