Table of Contents  

Merkel and Hohenberger: Quality management during development and implementation of complete mesocolic excision in colon carcinoma

Introduction

The surgeon is a proven prognostic factor in colorectal carcinoma surgery.1 It has been observed that the prognosis of patients with rectal carcinoma improved considerably after the introduction of total mesorectal excision (TME)2 and neoadjuvant radiochemotherapy for the treatment of locally advanced disease [pT3,4 or lymph node involvement (pN+)].3 The corresponding advances in the treatment of colon carcinoma are complete mesocolic excision (CME)4 and adjuvant chemotherapy in node-positive stage III. The concept of CME was first described in 2009 and is still controversial. It is recommended that more controlled clinical trials are carried out before this surgical technique is considered routine and universal adoption can be proposed.5,6

In Scandinavia, CME had already been implemented in different ways. Between 2004 and 2008, the Stockholm Colon Cancer Project7 established CME in workshops, lectures and surgeries that focused on a multidisciplinary team approach in preoperative staging, surgery and histopathology and consequently contributed to improved survival. In Aarhus, Denmark,8 CME was introduced simultaneously with laparoscopy-assisted surgery between 2008 and 2011. The continuous feedback to the surgeons from pathological quality indicators [number of examined lymph nodes, distance from the bowel to the high tie, quality of the plane of mesocolic resection and rate of curative (R0) resection]9 was found to be important. Recently, it has been demonstrated that CME is associated with significantly increased disease-free survival compared with conventional colon resection.10

In Erlangen, Germany, quality management started in 1978 and subsequently the concept of CME4 was developed in the 1980s, and has being applied in every case since 1995. It was accompanied by a detailed quality management programme with continual surveillance of indicators of process quality and, in particular, indicators of outcome quality. This has enabled an evaluation of CME and the continuous development and improvement in the treatment of primary colon carcinoma. While improvement in prognosis has been presented previously4,11 the focus here is on quality management that accompanied this development.

Patients and methods

Between 1978 and 2014, a total of 2019 consecutive patients with primary colon carcinoma underwent surgery at the Department of Surgery in the University Hospital Erlangen, Germany. The following inclusion criteria were used: solitary invasive colon carcinoma (at least into the submucosa) with a distal margin > 16 cm from the anal verge; no appendix carcinoma; no other malignant tumours either synchronous with or before diagnosis; carcinoma not associated with familial adenomatous polyposis, ulcerative colitis or Crohn’s disease; no distant metastases (stage I–III); and no neoadjuvant treatment.

The majority of patients were scheduled for elective surgery. In those with an emergency presentation (9.3%), surgery was performed within 48 hours of admission.12

Technique of complete mesocolic excision

The main principles of CME are the sharp separation of the mesocolic plane from the parietal plane; the supplying arteries are ligated flush with the central vessels, to achieve maximal lymph node harvest. The extent of the surgery is always determined by the location of the tumour and its potential lymphatic spread. Thus, patients with tumours located between two draining areas (transverse colon, hepatic or splenic flexure) are treated with extended hemicolectomies or subtotal colectomies with dissection of two or more lymphatic drainage areas. In transverse colon cancer including the flexures, the corresponding right gastroepiploic artery and the lymph nodes over the pancreatic head and inferior aspect of the left pancreas were also removed. All CME procedures were performed or at least supervised by four or five experienced visceral surgeons, who changed over the years. Multivisceral resection was always performed en bloc if any extracolonic organs or structures were attached to the tumour.

Residual tumour was classified by clinical and histopathological examination. Detailed documentation of the histopathological findings allowed classification of the carcinomas in accordance with the 7th edition of the classification of malignant tumours of the Union for International Cancer Control (UICC).13

Anastomotic leakage was diagnosed clinically as grade B or C according to the classification of anastomotic leakages in rectal cancer of Rahbari et al.14

Adjuvant chemotherapy was introduced in 1995 and gradually became a standard of care in the treatment of patients with pathological stage III disease after R0 resection.

Locoregional recurrence was defined as the presence – diagnosed by clinical or pathological examination – of a recurrent tumour located at the anastomosis, in the tumour bed, or in the residual regional lymph nodes. Distant metastases were typically diagnosed by imaging. Histological confirmation of recurrence was encouraged.

The development of the short-term results and long-term outcome was accompanied by an intensive internal quality control programme with annual evaluations of the quality indicators, including the individual surgeons. These data have been collected prospectively in the Erlangen Registry of Colorectal Carcinomas, which was established in 1978, and detailed case report forms have been added since its establishment.

For analysis of long-term prognosis we included only patients who were treated between 1978 and 2009 and had R0 disease. Twenty-six patients (1.5%) for whom follow-up data were incomplete were excluded. Thus, a total of 1716 patients were included in the analyses of prognosis.

The patients were followed for at least 5 years. A physical examination, analysis of carcinoembryonic antigen levels and abdominal ultrasonography were performed at 3-month intervals for the first 2 years and at 6-month intervals thereafter. In 2004, the follow-up intervals were changed to semiyearly for the first 2 years and then yearly up to 5 years postoperatively, in accordance with the first edition of the guidelines for colorectal carcinoma.15 Chest radiography was carried out annually, and complete colonoscopy after 1 year and every 5 years thereafter if the result was negative. The follow-up data were collected either during follow-up protocol at the surgical department of the hospital or in writing from the patients’ family doctors. In addition, the vital status of each patient was regularly monitored through enquiries at the patient’s local registrar’s office.

Statistical analysis

To compare frequencies, a chi-squared test was applied. Differences in the quantitative data were tested using the Kruskal–Wallis test. The Kaplan–Meier method was used to calculate the 5-year rates of locoregional recurrences, distant metastases and survival. The endpoint of overall survival was death from any cause. The endpoint of cancer-related survival was defined as death from colon cancer, either because of recurrence (locoregional or distant) or because of postoperative death after primary treatment or after reoperation. The survival curves were compared using a log-rank test. Factors found to be significant in the univariate analysis by the log-rank test were included in a multivariate Cox regression model. This model was adjusted for age for analysis of overall and cancer-related survival. P-values < 0.050 were considered significant. We used the statistical software package IBM SPSS Statistics version 21 (IBM, Armonk, NY, USA) for all analyses.

Results

Patient demographics and tumour and treatment characteristics of the 2019 patients are shown in Table 1. These data provide a comparison among five time intervals: 1978–1984 (pre-CME), 1985–1994 (CME development), 1995–2002 (CME implementation), 2003–2009 (CME) and 2010–2014 (CME). Over the 37-year period, the patients became older, more patients presented in the prognostically favourable stage I and fewer patients had regional lymph node metastases (stage III). A shift to more right-sided carcinomas was observed, and more extended resections with dissection of two or more lymphatic drainage areas were performed.

TABLE 1

Demographic and tumour and treatment characteristics for 2019 patients

1978–1984 (n = 429) 1985–1994 (n = 491) 1995–2002 (n = 414) 2003–2009 (n = 432) 2010–2014 (n = 253) P-valuea
Age (median/range) 65/27–89 63/24–93 66/28–90 67/17–93 67/23–91 <0.001b
Sex ratio (male:female) 221:208 279:212 243:171 254:178 150:103 0.145
Site
Right colon 73 (17.0) 119 (24.2) 109 (26.3) 144 (33.3) 82 (32.4) <0.001
Transverse colon and flexures 81 (18.9) 80 (16.3) 78 (18.8) 75 (17.4) 48 (19.0)
Left colon 275 (64.1) 292 (59.5) 227 (54.8) 213 (49.3) 123 (48.6)
Emergency surgery 31 (7.2) 50 (10.2) 44 (10.6) 35 (8.1) 28 (11.1) 0.270
Extended resections 56 (13.1) 105 (21.4) 91 (22.0) 86 (19.9) 50 (19.8) 0.007
Multivisceral resection 44 (10.3) 42 (8.6) 40 (9.7) 30 (6.9) 15 (5.9) 0.204
pT
pT1 28 (6.5) 48 (9.8) 48 (11.6) 72 (16.7) 24 (9.5) <0.001
pT2 43 (10.0) 63 (12.8) 84 (20.3) 88 (20.4) 65 (25.7)
pT3 306 (71.3) 332 (67.6) 254 (61.4) 231 (53.5) 152 (60.1)
pT4 52 (12.1) 48 (9.8) 28 (6.8) 41 (9.5) 12 (4.7)
pN
pN0 246 (57.3) 292 (59.5) 268 (64.7) 289 (66.9) 172 (68.0) 0.010
pN1 116 (27.0) 134 (27.3) 96 (23.2) 107 (24.8) 58 (22.9)
pN2 67 (15.6) 65 (13.2) 50 (12.1) 36 (8.3) 23 (9.1)
Stage
Stage I 60 (14.0) 94 (19.1) 105 (25.4) 133 (30.8) 70 (27.7) <0.001
Stage II 186 (43.4) 198 (40.3) 163 (39.4) 156 (36.1) 102 (40.3)
Stage III 183 (42.7) 199 (40.5) 146 (35.3) 143 (33.1) 81 (32.0)

Values in parentheses are percentages unless indicated otherwise. pT1, pT2, pT3, pT4, pNO, pN1 and pN2 are defined according to UICC.13

a χ2 test, except

b Kruskal–Wallis test.

Indicators of process quality

Table 2 presents indicators of process quality. The median number of lymph nodes examined in all specimens was 31 (range 1–145). Overall, fewer than 12 lymph nodes were examined in 99 of 2019 patients (4.9%). In patients with pN0 disease who underwent standard resection (extended resections excluded), we found that the median number of regional lymph nodes examined varied significantly over time. However, the proportion of patients with at least 12 regional lymph nodes examined increased significantly, to 100% during the last time period. In addition, the R0 resection rate increased continuously to 100%, while the occurrence of intraoperative tumour cell dissemination decreased to zero. The use of adjuvant chemotherapy in stage III colon carcinoma increased significantly, from 52% in 1995–2002 to 79% in 2010–2014. The incidence of anastomotic leakage varied over the years, and overall morbidity increased after 1995, while in-hospital mortality was stable.

TABLE 2

Indicators of process quality

1978–1984 (n = 429) 1985–1994 (n = 491) 1995–2002 (n = 414) 2003–2009 (n = 432) 2010–2014 (n = 253) P-valuea
Lymph nodes examined in pN0, standard resection:
 Median 25 32 27 28 25 <0.001b
 ≥12 lymph nodes examined 184/217 (84.8) 221/236 (93.6) 197/211 (93.4) 223/232 (96.1) 139/139 (100) <0.001
R0 resection 416 (97.0) 485 (98.8) 410 (99.0) 431 (99.8) 253 (100) 0.001
Intraoperative tumour cell disseminationc 10/416 (2.4) 8/485 (1.6) 7/410 (1.7) 3/431 (0.7) 0/253 0.046
Adjuvant chemotherapy in stage III 0/167 (0) 12/189 (6.3) 72/138 (52.2) 104/136 (76.5) 62/78 (79.5) <0.001
Anastomotic leakd 18/417 (4.3) 9/480 (1.9) 11/404 (2.7) 18/424 (4.2) 3/246 (1.2) 0.047
Postoperative morbidity 74 (17.2) 69 (14.1) 85 (20.5) 95 (22.0) 54 (21.3) 0.013
In-hospital mortality 16 (3.7) 9 (1.8) 14 (3.4) 10 (2.3) 6 (2.4) 0.383

Values in parentheses are percentages unless indicated otherwise.

a χ2 test, except

b Kruskal–Wallis test.

c By cut-through or tear into the tumour in R0 resections.

d Only patients with an anastomosis.

Indicators of outcome quality

The median duration of follow-up of the 1716 patients included in the analyses of prognosis was 10 years (range 0–36 years). At the time of the analysis (1 January 2015), 1029 patients (60.0%) had died, 333 from colon carcinoma.

The 5-year rate of locoregional recurrence decreased significantly over time, from 6.7% to 2.1% (Table 3 and Figure 1). In the multivariate analysis, we found that the incidence of locoregional recurrence was independently influenced by pT, pN and date in the series chronology, whereby the date was found to be an independent prognostic factor (Table 3 and Figure 1). In stage III, in particular, we found a decrease in the 5-year locoregional recurrence rate from 14.8% [95% confidence interval (CI) 8.7–20.9%; n = 162] in 1978–1984 to 9.6% (95% CI 4.1–14.1%; n = 192) in 1985–1994, 7.1% (95 % CI 2.6–11.6%; n = 142) in 1995–2002 and 4.1% (95% CI 0.6–7.6; n = 140) in 2003–2009 (p = 0.046).

TABLE 3

Indicator of outcome quality – locoregional recurrences

n Univariate analysis Multivariate analysis
5-year rate 95% CI P-valuea Hazard ratio 95% CI P-value
All 1716 4.3 3.3–5.3
1978–1984 401 6.7 4.2–9.2 1.0
1985–1994 483 5.0 3.0–7.0 0.7 0.4–1.3 0.281
1995–2002 403 3.3 1.5–5.1 0.5 0.3–1.1 0.073
2003–2009 429 2.1 0.7–3.5 0.008 0.4 0.2–0.9 0.018
pT1 193 0.5 0–1.5 1.0
pT2 275 1.2 0–2.6 2.4 0.3–21.5 0.435
pT3 1095 4.3 2.9–5.7 4.3 0.6–31.8 0.153
pT4 153 15.1 9.0–21.2 <0.001 9.8 1.3–76.2 0.029
pN0 1080 1.5 0.7–2.3 1.0
pN1 433 5.7 3.3–8.1 2.7 1.4–5.1 0.003
pN2 203 18.5 12.2–24.8 <0.001 7.7 4.1–14.5 <0.001
Elective surgery 1572 4.0 3.0–5.0 1.0
Emergency surgery 144 7.9 3.0–12.8 0.037 1.4 0.7–2.8 0.399

a Log-rank test.

FIGURE 1

Indicator of outcome quality – locoregional recurrences, stages I–III: 1978–1984, n = 401; 1985–1994, n = 483; 1995–2002, n = 403; 2003–2009:, n = 429; p = 0.008 (log-rank test).

HMJ-9-3-6-fig1.jpg

The rate of distant metastases also decreased. It was significantly influenced by the date in the series chronology in univariate analysis (p = 0.01), although not in multivariate Cox regression, while advanced pT, pN and emergency presentation independently increased distant metastasis (Table 4 and Figure 2).

TABLE 4

Indicator of outcome quality – distant metastases

Univariate analysis Multivariate analysis
n 5-year rate 95% CI P-valuea Hazard ratio 95% CI P-value
All 1716 17.6 15.6–19.6
1978–1984 401 18.9 15.0–22.8 1.0
1985–1994 483 22.0 18.3–25.7 1.2 0.9–1.5 0.314
1995–2002 403 15.6 11.9–19.3 1.0 0.7–1.3 0.869
2003–2009 429 13.3 10.0–16.6 0.010 0.9 0.6–1.3 0.570
pT1 193 2.7 0.3–5.1 1.0
pT2 275 3.8 1.4–6.2 1.6 0.7–3.9 0.279
pT3 1095 20.4 17.9–22.9 4.3 2.0–9.2 <0.001
pT4 153 43.4 35.2–51.6 <0.001 6.6 2.9–14.7 <0.001
pN0 1080 8.9 7.1–10.7 1.0
pN1 433 22.3 18.2–26.4 2.0 1.5–2.6 <0.001
pN2 203 56.0 48.7–63.3 <0.001 5.1 3.8–6.7 <0.001
Elective surgery 1572 15.9 13.9–17.9 1.0
Emergency surgery 144 38.3 29.7–46.9 <0.001 2.0 1.5–2.7 <0.001

a Log-rank test.

FIGURE 2

Indicator of outcome quality – distant metastases, stages I–III: 1978–1984, n = 401; 1985–1994, n = 483; 1995–2002: n = 403; 2003–2009, n = 429; p = 0.010.

HMJ-9-3-6-fig2.jpg

Overall survival improved over time, but not significantly so (Table 5 and Figure 3). Here, pT, pN and emergency presentation were independent prognostic factors. We did, however, find a significant improvement over time in cancer-related 5-year survival, from 78.9% to 90.6%. The date of primary treatment independently influenced cancer-related survival (Table 6 and Figure 4). Again, this was particularly evident in patients with stage III disease, among whom 5-year cancer-related survival increased from 61.7% (95% CI 53.9–69.5) in 1978–1984 to 69.7% (95% CI 63.0–76.4) in 1985–1994, 75.4% (95% CI 68.1 to 82.7) in 1995–2002 and 80.9% in (95% CI 74.0–87.8) in 2003–2009 (p = 0.010).

TABLE 5

Indicator of outcome quality – overall survival

Univariate analysis Multivariate model (adjusted for age)
n 5-year rate 95% CI P-valuea Hazard ratio 95% CI P-value
All 1716 76.2 74.2–78.2
1978–1984 401 72.8 68.5–77.1
1985–1994 483 75.0 71.1–78.9
1995–2002 403 78.9 75.0–82.8
2003–2009 429 78.3 74.4–82.2 0.292
pT1 193 87.6 82.9–92.3 1.0
pT2 275 89.5 85.8–93.2 0.9 0.7–1.2 0.469
pT3 1095 74.6 72.1–77.1 1.3 1.0–1.6 0.032
pT4 153 49.7 41.9–57.5 <0.001 1.7 1.2–2.3 0.001
pN0 1080 83.8 81.6–86.0 1.0
pN1 433 73.0 68.9–77.1 1.1 1.0–1.3 0.103
pN2 203 42.8 35.9–49.7 <0.001 2.2 1.8–2.7 <0.001
Elective surgery 1572 78.4 76.4–80.4 1.0
Emergency surgery 144 51.6 43.4–59.8 <0.001 1.7 1.4–2.1 <0.001

a Log-rank test.

FIGURE 3

Indicator of outcome quality – overall survival, stages I–III: 1978–1984, n = 401; 1985–1994, n = 483; 1995–2002, n = 403; 2003–2009, n = 429; p = 0.292 (log-rank test).

HMJ-9-3-6-fig3.jpg
TABLE 6

Indicator of outcome quality – cancer-related survival

Univariate analysis Multivariate model (adjusted for age)
n 5-year rate 95% CI P-valuea Hazard ratio 95% CI P-value
All 1716 84.4 82.6–86.2
1978–1984 401 78.9 74.8–83.0 1.0
1985–1994 483 82.4 78.9–85.9 0.9 0.7–1.2 0.426
1995–2002 403 85.9 82.4–89.4 0.8 0.6–1.0 0.089
2003–2009 429 90.6 87.7–93.5 <0.001 0.5 0.4–0.8 0.001
pT1 193 96.7 94.2–99.2 1.0
pT2 275 97.0 95.0–99.0 1.4 0.6–3.3 0.500
pT3 1095 82.7 80.3–85.1 4.1 1.9–8.7 <0.001
pT4 153 58.4 50.4–66.4 <0.001 6.4 2.9–14.3 <0.001
pN0 1080 92.0 90.4–93.6 1.0
pN1 433 81.5 77.8–85.2 1.7 1.3–2.2 <0.001
pN2 203 49.5 42.4–56.6 <0.001 4.6 3.5–6.1 <0.001
Elective surgery 1572 86.4 84.6–88.2 1.0
Emergency surgery 144 62.4 54.2–70.6 <0.001 2.2 1.6–2.9 <0.001

a Log-rank test.

Postoperative deaths were not excluded.

FIGURE 4

Indicator of outcome quality – cancer-related survival, stages I–III, 1978–1984: n = 401, 1985–1994: n = 483, 1995–2002: n = 403, 2003–2009: n = 429; p <0.001 (log-rank test).

HMJ-9-3-6-fig4.jpg

In a separate analysis, the influence of adjuvant chemotherapy on the survival of stage III patients was examined. To reduce potential bias, only patients treated between 1995 and 2009 were analysed, and patients who died within 3 months after surgery (clearly not candidates for adjuvant treatment) were excluded. Overall survival of 175 patients with adjuvant chemotherapy and 89 patients without adjuvant chemotherapy differed significantly (5-year rate 78.2% vs. 62.9%; p <0.001) while the difference in cancer-related survival (5-year rate 82.3% vs. 78.4%; p = 0.112) was not significant.

Discussion

The concept of CME, as described in 20094 and demonstrated in workshops for 10 years at the author’s institution and elsewhere, is still controversial. It is frequently stated by surgeons that this procedure is nothing new, and has been performed for a long time.16,17 Nevertheless, the term CME has become accepted and is used worldwide among clinicians and in the literature.

As CME represents a combination of various surgical manoeuvres and comprises many factors potentially affecting oncological outcome, the precise component resulting in the favourable oncological outcome cannot be definitively declared at this time. The high tie and the complete mesocolic package act synergistically. To achieve the optimal oncological result while preserving function and quality of life,18 central vascular ligation is usually performed, with preservation of the para-aortic sympathic nerve structures. The para-aortic lymph nodes, defined as non-regional by the UICC,13 are not dissected routinely, and only if they appear to be metastatically involved clinically.

Comparisons of outcome figures summarizing all patients are challenging because the case mix may be different. Also, in our institution the case mix changed over the long period of our analysis. The patients became older, and their life expectancy increased. They presented with more right-sided colon carcinomas (which we had already observed in 200319) and there were more stage I and fewer stage III tumours – presumably because of early detection by colorectal screening. To keep potential bias low we adhered to a clear definition of quality indicators that played a key role in the development of CME.

Indicators of process quality

The median number of regional lymph nodes examined in pN0 standard resections decreased over time, but remained high (n = 25). At the same time, the number of patients in whom fewer than 12 lymph nodes were examined decreased to zero. Stage migration due to better retrieval of regional lymph nodes is used as an argument against CME. However, it is more an argument in favour of CME; a thorough lymph node dissection with removal of metastatically involved lymph nodes can prevent locoregional recurrence and encourages correct staging of regional lymph nodes – essential for the indication for adjuvant chemotherapy. The number of lymph nodes examined as well as the lymph node ratio in stage III are important prognostic factors in colon carcinoma surgery.20

A potential increase in postoperative morbidity and mortality as a result of the more extended form of surgery with CME, especially the central lymph node dissection, remains a concern. This involves the dissection of the superior mesenteric vein and artery with true central tie of the originating vessels for right-sided carcinoma and preservation, for example, of the denuded middle colic artery. This kind of surgery is close to vascular surgery. However, a meticulous dissection will inevitably clarify the wide individual variation in vascular anatomy and help to preserve the vascularization of the remaining bowel.

In our analysis, the rate of postoperative morbidity increased significantly from 1995 onwards. The cause for this remains unclear, with possibilities including a change in the cancer registry in 1997, more sophisticated monitoring and interpretation of postoperative complications or the increase in patient age. Today, a standardized assessment of postoperative complications, such as that proposed by Dindo et al.,21 helps to characterize morbidity in a more objective manner. The rate of anastomotic leakage varied slightly over time but was very low, with 1.2% in the last time interval. In-hospital mortality varied between 1.8% and 3.7% and was always at a low level, although 9.3% of patients required emergency operation, which was performed according to the same protocol as elective surgery.22

Adjuvant chemotherapy in stage III colon carcinoma, introduced in 1995, gradually evolved from levamisole plus fluorouracil regimens23 to the modern regimens that include oxaliplatin24 or irinotecan.25 The delayed introduction was caused by our institution’s participation in a randomized trial comparing adjuvant chemotherapy with no systemic treatment in stage III colon carcinoma.26 Today, approximately 80% of stage III patients who have had R0 resection undergo adjuvant chemotherapy, in accordance with the quality targets of the German S3 guidelines.15

From 2007 onwards, the quality of anatomical plane preservation was audited externally.2729 In prospective studies, the length of resected bowel, distance from the vascular tie to the bowel and the number of regional lymph nodes examined and with metastatic involvement were compared. Although the Erlangen CME specimens and those from Leeds, UK, were found to be significantly larger than the D3 specimens from Tokyo, Japan,30 the distance from the vascular tie to the bowel was similar in the Erlangen CME and Japanese D3 specimens and longer than that of the Leeds specimens. The number of lymph nodes examined was highest in the Erlangen CME specimens; however, the number of metastatically involved lymph nodes was similar. In an analogy to TME, a grading of the surgical plane was developed, classifying the specimen quality: muscularis propria, intramesocolic or mesocolic plane. The Erlangen CME specimens achieved the mesocolic plane category, reflecting the highest specimen quality, in more than 90% of samples. Tears to the muscularis propria were not found.27

Indicators of outcome quality

Locoregional recurrence from colon cancer is still underestimated. The Danish Colorectal Cancer Group reported 1144 locoregional recurrences in 8298 patients with stage I–III colon cancer (13.8%) treated between 2001 and 2008 before implementation of CME surgery.31 In our observation, CME has had the greatest impact on the locoregional recurrence of colon carcinomas. The already low 5-year local recurrence rate of 6.7% was further reduced to 2.1% and was particularly evident in patients with stage III disease, among whom the rate decreased from 14.8% to 4.1%. These rare locoregional recurrences were almost never anastomotic recurrences and rarely lymph node recurrences, but were mostly within the lymphatic drainage unrelated to regional lymph nodes. The negative impact of emergency presentation was in multivariate analysis found not to be relevant to local control. This finding confirms the feasibility of CME as a treatment option, even on an emergency basis. In contrast, the reduction in the rate of distant metastasis was presumably the result of the favourable stage distribution in the later years and the increasing use of chemotherapy in stage III.

Although overall survival improved only marginally (from 72.8% to 78.3%), cancer-related survival improved significantly to a 5-year rate of 90.6%. Each type of survival analysis has different objectives.32 The significant improvement of cancer-related survival cannot be explained solely by the optimization of primary surgery with CME. Adjuvant chemotherapy in stage III colon carcinoma is proven to reduce the rate of distant metastasis and thus may considerably enhance survival time. A comparison and interpretation of outcome figures of patients with and without adjuvant treatment in our non-selected cohort remains difficult.

For analysis of overall and cancer-related survival,32 improvements in diagnosis and treatment of distant metastasis also play an important role. Advances in imaging techniques allow the detection of more and smaller metastases – important for an accurate classification of the primary disease stage as well as for early diagnosis of metachronous distant metastases. Modern multimodal treatment strategies with perioperative chemotherapy, radiofrequency ablation, transarterial chemoembolization and cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy all complement surgical treatment of colorectal distant metastases and can further improve prognosis. In addition, palliative chemotherapy has improved with modern chemotherapy protocols, which are complemented by targeted therapies, such as bevacizumab (Avastin®, Roche, Basel, Switzerland)33 or cetuximab (Erbitux®, Merck Serono, Darmstadt, Germany).34

In summary, CME can be characterized as pivotal for the optimal stage-related treatment of patients with colon carcinoma. This is important for all stages, including lymph node-negative stages, as actual lymph node involvement is only defined postoperatively by the pathologist.

Quality management plays a key role in the continuous improvement of colon cancer treatment. In 1997, we published our quality management programme to improve outcome of rectal cancer surgery,12 which we then adopted for colon cancer. It is based on the prospective documentation with standard proformas for clinical data, intraoperative findings and surgical procedures, results of histopathological examinations, perioperative treatment and a detailed follow-up. (In our series, a detailed follow-up is present in 98.5% of cases.) These questionnaires are filled out by the surgeons and pathologists. Furthermore, every surgeon is documented after pseudonymization. Furthermore, since 1997, we have performed detailed annual analyses of all relevant quality indicators, including the surgeon, with a regular comparison with previous periods. In the case of a negative deviation, we carry out detailed subanalyses. If the quality of an individual surgeon declines, a structured dialogue with the department chair is conducted. The individual surgeon’s results are kept strictly confidential, known only to the chair and the head of the cancer registry. In contrast, the chair’s results are open to any staff surgeon in the department.

Current trends and future perspectives

Laparoscopic surgery for colon cancer is increasingly applied. If CME is used it may be challenging, particularly in obese patients, not only to preserve the integrity of the mesocolic plane, but also to gain safe access to the central vessels and the venous drainage on the right side. A learning curve is to be expected, as for open CME surgery. However, technical aspects for either open or laparoscopic access should never jeopardize specimen quality or obviate central lymph node dissection. In the present study, only 28 of 2019 patients (1.4%) underwent laparoscopy-assisted CME, as it was only recently implemented.

Between 2008 and 2011, at Aarhus University Hospital, CME and laparoscopy-assisted surgery were implemented simultaneously.8 Of 356 CME patients, 83 underwent laparoscopy-assisted surgery for either right- or left-sided colon carcinomas. Subbiah et al.35 preferred the laparoscopic initial retrocolic endoscopic tunnel approach (IRETA) for CME with central vascular ligation. In 83 of 212 patients with stage III disease, IRETA was considered especially useful.35 Melich et al.36 report that laparoscopic right hemicolectomy with CME takes longer than the conventional laparoscopic procedure, and that the number of lymph nodes was high (mean 31.3) and major complications were observed in only 3.7% of patients. West et al.37 confirmed in a study of 69 laparoscopically assisted CMEs that the technique produced a specimen similar to open CME with respect to mesocolic plane resection rate and distance from bowel wall to vascular ligation, while the number of lymph nodes removed was lower following laparoscopic CME (median 18 vs. 32 with open CME; p <0.001).

The routine quality management of the future should also include photo documentation of specimen quality, a classification of the plane of surgery (muscularis propria, intramesocolic or mesocolic) and the distance from bowel to the vascular tie. Although outstanding, outcome figures including those for node-positive cases that were reported 20 years ago by other authors, and population-based data from the western hemisphere to argue for true CME surgery remain lacking. After broad implementation of CME surgery, more series including large numbers of patients are needed because a randomized trial is not feasible.

Conclusion

In summary, the quality indicators of process and outcome quality improved with CME. The reduction of locoregional recurrences was particularly evident in stage III, with a decrease in 5-year recurrence rates from 14.8% to 4.1%. Further contributions to improved outcome are adjuvant chemotherapy in stage III and multidisciplinary approaches in patients with metachronous distant metastases. Strict quality management is mandatory to accompany changes in treatment.

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