- Email: [email protected]
The Malignant Large-bowel Polyp— Conservative or Radical Treatment?
1387
embedded, fixed, sectioned, and examined.3 If the histologist identifies malignant change in a pedunculated adenoma, should conservative or radical
The Malignant Large-bowel Polyp— Conservative or Radical Treatment? AN adenomatous large-bowel polyp is a benign new growth with a potential for malignant change and centrifugal spread. The head of this type of polyp consists of a mass of neoplastic glandular tubules lined by columnar cells. The stalk, which may be a product of peristalsis, is composed of normal large-bowel mucosa and muscularis mucosae, with a central core of submucosal areolar tissue. Lymphatic tissue
accompanies the muscularis mucosae up to the head of the polyp, where it is found beneath the mucosa. An invasive adenocarcinoma is diagnosed when malignant change in the cells of the adenomatous head of the polyp is seen to extend through the muscularis into the submucosa, thus permitting mucosae lymphatic dissemination. When such a breach in the integrity of the muscularis mucosae is evident, the extent of replacement of the benign adenoma by carcinoma is important. A malignant polypoidal tumour with no residual benign adenomatous tissue must be diagnosed as a polypoidal adenocarcinoma. Some authorities recognise a premalignant stage of intramucosal carcinoma-in-situ, when potentially malignant changes in the adenomatous mucosa can be identified without any evidence of
a
breach in the
integrity of the muscularis mucosae.’1 Colonoscopy is-or should be-available in every district general hospital, since it facilitates excision biopsy of any pedunculated mucosal lesion by means of the diathermy snare.2 The polyp, together with its pedicle, must be retrieved after excision, correctly
surgery be advised?4 Clinical decisions must be based upon a reliable histological opinion about a correctly oriented section of the polyp and its pedicle.3 If the lesion shows no evidence of malignant breach of the muscularis mucosae, further surgery is not necessary. Polyps displaying so called carcinoma-insitu are benign.’ If the lesion is a polypoidal cancer with invasive carcinoma extending into the base of the pedicle, conventional large-bowel surgery is indicated. For the patient who is unfit or refuses major surgery local excision may be cautiously considered, provided that the muscularis propria is not penetrated by centrifugal spread of the cancer (if it is, or if the tumour is poorly differentiated, lymph node metastases can be anticipated in 12% of patients4). If the lesion is a true malignant polyp-a pedunculated adenoma with a breach in the muscularis mucosae by malignant change in the adenomatous mucosa-treatment is controversial. The crucial question is whether there is any risk of undetected extramural lymph-node metastases after complete and apparently successful endoscopic resection of such a polyp.4 A new paper from St Mark’s Hospital recommends conservative treatment of the malignant polyp provided that excision by endoscopic polypectomy is clinically complete, the specimen is correctly oriented, the carcinoma is not poorly differentiated, and the margin of the specimen is free from malignant invasion.3 Other papers emphasise a further requirement-absence of malignant lymphatic and venous invasion.4If all these criteria are satisfied, the mortality rate of a large-bowel resection (about 2%) may exceed the risk of lymph-node metastases.4 The possibility of such metastases cannot, however, be directly excluded by the St Mark’s criteria, and a review from the College of Physicians and Surgeons at Columbia University, New York, records transmural lymph-node metastases in 25% of 24 malignant colonic polyps after conventional colectomy.5 All the patients had previously undergone endoscopic polypectomy and at that time a margin of normal tissue had been identified histologically in the stalk. No residual cancer was identified in any patient at the polypectomy site after the subsequent colectomy.5 This means that a further operation was unnecessary in 75% of these patients but the other 25% had a Dukes C lesion at the time of radical surgery. The New York workers conclude that conventional large-bowel surgery is justified in patients with a malignant polyp after successful polypectomy, because radical excision is the of cure of a only treatment that offers any prospect Dukes C tumour of the large bowel.5 BC, Whiteway JE, Jones EA, Macrae FA, Williams CB. Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy. Gut
3. Morson 1. Shatney
CH, Lober PH, Gilbertson VA, Sosin H. The treatment of pedunculated adenomatous colorectal polyps with focal cancer. Surgery Gynecol Obstet 1974; 139: 845-50.
2. Editorial. Colonoscopy—essential service in 1311-12.
a
general hospital.
Lancet
1983; i;
1984; 25: 437-44. 4. De Cosse JJ. Malignant colorectal polyp. Gut 1984; 25: 433-36. 5. Colacchio TA, Forde KA, Scantlebury VP. Endoscopic polypectomy. Inadequate treatment for invasive colorectal cancer. Ann Surg 1981; 194: 704-07.
1388
It is difficult to argue convincingly in favour of radical surgery, perhaps with a permanent colostomy, when 75% of patients with a malignant large-bowel polyp do not require it, but we must avoid the temptation of capricious excision of large sessile colonic tumours, or piecemeal removal of large pedunculated lesions, with the colonoscope. There is a risk of transmural malignancy in these tumours, and they are best treated by transabdominal, transanal, or
ventilation in terms of tidal volume, minute volume, and blood-gases, some patients still "fight" the ventilator. This may be due purely to discomfort from the endotracheal tube, or to stimulation of receptors
transperineal excision, thus allowing full-thickness
to
excision of the wall of the diseased bowel.4 The St Mark’s criteria, although only indirect indices of transmural lymph-node metastases, seem to have stood the test of time for the sort of malignant polyp that can be excised endoscopically in one piece. These criteria must be strictly followed if the clinician decides upon a conservative approach. The decision must be made in consultation with an experienced histopathologist. In
tachycardia
future, computerised tomographic scanning, lymph-
imaging, and a more expert clinical assessment of mobility may reduce our reliance on indirect histological predictions. Until then patients with malignant colonic polyps who are treated conservatively will continue to run some risk of centrifugal metastasis after apparently successful polypectomy. node
tumour
within the
lung
activity. Some drugs in these
that result in increased
ventilatory
neuromuscular blocking patients without sedation; others are about unhappy paralysing conscious patients. Where there is cardiac or neurological disease, sedation is used dull the
centres use
physiological responses to stress, seen as and hypertension. In the neurosurgical
intensive-care unit, some sedatives have been shown to lower intracranial pressure and therefore improve cerebral perfusion.8 The ideal agent would sedate the patient with no effect on the ventilatory or cardiovascular systems. It would have no effect on the biodegradation of other drugs, and would itselfbe metabolised by pathways not dependent on normal renal, hepatic, or pulmonary function. Equally important, it would have a short elimination half-life. At present, no such drug exists. The drugs available for sedation are: Barbiturates
When given by continuous infusion these drugs have the disadvantages of direct myocardial depression and long durations of action. In primates they offer some protection against ischaemia, even if given up to an hour after the insult.9 In general, barbiturates lower the intracranial pressure, but the prolonged recovery is troublesome.
Sedation in the Intensive-care Unit IN the past ten months two intravenous hypnotic agents, etomidate and ’Althesin’ (alphaxalonealphadolone) have been essentially lost to intensivecare units in Britain. Etomidate, when given by longterm infusion, seriously hampers adrenal cortical function;’,2 and althesin has been withdrawn because of anaphylactoid reactions to the solvent.3 Their departure leaves a gap in the repertoire of drugs for sedation in intensive care. Why do patients in intensive-care units need sedation? Reports from former patients indicate that drugs are not always the best means of relieving distress:4°5 much anxiety can be averted by explanation of the medical and nursing procedures to be undertaken, combined with sympathetic care.Even so, many patients do need help from drugs. In a large multicentre study reported by Farina et al,7 40% of all patients received a sedative
agent,
usually
a
Benzodiazepines Diazepam is very widely used in intensive-care units.’"’" Despite its good safety record there is large interindividual variation in response, and effects can be long-lasting, especially after repeated doses (partly because one of the metabolites, desmethyldiazepam, is pharmacologically active). Midazolam, a water-soluble imidazole benzodiazepine, seems to have several advantages over diazepam. Potency is twice that of diazepam and onset of hypnosis is more rapid.12 The metabolites are inactive, which is an advantage if midazolam is to be given by continuous intravenous infusion. There is again a wide variation in the dose required to produce a given effect.l3 After bolus doses of midazolam and diazepam patients recover at about the same speed, 14, "but after midazolam the occasional critically ill patient takes more than 24 hours. as
Lorazepam has much the same pharmacological properties diazepam, but there are no active metabolites. In intensive
benzodiazepine. Despite adequate 8. Moss E, Gibson
JS, McDowall DG. The use of anaesthetic drugs to reduce ICP changes in head-injured patients. Acta Anaesth Belg 1980; 31: suppl 43-48. 9. Hoff JT, Smith AL, Hankinson HL, et al. Barbiturate protection from cerebral
Ledingham IMcA, Watt I. Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1983; i: 1270. 2. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 1984; 310: 1415-21 1.
3. Anon. ’Althesin’ discontinued. Lancet 1984; i: 694. 4. Henschell EO. The Guillain Barré syndrome. A personal experience.
Anesthesiology
1977; 47: 228-31. 5. Shovelton DS. Reflections on an intensive therapy unit. Br Med J 1979; i: 737-38. Nimmo WS, Macrae WA. Sedation and analgesia. In: Ledingham IMcA, Hanning CD, eds. Recent advances in critical care medicine 2. Edinburgh: Churchill Livingstone, 1983. 7. Farina ML, Levati A, Tognoni G. A multicentre study of ICU drug utilization. Intensive Care Med 1981, 7: 125-31.
6.
infarction
in primates. Stroke 1975; 6: 28. RA, Herraez FXV, Marcos RJ, et al. Drug use in an intensive care unit and its relation to survival. Intensive Care Med 1980; 6: 163-68. 11. Buchanan N, Cane RD. Drug utilization in a general intensive care unit. Intensive Care Med 1978; 4: 75-77. 12. Dundee JW, Samuel IO, Toner W, et al. Midazolam: a water soluble benzodiazepine. Studies in volunteers. Anaesthesia 1980; 35: 454-58. 13. Gamble JAS, Kawar P, Dundee J, et al. Evaluation of midazolam as an intravenous induction agent. Anaesthesia 1981; 36: 868-73. 14. Bergren L, Eriksson I, Mollenholt P. et al. Sedation for fibreoptic gastroscopy: a comparative study of midazolam and diazepam. Br J Anaesth 1983; 55: 289-96. 15. Whitwam JG, Al-Khudhain D, McCloy RF. Comparison of midazolam and diazepam in doses of comparable potency during gastroscopy. Br J Anaesth 1983; 55: 773-77.
10. Campos
embedded, fixed, sectioned, and examined.3 If the histologist identifies malignant change in a pedunculated adenoma, should conservative or radical
The Malignant Large-bowel Polyp— Conservative or Radical Treatment? AN adenomatous large-bowel polyp is a benign new growth with a potential for malignant change and centrifugal spread. The head of this type of polyp consists of a mass of neoplastic glandular tubules lined by columnar cells. The stalk, which may be a product of peristalsis, is composed of normal large-bowel mucosa and muscularis mucosae, with a central core of submucosal areolar tissue. Lymphatic tissue
accompanies the muscularis mucosae up to the head of the polyp, where it is found beneath the mucosa. An invasive adenocarcinoma is diagnosed when malignant change in the cells of the adenomatous head of the polyp is seen to extend through the muscularis into the submucosa, thus permitting mucosae lymphatic dissemination. When such a breach in the integrity of the muscularis mucosae is evident, the extent of replacement of the benign adenoma by carcinoma is important. A malignant polypoidal tumour with no residual benign adenomatous tissue must be diagnosed as a polypoidal adenocarcinoma. Some authorities recognise a premalignant stage of intramucosal carcinoma-in-situ, when potentially malignant changes in the adenomatous mucosa can be identified without any evidence of
a
breach in the
integrity of the muscularis mucosae.’1 Colonoscopy is-or should be-available in every district general hospital, since it facilitates excision biopsy of any pedunculated mucosal lesion by means of the diathermy snare.2 The polyp, together with its pedicle, must be retrieved after excision, correctly
surgery be advised?4 Clinical decisions must be based upon a reliable histological opinion about a correctly oriented section of the polyp and its pedicle.3 If the lesion shows no evidence of malignant breach of the muscularis mucosae, further surgery is not necessary. Polyps displaying so called carcinoma-insitu are benign.’ If the lesion is a polypoidal cancer with invasive carcinoma extending into the base of the pedicle, conventional large-bowel surgery is indicated. For the patient who is unfit or refuses major surgery local excision may be cautiously considered, provided that the muscularis propria is not penetrated by centrifugal spread of the cancer (if it is, or if the tumour is poorly differentiated, lymph node metastases can be anticipated in 12% of patients4). If the lesion is a true malignant polyp-a pedunculated adenoma with a breach in the muscularis mucosae by malignant change in the adenomatous mucosa-treatment is controversial. The crucial question is whether there is any risk of undetected extramural lymph-node metastases after complete and apparently successful endoscopic resection of such a polyp.4 A new paper from St Mark’s Hospital recommends conservative treatment of the malignant polyp provided that excision by endoscopic polypectomy is clinically complete, the specimen is correctly oriented, the carcinoma is not poorly differentiated, and the margin of the specimen is free from malignant invasion.3 Other papers emphasise a further requirement-absence of malignant lymphatic and venous invasion.4If all these criteria are satisfied, the mortality rate of a large-bowel resection (about 2%) may exceed the risk of lymph-node metastases.4 The possibility of such metastases cannot, however, be directly excluded by the St Mark’s criteria, and a review from the College of Physicians and Surgeons at Columbia University, New York, records transmural lymph-node metastases in 25% of 24 malignant colonic polyps after conventional colectomy.5 All the patients had previously undergone endoscopic polypectomy and at that time a margin of normal tissue had been identified histologically in the stalk. No residual cancer was identified in any patient at the polypectomy site after the subsequent colectomy.5 This means that a further operation was unnecessary in 75% of these patients but the other 25% had a Dukes C lesion at the time of radical surgery. The New York workers conclude that conventional large-bowel surgery is justified in patients with a malignant polyp after successful polypectomy, because radical excision is the of cure of a only treatment that offers any prospect Dukes C tumour of the large bowel.5 BC, Whiteway JE, Jones EA, Macrae FA, Williams CB. Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy. Gut
3. Morson 1. Shatney
CH, Lober PH, Gilbertson VA, Sosin H. The treatment of pedunculated adenomatous colorectal polyps with focal cancer. Surgery Gynecol Obstet 1974; 139: 845-50.
2. Editorial. Colonoscopy—essential service in 1311-12.
a
general hospital.
Lancet
1983; i;
1984; 25: 437-44. 4. De Cosse JJ. Malignant colorectal polyp. Gut 1984; 25: 433-36. 5. Colacchio TA, Forde KA, Scantlebury VP. Endoscopic polypectomy. Inadequate treatment for invasive colorectal cancer. Ann Surg 1981; 194: 704-07.
1388
It is difficult to argue convincingly in favour of radical surgery, perhaps with a permanent colostomy, when 75% of patients with a malignant large-bowel polyp do not require it, but we must avoid the temptation of capricious excision of large sessile colonic tumours, or piecemeal removal of large pedunculated lesions, with the colonoscope. There is a risk of transmural malignancy in these tumours, and they are best treated by transabdominal, transanal, or
ventilation in terms of tidal volume, minute volume, and blood-gases, some patients still "fight" the ventilator. This may be due purely to discomfort from the endotracheal tube, or to stimulation of receptors
transperineal excision, thus allowing full-thickness
to
excision of the wall of the diseased bowel.4 The St Mark’s criteria, although only indirect indices of transmural lymph-node metastases, seem to have stood the test of time for the sort of malignant polyp that can be excised endoscopically in one piece. These criteria must be strictly followed if the clinician decides upon a conservative approach. The decision must be made in consultation with an experienced histopathologist. In
tachycardia
future, computerised tomographic scanning, lymph-
imaging, and a more expert clinical assessment of mobility may reduce our reliance on indirect histological predictions. Until then patients with malignant colonic polyps who are treated conservatively will continue to run some risk of centrifugal metastasis after apparently successful polypectomy. node
tumour
within the
lung
activity. Some drugs in these
that result in increased
ventilatory
neuromuscular blocking patients without sedation; others are about unhappy paralysing conscious patients. Where there is cardiac or neurological disease, sedation is used dull the
centres use
physiological responses to stress, seen as and hypertension. In the neurosurgical
intensive-care unit, some sedatives have been shown to lower intracranial pressure and therefore improve cerebral perfusion.8 The ideal agent would sedate the patient with no effect on the ventilatory or cardiovascular systems. It would have no effect on the biodegradation of other drugs, and would itselfbe metabolised by pathways not dependent on normal renal, hepatic, or pulmonary function. Equally important, it would have a short elimination half-life. At present, no such drug exists. The drugs available for sedation are: Barbiturates
When given by continuous infusion these drugs have the disadvantages of direct myocardial depression and long durations of action. In primates they offer some protection against ischaemia, even if given up to an hour after the insult.9 In general, barbiturates lower the intracranial pressure, but the prolonged recovery is troublesome.
Sedation in the Intensive-care Unit IN the past ten months two intravenous hypnotic agents, etomidate and ’Althesin’ (alphaxalonealphadolone) have been essentially lost to intensivecare units in Britain. Etomidate, when given by longterm infusion, seriously hampers adrenal cortical function;’,2 and althesin has been withdrawn because of anaphylactoid reactions to the solvent.3 Their departure leaves a gap in the repertoire of drugs for sedation in intensive care. Why do patients in intensive-care units need sedation? Reports from former patients indicate that drugs are not always the best means of relieving distress:4°5 much anxiety can be averted by explanation of the medical and nursing procedures to be undertaken, combined with sympathetic care.Even so, many patients do need help from drugs. In a large multicentre study reported by Farina et al,7 40% of all patients received a sedative
agent,
usually
a
Benzodiazepines Diazepam is very widely used in intensive-care units.’"’" Despite its good safety record there is large interindividual variation in response, and effects can be long-lasting, especially after repeated doses (partly because one of the metabolites, desmethyldiazepam, is pharmacologically active). Midazolam, a water-soluble imidazole benzodiazepine, seems to have several advantages over diazepam. Potency is twice that of diazepam and onset of hypnosis is more rapid.12 The metabolites are inactive, which is an advantage if midazolam is to be given by continuous intravenous infusion. There is again a wide variation in the dose required to produce a given effect.l3 After bolus doses of midazolam and diazepam patients recover at about the same speed, 14, "but after midazolam the occasional critically ill patient takes more than 24 hours. as
Lorazepam has much the same pharmacological properties diazepam, but there are no active metabolites. In intensive
benzodiazepine. Despite adequate 8. Moss E, Gibson
JS, McDowall DG. The use of anaesthetic drugs to reduce ICP changes in head-injured patients. Acta Anaesth Belg 1980; 31: suppl 43-48. 9. Hoff JT, Smith AL, Hankinson HL, et al. Barbiturate protection from cerebral
Ledingham IMcA, Watt I. Influence of sedation on mortality in critically ill multiple trauma patients. Lancet 1983; i: 1270. 2. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 1984; 310: 1415-21 1.
3. Anon. ’Althesin’ discontinued. Lancet 1984; i: 694. 4. Henschell EO. The Guillain Barré syndrome. A personal experience.
Anesthesiology
1977; 47: 228-31. 5. Shovelton DS. Reflections on an intensive therapy unit. Br Med J 1979; i: 737-38. Nimmo WS, Macrae WA. Sedation and analgesia. In: Ledingham IMcA, Hanning CD, eds. Recent advances in critical care medicine 2. Edinburgh: Churchill Livingstone, 1983. 7. Farina ML, Levati A, Tognoni G. A multicentre study of ICU drug utilization. Intensive Care Med 1981, 7: 125-31.
6.
infarction
in primates. Stroke 1975; 6: 28. RA, Herraez FXV, Marcos RJ, et al. Drug use in an intensive care unit and its relation to survival. Intensive Care Med 1980; 6: 163-68. 11. Buchanan N, Cane RD. Drug utilization in a general intensive care unit. Intensive Care Med 1978; 4: 75-77. 12. Dundee JW, Samuel IO, Toner W, et al. Midazolam: a water soluble benzodiazepine. Studies in volunteers. Anaesthesia 1980; 35: 454-58. 13. Gamble JAS, Kawar P, Dundee J, et al. Evaluation of midazolam as an intravenous induction agent. Anaesthesia 1981; 36: 868-73. 14. Bergren L, Eriksson I, Mollenholt P. et al. Sedation for fibreoptic gastroscopy: a comparative study of midazolam and diazepam. Br J Anaesth 1983; 55: 289-96. 15. Whitwam JG, Al-Khudhain D, McCloy RF. Comparison of midazolam and diazepam in doses of comparable potency during gastroscopy. Br J Anaesth 1983; 55: 773-77.
10. Campos