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                                       Mesorectal excision for rectal                                   cancer



    Concern about world wide local recurrence rates                                                          Introduction
for rectal cancer of 20-45%, together with anxiety at                              To determine the standards of outcome that are
the recent proliferation of adjuvant therapies, led us                          acceptable   for surgical treatment of rectal cancer, we
to review the efficacy of total mesorectal excision                             examined our data on total mesorectal excision (TME),
(TME) with which no adjuvant therapy had been                                   which was first reported in 1982.1 The temptation to
combined.                                                                       dismiss our low local and overall recurrence rates as a
    Precise, sharp dissection is undertaken around                              statistical aberration-eg, the result of case mix and
the integral mesentery of the hind gut, which                                   analytical techniques-was scrutinised objectively. Further
envelopes the entire mid rectum. This procedure                                 objective corroboration was provided by an oncologist
adds to operative time and complications but has                                (R. D. H. R.) who has overseen our follow-up clinic for 14
                                                                                years.
been claimed to eliminate virtually all locally
recurrent         disease   after   "curative"   surgery.                                             Patients and methods
Independent analysis (J.          K. M.) of prospective                            Our independent validator and assessor (J. K. M.) reviewed all
follow-up data extended over a 13-year interval                                 cases of rectal cancer seen in our unit and updated the anterior
                                                                                resection results published in 1986.1 He then examined a high-risk
(1978-91; mean 7·5 years). The actuarial local
recurrence rate after curative anterior resection at 5                          group of patients who were most likely to recur according to the
                                                                                definitions of Krook et al from the North Central Cancer Treatment
years is 4% (95% Cl 0-7·5%) and the overall                              Group (NCCTG).4 These investigators excluded Dukes’ A (Astler
recurrence rate is 18% (10-25%). 10-year figures                                Coller A + Bl) lesions, those more than 12 cm from the anal verge,
are 4% (0-11%) and 19% (7-32%). In view of the                                  and those considered "not curative" by the surgeon. Figures 1 and 2
                                                                                show the distribution of cases according to the operative
high-risk classification used for the North Central                             management and Dukes’ stage, respectively. J. K. M. found 2
Cancer Treatment Group (NCCTG), which has led                                   patients who had received systemic 5-fluorouracil for six months
to a trend to chemoradiotherapy, a similar group of                             because of personal preference (one death, one survival), and he
high-risk Basingstoke cases was constructed for                                 excluded these to leave a high-risk group of 135 cases. Data are
                                                                                stored on a computer database and they are updated regularly by a
comparison purposes. This group included 135                                    full-time research worker. Patients are examined and undergo
consecutive Dukes’ B (B2) and Dukes C cancer
                                                                                carcinoembryonic antigen testing every three months for the first
operations, both anterior resection and abdominal-                              two years, then six monthly for three years, and yearly thereafter.
perineal excision, for tumours below 12 cm from the                             No patient was lost to follow up and all deaths have been
anal verge. Results from TM E alone are substantially                           documented; three doubtful cases were classified as rectal cancer
                                                                                deaths.
superior to the best reported (NCCTG) from                                         Recurrence and survival curves were generated by the Kaplan-
conventional surgery             plus radiotherapy or                           Meier method and the log-rank statistic was used for comparisons.
combination           chemoradiotherapy: 5% local                               Confidence intervals were taken at the 95% level. Our study is
recurrence at 5 years compared with 25% and                                     ongoing but this analysis is at a median follow-up time of 7-7 years,
13·5%, respectively; and 22% overall recurrence                          which corresponds with the NCCTG trial.

compared with 62·7% and 41·5%, respectively                       Definitions
(Dukes’ B cases [B2], 15%; Dukes’ C cases, 32%).                                  The operation was defined as curative when, at the end of the
     Meticulous TM E, which encompasses the whole
                                                                                procedure, the surgeon believed that all grossly detectable cancer
field of tumour spread, can improve cure rates and                              had been removed. Local and overall recurrence are defined as
reduce the variability of outcomes between                                      disease detected or suspected within the pelvis (local) and anywhere
surgeons. Far more genuine "cures" of rectal cancer
are possible by surgery alone than have generally                               ADDRESSES: University of British Columbia (Prof J. K. MacFarlane,
                                                                                MD), Vancouver, Canada; Wessex Radiotherapy Centre, (R. D. H.
been believed or are currently accepted. Better                                 Ryall, FRCR) Southampton, UK; Colorectal Research Unit (R. J.
surgical results are an essential background for the                            Heald, MChir), Basingstoke District Hospital, UK. Correspondence
                                                                                to Mr R. J. Heald, Colorectal Research Unit, Basingstoke District Hospital,
more selective use of adjuvant therapy in the future.
                                                                                Aldermaston Road, Basingstoke, Hampshire RG24 9NA, UK.
 458




    AR, anterior resection.
    AP, abdominal-perineal excision.

  (local or systemic) during life or at necropsy, respectively. The 25 %
  of procedures defined as non-curative included those with distant
  metastases, together with a smaller group (11% locally non-
  invasive) in which residual disease was believed to remain on the
  side wall of the pelvis. Low-risk exclusions included 51 cases of
  Dukes’ A cancer, with one case of local recurrence (probably due to
  implantation and which was subsequently cured) and two deaths
  from cancer. The exclusion of lesions 12-15 cm from the anal verge
  eliminated only five cases of tumour recurrence (none local).

  Surgical technique
     Meticulous sharp dissection of the avascular plane between
  mesorectum   and parietes is completed under direct vision. The
  excised specimen therefore includes the entire posterior, distal, and
lateral mesorectum out to the plane of the inferior hypogastric
  plexuses, which are carefully preserved. Anteriorly the specimen
  includes intact Denonvillier’s fascia and the peritoneal reflection
  (fig 3 upper). The characteristic smooth bi-lobed encapsulated
  appearance posteriorly and distally reflects the contours of the
  pelvic floor and the midline anococcygeal raphe (fig 3 middle).
  Implantation is prevented by aqueous washout below the clamp
  before the anorectum is divided, and in the pelvis itself.

                               Results
     The first part of our study provides current lifetables for
  comparison with the figures published in 1986 for curative
  anterior resections (fig 4).’ Actuarial local recurrence is
  unchanged at 4% (95% CI 0-7-5%) as is overall recurrence
  (18%; 10-25%). If locally non-curative anterior resections
  are included, these figures are altered to 6% (0-11%) and
  22% (13-29%). 10-year data for curative anterior
  resections show recurrence rates of 4% (0-11%) and 19 %                  Fig 3-Operative stages.
  (7-32%), respectively. Inclusion of abdominal-perineal                      Upper antenor aspect of mesorectum dunng surgery with seminal
  excisions alters overall recurrence to 19% at 5 years and                vesicals in front and Denonmllier’s fascia behind
  22% at 10 years. Extramural large-vein invasion and                         Middle posterior aspect of mesorectum dunng surgery showing the
  tumour differentiation have now become statistically                     characteristic bi-lobed lipoma appearance.
                                                                              Lower: the pnncipal parasympathetic engent nerve root preserved on
  significant indicators (p<0-001).   Recurrence in cases of               the right side of the pelvic wall


                                                                           Dukes’ C carcinoma has fallen from 42% to 32% at the
                                                                           5-year point, and there is a trend to fewer episodes of local
                                                                           recurrence in the second half of the series; only two of the six

                                                                           occurring after curative anterior resections between 1986
                                                                           and the end of 1992.
                                                                              The surgical results ofTME were then analysed in detail
                                                                           for 135 consecutive high-risk cases (table 1). 126 anterior
                                                                           resections and 9 abdominal-perineal excisions (6-1%) have
                                                                           been done in this group, although this figure is possibly low
                                                                           because    more     abdominal-perineal excisions were
                                                                           undertaken by other surgeons. There were 79 male and 56
                                                                           female patients and the average age at operation was 67 years
                                                                                                                                  459


                                                                       leakage, all patients having had a contrast enema; and units
                                                                       of blood transfused.
                                                                          Significant differences were found with the first four
                                                                       criteria. Cases of Dukes’ stage B (85 % 5-year survival) were
                                                                       significantly better for overall recurrence than cases of
                                                                       Dukes’ stage C (68%) (p 0-05-0-025) with no differences
                                                                                                  =



                                                                       in local recurrence (3 B, 2 C). Although numbers of
                                                                       abdominal-perineal excisions are small, 5/9 recurrences do
                                                                       yield significant worse results (p= <0 01). There were no
                                                                       differences or trends for any of the last six variables. During
                                                                       13 years of follow-up, 11 patients have developed non-
                                                                       colorectal malignancies (table II).

                                                                                               Discussion
                                                                          The management of the patient with rectal cancer has
                                                                       challenged oncologists for decades. Ten years ago, Silen
Fig  4-Life-table to recurrence            for   curative   anterior   observed that over half of all recurrences are located in the
  resections during 1978-91.
                                                                       pelvis and constitute a failure of surgery in a disease that is
(range 36-90). 3 patients died within 30 days of surgery: a            unique in its surgeon variability.s Disappointing results
2% peri-operative mortality rate.                                      from more traditional surgical practices have led to clinical
                                                                       trials of various regimens of radiotherapy and
  During 13-7 years, 38 patients have died of causes other
than rectal carcinoma. Their average age at surgery was 74-9           chemotherapy.". The current consensus is that irradiation
                                                                       reduces local recurrence but survival benefit remains
years (range 41-5-90-7) (table II).
   Overall recurrence-free cancer-specific survival was 78%            unproven.8,11Pahlman, in a Swedish trial, showed the
(95% CI 68-88%) according to life-table analysis at 5 years.           superiority of pre-operative over postoperative treatment,
24 patients had a recurrence, 84% of whom were apparent                and he has suggested that pre-operative radiotherapy would
within 3-5 years, 92% within 5 years, and 100% at 6 years.             approximately halve the risk of local recurrence in any given
Their average age at surgery was 69 4 years and survival               group at risk.12
                                                                          Krook and colleagues have claimed that the combination
averaged 2-7 years. Local recurrence rate was 5% on
life-table analysis at 5 years (95% CI 0-11%). 7 patients              of chemotherapy and radiotherapy improves "significantly
                                                                       and substantially" the surgical results for rectal cancer with a
developed a local recurrence, 5 after anterior resection
(5/128=3-8%), and 2 after abdominal-perineal excision                  "poor prognosis".4 However, should prognosis really be so
(2/9=22%); 4 of these cases were local alone, while 3 had              poor for Dukes’ B (B2) and Dukes’ C carcinoma? And are
metastases.                                                            current surgical techniques the best for the challenge posed

   Life tables for local and overall recurrence were                   by rectal cancer? We believe that the answer is no to both
constructed for subgroups according to the following                   questions.
criteria: choice of operation (anterior resection or                      Whilst the NCCTG and National Surgical Adjuvant
abdominal-perineal excision); Dukes’ stage; histological               Project for Breast and Bowel Cancers trials were proceeding,
                                                                       a prospective study of total mesorectal excision was under
grading; extramural vascular invasion (identified by section
of the mesorectum outside the cancer); tumour height above             way in Basingstoke.1 Despite similar criteria and consecutive
anal verge (providing anterior resection is chosen) (4-8 cm            patients, our high-risk cases may not be precisely
and 8-12 cm); anastomotic height above anal verge (2-4 cm              comparable, but the use of such groups does have two
and 4-6 cm); distal muscle tube margin (on the specimen                advantages. First, exclusion of Dukes’ A (or A+B1) and
without stretching and after fixation); sex; anastomotic               non-curative cases limits the effect of selection or referral
                                                                       factors. Second, the study groups comprise the cases most
TABLE I-LOCAL AN D TOTAL RECURRENCERATES FOR TME AND                   likely to be influenced by treatment so that differences
                      NCCTG DATA                                       become apparent more readily. 7 of our 8 local recurrences
                                                                       in the curative group took place in this subgroup and only 7
                                                                       recurrences of any kind occurred among excluded patients.
                                                                       This result suggests that the NCCTG definition of "high
                                                                       risk" is indeed valid and that such subgroups are ideal for
                                                                       comparisons between series. Inclusion of all locally non-
                                                                       curative anterior resections only increases local recurrence
                                                                       by 2% and overall by 4%.
              TABLE ll-DEATHS FROM OTHER CAUSES




                                                                       Fig 5-Comparison of lifetables for recurrence-free interval
Average age   at   operation 74.9 years.                                 between NCCTG series (left) and our series of TME (right).
460


   In the NCCTG control arm, surgery plus radiotherapy               recurrence rates   from 33% to only two local recurrences
produced a 5-year local recurrence rate of 25% and an                among   41 cases: simply by application of this technique and
overall recurrence rate of 62-7%.2 The addition of                   the support of his colleagues in referring cases.16 At least 6
chemotherapy to the treatment arm reduced these figures to           British colorectal surgeons, applying these principles, have
13-5% and 42%, respectively. It is these differences that            published   or presented single-figure local recurrence rates
have influenced treatment throughout the world. The                  after curative resections, and similar results are undoubtedly
Basingstoke actuarial local recurrence figure for high-risk          achieved by some surgeons in the USA and elsewhere.
cases is 5% and for overall recurrence is 22% (table I and           Institutional figures have almost invariably been inferior.
fig 5). These results are also superior to those from the            Specialisation could create a background of less variable
NSABP trial where a 5-year recurrence rate of 70% was                surgical results against which indications for adjuvant
seen in a similar group treated by surgery alone.7                   therapy can be more selectively defined by careful analysis of
   Such large differences imply that viable local tumour             risk factors for both local and disseminated recurrence.
residues remained more frequently after operation in these           Widespread adoption of the principles of TME outlined in
studies than in our own. The only credible explanation is            this paper should lead to a reduction in the number of
that the field of spread of cancer in the pelvis is susceptible to   patients requiring combination therapy, together with a
what may at first sight seem to be small differences in              greater certainty that they will benefit from such therapy.
surgical technique. TME is more difficult and time                      TME was developed from an anatomical understanding
consuming but not more radical. The dissection avoids the            based on what is surgically feasible: its importance depends
autonomic nerves by defining the place within them-this              on results. The data presented here suggest that the usual

"holy plane" is subjected to sharp dissection under direct           field of spread of rectal cancer is confined within the
vision throughout.13 Complete excision of the enveloping             mesorectal envelope and that rectal carcinoma is far more
mesorectal tissues in a covering of thin but recognisable            curable by surgery alone than has generally been believed or
fascia protects the pelvic walls, genito-urinary structures,         is currently accepted. Most carcinomas that recur initially
presacral nerves, parasympathetic roots (fig 3 lower), and           within the pelvis could probably have been cured by better
neurovascular bundles, and creates a specimen with a thin            surgery. Concentration of effort and resources into the
mobile covering of areolar tissue. The use of the same               improvement of training in surgical technique would pay
procedure in all cases, irrespective of the location of the          great dividends in the management of this common visceral
tumour in the rectal tube, requires specific surgical skills and     malignancy.
strengthens the case for specialised referral patterns. Over            We thank the dedication of Mrs Rosemary Sexton, our full-time research
90 % of all patients referred to our unit during this time were      assistant, the support of the Royal College of Surgeons and Physicians of
operated on by one surgeon (R. J. H.).                               Canada and the University of British Columbia, and the ongoing financial
   The cost of this success is not inconsequential. The              support of the Wessex Cancer Trust. We also thank Prof William Silen for his
meticulous dissection procedure requires additional                  help and advice with the manuscript.
operating time (up to 25 h) and blood transfusion                                                  REFERENCES
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