Surgical management of metastatic inguinal lymphadenopathy
http://www.100md.com
《英国医生杂志》
1 Department of Plastic and Reconstructive Surgery, Radcliffe Infirmary, Oxford OX2 6HE
Correspondence to: M C Swan marc.swan@surgery.oxford.ac.uk
Introduction
We searched the Cochrane Library and Medline online databases, using the terms "inguinal lymphadenectomy", "groin dissection", and "sentinel lymph node biopsy", combined with "melanoma", or "carcinoma" and either "vulva", "penis", or "anus". We reviewed abstracts and selected relevant articles.
Pathology
The lymphatic system is a physiological continuum, yet the inguinal lymph nodes are traditionally divided into two anatomical groups. The superficial inguinal nodes are found superficial to the fascia lata within the boundaries of the femoral triangle (fig 1). They receive afferent superficial lymphatics from the lower extremity, the scrotum, penis, vulva, clitoris, anus, and the infra-umbilical region of the anterior abdominal wall. The femoral triangle is bounded superiorly by the inguinal ligament, medially by adductor longus, and laterally by sartorius. The roof of the femoral triangle is formed by fascia lata, and the floor is comprised of the iliopsoas and pectineus muscles and contains the femoral neurovascular structures as they pass beneath the inguinal ligament.
Fig 1 Representation of the right groin, showing the landmarks of the femoral triangle
Deep to the fascia lata, medial to the femoral vein, reside six to eight deep inguinal nodes, including Cloquet's node, which is sited at the apex of the femoral canal. The deep nodes receive afferents from the superficial inguinal nodes and the deep lymphatic trunks associated with the femoral vessels, which in turn drain the popliteal nodes. The deep inguinal nodes drain into the external iliac nodes, which also receive direct afferents from the superficial inguinal group.
Clinical assessment
Outpatient pathological sampling of a palpable lymph node is performed by fine needle aspiration cytology. In the context of melanoma, adequate sampling is achieved in 89% of aspirations, with a subsequent sensitivity and specificity approaching 100%.6 Open biopsy of enlarged lymph nodes should be undertaken by specialist surgeons only, as an inappropriately placed incision may compromise subsequent surgery. Computed tomography or magnetic resonance imaging are undertaken to stage the disease accurately.
Prophylactic versus therapeutic inguinal lymphadenectomy
As a potential solution to the high morbidity associated with prophylactic inguinal lymphadenectomy, sentinel lymph node biopsy can be performed in order to identify those patients with micrometastatic nodal disease, therefore avoiding major surgery in patients without metastatic disease.
Theoretically, lymphatics from defined areas of the body follow a predetermined pattern of drainage, and consistently drain to a "sentinel" lymph node(s) in a nodal basin. The sentinel node will therefore be the first to contain metastatic tumour cells. If tumour cells are absent from the sentinel node, the remainder of the nodal basin is assumed to be tumour free.
On the day of surgery, technetium-99m radiolabelled nanocolloid (which has a half life of six hours) is injected at the site of the primary tumour or excision biopsy scar, and a lymphoscintogram is obtained that details the site and number of sentinel lymph nodes. At operation, blue dye is injected around the primary tumour or excision biopsy scar. The incision is made over the radioactive "hot spot" detected by the handheld gamma camera. The location of the sentinel node in the groin is determined by using the camera and by visualisation of blue dye in the node (fig 2). When this combined approach is used, 98% of sentinel nodes are successfully identified in our department—which corresponds favourably with the published literature.11
Fig 2 Intraoperative appearance of a left groin sentinel lymph node stained with blue dye
Sentinel lymph node biopsy has been studied most extensively in the context of malignant melanoma.12 The American Joint Committee on Cancer staging system for melanoma includes micrometastasis in the regional lymph nodes—sentinel lymph node biopsy positive.13 A recent report proposes a survival advantage for patients having lymphadenectomy for micrometastatic disease.14 However, the results of prospective randomised controlled trials dealing with this important issue are currently under way and are due to report in the near future.
Sentinel lymph node biopsy is now also being used to provide accurate staging information in other solid tumours, including squamous cell carcinoma of the vulva, penis, and anus.15 Experience of sentinel lymph node biopsy in these cancers is at an early stage, and large, multicentre, randomised controlled trials are required to define the role of the procedure in these and other solid tumours.16 w5 w6 However, sentinel lymph node biopsy may render prophylactic lymphadenectomy obsolete.
Surgical approach
No robust evidence exists for the optimal period for maintaining post-operative suction drainage. Some authorities advocate early drain removal at 24 hours after surgery, whereas others recommend removal once drainage falls beneath a specific threshold (30-50 ml over 24 hours)—which may take some weeks. In England, the mean inpatient stay is 12.8 days, although many surgeons advocate early discharge, often with suction drains in situ.1 Early ambulation is encouraged to minimise the risk of deep vein thrombosis, although mobilisation accelerates lymph flow from the lower extremity and may augment lymph drainage. Patients are unlikely to be fit to drive for at least four to six weeks after surgery.
Additional educational resources
Roberts DLL, Anstey AV, Barlow RJ, Cox NH, Newton Bishop JA, Corrie PG, et al. UK guidelines for the management of cutaneous melanoma. Br J Dermatol 2002;146: 7-17—guidelines for the management of malignant melanoma
www.netanatomy.com—an excellent free anatomy website which covers gross anatomy, radiographic anatomy, and cross sectional anatomy. The images are first class, and the format allows self testing
www.emedicine.com—this US based website provides up to date, peer reviewed information on topics across the whole of medicine including informative reviews on malignant melanoma, penile cancer, and vulval cancer
Information for patients
www.cancerhelp.org.uk—CancerHelp UK is a free information service about cancer and cancer care for people with cancer and their families provided by Cancer Research UK. The philosophy is that information about cancer should be freely available to all and written in a way that is easily understood. There are sections on individual cancers, treatments, and links to support organisations. The site is approved by the Plain English Campaign
http://cancerresearchuk.org/sunsmart—this website has activity ideas to help children learn about the sun, information on skin cancer, and practical tips on preventing sun damage
Ongoing research
www.cancerbacup.org.uk/cgi-bin/clinicaltrials/searchtrials.pl?d=26&t=&s=a&c=10&Submit=±search±—summary of ongoing trials of melanoma treatment, including further investigation into the role of sentinel lymph node biopsy
www.ncrn.org.uk/portfolio/summary.asp?DiseaseID=45&Status=34&type=0&GroupID=6—details of a trial evaluating chemotherapy for the treatment of locally advanced or metastatic or recurrent vulva cancer
www.cancerbacup.org.uk/cgi-bin/clinicaltrials/searchtrials.pl?d=1—information on current trials investigating the role of chemotherapy and radiation therapy in patients with anal cancer
Postoperative complications
Surgical management of inguinal lymph nodes forms a key element in the treatment algorithm for several malignancies. Clinicians should be aware of the indications for surgery, the high postoperative morbidity, and the need for further randomised controlled trials to ascertain the role of sentinel lymph node biopsy in the management of nodal disease.
Additional references w1-w16 are on bmj.com
Acknowledgements: We thank the patients who consented to involvement with this review, and Nick White from Oxford Medical Illustration for his assistance with the clinical photographs.
Contributors: MCS and DF wrote the commentary, which was critically revised by OCSC. OCSC is guarantor.
Funding: None.
Competing interests: MCS and OCSC are investigators for the Oxford Tisseel (Baxter Healthcare, Newbury, United Kingdom) trial; a prospective randomised controlled trial to determine whether fibrin sealant can reduce post-operative complications following axillary and inguinal lymphadenectomy. They receive no financial remuneration for their work.
Ethical approval: None required.
References
Office for National Statistics. Cancer registration statistics, England 2003. London: ONS, 2003.
Ornellas AA, Seixas AL, Marota A, Wisnescky A, Campos F, de Moraes JR. Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 1994;151: 1244-9.
Pecorelli S, Benedet JL, Creasman WT, Shepherd JH. FIGO staging of gynecologic cancer. 1994-1997 FIGO Committee on Gynecologic Oncology. International Federation of Gynecology and Obstetrics. Int J Gynaecol Obstet 1999;65: 243-9.
Roses DF, Harris MN, Hidalgo D, Valensi QJ, Dubin N. Primary melanoma thickness correlated with regional lymph node metastases. Arch Surg 1982;117: 921-3.
Guarischi A, Keane TJ, Elhakim T. Metastatic inguinal nodes from an unknown primary neoplasm. A review of 56 cases. Cancer 1987;59: 572-7.
Basler GC, Fader DJ, Yahanda A, Sondak VK, Johnson TM. The utility of fine needle aspiration in the diagnosis of melanoma metastatic to lymph nodes. J Am Acad Dermatol 1997;36: 403-8.
Van der Velden J, Ansink A. Primary groin irradiation vs primary groin surgery for early vulvar cancer. Cochrane Library, Issue 2, 2004. Chichester: John Wiley.
Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet 1998;351: 793-6.
Balch CM, Soong SJ, Bartolucci AA, Urist MM, Karakousis CP, Smith TJ, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg 1996;224: 255-63.
Roberts DL, Anstey AV, Barlow RJ, Cox NH, Newton Bishop JA, Corrie PG, et al. U.K. guidelines for the management of cutaneous melanoma. Br J Dermatol 2002;146: 7-17.
Hettiaratchy SP, Kang N, O'Toole G, Allan R, Cook MG, Powell BWEM. Sentinel lymph node biopsy in malignant melanoma: a series of 100 consecutive cases. Br J Plast Surg 2000;53: 559-62.
Cascinelli N, Belli F, Santinami M, Fait V, Testori A, Ruka W, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO melanoma program experience. Ann Surg Oncol 2000;7: 469-74.
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19: 3635-48.
Kretschmer L, Hilgers R, Mohrle M, Balda BR, Breuniger H, Konz B, et al. Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphanodectomy and early excision of their nodal disease. Eur J Cancer 2004;40: 212-8.
Gipponi M, Solari N, Di Somma FC, Bertoglio S, Cafiero F. New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: review of the literature and surgical perspectives. J Surg Oncol 2004;85: 171-9.
Moore RG, DePasquale SE, Steinhoff MM, Gajewski W, Steller M, Noto R, et al. Sentinel node identification and the ability to detect metastatic tumour to inguinal lymph nodes in squamous cell cancer of the vulva. Gynaecol Oncol 2003;89: 475-9.
Spratt J. Groin dissection. J Surg Oncol 2000;73: 243-62
Karakousis CP. Ilioinguinal lymph node dissection. Am J Surg 1983;141: 299-303.
Baronofsky ID. Technique of inguinal node dissection. Surgery 1948;24: 555-67.
Woodhall JP. Radical groin surgery with particular reference to postoperative healing. Surgery 1953;33: 886-95.
Tonouchi H, Ohmori Y, Kobayashi M, Konishi N, Tanaka K, Mohri Y, et al. Operative morbidity associated with groin dissections. Surg Today 2004;34: 413-8.
Zhang SH, Sood AK, Sorosky JI, Anderson B, Buller RE. Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva. Cancer 2000;89: 1520-5.
Paley PJ, Johnson PR, Adcock LL, Cosin JA, Chen MD, Fowler JM, et al. The effect of sartorius transposition on wound morbidity following inguinal-femoral lymphadenectomy. Gynecol Oncol 1997;64: 237-41.
Bland KI, Klamer TW, Polk HC Jr, Knutson CO. Isolated regional lymph node dissection: morbidity, mortality and economic considerations. Ann Surg 1981;193: 372-6.
Urist MM, Maddox WA, Kennedy JE, Balch CM. Patient risk factors and surgical morbidity after regional lymphadenectomy in 204 melanoma patients. Cancer 1983;51: 2152-6.(Marc C Swan, Royal Colleg)
Correspondence to: M C Swan marc.swan@surgery.oxford.ac.uk
Introduction
We searched the Cochrane Library and Medline online databases, using the terms "inguinal lymphadenectomy", "groin dissection", and "sentinel lymph node biopsy", combined with "melanoma", or "carcinoma" and either "vulva", "penis", or "anus". We reviewed abstracts and selected relevant articles.
Pathology
The lymphatic system is a physiological continuum, yet the inguinal lymph nodes are traditionally divided into two anatomical groups. The superficial inguinal nodes are found superficial to the fascia lata within the boundaries of the femoral triangle (fig 1). They receive afferent superficial lymphatics from the lower extremity, the scrotum, penis, vulva, clitoris, anus, and the infra-umbilical region of the anterior abdominal wall. The femoral triangle is bounded superiorly by the inguinal ligament, medially by adductor longus, and laterally by sartorius. The roof of the femoral triangle is formed by fascia lata, and the floor is comprised of the iliopsoas and pectineus muscles and contains the femoral neurovascular structures as they pass beneath the inguinal ligament.
Fig 1 Representation of the right groin, showing the landmarks of the femoral triangle
Deep to the fascia lata, medial to the femoral vein, reside six to eight deep inguinal nodes, including Cloquet's node, which is sited at the apex of the femoral canal. The deep nodes receive afferents from the superficial inguinal nodes and the deep lymphatic trunks associated with the femoral vessels, which in turn drain the popliteal nodes. The deep inguinal nodes drain into the external iliac nodes, which also receive direct afferents from the superficial inguinal group.
Clinical assessment
Outpatient pathological sampling of a palpable lymph node is performed by fine needle aspiration cytology. In the context of melanoma, adequate sampling is achieved in 89% of aspirations, with a subsequent sensitivity and specificity approaching 100%.6 Open biopsy of enlarged lymph nodes should be undertaken by specialist surgeons only, as an inappropriately placed incision may compromise subsequent surgery. Computed tomography or magnetic resonance imaging are undertaken to stage the disease accurately.
Prophylactic versus therapeutic inguinal lymphadenectomy
As a potential solution to the high morbidity associated with prophylactic inguinal lymphadenectomy, sentinel lymph node biopsy can be performed in order to identify those patients with micrometastatic nodal disease, therefore avoiding major surgery in patients without metastatic disease.
Theoretically, lymphatics from defined areas of the body follow a predetermined pattern of drainage, and consistently drain to a "sentinel" lymph node(s) in a nodal basin. The sentinel node will therefore be the first to contain metastatic tumour cells. If tumour cells are absent from the sentinel node, the remainder of the nodal basin is assumed to be tumour free.
On the day of surgery, technetium-99m radiolabelled nanocolloid (which has a half life of six hours) is injected at the site of the primary tumour or excision biopsy scar, and a lymphoscintogram is obtained that details the site and number of sentinel lymph nodes. At operation, blue dye is injected around the primary tumour or excision biopsy scar. The incision is made over the radioactive "hot spot" detected by the handheld gamma camera. The location of the sentinel node in the groin is determined by using the camera and by visualisation of blue dye in the node (fig 2). When this combined approach is used, 98% of sentinel nodes are successfully identified in our department—which corresponds favourably with the published literature.11
Fig 2 Intraoperative appearance of a left groin sentinel lymph node stained with blue dye
Sentinel lymph node biopsy has been studied most extensively in the context of malignant melanoma.12 The American Joint Committee on Cancer staging system for melanoma includes micrometastasis in the regional lymph nodes—sentinel lymph node biopsy positive.13 A recent report proposes a survival advantage for patients having lymphadenectomy for micrometastatic disease.14 However, the results of prospective randomised controlled trials dealing with this important issue are currently under way and are due to report in the near future.
Sentinel lymph node biopsy is now also being used to provide accurate staging information in other solid tumours, including squamous cell carcinoma of the vulva, penis, and anus.15 Experience of sentinel lymph node biopsy in these cancers is at an early stage, and large, multicentre, randomised controlled trials are required to define the role of the procedure in these and other solid tumours.16 w5 w6 However, sentinel lymph node biopsy may render prophylactic lymphadenectomy obsolete.
Surgical approach
No robust evidence exists for the optimal period for maintaining post-operative suction drainage. Some authorities advocate early drain removal at 24 hours after surgery, whereas others recommend removal once drainage falls beneath a specific threshold (30-50 ml over 24 hours)—which may take some weeks. In England, the mean inpatient stay is 12.8 days, although many surgeons advocate early discharge, often with suction drains in situ.1 Early ambulation is encouraged to minimise the risk of deep vein thrombosis, although mobilisation accelerates lymph flow from the lower extremity and may augment lymph drainage. Patients are unlikely to be fit to drive for at least four to six weeks after surgery.
Additional educational resources
Roberts DLL, Anstey AV, Barlow RJ, Cox NH, Newton Bishop JA, Corrie PG, et al. UK guidelines for the management of cutaneous melanoma. Br J Dermatol 2002;146: 7-17—guidelines for the management of malignant melanoma
www.netanatomy.com—an excellent free anatomy website which covers gross anatomy, radiographic anatomy, and cross sectional anatomy. The images are first class, and the format allows self testing
www.emedicine.com—this US based website provides up to date, peer reviewed information on topics across the whole of medicine including informative reviews on malignant melanoma, penile cancer, and vulval cancer
Information for patients
www.cancerhelp.org.uk—CancerHelp UK is a free information service about cancer and cancer care for people with cancer and their families provided by Cancer Research UK. The philosophy is that information about cancer should be freely available to all and written in a way that is easily understood. There are sections on individual cancers, treatments, and links to support organisations. The site is approved by the Plain English Campaign
http://cancerresearchuk.org/sunsmart—this website has activity ideas to help children learn about the sun, information on skin cancer, and practical tips on preventing sun damage
Ongoing research
www.cancerbacup.org.uk/cgi-bin/clinicaltrials/searchtrials.pl?d=26&t=&s=a&c=10&Submit=±search±—summary of ongoing trials of melanoma treatment, including further investigation into the role of sentinel lymph node biopsy
www.ncrn.org.uk/portfolio/summary.asp?DiseaseID=45&Status=34&type=0&GroupID=6—details of a trial evaluating chemotherapy for the treatment of locally advanced or metastatic or recurrent vulva cancer
www.cancerbacup.org.uk/cgi-bin/clinicaltrials/searchtrials.pl?d=1—information on current trials investigating the role of chemotherapy and radiation therapy in patients with anal cancer
Postoperative complications
Surgical management of inguinal lymph nodes forms a key element in the treatment algorithm for several malignancies. Clinicians should be aware of the indications for surgery, the high postoperative morbidity, and the need for further randomised controlled trials to ascertain the role of sentinel lymph node biopsy in the management of nodal disease.
Additional references w1-w16 are on bmj.com
Acknowledgements: We thank the patients who consented to involvement with this review, and Nick White from Oxford Medical Illustration for his assistance with the clinical photographs.
Contributors: MCS and DF wrote the commentary, which was critically revised by OCSC. OCSC is guarantor.
Funding: None.
Competing interests: MCS and OCSC are investigators for the Oxford Tisseel (Baxter Healthcare, Newbury, United Kingdom) trial; a prospective randomised controlled trial to determine whether fibrin sealant can reduce post-operative complications following axillary and inguinal lymphadenectomy. They receive no financial remuneration for their work.
Ethical approval: None required.
References
Office for National Statistics. Cancer registration statistics, England 2003. London: ONS, 2003.
Ornellas AA, Seixas AL, Marota A, Wisnescky A, Campos F, de Moraes JR. Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 1994;151: 1244-9.
Pecorelli S, Benedet JL, Creasman WT, Shepherd JH. FIGO staging of gynecologic cancer. 1994-1997 FIGO Committee on Gynecologic Oncology. International Federation of Gynecology and Obstetrics. Int J Gynaecol Obstet 1999;65: 243-9.
Roses DF, Harris MN, Hidalgo D, Valensi QJ, Dubin N. Primary melanoma thickness correlated with regional lymph node metastases. Arch Surg 1982;117: 921-3.
Guarischi A, Keane TJ, Elhakim T. Metastatic inguinal nodes from an unknown primary neoplasm. A review of 56 cases. Cancer 1987;59: 572-7.
Basler GC, Fader DJ, Yahanda A, Sondak VK, Johnson TM. The utility of fine needle aspiration in the diagnosis of melanoma metastatic to lymph nodes. J Am Acad Dermatol 1997;36: 403-8.
Van der Velden J, Ansink A. Primary groin irradiation vs primary groin surgery for early vulvar cancer. Cochrane Library, Issue 2, 2004. Chichester: John Wiley.
Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet 1998;351: 793-6.
Balch CM, Soong SJ, Bartolucci AA, Urist MM, Karakousis CP, Smith TJ, et al. Efficacy of an elective regional lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg 1996;224: 255-63.
Roberts DL, Anstey AV, Barlow RJ, Cox NH, Newton Bishop JA, Corrie PG, et al. U.K. guidelines for the management of cutaneous melanoma. Br J Dermatol 2002;146: 7-17.
Hettiaratchy SP, Kang N, O'Toole G, Allan R, Cook MG, Powell BWEM. Sentinel lymph node biopsy in malignant melanoma: a series of 100 consecutive cases. Br J Plast Surg 2000;53: 559-62.
Cascinelli N, Belli F, Santinami M, Fait V, Testori A, Ruka W, et al. Sentinel lymph node biopsy in cutaneous melanoma: the WHO melanoma program experience. Ann Surg Oncol 2000;7: 469-74.
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 2001;19: 3635-48.
Kretschmer L, Hilgers R, Mohrle M, Balda BR, Breuniger H, Konz B, et al. Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphanodectomy and early excision of their nodal disease. Eur J Cancer 2004;40: 212-8.
Gipponi M, Solari N, Di Somma FC, Bertoglio S, Cafiero F. New fields of application of the sentinel lymph node biopsy in the pathologic staging of solid neoplasms: review of the literature and surgical perspectives. J Surg Oncol 2004;85: 171-9.
Moore RG, DePasquale SE, Steinhoff MM, Gajewski W, Steller M, Noto R, et al. Sentinel node identification and the ability to detect metastatic tumour to inguinal lymph nodes in squamous cell cancer of the vulva. Gynaecol Oncol 2003;89: 475-9.
Spratt J. Groin dissection. J Surg Oncol 2000;73: 243-62
Karakousis CP. Ilioinguinal lymph node dissection. Am J Surg 1983;141: 299-303.
Baronofsky ID. Technique of inguinal node dissection. Surgery 1948;24: 555-67.
Woodhall JP. Radical groin surgery with particular reference to postoperative healing. Surgery 1953;33: 886-95.
Tonouchi H, Ohmori Y, Kobayashi M, Konishi N, Tanaka K, Mohri Y, et al. Operative morbidity associated with groin dissections. Surg Today 2004;34: 413-8.
Zhang SH, Sood AK, Sorosky JI, Anderson B, Buller RE. Preservation of the saphenous vein during inguinal lymphadenectomy decreases morbidity in patients with carcinoma of the vulva. Cancer 2000;89: 1520-5.
Paley PJ, Johnson PR, Adcock LL, Cosin JA, Chen MD, Fowler JM, et al. The effect of sartorius transposition on wound morbidity following inguinal-femoral lymphadenectomy. Gynecol Oncol 1997;64: 237-41.
Bland KI, Klamer TW, Polk HC Jr, Knutson CO. Isolated regional lymph node dissection: morbidity, mortality and economic considerations. Ann Surg 1981;193: 372-6.
Urist MM, Maddox WA, Kennedy JE, Balch CM. Patient risk factors and surgical morbidity after regional lymphadenectomy in 204 melanoma patients. Cancer 1983;51: 2152-6.(Marc C Swan, Royal Colleg)