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Original Studies |
Department of Endocrinology (A.T., V.B.-B., B.C., P.R.), Department of Nuclear Medicine (N.V.), and Department of Radiology (F.L.), CHU de Bordeaux, Hopital Haut-Levêque, 33604 Pessac, France; Department of Endocrinology (P.C.), CHU de Bicêtre, 94275 Le Kremlin-Bicêtre, France; Department of Endocrinology (Y.B.), CHU de Grenoble, Hopital Nord, 38043 Grenoble Cedex 09, France; and Department of Internal Medicine and Endocrinology (V.R.), CHU d’Angers, 49033 Angers Cedex 01, France
Address all correspondence and requests for reprints to: Dr. A. Tabarin, Department of Endocrinology, CHU de Bordeaux, Hopital Haut-Levêque, Ave Magellan, 33604 Pessac, France. E-mail: antoine.tabarin{at}chu-aquitaine.fr
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Five patients had negative SRS and conventional imaging studies. The source of ACTH secretion remains occult despite 10–55 months of follow-up in four of these, whereas a 2-cm ileal carcinoid tumor, with liver micrometastases, was found at laparotomy in one patient, 14 months after presentation.
SRS was positive in 4 of 12 patients. It was false-positive in 1 patient with follicular thyroid adenoma. Nineteen months after presentation, SRS identified liver metastasis that was also visible using MRI in one patient, but the primary tumor remains occult. SRS identified a 10-mm pancreatic tumor that became detectable, using computed tomography (CT) scanning 9 months later, in 1 patient; and 2 mediastinal lymph nodes of 10 mm, previously ignored by MRI, in another patient, whereas no tumor was detectable within the parenchymal lung. SRS had little influence on therapeutic options in these 2 patients, in whom no final diagnosis could be made. Repetition of SRS during the follow-up of patients with previously negative scintiscans was useless.
Conventional imaging was positive in 6 of 12 patients. In the 2 patients with pancreatic tumor and isolated mediastinal lymph nodes, conventional imaging studies were interpreted as positive only after the results of SRS. One patient had liver metastasis that was also visible using SRS. Thin-section CT scanning visualized ACTH-secreting bronchial tumors and metastatic mediastinal lymph nodes of 10–15 mm in diameter in 3 patients after 14–72 months of follow-up, whereas SRS was negative.
There was no evident relationship between the endocrine status (hyper- or eucortisolism) and the results of SRS. The in vivo response of plasma cortisol to octreotide correlated to the results of SRS in 4 of 6 cases. In conclusion, both imaging procedures had a low diagnostic yield in this series. However, the sensitivity of SRS for the detection of bronchial carcinoids was lower than that of thin-section CT scanning. We therefore advocate the use of conventional imaging, including thin-section CT scanning of the chest, analyzed by experienced radiologists, as the first-line investigation in patients with occult EAS. SRS should not be repeated during the follow-up in patients with a previously negative scintigram.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Because neuroendocrine cells often express SRIF receptors (8, 9) and
because octreotide therapy has been shown to inhibit ACTH-secretion in
patients with the ectopic ACTH syndrome (EAS) (10), SRIF receptor
scintigraphy (SRS) has been proposed to localize ectopic ACTH-secreting
tumors. Indeed, several case reports have demonstrated that SRS can be
used to locate ACTH-secreting carcinoid tumors (11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26). However,
careful analysis of publications in English medical literature, and in
which adequate details are given, reveals that, in 18 of 20 cases with
positive SRS previously reported, the source of ACTH secretion was also
visible, using conventional imaging, or was not visualized because the
technique used was not appropriate for the detection of small
carcinoids (Table 1
). Conversely, and
despite the bias of publication rules that favors the report of
positive isolated clinical cases, patients in whom SRS was negative,
together with negative (11, 27, 28) or positive (11, 29) conventional
imaging, have also been described. Therefore, the usefulness of SRS for
the localization of truly occult ectopic ACTH-secreting tumors remains
unknown. We report herein our experience of SRS and compare it with
that of conventional imaging in 12 patients with EAS and in whom the
source of ACTH was occult at the time of presentation despite carefully
performed conventional imaging.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The 12 patients of this study (8 females and 4 males, 53 ±
19 yr old) were recruited in 4 French endocrine departments with strong
experience of Cushing’s syndrome. The diagnosis of ACTH-dependent
Cushing’s syndrome was based on standard criteria: clinical features,
increased 24-h urinary free cortisol excretion (UFC), and normal or
elevated plasma ACTH concentrations in the presence of
hypercortisolism. One patient had previously undergone unsuccessful
pituitary surgery, followed by radiotherapy, in another centre (patient
no. 7). This patient also underwent thymectomy, 19 months after
presentation, because of an enlarged thymus that proved to be only
hyperplastic. One had previously been cured of Cushing’s syndrome for
19 months, after removal of a 8-mm ACTH-secreting typical bronchial
carcinoid (patient no. 10). The results of endocrine investigations
performed in the 12 patients are given in Table 2. At the time of presentation, all
patients underwent pituitary magnetic resonance imaging (MRI),
associated with gadolinium injection using 0.5 or 1.5 Tesla
magnets and whole-body computed tomography (CT) scanning.
Scanning of the chest was carefully performed using high-resolution CT
with 3–5 mm contrast-enhanced contiguous sections. All patients
underwent whole-body CT scanning and/or MRI. In addition, spiral CT
scanning of the chest and pancreatic echoendoscopy were performed
initially in patients no. 1, 2, 9, and 10 and patients no. 1, 2, 3, 4,
and 9, respectively. Conventional imaging was negative in all patients
despite careful examination of the scans. Pituitary MRI was normal in
all but 1 patient (no. 5), who had a radiologically typical Rathke
cleft cyst.
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1.9 during BIPSS, combined with CRH injection, in six
patients (no. 1–5 and 7). BIPSS was performed, as previously
described, while patients were hypercortisolemic (30). The catheters
were properly positioned in the petrosal sinuses, as assessed by venous
angiography, excluding erroneous diagnosis of the source of ACTH caused
by dilution of the samples by nonpituitary blood. One patient (case no.
6) refused BIPSS, and the diagnosis of EAS was made based on the
patient’s advanced age (72 yr), devastating clinical features of
Cushing’s syndrome, spontaneous hypokalemia, no suppression of plasma
cortisol after the overnight high-dose dexamethasone test, and
unresponsiveness of plasma ACTH and cortisol after iv injection of 100
µg ovine CRH (Table 2
). After initial evaluation, an attempt to control hypercortisolism was performed using ketoconazole (n = 4), op’DDD alone or in association with metyrapone (n = 5), or bilateral adrenalectomy (n = 3). Thereafter, patients were followed and monitored with morphological reevaluation of the chest, abdomen, and pituitary at variable intervals. MRI of the pituitary gland remained normal during follow-up in all patients studied.
SRS
SRS was performed using [111-In] pentetreotide (Octreoscan 111 R, Mallinckrodt, Inc., Bondoufle, France). Labeling of pentetreotide with [111-In] was performed immediately before scintigraphy. After a standard bowel preparation, [111-In] pentetreotide was injected iv, when the patient was lying supine under a large field gamma camera DSX equipped with a medium-energy high-resolution collimator. A dose of 148 MBq (4 mCi) of [111-In] pentetreotide injected was in patients no. 1, 2, 4, 10, and one of 222 MBq (6 mCi) in the other patients. At 6 and 24 h after injection, a whole-body scan was performed at a speed of 8 cm/min, with posterior and anterior incidence. Axial tomography imaging [single-photon emission-computed tomography (SPECT)] was also performed in patients no. 3–9, 24 h after injection, with a single-head rotating camera with the following acquisition parameters: 60 projections, 64 x 64 matrix, and 45-sec acquisition time per projection. SPECT images were reconstructed with a filtered-back projection algorithm and Hann filter.
The first SRS was performed during initial investigations in 5 patients
or 11–88 months after presentation in 7 patients (Table 3). Conventional imaging was always
performed within a month of SRS. SRS was performed 19 times in the 12
patients of our series. It was performed once in 7 patients, twice in 4
patients, and 4 times in 1 patient. According to the results of 24
h urinary free cortisol and/or plasma cortisol measurements, SRS was
performed when patients demonstrated hypercortisolism or eucortisolism
in 10 and 9 cases, respectively.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Patient no. 5 showed abnormal intense uptake in the thyroid gland during her first SRS, performed 18 months after presentation. It corresponded to a 25-mm nodule in the right thyroid lobe. Plasma calcitonin was normal, and fine-needle aspiration of the nodule was consistent with benign follicular adenoma. Hypercortisolism was subsequently controlled using ketoconazole. Thirty-six months later, the scintigraphic pattern was similar, but the size of the nodule had increased to 40 mm. Total thyroidectomy was performed, and histopathological analysis revealed a benign follicular colloïd adenoma with negative ACTH immunostaining. A 24-h urinary free cortisol measurement, performed 4 days after thyroidectomy and 11 days after cessation of ketoconazole therapy, revealed recurrence of hypercortisolism.
SRS, performed 2 months after presentation, revealed two sites of
abnormal uptake in patient no. 6. One was located in the brain. MRI and
CT scanning were consistent with a meningioma of the left parietal
lobe. A faint abnormal uptake was found using SPECT in the area of the
pancreatic tail, whereas scintigraphic appearance of the abdomen was
normal using planar views (Fig. 1). MRI
of the pancreas, performed several days earlier, was interpreted as
normal. Reexamination of the MRI scans, guided by the results of
SRS, disclosed a questionable image in the same area. However, no tumor
was detected during echoendoscopy of the pancreas, and it was therefore
decided to perform a careful follow-up. CT scanning of the abdomen,
performed 9 months later, revealed an obvious 10-mm tumor of the
pancreatic tail (Fig. 1). It was decided to carry on surgical
exploration of the abdomen, but the patient died at home (of
bronchopneumonia) before surgery; and postmortem examination could not
be performed.
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). MRI scans of the chest, performed a
few days earlier, had been interpreted as normal. Reexamination of
these, after SRS, revealed 2 mediastinal lymph nodes, measuring about
10 mm; whereas no tumor was visible within the parenchymal lung.
Several months later, the patient presented neurological symptoms that
led to the discovery of a large cerebral glioblastoma (with negative
ACTH immunostaining). The patient underwent neurosurgery, followed by
antineoplastic chemotherapy. At the ultimate reevaluation in our
department, 111 months after presentation, there was no change in the
appearance of SRS, MRI, and CT scanning of the chest.
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SRS was normal in eight patients
In four patients (no. 1–4), the source of ACTH secretion remained occult despite repetition of conventional imaging, including thin-section CT scanning of the chest, during 10–55 months of follow-up. In these patients, SRS was performed either during initial work-up (no. 1, 2, and 3) and/or during follow-up (no. 3 and 4). Repetition of SRS in patient no. 4 proved to be of no help.
Similarly, SRS (including SPECT) and conventional imaging were negative, 11 months after presentation, in patient no. 9. Endoscopic adrenalectomy, performed 2 months later, allowed identification of several liver nodules (<10 mm in diameter). Histopathological analysis of liver biopsies was consistent with ACTH-secreting metastasis of a carcinoid tumor. A 20-mm ACTH-secreting typical carcinoid tumor of the ileon was removed, 1 month later, at laparotomy.
The source of ACTH secretion became detectable in 3 patients (no.
10–12), using CT scanning, whereas SRS (performed at the same time)
was normal. Typical ACTH-secreting bronchial carcinoid tumors, of 10
and 15 mm in diameter, were removed 41 and 72 months after presentation
in patients no. 11 and 12, respectively (Fig. 3). Patient no. 10 had recurrence of
Cushing’s syndrome, 19 months after being cured by removal of an 8-mm
bronchial tumor that proved to be a borderline typical/atypical
ACTH-secreting carcinoid. No lesion could be identified by conventional
imaging when Cushing’s syndrome recurred. Fourteen months after
recurrence, SRS was performed and proved to be normal, whereas
concurrent CT scanning revealed a 14-mm mediastinal lymph node (Fig. 4). At thoracotomy, 16 mediastinal lymph
nodes were removed. Five of these, including the node that had been
visualized using CT-scanning, proved to contain ACTH-secreting
metastasis of a carcinoid. The patient developed hypoadrenalism, caused
by ACTH deficiency, after excision of the nodes.
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SRS indicated ectopic sites of ACTH-secretion in one patient (no. 8). Whether or not the sites of abnormal uptake correspond to ectopic ACTH-secreting tissue in patients no. 6 and 7 remains unknown. At the time of SRS, patients no. 6 and 8 were hypercortisolemic, whereas patient no. 7 was eucortisolemic.
SRS, performed 15 times in the 9 remaining patients, was normal despite identification of ACTH-secreting tumors in 4 of these. SRS was performed while patients demonstrated hypercortisolism or eucortisolism, in 8 and 7 cases, respectively. In 3 cases (no. 3, 5, and 11), the first SRS was performed when patients demonstrated hypercortisolism and remained normal when performed later (while patients demonstrated eucortisolism).
Correlation between SRS and acute response to in vivo octreotide administration
The acute response of plasma cortisol, after sc injection of 200 µg octreotide, was studied in six patients (no. 1, 3, 5, 6, 8, and 12). SRS was normal in four patients (no. 1, 3, 5, and 12). Plasma cortisol concentration remained unchanged in three of these, whereas a 40% decrease from baseline level was noted 6 h after octreotide injection in patient no. 3. Large spontaneous fluctuations of plasma cortisol levels had been previously noted in this patient. Repetition of this test, several days later, induced only a transient 26% decrease in plasma cortisol levels 2 h after octreotide injection.
Plasma cortisol suppression reached only -29% from baseline level in patient no. 6 that showed uptake in the pancreatic tail. A 41% decrease of plasma cortisol was noted in patient no. 8, in whom SRS demonstrated two liver metastases. After 3 days of treatment with 600 µg octreotide sc, the 24-h UFC excretion in this patient dropped from 3741 to 575 µg/day (-85%).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The identification of type 2 SRIF receptors, using autoradiography, in
the majority of neuroendocrine tumors, including carcinoids (8), has
been the rationale for the development of SRS to localize
neuroendocrine tumors. This procedure has proved to be particularly
useful for the diagnosis and staging of gut carcinoids and gastrinomas
(34, 35). Because ACTH and cortisol secretion have also been shown to
decrease significantly after octreotide administration in some patients
with the EAS (10), SRS has also been proposed to localize the source of
ACTH secretion. Whereas normal scintigrams are observed in patients
with ACTH-secreting pituitary tumors (9, 11), SRS has demonstrated its
ability to localize ACTH-secreting carcinoid tumors, most of these
being located within the bronchial tree (Table 1). However, careful
analysis of the 20 cases of ACTH-secreting carcinoids reported with
sufficient details in English medical literature reveals that: 1) 12
were also evident using CT or MRI scanning (11, 12, 16, 18, 21, 22, 23, 24, 25); 2)
3 were not visualized initially because of the use of standard-cut CT,
and these tumors were visualized when high-resolution CT of the chest
was performed thereafter (17, 19, 20); and 3) SRS was useful only in
confirming a suspected lesion seen with conventional imaging in 3 cases
(13, 15, 26). Finally, SRS was of undeniable help and more sensitive
than conventional imaging in only 2 (10%) cases (14, 24). Conversely,
and despite the bias of publication rules that favors the report of
positive isolated clinical cases, patients in whom SRS was negative
together with negative (11, 27, 28) or positive (11, 29) conventional
imaging have also been described. Therefore, the sensitivity of SRS in
localizing occult ACTH-secreting tumors and its place in the diagnostic
strategy to be used in patients with EAS remains debatable. We
therefore reviewed retrospectively the data of our patients with
paraneoplastic Cushing’s syndrome seen during the last years and
selected all those with truly occult ectopic ACTH-secreting tumors at
the time of presentation and in whom SRS had been performed using the
most appropriate compound, [111-In]
pentetreotide (35).
The results of SRS in our series are disappointing because pathological uptake was noted in only four patients. Liver metastasis, identified using SPECT in one patient, were also visible using MRI, the latter depicting additional metastases that were not visualized with SRS, probably because of physiological accumulation of radioactivity in normal liver. SRS did not visualize the primary source of ACTH secretion. This illustrates, despite the use of [111-In] and SPECT, the difficulty of detecting small neuroendocrine tumors in the upper part of the abdomen, probably because of overprojection with the radioactivity accumulated in liver, spleen, and kidney (9, 35).
Abnormal uptake (that corresponded to a non-ACTH secreting follicular colloïd adenoma) and a meningioma were identified in two patients. Whether or not the uptake observed in the two remaining patients corresponds to the source of ACTH remains unknown. SRS may have identified a pancreatic source of ACTH secretion 9 months before it became detectable using conventional imaging in one patient, but pathological proof of the tumor is lacking. Although, pancreatic tumors, causing EAS, are radiologically obvious at presentation in most cases (36), cases that needed several months of follow-up to be visualized using CT-scanning have also been described (3, 37). Furthermore, SRS has been shown to identify small pancreatic gastrinomas, invisible using other imaging approaches, including echoendoscopy (34). Although we cannot exclude that surgery guided by the results of SRS could have been helpful for this patient at the time of negative conventional imaging, we were reluctant to proceed with laparotomy on the basis of positive scintigrams only. Similarly, SRS identified two hot spots in the mediastinum of one patient that corresponded to 10-mm lymph nodes that had been overlooked during the analysis of MRI scans performed earlier. However, no bronchial or lung tumor was noted, and these findings remained unchanged using MRI and CT scanning 23 months later. Metastatic nodes of bronchial carcinoids, in patients in whom parenchymal lung lesion cannot be found by imaging or even by thoracotomy, have been described (33). The hypothesis that the metastatic nodes could differ from the primary tumor during SRS is somehow surprising. Nevertheless, cases have been described in which the intensity of SRIF receptor expression (and hence, the results of SRS) differ between the primary tumor and its metastasis (11, 38). However, the alternative hypothesis of positive SRS, caused by a nonspecific inflammatory process in this patient, who underwent thymectomy previously, cannot be ruled out (9). In our opinion, three of the four cases of our series with positive scintigrams illustrate two main points concerning the use of SRS in patients with EAS. First, it should be kept in mind that SRS hot spots may be caused by non-ACTH secreting tumors or nonneoplastic associated pathological processes. Therefore, great care must be used in interpreting SRS. Second (and consequently), there is a need to combine the results of SRS with additional diagnostic techniques, such as conventional radiology and biopsy, to influence the therapeutic strategy.
SRS was negative in 8 of the 12 patients of our series. The source of ACTH secretion remains occult in 4 of these. Two bronchial carcinoids, a mediastinal lymph metastasis of a previously resected bronchial carcinoid, and a midgut carcinoid were identified in the 4 patients. The thoracic tumors were discovered using CT scanning after 14–72 months of follow-up, whereas SRS (without SPECT studies) was negative. Both imaging approaches were negative in the patient with the ileal carcinoid tumor.
Overall, SRS was positive in 4 of 12 patients. Conventional imaging was also positive in 1 of these (no. 8). SRS was false positive in 1 case (patient no. 5) and depicted abnormal uptake in 2 cases with no final diagnosis when conventional imaging was negative (patients no. 6 and 7). However, as mentioned before, SRS had little influence on therapeutic options in these 2 last patients. Conventional imaging was positive in 6 patients. SRS was also positive in 1 of these (no. 8). In 2 patients (no. 6 and 7), conventional imaging was considered as positive only after the results of SRS. Last, conventional imaging only visualized the responsible tumor in 3 patients (no. 10, 11, and 12). This allowed entire surgical resection of the ectopic ACTH-secreting carcinoid tumors. Therefore, and although both imaging procedures had a low diagnostic yield in this series, conventional imaging was clearly more helpful than SRS.
Several explanations can be drawn for the negativity of SRS. SPECT studies were not performed in 5 of the 12 patients studied. Indeed, SPECT imaging should be performed when searching small tumors potentially bearing SRIF receptor subtypes for octreotide. It is of invaluable aid when tumor tissue overlays areas of physiologic uptake, such as the spleen, liver, and kidneys (9, 35) but is less important in studying areas with spontaneous low background radioactivity, such as the lungs (35; also see Ref. 42). Therefore, we cannot exclude that SPECT imaging could have been helpful in 2 patients (no. 1 and 2), but it is unlikely that it would have been positive in patients no. 10, 11, and 12 with negative planar imaging but in whom CT scanning disclosed thoracic carcinoïds. A strong correlation between the presence of SRIF analog binding sites in vitro and positive in vivo SRS has been demonstrated (9, 35). It has also been shown that the positivity of SRS relies not on tumor size but on the density of SRIF receptor expressed (9, 35). Therefore, and although in vitro studies of SRIF receptor expression among tumors of our series was not performed, it is likely that a lack (or very low density) of SRIF receptor subtypes 2 and 5 is responsible for the negative SRS. For these reasons, and according to the results observed in patients in whom SRS was repeated, we believe that it is not useful to reevaluate patients with SRS during the follow-up when the first scintigrams are negative.
Our results of SRS, in occult ACTH-secreting carcinoid, contrast with the sensitivity of 0.55 reported in occult gastrinomas (34) and the results reported in gut carcinoid tumors (35). Although this discrepancy might be caused by the small number of patients in our series, one must note that in vitro studies of carcinoid of various origin revealed that the majority of SRIF receptor negative tumors were mainly bronchial carcinoid (8). Clinical, biochemical, histological, and cytological heterogeneity (in relation to the site of origin of the carcinoid) has been clearly demonstrated (39). That the prevalence or intensity of octreotide receptor expression is also linked to the site of origin of the tumor might be suggested. Alternatively, it has been observed once that a negative or low expression of SRIF receptors may be associated with a low differentiation grade (8). However, careful examination of the tumors removed in patients 9–12 of our series does not support this hypothesis (40). Inhibition of SRIF receptor expression by exposure to elevated cortisol levels has been suggested for ACTH-secreting pituitary adenomas that do not show up during SRS (41). Whether SRIF receptor expression might also be negatively influenced by hypercortisolism in some ectopic tumors remains debatable (42). In the literature, positive SRS has been observed both in patients with hypercortisolism and after bilateral adrenalectomy. The analysis of the relationship between the results of SRS and the endocrine status of the patients of our series does not support this hypothesis either. Indeed, in three patients, SRS was negative while they were hypercortisolemic, and it remained so later (when these patients were eucortisolemic).
Because SRS is expansive, and because a positive scan has been shown to be closely correlated to a lowering effect of octreotide treatment on circulating ACTH and cortisol levels (11), the cortisol response to an acute injection of octreotide could be useful to select patients for SRS. The acute octreotide test was performed in only six patients of our series, preventing any definitive conclusion on this point. However, the results of the test and SRS were discordant in two of six patients: one patient with a negative SRS exhibited a clear cortisol response to octreotide (-40%) once, whereas the response of a patient with a pancreatic uptake was ambiguous (-29%). Similar discrepancies have been previously described in the EAS (20, 26, 43). The absence of response to octreotide, in the presence of a positive SRS, suggests defects in intracellular postreceptor mechanisms or a lack of sensitivity of the acute test, as has been suggested in acromegalic patients (44). The comparison of the lowering effect of an acute injection of 200 µg octreotide on cortisol levels in one patient (-41%), with that of a 600-µg/day regimen for 3 days (-85%), support this last hypothesis. Alternatively, an apparent fall in cortisol levels must be interpreted cautiously, because ACTH-secreting tumors are known to have unpredictable spontaneous fluctuations.
In conclusion, this study illustrates the diagnostic difficulties encountered in patients with occult EAS, because both SRS and conventional imaging had a low diagnostic yield. However, the diagnostic and therapeutic help provided by conventional imaging was superior to that of SRS. Therefore, SRS should not be performed until the diagnosis of Cushing’s disease has been ruled out with usual diagnostic means, including dynamic endocrine testing, pituitary MRI, and (in selected cases) BIPSS. When EAS is suspected, we favor the use of conventional imaging, including thin-section and spiral CT scanning of the chest, analyzed by experienced radiologists, as the first-line investigation. In patients with a small ambiguous lesion, SRS can be performed secondarily, in order to confirm its neuroendocrine origin. SRS may also be performed when conventional imaging is negative, but our data suggest that it will be helpful in a minority of cases. Because repetition of SRS during the follow-up of patients with previously negative scintigrams proved to be useless, our results also favor the use of conventional imaging in the follow-up of patients with occult EAS. In such instances, whole-body conventional imaging at 6 months intervals, with particular attention to the chest, is recommended (1, 2, 3, 7, 25, 37).
Received October 20, 1998.
Revised December 23, 1998.
Accepted December 29, 1998.
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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