The Heidelberg Results after TME
Alexis Ulrich, Jan Schmidt, Jürgen Weitz, Markus W. Büchler
A. Ulrich ( u)
Department of General, Visceral and Trauma Surgery,
Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
e-mail: alexis.ulrich@med.uni-heidelberg.de
Abstract
The introduction of the total mesorectal excision (TME) has changed the treatment of rectal cancer dramatically by reducing the local recurrence rate. We report the results of 208 patients undergoing a low anterior resection (LAR, n=180) or abdominoperineal resection (APR, n=28) with TME between 1 October 2001 and 30 September 2003. No adjuvant therapy was administered to any patient;
however, 108 patients received neoadjuvant radiotherapy or radiochemotherapy.
Since February 2002, 51 patients underwent a short-course radiotherapy with 5×5 Gy prior to surgery in cases of a T3 tumor or positive lymph node in the preoperative CT-scan or endoanal ultrasound. Patients with a T4 tumor or T3 tumor close to the sphincter received radiochemotherapy. We discuss the results for mortality, morbidity, functional outcome, and overall survival between the LAR and APR groups. The mortality rate was 3% in the LAR and 0% in the APR group, whereas the morbidity was higher in the APR group. Anastomotic leakages occurred in eight patients (7%), and reoperations had to be performed in14 LAR and four APR patients. After a median follow-up of 11 months, the overall survival was 93% for LAR and 89% for APR. To assess the functional outcome after TME, questionnaires were sent to all patients undergoing LAR and APR.
In conclusion, the TME has become the gold standard for rectal cancer surgery.
Neoadjuvant treatment modalities such as preoperative short term radiotherapy (5×5 Gy) or combined radiochemotherapy will most likely replace the adjuvant combined radiochemotherapy.
Introduction
The treatment of rectal cancer patients has changed dramatically within the last two decades. This is mainly due to the introduction of the total mesorectal excision (TME) by Heald in 1980, allowing the reduction of the local recurrence rate to 4%–
10% even without neo- or adjuvant therapy [4, 9, 10, 16]. In comparison, Hermanek
Recent Results in Cancer Research, Vol. 165Springer-Verlag Berlin Heidelberg 2005c
Table 1. Comparison of local recurrence rates after surgery alone [classic technique (OP) and TME] and combination with radio- (RT) or radiochemotherapy (RCT), respectively
Trial GITSG [6] NCCTG [18] Tveit [25]
OP OP+RCT OP+RT OP+RCT OP OP+RCT
LR (%) 24 11 25 14 30 12
Trial Heald [10] DCRCG [13] CAO / ARO / AIO-94 [24]
TME TME TME+nRT TME+nRCT TME+RCT
LR (%) 3.9 8.2 2.4 7 11
LR, local recurrence rate; nRT, neoadjuvant radiotherapy; nRCT, neoadjuvant radiochemotherapy.
et al. reported local recurrence rates of 4%–55%, with a median of 20%, as the results of a German multicenter trial including TME and classical surgery in 1995 [11].
Even comparing the local recurrence rates of TME and classical surgery combined with neo- or adjuvant therapy—as proposed in the consensus guidelines of the German Cancer Society and the National Institutes of Health—shows a superior outcome after TME alone (Table 1).
What is so special about the total mesorectal excision? By respecting the integrity of the fascia pelvis, a separation plane between the mesorectum and the pelvine structures, called “the holy plane” by Heald, the mesorectum can be removed completely. This is so important as the mesorectum surrounds the vessels and lymphatic system of the rectum, reducing the risk of local recurrence. Additionally, the risk of damaging the inferior hypogastric plexus is reduced, resulting in less functional impairment of the genitourinary system [9].
Therefore, the total mesorectal excision is regarded as the “gold standard” for rectal cancer surgery and routinely performed at the surgical department of the University of Heidelberg.
We discuss our results obtained with TME between 1 October 2001 and 30 September 2003 in Heidelberg.
Results
TME in Heidelberg
Within the above-mentioned time span, 1,084 colorectal operations were per-
formed in total, 563 for colorectal cancer, comprising 322 colon cancer and 241
rectal cancer patients. The 241 patients with rectal cancer underwent a low anterior
or anterior resection (LAR) in 180 cases (75%), in 28 cases an abdominoperineal
resection (APR) (12%), in 11 cases a pelvic exenteration (4%), and in 22 cases other
procedures as local excision, explorative laparotomy with creation of an ileostomy,
Table 2. Data of 208 patients undergoing low anterior resection or abdominoperineal resection for rectal cancer between 1 October 2001 and 30 September 2003
LAR (n=180) APR (n=28)
Average age (range) 62 (37–89) 60 (15–74)
Male:female 133:47 16:12
Tumor level (cm from anal verge) 8 4
Preoperative radiotherapy (5×5 Gy) 51 3
Preoperative radiochemotherapy 42 12
etc. (9%). Seventeen of the patients had a local recurrence at the time of their operation (7%).
In the following, we focus on the 208 patients with LAR and APR. The patient data are shown in Tables 2 and 3. The tumor level of the 180 patients with sphincter preservation was (median) 8 cm above the anal verge, for the 28 patients with APR 4 cm. The high percentage of sphincter-preserving procedures (87%) is explained by the widespread opinion that a 1-cm safety margin to the distal border of the tumor is sufficient for curative resection [3, 14, 21]. Looking at the histological tumor stage, 70 of the180 patients with LAR were UICC stage I, a stage not seen in any patient undergoing APR; 44 and 40 patients were stage II and III in the LAR group, respectively. Stage III was the most often diagnosed stage in patients undergoing APR, seen in 12 patients (43%). Stage IV accounted for 9% in the LAR and 25% in the APR group (Table 3). Although 10 of the 180 patients with LAR had a recurrent tumor at the time of surgery, the R0-resection rate was 97% (176 of 180 patients). Seven of the 28 patients with APR had recurrent disease, and R0-resection could be achieved in 20 patients (71%) (Table 3).
No adjuvant radiotherapy was administered to any patient; however, a total of 108 patients underwent neoadjuvant radiotherapy or radiochemotherapy.
Fifty-one patients had a short-course preoperative radiotherapy with 5×5 Gy (5 Gy each day for 5 consecutive days, surgery within 2 days after completion of the radiotherapy) prior to LAR, three patients prior to APR. The short-course radiotherapy was introduced in Heidelberg in February 2002 for patients with a T3
Table 3. Data of 208 patients undergoing low anterior resection or abdominoperineal resection for rectal cancer between 1 October 2001 and 30 September 2003
LAR (n=180) APR (n=28)
UICC I 70 0
UICC II 44 7
UICC III 40 12
UICC IV 16 6
Recurrent tumor 10 7
R0-resection 176 20
Table 4. Operative results of 208 patients undergoing low anterior resection or abdominoperineal resection for rectal cancer between 1 October 2001 and 30 September 2003
LAR (n=180) APR (n=28)
Operating time (median, min) 260 (120–420)
290 (150–480) Blood loss (median, ml)
650 (200–2500) 800 (200–4000)
Blood transfusions (median, n) 0 (0–12)
0 (0–9) Hospital stay (days)
12 (7–48) 14 (9–46)
tumor or positive lymph nodes in the preoperative CT scan or endoanal ultrasound.
Before February 2002 these patients received preoperative radiochemotherapy (50 Gy, combined with 5-FU chemotherapy), as did patients with T4 tumors or T3 tumors close to the sphincter.
The operative and postoperative results are shown in Tables 4 and 5. The mean operating time was slightly higher for the APR than the LAR (290 min vs. 260 min) as was the median blood loss (650 ml vs. 800 ml). However, no differences were seen in the median number of blood transfusions. The hospital stay was a slightly shorter for LAR than APR patients (Table 4).
Five patients with LAR (3%) died within the first 60 days after the operation, two patients from aspiration pneumonia, one from pulmonary embolism, one from a heart attack, and one from sepsis due to an anastomotic leakage with peritonitis.
None of the patients undergoing APR died within the above-mentioned period. The morbidity was higher in the APR than the LAR group (36% vs. 26%). Anastomotic leakages occurred in 12 patients (7%), wound infections and abscesses in 8% of the patients with LAR. In the APR group, the latter were the most common complica- tions with 25%. Voiding problems (n=13) and bleeding (n=2) were other surgical complications seen. Cardiopulmonary complications occurred in seven patients with LAR; four of these patients died during their hospital stay. Re-operations had to be performed in 14 LAR and four APR patients (8% vs. 14%) (Table 5). Eight of these re-operations in the LAR group and all four in the APR group were due to anastomotic leakages or abscesses; the remainder of the relaparotomies were performed due to wound dehiscence and bleeding.
After a median follow-up of 11 months, local recurrences occurred in three
patients (1.5%) after LAR and none after APR. In one of the three patients with
local recurrence, the LAR was performed for a locally recurrent tumor. The overall
Table 5. Postoperative results of 208 patients undergoing low anterior resection or abdominoperineal resection for rectal cancer between 1 October 2001 and 30 September 2003
LAR (n=180) APR (n=28)
Mortality (n) 5 (3%) 0
Morbidity (n) 50 (28%) 10 (36%)
Anastomotic leakage (n) 12 (7%)
Wound infection / abscess (n) 14 (8%) 7 (25%)
Bleeding (n) 2 (1%)
Voiding problems (n) 10 (5%) 3 (11%)
Cardio/pulmonary (n) 7 (4%)
Others (n) 5 (3%)
Re-operation (n) 14 (8%) 4 (14%)
Table 6. Outcome of 208 patients undergoing low anterior resection or abdominoperineal resection for rectal cancer between 1 October 2001 and 30 September 2003
LAR (n=180) APR (n=28)
Median follow-up (months) 11 11
Local recurrence (n) 3 (1.5%) 0
Hepatic metastases (n) 11 (6%) 2 (7%)
Pulmonary metastases (n) 2 (1%) 0
Overall survival (n) 168 (93%) 25 (89%)
survival after 11 months’ median follow-up was 93% for LAR and 89% for APR.
Hepatic metastases have been diagnosed in 11 LAR (6%) and two APR (7%) patients, pulmonary metastases in two patients (LAR) (Table 6).
Rectal Reservoir Reconstruction
Of the 180 patients with LAR, 128 received a pouch reconstruction; the remaining 51 patients a straight anastomosis. In 106 cases, the reconstruction was created as a transverse coloplasty pouch (TCP) (59%), in 22 cases as a colon J pouch (CJP).
All 22 CJPs and 24 TCPs were performed as part of a randomized controlled trial comparing the two techniques. The trial started in October 2002 and will be closed when a total of 130 patients have been enrolled.
Genitourinary Function
To assess the functional outcome after TME, we send questionnaires to all patients
undergoing LAR or APR concerning bladder and genital function. One hundred-
twenty-three patients with LAR (68%) and 20 patients with APR (71%) answered
the questionnaire regarding the questions on bladder function. However, for the genital function, these figures were much lower; 72 patients (LAR, 40%) and nine patients (APR, 32%), all male. Questions on erection and ejaculations disorders were answered by only 40 patients with LAR.
Bladder dysfunction (voiding problems, urge, or incontinence) was seen in 25%
of the patients, which is in line with the literature, reporting a range of 5%–32% for the TME [7, 8, 19]. With the classical surgical technique, bladder dysfunction was seen even in up to 60% [12, 15]. The data concerning the genital function must be interpreted more carefully due to the low response (the answers were voluntary).
Thirteen of the 40 answering patients (33%) reported erection problems and 12 patients (30%) ejaculation problems. Based on the literature, erection disorders range between 13% and 24% after TME and 32% to 80% after classical operation.
Ejaculation disorders occurred in 11%–45% after TME and 30%–81% after classical operation, respectively [12, 15, 17, 19, 20, 22].
Discussion
The total mesorectal excision has become the gold standard for rectal cancer
surgery. The Heidelberg results document the safety of the procedure with low
mortality and morbidity rates. Especially the local recurrence rate could be re-
duced significantly with the new technique. Reported rates range between 4% and
11% after TME, compared with 4–55% (median 20%) with the classical technique
(Tumori). The Dutch Colorectal Cancer Group was the first to prove that the local
recurrence rate can be further reduced by neoadjuvant therapy as it dropped from
8.2% to 2.6% due to short-term preoperative radiotherapy with 5×5 Gy [13]. A su-
periority compared to the postoperative radiochemotherapy, still recommended
by the consensus guidelines of the National Institutes of Health and the German
Cancer Society, was seen for the preoperative radiochemotherapy in a randomized
controlled trial, as the local recurrence rate was lower in the neoadjuvant treat-
ment group (7% vs. 11%) [23,24]. In Heidelberg we have the following treatment
concept: Patients with T3- or node-positive rectal cancer receive a preoperative
short-term radiotherapy (5×5 Gy). The benefits are the low costs and the short
delay of surgery, as the operation should be performed within 2 days after com-
pletion of the radiotherapy. Randomized controlled trials as well as meta-analyses
have shown that the short-term radiotherapy can significantly reduce the local
recurrence rate and increase the overall survival [1, 2, 5, 13, 26]. Furthermore,
the acute toxicity is lower compared to preoperative radiochemotherapy. In cases
of a T4 tumor or lesion close to the sphincter, radiochemotherapy is preferred
preoperatively to achieve a downsizing of the tumor and possible preservation of
the sphincter. Postoperative radiotherapy is not performed anymore. With this
concept, we report a very low local recurrence rate of 1.5% in our series, so far,
which could be in part explained by the short follow-up of 11 months, though it
is known that 80% of the local recurrences occur within the first 2 years after the
operation.
Additionally, the functional outcome after low anterior resection could be im- proved significantly by respecting the integrity of the fascia pelvis. Damage to the nerves responsible for bladder and genital function can be avoided, reducing the incidence of voiding problems, impotence, and retrograde ejaculation. With the classical surgical technique, bladder dysfunction was seen in 50%–60% of the patients; after introduction of the TME only in 3%–33% [7, 8, 12, 15, 19]. Similar improvements were reported for the genital function with impotence of 30%–81%
of the patients after classical surgery compared to 11%–24% after TME [12, 15, 17, 19, 20, 22].
To reconstruct the rectum we prefer the transverse coloplasty pouch over the colon J-pouch as it can be done safely and easily, saves operating time, and has functional results comparable to those of the J-pouch [27], but as to avoiding late evacuation problems, however, we still await the results of our randomized trial.
Conclusion
Total mesorectal excision represents the gold standard for rectal cancer surgery.
Neoadjuvant treatment modalities such as preoperative short-term radiotherapy (5×5 Gy) or combined radiochemotherapy will most likely replace the adjuvant combined radiochemotherapy.
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