Dec 8, 1988 - Ann Surg 1984;200:685-90. 13 Bradpiece HA, Benjamin IS, Halevy A, Blumgart LH. Major hepatic resection for colorectal livermetastases. BrJ.
Annals of the Royal College of Surgeons of England (1989) vol. 71
Surgery for recurrent is it worthwhile?
colorectal carcinoma
S G POLLARD BSc FRCS Research Registrar
R MACFARLANE
MA FRCS
Surgical Registrar
W G EVERETT MCh FRCS Consultant Surgeon Department of Surgery, Addenbrooke's Hospital, Cambridge Key words: RECURRENT COLORECTAL CARCINOMA; CURATIVE RESECTION; PALLIATIVE RESECTION; PARTIAL HEPATECTOMY; TUMOUR MARKERS
Summary A series of 45 patients undergoing a second operation for recurrent colorectal cancer is reported. The majority developed recurrence within 2years of their initial surgery. Despite regular follow-up, in only 27% of patients submitted to further surgery was the recurrence detected at routine review, and only three of these were asymptomatic at the time of diagnosis. A potentially curative second procedure was undertaken in 47% of cases, with a 2-year survival of 71% and a 5-year survival of 29%. Of those undergoing palliative surgery, this was worthwhile in 64%, providing palliation for more than 6 months. Mean survival following a palliative procedure was 10 months. Palliation was better, and operative mortality lower, when the bulk of the tumour could be removed. In obstructed patients the outcome following palliative resection was better than for palliative bypass procedures. Following resection of metastases there is the prospect of long-term survival, but it is difficult to predict those patients who will do well. Introduction About 24 000 new cases of colorectal carcinoma occur annually in England and Wales (1). At the time of presentation 25% will have hepatic metastases (2); others will have either advanced disease or be unfit for major surgery, leaving 55-70% to undergo a resection for cure (3-6). Unfortunately, within 5 years 23-29% of this group will have developed recurrent disease, with two-thirds of these being within 2 years of operation (4,7-10). Overall, local recurrence will develop in 1025% of cases (3,11-12), and hepatic metastases in 4070% (13). Much has been written on factors influencing the development of recurrence, the benefits of routine followup, and the value of further surgery for attempted cure or
Correspondence to: Mr S G Pollard, Department of Surgery, Level 9, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ
palliation. In an attempt to evaluate the role of surgery in these patients, a retrospective review of a personal series of 45 cases over a period of 18 years is reported.
Patients and methods The hospital records of 45 patients undergoing surgery for recurrent colorectal cancer between 1969 and 1987 have been reviewed. All were under the care of a single surgeon (WGE). During this period 990 new cases of colorectal cancer were seen, and 927 underwent resection. All patients were seen at 3 monthly intervals for the first 2 years postoperatively, 6 monthly for 5 years, and annually thereafter. Follow-up consisted of clinical examination with sigmoidoscopy at each visit, and more recently tumour marker estimations. Barium enema was performed every 5 years or if clinically indicated. Patients who underwent examination under anaesthetic, and/or simple biopsy (without exploration) have been excluded from the study. During the study period 535 patients (58%) developed recurrence, the majority of these were managed nonoperatively. Forty-five patients underwent further surgery. The group consisted of 23 males and 22 females with a mean age of 61 years (range 28-85 years) at the time of
their first operation. In 32 the tumour occurred in the sigmoid; in 13 it was more proximal. Five patients were noted to have liver secondaries at the time of their first operation and were electively re-explored with a view to resection. The remaining 40 patients were attending regular follow-up when they developed their recurrence. Five patients, known to have residual tumour at their first laparotomy presented as emergencies with obstruction. Of the remainder (35), 8 presented as emergencies, 15 had early or urgent clinic appointments, and 12 were detected at routine clinical follow-up, of which 3 were asymptomatic-two with palpable masses and one with rising tumour markers. rectum or
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TABLE I Outcome in patients undergoing second operative procedure. Palliation and survival figures do not include operative deaths or surviving patients. All figures are in months, shown as mean and (range) if more than two patients in the group
Site
Procedure
Liver
Bypass
(n=9)
(n=2)
Resection (n=5) Cannulation (n=1) Inoperable
Interval from first operation
Operative deaths
Survivors to date
Palliation
Survival
1
0
15
17
13 (3-19)
1
3
26
30
22
0
0
12
29
5
0
0
0
8
18 (4-43)
1
0
3.5 (0-7)
4.5 (1-9)
22 (7-44)
0
3
14 (6-24)
18 (6-31)
1
0
0
1
0
2
5,76
9,80
1
0
0
3
27 (12-84)
1
2
11 (2-29)t
15 (3-38)t
15
0
0
0
3
30,32
0
0
2,11
4,17
38
0
0
27
48
8,20
(n=1) Gut
Pelvis
Bypass (n=6) Resection (n=9) Inoperable (n=2) Resection (n=4) Inoperable (n=2) Resection
(n= 10)
(n=9)
(n= 17)
Abdominal wall (n=6)
CNS
Inoperable (n= 1) Resection
(n=2)
(n=2)
Lung (n= 1)
Resection
3,22 25 (15-38)
8,14
(n= 1)
* Includes one death from unrelated causes after 6 months t Includes four patients undergoing a third operation
The diagnosis of recurrence was initially made on clinical grounds in all but one patient who had rising tumour markers. The patients have been grouped according to the major site of recurrence and each group will be considered in turn. The interval between the first and second operations is shown in Table I.
one. In three there was a solitary deposit, in one there were two metastases in the left lateral segment, and in the fifth there were multiple secondaries confined to the right lobe of the liver. In two patients a palliative hepaticojejunostomy was performed for obstructive jaundice secondary to malignant infiltration of nodes at the porta hepatis.
I HEPATIC DISEASE
2 GASTROINTESTINAL TRACT
Nine patients underwent surgery for liver metastases. Of these, seven patients underwent laparotomy with the intention of performing a segmental resection of the liver for parenchymal deposits. In five patients the metastasis was noted at the time of the original laparotomy, and elective resection was undertaken 3-13 months later. The other two patients subsequently developed overt liver metastases, and presented with hepatic pain. In all patients, liver scans, ultrasound, coeliac angiography, and, more recently, CT scanning were performed to exclude metastases in both lobes or extrahepatic deposits. Despite this, two patients were found to have widespread metastatic disease at laparotomy. In one asymptomatic patient no procedure was undertaken; in the other, a patient with severe hepatic pain, the hepatic artery was ligated, and a gastroepiploic vein cannulated for infusion of cytotoxic drugs. In five patients a potentially curative liver resection was undertaken-a right hemihepatectomy in four (extended to include the caudate lobe in one), and a left lateral segmentectomy in
Two patients developed recurrent symptomatic disease involving the stomach and adjacent structures following resection of locally invasive carcinomas at the splenic flexure. In both the recurrence was resected. In one this necessitated en bloc removal of the spleen, tail of pancreas, proximal jejunum and left kidney; in the other a partial gastrectomy with resection of the overlying abdominal wall was undertaken. The former patient received adjuvant radiotherapy. Both were considered potentially curative procedures. Twelve patients with intestinal obstruction underwent semi-elective laparotomy for secondary deposits involving the small intestine. In four a potentially curative small bowel resection was undertaken, combined with a partial cystectomy in one, and resection of adjacent abdominal wall in another. Of the remaining patients, one had a palliative resection, five a palliative bypass, and in two no procedure was possible. Three patients with colonic recurrence underwent laparotomy-two patients with obstructive symptoms
Surgery for recurrent colorectal carcinoma underwent palliative resection and palliative bypass. In one the recurrence was detected following investigation for rising tumour markers and a potentially curative resection was performed. 3 ABDOMINAL WALL AND PERINEUM
Six patients suffered recurrence confined to the abdominal wall. In two patients a painful perineal mass following abdominoperineal excision of the rectum was excised. In four patients the recurrence involved the anterior abdominal wall, presenting as a painful mass. In two patients this was related to the laparotomy scar and both underwent excision of the deposit, combined with radiotherapy in one. In the other two patients there was deep seated intraperitoneal recurrence with invasion of the abdominal wall which proved too extensive to resect. 4 PELVIS
Ten patients were explored for pelvic recurrence; four subsequently underwent a third procedure. In eight patients the pelvic recurrence followed anterior resection of the rectum, presenting as obstruction due to involvement of the rectum in six, and accompanied by rectovaginal fistula in one. One patient presented with vaginal bleeding, and one with pelvic pain. In seven of these eight patients, the recurrence was excised from the side walls of the pelvis. In six patients this necessitated abdominoperineal excision of the rectum, combined with resection of adherent small bowel in three, with an additional partial cystectomy in one. One of these underwent a further laparotomy and palliative bypass 2 years later for obstruction from further recurrence. In one patient hysterectomy alone was performed, combined with 5-fluorouracil and radiotherapy. Six months later this patient underwent excision of a recurrence in the abdominal scar. One case was inoperable. In three of the eight patients it was considered that all macroscopic growth had been removed. In two cases, pelvic recurrence followed abdominoperineal excision, and presented with perineal pain or urinary incontinence. Both underwent resection of the recurrence together with the uterus in one, and the uterus and bladder in the other. Both patients subsequently underwent third operations. In one, laparotomy with division of adhesions was performed 1 month postoperatively for obstruction; in the other a cordotomy for intractable pain was required after 8 months. 5 OTHER
In one patient, two pulmonary metastases causing haemoptysis were resected, and he subsequently received chemotherapy and radiotherapy. In a second patient an extrathecal metastasis in the thoracic spine causing paraplegia was removed, and in a third patient with headaches, a metastasis was excised from the posterior cranial fossa.
Results All patients have been reviewed regularly and no patient has defaulted from follow-up. The results are summarised in Table I. We have defined worthwhile palliation as hospital-independent existence for at least 6 months, without frequent readmissions or troublesome symptoms, and not requiring regular opiate analgesia.
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I LIVER DISEASE
Five patients underwent hepatic resection. Both those with multiple metastases are clinically disease-free after 3 and 18 years. The third survivor has developed cerebral secondaries. One patient died postoperatively from a cerebrovascular accident, and the fifth died of metastases after 2.5 years. Of those patients who underwent hepaticojejunostomy, one died postoperatively from pulmonary embolus, the other remained well and free from jaundice for a further 15 months, dying of liver metastases 17 months later. 2 GASTROINTESTINAL TRACT
The two patients who underwent gastrectomy had palliation for 7 and 18 months before developing inoperable recurrence. Four patients had potentially curative small bowel resections. Two remain alive and well after 7 and 12 years. One patient died of unrelated causes after 6 months, and the fourth patient died of cerebral metastases after 2.5 years. Six patients underwent palliative resection or bypass. Three patients died within I month of surgery; the remainder received palliation of 2, 7 and 10 months. One patient underwent potentially curative resection of a colonic secondary and is well 2 years later. The patients undergoing palliative bypass and palliative resection of colonic recurrence survived 6 and 20 months respectively. 3 ABDOMINAL WALL AND PERINEUM
The two patients with resected perineal recurrences have survived for 11 and 15 years. The two patients with operable recurrence in the abdominal wall survived for 5 months and 6.5 years before suffering further local recurrence from which they died. 4 PELVIS
The two patients undergoing pelvic clearance for recurrence following abdominoperineal excision of the rectum had palliation for 8 and 13 months before developing symptoms of further pelvic recurrence. The former patient underwent a cordotomy for the pain, from which she derived little benefit. They survived for 12 and 16 months. Six patients survived pelvic clearance of recurrent tumour following anterior resection. Two remain alive and disease free after 2.5 and 3 years, and the others were restored to reasonable health before developing symptoms of further pelvic recurrence from which they died. One of these had a scar recurrence excised during this period, and a second underwent palliative bypass for obstruction after 23 months, surviving for a further 15 months. 5 OTHER
The patient undergoing lung resection developed further symptomatic pulmonary metastases after 27 months, and survived for 4 years. The patient with an extrathecal deposit enjoyed complete resolution of his spasticity, weakness and incontinence, dying of liver metastases 17 months later. Finally, the patient who had a secondary removed from the posterior fossa survived for 4 months, dying from further cerebral deposits.
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In this series there were six perioperative deaths, two occurring in patients in whom no procedure was possible. Complications were observed in six patients. One patient developed a subphrenic collection after hepatic resection, and a second developed an empyema after lung resection. There were two cases of deep vein thrombosis, one faecal fistula, and one case of retention of urine. The degree of differentiation of the primary tumour was recorded in all patients and all but two of the 45 were moderately or well differentiated. The original Dukes' stage was recorded in all cases. Of those with resectable liver metastases none showed lymph node metastases in their original specimen, although the two inoperable cases and the two cases undergoing hepaticojejunostomy all had lymph node involvement. Of the patients undergoing potentially curative resection of gastrointestinal recurrence, all but one was Dukes' stage B, and all those surviving were Dukes' B. In those patients where only a bypass or palliative resection could be performed, three of the seven were originally Dukes' stage C. Patients undergoing resection of pelvic recurrence were all Dukes' stage B except for one who was stage C, and all survivors were stage B. Overall, 21 of the 45 patients underwent surgery which was considered at the time to be potentially curative, although 10 of these patients subsequently developed further tumour recurrence. Of the 21 patients, 15 have survived for 2 years, and six of these have survived for 5 years. Five are currently alive after periods of 2-5 years (one with overt recurrence). Of the 10 developing further recurrence, 9 (90%) were palliated for more than 6 months, 7 (70%) for more than 1 year, and 4 (40%) for more than 2 years (mean period 20 months). Their average survival was 29 months. Although not cured, patients who underwent very extensive debulking of tumour recurrence fared considerably better than patients in whom only a limited palliative procedure was attempted. The remaining 24 patients underwent operation but were known at the time to be incurable. In six patients no procedure was undertaken, and there were three operative deaths. Of the 15 survivors, 9 had palliation for more than 6 months, 4 had palliation for more than 1 year, and one had palliation for more than 2 years. The mean survival in this group was 10 months, with a mean palliation of 8 months. Patients undergoing palliative resection for intestinal obstruction fared better than those undergoing palliative bypass.
Discussion Despite the fact that approximately two-thirds of patients undergo potentially curative resection of colorectal carcinoma, in only about 50% is a cure achieved (14). The reason for this is usually failure to appreciate the extent of the disease, or failure to eradicate the primary tumour. Operative technique is important, with local recurrence rates varying from less than 5% to over 20% between different surgeons (3). Wherever possible, histological confirmation of recurrence must be obtained, because many benign conditions such as anastomotic stricture, adhesions, chronic sepsis, or hepatic cysts may mimic recurrent disease (15).
Opinions vary regarding the value of rigorous followup in the detection of recurrence or of a second primary colonic neoplasm. About 70-75% of local recurrence follows excision of rectal or sigmoid lesions (5,16), and most of these will occur within 2 years of surgery (5,8,9,14). Assessment should be most rigorous during this period. A small proportion of patients, however, will develop recurrence more than 10 years after treatment of their primary (17), suggesting that if patients are to be followed up, it should be for life. In a review of 4884 patients from St Mark's Hospital (18), Heald et al. were able to demonstrate earlier detection and improved prognosis for patients attending outpatient clinic at the time of relapse, than for those who had been discharged. No less than 69% were Dukes' stage A or B compared with 41 % for non-attenders, and the percentage of inoperable recurrences were 9% and 47% respectively. This, however, has not been the experience of others (4). A prospective study of 168 patients was undertaken at the Mayo Clinic following apparently curative resection for Dukes' stage B or C colorectal cancer (7). Patients were seen at least every 15 weeks for up to 4 years and screening involved a minimum of thorough clinical and biochemical assessment, including tumour markers, together with annual barium enema and liver scan. Despite this rigorous follow-up, 85% of patients had symptoms before or at the time of detection of their recurrence. Other series have reported similar findings (4,8,19). Our policy has been to review all colorectal cancer patients, at least annually, for life. Although one patient was operated on for recurrence 7 years after initial resection, the average interval for the group was 21 months, and in only 30% of cases was recurrence diagnosed at routine follow-up. In our unit, routine screening has been more successful in detecting second primary tumours than asymptomatic recurrent disease. Wangensteen et al. (20) adopted a strategy of secondlook surgery for asymptomatic patients with Dukes' stage C lesions. Although he reported favourable results, this policy has few advocates owing to its attendant morbidity and mortality, combined with the expense and burden placed upon resources. Considerable interest has been centred upon the potential benefit of tumour markers in the prediction of patients likely to relapse after surgery, and in the early detection of recurrent disease. Although there are many markers, carcinoembryonic antigen (CEA) is the most important and widely used. It is of no value as a screening test for primary colorectal carcinoma, but the risk of recurrence is increased if the initial CEA is elevated (8). Unfortunately, since CEA is related to the volume of tumour, it is less sensitive for local recurrence than for disseminated disease (7). Even though there may be a lead time of rising CEA titres before the clinical detection of recurrence, some series have found that early detection has not improved survival (21). Others have measured CEA levels at 3-monthly intervals and performed slope analysis, basing second-look surgery upon a rising trend, even in the absence of confirmatory evidence of recurrence, or of CEA values much outside the normal range (22,23). Of 146 asymptomatic patients investigated in Ohio for rising CEA levels alone, 95% had recurrence and 58% had resections for potential cure (22). Overall 5-year survival following reoperation was 31 %. A rapidly rising slope was often indicative of liver metastases,
Surgery for recurrent colorectal carcinoma and a lower probability of a curative resection. However, not all studies advocate second-look surgery based on CEA diagnosis alone, having found that such patients often have disseminated deposits which cannot be resected (24). We are currently evaluating a new tumour marker, B5 (25), and comparing it with CEA in the early detection of recurrence. About 75% of local recurrence follows anterior resection or abdominoperineal excision of the rectum (5,16). The incidence varies from less than 4% to more than 20% (3), with a peak in the first few years after surgery (16,26). Locally advanced tumours do not appear to have a significantly higher incidence of local recurrence than less advanced lesions of a similar Dukes' stage (27). Although 60(80% of local recurrences will develop within 2 years, and over 90% within 5 years (5,8,9,14), even patients alive 10 years after surgery are still at risk (28). Resectability for cure following local recurrence is of the order of 50% (10,16,24). Although 47% of our patients underwent a potentially curative resection, less than one-third were alive at 5 years. Following an anterior resection, surgery for local recurrence will often require an abdominoperineal excision of the rectum (16), which we found necessary in 75% of cases. Even when local recurrence is combined with distant metastases, as occurs in 25% of cases (16), worthwhile palliation can still be achieved, particularly for the control of sacral pain (16,29). Resection is preferable to bypass procedures when treating either large or small bowel recurrence, resulting in improved survival without an attendant increase in morbidity or mortality (10). Emergency procedures are associated with a worse prognosis (5,10). Liver metastases account for the major source of relapse following surgery, and it has been estimated that around 29% of patients who undergo 'curative' surgery have occult secondaries at the time of the initial resection (30). Unfortunately, at the time of diagnosis 73% will involve both lobes, and will therefore not be amenable to resection. Of the remainder, 14% will be solitary, and 13% multiple but confined to one segment or lobe (31). The size of the metastasis appears to be unimportant (32). Between 20 and 30% of patients with liver metastases could potentially benefit from resection (13). Some of these will be excluded because of age, general conditions, or through involvement of the inferior vena cava or portal vein (33). Our patients who were found to have synchronous hepatic secondaries amenable to resection were left for a minimum of 3 months, and then reinvestigated. This allowed time for occult secondaries to become manifest, and thereby excluded patients unlikely to benefit from resection. Wedge excision is as effective as lobectomy providing that all tumour is removed (33-36); a minimum resection margin of 5 mm is required (13). Operative mortality is around 2-7% (33-35,37), and 5-year survival about 25% (39,43), rising to 42% for resection of solitary secondaries (39,40). The prognosis for a resected solitary metastasis is therefore little different to that of a Dukes' C carcinoma. Our longest survivor is currently disease-free 18 years after resection. Despite the benefit in this selected group, the number referred for hepatic resection is small (13). This is possibly due in part to the fact that only about one-half of the patients apparently suitable for surgery will actually benefit from major resection (41) . If CEA-based secondlook surgery ever becomes accepted in this country, then
297
there will inevitably be an increasing number of hepatic resections performed. Although follow-up is directed primarily to the detection of local recurrence, in the best series, hepatic or distant secondaries are five times more common (26). The results of surgery must, however, be viewed in relation to the natural history of liver metastases, since some patients will have reasonable longevity without treatment (42). The two patients who underwent hepaticojejunostomy were treated some years agonowadays both would be stented. At autopsy, pulmonary metastases are found in 3050% of patients with colorectal cancer (43). In most instances these are multiple and associated with disseminated deposits elsewhere. In a minority they are isolated, and in this group surgical resection may have a role. In one series of 27 patients undergoing pneumonectomy, lobectomy, or wedge excision for unilateral lesions, eight of which were multiple, median survival was 27 months (43). Survival with single lesions was significantly better, and one patient was alive 12 years after resection. One of our patients developed troublesome haemoptysis from two metastases in the lingula and left lower lobe. Both were removed by wedge resection, providing good palliation for over 2 years. The extent of recurrence correlates well with survival, and those patients requiring an emergency procedure fare significantly worse than those undergoing elective surgery (10). The majority of our patients had well or moderately well differentiated tumours, and the original Dukes' staging was favourable. Overall 5-year survival for untreated recurrent disease is 9%; increased to 13% for those receiving palliative surgery, and 31-43% for those having a radical resection (10,22). Although only a relatively small number of patients with recurrence will benefit from further surgery, some can undoubtedly be cured or given worthwhile palliation. Unfortunately, even in restrospect, it has not always been possible to predict those patients who are likely to benefit from further surgery. Local, liver, pelvic, peritoneal, and scar recurrence have all been treated successfully in a few individuals.
References I Office of Population Censuses and Surveys. Cancer statistics. Registrations. Series MBI no. 15. London: H.M.S.O., 1983:5. 2 Bengmark S, Hafstrom L. The natural history of primary and secondary malignant tumours of the liver. 1. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer 1969;23:198-
202. 3 Phillips RKS, Hittinger R, Blesovsky L, Fry JS, Fielding LP. Local recurrence following 'curative' surgery for large bowel cancer: I. The overall picture. BrJ Surg 1984;71:1216. 4 Ekman C-A, GustavsonJ, Henning A. Value of a follow-up study of recurrent carcinoma of the colon and rectum. Surg Gynecol Obstet 1977;145:895-7. 5 Waldron RP, Donovan IA. Clinical follow-up and treatment of locally recurrent colorectal cancer. Dis Colon Rectum 1987;30:42-30. 6 Phillips RKS, 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.
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S G Pollard et al.
7 Beart RW, O'Connell MJ. Postoperative follow-up of patients with carcinoma of the colon. Mayo Clin Proc 1983;58:361-3. 8 Welch JP, Donaldson GA. Detection and treatment of recurrent cancer of the colon and rectum. Am J Surg 1978; 135:505-1 1. 9 GilbertJM, Jeffrey I, Evans M, Kark AE. Sites of recurrent tumour after 'curative' colorectal surgery: implications for adjuvant therapy. BrJ Surg. 1984;71:203-5. 10 MakelaJ, Kairaluoma MI. Reoperation for colorectal cancer. Acta Chir Scand 1986;152:151-5. 11 Umpleby HC, Bristol JB, Rainey JB, Williamson RCN. Survival of 727 patients with single carcinomas of the large bowel. Dis Colon Rectum 1984;27:803-10. 12 Willett CG, Tepper JE, Cohen AM, Orlow E, Welch CE. Failure patterns following curative resection of colonic carcinoma. Ann Surg 1984;200:685-90. 13 Bradpiece HA, Benjamin IS, Halevy A, Blumgart LH. Major hepatic resection for colorectal liver metastases. BrJ Surg 1987;74:324-6. 14 Morson BC, Vaughan EG, Bussey HJR. Pelvic recurrence after excision of rectum for carcinoma. Br MedJ 1963;2: 1318. 15 Ellis H. Recurrent cancer of the large bowel. Br Med J 1983;287: 1741-2. 16 Schiessel R, Wunderlich M, Herbst F. Local recurrence of colorectal cancer: effect of early detection and aggressive surgery. BrJ Surg 1986;73:342-4. 17 Berge T, Ekelund G, Mellner C, Pihl B, Wenckert A. Carcinoma of the colon and rectum in a defined population. Recurrences. Series of the surgical department. Acta Chir Scand [Suppl.] 1973;438.vi: 39-43. 18 Heald RJ, Lockhart-Mummery HE. The lesion of the second cancer of the large bowel. BrJ Surg 1972;59:16-19. 19 Cochrane JPS, Williams JT, Faber RG, Slack WW. Value of outpatient follow-up after curative surgery for carcinoma of the large bowel. Br MedJ 1980;1:593-5. 20 Wangensteen OHW, Lewis FJ, Arhelger SW, Muller Jj, MacLean LD. An interim report upon the 'second-look' procedure for cancer of the stomach, colon, and rectum and for 'limited intraperitoneal carcinosis'. Surg Gynecol Obstet 1954;99:257-67. 21 Allen-Mersh TG. Serum CEA in the follow-up of colorectal carcinoma: experience in a district general hospital. Ann R
Coll Surg Engl 1984;66:14-16. 22 Martin EW, Minton JP, Carey LC. CEA-directed secondlook surgery in the asymptomatic patient after primary resection of colorectal carcinoma. Ann Surg 1985;202:31017. 23 Staab HJ, Anderer FA, Stumpf E, Hornung A, Fischer R, Kieninger G. Eighty-four potential second-look operations based on sequential carcinoembryonic antigen determinations and clinical investigations in patients with recurrent gastrointestinal cancer. Am J Surg 1985; 149:198-204. 24 Fucini C, Tommasi SM, Rosi S et al. Follow-up of colorectal cancer resected for cure. An experience with CEA, TPA, Ca 19-9 analysis and second-look surgery. Dis Colon Rectum 1987;30:273-7. 25 MilnerJ, Metcalfe SM. Monoclonal antibody which agglutinates erythrocytes from cancer patients. Lancet 1982; 2:1100-1.
26 Heald RJ, Ryall RDH. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;1:147982. 27 Pittam MR, Thornton H, Ellis H. Survival after extended resection for locally advanced carcinomas of the colon and rectum. Ann R Coll Surg Engl 1984;66:81-4. 28 Carlsson U, Lasson A, Ekelund G. Recurrence rates after curative surgery for rectal carcinoma, with special reference to their accuracy. Dis Colon Rectum 1987;30:431-4. 29 Ketcham AS. The management of recurrent rectal carcinoma. CanJ Surg 1985;28:422-4. 30 Finlay IG, Meek DR, Gray HW, Duncan JG, McArdle CS. Incidence and detection of occult hepatic metastases in colorectal carcinoma. Br Med J 1982;284:803-5. 31 Wood CB. Natural history of liver metastases. In: Van de Velde CJH, Sugerbaker PH eds. Liver Metastases. Amsterdam: Martinus Nijhoff. 1984;47-54. 32 Adson MA, Van Heerden JA. Major hepatic resections for metastatic colorectal cancer. Ann Surg 1980;191:576-83. 33 Taylor I. Colorectal liver metastases-to treat or not to treat? BrJ Surg 1985;72:511-16. 34 Coppa GF, Eng K, Ranson JHC, Gouge TH, Localio SA. Hepatic resection for metastatic colon and rectal cancer. An evaluation of preoperative and postoperative factors. Ann
Surg 1985;202:203-8. 35 Fortner JG, Silva JS, Golbey RB, Cox EB, Maclean BJ. Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. 1. Treatment by hepatic resection. Ann Surg 1984;199:30616. 36 Rajpal S, Dasmahapatra KS, Ledesma EJ, Mittelman A. Extensive resections of isolated metastasis from carcinoma of the colon and rectum. Surg Gynecol Obstet 1982; 155:813-16. 37 Gennari L, Doci R, Bozzetti F, Bignami P. Surgical treatment of hepatic metastases from colorectal cancer. Ann Surg 1986;203:49-54. 38 Morrow CE, Grage TB, Sutherland DER, Najarian JS. Hepatic resection for secondary neoplasms. Surgery 1982;
92:610-14. 39 Wilson SM, Adson MA. Surgical treatment of hepatic metastases from colorectal cancers. Arch Surg 1976; 111:330-4. 40 Adson MA, Van Heerden JA. Major hepatic resections for metastatic colorectal cancer. Ann Surg 1980;191:576-83. 41 Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM. The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Ann Surg 1984;199:502-7. 42 Finan PJ, Marshall RJ, Cooper EH, Giles GR. Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: a clinical and computer analysis. BrJ Surg 1985;72:373-7. 43 Wilking N, Petrelli NJ, Herrera L, Regal A-M, Mittelman A. Surgical resection of pulmonary metastases from colorectal adenocarcinoma. Dis Colon Rectum 1985;28:562-4.
Received 8 December 1988
