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Preoperative imaging of parathyroid glands
cases. Three discordant patients underwent surgery, and adenomas were present in two who had positive sestamibi but negative ultrasonography. The third patient, who had been positive on ultrasonography alone, was found to have hyperplasia only. These findings show both the sensitivity and specificity of Tc-99m sestamibi to be high and reinforces its important role in the detection of parathyroid adenomas. No patient with a negative Tc-99m sestamibi was found on follow-up to have a parathyroid adenoma. Therefore, we suggest that dual-phase Tc-99m sestamibi SPECT offers a reasonable alternative method to identify clinically relevant parathyroid adenomas, because it is accurate and has lower cost and radiation dose than the method Hindie and colleagues described. JRB has acted as a paid consultant to DuPont Pharma, manufacturers of sestamibi.
*E L Loney, J R Buscombe, A J W Hilson, A Davenport, I S Francis Departments of Radiology, Nuclear Medicine and Nephrology, Royal Free Hospital, London NW3 2QG, UK 1
Hindie E, Urena P, Jeanguillaume C, et al. Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism. Lancet 1999; 353: 2200–04. 2 Taillefer R, Boucher Y, Potvin C, Lambert R. Detection and localisation of parathyroidism adenomas in patients with hyperthyroidism using a single radionuclide imaging procedure with technetium-99m MIBI (dual phase study). J Nucl Med 1992; 33: 1801–07. 3 Francis IS, Loney EL, Buscombe JR, Thakrar DS, Berger L, Hilson AJW. 99mtechnetium-sestamibi dual-phase SPECT imaging: concordance with ultrasound. Nucl Med Commun 1999; 20: 487–88 (abstr).
Sir—Elif Hindie and colleagues1 describe an important development in the radionuclide imaging of parathyroid glands in patients with secondary hyperparathyroidism. By simultaneous administration of double isotopes and data acquisition, artifacts related to patient movement are kept to a minimum. However, the results of this study need to be interpreted with caution. They state that the “degree of subtraction was chosen interactively, with the real time display”, which means that knowing that four glands are (usually) expected, the images can be manipulated until four glands are shown. There is an implicit danger of under-reporting if more than four glands are present, and of overreporting if there are less than four.
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With only 11 patients in the study, they were perhaps lucky to avoid more of such difficult cases. Until an imaging technique is guaranteed not to miss any glands, its usefulness to the surgeon will be limited. Surgeons are obliged to look in all the common positions for glands, because no imaging technique can be wholly trusted. A subjective method of analysis, such as the one described, is likely to lead to extra glands being under-reported because they are so uncommon. In an attempt to overcome this difficulty, we have described a change detection technique,2 incorrectly described by Hindie and colleagues as a “subtraction technique”, that gives an objective report on the differences between the thyroid and sestamibi images by stating the level of the significance of difference between the thyroid and the sestamibi image. Our technique uses technetium99m for thyroid and parathyroid imaging. Use of the same isotope guarantees the same attenuation and scattering properties for both images. By using iodine-123 and Tc-99m, Hindie and colleagues are able to exploit the advantages of simultaneous data acquisition, but the differences in g-radiation prevent a rigorous comparison of the two images. Our results are similar to those of Hindie and co-workers even though we did not use simultaneous data acquisition from two isotopes. If Hindie and colleagues had predicted that each of their patients had four glands in the standard anatomical positions, they would have achieved greater sensitivity than they did with their imaging technique. Nevertheless, continuing refinement of radionuclide imaging and experience in reporting in patients with secondary hyperparathyroidism is gradually leading to increasing confidence in the localisation of parathyroid glands. A M S Chesser, M J Carroll, K E Britton, *L R I Baker *Renal Unit, Department of Nephrology, and Department of Nuclear Medicine, St Bartholomew’s Hospital, London E C 1 A7 B E ,U K 1
2
Hindie E, Urena P, Jeanguillaume C, et al. Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism. Lancet 1999; 353: 2200–04. Chesser AMS, Carroll MC, Lightowler C, Macdougall IC, Britton KE, Baker LRI. Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure. Nephrol Dial Transplant 1997; 12: 97–100.
Microchimerism in a human hand allograft Sir—P J Horton and colleagues (July 31, p 424)1 comment on long-term survival of the allogeneic arm transplant that was done almost 1 year ago in Lyon.2 They argue that the allograft was successful because the recipient became, at least for a short time, a haemopoietic chimera, because of the allogeneic bone marrow transplanted as part of the composite allograft. They correctly suggest that this issue could be solved by studying the origin of the infiltrating cells by PCR or immunohistochemistry. This issue was indeed settled with immunohistochemical studies. 3 Sequential skin biopsies from the allograft were obtained at various time points after the graft and studied immunohistochemically with a wide panel of differentiation antigens. The origin of cells (donor vs recipient) was studied with a mouse monoclonal antibody to the recipient’s HLA-A24 antigen. The dermal mononuclear cell infiltrate, present at days 57, 63, and 77 after the graft, was made predominantly of lymphocytes positive for CD3, CD4, and HLA-A24, which showed unequivocally that they originated from the recipient. Epidermal and adnexal keratinocytes were from the donor (HLA-A24 negative). The epidermis contained normal numbers of Langerhans’ cells, which were evaluated with three different markers (CD1a, Lag, and S100 protein). From day 77 after the graft, some rare dendritic cells expressing HLA-A24 from the recipient were seen in the epidermis; double-labelling experiments confirmed that these were Langerhans’ cells, as shown by the simultaneous expression of the CD1a antigen. At that time, no microchimerism was detected in the blood by DNA typing. Our findings show that the dermis was transiently infiltrated by mononuclear cells of recipient’s origin, whereas recipient’s bone-marrowderived antigen-presenting cells (ie, Langerhans’ cells) progressively replaced the donor’s cells in the epidermis. That microchimerism was not detected is not surprising, since the mass of bone-marrow engrafted with the composite allograft was far less important than the recipient’s own bone-marrow; therefore, the recipient’s blood-borne cells were more likely to be present in the allograft than were the donor’s cells. However, rapid replacement of Langerhans’ cells of the allograft by the recipient’s cells is interesting, and in the future more and
THE LANCET • Vol 354 • November 20, 1999
*E L Loney, J R Buscombe, A J W Hilson, A Davenport, I S Francis Departments of Radiology, Nuclear Medicine and Nephrology, Royal Free Hospital, London NW3 2QG, UK 1
Hindie E, Urena P, Jeanguillaume C, et al. Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism. Lancet 1999; 353: 2200–04. 2 Taillefer R, Boucher Y, Potvin C, Lambert R. Detection and localisation of parathyroidism adenomas in patients with hyperthyroidism using a single radionuclide imaging procedure with technetium-99m MIBI (dual phase study). J Nucl Med 1992; 33: 1801–07. 3 Francis IS, Loney EL, Buscombe JR, Thakrar DS, Berger L, Hilson AJW. 99mtechnetium-sestamibi dual-phase SPECT imaging: concordance with ultrasound. Nucl Med Commun 1999; 20: 487–88 (abstr).
Sir—Elif Hindie and colleagues1 describe an important development in the radionuclide imaging of parathyroid glands in patients with secondary hyperparathyroidism. By simultaneous administration of double isotopes and data acquisition, artifacts related to patient movement are kept to a minimum. However, the results of this study need to be interpreted with caution. They state that the “degree of subtraction was chosen interactively, with the real time display”, which means that knowing that four glands are (usually) expected, the images can be manipulated until four glands are shown. There is an implicit danger of under-reporting if more than four glands are present, and of overreporting if there are less than four.
1820
With only 11 patients in the study, they were perhaps lucky to avoid more of such difficult cases. Until an imaging technique is guaranteed not to miss any glands, its usefulness to the surgeon will be limited. Surgeons are obliged to look in all the common positions for glands, because no imaging technique can be wholly trusted. A subjective method of analysis, such as the one described, is likely to lead to extra glands being under-reported because they are so uncommon. In an attempt to overcome this difficulty, we have described a change detection technique,2 incorrectly described by Hindie and colleagues as a “subtraction technique”, that gives an objective report on the differences between the thyroid and sestamibi images by stating the level of the significance of difference between the thyroid and the sestamibi image. Our technique uses technetium99m for thyroid and parathyroid imaging. Use of the same isotope guarantees the same attenuation and scattering properties for both images. By using iodine-123 and Tc-99m, Hindie and colleagues are able to exploit the advantages of simultaneous data acquisition, but the differences in g-radiation prevent a rigorous comparison of the two images. Our results are similar to those of Hindie and co-workers even though we did not use simultaneous data acquisition from two isotopes. If Hindie and colleagues had predicted that each of their patients had four glands in the standard anatomical positions, they would have achieved greater sensitivity than they did with their imaging technique. Nevertheless, continuing refinement of radionuclide imaging and experience in reporting in patients with secondary hyperparathyroidism is gradually leading to increasing confidence in the localisation of parathyroid glands. A M S Chesser, M J Carroll, K E Britton, *L R I Baker *Renal Unit, Department of Nephrology, and Department of Nuclear Medicine, St Bartholomew’s Hospital, London E C 1 A7 B E ,U K 1
2
Hindie E, Urena P, Jeanguillaume C, et al. Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism. Lancet 1999; 353: 2200–04. Chesser AMS, Carroll MC, Lightowler C, Macdougall IC, Britton KE, Baker LRI. Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure. Nephrol Dial Transplant 1997; 12: 97–100.
Microchimerism in a human hand allograft Sir—P J Horton and colleagues (July 31, p 424)1 comment on long-term survival of the allogeneic arm transplant that was done almost 1 year ago in Lyon.2 They argue that the allograft was successful because the recipient became, at least for a short time, a haemopoietic chimera, because of the allogeneic bone marrow transplanted as part of the composite allograft. They correctly suggest that this issue could be solved by studying the origin of the infiltrating cells by PCR or immunohistochemistry. This issue was indeed settled with immunohistochemical studies. 3 Sequential skin biopsies from the allograft were obtained at various time points after the graft and studied immunohistochemically with a wide panel of differentiation antigens. The origin of cells (donor vs recipient) was studied with a mouse monoclonal antibody to the recipient’s HLA-A24 antigen. The dermal mononuclear cell infiltrate, present at days 57, 63, and 77 after the graft, was made predominantly of lymphocytes positive for CD3, CD4, and HLA-A24, which showed unequivocally that they originated from the recipient. Epidermal and adnexal keratinocytes were from the donor (HLA-A24 negative). The epidermis contained normal numbers of Langerhans’ cells, which were evaluated with three different markers (CD1a, Lag, and S100 protein). From day 77 after the graft, some rare dendritic cells expressing HLA-A24 from the recipient were seen in the epidermis; double-labelling experiments confirmed that these were Langerhans’ cells, as shown by the simultaneous expression of the CD1a antigen. At that time, no microchimerism was detected in the blood by DNA typing. Our findings show that the dermis was transiently infiltrated by mononuclear cells of recipient’s origin, whereas recipient’s bone-marrowderived antigen-presenting cells (ie, Langerhans’ cells) progressively replaced the donor’s cells in the epidermis. That microchimerism was not detected is not surprising, since the mass of bone-marrow engrafted with the composite allograft was far less important than the recipient’s own bone-marrow; therefore, the recipient’s blood-borne cells were more likely to be present in the allograft than were the donor’s cells. However, rapid replacement of Langerhans’ cells of the allograft by the recipient’s cells is interesting, and in the future more and
THE LANCET • Vol 354 • November 20, 1999