- Email: [email protected]
IS DUODENITIS A DYSPEPTIC MYTH?
1197
tients but substantially greater than that described Bohnet et al.7
by
In the present state of admittedly meagre knowledge, surgery, possibly followed by external irradiation, is probably the treatment of choice when a pituitary tumour extends beyond the sella (macroadenoma). Despite this, none of our patients treated surgically has shown a reduction of prolactin levels to normal, suggesting that surgery is usually incomplete-at least in our unit. Because of the risks of tumour enlargement during pregnancy," we will not treat patients with pituitary tumours medically without prior surgical intervention. We have already seen a patient referred when pregnant (and for that reason not included in this series) whose untreated extrasellar tumour expanded rapidly during pregnancy after ovulation had been induced with bro-
mocriptine. For the patient
with hyperprolactinaemia lacking evidence of tumour, bromocriptine is the treatment of first choice.9 10 So far, 5 of 9 patients in this series have conceived following bromocriptine treatment. The other 4 are ovulating normally. For these women this treatment is far more specific than clomiphene or gonadotrophins. The management appropriate for patients with small adenomata confined to the fossa (microadenoma) is arguable. We are treating these patients with external cobalt irradiation followed by bromocriptine, on the unproven assumption that the tumour is less likely to enlarge in subsequent pregnancy. It is still too early to determine the results of this treatment. Patients in this group who do not wish to become pregnant are not treated at all but followed up closely. For the future, it must be remembered that some of these patients without detectable tumours may ultimately develop such evidence. Only long-term follow-up will resolve this problem. Further, we cannot be sure whether these tumours are autonomous neoplasms or result simply from hypothalamic "overdrive". The commonest clinical association in this series, as in our ealier group of patients, is a history of amenorrhoea becoming evident after stopping treatment with oral contraceptives. It should be emphasised that pituitary tumours will be found relatively frequently in these women, as they may in any group of patients with secondary amenorrhoea. Cone views of the pituitary fossa and prolactin and T.S.H. assays are mandatory in all patients with secondary amenorrhoea. If either of the first two is abnormal, more detailed radiological assessment must be done before appropriate treatment can be decided. The T.S.H. assay is necessary because clinically undetected hypothyroidism with high T.S.H. levels may be associated with hyperprolactinaemia and galactorrhoea. We should like
to
thank the Laura Bushell Trust for support. Bro-
supplied by Sandoz Pty, Ltd, Australia. We are grateful to our colleagues in the departments of radiology, neurosurgery, and endocrinology at the Royal Prince Alfred Hospital for assistance. Requests for reprints should be addressed to R. P. S., Department of Obstetrics and Gynaecology, University of Sydney, 2006, Australia. mocriptine
was
REFERENCES 1. Shearman, R. P., Smith, I. D. J. Obstet. Gynæc. Br. Commonw. 1972, 79, 654. 2. Shearman, R. P. Lancet, 1971, ii, 64. 3. Shearman, R. P. in Integrated Obstetrics and Gynæcology (edited by C. J. Dewhurst); p. 62. Oxford, 1976.
Unsettled Questions IS DUODENITIS A DYSPEPTIC MYTH? W. O. THOMSON A. G. ROBERTSON C. W. IMRIE
S. N. JOFFE F. D. LEE L. H. BLUMGART
University Departments of Surgery and Pathology, Royal Infirmary, Glasgow, G4 OSF In 502
fibreoptic œsophagogastroduodenoscopies performed over 30 months, 14 cases (2·8%) of symptomatic duodenitis without an associated duodenal ulcer were diagnosed. Follow-up (1 to 3·5 years) including repeat endoscopy and double-
Summary
barium meal showed that duodenal ulcers later in 6 patients. All have undergone surgery. A further 2 patients continued to complain of dyspepsia, and repeat endoscopy showed duodenitis, confirmed by conventional light microscopy (hæmatoxylin and eosin). The remaining patients are symptom-free. Repeat endoscopy and histological examination were either normal or showed mild inflammation of the duodenal mucosa. These findings suggest that duodenitis can cause symptoms and may be a part of the pathophysiological spectrum of duodenal ulceration rather than a separate disease. It may represent both the production and healing phases of duodenal ulceration.
contrast
developed
INTRODUCTION
THE clinical importance of duodenal inflammation in the absence of ulceration-"duodenitis"-remains controversial. Some patients with clinical symptoms resembling those of duodenal ulcer have a radiologically noror mal duodenum, prominent mucosal folds, associated with a spastic duodenal bulb, but occasionally no duodenal ulcer.’-3 Oesophagogastroduodenoscopy often reveals inflammatory changes of the duodenal mucosa without ulceration in these patients.3,4 It is still not clear whether this duodenitis is a separate entity,S or possibly a variant of peptic-ulcer disease.6 The present study attempts to answer this question by studying the natural history of patients with endoscopically diagnosed duodenitis. PATIENTS AND METHODS
In a total of 502 fibreoptic oesophagogastroduodenoscopies, performed during a 30-month period, symptomatic duodenitis was diagnosed in only 14 patients (2-8%). No biopsy specimens were taken at the initial investigation, but the procedures were carried out by three experienced endoscopists. All patients who had evidence of cesophagitis, gastritis, or gastric or duodenal ulceration on endoscopy and/or barium meal were excluded.
Mortimer, C. H., Besser, G. M., McNeilly, A. S., Tunbridge, W. M. G., Gomez-Pan, A., Hall, R. Clin. Endocr. 1973, 2, 317. 5. Shearman, R. P., Turtle, J. Am. J. Obstet. Gynec. 1970, 106, 818. 6. Seppälä, M., Hirvonen, E., Ranta, T., Virkkunen, P. , Leppäluoto, J. Br. med. J. 1975, ii, 305. 7. Bohnet, H. G., Dahlen, H. G., Wuttke, W., Schneider, H. P. G. J. clin. Endocr. Metab. 1975, 42, 132. 8. Gemzell, C. A. Am. J. Obstet. Gynec. 1975, 121, 311. 9. del Pozo, E., Barga, L., Wyss, H., Tocis, G., Friesen, H., Wenner, R., Vetter, L., Uettwiler, A. J clin. Endocr. Metab. 1974, 39, 18. 10. Lloyd, S. r, Josimovich, J. R., Archer, D. F. Am. J. Obstet. Gynec. 1975, 4.
122, 85.
1198 The 14 patients included 10 men and 4 women (mean age of 37.6 [range 18-61] years) with a mean duration of dyspeptic symptoms of 4 years (0-5-15 years). The follow-up study over 1 to 3.3(mean 16) years has included clinical examination, repeat endoscopy with an end-viewing Olympus GIF oesophagogastroduodenoscope, and in some instances a side-viewing instrument (JFB2). Multiple biopsy specimens of the duodenum were obtained for histology, and a double-contrast barium meal’ was performed. RESULTS
At
follow-up 6 of the 14 patients were symptom-free. 1 patient refused further investigations. Repeat endoscopy and conventional light microscopy (4aematoxylin and eosin), reported without prior knowledge of the pathological abnormality in 5 of the symptom-free patients, showed a normal duodenal mucosa in 4 and mild duodenitis in 1 (see accompanying table). 2 patients continued to complain of dyspepsia, and repeat endoscopy demonstrated duodenitis with no duodenal ulceration in both. Light microscopy of the duodenal biopsy specimens showed gastric metaplasia with epithelial degradation and neutrophil infiltration indicative of "active" duodenitis. The remaining 6 patients studied continued to complain of intractable dyspepsia, and 2 were admitted to hospital with an upper-gastrointestinal-tract hoemorrhage before review. At follow-up a duodenal ulcer was found to have developed in all 6 patients. All 6 underwent elective surgery. Highly selective vagotomy was performed in 3 patients, vagotomy and antrectomy in 2, and a vagotomy and pyloroplasty in 1. The findings at operation included the typical serosal scarring of duodenal ulceration, and the ulcer was confirmed in the 3 patients in whom the duodenum was opened. DISCUSSION
The existence of clinically important duodenal inflammation in the absence of ulceration--duodenitisremains controversial despite many published reports OUTCOME IN PATIENTS WITH AN ENDOSCOPIC DIAGNOSIS OF DUODENITIS FOLLOWED FOR
1
TO
3.5YEARS
dating back to 18 37." The early studies were based on operative or post-mortem specimens of the duodenal mucosa. Radiology alone is unreliable in this condition except to exclude obvious ulceration.3 However, fibreoptic endoscopy allows complete display and biopsy of the oesophagus, stomach, and duodenum. With the use of these newer methods of investigation it has become apparent that to be of clinical importance the histotogical definition of duodenitis must include evidence of epithelial damage. An increase in round-cell infiltration in the lamina propria is by itself not sufficient evidence of such damage .6.9 Progressive damage of the mucosa with petechial haemorrhages, mucosal erosions, and finally ulceration through the muscularis mucosae is seen during the production of experimental duodenal ulcers.lO With healing of these acute duodenal ulcers there is a blunting and flattening of the villi, neutrophil migration through the epithelia, and round-cell infiltration of the lamina propria.11 The changes preceding the experimentally induced ulceration resemble duodenitis. In patients with duodenal ulceration, studies have shown that histological duodenitis is usually confined to the ulcer area.6,12 This suggests that duodenal ulcer and active duodenitis are focal conditions and may be related. Severe duodenal ulceration developed in 6 of the 14 patients with duodenitis. All required operation within a short period of follow-up. These duodenal ulcers were shown by radiology and endoscopy, and confirmed at operation. However, an ulcer may have been missed at the initial investigations. A further 6 patients are now symptom-free and, although 2 have a deformed duodenal cap on barium meal, none has acquired a duodenal ulcer. The 2 patients with persistent dyspepsia have duodenitis on endoscopy, which was confirmed by histological criteria. Duodenitis seems to be a definite clinical syndrome, the diagnosis being made on the symptoms of dyspepsia with a negative double-contrast barium meal, and proven by resophagogastroduodenoscopy with biopsy. Furthermore, these findings accord with the idea that duodenitis is part of the pathophysiological spectrum of the duodenal-ulcer diathesis rather than a separate disease, Duodenitis probably represents both the early development or the later stage of healing of a peptic ulcer and requires careful clinical, radiological, endoscopic, and
histological assessment. Requests for reprints should be addressed to S. N. J., University Department of Surgery, Royal Infirmary, Glasgow, G4 OSF. REFERENCES 1. Schulman, A. Br. J. Radiol. 1970, 2. Rhodes, J., Evans, K. T., Lawne,
43, 787. J. H., Forrest,
A. P. M. Q.
Jl Med. 1968,
145, 151. 3. Cotton, P. B. Br. J. Hosp. Med. 1976, 16, 7. 4. Classen, M., Koch, H., Demling, L. Bibl. Gastroent. 1970, 5. Gelzayd, E. A., Bierderman, M. A., Gelfand, D. W. Am.
9, 48. J. Gastroent. 1972,
213, 6. Cotton, P. B., Price, A. B.,
Tighe,
D. R.,
Beales, J. S. M. Br med. J. 1973,
iii, 430. I. M., Sokhi, G. S., Moule, B., Joffe, S. N., Blumgart, L. H. Lancet, 1976, i, 901. 8. Baudin, J. B. M.D. thesis, University of Paris, 1837, Cited by Ostrow, J. D. Resnick, R. H. Ann. intern. Med. 1959, 51, 1303. 9. Whitehead, R., Roca, M., Meikle, D. D., Skinner, J., Truelove, S. C. Digestion, 1975, 13, 129. 10. Joffe, S. N., Gaskin, R., Barros D’Sa, A. A. J., Baron, J. H. Br J. Surg 7.
Rogers,
1977, 64, 218. J., Gad, A., Barros D’Sa, troenterology, 1975, 69, 903. 12. Cheli, R. Digestion, 1968, 1, 175. 11. Gaskin, R.
D.u.=duodenal ulcer.
A. A.
J., Joffe, S. N., Baron, J. H. Gas-
tients but substantially greater than that described Bohnet et al.7
by
In the present state of admittedly meagre knowledge, surgery, possibly followed by external irradiation, is probably the treatment of choice when a pituitary tumour extends beyond the sella (macroadenoma). Despite this, none of our patients treated surgically has shown a reduction of prolactin levels to normal, suggesting that surgery is usually incomplete-at least in our unit. Because of the risks of tumour enlargement during pregnancy," we will not treat patients with pituitary tumours medically without prior surgical intervention. We have already seen a patient referred when pregnant (and for that reason not included in this series) whose untreated extrasellar tumour expanded rapidly during pregnancy after ovulation had been induced with bro-
mocriptine. For the patient
with hyperprolactinaemia lacking evidence of tumour, bromocriptine is the treatment of first choice.9 10 So far, 5 of 9 patients in this series have conceived following bromocriptine treatment. The other 4 are ovulating normally. For these women this treatment is far more specific than clomiphene or gonadotrophins. The management appropriate for patients with small adenomata confined to the fossa (microadenoma) is arguable. We are treating these patients with external cobalt irradiation followed by bromocriptine, on the unproven assumption that the tumour is less likely to enlarge in subsequent pregnancy. It is still too early to determine the results of this treatment. Patients in this group who do not wish to become pregnant are not treated at all but followed up closely. For the future, it must be remembered that some of these patients without detectable tumours may ultimately develop such evidence. Only long-term follow-up will resolve this problem. Further, we cannot be sure whether these tumours are autonomous neoplasms or result simply from hypothalamic "overdrive". The commonest clinical association in this series, as in our ealier group of patients, is a history of amenorrhoea becoming evident after stopping treatment with oral contraceptives. It should be emphasised that pituitary tumours will be found relatively frequently in these women, as they may in any group of patients with secondary amenorrhoea. Cone views of the pituitary fossa and prolactin and T.S.H. assays are mandatory in all patients with secondary amenorrhoea. If either of the first two is abnormal, more detailed radiological assessment must be done before appropriate treatment can be decided. The T.S.H. assay is necessary because clinically undetected hypothyroidism with high T.S.H. levels may be associated with hyperprolactinaemia and galactorrhoea. We should like
to
thank the Laura Bushell Trust for support. Bro-
supplied by Sandoz Pty, Ltd, Australia. We are grateful to our colleagues in the departments of radiology, neurosurgery, and endocrinology at the Royal Prince Alfred Hospital for assistance. Requests for reprints should be addressed to R. P. S., Department of Obstetrics and Gynaecology, University of Sydney, 2006, Australia. mocriptine
was
REFERENCES 1. Shearman, R. P., Smith, I. D. J. Obstet. Gynæc. Br. Commonw. 1972, 79, 654. 2. Shearman, R. P. Lancet, 1971, ii, 64. 3. Shearman, R. P. in Integrated Obstetrics and Gynæcology (edited by C. J. Dewhurst); p. 62. Oxford, 1976.
Unsettled Questions IS DUODENITIS A DYSPEPTIC MYTH? W. O. THOMSON A. G. ROBERTSON C. W. IMRIE
S. N. JOFFE F. D. LEE L. H. BLUMGART
University Departments of Surgery and Pathology, Royal Infirmary, Glasgow, G4 OSF In 502
fibreoptic œsophagogastroduodenoscopies performed over 30 months, 14 cases (2·8%) of symptomatic duodenitis without an associated duodenal ulcer were diagnosed. Follow-up (1 to 3·5 years) including repeat endoscopy and double-
Summary
barium meal showed that duodenal ulcers later in 6 patients. All have undergone surgery. A further 2 patients continued to complain of dyspepsia, and repeat endoscopy showed duodenitis, confirmed by conventional light microscopy (hæmatoxylin and eosin). The remaining patients are symptom-free. Repeat endoscopy and histological examination were either normal or showed mild inflammation of the duodenal mucosa. These findings suggest that duodenitis can cause symptoms and may be a part of the pathophysiological spectrum of duodenal ulceration rather than a separate disease. It may represent both the production and healing phases of duodenal ulceration.
contrast
developed
INTRODUCTION
THE clinical importance of duodenal inflammation in the absence of ulceration-"duodenitis"-remains controversial. Some patients with clinical symptoms resembling those of duodenal ulcer have a radiologically noror mal duodenum, prominent mucosal folds, associated with a spastic duodenal bulb, but occasionally no duodenal ulcer.’-3 Oesophagogastroduodenoscopy often reveals inflammatory changes of the duodenal mucosa without ulceration in these patients.3,4 It is still not clear whether this duodenitis is a separate entity,S or possibly a variant of peptic-ulcer disease.6 The present study attempts to answer this question by studying the natural history of patients with endoscopically diagnosed duodenitis. PATIENTS AND METHODS
In a total of 502 fibreoptic oesophagogastroduodenoscopies, performed during a 30-month period, symptomatic duodenitis was diagnosed in only 14 patients (2-8%). No biopsy specimens were taken at the initial investigation, but the procedures were carried out by three experienced endoscopists. All patients who had evidence of cesophagitis, gastritis, or gastric or duodenal ulceration on endoscopy and/or barium meal were excluded.
Mortimer, C. H., Besser, G. M., McNeilly, A. S., Tunbridge, W. M. G., Gomez-Pan, A., Hall, R. Clin. Endocr. 1973, 2, 317. 5. Shearman, R. P., Turtle, J. Am. J. Obstet. Gynec. 1970, 106, 818. 6. Seppälä, M., Hirvonen, E., Ranta, T., Virkkunen, P. , Leppäluoto, J. Br. med. J. 1975, ii, 305. 7. Bohnet, H. G., Dahlen, H. G., Wuttke, W., Schneider, H. P. G. J. clin. Endocr. Metab. 1975, 42, 132. 8. Gemzell, C. A. Am. J. Obstet. Gynec. 1975, 121, 311. 9. del Pozo, E., Barga, L., Wyss, H., Tocis, G., Friesen, H., Wenner, R., Vetter, L., Uettwiler, A. J clin. Endocr. Metab. 1974, 39, 18. 10. Lloyd, S. r, Josimovich, J. R., Archer, D. F. Am. J. Obstet. Gynec. 1975, 4.
122, 85.
1198 The 14 patients included 10 men and 4 women (mean age of 37.6 [range 18-61] years) with a mean duration of dyspeptic symptoms of 4 years (0-5-15 years). The follow-up study over 1 to 3.3(mean 16) years has included clinical examination, repeat endoscopy with an end-viewing Olympus GIF oesophagogastroduodenoscope, and in some instances a side-viewing instrument (JFB2). Multiple biopsy specimens of the duodenum were obtained for histology, and a double-contrast barium meal’ was performed. RESULTS
At
follow-up 6 of the 14 patients were symptom-free. 1 patient refused further investigations. Repeat endoscopy and conventional light microscopy (4aematoxylin and eosin), reported without prior knowledge of the pathological abnormality in 5 of the symptom-free patients, showed a normal duodenal mucosa in 4 and mild duodenitis in 1 (see accompanying table). 2 patients continued to complain of dyspepsia, and repeat endoscopy demonstrated duodenitis with no duodenal ulceration in both. Light microscopy of the duodenal biopsy specimens showed gastric metaplasia with epithelial degradation and neutrophil infiltration indicative of "active" duodenitis. The remaining 6 patients studied continued to complain of intractable dyspepsia, and 2 were admitted to hospital with an upper-gastrointestinal-tract hoemorrhage before review. At follow-up a duodenal ulcer was found to have developed in all 6 patients. All 6 underwent elective surgery. Highly selective vagotomy was performed in 3 patients, vagotomy and antrectomy in 2, and a vagotomy and pyloroplasty in 1. The findings at operation included the typical serosal scarring of duodenal ulceration, and the ulcer was confirmed in the 3 patients in whom the duodenum was opened. DISCUSSION
The existence of clinically important duodenal inflammation in the absence of ulceration--duodenitisremains controversial despite many published reports OUTCOME IN PATIENTS WITH AN ENDOSCOPIC DIAGNOSIS OF DUODENITIS FOLLOWED FOR
1
TO
3.5YEARS
dating back to 18 37." The early studies were based on operative or post-mortem specimens of the duodenal mucosa. Radiology alone is unreliable in this condition except to exclude obvious ulceration.3 However, fibreoptic endoscopy allows complete display and biopsy of the oesophagus, stomach, and duodenum. With the use of these newer methods of investigation it has become apparent that to be of clinical importance the histotogical definition of duodenitis must include evidence of epithelial damage. An increase in round-cell infiltration in the lamina propria is by itself not sufficient evidence of such damage .6.9 Progressive damage of the mucosa with petechial haemorrhages, mucosal erosions, and finally ulceration through the muscularis mucosae is seen during the production of experimental duodenal ulcers.lO With healing of these acute duodenal ulcers there is a blunting and flattening of the villi, neutrophil migration through the epithelia, and round-cell infiltration of the lamina propria.11 The changes preceding the experimentally induced ulceration resemble duodenitis. In patients with duodenal ulceration, studies have shown that histological duodenitis is usually confined to the ulcer area.6,12 This suggests that duodenal ulcer and active duodenitis are focal conditions and may be related. Severe duodenal ulceration developed in 6 of the 14 patients with duodenitis. All required operation within a short period of follow-up. These duodenal ulcers were shown by radiology and endoscopy, and confirmed at operation. However, an ulcer may have been missed at the initial investigations. A further 6 patients are now symptom-free and, although 2 have a deformed duodenal cap on barium meal, none has acquired a duodenal ulcer. The 2 patients with persistent dyspepsia have duodenitis on endoscopy, which was confirmed by histological criteria. Duodenitis seems to be a definite clinical syndrome, the diagnosis being made on the symptoms of dyspepsia with a negative double-contrast barium meal, and proven by resophagogastroduodenoscopy with biopsy. Furthermore, these findings accord with the idea that duodenitis is part of the pathophysiological spectrum of the duodenal-ulcer diathesis rather than a separate disease, Duodenitis probably represents both the early development or the later stage of healing of a peptic ulcer and requires careful clinical, radiological, endoscopic, and
histological assessment. Requests for reprints should be addressed to S. N. J., University Department of Surgery, Royal Infirmary, Glasgow, G4 OSF. REFERENCES 1. Schulman, A. Br. J. Radiol. 1970, 2. Rhodes, J., Evans, K. T., Lawne,
43, 787. J. H., Forrest,
A. P. M. Q.
Jl Med. 1968,
145, 151. 3. Cotton, P. B. Br. J. Hosp. Med. 1976, 16, 7. 4. Classen, M., Koch, H., Demling, L. Bibl. Gastroent. 1970, 5. Gelzayd, E. A., Bierderman, M. A., Gelfand, D. W. Am.
9, 48. J. Gastroent. 1972,
213, 6. Cotton, P. B., Price, A. B.,
Tighe,
D. R.,
Beales, J. S. M. Br med. J. 1973,
iii, 430. I. M., Sokhi, G. S., Moule, B., Joffe, S. N., Blumgart, L. H. Lancet, 1976, i, 901. 8. Baudin, J. B. M.D. thesis, University of Paris, 1837, Cited by Ostrow, J. D. Resnick, R. H. Ann. intern. Med. 1959, 51, 1303. 9. Whitehead, R., Roca, M., Meikle, D. D., Skinner, J., Truelove, S. C. Digestion, 1975, 13, 129. 10. Joffe, S. N., Gaskin, R., Barros D’Sa, A. A. J., Baron, J. H. Br J. Surg 7.
Rogers,
1977, 64, 218. J., Gad, A., Barros D’Sa, troenterology, 1975, 69, 903. 12. Cheli, R. Digestion, 1968, 1, 175. 11. Gaskin, R.
D.u.=duodenal ulcer.
A. A.
J., Joffe, S. N., Baron, J. H. Gas-