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The diagnosis of acoustic neuromas
The Diagnosis
of Acoustic
Neuromas
By GALDINO FL VALVASSORI, M.D. HE REFINEMENT OF SURGICAL TECHNIQUE for the removal of acoustic neuroma through the use of the otomicroscope and the discovery of new surgical approaches to the internal auditory carraW have raised new challenges to the earlier diagnosis of these lesions. Whereas in the past an acoustic neuroma was often not suspected until it involved multiple cranial nerves or caused increased intracranial pressure, the possibility of an acoustic neuroma is now considered in all patients with unilateral sensorineural hearing or vestibuIar loss of unknown origin. Although new or refined audiometric, vestibular, and neurologic tests are available, none is conclusive.3 In the final analysis, the preoperative diagnosis of a space-occupying lesion in the internal auditory canal and cerebellopontine cistern must be established radiographically. Furthermore, the task of the radiologist is not merely confined to diagnosing the tumor, but includes establishing its exact size and location, since the surgical approach will be determined mainly from this information.5~6
T
ANATOMY The petrous pyramids lie in the base of the skull at approximately 45” to the sagittal plane. The internal auditory canal enters the petrous pyramid from its posteromedial surface at the junction of the anterior two fifths with the posterior three fifths of the long axis of the pyramid. The long axis of the canal forms a right angle with the sagittal plane of the skull and an angle of about 45” with the long axis of the petrous pyramid (Fig. 1). The internal opening, or porus of the canal, is shaped much like the bevel of a needle with its maximum diameter, in the same axis as the petrous pyramid. The posterior, superior, and inferior lips of the porus are prominent and are made up of dense bone; the anterior lip is usually poorly demarcated so that the anterior wall of the canal blends smoothly with the posteriomedial wall of the petrous apex. The internal auditory canal contains the facial nerve, the nervus intermediUS, the acoustic nerve (which divides within the canal into its co&ear and vestibular portions ) , and the internal auditory branch of the basilar artery. All three nerves are enclosed within a common sheath. The lateral end of the canal is closed by a vertical plate (lamina cribrosa). Arising from the lamina cribrosa is a horizontal crest (crista falciformis), which divides the lateral part of the internal auditory canal into two unequal portions, the larger being the inferior one. Beneath the crista falciformis are three groups of foramina: the anterior one for the cochlear nerve and the two posterior ones for the two branches of the inferior vestibular nerve, which terminate in the saccule and posterior semicircular canal. Above the crista falciformis are two groups of foramina: the anterior for the facial nerve and GALDINO E. VALVASSOFU,M.D.: Professor of Radiology, of Medicine, Chicago, Ill.
University
SEMRURS IN ROENTGENOLOGY,VOL. 4, Np. 2 (APRIL), 1969
of Illinois
Co&w
171
172
GALDINO E. VALVASSORI
Fig. l.-Horizontal tomogram of petrous pyramids showing the relationship of the long axis of the petrous pyramids and internal auditory canals to the sagittal plane of the skull. C-cochlea; IAC-internal auditory canal. nervus intermedius, and the posterior for the superior vestibular nerve which terminates in the utricle, saccule, and lateral and superior semicircular canals. RADIOGRAPHY OF THE INTERNAL AUDITORY CANAL
Conventional Radiography On the basis of the above anatomic considerations, it appears that the frontal projection is best for the study of the internal auditory canal in its full length. I prefer a transorbital view, obtained with a small cone oentered on each orbit in AP projection, In the Stenvers view, the porus of the internal auditory canal is well seen en face, but the canal itself is foreshortened. Unfortunately, conventional radiography is unsatisfactory unless the destructive process is extensive because superimposition of other structures makes the recognition of the normal or altered walls of the internal auditory canal difhcult or impossible. This is particularly true when the petrous pyramids are extensively or asymmetrically pneumatized.
Tomography Tomography, when performed with an apparatus furnishing a sufficiently thin “cut” and a good coeflicient of sharpness, permits the use of the best anatomic projections and avoids the superimposition of undesired structures. Tomography should always be performed in two planes. The frontal sections (Fig. 2A) are the most satisfactory for studying the shape and size of
DIAGNOSIS OF ACOUSTIC NEUROMAS
173
.he internal
auditory canal and for the length of its posterior wall; the lateral sections reveal important details concerning the status of the cortex and poms of the canal (Fig. 2B ). Both sides should always be examined for comparison purposes since normally there are slight variations in size and shape of the two internal auditory canals. In order to establish the limits of normal variation among different individuals, several hundred internal auditory canals were measured in anatomic specimens and tomograms of ,patients having roentgen examinations of the temporal bone for conditions unrelated to the internal auditory cana1.7 The three most important parameters revealed the following measurements: ( 1) Vertical diameter of the internal auditory canal: it ranged from 2 to 9 mm. with an average of 4.5 mm. However, in over 90 per cent the diiference in the vertical diameter between the internal auditory canals on the two sides of the same subject did not exceed 1 mm. (2) Length of the posterior wall of the internal auditory canal: it measured from 4 to 12 mm. with an average of 8 mm. Again, in over 90 per cent the difference in length on the two sides did not exceed 2 mm. (3) Crista falcifomns: it was extremely variable in length and thickness but was always located at or above the midpoint of the vertical diameter of the internal auditory canal. In over 90 per cent of the cases the difference in position on the two sides, measured From the crista to the superior and inferior walls of the canal, did not exceed 1 mm. RADIOGRAPHY OF THE CEREBELLOPONTINE
CISTERNS
Opaque cistemogmp~y is, in my opinion, preferable to pneumoencephalography for demonstrating the cerebellopontine angles. The small amount of in the cerebellopontine cisterns and within the internal auditory air c~llwted canals does not provide sufficient contrast to consistently recognize soft-tissue masses, especially when small. Injection of 2 to 3 cc. of Pantopaque is made into the subarachnoid space by lumbar puncture. Under fluoroscopic control,. the contrast material is advanced into the posterior cranial fossa by tilting the table into the Trendelenburg position. During this maneuver the patient is kept in the lateral decubitus so that the contrast material will collect in the cerebellopontine cistern
Fig. Z.-Normal tomogram.
right internal auditory canal. A. Frontal tomogram. B. Lateral
IAC-internal
auditory
canal; CF-crista
falciformis;
OW-oval
window.
174
GALDINO E. VALVASSOIU
on the dependent side. The head is then rotated to an oblique Stenvers-like projection and finally to a full face-down view. This latter projection is extremely important for the visualization of the entire internal auditory canal without superimposition of the contrast material that has collected in the cistern (Fig. 3). During the study, multiple spot films are obtained at different angulations of the patient’s head. Whenever a spot film shows a small or questionable intracanalicular defect, multiple lateral and frontal tomograms are obtained. Vertebral arteriography has not been as useful in my hands for the demonstration of acoustic neuroma. Subtraction technique has improved visuahzation of the vessels in the region of the cerebellopontine cistern and tumor circulation is also better demonstrated than formerly. However, the many variations in course and size of the branches of the vertebral and basilar arteries detract from the reliability of the findings unless the lesion is large enough to produce unmistakable changes. ABNORMAL ROENTGEN FINDINGS
Since most acoustic neuromas originate within the internal auditory canal, we consider the tomographic study the most reliable screening method for detecting them. The internal auditory canal is considered abnmmul when we observe: (1) enlargement of 2 mm. or more of any portion, as compared with the opposite side (Fig. 4) ; (2) shortening of the posterior wall by at least 3 mm. compared with the opposite normal side; (3) the position of the crista falciformis differing by at least 2 mm. in comparison with the normal side;
DIAGNt
175
Fig. 4.-Right acoustic neuroma. Frontal tomographic sections show enlargement of the right internal auditory canal (A) compared with the normal left side (B). The distance from the crista falciformis to the floor of the canal is larger in the right canal.
(4) destruction of the cortical outline of the internal auditory canal, best seen on the lateral tomogram (Fig. 5). The internal auditory canal is considered 9uestionabZ,y normal if: ( 1) widening of the canal is only 1 to 2 mm.; (2) there is 2 to 3 mm. shortening of the posterior wall; (3) the difference in position of the crista falciformis on the two sides measures between 1 and 2 mm.; (4) the cortical outline of the internal auditory canal is demineralized but not frankly destroyed. At this point the results of the tomographic study are correlated with those of the audiometric, vestibular, and neurologic examinations in order to select the patients who require opaque cistemography. This study is, ol course, performed in all positive cases to confirm the diagnosis and to establish the size of the tumor mass. In the questionable group, if the other tests are suggestive of a retrocochlear lesion, opaque cistemography is performed immediately. If they are equivocal or negative, the patient is observed for a year and then, if there is worsening clinically or radiographically, a cistemo’gram is performed. Finally, a cistemogram is performed if the audiometric and vestibular tests consistently indicate a retrocochlear lesion in spite of a negative tomographic study since a tumor may be limited to the cistern or may be too small to produce osseous changes. Opaque cistemography constitutes the final and most coaclusive diagnostic test. Failure to fill the internal auditory canal (Fig. 6) and demonstration of a filling defect in the cerebellopontine cistern (Fig. 7) are positive evidence of a space-occupying lesion.
Fig. 5.-Right acoustic neuroma. Lateral tomogram reveals enlargement of the right internal auditory canal and erosion of its cortical outline (A). These appear intact in the normal left canal (B).
176
GALDINO E. VALVASSORI
Fig. 6.-Acoustic neuroma limited to the right internal auditory canal.
Cerebellopontine cisternogram shows normal filling of the cistern but a block at the porus. A small tumor limited to the internal auditory canal was removed through a translabrinthine approach with sparing of the facial nerve.
REVIEW OF CASES
During the last 4 years, I have diagnosed 89 tumors of the oerebellopontine angle, 83 of which have been surgically proved. This represents approximately 10 per cent of the 900 patients who were referred to me for tomographic studies of the internal auditory canals because of unilateral neurosensory hearing, or vestibular loss of unknown origin. Opaque cisternography was performed on approximately a third of the 900 patients and a tumor was found in 30 per cent. In 90 per cent of the surgically proved cases the space-occupying lesion was an acoustic neuroma; in the other 10 per cent lesions such as primary cholesteatoma, meningoma, aneurysm of the internal auditory canal artery, or arachnoid cyst were found. In 78 per cent of the surgically proved cases, the correct diagnosis of acoustic neuroma was made by tomography prior to opaque cisternography. This figure emphasizes the importance of tomography as a
Fig.
‘I.-Acoustic
neuroma
ex-
tending. from the internal auditory canal into the cerebellopontine cistern. The opaque cistemogram shows a mass 1.7 cm. in diameter in the cistern and absence of filling of the internal auditory canal. A tumor was successfully removed through a translabyrinthine approach.
DIAGNOSIS
OF
ACOUSTIC
177
NEUROMAS
preliminary study over conventional radiography which, at best, yields a positive diagnosis in only 50 per cent of the cases. The tomographic findings were negative in 9 per cent, and suggestive but not conclusive of a lesion in the remaining 13 per cent. The diagnosis of the cisternographic study was confirmed at surgery in all instances but one. In this case, we were unable to fill the lateral third of the internal auditory canal; however, a similar finding was observed when the opposite normal canal was examined, It should be noted that in our series of 300 iophendylate (Pantopaque) cistemograms we have encountered no complications except for headache immediately after the examination and occasionally backache and sciatic pain for a few weeks following the study. REFERENCES 1. House, W. F.: Surgical exposure of the internal auditory canal and its contents through the middle, cranial fossa. Laryngoscope 71: 1363, 1961. 2. House, W. F. (Ed.): Transtemporal bone microsurgical removal of acoustic neuromas. Arch. Otolaryngol. 80: 597, 1964. 3. Johnson, E. W.: Confirmed retrocochlear lesions: Auditory test results in 163 patients. Arch. Otolaryngol., 84:247, 1966. 4. Shambaugh, G. E.: Surgery of the
t
W. B. Saunders, E ar, 2 ed. Philadelphia, 1967. 5. Valvassori, G. E.: II. The contribution of radiology to the diagnosis of acoustic neuroma. Laryngoscope 76: 1104, 1966. 6. Valvassori, G. E.: The radiological diagnosis of acoustic neuromas. Arch. Otolaryngol., 83:582, 1966. 7. Valvassori, C. E., and Pierce, Il. H.: The normal internal auditory canal. Amer. J. Roentgen. 92:1232, 1964.
-a-ACE IN THE HOLE
Everything is self-explanatory in this commemorative stamp, down to the stylized roentgen image of the colon seen through the center hole which in this context obviously represents the business end of the antipodal, proctologic fraternity.-E. R. N. Grigg, M.D.
of Acoustic
Neuromas
By GALDINO FL VALVASSORI, M.D. HE REFINEMENT OF SURGICAL TECHNIQUE for the removal of acoustic neuroma through the use of the otomicroscope and the discovery of new surgical approaches to the internal auditory carraW have raised new challenges to the earlier diagnosis of these lesions. Whereas in the past an acoustic neuroma was often not suspected until it involved multiple cranial nerves or caused increased intracranial pressure, the possibility of an acoustic neuroma is now considered in all patients with unilateral sensorineural hearing or vestibuIar loss of unknown origin. Although new or refined audiometric, vestibular, and neurologic tests are available, none is conclusive.3 In the final analysis, the preoperative diagnosis of a space-occupying lesion in the internal auditory canal and cerebellopontine cistern must be established radiographically. Furthermore, the task of the radiologist is not merely confined to diagnosing the tumor, but includes establishing its exact size and location, since the surgical approach will be determined mainly from this information.5~6
T
ANATOMY The petrous pyramids lie in the base of the skull at approximately 45” to the sagittal plane. The internal auditory canal enters the petrous pyramid from its posteromedial surface at the junction of the anterior two fifths with the posterior three fifths of the long axis of the pyramid. The long axis of the canal forms a right angle with the sagittal plane of the skull and an angle of about 45” with the long axis of the petrous pyramid (Fig. 1). The internal opening, or porus of the canal, is shaped much like the bevel of a needle with its maximum diameter, in the same axis as the petrous pyramid. The posterior, superior, and inferior lips of the porus are prominent and are made up of dense bone; the anterior lip is usually poorly demarcated so that the anterior wall of the canal blends smoothly with the posteriomedial wall of the petrous apex. The internal auditory canal contains the facial nerve, the nervus intermediUS, the acoustic nerve (which divides within the canal into its co&ear and vestibular portions ) , and the internal auditory branch of the basilar artery. All three nerves are enclosed within a common sheath. The lateral end of the canal is closed by a vertical plate (lamina cribrosa). Arising from the lamina cribrosa is a horizontal crest (crista falciformis), which divides the lateral part of the internal auditory canal into two unequal portions, the larger being the inferior one. Beneath the crista falciformis are three groups of foramina: the anterior one for the cochlear nerve and the two posterior ones for the two branches of the inferior vestibular nerve, which terminate in the saccule and posterior semicircular canal. Above the crista falciformis are two groups of foramina: the anterior for the facial nerve and GALDINO E. VALVASSOFU,M.D.: Professor of Radiology, of Medicine, Chicago, Ill.
University
SEMRURS IN ROENTGENOLOGY,VOL. 4, Np. 2 (APRIL), 1969
of Illinois
Co&w
171
172
GALDINO E. VALVASSORI
Fig. l.-Horizontal tomogram of petrous pyramids showing the relationship of the long axis of the petrous pyramids and internal auditory canals to the sagittal plane of the skull. C-cochlea; IAC-internal auditory canal. nervus intermedius, and the posterior for the superior vestibular nerve which terminates in the utricle, saccule, and lateral and superior semicircular canals. RADIOGRAPHY OF THE INTERNAL AUDITORY CANAL
Conventional Radiography On the basis of the above anatomic considerations, it appears that the frontal projection is best for the study of the internal auditory canal in its full length. I prefer a transorbital view, obtained with a small cone oentered on each orbit in AP projection, In the Stenvers view, the porus of the internal auditory canal is well seen en face, but the canal itself is foreshortened. Unfortunately, conventional radiography is unsatisfactory unless the destructive process is extensive because superimposition of other structures makes the recognition of the normal or altered walls of the internal auditory canal difhcult or impossible. This is particularly true when the petrous pyramids are extensively or asymmetrically pneumatized.
Tomography Tomography, when performed with an apparatus furnishing a sufficiently thin “cut” and a good coeflicient of sharpness, permits the use of the best anatomic projections and avoids the superimposition of undesired structures. Tomography should always be performed in two planes. The frontal sections (Fig. 2A) are the most satisfactory for studying the shape and size of
DIAGNOSIS OF ACOUSTIC NEUROMAS
173
.he internal
auditory canal and for the length of its posterior wall; the lateral sections reveal important details concerning the status of the cortex and poms of the canal (Fig. 2B ). Both sides should always be examined for comparison purposes since normally there are slight variations in size and shape of the two internal auditory canals. In order to establish the limits of normal variation among different individuals, several hundred internal auditory canals were measured in anatomic specimens and tomograms of ,patients having roentgen examinations of the temporal bone for conditions unrelated to the internal auditory cana1.7 The three most important parameters revealed the following measurements: ( 1) Vertical diameter of the internal auditory canal: it ranged from 2 to 9 mm. with an average of 4.5 mm. However, in over 90 per cent the diiference in the vertical diameter between the internal auditory canals on the two sides of the same subject did not exceed 1 mm. (2) Length of the posterior wall of the internal auditory canal: it measured from 4 to 12 mm. with an average of 8 mm. Again, in over 90 per cent the difference in length on the two sides did not exceed 2 mm. (3) Crista falcifomns: it was extremely variable in length and thickness but was always located at or above the midpoint of the vertical diameter of the internal auditory canal. In over 90 per cent of the cases the difference in position on the two sides, measured From the crista to the superior and inferior walls of the canal, did not exceed 1 mm. RADIOGRAPHY OF THE CEREBELLOPONTINE
CISTERNS
Opaque cistemogmp~y is, in my opinion, preferable to pneumoencephalography for demonstrating the cerebellopontine angles. The small amount of in the cerebellopontine cisterns and within the internal auditory air c~llwted canals does not provide sufficient contrast to consistently recognize soft-tissue masses, especially when small. Injection of 2 to 3 cc. of Pantopaque is made into the subarachnoid space by lumbar puncture. Under fluoroscopic control,. the contrast material is advanced into the posterior cranial fossa by tilting the table into the Trendelenburg position. During this maneuver the patient is kept in the lateral decubitus so that the contrast material will collect in the cerebellopontine cistern
Fig. Z.-Normal tomogram.
right internal auditory canal. A. Frontal tomogram. B. Lateral
IAC-internal
auditory
canal; CF-crista
falciformis;
OW-oval
window.
174
GALDINO E. VALVASSOIU
on the dependent side. The head is then rotated to an oblique Stenvers-like projection and finally to a full face-down view. This latter projection is extremely important for the visualization of the entire internal auditory canal without superimposition of the contrast material that has collected in the cistern (Fig. 3). During the study, multiple spot films are obtained at different angulations of the patient’s head. Whenever a spot film shows a small or questionable intracanalicular defect, multiple lateral and frontal tomograms are obtained. Vertebral arteriography has not been as useful in my hands for the demonstration of acoustic neuroma. Subtraction technique has improved visuahzation of the vessels in the region of the cerebellopontine cistern and tumor circulation is also better demonstrated than formerly. However, the many variations in course and size of the branches of the vertebral and basilar arteries detract from the reliability of the findings unless the lesion is large enough to produce unmistakable changes. ABNORMAL ROENTGEN FINDINGS
Since most acoustic neuromas originate within the internal auditory canal, we consider the tomographic study the most reliable screening method for detecting them. The internal auditory canal is considered abnmmul when we observe: (1) enlargement of 2 mm. or more of any portion, as compared with the opposite side (Fig. 4) ; (2) shortening of the posterior wall by at least 3 mm. compared with the opposite normal side; (3) the position of the crista falciformis differing by at least 2 mm. in comparison with the normal side;
DIAGNt
175
Fig. 4.-Right acoustic neuroma. Frontal tomographic sections show enlargement of the right internal auditory canal (A) compared with the normal left side (B). The distance from the crista falciformis to the floor of the canal is larger in the right canal.
(4) destruction of the cortical outline of the internal auditory canal, best seen on the lateral tomogram (Fig. 5). The internal auditory canal is considered 9uestionabZ,y normal if: ( 1) widening of the canal is only 1 to 2 mm.; (2) there is 2 to 3 mm. shortening of the posterior wall; (3) the difference in position of the crista falciformis on the two sides measures between 1 and 2 mm.; (4) the cortical outline of the internal auditory canal is demineralized but not frankly destroyed. At this point the results of the tomographic study are correlated with those of the audiometric, vestibular, and neurologic examinations in order to select the patients who require opaque cistemography. This study is, ol course, performed in all positive cases to confirm the diagnosis and to establish the size of the tumor mass. In the questionable group, if the other tests are suggestive of a retrocochlear lesion, opaque cistemography is performed immediately. If they are equivocal or negative, the patient is observed for a year and then, if there is worsening clinically or radiographically, a cistemo’gram is performed. Finally, a cistemogram is performed if the audiometric and vestibular tests consistently indicate a retrocochlear lesion in spite of a negative tomographic study since a tumor may be limited to the cistern or may be too small to produce osseous changes. Opaque cistemography constitutes the final and most coaclusive diagnostic test. Failure to fill the internal auditory canal (Fig. 6) and demonstration of a filling defect in the cerebellopontine cistern (Fig. 7) are positive evidence of a space-occupying lesion.
Fig. 5.-Right acoustic neuroma. Lateral tomogram reveals enlargement of the right internal auditory canal and erosion of its cortical outline (A). These appear intact in the normal left canal (B).
176
GALDINO E. VALVASSORI
Fig. 6.-Acoustic neuroma limited to the right internal auditory canal.
Cerebellopontine cisternogram shows normal filling of the cistern but a block at the porus. A small tumor limited to the internal auditory canal was removed through a translabrinthine approach with sparing of the facial nerve.
REVIEW OF CASES
During the last 4 years, I have diagnosed 89 tumors of the oerebellopontine angle, 83 of which have been surgically proved. This represents approximately 10 per cent of the 900 patients who were referred to me for tomographic studies of the internal auditory canals because of unilateral neurosensory hearing, or vestibular loss of unknown origin. Opaque cisternography was performed on approximately a third of the 900 patients and a tumor was found in 30 per cent. In 90 per cent of the surgically proved cases the space-occupying lesion was an acoustic neuroma; in the other 10 per cent lesions such as primary cholesteatoma, meningoma, aneurysm of the internal auditory canal artery, or arachnoid cyst were found. In 78 per cent of the surgically proved cases, the correct diagnosis of acoustic neuroma was made by tomography prior to opaque cisternography. This figure emphasizes the importance of tomography as a
Fig.
‘I.-Acoustic
neuroma
ex-
tending. from the internal auditory canal into the cerebellopontine cistern. The opaque cistemogram shows a mass 1.7 cm. in diameter in the cistern and absence of filling of the internal auditory canal. A tumor was successfully removed through a translabyrinthine approach.
DIAGNOSIS
OF
ACOUSTIC
177
NEUROMAS
preliminary study over conventional radiography which, at best, yields a positive diagnosis in only 50 per cent of the cases. The tomographic findings were negative in 9 per cent, and suggestive but not conclusive of a lesion in the remaining 13 per cent. The diagnosis of the cisternographic study was confirmed at surgery in all instances but one. In this case, we were unable to fill the lateral third of the internal auditory canal; however, a similar finding was observed when the opposite normal canal was examined, It should be noted that in our series of 300 iophendylate (Pantopaque) cistemograms we have encountered no complications except for headache immediately after the examination and occasionally backache and sciatic pain for a few weeks following the study. REFERENCES 1. House, W. F.: Surgical exposure of the internal auditory canal and its contents through the middle, cranial fossa. Laryngoscope 71: 1363, 1961. 2. House, W. F. (Ed.): Transtemporal bone microsurgical removal of acoustic neuromas. Arch. Otolaryngol. 80: 597, 1964. 3. Johnson, E. W.: Confirmed retrocochlear lesions: Auditory test results in 163 patients. Arch. Otolaryngol., 84:247, 1966. 4. Shambaugh, G. E.: Surgery of the
t
W. B. Saunders, E ar, 2 ed. Philadelphia, 1967. 5. Valvassori, G. E.: II. The contribution of radiology to the diagnosis of acoustic neuroma. Laryngoscope 76: 1104, 1966. 6. Valvassori, G. E.: The radiological diagnosis of acoustic neuromas. Arch. Otolaryngol., 83:582, 1966. 7. Valvassori, C. E., and Pierce, Il. H.: The normal internal auditory canal. Amer. J. Roentgen. 92:1232, 1964.
-a-ACE IN THE HOLE
Everything is self-explanatory in this commemorative stamp, down to the stylized roentgen image of the colon seen through the center hole which in this context obviously represents the business end of the antipodal, proctologic fraternity.-E. R. N. Grigg, M.D.