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The carcinoembryonic antigen assay: Prognostic value in neural crest tumors
Vohtme 88 Number 4, part 1
Brief clinical and laboratory observations
Fig. 2. Pedigree of the family. their severe mental deficiency, only one of these brothers is institutionalized. Their extremely affable, extroverted personalities have contributed to a very adequate social adjustment. The pedigree is most consistent with an X-linked recessive pattern of inheritance. An older paternal age effect has been demonstrated in maternal grandfathers of fresh mutational cases of certain X-linked recessive disorders. 2 The maternal grandfather of these three patients
The carcinoembryonic antigen assay: Prognostic value in neural crest tumors David B. Frens, M.D.,* Patrick F. Bray, M.D., James T. Wu, Ph.D., and M. Eugene Lahey, M.D., Salt Lake City, Utah
NEURAL CREST TUMORS are common childhood neoplasms whose prognosis depends largely on the age of the child, the clinical stage of the disease, and the From the Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Utah College of Medicine and the Primary Children's Medical Center. Supported in part under National Institutes of Health Training Grants Nos. 5TO1-NS 5503 and 5TO1-NS 5309; National Institutes of Health Special Fellowship No. 5Fll-NS 2579 (Dr. Frens); Utah State Health Contract No. 73-1230; Helms Foundation Inc.; Clinical Cancer Training Grant, National Cancer Institute; contributions from the Eleanor Roosevelt Cancer Research Foundation and Hoffmann-LaRoche, Inc. Presented in part to The Society for Pediatric Research, Denver, April, 1975. *Reprint address: Department of Pediatrics, 50 N. Medical Dr., Salt Lake City, Utah 84132
591
was 41-years-old at the time of their mother's birth. The mother, who shares several features of the syndrome with her affected sons, could represent partial expression of an X-linked disorder. However, autosomal recessive inheritance cannot be excluded. Analysis of the XgA blood group, perfQrmed on all patients and their first degree relatives, was not informative. The authors thank Carol Cerrudo for her secretarial assistance.
REFERENCES I. SmithDW, and Gong BT: Scalp hair patterning as a clue to early fetal brain development, 3 PEmATR83:374, 1973. 2. JonesKL, Smith DW, Harvey MAS, Hall BD, and Quan L: Older paternal age and fresh gene mutation; data on additional disorders, J PEDIATR86:84, 1975.
histologic differentiation of the tumor at the time of diagnosis? 3 Unfortunately, the behavior of these tumors is sufficiently variable so that this information, as well as the initial level of urinary catecholamine excretion, is not always completely reliable in predicting outcomer For three years we have measured plasma carcinoembryonic antigen levels in children with neural crest tumors in order to determine the usefulness of this assay in aiding early diagnosis, making accurate prognosis, and assessing tumor activity during treatment. Our results indicate that, although elevated in many cases, the CEA assay contributes very little adjunctive information critical to the early diagnosis of a neural crest tumor. However, a CEA level obtained at the time of diagnosis does appear to be related to outcome, and CEA levels obtained during follow-up accurately reflect tumor activity. Abbreviations used CEA: carcinoembryonic antigen VMA: vanillylmandelic acid
M A T E R I A L S AND M E T H O D S Fourteen children with histologically confirmed neuroblastoma or ganglioneuroblastoma were included in this study (Table I). Their ages ranged from several days to 1 l years, at the time of diagnosis, and their disease was staged according to the criteria of Evans and associates? Treatment included total or partial surgical excision in every case, followed by radiation and chemotherapy in those cases requiring further therapy. Absence of active tumor was suggested by the failure to demonstrate bone
592
Brief clinical and laboratory observations
The Journal of Pediatrics April 1976
Table I. Clinical d a t a o n 14 c h i l d r e n with n e u r a l crest t u m o r s
CEA (nglml)
Patient No.
Age at Dx (mo)
1
9
I
2
19
III
3
42
I
4
37
II
5
130
IV
6
6
II
7
132
I
8
1 day
IVS
9
18
II
10
8
IV
11
5
II
12
30
IV
13
39
III
14
6
IVS
Histology and tumor site~f
Catecholamine excretion at Dx~.
N
E
Abdomen N Abdomen GN Abdomen GN Cervical N Abdomen N Thorax
N
N
E
Thorax N Thorax N Presacral N Abdomen N Abdomen N Abdomen N Abdomen N Thorax
Surgeryw
Therapy radiation
Yes (T) Yes (T) Yes (T) Yes (P) Yes (P) Yes (T) Yes (T) Yes (P) Yes (T) Yes (P) Yes (T) Yes (P) Yes (P) Yes (P)
E E
E E
E E E E E N
Outcomell
No
No
0.6
Yes
No
1.2
No
No
1.6
Yes
Yes
2.2
1.3
Yes
Yes
2.9
0.6
Yes
Yes
3.4
1.5
No
No
3.4
Yes
Yes
3.0
1.9
Yes
No
4.0
1.8
Yes
Yes
4.0
2.7
Yes
No
5.0
1.6
Yes
Yes
7.0
4.8
Yes
Yes
--
6.3
Yes
Yes
--
0.3
NED 18 mo NED 31 mo NED 19 mo NED 33 mo NED 22 mo NED 40 mo NED 23 mo NED 22 mo NED 31 mo Died 4 mo NED 18 mo Died 16 mo Died 20 mo NED 22 mo
0.8
*Tumor stage: I, tumor confined to the organ or structure of origin; II, tumor extending in continuity beyond the organ or structure of origin but not crossing the midline; III, tumor extending in continuity beyond the midline; IV, remote neoplastic disease; IVS, patients who would otherwise be stage I or II but who have remote disease confined to liver, skin, or bone marrow. F' tN = Neuroblastoma; GN = ganglioneuroblastoma. :~E = Elevated; N = normal. w = Total excision; P = partial excision. []NED = no evident disease.
m a r r o w or u r i n a r y c a t e c h o l a m i n e a b n o r m a l i t i e s clinically or radiologically. P l a s m a C E A levels were m e a s u r e d
at t h e t i m e o f
diagnosis in 12 p a t i e n t s a n d s e q u e n t i a l l y d u r i n g
the
follow-up p e r i o d in 11 patients. T h e C E A levels w e r e d e t e r m i n e d b y t h e z i r c o n i u m p h o s p h a t e gel r a d i o i m m u -
U r i n a r y c a t e c h o l a m i n e e x c r e t i o n w a s also d e t e r m i n e d at the time o f diagnosis a n d s e q u e n t i a l l y d u r i n g t h e follow-up
period.
Several
different
methods
were
e m p l o y e d in m a k i n g t h e s e m e a s u r e m e n t s . I n n i n e o f t h e cases t h e c a t e c h o l a m i n e e x c r e t i o n was d e t e r m i n e d b y t w o dimensional, thin-layer
chromatography
with
results
n o a s s a y m e t h o d ? All d e t e r m i n a t i o n s w e r e c a r r i e d o u t in
expressed as m i l l i g r a m s V M A p e r g r a m o f c r e a t i n i n e o r
triplicate. C o n t r o l d a t a were t a k e n f r o m t h e c o o p e r a t i v e
milligrams V M A p e r 24 h o u r u r i n e ? A v a l u e w a s c o n s i d -
study c o n d u c t e d b y H o f f m a n n - L a R o c h e , Inc., in w h i c h
ered elevated if it e x c e e d e d a g e - d e p e n d e n t n o r m a l v a l u e s
our l a b o r a t o r y p a r t i c i p a t e d . ~ This s t u d y s h o w e d t h a t 97%
o f Gitlow a n d associates? I n five o f t h e cases G i t l o w ' s
o f healthy, n o n s m o k i n g i n d i v i d u a l s o f all ages h a d p l a s m a
p a r a - n i t r o a n i l i n e s c r e e n i n g test was u s e d to d e t e r m i n e
C E A levels b e t w e e n 0 a n d 2.5 n g / m l . C o n s e q u e n t l y , a
c a t e c h o l a m i n e excretion. T h e later results are e x p r e s s e d as e l e v a t e d or n o r m a l ; a n e l e v a t e d result c o r r e s p o n d s to a u r i n a r y V M A level o f at least 20 m g / g m o f creatinine. TM
C E A level w h i c h e x c e e d e d 2.5 n g / m l in t h e s e c h i l d r e n was c o n s i d e r e d elevated.
Volume 88 Number 4, part 1 RESULTS
A CEA level was measured at the time of diagnosis in 12 of the 14 children. Eight children had an initial CEA value above 2.5 n g / m l ; the four others had a level clearly within the normal range. A n accompanying catecholamine excretion level was available for each child. This was elevated in 11 and not evaluated in one who had a negative VMA screening test. One or more CEA and urinary catecholamine excretion levels were available for 11 of 14 children during the follow-up period. At the most recent determination, eight had a normal CEA value. In five of these children, sequential CEA values had declined from an initially elevated level into the normal range. All seven children had normal catecholamine excretion, and all were without evidence of active tumor at a minimal follow-up time of 24 months. Three children had CEA values which r e m a i n e d elevated on follow-up. All of these had an associated increase in catecholamine excretion, and all died. DISCUSSION The plasma CEA assay had been evaluated extensively in a collaborative study, and results show that the highest percentage of elevated titers and the highest titer values are to be found in patients with colorectal, pulmonary, and pancreatic carcinoma. Less strikingly elevated titers are also seen in noncarcinomatous malignant disease such as lymphomas and in clinically active n o n m a l i g n a n t diseases such as inflammatory conditions of the respiratory and gastrointestinal t r a c t - a reflection of the test's nonspecific nature. Most workers have concluded that the assay has its greatest usefulness in monitoring response of malignant disease to therapy, that it should be used as an adjunctive diagnostic test, and that it has no real place as a screening device. 7, lo Early in this study we inspected our data to evaluate the role of CEA in diagnosis. Eight of the 12 patients studied before treatment showed elevated values (greater than 2.5 ng/ml), but each of these children also had clinical, radiographic, bone marrow or catecholamine excretion evidence of a neural crest tumor. Even though such data are of biologic interest to some from the standpoint of marker tumor proteins, our experience suggests that the test is less sensitive than conventional diagnostic methods. As data in this small series accumulated, one could see a relationship between the CEA titers, both initial and sequential, and the patient's outcome. All eight children with an initial CEA level below 4.0 n g / m l had long-term survival without evidence of tumor recurrence, in spite of their varying age and clinical stage at the time of
Brief clinical and laboratory observations
593
diagnosis. Within the clinical course of the four patients whose initial CEA values were 4.0 n g / m l or higher, the sequential values remained slightly elevated in the two who died and became normal in the ones who appeared cured (See Table I). A third death occurred in a patient (No. 13 in Table I) who was treated before a CEA level could be obtained and whose follow-up determinations ranged above 4.0 ng/ml. SUMMARY
Plasma carcinoembryonic antigen levels were measured before and after treatment in 14 children with histologically proved neural crest tumors. All eight children with a pretreatment CEA value below 4.0 n g / m l had long-term survival without evidence of tumor recurrence. Six patients had values of 4.0 n g / m l or above--the three who appear cured showed follow-up values in the normal range and the three who died had persistently elevated levels. We conclude from these data that: (1) slight but definite elevations in plasma CEA can be expected in most infants and children with neural crest tumors an interesting biologic note; (2) the test adds little to currently available methods of early diagnosis; and (3) the assay may have value in monitoring response to therapy; our data suggest that values below 4.0 n g / m l are associated with a good outcome whereas values above this level call for a guarded prognosis. REFERENCES
1. Williams TE, and Donaldson MH: Neuroblastoma, in Sutow W-W, Vietti TJ, and Ferback D J, editors: Clinical pediatric oncology, St. Louis, 1973, The CV Mosby Company, pp 384-410. 2. Kinnier-Wilson LM, and Draper GJ: Neuroblastoma, its natural history and prognosis: A study of 487 cases, Br Med J 3:301, 1974. 3. Hughes H, Marsden HB, and Palmer MK: Histologic pattern of neuroblastoma related to prognosis and clinical staging, Cancer 34:1706, 1975. 4. Gitlow SE, Dziedzic LB, Strauss L, Greenwood SM, and Dziedzic SW: Biochemical and histologic determinants in the prognosis of neuroblastoma, Cancer 32:898, 1973. 5. Evans EA, D'Angio JD, and Randolph J: A proposed staging for children with neuroblastoma, Cancer 27:374, 1971. 6. Thomson DMP, Krupey J, Freedman SO, and Gold P: The radioimmunoassay of circulating carcinoembryonic antigen of the human digestive tract, Proc Natl Acad Sci, USA, 64:161, 1969. 7. Hansen HJ, Snyder JJ, Miller E, Vandevoorde JP, Miller ON, Hines LR, and Burns JJ: Carcinoembryonic Antigen (CEA) assay, Hum Path 5:139, 1974. 8. Armstrong MD, McMillan A, and Shaw KNF: 3-Methocoxy-4-hydroxy-mandelic acid, a urinary metabolite of norepinephrin, Biochem Biophys Acta 25:422, 1957.
594
Brief clinical and laboratory observations
9. Gitlow SE, Bertani IM, Rausen A, Gribetz D, and Dziedzic SW: Diagnosis of neuroblastoma by qualitative and quantitative determination of catecholamine metabolites in urine, Cancer 25:1377, 1970.
The Journal of Pediatrics April 1976
10. Sorokin JJ, Sugarbaker PH, Zamcheck N, Pisick M, Kupchick HZ, and Moore FD: Serial carcinoembryonic antigen assays, JAMA 228:49, 1974.
Intrathoracic gastrogenic cysts and hemoptysis Sheng H. Chang, M.D., Ph.D., Lemuel Morrison, M.D., Louis Shaffner, M.D., and James E. Crowe, M.D., Winston-Salem, N. C. INTRATHORACIC GASTROGENIC CYSTS are rare congenital foregut m a l f o r m a t i o n s that usually p r o d u c e respiratory symptoms in early i n f a n c y ? It is n o t c o m m o n l y recognized that they m a y cause hemoptysis, which can be fatal, s, :' Early diagnosis o f potentially lethal gastrogenic cysts is especially i m p o r t a n t , since they are surgically correctable lesions.
Fig. 1A. Chest shows mass posteromedially in the upper portion of the left side of the thorax. This appearance remained the same over a one-month period.
CASE REPORT The patient, a 6-week-old female, was initially seen at a nearby hospital with a history of hemoptysis since 3 weeks of age. Physical examination was normal. Laboratory values on admission were: hemoglobin, 10.5 gm/dl; hematocrit, 30%; white blood cell count, 13,100/mm ~. Chest roentgenograms showed a round, homogenous shadow of water density with indistinct margins, located posteromedially in the left side of the thorax (Fig. 1A). An upper gastrointestinal series showed a normal esophagus and stomach. Several episodes of hemoptysis occurred following prolonged crying during this hospitalization. No consistent relationship between feedings and hemoptysis was noted. No change in the frequency of hemoptysis or the appearance of the chest on roentgenograms followed treatment with antibiotics and antitussives. The infant was transferred to North Carolina Baptist Hospital at 8 weeks of age. Physical examination was normal except for coarse rgfles and ronchi over the left side of the chest. The hemoglobin had dropped to 9.0 gm/dl; the hematocrit, to 25%. Stool examination was strongly positive for occult blood. Roentgenograms of the cervical and thoracic spine showed no abnormality. A chest roentgenogram showed no change from the earlier examinations. The initial impression was that the
From the Departments of Pathology, Pediatrics, Surgery and Radiology, Bowman Gray School of Medicine and North Carolina Baptist Hospital.
Fig. lB. Pulmonary angiogram reveals stretched, displaced pulmonary arteries, none of which supply the mass. abnormal shadow represented pneumonia involving the superior segment of the left lower lobe, or an interlobar effusion. Examination of the nasopharynx, direct laryngoscopy, and bronchoscopy showed no abnormalities. The infant was treated
Brief clinical and laboratory observations
Fig. 2. Pedigree of the family. their severe mental deficiency, only one of these brothers is institutionalized. Their extremely affable, extroverted personalities have contributed to a very adequate social adjustment. The pedigree is most consistent with an X-linked recessive pattern of inheritance. An older paternal age effect has been demonstrated in maternal grandfathers of fresh mutational cases of certain X-linked recessive disorders. 2 The maternal grandfather of these three patients
The carcinoembryonic antigen assay: Prognostic value in neural crest tumors David B. Frens, M.D.,* Patrick F. Bray, M.D., James T. Wu, Ph.D., and M. Eugene Lahey, M.D., Salt Lake City, Utah
NEURAL CREST TUMORS are common childhood neoplasms whose prognosis depends largely on the age of the child, the clinical stage of the disease, and the From the Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Utah College of Medicine and the Primary Children's Medical Center. Supported in part under National Institutes of Health Training Grants Nos. 5TO1-NS 5503 and 5TO1-NS 5309; National Institutes of Health Special Fellowship No. 5Fll-NS 2579 (Dr. Frens); Utah State Health Contract No. 73-1230; Helms Foundation Inc.; Clinical Cancer Training Grant, National Cancer Institute; contributions from the Eleanor Roosevelt Cancer Research Foundation and Hoffmann-LaRoche, Inc. Presented in part to The Society for Pediatric Research, Denver, April, 1975. *Reprint address: Department of Pediatrics, 50 N. Medical Dr., Salt Lake City, Utah 84132
591
was 41-years-old at the time of their mother's birth. The mother, who shares several features of the syndrome with her affected sons, could represent partial expression of an X-linked disorder. However, autosomal recessive inheritance cannot be excluded. Analysis of the XgA blood group, perfQrmed on all patients and their first degree relatives, was not informative. The authors thank Carol Cerrudo for her secretarial assistance.
REFERENCES I. SmithDW, and Gong BT: Scalp hair patterning as a clue to early fetal brain development, 3 PEmATR83:374, 1973. 2. JonesKL, Smith DW, Harvey MAS, Hall BD, and Quan L: Older paternal age and fresh gene mutation; data on additional disorders, J PEDIATR86:84, 1975.
histologic differentiation of the tumor at the time of diagnosis? 3 Unfortunately, the behavior of these tumors is sufficiently variable so that this information, as well as the initial level of urinary catecholamine excretion, is not always completely reliable in predicting outcomer For three years we have measured plasma carcinoembryonic antigen levels in children with neural crest tumors in order to determine the usefulness of this assay in aiding early diagnosis, making accurate prognosis, and assessing tumor activity during treatment. Our results indicate that, although elevated in many cases, the CEA assay contributes very little adjunctive information critical to the early diagnosis of a neural crest tumor. However, a CEA level obtained at the time of diagnosis does appear to be related to outcome, and CEA levels obtained during follow-up accurately reflect tumor activity. Abbreviations used CEA: carcinoembryonic antigen VMA: vanillylmandelic acid
M A T E R I A L S AND M E T H O D S Fourteen children with histologically confirmed neuroblastoma or ganglioneuroblastoma were included in this study (Table I). Their ages ranged from several days to 1 l years, at the time of diagnosis, and their disease was staged according to the criteria of Evans and associates? Treatment included total or partial surgical excision in every case, followed by radiation and chemotherapy in those cases requiring further therapy. Absence of active tumor was suggested by the failure to demonstrate bone
592
Brief clinical and laboratory observations
The Journal of Pediatrics April 1976
Table I. Clinical d a t a o n 14 c h i l d r e n with n e u r a l crest t u m o r s
CEA (nglml)
Patient No.
Age at Dx (mo)
1
9
I
2
19
III
3
42
I
4
37
II
5
130
IV
6
6
II
7
132
I
8
1 day
IVS
9
18
II
10
8
IV
11
5
II
12
30
IV
13
39
III
14
6
IVS
Histology and tumor site~f
Catecholamine excretion at Dx~.
N
E
Abdomen N Abdomen GN Abdomen GN Cervical N Abdomen N Thorax
N
N
E
Thorax N Thorax N Presacral N Abdomen N Abdomen N Abdomen N Abdomen N Thorax
Surgeryw
Therapy radiation
Yes (T) Yes (T) Yes (T) Yes (P) Yes (P) Yes (T) Yes (T) Yes (P) Yes (T) Yes (P) Yes (T) Yes (P) Yes (P) Yes (P)
E E
E E
E E E E E N
Outcomell
No
No
0.6
Yes
No
1.2
No
No
1.6
Yes
Yes
2.2
1.3
Yes
Yes
2.9
0.6
Yes
Yes
3.4
1.5
No
No
3.4
Yes
Yes
3.0
1.9
Yes
No
4.0
1.8
Yes
Yes
4.0
2.7
Yes
No
5.0
1.6
Yes
Yes
7.0
4.8
Yes
Yes
--
6.3
Yes
Yes
--
0.3
NED 18 mo NED 31 mo NED 19 mo NED 33 mo NED 22 mo NED 40 mo NED 23 mo NED 22 mo NED 31 mo Died 4 mo NED 18 mo Died 16 mo Died 20 mo NED 22 mo
0.8
*Tumor stage: I, tumor confined to the organ or structure of origin; II, tumor extending in continuity beyond the organ or structure of origin but not crossing the midline; III, tumor extending in continuity beyond the midline; IV, remote neoplastic disease; IVS, patients who would otherwise be stage I or II but who have remote disease confined to liver, skin, or bone marrow. F' tN = Neuroblastoma; GN = ganglioneuroblastoma. :~E = Elevated; N = normal. w = Total excision; P = partial excision. []NED = no evident disease.
m a r r o w or u r i n a r y c a t e c h o l a m i n e a b n o r m a l i t i e s clinically or radiologically. P l a s m a C E A levels were m e a s u r e d
at t h e t i m e o f
diagnosis in 12 p a t i e n t s a n d s e q u e n t i a l l y d u r i n g
the
follow-up p e r i o d in 11 patients. T h e C E A levels w e r e d e t e r m i n e d b y t h e z i r c o n i u m p h o s p h a t e gel r a d i o i m m u -
U r i n a r y c a t e c h o l a m i n e e x c r e t i o n w a s also d e t e r m i n e d at the time o f diagnosis a n d s e q u e n t i a l l y d u r i n g t h e follow-up
period.
Several
different
methods
were
e m p l o y e d in m a k i n g t h e s e m e a s u r e m e n t s . I n n i n e o f t h e cases t h e c a t e c h o l a m i n e e x c r e t i o n was d e t e r m i n e d b y t w o dimensional, thin-layer
chromatography
with
results
n o a s s a y m e t h o d ? All d e t e r m i n a t i o n s w e r e c a r r i e d o u t in
expressed as m i l l i g r a m s V M A p e r g r a m o f c r e a t i n i n e o r
triplicate. C o n t r o l d a t a were t a k e n f r o m t h e c o o p e r a t i v e
milligrams V M A p e r 24 h o u r u r i n e ? A v a l u e w a s c o n s i d -
study c o n d u c t e d b y H o f f m a n n - L a R o c h e , Inc., in w h i c h
ered elevated if it e x c e e d e d a g e - d e p e n d e n t n o r m a l v a l u e s
our l a b o r a t o r y p a r t i c i p a t e d . ~ This s t u d y s h o w e d t h a t 97%
o f Gitlow a n d associates? I n five o f t h e cases G i t l o w ' s
o f healthy, n o n s m o k i n g i n d i v i d u a l s o f all ages h a d p l a s m a
p a r a - n i t r o a n i l i n e s c r e e n i n g test was u s e d to d e t e r m i n e
C E A levels b e t w e e n 0 a n d 2.5 n g / m l . C o n s e q u e n t l y , a
c a t e c h o l a m i n e excretion. T h e later results are e x p r e s s e d as e l e v a t e d or n o r m a l ; a n e l e v a t e d result c o r r e s p o n d s to a u r i n a r y V M A level o f at least 20 m g / g m o f creatinine. TM
C E A level w h i c h e x c e e d e d 2.5 n g / m l in t h e s e c h i l d r e n was c o n s i d e r e d elevated.
Volume 88 Number 4, part 1 RESULTS
A CEA level was measured at the time of diagnosis in 12 of the 14 children. Eight children had an initial CEA value above 2.5 n g / m l ; the four others had a level clearly within the normal range. A n accompanying catecholamine excretion level was available for each child. This was elevated in 11 and not evaluated in one who had a negative VMA screening test. One or more CEA and urinary catecholamine excretion levels were available for 11 of 14 children during the follow-up period. At the most recent determination, eight had a normal CEA value. In five of these children, sequential CEA values had declined from an initially elevated level into the normal range. All seven children had normal catecholamine excretion, and all were without evidence of active tumor at a minimal follow-up time of 24 months. Three children had CEA values which r e m a i n e d elevated on follow-up. All of these had an associated increase in catecholamine excretion, and all died. DISCUSSION The plasma CEA assay had been evaluated extensively in a collaborative study, and results show that the highest percentage of elevated titers and the highest titer values are to be found in patients with colorectal, pulmonary, and pancreatic carcinoma. Less strikingly elevated titers are also seen in noncarcinomatous malignant disease such as lymphomas and in clinically active n o n m a l i g n a n t diseases such as inflammatory conditions of the respiratory and gastrointestinal t r a c t - a reflection of the test's nonspecific nature. Most workers have concluded that the assay has its greatest usefulness in monitoring response of malignant disease to therapy, that it should be used as an adjunctive diagnostic test, and that it has no real place as a screening device. 7, lo Early in this study we inspected our data to evaluate the role of CEA in diagnosis. Eight of the 12 patients studied before treatment showed elevated values (greater than 2.5 ng/ml), but each of these children also had clinical, radiographic, bone marrow or catecholamine excretion evidence of a neural crest tumor. Even though such data are of biologic interest to some from the standpoint of marker tumor proteins, our experience suggests that the test is less sensitive than conventional diagnostic methods. As data in this small series accumulated, one could see a relationship between the CEA titers, both initial and sequential, and the patient's outcome. All eight children with an initial CEA level below 4.0 n g / m l had long-term survival without evidence of tumor recurrence, in spite of their varying age and clinical stage at the time of
Brief clinical and laboratory observations
593
diagnosis. Within the clinical course of the four patients whose initial CEA values were 4.0 n g / m l or higher, the sequential values remained slightly elevated in the two who died and became normal in the ones who appeared cured (See Table I). A third death occurred in a patient (No. 13 in Table I) who was treated before a CEA level could be obtained and whose follow-up determinations ranged above 4.0 ng/ml. SUMMARY
Plasma carcinoembryonic antigen levels were measured before and after treatment in 14 children with histologically proved neural crest tumors. All eight children with a pretreatment CEA value below 4.0 n g / m l had long-term survival without evidence of tumor recurrence. Six patients had values of 4.0 n g / m l or above--the three who appear cured showed follow-up values in the normal range and the three who died had persistently elevated levels. We conclude from these data that: (1) slight but definite elevations in plasma CEA can be expected in most infants and children with neural crest tumors an interesting biologic note; (2) the test adds little to currently available methods of early diagnosis; and (3) the assay may have value in monitoring response to therapy; our data suggest that values below 4.0 n g / m l are associated with a good outcome whereas values above this level call for a guarded prognosis. REFERENCES
1. Williams TE, and Donaldson MH: Neuroblastoma, in Sutow W-W, Vietti TJ, and Ferback D J, editors: Clinical pediatric oncology, St. Louis, 1973, The CV Mosby Company, pp 384-410. 2. Kinnier-Wilson LM, and Draper GJ: Neuroblastoma, its natural history and prognosis: A study of 487 cases, Br Med J 3:301, 1974. 3. Hughes H, Marsden HB, and Palmer MK: Histologic pattern of neuroblastoma related to prognosis and clinical staging, Cancer 34:1706, 1975. 4. Gitlow SE, Dziedzic LB, Strauss L, Greenwood SM, and Dziedzic SW: Biochemical and histologic determinants in the prognosis of neuroblastoma, Cancer 32:898, 1973. 5. Evans EA, D'Angio JD, and Randolph J: A proposed staging for children with neuroblastoma, Cancer 27:374, 1971. 6. Thomson DMP, Krupey J, Freedman SO, and Gold P: The radioimmunoassay of circulating carcinoembryonic antigen of the human digestive tract, Proc Natl Acad Sci, USA, 64:161, 1969. 7. Hansen HJ, Snyder JJ, Miller E, Vandevoorde JP, Miller ON, Hines LR, and Burns JJ: Carcinoembryonic Antigen (CEA) assay, Hum Path 5:139, 1974. 8. Armstrong MD, McMillan A, and Shaw KNF: 3-Methocoxy-4-hydroxy-mandelic acid, a urinary metabolite of norepinephrin, Biochem Biophys Acta 25:422, 1957.
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Brief clinical and laboratory observations
9. Gitlow SE, Bertani IM, Rausen A, Gribetz D, and Dziedzic SW: Diagnosis of neuroblastoma by qualitative and quantitative determination of catecholamine metabolites in urine, Cancer 25:1377, 1970.
The Journal of Pediatrics April 1976
10. Sorokin JJ, Sugarbaker PH, Zamcheck N, Pisick M, Kupchick HZ, and Moore FD: Serial carcinoembryonic antigen assays, JAMA 228:49, 1974.
Intrathoracic gastrogenic cysts and hemoptysis Sheng H. Chang, M.D., Ph.D., Lemuel Morrison, M.D., Louis Shaffner, M.D., and James E. Crowe, M.D., Winston-Salem, N. C. INTRATHORACIC GASTROGENIC CYSTS are rare congenital foregut m a l f o r m a t i o n s that usually p r o d u c e respiratory symptoms in early i n f a n c y ? It is n o t c o m m o n l y recognized that they m a y cause hemoptysis, which can be fatal, s, :' Early diagnosis o f potentially lethal gastrogenic cysts is especially i m p o r t a n t , since they are surgically correctable lesions.
Fig. 1A. Chest shows mass posteromedially in the upper portion of the left side of the thorax. This appearance remained the same over a one-month period.
CASE REPORT The patient, a 6-week-old female, was initially seen at a nearby hospital with a history of hemoptysis since 3 weeks of age. Physical examination was normal. Laboratory values on admission were: hemoglobin, 10.5 gm/dl; hematocrit, 30%; white blood cell count, 13,100/mm ~. Chest roentgenograms showed a round, homogenous shadow of water density with indistinct margins, located posteromedially in the left side of the thorax (Fig. 1A). An upper gastrointestinal series showed a normal esophagus and stomach. Several episodes of hemoptysis occurred following prolonged crying during this hospitalization. No consistent relationship between feedings and hemoptysis was noted. No change in the frequency of hemoptysis or the appearance of the chest on roentgenograms followed treatment with antibiotics and antitussives. The infant was transferred to North Carolina Baptist Hospital at 8 weeks of age. Physical examination was normal except for coarse rgfles and ronchi over the left side of the chest. The hemoglobin had dropped to 9.0 gm/dl; the hematocrit, to 25%. Stool examination was strongly positive for occult blood. Roentgenograms of the cervical and thoracic spine showed no abnormality. A chest roentgenogram showed no change from the earlier examinations. The initial impression was that the
From the Departments of Pathology, Pediatrics, Surgery and Radiology, Bowman Gray School of Medicine and North Carolina Baptist Hospital.
Fig. lB. Pulmonary angiogram reveals stretched, displaced pulmonary arteries, none of which supply the mass. abnormal shadow represented pneumonia involving the superior segment of the left lower lobe, or an interlobar effusion. Examination of the nasopharynx, direct laryngoscopy, and bronchoscopy showed no abnormalities. The infant was treated