HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kamel, I. R. Articles by Raptopoulos, V. Search for Related Content PubMed PubMed Citation Articles by Kamel, I. R. Articles by Raptopoulos, V. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?

Accuracy of Volumetric Measurements After Virtual Right Hepatectomy in Potential Donors Undergoing Living Adult Liver Transplantation

¹ Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave., Boston, MA 02215.
² Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215.
³ Present address: Institute of Liver Transplantation, Lahey Clinic Medical Center, 41 Mall Rd., Burlington, MA 01805.

Received June 14, 2000; accepted after revision August 7, 2000.

 
Address correspondence to V. Raptopoulos.

Abstract

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
OBJECTIVE. The purpose of this study was to evaluate accuracy for determining the total and lobar liver volumes using a multidetector CT scanner in potential donors undergoing living adult right lobe liver transplantation.

SUBJECTS AND METHODS. Fifty-two adult donors underwent CT using a multidetector scanner after IV injection of 180 mL of contrast material. For volumetric determination, portal venous phase images were acquired at 60 sec. Hand-tracing was used to isolate the entire liver, and a curved hepatectomy plane was then identified in a manner simulating the surgical incision. Two observers performed hand-tracing of the entire liver to calculate total liver volume, and of the right lobe to calculate expected graft volume.

RESULTS. The mean volume of the entire liver, right lobe, and left lobe was 1807 mL, 990 mL, and 817 mL, respectively, for observer 1, and 1788 mL, 1007 mL, and 781 mL, respectively, for observer 2. There was significant agreement between the two observers in determining total and lobar liver volumes (r = 0.996, 0.977, and 0.965 for total, right lobe, and left lobe volumes, respectively; p < 0.0001). There was no statistically significant difference between the two observers in measuring total or lobar liver volumes (p < 0.0001). There was significant agreement between right lobe volume measured by each observer and graft weight obtained in 14 donors at surgery (r = 0.898 and 0.879, for observers 1 and 2, respectively; p < 0.001).

CONCLUSION. Total and lobar volume determinations after virtual right hemihepatectomy provides accurate and reproducible information that is critical in selecting potential living liver donors.

Introduction

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
Living related liver transplantation in the adult is a new surgical procedure that allows healthy adults to donate a portion of their liver to compatible recipients [1,2,3]. This innovative procedure is performed to overcome the shortage of available cadaveric livers. Surgery involves removal of the right lobe of the liver (segments V-VIII) from a healthy donor, without endangering the vascular supply or metabolic function of the remaining left lobe. Liver procurement is possible because of its unique bilobar multisegmental anatomy. In addition, regeneration of the remaining left lobe compensates for the loss of hepatic mass. Donor selection is based on total and segmental liver volumes because graft size has been one of the major factors determining a successful outcome. A small graft may result in malfunction or may not sustain metabolic function in the recipient. A large graft is associated with a risk of graft compression and poor perfusion [4]. In addition, in potential donors, sufficient left lobe liver volume must be preserved to permit metabolic function during regeneration. Therefore, accuracy of total and segmental liver volumes is important to avoid donor-recipient volume mismatch [5].

Our earlier work has described optimization of multidetector multiphase CT in preoperative liver donor evaluation, and in defining an avascular hemihepatectomy plane between the right and left lobes [6]. In this study we evaluated the accuracy of total and segmental liver volume measurements using multidetector CT in potential donors undergoing adult right lobe liver transplantation.

Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
Between December 1998 and May 2000, 52 consecutive patients underwent multiphasic CT of the liver. Imaging was performed as part of preoperative workup for potential adult right lobe liver transplantation. There were 35 men and 17 women, with a mean age of 39 years (age range, 18-57 years). Patients' height and weight were recorded at the time of CT. Body surface area was calculated using the equation described by DuBois and DuBois [7].

Imaging
CT was performed using a Lightspeed scanner (General Electric Medical Systems, Milwaukee, WI) with interleaved multidetector capability, as described in a prior study [6]. Multiphase scanning was performed after IV injection of 180 mL of Optiray (Ioversol 68%; Mallinckrodt, St. Louis, MO) at a rate of 5 mL/sec. Arterial dominant phase images were acquired at 18 sec (collimation, 1.25 mm; table speed, 7.5 mm), and portal dominant phase images were acquired at 60 sec (collimation, 2.5 mm; table speed, 15 mm). Axial images were reconstructed using a standard algorithm, and postprocessing was performed on a commercially available workstation (Advantage Windows 3.1; General Electric Medical Systems).

Two observers independently measured total liver volume by hand-tracing the liver outline on the axial portal venous phase images (Fig. 1). Both observers were fellowship-trained radiologists, experienced in image processing. Hand-tracing was performed to isolate the liver from surrounding structures of similar attenuation, such as the stomach and spleen. Hand-tracing was not performed with every axial image, but the frequency was dependent on the change in liver contour. In general, hand-tracing was performed on every third image in the upper half of the liver, and every sixth image in the lower half, allowing automatic interpolation between the handtraced images. To enhance our accuracy in volumetric measurement, we carefully excluded large vessels (including the inferior vena cava and extrahepatic portal vein) and major fissures (such as the fissure for the ligamentum teres). A three-dimensional model of the liver was then generated using the "paintbrush" method, with commercially available software (Fig. 2). Using the liver and hepatic vein models for guidance, each observer performed a virtual right hepatectomy in a curved plane. The plane was defined in conjunction with our transplantation team in a manner simulating the anticipated surgical incision. The plane avoided major vessels traversing between the right and left lobes, immediately to the right of the middle hepatic vein (Fig. 3A,3B). This relatively avascular plane lies along the main portal scissura, which corresponds to the anatomic Cantlie's line. We perform the hepatectomy in a craniocaudal direction, using the middle hepatic vein as a landmark, and extending along the gallbladder fossa anteriorly and the portal bifurcation posteriorly. The caudate lobe (segment I) is typically spared. Subsequent to the virtual hepatectomy, the right and left lobe volumes were calculated. The total time required for image processing and interpretation is approximately 10-15 min. During surgery, the hepatectomy images were available to the surgeons who followed the virtual hepatectomy plane with the guidance of intraoperative sonography.

View larger version (144K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1. —32-year-old male potential liver donor. Hand-tracing of liver outline on axial CT scan acquired during portal venous phase shows isolation of liver from surrounding tissues of similar attenuation, such as stomach and spleen. With hand-tracing, care is exercised to exclude vascular structures such as inferior vena cava (arrowhead), extrahepatic portal vein (arrow), and major fissures such as fissure for ligamentum teres.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2. —32-year-old male potential liver donor. Three-dimensional model of liver in frontal projection, was generated using commercially available software after hand-tracing liver outline on axial images, as shown in Figure 1. Model shows size, shape, and surface contour of liver. These will determine if graft can be safely accommodated in recipient's abdominal cavity.

View larger version (86K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A. —32-year-old male potential liver donor. Three-dimensional model of right lobe of liver, hepatic veins, and portal vein in frontal projection showing hepatectomy plane immediately to right of middle hepatic vein (arrow).

View larger version (80K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B. —32-year-old male potential liver donor. Same model as in A, seen from inferior projection.

Statistical Analysis
Scatterplots were used to identify the correlation between observers 1 and 2 in measuring total and segmental liver volumes in all 52 patients. A linear regression equation was generated for each scatterplot, and the correlation coefficient (r) was calculated. The Student's t test was used to determine equality of the volumes as determined by each observer. The null hypothesis was rejected when p was less than 0.05.

In 14 donors who underwent right hepatectomy, the flushed graft weight was measured immediately after donor hepatectomy. It was assumed that the absolute graft weight is the actual graft volume because the liver has nearly the same density as water [8]. Scatterplots were also used to identify the correlation between the right lobe volume as measured by each observer and the graft weight. A linear-regression equation was generated for each scatterplot, and the correlation coefficient was calculated. The Student's t test was also used to determine equality of the volume to graft weight as determined by each observer. The Newman-Keuls multiple range test was performed to determine if the difference between the measured volume by each observer and the actual graft weight was statistically significant. The null hypothesis was rejected at p < 0.05.

To compare our results with previously reported methods of estimating liver volume, scatterplots were used to identify the correlation between total liver volume and body weight, body height, and body surface area. Scatterplots were also generated between total measured liver volume, and the calculated liver volume described in other studies [9,10,11].

Results

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
Total liver volume was 1807 mL ± 357 mL and 1788 mL ± 350 mL for observers 1 and 2, respectively. Right lobe volume was 990 mL ± 203 mL and 1007 mL ± 216 mL for observers 1 and 2, respectively. There was a significant agreement between the two observers in determining total and lobar liver volumes (Fig. 4). The correlation coefficients were 0.996, 0.977, and 0.965 for total, right lobe, and left lobe volumes, respectively (p < 0.0001). The coefficient of variation for interobserver variability was 1.2%, 1.1%, and 1.3% for total, right lobe, and left lobe volumes, respectively. Additionally, the Student's t test showed no statistically significant difference between the 2 observers in measuring total or lobar liver volume (p < 0.0001).

View larger version (9K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4. —Scatterplot shows total liver volume (mL) determined by observers 1 and 2 for 52 potential donors. Note tight correlation between measurements obtained by 2 observers (r = 0.996; p < 0.0001).

Liver volume for 14 donors who underwent right hepatectomy measured 1003 mL ± 130 mL and 992 mL ± 148 mL as determined by observers 1 and 2, respectively. There was significant agreement between right lobe volume measured by each observer and graft weight (Fig. 5). Correlation coefficient for observers 1 and 2 was 0.898 and 0.879, respectively (p < 0.001). The coefficients of variation were 3% and 2% for observers 1 and 2, respectively. The Newman-Keuls multiple range test showed no statistically significant difference between the right lobe volume measured by the two observers, or between the right lobe volume measured by each observer and the actual graft weight at hepatectomy (p < 0.05).

View larger version (7K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5. —Scatterplot shows right lobe liver volume (mL) determined by each observer compared with graft weight (gm). Note tight correlation between measured volume and graft weight (r = 0.898 and 0.879 for observers 1 and 2, respectively; p < 0.001). + = observer 1, = observer 2.

Scatterplots showed poor correlation between total liver volume and body weight (r = 0.437, p > 0.05), body height (r = 0.443, p > 0.05), and body surface area (r = 0.637, p > 0.05). Poor correlation was also noted between total liver volume as measured in the current study and those calculated in prior studies. The correlation coefficient was 0.661, 0.637, and 0.630 for volumes calculated using equations from DeLand and North [9], Urata et al. [10], and Lin et al. [11], respectively (p > 0.05).

Discussion

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
In our experience with 52 patients being evaluated for potential liver donation, multidetector CT permitted accurate and reproducible volumetric determination of potential donors before adult right lobe liver transplantation. There was significant agreement between the two observers in measuring total and segmental liver volumes. In addition, there was significant agreement between the volume calculated by each observer and graft weight measured at the time of surgery. The described technique is relatively simple and can easily be performed with high accuracy.

The donor operation consists of cholecystectomy followed by right hepatectomy. The right hepatic artery and right portal vein are dissected followed by the retrohepatic vena cava, isolating the origin of the right hepatic vein. The right bile duct is isolated last. The recipient's liver is then removed, leaving the inferior vena cava intact. This is followed by implantation of the donor graft into the recipient. The vascular anastomosis is performed in the following order: end-to-end right hepatic vein, end-to-end portal vein, and end-to-end hepatic artery. The bile duct is reconstructed last, using a Rouxen-Y choledochoenterostomy.

Minimizing donor morbidity is a major concern, and preoperative evaluation includes extensive clinical, laboratory, psychologic, and radiologic examinations. Radiologic evaluation of donors must provide total and lobar liver volumes. Imaging should also depict the anatomy of the hepatic veins that will drain the graft and the remaining left lobe, and will determine choice of hepatectomy plane. The donor is left with only the left lobe of the liver, and, therefore, the critical volume and the quality of the remnant liver are important considerations in patient selection. Liver remnant volume of 30-40% of the total liver volume is sufficient for the donor to survive, provided that the liver parenchyma is normal without evidence of fatty infiltration [12]. Determination of the right lobe volume is essential to reduce the risk of graft malfunction. It has been estimated that the minimum graft volume required to provide sufficient functional hepatocytes to the recipient is approximately 40% of the standard liver mass [12], as calculated using the body surface area [10]. A large graft makes implantation more challenging especially when performing the vascular anastomosis and when controlling bleeding. Moreover, closure of the abdominal wall may be difficult [13]. Small-for-size grafts are prone to dysfunction, not only because of insufficient functional hepatic mass but also because the graft and sinusoidal cells may be injured by excessive portal perfusion [5]. A small graft is also prone to torsion. However, this rare complication can be prevented by ligating the falciform ligament to the anterior aspect of the abdominal cavity.

Total liver volume is reported to have a relatively constant relation to body weight, ranging between 2-2.7% in healthy subjects [14]. However, the right and left lobe volumes are widely variable [15]. Therefore, graft size cannot be predicted preoperatively by body weight. Volume calculations using conventional and helical CT are reported to be relatively accurate [9,10,11, 13,14,15,16]. These calculations are performed by manually tracing around the margins of the hepatic parenchyma on each CT image using an electronic cursor. The cross-sectional area (cm²) within the region of interest is determined, and all individual areas are summed, yielding the total liver volume (cm³). The use of multidetector technology has dramatically increased the speed of data acquisition, resulting in thin-slice (1.25 mm) acquisitions and decreased motion artifacts, compared with that of conventional scanners. However, its accuracy in volume determination has not been tested. Commercially available software allows interpolation between the hand-traced slices, and automatic determination of the liver volume, resulting in faster image processing. The thin-slice axial images allow accurate three-dimensional reconstructions of the liver and depiction of the shape of the graft, which help the surgeon in determining that the graft can be safely accommodated in the abdominal cavity of the recipient. The determination of liver volume can be performed by simpler techniques and less sophisticated equipment. However, for living related right lobe harvesting when the graft weight and the remaining left lobe volume are critical for maintaining donor and recipient metabolic function, accurate volumetric measurements must be obtained.

Several reports in the literature describe alternate methods for calculating liver volume on the basis of body weight or surface area. In their study, DeLand and North [9] described a linear relation between liver weight in kilograms and body surface area in square meters. Applying their equation to our patient data resulted in overestimation of liver volume and poor correlation with our measured volume (r = 0.661). The DeLand and North study was based on autopsy findings of 550 patients, and liver weight may have included weight of the gallbladder, attached ligaments, and intrahepatic vena cava. These structures were excluded from our measurements. In addition, postmortem accumulation of blood in the liver may increase liver weight in autopsy measurements.

A 1995 publication of a study by Urata et al. [10] described a linear correlation between the measured liver volume and body surface area. However, in our study, we found poor correlation between our measured liver volume and the calculated volume using the equation of Urata et al. (r = 0.637). One possible explanation for this poor correlation is the fact that their study was based on findings in children and young adults, with a wide age range (age range, 1 month-27 years). Moreover, the study was performed on Japanese patients whose livers weigh less than those of the European and American patients [17]. Similarly, applying our data to the formula developed by Lin et al. [11] also resulted in poor correlation between measured and calculated liver volumes (r = 0.630).

Conclusion

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 
Multidetector CT provides accurate and reproducible volumetric evaluation of potential donors undergoing living adult right lobe liver transplantation. This information is essential for patient selection and preoperative surgical planning. Current models to predict liver volume on the basis of body weight and surface area may not be applicable to the patient population in the United States. Until appropriate nomograms become available, liver volume should be individually calculated.

References

Top Abstract Introduction Subjects and Methods Results Discussion Conclusion References

 

1. Broelsch CE, Burdelski M, Rogiers X, et al. Living donor for liver transplantation. Hepatology 1994;20[suppl]:49S -55S[Medline]
2. Hashikura V, Makuuchi M, Kawasaki S, et al. Successful living-related partial liver transplantation to an adult patient. Lancet 1994;343:1233 -1234[Medline]
3. Kawasaki S, Machuuchi M, Maatsunami H, et al. Living-related liver transplantation in adults. Ann Surg 1998;227:269 -274[Medline]
4. Kasi H, Makuuchi M, Kawasaki S, et al. Intraoperative color Doppler ultrasonography for partial-liver transplantation from the living donors in pediatric patients. Transplantation 1992;54:173 -175[Medline]
5. Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors: implications for the treatment of older patients. Ann Surg 1996;224:544 -554[Medline]
6. Kamel IR, Kruskal JB, Pomfret EA, Keogan MT, Warmbrand G, Raptopoulos V. Impact of multidetector CT on donor selection and surgical planning before living adult right lobe liver transplantation. AJR 2000;176:193 -200[Abstract/Free Full Text]
7. DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916;17:863 -871
8. Van Thiel DH, Hagler NG, Schade RR, et al. In vivo hepatic volume determination using sonography and computed tomography. Gastroenterology 1985;88:1812 -1817[Medline]
9. DeLand FH, North WA. Relationship between liver size and body size. Radiology 1968;91:1195 -1198[Medline]
10. Urata K, Kawasaki S, Matsunami H, et al. Calculation of child and adult standard liver volume for liver transplantation. Hepatology 1995;21:1317 -1321[Medline]
11. Lin X, Sun Y, Liu Y, et al. Liver volume in patients with and without chronic liver disease. Hepatogastroenterology 1998;45:1069 -1074[Medline]
12. Lo CM, Fan ST, Liu CL, et al. Adult-to-adult living donor liver transplantation using extended right lobe grafts. Ann Surg 1997;226:261 -270[Medline]
13. Redvanly RD, Nelson RC, Stieber AC, Dodd GD III. Imaging in the preoperative evaluation of adult transplant candidates: goals, merits of various procedures, and recommendations. AJR 1995; 164:611 -617[Abstract/Free Full Text]
14. Henderson JM, Heymsfield SB, Horowitz J, Kutner MH. Measurement of liver and spleen volume by computed tomography. Radiology 1981;141:525 -527[Abstract/Free Full Text]
15. Kawasaki S, Makuuchi M, Matsunami H, et al. Preoperative measurement of segmental liver volume of donors for living related liver transplantation. Hepatology 1993;18:1115 -1120[Medline]
16. Stapakis J, Stamm E, Townsend R, Thickman D. Liver volume assessment by conventional vs. helical CT. Abdom Imaging 1995;20:209 -210[Medline]
17. Tanaka G, Kawamura H. Reference Japanese man. I. Mass of organs and the other characteristics of normal Japanese. Health Physics 1979;36:333 -346[Medline]

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Zappa, F. Dondero, A. Sibert, M.-P. Vullierme, J. Belghiti, and V. Vilgrain Liver Regeneration at Day 7 after Right Hepatectomy: Global and Segmental Volumetric Analysis by Using CT Radiology, August 1, 2009; 252(2): 426 - 432. [Abstract] [Full Text] [PDF]

				M. Zappa, F. Dondero, A. Sibert, M.-P. Vullierme, J. Belghiti, and V. Vilgrain Liver Regeneration at Day 7 after Right Hepatectomy: Global and Segmental Volumetric Analysis by Using CT Radiology, June 22, 2009; (2009) 2523080922. [Abstract] [Full Text]

				Y. Nakayama, Q. Li, S. Katsuragawa, R. Ikeda, Y. Hiai, K. Awai, S. Kusunoki, Y. Yamashita, H. Okajima, Y. Inomata, et al. Automated Hepatic Volumetry for Living Related Liver Transplantation At Multisection CT Radiology, September 1, 2006; 240(3): 743 - 748. [Abstract] [Full Text] [PDF]

				A.-J. Lemke, M. J. Brinkmann, T. Schott, S. M. Niehues, U. Settmacher, P. Neuhaus, and R. Felix Living Donor Right Liver Lobes: Preoperative CT Volumetric Measurement for Calculation of Intraoperative Weight and Volume Radiology, September 1, 2006; 240(3): 736 - 742. [Abstract] [Full Text] [PDF]

				T. Schroeder, A. Radtke, H. Kuehl, J. F. Debatin, M. Malago, and S. G. Ruehm Evaluation of Living Liver Donors with an All-inclusive 3D Multi-Detector Row CT Protocol Radiology, March 1, 2006; 238(3): 900 - 910. [Abstract] [Full Text] [PDF]

				A. Alonso-Torres, J. Fernandez-Cuadrado, I. Pinilla, M. Parron, E. de Vicente, and M. Lopez-Santamaria Multidetector CT in the Evaluation of Potential Living Donors for Liver Transplantation RadioGraphics, July 1, 2005; 25(4): 1017 - 1030. [Abstract] [Full Text] [PDF]

				Y. Onodera, T. Omatsu, J. Nakayama, T. Kamiyama, H. Furukawa, S. Todo, T. Nishioka, and K. Miyasaka Peripheral Anatomic Evaluation Using 3D CT Hepatic Venography in Donors: Significance of Peripheral Venous Visualization in Living-Donor Liver Transplantation Am. J. Roentgenol., October 1, 2004; 183(4): 1065 - 1070. [Abstract] [Full Text] [PDF]

				A. Napoli, C. Catalano, G. Silecchia, P. Fabiano, F. Fraioli, F. Pediconi, F. Venditti, N. Basso, and R. Passariello Laparoscopic Splenectomy: Multi-Detector Row CT for Preoperative Evaluation Radiology, August 1, 2004; 232(2): 361 - 367. [Abstract] [Full Text] [PDF]

				N. Erbay, V. Raptopoulos, E. A. Pomfret, I. R. Kamel, and J. B. Kruskal Living Donor Liver Transplantation in Adults: Vascular Variants Important in Surgical Planning for Donors and Recipients Am. J. Roentgenol., July 1, 2003; 181(1): 109 - 114. [Abstract] [Full Text] [PDF]

				T. Schroeder, S. Nadalin, J. Stattaus, J. F. Debatin, M. Malago, and S. G. Ruehm Potential Living Liver Donors: Evaluation with an All-in-One Protocol with Multi-Detector Row CT Radiology, August 1, 2002; 224(2): 586 - 591. [Abstract] [Full Text] [PDF]

				S. N. Goldberg, I. R. Kamel, J. B. Kruskal, K. Reynolds, W. L. Monsky, K. E. Stuart, M. Ahmed, and V. Raptopoulos Radiofrequency Ablation of Hepatic Tumors: Increased Tumor Destruction with Adjuvant Liposomal Doxorubicin Therapy Am. J. Roentgenol., July 1, 2002; 179(1): 93 - 101. [Abstract] [Full Text] [PDF]

				I. R. Kamel, J. B. Kruskal, M. T. Keogan, S. N. Goldberg, G. Warmbrand, and V. Raptopoulos Multidetector CT of Potential Right-Lobe Liver Donors Am. J. Roentgenol., September 1, 2001; 177(3): 645 - 651. [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kamel, I. R. Articles by Raptopoulos, V. Search for Related Content PubMed PubMed Citation Articles by Kamel, I. R. Articles by Raptopoulos, V. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?