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Randomized clinical trial of conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal cancer
The American Journal of Surgery (2012) 204, 274 –282
Clinical Science
Randomized clinical trial of conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal cancer Jia Gang. Han, M.D., Zhen Jun. Wang, M.D.*, Guang Hui. Wei, M.D., Zhi Gang. Gao, M.D., Yong Yang, M.D., Bao Cheng. Zhao, M.D. Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China KEYWORDS: Cylindrical abdominoperineal resection; Human acellular dermal matrix; Circumferential resection margin; Morbidity; Survival
Abstract BACKGROUND: An alternative treatment for low rectal cancer is the cylindrical technique. We aim to compare the outcomes of patients undergoing conventional abdominoperineal resection (APR) versus cylindrical APR. METHODS: A prospective, randomized, open-label, parallel controlled trial was conducted between January 2008 and December 2010. Sixty-seven patients with T3-T4 low rectal cancer were identified during the study period (conventional n ⫽ 32, cylindrical n ⫽ 35). RESULTS: Patients who received cylindrical APR had less operative time for the perineal portion (P ⬍ .001), larger perineal defect (P ⬍ .001), less intraoperative blood loss (P ⫽ .001), larger total cross-sectional tissue area (P ⬍ .001), similar total operative time (P ⫽ .096), and more incidence of perineal pain (P ⬍ .001). The local recurrence of the cylindrical APR group was improved statistically (P ⫽ .048). CONCLUSIONS: Cylindrical APR in the prone jackknife position has the potential to reduce the risk of local recurrence without increased complications when compared with conventional APR in the lithotomy position for the treatment of low rectal cancer. © 2012 Elsevier Inc. All rights reserved.
Supported by the Program for Outstanding Medical Academic Leader, Beijing, China (Number 2009-1-03), the New Century National Hundred, Thousand and Ten Thousand Talent Project, China (Numbers 09-911-002 and 08-009) National Natural Science Fund Projects, China (81141025), Training Programme Foundation for the Talents of Beijing (2011D003034000003), Capital Medical Development Scientific Research Fund (2009-3109), the Basic and Clinical Cooperation Project of Capital Medical University (10JL04), and the Youth Foundation of Beijing Chaoyang Hospital. Presented in part at the Chinese Surgical Week, September 7–10, 2011, Beijing, China, and 2011 European Multidisciplinary Cancer Congress, September 23–27, 2011, Stockholm, Sweden (poster). * Corresponding author. Tel: ⫹86-10-8523-1604; fax: ⫹86-01360139-3711. E-mail address: [email protected] Manuscript received January 21, 2012; revised manuscript May 18, 2012
0002-9610/$ - see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2012.05.001
Since the description of total mesorectal excision (TME) by Heald et al1 in 1982, local control of rectal cancer and patient survival have been improved remarkably. Despite this, a high rate of bowel perforation, circumferential resection margin (CRM) involvement, and local recurrence after abdominoperineal resection (APR) has been reported constantly.2–5 In a UK study involving 608 patients, patients who underwent APR had a higher local recurrence and lower survival when compared with patients who had low anterior resection (LAR).4 Heald et al6 even stated that APR was an endangered operation and would be well buried for all but very occasional cancers. This may be secondary to smaller tissue volume removed adjacent to the tumor. When performing a conventional APR, the resected specimen usually narrows at the lower border of the mesorectum at the level just above the levator muscle where
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lesions are most commonly located.7 At this point, the CRM is often close to the rectal muscle tube.7 It is well established that bowel perforation and tumor involvement of the CRM are strong predictors of local recurrence and survival in rectal cancer.8 To reduce CRM positivity, extralevator APR7 (cylindrical APR) and abdominosacral resection9 were performed in patients with T3-T4 tumors, which aimed to create a more cylindrical specimen without a waist. Recent long-term experience10 and a multicenter trial11 both have shown that extended operations for rectal cancer were associated with a lower risk of bowel perforation and CRM involvement than conventional APR. Several perineal wound complications may occur after APR, including infection, breakdown, sinus, and delayed healing. The incidence of perineal wound complications after APR can range from 26% to 41%.12–14 It has been suggested that extended resection, such as the cylindrical APR, may be associated with greater morbidity because of the formation of a large perineal defect. A multicenter trial showed that the perineal wound complication rate was about twice as high in patients treated with cylindrical APR than in those treated with conventional APR.11 We have reported our initial experience using human acellular dermal matrix (HADM) (Ruinuo; Qingyuanweiye Bio-Tissue Engineering, Ltd; Beijing, China) for single-stage, pelvic floor reconstruction after extended resection of rectal cancer previously, and the preliminary results showed that HADM could provide a safe alternative for the reconstruction of large pelvic defect without severe complications.15 This study was undertaken to further report the complications of patients whose locally advanced lower rectal cancer were managed with cylindrical APR and large pelvic defects were reconstructed with HADM and compare surgical and oncologic outcomes in patients who received cylindrical APR in the prone jackknife position versus conventional APR in the lithotomy position.
Methods Patients Between January 2008 and December 2010, 67 patients with T3-T4 low rectal cancer were enrolled in this prospective study (NCT00949273). Eligibility criteria are listed in Table 1. The operations were mainly performed by two of the authors (WZJ and WGH) who performed both procedures in cooperation with an experienced blinded pathologist. Randomization was performed on the day before surgery through sealed opaque envelopes containing a surgical method. Preoperatively, patients underwent digital rectal examination, magnetic resonance imaging, and/or endoscopic ultrasonography for staging of the rectal cancer. All patients with clinical staging of T3 N1-N2 or T4 tumors were en-
275 Table 1
Study inclusion and exclusion criteria
Inclusion criteria 1. Tumor within 5 cm of the anal verge or with a very narrow pelvis 2. T3-T4 as determined by preoperative magnetic resonance imaging or endorectal ultrasonography examination or a low tumor is fixed or tethered at rectal examination 3. Absence of distant metastases 4. Absence of intestinal obstruction Exclusion criteria 1. T1-T2 as determined by preoperative magnetic resonance imaging or endorectal ultrasonography examination 2. With distant metastases 3. With intestinal obstruction 4. Pregnancy or lactation 5. Allergic constitution to heterogeneous protein 6. With operation contraindication
couraged to receive neoadjuvant chemoradiotherapy. This consisted of 3 cycles of FOLFOX4 (oxaliplatin, 5-fluorouracil, and leucovorin) repeated every 2 weeks. Radiotherapy was added after the first cycle of chemotherapy (5-Gy fractions daily for 5 days followed by 2.5-Gy fractions daily for 2 days). For patients who received neoadjuvant therapy, we performed magnetic resonance imaging/computed tomography scans afterward to restage these patients. The study was approved by the institutional review board of Beijing Chaoyang Hospital. All patients gave informed consent for use of their data in this study.
Surgical technique Cylindrical APR. The cylindrical APR surgical procedure was performed according to the methods previously described by Holm et al.7 Pelvic dissection is stopped before the mesorectum is dissected off the levator ani muscles.7,11 The patient was then turned over into the prone jackknife position. The coccyx or S5 vertebra was disarticulated from the sacrum according to the level of tumor and the guiding of preoperative MRI. The levator muscles were divided laterally at its insertion onto the pelvic side wall on both sides. After the cylindrical specimen was removed (Fig. 1A), the pelvic reconstruction was performed according to our previous study (Fig. 2A and B).15 One sheet of 8 ⫻ 10 cm HADM mesh (Ruinuo) was sutured directly to the residual pelvic floor muscle and fascia using interrupted or continuous sutures (2/0 Vicryl, Johnson & Johnson, Sint Stevens Woluwe, Belgium) with an appropriate amount of tension with about 1-cm intervals, ensuring at least a 3-cm overlap circumferentially. One must be careful not to suture the nerves of the genital organs that run along the lateral wall of the ischioanal fossa. One perineal drain was placed in the pelvic cavity near the mesh along the pelvic sidewall with at least 1 side hole above the mesh and 1 under the mesh. The
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Pathologic data All APR specimens underwent routine pathologic processing, which included fixation in 10% formalin, painting of the CRM, and serial slicing along the tumor at 3- to 5-mm intervals as described previously.16 Digital photographic images of the whole specimen and of serial cross-sectional slices alongside a metric scale were taken and were stored in the computer. Precise tissue quantitation was performed with the Image-Pro plus 6.0 (Media Cybernetics, Inc, Silver Spring, MD) on all slices that contained a tumor by using a method described previously.17 The total cross-sectional tissue area and crosssectional area of the tissue outside the internal sphincter (IS) or the muscularis propria (MP) were obtained. Any tumor located less than 1 mm from the circumferential margin was defined as positive according to previous evidence.18 Figure 1 A surgical specimen of the rectum. (A) Cylindrical APR leaves the levator attached to the mesorectum, which creates a cylindrical specimen. (B) Conventional APR creates a waist on the specimen.
ischiorectal fat and skin were closed primarily using interrupted sutures over the HADM mesh. Patients were encouraged to be out of bed and ambulating on postoperative day 1. The drain was removed when the output was less than 20 mL/d. Conventional APR. When performing conventional APR, the surgeon follows the plane outside the mesorectum down to the pelvic floor to the top of the anal canal, and the mesorectum is mobilized from the levator muscles. The perineal part of the operation is then performed from below in the same lithotomy position, with excision of the anal canal including the surrounding skin, ischiorectal fat, and the lower portions of the levator muscles (Fig. 1B). The perineal wound is closed primarily in multiple layers including the muscle layer of the pelvis floor, perineal fat, and skin.
Follow-up Patients with a T3/T4 tumor or lymph node metastases received postoperative systemic chemotherapy with either oxaliplatin, 5-fluorouracil, and leukovorin or capecitabine and oxaliplatin for a duration of 6 months including the period of preoperative chemotherapy. Follow-up was arranged every 3 months for 2 years and then 6 months thereafter. In addition, data from the last available follow-up visit were included in the analyses. Colonoscopy was performed 1 year after the operation and then will be repeated every 3 years if no lesion was found. Colonoscopy was performed at 3-6 months if no complete visualization of the colon had been done preoperatively.
Statistics Statistical analysis was performed using SPSS for Windows (version 16.0; SPSS Inc, Chicago, IL). Continuous variables (eg, age, distance of from the dentate line, and so on) are presented as median values with ranges in parentheses. Survival analysis was performed using the Kaplan-
Figure 2 Pelvic floor reconstruction after cylindrical APR in the prone jackknife position. (A) The pelvic floor defect after cylindrical APR in the prone position. (B) Using human acellular dermal matrix for reconstruction of the pelvic floor.
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Clinical characteristics grouped by surgical technique
Age (y), median (range) Male/female BMI (kg/m2), median (range) Neoadjuvant therapy Tumor Distance from anal verge (cm), median (range) Maximum tumor diameter (cm), median (range) Preoperative tumor stage T3 N0 M0 T3 N1-2 M0 T4 N1-2 M0 Postoperative tumor stage T3 N0 M0 T3 N1-2 M0 T4 N1-2 M0 Perineal defect size (cm2), median (range) Total operative time (min), median (range) The time to reposition the patient (min), median (range) Operative time for perineal portion (min), median (range) Intraoperative blood loss (mL), median (range) Positive CRM Bowel perforation Hospital stay (d), median (range) Postoperative follow-up (mo), median (range) VAS pain score at 3 mo postoperatively, median (range) VAS pain score at 12 mo postoperatively, median (range)
Cylindrical APR (n ⫽ 35)
Conventional APR (n ⫽ 32)
P value
63 (44–81) 20/15 27.0 (21.2–35.0) 10
68 (32–84) 21/11 27.0 (21.0–35.6) 9
.168* .785† .736* .968†
3.0 (2.0–5.0) 5.75 (4.5–8.5)
.840* .310* .684†
3.0 (2.0–7.0) 6.0 (4.0–10.0) 5 19 11
6 14 12
10 20 5 64 190 15 32 200 2 2 9 29 4 3
10 14 7 42 215 — 46 300 9 5 11 22 1 0
.562†
(38–100) (140–420) (10–40) (20–50) (100–500) (7–18) (12–48) (0–10) (0–9)
(24–80) (160–330) (32–65) (150–600) (7–22) (14–46) (0–8) (0–6)
⬍.001* .096* — ⬍.001* .001* .013† .246† .056* .185* ⬍.001* .001
*Mann-Whitney U test. †Chi-square analysis.
Meier curve. Comparisons between groups were analyzed using chi-square analysis or a rank sum test (Mann-Whitney U test). Significance was defined as P ⬍ .05.
Results Patient characteristics The characteristics of patients, tumors, and operations are summarized in Table 2. Two hundred eighty-nine patients underwent surgical resection for the treatment of rectal cancer at our institution. Sixty-seven eligible patients were randomly entered into this study: 32 to receive conventional APR and 35 to receive cylindrical APR. The age and sex distribution between the 2 groups were not significantly different. Preoperatively, 10 patients (29%) in the cylindrical APR group and 9 patients (28%) in the conventional APR group underwent neoadjuvant therapy. Twenty-five patients in the cylindrical APR and 23 patients in the conventional APR group did not receive neoadjuvant therapy for many reasons (eg, elderly, comorbidities, patient choice, and surgeon’s neglect in the early research from 2008 to 2009). There was no major complication from the neoadjuvant therapy.
The median time for the perineal portion was significantly shorter in the cylindrical APR group than in the conventional group (32 vs 46 minutes, P ⬍ .001). Patients in the conventional APR group had smaller perineal defects (42 vs 64 cm2, P ⬍ .001) but more intraoperative blood loss (300 v 200 mL, P ⫽ .001) compared with those in the cylindrical APR group. The median total operative time (including the time to reposition the patient in the cylindrical APR group) for cylindrical APR was 190 minutes (range 140 – 420 minutes), which was similar to patients who underwent conventional APR (215 minutes [range 160 –330 minutes], P ⫽ .096, Table 2).
Tissue morphometry The cylindrical APR removed approximately 50% more total cross-sectional tissue (P ⬍ .001) and 77% more tissue outside the IS/MP (P ⬍ .001) in slices that contained macroscopic evidence of tumors. The CRM of the cylindrical APR group was significantly longer than the conventional APR group (2.2 vs 1.85 mm, P ⫽ .002, Table 3).
Tumor characteristics According to the American Joint Committee on Cancer TNM classification, there were 30 patients in the cylindrical
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Table 3
Tissue morphometry in slices that contained tumors
CRM (mm), median (range) Total cross sectional tissue area (mm2), median (range) Cross-sectional tissue area outside the IS or MP (mm2), median (range)
Cylindrical APR (n ⫽ 35)
Conventional APR (n ⫽ 32)
P value*
2.2 (1.0–4.9) 2600 (999–3,812) 2146 (793–3,348)
1.85 (.2–5.0) 1738 (1,100–2,390) 1211 (608–1,765)
.002 ⬍.001 ⬍.001
*Mann-Whitney U test.
APR and 20 patients in the conventional APR group who had pathologic stage T3 cancer; 5 patients and 7 patients had T4 cancer, respectively (P ⫽ .562). The organs involved in the T4 cancers were vagina (n ⫽ 1), prostate (n ⫽ 2), and sacrum (n ⫽ 2) in the cylindrical APR group and vagina (n ⫽ 3), prostate (n ⫽ 3), and coccyx (n ⫽ 1) in the conventional APR group. In the patients with T4 tumors, 1 patient had a positive CRM and 1 had bowel perforation in the cylindrical APR group (n ⫽ 5), and seven had a positive CRM and 3 had bowel perforation in the conventional APR group (n ⫽ 7). In total, there were fewer patients with a positive CRM in the cylindrical APR versus the conventional APR (5.7% vs 28.1%, P ⫽ .013). A lower frequency of bowel perforation was also observed in the cylindrical APR group, but the difference was not statistically significant (5.7% vs 15.6%, P ⫽ .246).
Mortality and morbidity There was no postoperative mortality documented. Eighteen patients (51%) in the cylindrical APR group and 19 patients (59%) in the conventional APR group developed postoperative complications (P ⫽ .515). Sexual dysfunction, urinary retention, peristomal hernia, and perineal wound complications were the 4 most common complications observed in both groups (Table 4). Patients were excluded from sexual analysis if they were not sexually active preoperatively. Twenty-seven patients (77%) in the cylindrical APR group and 20 patients (63%) in the conventional APR group were sexually active preoperatively.
Table 4
The rate of sexual dysfunction was 74% (20/27) and 60% (12/20), respectively, at 1 year after cylindrical and conventional APR (P ⫽ .306). The incidence of chronic perineal pain was significantly higher in the cylindrical APR group (P ⬍ .001). Visual analog scale (VAS, with a score of 1-10) was used to evaluate the postoperative perineal pain severity. A VAS score ⬎4 was considered positive. The VAS pain score at 3 months postoperatively was significantly higher in the cylindrical APR group than in the conventional APR group (median 4 vs 1, P ⬍ .001) and was also significantly higher at 12 months postoperatively (median 3 vs 0, P ⫽ .001, Table 2). Among the patients with a positive VAS score, 5 required oral nonsteroidal anti-inflammatory drugs for pain relievers, and 3 required oral tramadol. In the cylindrical APR group, a positive VAS score (score ⫽ 6, 6, and 4, respectively) in 3 patients (3/18) at 3 months postoperatively changed into a negative score at 12 months postoperatively. At 18 months postoperatively, a positive VAS score (score ⫽ 8, 8, 7, 7, and 6, respectively) in 5 (5/18) patients changed into a negative score.
Oncologic results The median follow-up time was 29 months (range 12– 48 months) in the cylindrical APR group and 22 months (range 14 – 46 months) in the conventional APR group. Within the cylindrical APR group, 1 patient had local recurrence, 1 patient had liver metastases, and 2 patients had combined liver and pulmonary metastases. In the conventional APR group, local recurrence occurred in 4 patients with a positive
Postoperative complications
Complications
Cylindrical APR n (% of total)
Urinary retention Chronic perineal pain Perineal wound infection Urinary system infection Pulmonary infection Perineal seroma Peristomal hernia Abdominal wound infection Perineal herniation
14 18 4 2 4 4 16 2 5
*Chi-square analysis.
(40.0) (51.4) (11.4) (5.7) (11.4) (11.4) (45.7) (5.7) (14.3)
Conventional APR n (% of total) 9 2 6 3 5
(28.1) (6.3) (18.8) (9.4) (15.6)
0 13 (40.6) 3 (9.4) 4 (12.5)
P value* .307 ⬍.001 .501 .664 .727 .115 .675 .664 1.000
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Figure 3 Survival of low rectal cancer patients. (A) Kaplan-Meier curves showing the overall survival after cylindrical and conventional APR for rectal cancer (P ⫽ .202). (B) Kaplan-Meier curves showing disease-free survival after cylindrical and conventional APR for rectal cancer (P ⫽ .165).
CRM, combined local recurrence and liver metastases in 2 patients, and combined liver and pulmonary metastases in 1 patient. The difference of local recurrence was statistically significant (2.8% vs 18.8%, P ⫽ .048). Two patients (5.7%) in the cylindrical APR group and 5 patients (15.6%) in the conventional APR group died of tumor recurrence. One patient in the cylindrical APR group who was free of tumor recurrence died of a heart attack 35 months after surgery. Overall survival and disease-free survival between the 2 groups were examined, and no statistically significant difference was shown. The mean length of the overall survival in the cylindrical APR group was 45 months and 40 months in the conventional APR group (P ⫽ .202, log-rank test; Fig. 3A), and the mean length of disease-free survival was 44 months and 38 months, respectively (P ⫽ .165, log-rank test; Fig. 3B).
Comments Although the use of very low anterior resection is becoming more popular because the safety of the procedure increased through the use of improved suture instruments, APR is still a common procedure for patients with T3/T4 low rectal cancer. With conventional APR, the risk of inadvertent bowel perforation is high, the resulting specimen frequently has a waist at the lower border of the mesorectum, and the CRM is often close to the rectal muscle tube.3 A recent meta-analysis of 5 European randomized clinical trials on rectal cancer revealed that the APR procedure is a significant predictor for nonradical resections and increased risk of local recurrence with decreased cancer-specific survival.19 Whenever possible, a more radical operation should be considered for low rectal cancer for these reasons. Cylindrical APR introduced by Holm et al7 may be an alternative to conventional synchronous combined APR. The main differences between this procedure and conven-
tional APR are (1) the mesorectum is not dissected off the levator muscles, (2) the perineal part of the operation is performed with the patient in the prone jackknife position, and (3) the entire levator muscle is resected en bloc with the anal canal and lower rectum. This creates a cylindrical specimen with more tissue removed surrounding the tumor in low rectal cancer as shown in our study. By leaving the levator muscles and ischiorectal fossa fat attached to the specimen in the cylindrical APR group, more clearance will be obtained, thus reducing the chances of CRM involvement and intraoperative perforations and removing more tissue outside the IS or MP, which will help the patients in terms of the removal of cancer. A multicenter trial indicated that cylindrical APR was associated with less CRM involvement and intraoperative perforation than standard surgery,11 which was confirmed by our study. The CRM of the cylindrical APR group was significantly longer than the conventional APR group (2.2 vs 1.85 mm, P ⫽ .002) in our study. However, .35 mm was not a clinically significant difference for CRM positivity. The statistical significance might actually be irrelevant. A previous study showed that the cylindrical technique has the potential to improve local recurrence rates and survival rates in patients with low rectal cancers.2 In a Polish study involving 210 low rectal cancer patients who underwent extended APR, the observed 2-year local recurrence rate was 4.4%, whereas the 5-year observed and relative survivals were 68.3% and 73.2%, respectively.10 We compared the local recurrence and survivals of the cylindrical APR group with those of the conventional APR group. Although the survivals between the 2 groups were really not statistically significant, the local recurrence was improved statistically in the cylindrical APR group. These results suggested that the oncologic benefits of cylindrical APR might be better than those of conventional APR in patients with advanced lower rectal cancer. There was a difference of bowel perforation between cylindrical APR
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and conventional APR group (5.7% vs 15.6%), but this was not statistically significant. After the completion of cylindrical APR, reconstruction of the pelvic defect poses a difficult challenge for surgeons. With an extended resection of the levator muscles, there is only fatty tissue and skin to cover the perineal defect. In the past, these defects were closed primarily, resulting in complication rates as high as 62.5%.20 These complications can include wound infection, dehiscence, and herniation. Various myocutaneous flaps are probable solutions, but all carry the risk of donor-site morbidity, longer bed rest, flap necrosis, or potentially impaired ambulation.7,21–23 A biological tissue graft (Surgisis BioDesign, Cook Surgical Inc, Bloomington, IN) for pelvic floor reconstruction after cylindrical APR was described by Boereboom et al,24 but the detailed results of the operation were not provided. Wille-Jørgensen et al25 reported 11 consecutive patients with pelvic floor reconstruction after APR, and the use of crosslinked porcine dermis (Permacol, Tissue Science Laboratories, Aldershot, Hampshire, UK) was feasible with satisfactory results. HADM is a biological material consisting of dermis without its cellular components. Several experimental and clinical studies have shown that HADM can be used to repair complex abdominal defects even in contaminated or potentially contaminated surgical fields.26,27 However, its application in pelvic reconstruction has not gained widespread use. Our study confirms that large pelvic floor defects after cylindrical APR can be successfully closed in a single-stage, tension-free repair using HADM without an increased risk of serious complications. To the best of our knowledge, sexual function after cylindrical APR has rarely been reported before.11 Sexual dysfunction was the most popular complication in both the cylindrical and conventional APR groups in our study. There was no significant difference between them. Our results were similar to those of West et al.11 Hendren et al28 reported that sex life was affected negatively in 84% pa-
tients undergoing APR. In a series of 261 patients, the rate of sexual dysfunction at 1 year postoperative was 79% after APR.29 Sexual function has been known to depend on the integrity of the pelvic autonomic nervous plexuses. Sexual dysfunction can be caused by damage at the level of the superior hypogastric plexus or the hypogastric nerves before they join together with the parasympathetic nerves at the inferior hypogastric plexus.30 APR is one of the most common risk factors for postoperative sexual dysfunction, whereas the stage and the size of the tumor do not seem to have an influence.31 A recent study on anatomic dissection reported that the clear identification of pelvic anatomic landmarks might be useful for the successful achievement of both negative CRMs and the preservation of urogenital functions during cylindrical APR.32 We suggested that, with the familiarity with pelvic anatomy and precise surgical procedure, the cylindrical technique may remove more tissue in the distal rectum compared with the conventional APR without improving sexual dysfunction. According to anatomic research, the nerves of the genital organs run along the lateral wall of the ischioanal fossa in which the pudendal nerve extends within the pudendal canal.32,33 For the pelvic floor to be removed completely, the lateral incision of the pelvic floor should be close to this area and thus may damage the nerve.33 We suppose that the cylindrical APR technique may be performed according to individual conditions. For the rectal tumors suitable for cylindrical APR, most of them were circular or nearly circular infiltrating tumors. Patients with these rectal tumors should receive full cylindrical APR resection. In those rectal tumors not involving the levator ani muscle, the dissection plane may continue close to the external anal sphincter and the levator ani muscle, leaving the ischioanal fat and the terminal branches of the pudendal nerve intact (Fig. 4).32 If the tumor has only penetrated into 1 side of the levator ani muscle, the dissection might include the levator ani muscle and the fat of the ischioanal fossa on the side of the tumor
Figure 4 Individual cylindrical APR technique according to individual conditions. (A) If the tumor penetrates into the levator ani muscle, the dissection should include the fat of the ischioanal fossa to achieve a clear CRM (right). If the tumor only involves the levator ani muscle, the dissection plane may continue close to the external anal sphincter and the levator ani muscle (left). (B) The dissection includes the levator ani muscle and the fat of the ischioanal fossa on the side of the tumor (right), whereas the ischioanal fat and levator ani muscle on the other side of the tumor might be left (left).
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to achieve a clear CRM, whereas the ischioanal fat and levator ani muscle on the other side of the tumor may be left (Fig. 4B). This individual cylindrical APR may be as effective as full cylindrical APR while minimizing the operative trauma and the damage to the nerves of the genital organs. Chronic perineal pain was the most popular postoperative complication in our cylindrical APR group (51.4%). The patients felt pain in the operated sacrococcygeal region and had difficulty sitting for an extended amount of time. Eight patients (44.4%) required pain-relieving drugs. The long-lasting perineal pain was also observed in patients (54.5%) whose pelvic floor defects were repaired with Permacol after APR.25 The chronic pain may be related to the activation of the inflammatory cytokines at the mesh site,25 the coccygectomy, the damage to the pudendal nerve, the wider excision of the levator ani muscles and ischiorectal fossa fat, and the suturing of the mesh itself close to the pelvic wall. The coccygectomy may be the main reason. To reduce the postoperative chronic perineal pain, C1/S5 sacrectomy may not be necessary for anterior rectal tumors. According to our study, we considered that relatively lighter pain might gradually ease over time. Several studies, including our initial report, have shown that HADM was safe and effective in abdominal wall and pelvic floor repair.15,26,34,35 However, disadvantages of HADM have appeared with increasing use. Specifically, one of the most prominent concerns with HADM is the laxity with time, leading to a bulge or recurrent hernia after abdominal wall repair.26 Few studies have reported perineal hernia after pelvic floor reconstruction with biological mesh.25,36 One study compared perineal defect reconstruction with a fasciocutaneous gluteal flap versus biological mesh after cylindrical APR.36 There were 33 patients with gluteal flap and 24 with biological mesh reconstruction, and perineal hernia developed in 7 (21%) patients in the gluteal flap group and none of the patients in the mesh group.36 Wille-Jørgensen et al25 also reported no perineal hernia after pelvic floor reconstruction. In our study, the perineal hernia rate after pelvic floor reconstruction with HADM was 14.3%. The laxity of HADM with time may be the main reason.26 Suturing the HADM to the residual pelvic floor muscle and fascia with a great deal of tension might reduce the hernia rate. Furthermore, the high hernia recurrence rate warrants a continued search for alternative biological materials to improve outcomes. In our series, the cylindrical APR group had a statistically less median operative time for perineal portion compared with the conventional APR group, partly because of the prone jackknife position and the simplified perineal part of the operation. Performing the perineal portion of the operation in the prone jackknife position resulted in a further reduction of intraoperative blood loss. The cylindrical APR group had a similar total operative time compared with the conventional APR group despite adding the time to reposition the patient, probably because of less pelvic dissection and the simplified perineal part of the opera-
281 tion. Although a recent study reported that the prone jackknife position during perineal dissection in an APR did not affect perioperative morbidity or oncologic outcomes compared with the lithotomy position,37 we prefer to use the prone position because of the excellent exposure of the perineal structures, the optimal access to the sacrum, and the possibility of immediate closure of large pelvic floor defects. However, it should be addressed that the prone jackknife position was only part of the cylindrical APR procedure that facilitated the surgical procedure. We considered that the reduced tumor involved resection margins and intraoperative bowel perforation could not be achieved only with the prone jackknife position without cylindrical APR. The time for reconstruction of the pelvic floor with HADM averaged around 10 minutes in our study. This was shorter compared with the time required to perform the myocutaneous flap reconstruction, which varied from 30 to 100 minutes depending on the literature.7,38 Furthermore, patients who underwent reconstruction using the myocutaneous flap were asked to avoid direct pressure on the flap and no ambulation for as long as 14 days after the original operation.7,21 In our series, the postoperative care in the cylindrical APR group was the same as patients who had undergone conventional APR without pelvic floor reconstruction. Previous studies showed that HADM supported vascular ingrowth and exhibited increased breaking strength when used as a fascial interposition graft for abdominal wall reconstruction.27,34,35 Furthermore, Christensen et al36 suggested that it was unable to show a difference between HADM and synthetic mesh in their ability to repair ventral hernias even at 9 months. We believed that the ability of HADM makes it possible to reconstruct the pelvic floor, and early ambulation dose not interfere with wound healing. We consider that most patients with T3-T4 or nodepositive low rectal cancer should receive preoperative chemoradiotherapy, but there were only 10 patients (29%) in the cylindrical APR and 9 patients (28%) in the conventional APR group who underwent neoadjuvant therapy in our study. The 18.8% local recurrence rate of our study is extremely high compared with the 11.9% local recurrence rate reviewed by Stelzner et al39 for conventional abdominal perineal resection. We considered that the lack of preoperative radiation therapy may have resulted in this poor result,40 and this was an extremely serious defect in our study. This might not be applicable to patients in whom preoperative chemoradiotherapy was able to shrink the tumors and might make the patient group abnormal and, therefore, not able to be truly evaluated. In our series we tried to compare the results of consecutive patients who underwent cylindrical versus conventional APR, and the study proposed that cylindrical APR in the prone position has the potential to reduce the risk of local recurrence without increased complications. A multicenter study with a larger patient number is currently in progress to evaluate the true outcomes of the technique.
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Acknowledgments The authors thank Judy Jin, M.D., of the Department of Surgery, University Hospitals Case Medical Center, Cleveland, OH, and Hui Chen, Ph.D., of Capital Medical University, Beijing, PR China for her statistical assistance.
References 1. Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg 1982;69:613– 6. 2. West NP, Finan PJ, Anderin C, et al. Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer. J Clin Oncol 2008;26:3517–22. 3. Nagtegaal ID, van de Velde CJ, Marijnen CA, et al. Low rectal cancer: a call for a change of approach in abdominoperineal resection. J Clin Oncol 2005;23:9257– 64. 4. Marr R, Birbeck K, Garvican J, et al. The modern abdominoperineal excision: the next challenge after total mesorectal excision. Ann Surg 2005;242:74 – 82. 5. Wibe A, Syse A, Andersen E, et al. Oncological outcomes after total mesorectal excision for cure for cancer of the lower rectum: anterior vs. abdominoperineal resection. Dis Colon Rectum 2004;47:48 –58. 6. Heald RJ, Smedh RK, Kald A, et al. Abdominoperineal excision of the rectum—an endangered operation. Norman Nigro lectureship. Dis Colon Rectum 1997;40:747–51. 7. Holm T, Ljung A, Häggmark T, et al. Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer. Br J Surg 2007;94:232– 8. 8. Bernstein TE, Endreseth BH, Romundstad P, et al. Colorectal Cancer Group. Circumferential resection margin as a prognostic factor in rectal cancer. Br J Surg 2009;96:1348 –57. 9. Bebenek M, Pudełko M, Cisarz K, et al. Therapeutic results in lowrectal cancer patients treated with abdominosacral resection are similar to those obtained by means of anterior resection in mid- and upperrectal cancer cases. Eur J Surg Oncol 2007;33:320 –3. 10. Bebenek M. Abdominosacral amputation of the rectum for low rectal cancers: ten years of experience. Ann Surg Oncol 2009;16:2211–7. 11. West NP, Anderin C, Smith KJ, et al. Multicentre experience with extralevator abdominoperineal excision for low rectal cancer. Br J Surg 2010;97:588 –99. 12. Artioukh DY, Smith RA, Gokul K. Risk factors for impaired healing of the perineal wound after abdominoperineal resection of rectum for carcinoma. Colorectal Dis 2007;9:362–7. 13. Bullard KM, Trudel JL, Baxter NN, et al. Primary perineal wound closure after preoperative radiotherapy and abdominoperineal resection has a high incidence of wound failure. Dis Colon Rectum 2005; 48:438 – 43. 14. Christian CK, Kwaan MR, Betensky RA, et al. Risk factors for perineal wound complications following abdominoperineal resection. Dis Colon Rectum 2005;48:43– 8. 15. Han JG, Wang ZJ, Gao ZG, et al. Pelvic floor reconstruction using human acellular dermal matrix after cylindrical abdominoperineal resection. Dis Colon Rectum 2010;53:219 –23. 16. Quirke P, Dixon MF. The prediction of local recurrence in rectal adenocarcinoma by histopathological examination. Int J Colorectal Dis 1988;3:127–31. 17. Marr R, Birbeck K, Garvican J, et al. The modern abdominoperineal excision: the next challenge after total mesorectal excision. Ann Surg 2005;242:74 – 82. 18. Adam IJ, Mohamdee MO, Martin IG, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994;344:707–11.
19. den Dulk M, Putter H, Collette L, et al. The abdominoperineal resection itself is associated with an adverse outcome: the European experience based on a pooled analysis of five European randomised clinical trials on rectal cancer. Eur J Cancer 2009;45:1175– 83. 20. Tei TM, Stolzenburg T, Buntzen S, et al. Use of transpelvic rectus abdominis musculocutaneous flap for anal cancer salvage surgery. Br J Surg 2003;90:575– 80. 21. Bell SW, Dehni N, Chaouat M, et al. Primary rectus abdominis myocutaneous flap for repair of perineal and vaginal defects after extended abdominoperineal resection. Br J Surg 2005;92:482– 6. 22. Abbott DE, Halverson AL, Wayne JD, et al. The oblique rectus abdominal myocutaneous flap for complex pelvic wound reconstruction. Dis Colon Rectum 2008;51:1237– 41. 23. Miles WK, Chang DW, Kroll SS, et al. Reconstruction of large sacral defects following total sacrectomy. Plast Reconstr Surg 2000;105: 2387–94. 24. Boereboom CL, Watson NF, Sivakumar R, et al. Biological tissue graft for pelvic floor reconstruction after cylindrical abdominoperineal excision of the rectum and anal canal. Tech Coloproctol 2009;13:257– 8. 25. Wille-Jørgensen P, Pilsgaard B, Møller P. Reconstruction of the pelvic floor with a biological mesh after abdominoperineal excision for rectal cancer. Int J Colorectal Dis 2009;24:323–5. 26. Jin J, Rosen MJ, Blatnik J, et al. Use of acellular dermal matrix for complicated ventral hernia repair: does technique affect outcomes? J Am Coll Surg 2007;205:654 – 60. 27. Wong AK, Schonmeyr B, Singh P, et al. Histologic analysis of angiogenesis and lymphangiogenesis in acellular human dermis. Plast Reconstr Surg 2008;121:1144 –52. 28. Hendren SK, O’Connor BI, Liu M, et al. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg 2005;242:212–23. 29. Schmidt CE, Bestmann B, Küchler T, et al. Ten-year historic cohort of quality of life and sexuality in patients with rectal cancer. Dis Colon Rectum 2005;48:483–92. 30. Eveno C, Lamblin A, Mariette C, et al. Sexual and urinary dysfunction after proctectomy for rectal cancer. J Visc Surg 2010;147:e21–30. 31. Havenga K, Enker WE, McDermott K, et al. Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum. J Am Coll Surg 1996;182:495–502. 32. Stelzner S, Holm T, Moran BJ, et al. Deep pelvic anatomy revisited for a description of crucial steps in extralevator abdominoperineal excision for rectal cancer. Dis Colon Rectum 2011;54:947–57. 33. Açar HI˙, Kuzu MA. Perineal and pelvic anatomy of extralevator abdominoperineal excision for rectal cancer: cadaveric dissection. Dis Colon Rectum 2011;54:1179 – 83. 34. Menon NG, Rodriguez ED, Byrnes CK, et al. Revascularization of human acellular dermis in full-thickness abdominal wall reconstruction in the rabbit model. Ann Plast Surg 2003;50:523–7. 35. Silverman RP, Li EN, Holton LH 3rd, et al. Ventral hernia repair using allogenic acellular dermal matrix in a swine model. Hernia 2004;8: 336 – 42. 36. Christensen HK, Nerstrøm P, Tei T, et al. Perineal repair after extralevator abdominoperineal excision for low rectal cancer. Dis Colon Rectum 2011;54:711–7. 37. de Campos-Lobato LF, Stocchi L, Dietz DW, et al. Prone or lithotomy positioning during an abdominoperineal resection for rectal cancer results in comparable oncologic outcomes. Dis Colon Rectum 2011; 54:939 – 46. 38. Kouraklis G. Reconstruction of the pelvic floor using the rectus abdominis muscles after radical pelvic surgery. Dis Colon Rectum 2002; 45:836 –9. 39. Stelzner S, Koehler C, Stelzer J, et al. Extended abdominoperineal excision vs. standard abdominoperineal excision in rectal cancer—a systematic overview. Int J Colorectal Dis 2011;26:1227– 40. 40. Law WL, Chu KW. Abdominoperineal resection is associated with poor oncological outcome. Br J Surg 2004;91:1493–9.
Clinical Science
Randomized clinical trial of conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal cancer Jia Gang. Han, M.D., Zhen Jun. Wang, M.D.*, Guang Hui. Wei, M.D., Zhi Gang. Gao, M.D., Yong Yang, M.D., Bao Cheng. Zhao, M.D. Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China KEYWORDS: Cylindrical abdominoperineal resection; Human acellular dermal matrix; Circumferential resection margin; Morbidity; Survival
Abstract BACKGROUND: An alternative treatment for low rectal cancer is the cylindrical technique. We aim to compare the outcomes of patients undergoing conventional abdominoperineal resection (APR) versus cylindrical APR. METHODS: A prospective, randomized, open-label, parallel controlled trial was conducted between January 2008 and December 2010. Sixty-seven patients with T3-T4 low rectal cancer were identified during the study period (conventional n ⫽ 32, cylindrical n ⫽ 35). RESULTS: Patients who received cylindrical APR had less operative time for the perineal portion (P ⬍ .001), larger perineal defect (P ⬍ .001), less intraoperative blood loss (P ⫽ .001), larger total cross-sectional tissue area (P ⬍ .001), similar total operative time (P ⫽ .096), and more incidence of perineal pain (P ⬍ .001). The local recurrence of the cylindrical APR group was improved statistically (P ⫽ .048). CONCLUSIONS: Cylindrical APR in the prone jackknife position has the potential to reduce the risk of local recurrence without increased complications when compared with conventional APR in the lithotomy position for the treatment of low rectal cancer. © 2012 Elsevier Inc. All rights reserved.
Supported by the Program for Outstanding Medical Academic Leader, Beijing, China (Number 2009-1-03), the New Century National Hundred, Thousand and Ten Thousand Talent Project, China (Numbers 09-911-002 and 08-009) National Natural Science Fund Projects, China (81141025), Training Programme Foundation for the Talents of Beijing (2011D003034000003), Capital Medical Development Scientific Research Fund (2009-3109), the Basic and Clinical Cooperation Project of Capital Medical University (10JL04), and the Youth Foundation of Beijing Chaoyang Hospital. Presented in part at the Chinese Surgical Week, September 7–10, 2011, Beijing, China, and 2011 European Multidisciplinary Cancer Congress, September 23–27, 2011, Stockholm, Sweden (poster). * Corresponding author. Tel: ⫹86-10-8523-1604; fax: ⫹86-01360139-3711. E-mail address: [email protected] Manuscript received January 21, 2012; revised manuscript May 18, 2012
0002-9610/$ - see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjsurg.2012.05.001
Since the description of total mesorectal excision (TME) by Heald et al1 in 1982, local control of rectal cancer and patient survival have been improved remarkably. Despite this, a high rate of bowel perforation, circumferential resection margin (CRM) involvement, and local recurrence after abdominoperineal resection (APR) has been reported constantly.2–5 In a UK study involving 608 patients, patients who underwent APR had a higher local recurrence and lower survival when compared with patients who had low anterior resection (LAR).4 Heald et al6 even stated that APR was an endangered operation and would be well buried for all but very occasional cancers. This may be secondary to smaller tissue volume removed adjacent to the tumor. When performing a conventional APR, the resected specimen usually narrows at the lower border of the mesorectum at the level just above the levator muscle where
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lesions are most commonly located.7 At this point, the CRM is often close to the rectal muscle tube.7 It is well established that bowel perforation and tumor involvement of the CRM are strong predictors of local recurrence and survival in rectal cancer.8 To reduce CRM positivity, extralevator APR7 (cylindrical APR) and abdominosacral resection9 were performed in patients with T3-T4 tumors, which aimed to create a more cylindrical specimen without a waist. Recent long-term experience10 and a multicenter trial11 both have shown that extended operations for rectal cancer were associated with a lower risk of bowel perforation and CRM involvement than conventional APR. Several perineal wound complications may occur after APR, including infection, breakdown, sinus, and delayed healing. The incidence of perineal wound complications after APR can range from 26% to 41%.12–14 It has been suggested that extended resection, such as the cylindrical APR, may be associated with greater morbidity because of the formation of a large perineal defect. A multicenter trial showed that the perineal wound complication rate was about twice as high in patients treated with cylindrical APR than in those treated with conventional APR.11 We have reported our initial experience using human acellular dermal matrix (HADM) (Ruinuo; Qingyuanweiye Bio-Tissue Engineering, Ltd; Beijing, China) for single-stage, pelvic floor reconstruction after extended resection of rectal cancer previously, and the preliminary results showed that HADM could provide a safe alternative for the reconstruction of large pelvic defect without severe complications.15 This study was undertaken to further report the complications of patients whose locally advanced lower rectal cancer were managed with cylindrical APR and large pelvic defects were reconstructed with HADM and compare surgical and oncologic outcomes in patients who received cylindrical APR in the prone jackknife position versus conventional APR in the lithotomy position.
Methods Patients Between January 2008 and December 2010, 67 patients with T3-T4 low rectal cancer were enrolled in this prospective study (NCT00949273). Eligibility criteria are listed in Table 1. The operations were mainly performed by two of the authors (WZJ and WGH) who performed both procedures in cooperation with an experienced blinded pathologist. Randomization was performed on the day before surgery through sealed opaque envelopes containing a surgical method. Preoperatively, patients underwent digital rectal examination, magnetic resonance imaging, and/or endoscopic ultrasonography for staging of the rectal cancer. All patients with clinical staging of T3 N1-N2 or T4 tumors were en-
275 Table 1
Study inclusion and exclusion criteria
Inclusion criteria 1. Tumor within 5 cm of the anal verge or with a very narrow pelvis 2. T3-T4 as determined by preoperative magnetic resonance imaging or endorectal ultrasonography examination or a low tumor is fixed or tethered at rectal examination 3. Absence of distant metastases 4. Absence of intestinal obstruction Exclusion criteria 1. T1-T2 as determined by preoperative magnetic resonance imaging or endorectal ultrasonography examination 2. With distant metastases 3. With intestinal obstruction 4. Pregnancy or lactation 5. Allergic constitution to heterogeneous protein 6. With operation contraindication
couraged to receive neoadjuvant chemoradiotherapy. This consisted of 3 cycles of FOLFOX4 (oxaliplatin, 5-fluorouracil, and leucovorin) repeated every 2 weeks. Radiotherapy was added after the first cycle of chemotherapy (5-Gy fractions daily for 5 days followed by 2.5-Gy fractions daily for 2 days). For patients who received neoadjuvant therapy, we performed magnetic resonance imaging/computed tomography scans afterward to restage these patients. The study was approved by the institutional review board of Beijing Chaoyang Hospital. All patients gave informed consent for use of their data in this study.
Surgical technique Cylindrical APR. The cylindrical APR surgical procedure was performed according to the methods previously described by Holm et al.7 Pelvic dissection is stopped before the mesorectum is dissected off the levator ani muscles.7,11 The patient was then turned over into the prone jackknife position. The coccyx or S5 vertebra was disarticulated from the sacrum according to the level of tumor and the guiding of preoperative MRI. The levator muscles were divided laterally at its insertion onto the pelvic side wall on both sides. After the cylindrical specimen was removed (Fig. 1A), the pelvic reconstruction was performed according to our previous study (Fig. 2A and B).15 One sheet of 8 ⫻ 10 cm HADM mesh (Ruinuo) was sutured directly to the residual pelvic floor muscle and fascia using interrupted or continuous sutures (2/0 Vicryl, Johnson & Johnson, Sint Stevens Woluwe, Belgium) with an appropriate amount of tension with about 1-cm intervals, ensuring at least a 3-cm overlap circumferentially. One must be careful not to suture the nerves of the genital organs that run along the lateral wall of the ischioanal fossa. One perineal drain was placed in the pelvic cavity near the mesh along the pelvic sidewall with at least 1 side hole above the mesh and 1 under the mesh. The
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Pathologic data All APR specimens underwent routine pathologic processing, which included fixation in 10% formalin, painting of the CRM, and serial slicing along the tumor at 3- to 5-mm intervals as described previously.16 Digital photographic images of the whole specimen and of serial cross-sectional slices alongside a metric scale were taken and were stored in the computer. Precise tissue quantitation was performed with the Image-Pro plus 6.0 (Media Cybernetics, Inc, Silver Spring, MD) on all slices that contained a tumor by using a method described previously.17 The total cross-sectional tissue area and crosssectional area of the tissue outside the internal sphincter (IS) or the muscularis propria (MP) were obtained. Any tumor located less than 1 mm from the circumferential margin was defined as positive according to previous evidence.18 Figure 1 A surgical specimen of the rectum. (A) Cylindrical APR leaves the levator attached to the mesorectum, which creates a cylindrical specimen. (B) Conventional APR creates a waist on the specimen.
ischiorectal fat and skin were closed primarily using interrupted sutures over the HADM mesh. Patients were encouraged to be out of bed and ambulating on postoperative day 1. The drain was removed when the output was less than 20 mL/d. Conventional APR. When performing conventional APR, the surgeon follows the plane outside the mesorectum down to the pelvic floor to the top of the anal canal, and the mesorectum is mobilized from the levator muscles. The perineal part of the operation is then performed from below in the same lithotomy position, with excision of the anal canal including the surrounding skin, ischiorectal fat, and the lower portions of the levator muscles (Fig. 1B). The perineal wound is closed primarily in multiple layers including the muscle layer of the pelvis floor, perineal fat, and skin.
Follow-up Patients with a T3/T4 tumor or lymph node metastases received postoperative systemic chemotherapy with either oxaliplatin, 5-fluorouracil, and leukovorin or capecitabine and oxaliplatin for a duration of 6 months including the period of preoperative chemotherapy. Follow-up was arranged every 3 months for 2 years and then 6 months thereafter. In addition, data from the last available follow-up visit were included in the analyses. Colonoscopy was performed 1 year after the operation and then will be repeated every 3 years if no lesion was found. Colonoscopy was performed at 3-6 months if no complete visualization of the colon had been done preoperatively.
Statistics Statistical analysis was performed using SPSS for Windows (version 16.0; SPSS Inc, Chicago, IL). Continuous variables (eg, age, distance of from the dentate line, and so on) are presented as median values with ranges in parentheses. Survival analysis was performed using the Kaplan-
Figure 2 Pelvic floor reconstruction after cylindrical APR in the prone jackknife position. (A) The pelvic floor defect after cylindrical APR in the prone position. (B) Using human acellular dermal matrix for reconstruction of the pelvic floor.
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Clinical characteristics grouped by surgical technique
Age (y), median (range) Male/female BMI (kg/m2), median (range) Neoadjuvant therapy Tumor Distance from anal verge (cm), median (range) Maximum tumor diameter (cm), median (range) Preoperative tumor stage T3 N0 M0 T3 N1-2 M0 T4 N1-2 M0 Postoperative tumor stage T3 N0 M0 T3 N1-2 M0 T4 N1-2 M0 Perineal defect size (cm2), median (range) Total operative time (min), median (range) The time to reposition the patient (min), median (range) Operative time for perineal portion (min), median (range) Intraoperative blood loss (mL), median (range) Positive CRM Bowel perforation Hospital stay (d), median (range) Postoperative follow-up (mo), median (range) VAS pain score at 3 mo postoperatively, median (range) VAS pain score at 12 mo postoperatively, median (range)
Cylindrical APR (n ⫽ 35)
Conventional APR (n ⫽ 32)
P value
63 (44–81) 20/15 27.0 (21.2–35.0) 10
68 (32–84) 21/11 27.0 (21.0–35.6) 9
.168* .785† .736* .968†
3.0 (2.0–5.0) 5.75 (4.5–8.5)
.840* .310* .684†
3.0 (2.0–7.0) 6.0 (4.0–10.0) 5 19 11
6 14 12
10 20 5 64 190 15 32 200 2 2 9 29 4 3
10 14 7 42 215 — 46 300 9 5 11 22 1 0
.562†
(38–100) (140–420) (10–40) (20–50) (100–500) (7–18) (12–48) (0–10) (0–9)
(24–80) (160–330) (32–65) (150–600) (7–22) (14–46) (0–8) (0–6)
⬍.001* .096* — ⬍.001* .001* .013† .246† .056* .185* ⬍.001* .001
*Mann-Whitney U test. †Chi-square analysis.
Meier curve. Comparisons between groups were analyzed using chi-square analysis or a rank sum test (Mann-Whitney U test). Significance was defined as P ⬍ .05.
Results Patient characteristics The characteristics of patients, tumors, and operations are summarized in Table 2. Two hundred eighty-nine patients underwent surgical resection for the treatment of rectal cancer at our institution. Sixty-seven eligible patients were randomly entered into this study: 32 to receive conventional APR and 35 to receive cylindrical APR. The age and sex distribution between the 2 groups were not significantly different. Preoperatively, 10 patients (29%) in the cylindrical APR group and 9 patients (28%) in the conventional APR group underwent neoadjuvant therapy. Twenty-five patients in the cylindrical APR and 23 patients in the conventional APR group did not receive neoadjuvant therapy for many reasons (eg, elderly, comorbidities, patient choice, and surgeon’s neglect in the early research from 2008 to 2009). There was no major complication from the neoadjuvant therapy.
The median time for the perineal portion was significantly shorter in the cylindrical APR group than in the conventional group (32 vs 46 minutes, P ⬍ .001). Patients in the conventional APR group had smaller perineal defects (42 vs 64 cm2, P ⬍ .001) but more intraoperative blood loss (300 v 200 mL, P ⫽ .001) compared with those in the cylindrical APR group. The median total operative time (including the time to reposition the patient in the cylindrical APR group) for cylindrical APR was 190 minutes (range 140 – 420 minutes), which was similar to patients who underwent conventional APR (215 minutes [range 160 –330 minutes], P ⫽ .096, Table 2).
Tissue morphometry The cylindrical APR removed approximately 50% more total cross-sectional tissue (P ⬍ .001) and 77% more tissue outside the IS/MP (P ⬍ .001) in slices that contained macroscopic evidence of tumors. The CRM of the cylindrical APR group was significantly longer than the conventional APR group (2.2 vs 1.85 mm, P ⫽ .002, Table 3).
Tumor characteristics According to the American Joint Committee on Cancer TNM classification, there were 30 patients in the cylindrical
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Table 3
Tissue morphometry in slices that contained tumors
CRM (mm), median (range) Total cross sectional tissue area (mm2), median (range) Cross-sectional tissue area outside the IS or MP (mm2), median (range)
Cylindrical APR (n ⫽ 35)
Conventional APR (n ⫽ 32)
P value*
2.2 (1.0–4.9) 2600 (999–3,812) 2146 (793–3,348)
1.85 (.2–5.0) 1738 (1,100–2,390) 1211 (608–1,765)
.002 ⬍.001 ⬍.001
*Mann-Whitney U test.
APR and 20 patients in the conventional APR group who had pathologic stage T3 cancer; 5 patients and 7 patients had T4 cancer, respectively (P ⫽ .562). The organs involved in the T4 cancers were vagina (n ⫽ 1), prostate (n ⫽ 2), and sacrum (n ⫽ 2) in the cylindrical APR group and vagina (n ⫽ 3), prostate (n ⫽ 3), and coccyx (n ⫽ 1) in the conventional APR group. In the patients with T4 tumors, 1 patient had a positive CRM and 1 had bowel perforation in the cylindrical APR group (n ⫽ 5), and seven had a positive CRM and 3 had bowel perforation in the conventional APR group (n ⫽ 7). In total, there were fewer patients with a positive CRM in the cylindrical APR versus the conventional APR (5.7% vs 28.1%, P ⫽ .013). A lower frequency of bowel perforation was also observed in the cylindrical APR group, but the difference was not statistically significant (5.7% vs 15.6%, P ⫽ .246).
Mortality and morbidity There was no postoperative mortality documented. Eighteen patients (51%) in the cylindrical APR group and 19 patients (59%) in the conventional APR group developed postoperative complications (P ⫽ .515). Sexual dysfunction, urinary retention, peristomal hernia, and perineal wound complications were the 4 most common complications observed in both groups (Table 4). Patients were excluded from sexual analysis if they were not sexually active preoperatively. Twenty-seven patients (77%) in the cylindrical APR group and 20 patients (63%) in the conventional APR group were sexually active preoperatively.
Table 4
The rate of sexual dysfunction was 74% (20/27) and 60% (12/20), respectively, at 1 year after cylindrical and conventional APR (P ⫽ .306). The incidence of chronic perineal pain was significantly higher in the cylindrical APR group (P ⬍ .001). Visual analog scale (VAS, with a score of 1-10) was used to evaluate the postoperative perineal pain severity. A VAS score ⬎4 was considered positive. The VAS pain score at 3 months postoperatively was significantly higher in the cylindrical APR group than in the conventional APR group (median 4 vs 1, P ⬍ .001) and was also significantly higher at 12 months postoperatively (median 3 vs 0, P ⫽ .001, Table 2). Among the patients with a positive VAS score, 5 required oral nonsteroidal anti-inflammatory drugs for pain relievers, and 3 required oral tramadol. In the cylindrical APR group, a positive VAS score (score ⫽ 6, 6, and 4, respectively) in 3 patients (3/18) at 3 months postoperatively changed into a negative score at 12 months postoperatively. At 18 months postoperatively, a positive VAS score (score ⫽ 8, 8, 7, 7, and 6, respectively) in 5 (5/18) patients changed into a negative score.
Oncologic results The median follow-up time was 29 months (range 12– 48 months) in the cylindrical APR group and 22 months (range 14 – 46 months) in the conventional APR group. Within the cylindrical APR group, 1 patient had local recurrence, 1 patient had liver metastases, and 2 patients had combined liver and pulmonary metastases. In the conventional APR group, local recurrence occurred in 4 patients with a positive
Postoperative complications
Complications
Cylindrical APR n (% of total)
Urinary retention Chronic perineal pain Perineal wound infection Urinary system infection Pulmonary infection Perineal seroma Peristomal hernia Abdominal wound infection Perineal herniation
14 18 4 2 4 4 16 2 5
*Chi-square analysis.
(40.0) (51.4) (11.4) (5.7) (11.4) (11.4) (45.7) (5.7) (14.3)
Conventional APR n (% of total) 9 2 6 3 5
(28.1) (6.3) (18.8) (9.4) (15.6)
0 13 (40.6) 3 (9.4) 4 (12.5)
P value* .307 ⬍.001 .501 .664 .727 .115 .675 .664 1.000
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Figure 3 Survival of low rectal cancer patients. (A) Kaplan-Meier curves showing the overall survival after cylindrical and conventional APR for rectal cancer (P ⫽ .202). (B) Kaplan-Meier curves showing disease-free survival after cylindrical and conventional APR for rectal cancer (P ⫽ .165).
CRM, combined local recurrence and liver metastases in 2 patients, and combined liver and pulmonary metastases in 1 patient. The difference of local recurrence was statistically significant (2.8% vs 18.8%, P ⫽ .048). Two patients (5.7%) in the cylindrical APR group and 5 patients (15.6%) in the conventional APR group died of tumor recurrence. One patient in the cylindrical APR group who was free of tumor recurrence died of a heart attack 35 months after surgery. Overall survival and disease-free survival between the 2 groups were examined, and no statistically significant difference was shown. The mean length of the overall survival in the cylindrical APR group was 45 months and 40 months in the conventional APR group (P ⫽ .202, log-rank test; Fig. 3A), and the mean length of disease-free survival was 44 months and 38 months, respectively (P ⫽ .165, log-rank test; Fig. 3B).
Comments Although the use of very low anterior resection is becoming more popular because the safety of the procedure increased through the use of improved suture instruments, APR is still a common procedure for patients with T3/T4 low rectal cancer. With conventional APR, the risk of inadvertent bowel perforation is high, the resulting specimen frequently has a waist at the lower border of the mesorectum, and the CRM is often close to the rectal muscle tube.3 A recent meta-analysis of 5 European randomized clinical trials on rectal cancer revealed that the APR procedure is a significant predictor for nonradical resections and increased risk of local recurrence with decreased cancer-specific survival.19 Whenever possible, a more radical operation should be considered for low rectal cancer for these reasons. Cylindrical APR introduced by Holm et al7 may be an alternative to conventional synchronous combined APR. The main differences between this procedure and conven-
tional APR are (1) the mesorectum is not dissected off the levator muscles, (2) the perineal part of the operation is performed with the patient in the prone jackknife position, and (3) the entire levator muscle is resected en bloc with the anal canal and lower rectum. This creates a cylindrical specimen with more tissue removed surrounding the tumor in low rectal cancer as shown in our study. By leaving the levator muscles and ischiorectal fossa fat attached to the specimen in the cylindrical APR group, more clearance will be obtained, thus reducing the chances of CRM involvement and intraoperative perforations and removing more tissue outside the IS or MP, which will help the patients in terms of the removal of cancer. A multicenter trial indicated that cylindrical APR was associated with less CRM involvement and intraoperative perforation than standard surgery,11 which was confirmed by our study. The CRM of the cylindrical APR group was significantly longer than the conventional APR group (2.2 vs 1.85 mm, P ⫽ .002) in our study. However, .35 mm was not a clinically significant difference for CRM positivity. The statistical significance might actually be irrelevant. A previous study showed that the cylindrical technique has the potential to improve local recurrence rates and survival rates in patients with low rectal cancers.2 In a Polish study involving 210 low rectal cancer patients who underwent extended APR, the observed 2-year local recurrence rate was 4.4%, whereas the 5-year observed and relative survivals were 68.3% and 73.2%, respectively.10 We compared the local recurrence and survivals of the cylindrical APR group with those of the conventional APR group. Although the survivals between the 2 groups were really not statistically significant, the local recurrence was improved statistically in the cylindrical APR group. These results suggested that the oncologic benefits of cylindrical APR might be better than those of conventional APR in patients with advanced lower rectal cancer. There was a difference of bowel perforation between cylindrical APR
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and conventional APR group (5.7% vs 15.6%), but this was not statistically significant. After the completion of cylindrical APR, reconstruction of the pelvic defect poses a difficult challenge for surgeons. With an extended resection of the levator muscles, there is only fatty tissue and skin to cover the perineal defect. In the past, these defects were closed primarily, resulting in complication rates as high as 62.5%.20 These complications can include wound infection, dehiscence, and herniation. Various myocutaneous flaps are probable solutions, but all carry the risk of donor-site morbidity, longer bed rest, flap necrosis, or potentially impaired ambulation.7,21–23 A biological tissue graft (Surgisis BioDesign, Cook Surgical Inc, Bloomington, IN) for pelvic floor reconstruction after cylindrical APR was described by Boereboom et al,24 but the detailed results of the operation were not provided. Wille-Jørgensen et al25 reported 11 consecutive patients with pelvic floor reconstruction after APR, and the use of crosslinked porcine dermis (Permacol, Tissue Science Laboratories, Aldershot, Hampshire, UK) was feasible with satisfactory results. HADM is a biological material consisting of dermis without its cellular components. Several experimental and clinical studies have shown that HADM can be used to repair complex abdominal defects even in contaminated or potentially contaminated surgical fields.26,27 However, its application in pelvic reconstruction has not gained widespread use. Our study confirms that large pelvic floor defects after cylindrical APR can be successfully closed in a single-stage, tension-free repair using HADM without an increased risk of serious complications. To the best of our knowledge, sexual function after cylindrical APR has rarely been reported before.11 Sexual dysfunction was the most popular complication in both the cylindrical and conventional APR groups in our study. There was no significant difference between them. Our results were similar to those of West et al.11 Hendren et al28 reported that sex life was affected negatively in 84% pa-
tients undergoing APR. In a series of 261 patients, the rate of sexual dysfunction at 1 year postoperative was 79% after APR.29 Sexual function has been known to depend on the integrity of the pelvic autonomic nervous plexuses. Sexual dysfunction can be caused by damage at the level of the superior hypogastric plexus or the hypogastric nerves before they join together with the parasympathetic nerves at the inferior hypogastric plexus.30 APR is one of the most common risk factors for postoperative sexual dysfunction, whereas the stage and the size of the tumor do not seem to have an influence.31 A recent study on anatomic dissection reported that the clear identification of pelvic anatomic landmarks might be useful for the successful achievement of both negative CRMs and the preservation of urogenital functions during cylindrical APR.32 We suggested that, with the familiarity with pelvic anatomy and precise surgical procedure, the cylindrical technique may remove more tissue in the distal rectum compared with the conventional APR without improving sexual dysfunction. According to anatomic research, the nerves of the genital organs run along the lateral wall of the ischioanal fossa in which the pudendal nerve extends within the pudendal canal.32,33 For the pelvic floor to be removed completely, the lateral incision of the pelvic floor should be close to this area and thus may damage the nerve.33 We suppose that the cylindrical APR technique may be performed according to individual conditions. For the rectal tumors suitable for cylindrical APR, most of them were circular or nearly circular infiltrating tumors. Patients with these rectal tumors should receive full cylindrical APR resection. In those rectal tumors not involving the levator ani muscle, the dissection plane may continue close to the external anal sphincter and the levator ani muscle, leaving the ischioanal fat and the terminal branches of the pudendal nerve intact (Fig. 4).32 If the tumor has only penetrated into 1 side of the levator ani muscle, the dissection might include the levator ani muscle and the fat of the ischioanal fossa on the side of the tumor
Figure 4 Individual cylindrical APR technique according to individual conditions. (A) If the tumor penetrates into the levator ani muscle, the dissection should include the fat of the ischioanal fossa to achieve a clear CRM (right). If the tumor only involves the levator ani muscle, the dissection plane may continue close to the external anal sphincter and the levator ani muscle (left). (B) The dissection includes the levator ani muscle and the fat of the ischioanal fossa on the side of the tumor (right), whereas the ischioanal fat and levator ani muscle on the other side of the tumor might be left (left).
J.G. Han et al.
Cylindrical abdominoperineal resection
to achieve a clear CRM, whereas the ischioanal fat and levator ani muscle on the other side of the tumor may be left (Fig. 4B). This individual cylindrical APR may be as effective as full cylindrical APR while minimizing the operative trauma and the damage to the nerves of the genital organs. Chronic perineal pain was the most popular postoperative complication in our cylindrical APR group (51.4%). The patients felt pain in the operated sacrococcygeal region and had difficulty sitting for an extended amount of time. Eight patients (44.4%) required pain-relieving drugs. The long-lasting perineal pain was also observed in patients (54.5%) whose pelvic floor defects were repaired with Permacol after APR.25 The chronic pain may be related to the activation of the inflammatory cytokines at the mesh site,25 the coccygectomy, the damage to the pudendal nerve, the wider excision of the levator ani muscles and ischiorectal fossa fat, and the suturing of the mesh itself close to the pelvic wall. The coccygectomy may be the main reason. To reduce the postoperative chronic perineal pain, C1/S5 sacrectomy may not be necessary for anterior rectal tumors. According to our study, we considered that relatively lighter pain might gradually ease over time. Several studies, including our initial report, have shown that HADM was safe and effective in abdominal wall and pelvic floor repair.15,26,34,35 However, disadvantages of HADM have appeared with increasing use. Specifically, one of the most prominent concerns with HADM is the laxity with time, leading to a bulge or recurrent hernia after abdominal wall repair.26 Few studies have reported perineal hernia after pelvic floor reconstruction with biological mesh.25,36 One study compared perineal defect reconstruction with a fasciocutaneous gluteal flap versus biological mesh after cylindrical APR.36 There were 33 patients with gluteal flap and 24 with biological mesh reconstruction, and perineal hernia developed in 7 (21%) patients in the gluteal flap group and none of the patients in the mesh group.36 Wille-Jørgensen et al25 also reported no perineal hernia after pelvic floor reconstruction. In our study, the perineal hernia rate after pelvic floor reconstruction with HADM was 14.3%. The laxity of HADM with time may be the main reason.26 Suturing the HADM to the residual pelvic floor muscle and fascia with a great deal of tension might reduce the hernia rate. Furthermore, the high hernia recurrence rate warrants a continued search for alternative biological materials to improve outcomes. In our series, the cylindrical APR group had a statistically less median operative time for perineal portion compared with the conventional APR group, partly because of the prone jackknife position and the simplified perineal part of the operation. Performing the perineal portion of the operation in the prone jackknife position resulted in a further reduction of intraoperative blood loss. The cylindrical APR group had a similar total operative time compared with the conventional APR group despite adding the time to reposition the patient, probably because of less pelvic dissection and the simplified perineal part of the opera-
281 tion. Although a recent study reported that the prone jackknife position during perineal dissection in an APR did not affect perioperative morbidity or oncologic outcomes compared with the lithotomy position,37 we prefer to use the prone position because of the excellent exposure of the perineal structures, the optimal access to the sacrum, and the possibility of immediate closure of large pelvic floor defects. However, it should be addressed that the prone jackknife position was only part of the cylindrical APR procedure that facilitated the surgical procedure. We considered that the reduced tumor involved resection margins and intraoperative bowel perforation could not be achieved only with the prone jackknife position without cylindrical APR. The time for reconstruction of the pelvic floor with HADM averaged around 10 minutes in our study. This was shorter compared with the time required to perform the myocutaneous flap reconstruction, which varied from 30 to 100 minutes depending on the literature.7,38 Furthermore, patients who underwent reconstruction using the myocutaneous flap were asked to avoid direct pressure on the flap and no ambulation for as long as 14 days after the original operation.7,21 In our series, the postoperative care in the cylindrical APR group was the same as patients who had undergone conventional APR without pelvic floor reconstruction. Previous studies showed that HADM supported vascular ingrowth and exhibited increased breaking strength when used as a fascial interposition graft for abdominal wall reconstruction.27,34,35 Furthermore, Christensen et al36 suggested that it was unable to show a difference between HADM and synthetic mesh in their ability to repair ventral hernias even at 9 months. We believed that the ability of HADM makes it possible to reconstruct the pelvic floor, and early ambulation dose not interfere with wound healing. We consider that most patients with T3-T4 or nodepositive low rectal cancer should receive preoperative chemoradiotherapy, but there were only 10 patients (29%) in the cylindrical APR and 9 patients (28%) in the conventional APR group who underwent neoadjuvant therapy in our study. The 18.8% local recurrence rate of our study is extremely high compared with the 11.9% local recurrence rate reviewed by Stelzner et al39 for conventional abdominal perineal resection. We considered that the lack of preoperative radiation therapy may have resulted in this poor result,40 and this was an extremely serious defect in our study. This might not be applicable to patients in whom preoperative chemoradiotherapy was able to shrink the tumors and might make the patient group abnormal and, therefore, not able to be truly evaluated. In our series we tried to compare the results of consecutive patients who underwent cylindrical versus conventional APR, and the study proposed that cylindrical APR in the prone position has the potential to reduce the risk of local recurrence without increased complications. A multicenter study with a larger patient number is currently in progress to evaluate the true outcomes of the technique.
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Acknowledgments The authors thank Judy Jin, M.D., of the Department of Surgery, University Hospitals Case Medical Center, Cleveland, OH, and Hui Chen, Ph.D., of Capital Medical University, Beijing, PR China for her statistical assistance.
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