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Management of early neoplasms and surgical complications of the rectum

Musters, G.D.

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Citation for published version (APA):Musters, G. D. (2016). Management of early neoplasms and surgical complications of the rectum.

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Download date: 29 Jul 2020

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CHAPTER 2Perineal wound healing after abdominoperineal resection for rectal cancer; a systematic review and meta-analysis G.D Musters, C.J. Buskens, W.A. Bemelman, and P.J. Tanis

Dis Colon Rectum 2014;57(9):1129-1139.

Chapter 2

34

ABSTRACT

Aim:The primary aim of this systematic review with meta-analysis was to determine the impact of neoadjuvant (chemo)radiotherapy and an extralevator approach on perineal wound healing after abdominoperineal resection for rectal cancer.

Methods:In March 2014, electronic databases were searched. Studies describing any outcome measure on perineal wound healing after abdominoperineal resection for rectal cancer were included. The primary endpoint was overall perineal wound problems within 30 days after conventional or extralevator abdominoperineal resection with or without neoadjuvant radiotherapy. Secondary endpoints were primary wound healing, perineal hernia rate, and the effect of biological mesh closure on perineal wound problems.

Results: A total of 32 studies were included. The pooled percentage of perineal wound problems after primary perineal wound closure in patients who did not undergo neoadjuvant radiotherapy was 15.3% (95% Ci, 12.1–19.2) after conventional abdominoperineal resection and 14.8% (95% Ci, 9.5–22.4) after extralevator abdominoperineal resection. after neoadjuvant radiotherapy, perineal wound problems occurred in 30.2% (95% Ci, 19.2–44.0) after conventional abdominoperineal resection and in 37.6% (95% Ci, 18.6–61.4) after extralevator abdominoperineal resection. Radiotherapy significantly increased perineal wound problems after abdominoperineal resection (OR 2.22; 95% Ci, 1.45–3.40; p < 0.001). After biological mesh closure of the pelvic floor following extralevator abdominoperineal resection with neoadjuvant radiotherapy, the percentage of perineal wound problems was 7.3% (95% Ci, 1.5–29.3).

Conclusion: Neoadjuvant radiotherapy significantly increases perineal wound problems after abdominoperineal resection for rectal cancer.

Perineal wound healing after abdominoperineal resection for rectal cancer

35

2

INTRODUCTION

Perineal wound problems after abdominoperineal resection (APR) for rectal cancer is reported in up to 57% of patients.1 If the perineum does not heal primarily, secondary wound healing may prolong hospital stay, may necessitate surgical reintervention, and often requires intensive wound care for several months, with the risk of developing a persistent sinus after 1 year.2–4 In the past decade, perineal wound healing after APR has gained more attention because of the intensified treatment of distal rectal cancer. After the widespread adoption of the technique of total mesorectal excision and the increasing use of neoadjuvant radiotherapy, locoregional disease control and survival of rectal cancer have improved.5,6 The oncological outcome remained poor due to positive circumferential resection margins and tumour perforations in patients with low rectal cancer undergoing APR.7 When the total mesorectal excision plane is followed all the way down to the pelvic floor, as performed in conventional APR (cAPR), a typical coning of the specimen occurs by which the resection margins are compromised. To overcome this problem, wider excisions with en bloc resection of the distal rectum, sphincter complex, and levator muscles have been introduced, resulting in a cylindrical specimen. This extralevator APR (eAPR) reduces the rate of positive resection margins and tumour perforation in distal rectal cancer, and improves oncological outcome.8,9

As a downside of improved oncological outcome, both radiotherapy and extended resections have been suggested to increase perineal wound healing problems after APR.10 Therefore, the aim of this systematic review with meta-analysis was to determine the impact of these changes in rectal cancer management on perineal wound healing after APR. Secondarily, the recent introduction of biological mesh reconstruction of the pelvic floor, aiming at improved perineal wound healing and the prevention of perineal hernia, was evaluated.

METHODS

Search strategyAll studies reporting on perineal wound healing after either cAPR or eAPR for rectal cancer were considered eligible for review. The electronic databases of the national institutes of health Pubmed (1952–2014), EMBASE (1984–2014), and Cochrane library (2008–2013) were systematically searched in March 2014. The following medical subject heading (mesh) terms were used; rectal neoplasms, rectal, neoplasms, abdomen, perineum, colorectal surgery, surgical procedures, operative, general surgery, wound healing, reconstructive surgical procedures, wounds, and injuries. Other search terms were abdominal perineal resection, abdominoperineal resection, abdominoperineal excision, abdominal perineal excision, perineum surgery, perineal surgery, primary healing, repair, wound, and healing. No restrictions considering patient age or technique of APR were applied. Anal cancer, benign disorders, gynaecological cancers, exenterative procedures, sacral resections, use of myocutaneous flaps for perineal closure, delayed perineal wound closure, animal studies, non-English articles, congress abstracts, studies before 1990, previously published data, and studies with fewer than 5 patients were excluded. Of the initially identified publications, titles and abstracts

Chapter 2

36

were screened to exclude nonrelated publications. Then, the full text of the remaining articles was read to determine whether they were eligible for inclusion. Of the included articles, the references were cross-checked to identify any additional studies of interest. Studies were included by two independent authors (G.M., P.T.). Any disagreements between both reviewers were resolved by consultation with an expert specialist (W.B.).

Outcome parametersThe primary end point was the percentage of overall perineal wound problems within 30 days after cAPR or eAPR with or without neoadjuvant radiotherapy. Besides this combined end point, a distinction between superficial (wound infection and dehiscence) and deep perineal wound problems (perineal abscess and presacral abscess) was made if relevant data were provided by the selected articles. Secondary outcome measures were superficial perineal wound problems, deep perineal wound problems, primary wound healing rate, perineal hernia rate at the end of follow-up, and the effect of biological mesh assisted closure on perineal wound problems and perineal hernia. Primary wound healing was included as a secondary end point, because this is not always the complement of perineal wound problems. For example, a seroma or hematoma may be present, while the perineal wound has been healed primarily. Furthermore, some studies only report on perineal wound healing rate without mentioning the perineal wound complications.

Validity and eligibility assessment All included studies were assessed for methodological quality and risk of bias. For cohort studies, the Newcastle Ottawa quality assessment scale for cohort studies was used to assess risk of bias.11 The quality items scored were as follows: representativeness of the exposed cohort, selection of the nonexposed cohort, ascertainment of exposure, the absence of outcome of interest at the start of the study, comparability of the design or analysis, assessment of outcome, duration of follow-up and lost to follow-up. For randomised controlled trials (RCTs), the Jadad scoring system was used to assess the risk of bias.12 When the randomised groups of the RCTs were not used as described in the RCT, the Newcastle Ottawa quality assessment scale for cohort studies was also used to assess risk of bias.11

Data extractionTwo authors independently extracted data from the included studies (G.M., P.T.). Disagreements were resolved by discussion between the two reviewers. If no consensus could be reached, a third specialist author was consulted and decided (W.B.). In the case of RCTs on oncological interventions in which perineal wound healing was a secondary outcome parameter, data of both arms of the trial were combined or data from the appropriate arm was used. Data on outcome measures were extracted for specific subgroups of patients from the included articles depending on the availability of separate data with regard to the extent of resection (eAPR or cAPR) and the use of neoadjuvant radiotherapy.


37

2

Statistical analysis From each study, a weighted average of the logit proportions was determined by the use of the generic inverse variance method. The logit proportions were back transformed to the summary estimate and 95% CIs were obtained in a summary proportion. Heterogeneity was assessed by using the I2 and χ2 statistics, and the data were considered significant if the p value (χ2) was <0.1 and I2 was >75%. Analyses were performed with the use of Review manager (Revman, Version 5.2. Copenhagen: the nordic Cochrane Centre, the Cochrane Collaboration, 2012). Analyses were performed with the inverse variance analysis by using a random-effects model. The estimated pooled OR and the corresponding 95% CIs were illustrated in forest plots. The pooled data were considered statistically significant if the p-value was <0.05. Publication bias was assessed by using a funnel plot.

RESULTS

The systematic search resulted in a total of 2318 articles. After the removal of duplicates, 2039 articles remained. After screening of publication titles and abstracts, 145 publications were retrieved for full text review. Of these 145 articles, 118 were excluded for reasons as summarized in figure 1. Of the included articles, the reference lists were checked, which resulted in 5 additional eligible studies. In total, 32 publications were included with a total number of 7247patients. Seven studies were RCTs,13–19 and 25 were cohort studies. Of the cohort studies, 17 studies were consecutive series.1,2,4,9,10,20–31 The following groups of the RCTs were used: in 1 RCT, only the control arm of the study was included because local gentamicin was used in the experimental arm.15 In 1 RCT, only 1 study arm was included, because in the other study arm the perineum was packed and not primarily closed.13 In 1 RCT, only the patients undergoing a cAPR were included.17 In 1 RCT, only the patients receiving preoperative radiotherapy and no postoperative radiotherapy were included.19 In 2 RCTs, both study arms were merged and described as one,14,18 and each individual study arm was included of the remaining RCTs.16 This resulted in a final number of 3941 patients to be included for data analysis. The risk of bias of all included studies is displayed in appendix 1.

Study characteristics APR with primary perineal closure Of the 32 included studies, primary perineal wound closure after cAPR was described in 21 studies, with a total number of 2989 patients (table 1).1,2,9,10,13–20,22,25,29,30,32–36 Five studies described the use of an extralevator approach (eAPR) in 728 patients.4,21,32,37,38 All patients underwent APR for primary rectal cancer, with the exception of 2 studies in which a minority of patients had recurrent rectal cancer (n=41;1%).25,39 Only 3% (n=115) of the patients underwent minimally invasive surgery as described in 3 studies.9,25,32 The use of an omentoplasty was described in 3 studies and ranged between 20% and 88%.14,35,37 The use of a presacral drain was described in 14 studies (56%–100%)1,13–

15,18,21,29,32–38 and a perineal wound drain in 3 studies.20,36,38 Radiotherapy was applied in 16 studies, and the proportion of patients receiving radiotherapy ranged from 28% to 100%.1,2,4,9,10,16–21,32,33,36–38

Chapter 2

38

Figure 1 Flow-diagram

Perineal wound problems after APR with primary perineal wound closureThe percentages of perineal wound problems after primary perineal wound closure for each individual study are displayed in Table 1. After cAPR without neoadjuvant radiotherapy (6 studies; 1000 patients; Table 2), overall perineal wound problems occurred in a pooled percentage of 15.3% (95% CI 12.1-19.2; I2=50%, χ2=0.07).2,10,14,15,17,36 Assuming that radiotherapy was not applied in an additional number of four studies published between 1991 and 1995, although this was not explicitly described, the pooled percentage of all perineal wound problems was 18.7% (95% CI 13.9-24.9; I2=78%, χ2<0.01; 10 studies, n=1218).2,10,13-15,17,29,34-36 Superficial perineal wound problems occurred with a pooled percentage of 15.0% (95% CI 10.3-21.6; I2=78%, χ2<0.01; 8 studies, n=1032)2,10,15,17,29,34-36 and deep perineal wound problems with a pooled percentage of 8.8% (95% CI 2.7- 25.0, I2=92%, χ2<0.01; 5 studies, n=744).2,13-15,36

After cAPR with neoadjuvant radiotherapy in all patients, the pooled percentage of perineal wound problems was 30.2% (95% CI 19.2-44.0, I2=90%, χ2<0.01;5 studies, n= 730).1,2,10,17,36 Superficial perineal wound problems had a pooled percentage of 19.4% (95% CI 14.5-25.4; I2=64%, χ2=0.026;


39

2

5 studies, n=730)1,2,10,17,36 and deep perineal wound problems had a pooled percentage of 7.1% (95% CI 1.3-31.1; I2=87%, χ2<0.01; 3 studies, n=362).1,2,36 Radiotherapy showed a significant increase in overall perineal wound problems after cAPR (OR 1.74; 95% CI 1.29-2.34; p=0.0003; I2=13%, χ2=0.33; 4 studies, n=1496). 2,10,17,36

The pooled percentage of overall perineal wound problems after eAPR without neoadjuvant radiotherapy was 14.8% (95% CI 9.5-22.4; I2=30%, χ2=0.233; 2 studies, n=217).4,37 In patients who underwent neoadjuvant radiotherapy, the pooled percentage of perineal wound problems after eAPR was 37.6% (95% CI 18.6-61.4; I2=85%, χ2=0.01; 2 studies, n=169).4,37 Neoadjuvant radiotherapy significantly increased the risk of perineal wound problems after both cAPR and eAPR (OR 2.22; 95% CI 1.45-3.40; p=0.0003; Figure 2). The pooled percentages with 95% confidence intervals of the different subgroups are summarized in Figure 3.

Figure 2 Forrest plot of perineal wound problems after cAPR and eAPR in patients who underwent neoadjuvant radiotherapy compared to those who did not undergo radiotherapy

Figure 4 Forrest plot of perineal wound healing after cAPR and eAPR in patients who underwent neoadjuvant radiotherapy compared to those who did not undergo radiotherapy

Perineal wound healing and perineal hernia after APR with primary perineal wound closureAfter cAPR without radiotherapy, primary perineal wound healing had a pooled weighted estimate of 81.8% (95% CI 64.7-91.7; I2=93%, χ2<0.01; 5 studies, n=736).2,10,14,15,33 After neoadjuvant radiotherapy, primary perineal wound healing had a pooled estimate of 63.9% (95% CI 45.7-

Chapter 2

40

78.8; I2=93%, χ2<0.01; 5 studies, n=650).1,2,10,19,33 There was only one study reporting the primary perineal wound healing rate after eAPR with all patients undergoing radiotherapy, which was 43% (n=53/123).4 Radiotherapy showed a significant reduction in primary perineal wound healing after both cAPR and eAPR (OR 0.27; 95% CI 0.16-0.45;p<0.001; Figure 4).2,4,10,33

Perineal hernias after cAPR occurred in a pooled percentage of 1.8% (95% CI 0.4-8.3; I2=84%, χ2<0.01; 4 studies, n=1012)2,9,10,16, and in 2.0% after eAPR (95% CI 0.5-7.0; I2=59%, χ2=0.09; 3 studies, n=367).21,37,38

Perineal wound problems and perineal hernia after biological mesh assisted closureBiological mesh assisted perineal wound closure was performed in 224 patients from 8 studies (Table 3). 16,23,24,26-28,31,39 All 224 patients underwent eAPR. The use of a presacral drain was reported in two studies26,39 and a perineal wound drain was reported in four studies.16,24,27,39 The proportion of patients receiving radiotherapy ranged from 43% to 100% and an omentoplasty was used in 28% (n=36) and described in two studies.23,31

The biological meshes consisted in four studies of cross linked porcine meshes23,26,27,39, and in one studies of non-cross linked porcine meshes.28 In one study, both cross linked and non-cross linked meshes were used31, and in two studies human dermal meshes were used.16,24 Perineal wound problems after eAPR and at least 75% of the patients treated with radiotherapy occurred in a pooled percentage of 24.3% (95% CI 14.1-38.6; I2=21%, χ2=0.28; 4 studies, n=78).24,28,31,39 If only two studies were included in which all patients underwent neoadjuvant radiotherapy, perineal wound problems after eAPR occurred in a pooled percentage of 7.3% (95% CI 1.5-29.3; I2=0%, χ2=0.81; n=20).24,31

Perineal hernias after biological mesh closure following eAPR were reported in a pooled percentage of 8.2% (95% CI 4.8-13.6; I2=0%, χ2=0.45; 6 studies, n=188).16,23,24,26,28,39

Figure 3 The pooled percentages with 95% confidence intervals


41

2

DISCUSSION

Neoadjuvant radiotherapy significantly increased perineal wound problems after APR for rectal cancer with an Odds Ratio of 2.22. Although an extralevator approach has also been associated with higher wound complication rates, similarly weighted pooled percentages of perineal wound problems after cAPR and eAPR were found in homogeneous subgroups depending on whether or not radiotherapy was applied. Without neoadjuvant radiotherapy, perineal wound problems occurred in 15.3% after cAPR and 14.8% after eAPR; corresponding wound problem rates following radiotherapy were 30.2% and 37.6%. This suggests that, not the extent of the resection, but mainly neoadjuvant radiotherapy is the most important therapy-related risk factor for perineal wound complications.

The majority of the available studies have significant methodological shortcomings, and these data should be interpreted with caution, especially the studies with high statistical heterogeneity. The relatively high statistical heterogeneity could be the result of the non-standardized prospective evaluation and registration of the perineal wounds and the non-uniform definitions used for classifying perineal wound complications. Both the use of neoadjuvant radiotherapy and an extralevator approach for the APR procedure have increased over time, with more focus on perineal wound complications in more recently published articles. Therefore, a restriction of the studies before 1990 was applied, and subgroup analyses for the amount of radiotherapy and the extent of resection have been performed in this systematic review. Also, a detailed description of the different types of perineal wound problems is lacking in a substantial number of studies, such as superficial wound infection, dehiscence without infection, and deep pelvic abscess. This was the reason for choosing a combined end point of all perineal wound problems as primary outcome measure for the present analysis. Although all these limitations may have influenced the pooled analyses, the presently reported data are the best available evidence at this time. Neoadjuvant radiotherapy might increase perineal wound problems and reduce perineal wound healing because it damages DNA and proteins, which could lead to apoptotic cell death.40Apoptosis in endothelial cells leads to increased vascular permeability. This permeability results in thrombosis and intima proliferation.40 Furthermore, radiotherapy affects pro-inflammatory cytokines in the early phase.40 Therefore, inflammation may not resolve adequately, leading to uncontrolled matrix accumulation and fibrosis. Also decreased levels of nitric oxide and matrix metalloproteinase may contribute to the inadequate soft tissue reconstruction.41

Primary perineal wound closure after APR has been the standard technique for a long period of time. This entails a layered closure of the remaining structures, namely, the remnants of the pelvic floor, ischioanal and subcutaneous fat, and perineal skin. After an extralevator approach, only the fat and perineal skin can be closed because the pelvic floor has been resected. Despite the much larger pelvic defect, satisfying outcome on perineal wound healing has been published for primary perineal closure after eAPR.4,21,37 But this is not uniformly reported, and others have used additional surgical procedures to improve perineal wound healing after eAPR. Autologous tissue flap such as the vertical rectus abdominis myocutaneous flap and gluteal flap, have been used for closure of large perineal defects after extended resections for primary or recurrent rectal cancer or salvage surgery for anal cancer.42–45 Because of the donor site morbidity, increased operative time, and higher

Chapter 2

42

costs, it is questioned whether autologous tissue flap should be performed as a routine in patients undergoing APR for rectal cancer. Pelvic floor reconstruction with the use of a biological mesh has been introduced recently and appears to be an attractive alternative for tissue flap based on a recent systematic review.46 However, a comparison between primary perineal wound closure and biological mesh-assisted closure has not yet been made. Literature on biological mesh-assisted perineal closure after APR is scarce (table 3). In contrast, most of the APR studies have a primary oncological focus, whereas perineal wound healing and perineal hernia formation are often primary outcome measures in biological mesh studies. This does not allow for a formal comparison between primary perineal wound closure and biological mesh assisted closure based on literature data. Although the pooled analysis suggests a reduced percentage of perineal wound problems after biological mesh assisted closure, RCTs are needed to draw definitive conclusions. To date, 2 multicentre trials are being conducted in which pelvic floor reconstruction using a biological mesh is compared with primary perineal wound closure (BIOPEX-study; Clinicaltrials.gov identifier NCT01927497) or gluteus maximus myocutaneous flap closure (NEAPE; Clinicaltrials.gov identifier NCT01347697).

Perineal wound problems are also likely to be related to the dead space in the pelvis with bacterial contamination. An omentoplasty may solve this problem by filling of the pelvic cavity, improving the local immune response and promoting angiogenesis.47,48 Therefore, the application of an omentoplasty has been suggested to improve primary perineal wound healing.49,50 Only five selected studies described the use of an omentoplasty without separate data on perineal wound healing. The effect of this additional surgical procedure could therefore not be analysed in the present meta-analysis.

In our systematic review, we found a rather high weighted pooled percentage of perineal hernia in patients undergoing pelvic floor reconstruction using a biological mesh. This contradictory finding is most likely related to a more detailed description of perineal complications with more adequate follow-up in biological mesh studies compared to oncological APR studies using primary perineal wound closure. In addition, the extent of the resection (only eAPR in biological mesh studies) and a learning curve effect of a new surgical technique may explain the relatively high perineal hernia rate.

In conclusion, our systematic review demonstrates that neoadjuvant radiotherapy significantly increases perineal wound problems after APR, while the extralevator approach seems to be of less influence. Biological mesh assisted perineal wound closure is a promising technique to improve perineal wound healing, but we have to await results of ongoing randomised trials.


43

2

Tabl

e 1 P

erin

eal w

ound

pro

blem

s afte

r APR

with

prim

ary p

erin

eal c

losu

re fo

r rec

tal c

ance

r

Inclu

ded

studi

esSt

udy c

hara

cter

istic

sO

pera

tion

Preo

pera

tive

antib

iotic

sNe

oadj

uvan

t tre

atm

ent

Perin

eal w

ound

Fo

llow-

up

First

auth

orye

arn

Stud

y de

sign

Cons

ecut

ive

serie

scA

PR/

eAPR

#(Y

es/n

o)Ra

diot

hera

pyn(

%)

Conc

omita

ntch

emot

hera

pyn(

%)

sPW

Pn(

%)*

dPW

Pn(

%)*

cPW

Pn(

%)*

PWH

n(%

)In

cisio

nal

hern

ian(

%)

Mon

ths

(rang

e)

Haw

kins

AT

et al

.2520

1323

9 of

249

Coho

rt Ye

scA

PR-

--

65 (2

7)-

65 (2

7)-

-45

(1-1

30) +

Han

JG et

al.16

20

1232

of 6

7RC

T-

cAPR

-9

(28)

9 (2

8)6

(19)

-6

(19)

-4

(13)

29 (1

2-48

)+

Aspl

und

D et

al.32

20

1179

of 1

58Co

hort

No

cAPR

-66

(84)

5 (6

)22

(28)

-22

(28)

26 (3

3)-

45 (1

-89)

+

Pram

ateft

akis

MG

et al

.18

2011

75RC

T-

cAPR

Yes

25 (3

3)25

(33)

14 (1

9)1

(1)

15 (2

0)61

(81)

-60

^

Zorc

olo

L et

al.3

620

1015

5Co

hort

No

cAPR

Yes

68(4

4)40

(26)

23 (1

5)0

23 (1

5)-

-34

(25-

57)~

El-G

azza

z G et

al.2

2009

696

Coho

rt Ye

scA

PR-

273

(39)

273

(39)

80 (1

1)26

(4)

106

(15)

633

(91)

7 (1

)-

Seba

g-M

onte

fiore

D et

al.19

2009

202

of 1

350

RCT

-cA

PR-

202

(100

)-

--

-13

2 (6

5)-

60^

Wes

t NP

et al

.9 20

0912

4 of

176

Coho

rt Ye

scA

PR-

90 (7

3)48

(39)

7 (6

)-

7 (6

)-

1 (1

)-

De B

ruin

AF

et.al

.1 20

0821

of 4

0Co

hort

Yes

cAPR

Yes

21 (1

00)

-6

(29)

6 (2

9)12

(57)

9 (4

3)-

-Ch

an S

et al

.22

2008

18 o

f 51

Coho

rt Ye

scA

PR-

--

3 (1

7)0

3 (1

7)-

-38

(16-

58) ~

Artio

ukh

DY et

al.20

20

0629

of 3

8Co

hort

Yes

cAPR

--

--

--

25 (8

6)-

-Ch

adwi

ck M

A et

al.33

20

0694

Coho

rt Un

clear

cAPR

Yes

39 (4

1)-

44 (4

7)-

44 (4

7)57

(61)

-40

(25-

55) +

Bulla

rd K

M et

al.10

20

0516

0Co

hort

Yes

cAPR

-11

7 (7

3)10

7 (6

7)65

(41)

-65

(41)

122

(76)

1 (1

)-

Gru

essn

er U

et al

.15

2001

48 o

f 97

RCT

-cA

PRYe

s0

-5

(10)

5 (1

0)10

(21)

36 (7

5)-

2^

Kapi

teijn

E et

al.17

20

0148

5 of

180

5RC

T-

cAPR

-25

1 (5

2)0

107

(22)

-10

7 (2

2)-

-24

+

Sche

ibac

h H

et al

.30

2001

149

of 2

31Co

hort

Yes

cAPR

--

--

--

111

(74)

-25

~

Fing

erhu

t A et

al.1

419

9516

5RC

T-

cAPR

Yes

0 -

-18

(11)

18 (1

1)11

2 (6

8)-

12^

Dela

lande

JP et

al.13

19

9421

of 4

5RC

T-

cAPR

Yes

--

-10

(48)

10 (4

8)6

(29)

-12

^

Wan

g JY

et al

.35

1994

83 o

f 103

Coho

rt N

ocA

PR-

--

19 (2

3)-

19 (2

3)74

(89)

-6^

Chapter 2

44

Robl

es C

ampo

s R et

al.29

19

9268

of 1

02Co

hort

Yes

cAPR

Yes

--

21 (3

1)-

21 (3

1)47

(69)

--

Maz

ier W

P et

al.34

19

9146

of 2

88Co

hort

No

cAPR

Yes

--

2 (4

)-

2 (4

)7

(15)

--

Tosh

niwa

l S et

al.38

20

1353

Coho

rt N

oeA

PR-

46 (8

7)46

(87)

6 (1

1)-

6 (1

1)-

3 (6

)60

^

Aspl

und

D et

al.32

20

1179

of 1

58Co

hort

No

eAPR

-60

(76)

15 (1

9)36

(46)

-36

(46)

19 (2

4)-

26 (1

-88)

+

Bębe

nek

M et

al.21

2009

210

Coho

rt Ye

seA

PR-

65 (3

1)19

(9)

34 (1

6)3

(1)

37 (1

8)-

2 (1

)30

(1-9

1) +

De B

roux

E et

al.37

20

0510

4Co

hort

No

eAPR

Yes

62 (6

0)16

(15)

12 (1

2)6

(6)

18 (1

7)83

(80)

1 (1

)24

~

Niss

an A

et al

.4 20

0128

2Co

hort

Yes

eAPR

Yes

123(

44)

-69

(24)

18 (6

)87

(31)

182

(65)

-12

0^

+= m

edia

n fo

llow-

up. ^

= pr

otoc

olise

d fo

llow-

up.

~= m

ean

follo

w-up

. RC

T= ra

ndom

ised

cont

rolle

d tri

al. c

APR=

con

vent

iona

l abd

omin

oper

inea

l res

ectio

n. e

APR=

ext

ralev

ator

ab

dom

inop

erin

eal r

esec

tion.

sPW

P=su

perfi

cial p

erin

eal w

ound

pro

blem

s (in

fectio

ns a

nd d

ehisc

ence

) with

in 3

0 da

ys. d

PWP=

deep

per

inea

l wou

nd p

robl

ems (

perin

eal a

nd p

resa

cral

ab

sces

ses)

with

in 3

0 da

ys. c

PWP=

com

bine

d pe

rinea

l wou

nd p

robl

ems (

infec

tions

, deh

iscen

ce, p

erin

eal a

bsce

sses a

nd p

resa

cral

abs

cesse

s) wi

thin

30

days

. *=a

pat

ient w

as o

nly c

ount

ed

once

if m

ore t

han

one c

ompli

catio

n wa

s pre

sent

. PW

H=p

rimar

y per

inea

l wou

nd h

ealin

g.

Cont

inua

tion

of T

able

1


45

2

Tabl

e 2 P

erin

eal w

ound

pro

blem

s afte

r APR

with

prim

ary p

erin

eal c

losu

re in

pat

ients

bein

g tre

ated

with

or w

ithou

t neo

adju

vant

radi

othe

rapy

.

Inclu

ded

studi

esO

pera

tion

Radi

othe

rapy

Perin

eal w

ound

First

auth

orcA

PR/e

APR#

NYe

s/no

sPW

Pn(

%)

dPW

Pn(

%)

cPW

Pn(

%)*

PWH

n(%

)In

cisio

nal h

erni

a n(

%)

Bulla

rd K

M et

al.10

cAPR

117

Yes

16 (1

4)-

55 (4

7)86

(74)

1 (1

)cA

PR43

No

0-

10 (2

3)36

(84)

-Ch

adwi

ck M

A et

al.33

cAPR

37Ye

s-

--

13 (3

5)-

cAPR

57N

o-

--

44 (7

7)-

El-G

azza

z G et

al.2

cAPR

273

Yes

49 (1

8)14

(5)

55 (2

0)23

4 (8

6)1

(0.4

)cA

PR42

3N

o46

(11)

12 (3

)51

(12)

399

(94)

6 (1

)Ka

pite

ijn E

et al

.17^

cAPR

251

Yes

65 (2

6)-

65 (2

6)-

-cA

PR23

4N

o42

(18)

-42

(18)

--

Zorc

olo

L et

al.36

cAPR

68Ye

s10

(15)

010

(15)

--

cAPR

87N

o13

(15)

013

(15)

--

De B

roux

E et

al.37

eAPR

46Ye

s-

-12

(26)

--

eAPR

58N

o-

-6

(10)

--

Niss

an A

et al

.4eA

PR12

3Ye

s48

(39)

12 (1

0)60

(49)

53 (4

3)6

(5)

eAPR

159

No

21 (1

3)6

(4)

27 (1

7)12

9 (8

1)

5 of

94

(5)

cAPR

= co

nven

tiona

l abd

omin

oper

inea

l res

ectio

n. eA

PR=

extra

levat

or a

bdom

inop

erin

eal r

esec

tion.

*=a

patie

nt w

as o

nly c

ount

ed o

nce i

f mor

e tha

n on

e com

plica

tion

was p

rese

nt. s

PWP=

supe

rficia

l per

inea

l wou

nd pr

oblem

s (in

fectio

ns an

d de

hisc

ence

) with

in 30

day

s. dP

WP=

dee

p pe

rinea

l wou

nd

prob

lems (

perin

eal a

nd p

resa

cral

absc

esse

s) wi

thin

30

days

. cPW

P= co

mbi

ned

perin

eal w

ound

pro

blem

s (in

fectio

n, ab

sces

ses a

nd d

ehisc

ence

) with

in

30 d

ays.

PWH

= pr

imar

y per

inea

l wou

nd h

ealin

g. ^=

this

study

is a

rand

omise

d co

ntro

lled

trial

.

Chapter 2

46

Tabl

e 3 B

iolo

gica

l mes

h as

siste

d clo

sure

of t

he p

erin

eum

after

APR

for r

ecta

l can

cer

Inclu

ded

studi

esSt

udy c

hara

cter

istics

Ope

ratio

nPr

eope

rativ

e an

tibio

tics

Neoa

djuv

ant t

reat

men

tPe

rinea

l wou

ndFo

llow-

up

First

auth

orye

arn

Stud

y de

sign

Cons

ecut

ive

serie

scA

PR/e

APR#

(Yes

/no)

Radi

othe

rapy

n(%

)Co

ncom

itant

chem

othe

rapy

n(%

)

sPW

Pn(

%)*

dPW

Pn(

%)*

cPW

Pn(

%)*

PWH

n(%

)In

cisio

nal

hern

ian(

%)

Mon

ths

(rang

e)

Jens

en K

K et

al.26

2013

53Co

hort

Yes

eAPR

-23

(43)

23 (4

3)12

(23)

4 (8

)16

(30)

-3

(6)

36 (1

-67)

+

Kipl

ing S

L et

al.27

2013

28Co

hort

Yes

eAPR

-19

(67)

17 (6

1)3

(11)

-3

(11)

--

38 (2

3-66

) +

Peac

ock

O et

al.28

2013

34Co

hort

Yes

eAPR

-28

(82)

26 (7

6)8

(24)

3 (9

)11

(32)

20 (5

9)1

(3)

21 (2

-54)

+

Han

JG et

al.16

2012

35 o

f 67

RCT

-eA

PR-

10 (2

9)10

(29)

4 (1

1)-

4 (1

1)-

5 (1

4)22

(16-

46)+

Chris

tens

en H

K et

al.39

2011

24 o

f 57

Coho

rt N

oeA

PRYe

s20

(83)

20 (8

3)6

(25)

-6

(25)

-0

20 (5

-26)

+

Dalt

on R

SJ et

al.23

2011

30 o

f 31

Coho

rt Ye

seA

PR-

14 (4

7)14

(47)

15 (5

0)-

15 (5

0)-

3 (1

0)20

(0-4

5) +

Vaug

han-

Shaw

PG

et al

.3120

118

of 1

3Co

hort

Yes

eAPR

-8

(100

)-

0 0

08

(100

)-

9 (0

-21)

+

Han

JG et

al.24

2010

12Co

hort

Yes

eAPR

-12

(100

)12

(100

)1

(8)

01

(8)

11 (9

2)0

8 (2

-16)

+

+= m

edia

n fo

llow-

up.

RCT=

rand

omise

d co

ntro

lled

trial

. cAP

R= co

nven

tiona

l abd

omin

oper

inea

l res

ectio

n. e

APR=

ext

ralev

ator

abd

omin

oper

inea

l res

ectio

n. *=

a p

atien

t was

onl

y co

unted

once

if m

ore t

han

one c

ompl

icatio

n wa

s pre

sent

. sPW

P= su

perfi

cial p

erin

eal w

ound

prob

lems (

infec

tions

and

dehi

scen

ce) w

ithin

30 da

ys. d

PWP=

deep

perin

eal w

ound

prob

lems

(per

inea

l and

pres

acra

l abs

cesse

s) wi

thin

30 d

ays.

cPW

P= co

mbi

ned

perin

eal w

ound

prob

lems (

infec

tions

, deh

iscen

ce, p

erin

eal a

bsce

sses a

nd pr

esac

ral a

bsce

sses)

with

in 30

day

s. PW

H=

prim

ary p

erin

eal w

ound

hea

ling.


47

2

Appendix 1

Newcatle Ottawa quality assessment scale1 cohort studies

Included Studies Jadad et al.2

(0-5)Selection

(0-4)Comparability

(0-2)Outcome

(0-3)Total(0-9)

Artioukh DY 200620 - * - ** 3Asplund D 201132 - *** - ** 5Bębenek M 200921 - * - ** 3Bullard KM 200510 - *** ** * 6Chadwick MA 200633 - * - ** 3Chan S 200822 - ** - ** 4Christensen HK 201139 - *** - * 4Dalton RSJ 201123 - ** - ** 4De Broux E 200537 - *** - ** 5De Bruin AF 20081 - ** - * 3Delalande JP 199413 3 ** - ** 4El-Gazzaz G 20092 - ** - ** 4Fingerhut A 199514 3 ** - ** 4Gruessner U 200115 1 ** - ** 4Han JG 201216 1 ** - ** 4Han JG 201024 - - - ** 2Hawkin AT 201325 - ** * ** 5Jensen KK 201326 - * - * 2Kapiteijn E 200117 3 ** - ** 4Kipling SL 201327 - * - * 2Mazier WP 199134 - *** - * 4Nissan A 20014 - *** - ** 5Peacock O 201328 - ** - ** 4Pramateftakis MG 201118 3 ** - ** 4Robles Campos R 199229 - ** - ** 4Sebag-Montefiore D 200919 3 ** - * 3Scheidbach H 200130 - ** - ** 4Toshniwal S 201338 - ** - * 3Vaughan-Shaw PG 201131 - * - ** 3Wang JY 199435 - ** - * 3West NP 20099 - *** ** ** 7Zorcolo L 201036 - *** - ** 5

Chapter 2

48

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49

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