277
different
and
the
ability to generate implantation metastases experimentally. Tumour cells adhere in greater quantities to braided sutures sutures
than to monofilaments such as steel. 23 If staples are safer than stitches, the risks are further reduced with sutureless anastomoses. Several compression devices are now available for clinical use24-27 and other sutureless techniques for establishing gastrointestinal anastomoses such as laser welding are under investigation.28 Akyol AM, McGregor JR, Galloway DJ, Murray G, George WD. Recurrence of colorectal cancer after sutured and stapled large bowel anastomoses. Br J Surg 1991; 78: 1297-300. 2. Reid JD, Robins RE, Atkinson KG. Pelvic recurrence after anterior resection and EEA stapling anastomosis for potentially curable carcinoma of the rectum. Am J Surg 1984; 147: 629-32. 3. Bisgaard C, Svanholm H, Jensen AS. Recurrent carcinoma after low anterior resection of the rectum using the EEA staple gùn. Acta Chir 1.
Scand 1986; 152: 157-60.
Phillips RK, Hittinger R, Blesovsky L, Fry JS, Fielding LP. Local recurrence following "curative" surgery for large bowel cancer, II: the rectum and rectosigmoid. Br J Surg 1984; 71: 17-20. 5. Rosen CB, Beart RW, Ilstrup DM. Local recurrence of rectal carcinoma after hand-sewn and stapled anastomoses. Dis Colon Rectum 1985; 28: 4.
305-09. 6. Amato A,
Pescatori M, Butti A. Local recurrence following abdominoperineal excision and anterior resection for rectal carcinoma.
Dis Colon Rectum 1991; 34: 317-22. Finlay IG, Meek DR, Gray HW, Duncan JG, McArdle CS. Incidence and detection of occult hepatic metastases in colorectal carcinoma. BMJ 1982; 284: 803-05. 8. McGregor JR. Clinical and experimental studies of gastro-intestinal anastomotic techniques. MD thesis, University of Glasgow, 1988. 9. Kanazawa K, Yamamoto T, Sato S. Experimental induction of colonic 7.
carcinomas in rats: analysis of factors influencing the incidence. Jpn J Exp Med 1975; 45: 439-56. 10. Roe R, Fermor B, Williamson RC. Proliferative instability and experimental carcinogenesis at colonic anastomoses. Gut 1987; 28: 808-15. 11. McGregor JR, Galloway DJ, Jarrett F, Brown IL, George WD. Anastomotic suture materials and experimental colorectal carcinogenesis. Dis Colon Rectum 1991; 34: 987-92. 12. McCue JL, Sheffield JP, Uff C, Phillips RK. Experimental carcinogenesis at sutured and sutureless colonic anastomoses. Br J Surg 1991; 78: 1492. 13. Bleiberg H, Mainguet P, Galand P, Chretien J, Dupont Mairesse N. Cell renewal in the human rectum: in vitro autoradiographic study on active ulcerative colitis. Gastroenterology 1970; 58: 851-55. 14. Deschner EE, Lipkin M. Proliferative patterns in colonic mucosa in familial polyposis. Cancer 1975; 35: 413-18. 15. Risio M, Coverlizza S, Candelaresi GL, et al. Late cytokinetic abnormalities in irradiated rectal mucosa. Int J Colorect Dis 1990; 5: 98-102. 16. O’Donnell AF, O’Connell PR, Royston D, et al. Suture technique affects perianastomotic colonic crypt cell production and tumour formation.
Br J Surg 1991; 78: 671-74. JL, Phillips RKS. Altered cell kinetics at colonic anastomoses may explain enhanced carcinogenesis. Br J Surg 1991; 78: 1497. 18. Vink M. Local recurrence of cancer in the large bowel: the role of implantation metastases and bowel disinfection. Br J Surg 1954; 41: 17. McCue
431-33. 19. Haverback CZ, Smith RR. Transplantation of tumor by suture thread and its prevention: an experimental study. Cancer 1959; 12: 1029-42. 20. Cohn I. Implantation in cancer of the colon. Surg Gynecol Obstet 1967; 124: 501-08. 21. Yu SK, Cohn I. Tumor implantation on colonic mucosa. Arch Surg 1968; 96: 956-58. 22. O’Dwyer P, Ravikumar TS, Steele G. Serum dependent variability in the adherence to tumour cells to surgical sutures. Br J Surg 1985; 72: 466-69. 23. McGregor JR, Galloway DJ, McCulloch P, George WD. Anastomotic suture materials and implantation metastasis: Br J Surg 1989; 76: 331-34. 24. Hardy TG, Pace WG, Maney JW, Katz AR, Kaganov AL. A biofragmentable ring for sutureless bowel anastomosis: Dis Colon Rectum 1985; 28: 484-90.
25.
26.
Eigler FW, Gross E. Die maschinelle Kompressionanastomose (AKA-2) an Colon und Rectum. Ergebnisse einer prospektiven klinischen Studie. Chirurg 1986; 57: 230-35. Malthaner RA, Hakki FZ, Saini N, Andrews BL, Harmon JW. Anastomotic compression button: a new mechanical device for
sutureless bowel anastomosis. Dis Colon Rectum 1990; 33: 291-97. 27. Thiede A, Schubert G, Kliman J, Schmidt L. Gastrointestinal anastomoses using the biofragmentable Valtrac ring. Chirurg 1991; 62: 819-24. 28. McCue JL, Phillips RK. Sutureless intestinal anastomoses. Br J Surg 1991; 78: 1291-96.
Specialist medical training and the EC: secrets are edged tools The General Medical Council (GMC) and other medical institutions in Britain face a charge of acting illegally in the way they deal with specialist registration; their instinctive reaction has been to go into the sort of secret huddle that got them into trouble in the first place. Stirred by the threat of legal action, the Department of Health (DoH) convened a meeting on June 22 of representatives, all sworn to secrecy, of some of the parties involved. The GMC, the British Medical Association, Royal Colleges, and Deans were duly represented but not two organisations that might have challenged the status quo-the Hospital Doctors’ Association and the Hospital Consultants and Specialists Association. The DoH had received legal advice that the GMC was breaking Community law by awarding European Community (EC) certificates-which should represent completion of specialist training-to people who had not fully completed their UK training, and that it would have a problem defending its present criteria for awarding the T annotation (T standing for trained) in the Medical Register because it would be difficult to argue "that a doctor with an EC certificate had not completed specialist training and should not receive a (T)". The UK system, said the lawyers, also breaches Community law by not acknowledging that those who hold EC specialist certificates from other member states are suitably trained for accreditation, consultant status, and recognition by insurance companies for reimbursement of private fees. Moreover, the Royal Colleges were warned that the advice they issue to advisory appointment committees was discriminatory "where it insists on accreditation [a purely UK non-statutory qualification] for consultant posts unless it also embraces the EC certificate". Under Community law, once doctors hold an EC specialist certificate, no additional training or qualification can be required before they are considered eligible for appointment as consultants. Those attending the meeting were told that "preserving the status quo or making minor presentational changes to the current system are not an
option".
The trouble in which UK medicine now finds itself can be traced to a series of meetings held in 1976, of which a key one-held behind closed doors of course-was convened at the then Department of
278
Health and Social Security in July of that year. This meeting was attended by the government’s Chief Medical Officers and representatives of the GMC and the Joint Committee on Higher Medical Training (JCHMT). Prof John Crofton, then chairman of the JCHMT, expressed a worry that a doctor returning from "the continent" with an EC specialist certificate might, through the courts, achieve the right to be acknowledged as a specialist and therefore to be appointed as a National Health Service consultant. However, the GMC representatives assured him that the Council had legal advice that it could issue a "certificate of specialist training" and not a "certificate of completion of specialist training", and indeed claimed that the apparent need to have the word "complete" in the text arose only because of "a mistake in the English translation of the directives". If the issues had been debated in a more open forum the problems of specialist registration might well have been resolved in a different way. Instead, they were discussed in private and largely by those who were not eager for change. And in many of the meetings there was such disparity between the content of the discussion and the decisions eventually reached that an observer could be forgiven for concluding that some of the participants were working to a different agenda from everybody else. The latest crisis means that Britain’s postgraduate medical education and hospital career structure could face a radical shake-up. This should be achieved by open debate that involves those who will perforce be regulated. There seem to be only two courses of action the UK can take to comply with European law. The GMC could award EC certificates to UK doctors only on completion of their specialist training, which at present is either on accreditation or when they are appointed as consultants; that would disadvantage those wanting to work in other EC countries because they would have to train for more years than their European counterparts to get the certificate. The alternative is a radical revision of the existing hospital career structure, with the aim of providing posts to which holders of an EC Specialist Certificate might aspire but which would not undermine the present status or quality of consultants in the National Health Service. But who is going to be the first to define the difference between a consultant and a specialist? The government is to form a working group to study these issues, which will report within 6 months.
Pyridinium crosslinks as markers of bone resorption There has been considerable interest lately in non-invasive metabolism. 1,2
methods
of
monitoring bone Radioisotopic techniques and quantitative histomorphometry give very precise
information on rates of bone turnover but are unsuitable for repeated monitoring of therapy or for
screening studies. Measurement of urinary pyridinium crosslinks provides an index of bone resorption rates; this approach offers substantial advantages over urinary hydroxyproline estimations, which are non-specific and insensitive. Pyridinium crosslinks are products of a unique series of reactions during the maturation of collagen fibrils that lead to the formation of pyridinoline (also known as hydroxylysyl pyridinoline) and deoxypyridinoline (or lysyl pyridinoline). Bone collagen contains both pyridinoline (Pyd) and deoxypyridinoline (Dpd) and release of these components from bone undergoing resorption constitutes the main source of both crosslinks in urine. The Pyd:Dpd ratio in urine is usually similar to that found in bone, and the values for the two crosslinks in urine are highly correlated. Pyridinoline has the wider
distribution, being prevalent in cartilage and tendon,3but, because of their slow turnover, these tissues make a negligible contribution to urinary Unlike output. hydroxyproline, pyridinium crosslinks are not metabolised in the body; this feature enables quantitation of bone resorption rates. Development of methods for measuring the crosslinks in urine4 led to their application in clinical studies. Excretion of crosslinks is greatly increased in patients with Paget’s disease, primary hyperparathyroidism, osteomalacia, and osteoporosis, and these assays are especially useful for monitoring therapy.9 The good correlations between pyridinium crosslink excretion and bone turnover rates measured by radioisotope methods10 or histomorphometryll provide direct validation of the urinary markers. The variable relations between urinary crosslinks and hydroxyproline may be explained by fluctuations in dietary control for hydroxyproline; pyridinium crosslinks are not susceptible to dietary influences. 12 Crosslink tissue
have been used to show increased bone associated with rheumatoid arthritis and resorption and to document the efficacy of diseaseosetoarthritis, The increased resorption modifying drugs.l3 associated with hyperthyroidism has likewise been confirmed, and this method may be useful for monitoring thyroxine treatment.14 Other promising areas include identification of bone metastases in breast cancer, 15 and monitoring of in tumour-associated antiosteolytic therapy hypercalcaemia.16 Excretion of the crosslinks in children is much higher than in adults,17 and these markers have considerable potential in assessing treatment of growth deficiencies. Some questions remain to be resolved concerning standardisation between laboratories and we need to know more about normal physiological variation. Crosslink excretion changes with age in adults,13,18 but the extent of variation over 24 h is uncertain.19,20 Excretion rate is usually higher at night. It seems best to measure them relative to creatinine on an early morning spot urine sample. measurements
different
and
the
ability to generate implantation metastases experimentally. Tumour cells adhere in greater quantities to braided sutures sutures
than to monofilaments such as steel. 23 If staples are safer than stitches, the risks are further reduced with sutureless anastomoses. Several compression devices are now available for clinical use24-27 and other sutureless techniques for establishing gastrointestinal anastomoses such as laser welding are under investigation.28 Akyol AM, McGregor JR, Galloway DJ, Murray G, George WD. Recurrence of colorectal cancer after sutured and stapled large bowel anastomoses. Br J Surg 1991; 78: 1297-300. 2. Reid JD, Robins RE, Atkinson KG. Pelvic recurrence after anterior resection and EEA stapling anastomosis for potentially curable carcinoma of the rectum. Am J Surg 1984; 147: 629-32. 3. Bisgaard C, Svanholm H, Jensen AS. Recurrent carcinoma after low anterior resection of the rectum using the EEA staple gùn. Acta Chir 1.
Scand 1986; 152: 157-60.
Phillips RK, Hittinger R, Blesovsky L, Fry JS, Fielding LP. Local recurrence following "curative" surgery for large bowel cancer, II: the rectum and rectosigmoid. Br J Surg 1984; 71: 17-20. 5. Rosen CB, Beart RW, Ilstrup DM. Local recurrence of rectal carcinoma after hand-sewn and stapled anastomoses. Dis Colon Rectum 1985; 28: 4.
305-09. 6. Amato A,
Pescatori M, Butti A. Local recurrence following abdominoperineal excision and anterior resection for rectal carcinoma.
Dis Colon Rectum 1991; 34: 317-22. Finlay IG, Meek DR, Gray HW, Duncan JG, McArdle CS. Incidence and detection of occult hepatic metastases in colorectal carcinoma. BMJ 1982; 284: 803-05. 8. McGregor JR. Clinical and experimental studies of gastro-intestinal anastomotic techniques. MD thesis, University of Glasgow, 1988. 9. Kanazawa K, Yamamoto T, Sato S. Experimental induction of colonic 7.
carcinomas in rats: analysis of factors influencing the incidence. Jpn J Exp Med 1975; 45: 439-56. 10. Roe R, Fermor B, Williamson RC. Proliferative instability and experimental carcinogenesis at colonic anastomoses. Gut 1987; 28: 808-15. 11. McGregor JR, Galloway DJ, Jarrett F, Brown IL, George WD. Anastomotic suture materials and experimental colorectal carcinogenesis. Dis Colon Rectum 1991; 34: 987-92. 12. McCue JL, Sheffield JP, Uff C, Phillips RK. Experimental carcinogenesis at sutured and sutureless colonic anastomoses. Br J Surg 1991; 78: 1492. 13. Bleiberg H, Mainguet P, Galand P, Chretien J, Dupont Mairesse N. Cell renewal in the human rectum: in vitro autoradiographic study on active ulcerative colitis. Gastroenterology 1970; 58: 851-55. 14. Deschner EE, Lipkin M. Proliferative patterns in colonic mucosa in familial polyposis. Cancer 1975; 35: 413-18. 15. Risio M, Coverlizza S, Candelaresi GL, et al. Late cytokinetic abnormalities in irradiated rectal mucosa. Int J Colorect Dis 1990; 5: 98-102. 16. O’Donnell AF, O’Connell PR, Royston D, et al. Suture technique affects perianastomotic colonic crypt cell production and tumour formation.
Br J Surg 1991; 78: 671-74. JL, Phillips RKS. Altered cell kinetics at colonic anastomoses may explain enhanced carcinogenesis. Br J Surg 1991; 78: 1497. 18. Vink M. Local recurrence of cancer in the large bowel: the role of implantation metastases and bowel disinfection. Br J Surg 1954; 41: 17. McCue
431-33. 19. Haverback CZ, Smith RR. Transplantation of tumor by suture thread and its prevention: an experimental study. Cancer 1959; 12: 1029-42. 20. Cohn I. Implantation in cancer of the colon. Surg Gynecol Obstet 1967; 124: 501-08. 21. Yu SK, Cohn I. Tumor implantation on colonic mucosa. Arch Surg 1968; 96: 956-58. 22. O’Dwyer P, Ravikumar TS, Steele G. Serum dependent variability in the adherence to tumour cells to surgical sutures. Br J Surg 1985; 72: 466-69. 23. McGregor JR, Galloway DJ, McCulloch P, George WD. Anastomotic suture materials and implantation metastasis: Br J Surg 1989; 76: 331-34. 24. Hardy TG, Pace WG, Maney JW, Katz AR, Kaganov AL. A biofragmentable ring for sutureless bowel anastomosis: Dis Colon Rectum 1985; 28: 484-90.
25.
26.
Eigler FW, Gross E. Die maschinelle Kompressionanastomose (AKA-2) an Colon und Rectum. Ergebnisse einer prospektiven klinischen Studie. Chirurg 1986; 57: 230-35. Malthaner RA, Hakki FZ, Saini N, Andrews BL, Harmon JW. Anastomotic compression button: a new mechanical device for
sutureless bowel anastomosis. Dis Colon Rectum 1990; 33: 291-97. 27. Thiede A, Schubert G, Kliman J, Schmidt L. Gastrointestinal anastomoses using the biofragmentable Valtrac ring. Chirurg 1991; 62: 819-24. 28. McCue JL, Phillips RK. Sutureless intestinal anastomoses. Br J Surg 1991; 78: 1291-96.
Specialist medical training and the EC: secrets are edged tools The General Medical Council (GMC) and other medical institutions in Britain face a charge of acting illegally in the way they deal with specialist registration; their instinctive reaction has been to go into the sort of secret huddle that got them into trouble in the first place. Stirred by the threat of legal action, the Department of Health (DoH) convened a meeting on June 22 of representatives, all sworn to secrecy, of some of the parties involved. The GMC, the British Medical Association, Royal Colleges, and Deans were duly represented but not two organisations that might have challenged the status quo-the Hospital Doctors’ Association and the Hospital Consultants and Specialists Association. The DoH had received legal advice that the GMC was breaking Community law by awarding European Community (EC) certificates-which should represent completion of specialist training-to people who had not fully completed their UK training, and that it would have a problem defending its present criteria for awarding the T annotation (T standing for trained) in the Medical Register because it would be difficult to argue "that a doctor with an EC certificate had not completed specialist training and should not receive a (T)". The UK system, said the lawyers, also breaches Community law by not acknowledging that those who hold EC specialist certificates from other member states are suitably trained for accreditation, consultant status, and recognition by insurance companies for reimbursement of private fees. Moreover, the Royal Colleges were warned that the advice they issue to advisory appointment committees was discriminatory "where it insists on accreditation [a purely UK non-statutory qualification] for consultant posts unless it also embraces the EC certificate". Under Community law, once doctors hold an EC specialist certificate, no additional training or qualification can be required before they are considered eligible for appointment as consultants. Those attending the meeting were told that "preserving the status quo or making minor presentational changes to the current system are not an
option".
The trouble in which UK medicine now finds itself can be traced to a series of meetings held in 1976, of which a key one-held behind closed doors of course-was convened at the then Department of
278
Health and Social Security in July of that year. This meeting was attended by the government’s Chief Medical Officers and representatives of the GMC and the Joint Committee on Higher Medical Training (JCHMT). Prof John Crofton, then chairman of the JCHMT, expressed a worry that a doctor returning from "the continent" with an EC specialist certificate might, through the courts, achieve the right to be acknowledged as a specialist and therefore to be appointed as a National Health Service consultant. However, the GMC representatives assured him that the Council had legal advice that it could issue a "certificate of specialist training" and not a "certificate of completion of specialist training", and indeed claimed that the apparent need to have the word "complete" in the text arose only because of "a mistake in the English translation of the directives". If the issues had been debated in a more open forum the problems of specialist registration might well have been resolved in a different way. Instead, they were discussed in private and largely by those who were not eager for change. And in many of the meetings there was such disparity between the content of the discussion and the decisions eventually reached that an observer could be forgiven for concluding that some of the participants were working to a different agenda from everybody else. The latest crisis means that Britain’s postgraduate medical education and hospital career structure could face a radical shake-up. This should be achieved by open debate that involves those who will perforce be regulated. There seem to be only two courses of action the UK can take to comply with European law. The GMC could award EC certificates to UK doctors only on completion of their specialist training, which at present is either on accreditation or when they are appointed as consultants; that would disadvantage those wanting to work in other EC countries because they would have to train for more years than their European counterparts to get the certificate. The alternative is a radical revision of the existing hospital career structure, with the aim of providing posts to which holders of an EC Specialist Certificate might aspire but which would not undermine the present status or quality of consultants in the National Health Service. But who is going to be the first to define the difference between a consultant and a specialist? The government is to form a working group to study these issues, which will report within 6 months.
Pyridinium crosslinks as markers of bone resorption There has been considerable interest lately in non-invasive metabolism. 1,2
methods
of
monitoring bone Radioisotopic techniques and quantitative histomorphometry give very precise
information on rates of bone turnover but are unsuitable for repeated monitoring of therapy or for
screening studies. Measurement of urinary pyridinium crosslinks provides an index of bone resorption rates; this approach offers substantial advantages over urinary hydroxyproline estimations, which are non-specific and insensitive. Pyridinium crosslinks are products of a unique series of reactions during the maturation of collagen fibrils that lead to the formation of pyridinoline (also known as hydroxylysyl pyridinoline) and deoxypyridinoline (or lysyl pyridinoline). Bone collagen contains both pyridinoline (Pyd) and deoxypyridinoline (Dpd) and release of these components from bone undergoing resorption constitutes the main source of both crosslinks in urine. The Pyd:Dpd ratio in urine is usually similar to that found in bone, and the values for the two crosslinks in urine are highly correlated. Pyridinoline has the wider
distribution, being prevalent in cartilage and tendon,3but, because of their slow turnover, these tissues make a negligible contribution to urinary Unlike output. hydroxyproline, pyridinium crosslinks are not metabolised in the body; this feature enables quantitation of bone resorption rates. Development of methods for measuring the crosslinks in urine4 led to their application in clinical studies. Excretion of crosslinks is greatly increased in patients with Paget’s disease, primary hyperparathyroidism, osteomalacia, and osteoporosis, and these assays are especially useful for monitoring therapy.9 The good correlations between pyridinium crosslink excretion and bone turnover rates measured by radioisotope methods10 or histomorphometryll provide direct validation of the urinary markers. The variable relations between urinary crosslinks and hydroxyproline may be explained by fluctuations in dietary control for hydroxyproline; pyridinium crosslinks are not susceptible to dietary influences. 12 Crosslink tissue
have been used to show increased bone associated with rheumatoid arthritis and resorption and to document the efficacy of diseaseosetoarthritis, The increased resorption modifying drugs.l3 associated with hyperthyroidism has likewise been confirmed, and this method may be useful for monitoring thyroxine treatment.14 Other promising areas include identification of bone metastases in breast cancer, 15 and monitoring of in tumour-associated antiosteolytic therapy hypercalcaemia.16 Excretion of the crosslinks in children is much higher than in adults,17 and these markers have considerable potential in assessing treatment of growth deficiencies. Some questions remain to be resolved concerning standardisation between laboratories and we need to know more about normal physiological variation. Crosslink excretion changes with age in adults,13,18 but the extent of variation over 24 h is uncertain.19,20 Excretion rate is usually higher at night. It seems best to measure them relative to creatinine on an early morning spot urine sample. measurements
