The American Society of Colon and Rectal Surgeons Clinical

1135

DISEASES OF THE COLON & RECTUM VOLUME 61: 10 (2018)

The American Society of Colon and Rectal Surgeons

(ASCRS) is dedicated to ensuring high-quality patient care

by advancing the science, prevention, and management

of disorders and diseases of the colon, rectum, and anus.

The Clinical Practice Guidelines Committee is charged

with leading international efforts in deﬁning quality care

for conditions related to the colon, rectum, and anus by

developing clinical practice guidelines based on the best

available evidence. These guidelines are inclusive, not pre-

scriptive, and are intended for the use of all practitioners,

healthcare workers, and patients who desire information

about the management of the conditions addressed by the

topics covered in these guidelines. Their purpose is to pro-

vide information on which decisions can be made rather

than to dictate a speciﬁc form of treatment.

STATEMENT OF THE PROBLEM

Radiation therapy is frequently used in many types of

cancer, including anal, cervical, prostate, and rectal. Al-

though radiation has beneﬁcial effects in treating tumors,

collateral damage to the GI tract can occur, and although

acute toxicity in the form of either proctitis or enteritis

may occur, the more concerning symptom is the devel-

opment of a chronic hemorrhagic radiation proctitis.

Chronic hemorrhagic radiation proctitis is a syndrome

marked by hematochezia, mucus discharge, tenesmus,

and, often, fecal incontinence.

The incidence of this

condition was previously reported to be as high as 30%

;

however, with recent advances in radiation techniques,

the delivery of a more targeted external beam radiation to

tumors will hopefully minimize collateral toxicity. Cur-

rent estimates are that ~1% to 5% of patients treated with

radiation for pelvic malignancy will experience chronic

radiation proctitis.

Because of the nature of the symp-

toms associated with this condition, colorectal surgeons

are frequently called on for management and should be

well versed in the various treatment options. This param-

eter will grade the evidence of the common interventions,

which have been described for chronic hemorrhagic ra-

diation proctitis.

METHODOLOGY

PubMed was used to search MEDLINE for all entries from

January 1990 to October 26, 2017, with the results limited

to human studies. Search terms included radiation proctitis

(n = 757 titles), radiation enteritis (n = 492), radiation proctitis

AND each of the following terms: antibiotics (n = 10), argon

beam (n = 16), aminosalicylate enema (n = 5), Carafate enema

(n = 16), endoscopy (n = 130), formalin (n = 90), hyperbaric

oxygen (n = 56), short chain fatty acid (n = 15), and steroid en-

ema (n = 13). The Cochrane Database of Systematic Reviews

was searched with the term radiation proctitis. These searches

yielded 1278 unique titles (PubMed = 1275, Cochrane = 3)

that were screened, and 365 references were directly reviewed,

ultimately yielding 56 references for inclusion. Prospective,

randomized controlled trials and meta-analyses were given

Funding/Support: None reported.

Financial Disclosure: None reported.

Correspondence: Scott R. Steele, M.D., M.B.A., Cleveland Clinic Foun-

dation, Cleveland, OH 44915. E-mail: steeles3@ccf.org

The American Society of Colon and Rectal Surgeons

Clinical Practice Guidelines for the Treatment of

Chronic Radiation Proctitis

Ian M. Paquette, M.D.

• Jon D. Vogel, M.D.

• Maher A. Abbas, M.D.

Daniel L. Feingold, M.D.

• Scott R. Steele, M.D., M.B.A.

On behalf of the Clinical Practice Guidelines Committee of The American Society of Colon and Rectal Surgeons

1 University of Cincinnati Medical Center, Cincinnati, Ohio

2 Anschutz Medical Campus, University of Colorado Denver, Denver, Colorado

3 Al Zahra Hospital, Dubai, United Arab Emirates

4 Columbia University Medical Center, New York, New York

5 Cleveland Clinic, Cleveland, Ohio

Dis Colon Rectum 2018; 61: 1135–1140

DOI: 10.1097/DCR.0000000000001209

CLINICAL PRACTICE GUIDELINES

PAQUETTE ET AL: TREATMENT OF CHRONIC RADIATION PROCTITIS

1136

preference in developing these guidelines. Directed searches

of the embedded references from the primary articles were

also performed in certain circumstances. The ﬁnal source

material used was evaluated for the methodologic quality,

the evidence base was examined, and a treatment guideline

was formulated by the subcommittee for this guideline. The

ﬁnal grade of recommendation was performed using the

Grade of Recommendation, Assessment, Development, and

Evaluation system

(Table 1). Members of the ASCRS Clinical

Practice Guidelines Committee worked in joint production

of these guidelines from inception to ﬁnal publication. Rec-

ommendations formulated by the subcommittee were then

reviewed by the entire Clinical Practice Guidelines Commit-

tee for edits and recommendations. Final recommendations

were approved by the ASCRS Clinical Guidelines Committee

and ASCRS Executive Committee. In general, each ASCRS

Clinical Practice Guideline is updated every 3 to 5 years.

Evaluation of Chronic Radiation Proctitis

A disease-speciﬁc history and physical examination

should be performed, emphasizing the degree and du-

ration of bleeding. Grade of Recommendation: Strong

recommendation based on low-quality evidence, 1C.

The typical patient with chronic radiation proctitis (CRP)

will present with hematochezia. Other common symptoms

are fecal urgency, tenesmus, or drainage of mucus from the

rectum.

1,2

It is important to review the history of the prima-

ry disease process and the radiation dose received. Because

the most common indications for pelvic radiation therapy

are malignancies (anal cancer, uterine cancer, cervical can-

cer, prostate cancer, and rectal cancer), it is important to as-

sess the patient for recurrence of his or her primary cancer

with physical examination or imaging where appropriate.

At a minimum, a digital rectal examination should be per-

formed to evaluate sphincter tone, as well as a proctoscopic

examination to evaluate the quality of the mucosa, distribu-

tion of disease, and to rule out malignancy.

Colonoscopy is

indicated if proctoscopy cannot delineate the full extent of

disease, if it is impossible to rule out another form of colitis,

or if the patient meets criteria for colonoscopy, as described

by the US Multi-Society Task Force on Colorectal Cancers.

Prophylactic measures, such as pedicled omental ﬂap

and tissue expander implant, have been described to de-

crease the incidence of radiation proctitis. These tech-

niques are insufﬁciently evaluated and are not routinely

recommended. Grade of Recommendation: Strong rec-

ommendation based on low-quality evidence, 1C.

TABLE 1. The Grade of Recommendation, Assessment, Development, and Evaluation system: grading recommendations

Description Benet vs risk and burdens

Methodologic quality of supporting

evidence Implications

1A Strong recommendation,

high-quality evidence

Benets clearly outweigh risk

and burdens or vice versa

RCTs without important limitations

or overwhelming evidence from

observational studies

Strong recommendation, can apply to

most patients in most circumstances

without reservation

1B Strong recommendation,

moderate-quality evidence

Benets clearly outweigh risk

and burdens or vice versa

RCTs with important limitations

(inconsistent results,

methodologic aws, indirect,

or imprecise) or exceptionally

strong evidence from

observational studies

Strong recommendation, can apply to

most patients in most circumstances

without reservation

1C Strong recommendation,

low- or very low–quality

evidence

Benets clearly outweigh risk

and burdens or vice versa

Observational studies or case

series

Strong recommendation but may

change when higher quality

evidence becomes available

2A Weak recommendation,

high-quality evidence

Benets closely balanced

with risks and burdens

RCTs without important limitations

or overwhelming evidence from

observational studies

Weak recommendation, best

action may dier depending on

circumstances or patient or societal

values

2B Weak recommendations,

moderate-quality evidence

Benets closely balanced

with risks and burdens

RCTs with important limitations

(inconsistent results,

methodologic aws, indirect,

or imprecise) or exceptionally

strong evidence from

observational studies

Weak recommendation, best

action may dier depending on

circumstances or patient or societal

values

2C Weak recommendation,

low- or very low–quality

evidence

Uncertainty in the estimates

of benets, risks, and

burden; benets, risk,

and burden may be closely

balanced

Observational studies or case

series

Very weak recommendations, other

alternatives may be equally

reasonable

Adapted and reprinted with permission from Chest. 2006;129:174–181.

RCT = randomized controlled trial.

DISEASES OF THE COLON & RECTUM VOLUME 61: 10 (2018)

1137

In the early 1990s, studies emerged describing methods to

exclude the small bowel from the pelvis and to decrease

the incidence of radiation enteritis. The ﬁrst such study

was a multicenter trial from Europe describing a mesh

sling to exclude the small bowel from the pelvis before

radiation.

There was no comparison group in this study,

and the fear of complications from pelvic mesh has led to

the abandonment of this approach. In the 1990s, pedicled

omentoplasty was described.

7–9

Although this approach

may reduce small-bowel enteritis, radiation proctitis was

still seen in as many as 33% of patients.

Other strategies,

such as tissue expander implant, have been described, but

there is not sufﬁcient evidence to support its use.

As ra-

diation techniques have become more precise, it is thought

that these adjuncts are not necessary to reduce complica-

tions.

Other adjuncts, such as oral glutamine during ra-

diation, have been described. Although 1 study suggested

decreased proctitis symptom severity in patients treated

with glutamine,

another relatively recent randomized

controlled trial suggested that the incidence of radiation

proctitis in a modern series is low and that no beneﬁt was

derived from prophylactic glutamine administration.

Short chain fatty acid enemas given during radiation ther-

apy were also studied in a randomized controlled trial and

showed no beneﬁt in preventing radiation proctitis.

Medical Treatments

Formalin application is an effective treatment for bleeding

in patients with CRP. Grade of Recommendation: Strong

recommendation based on moderate-quality evidence, 1B.

Formalin (ie, formaldehyde 4%–10%) has been used for >2

decades for the treatment of patients with CRP. The treat-

ment can be rendered in the outpatient clinic setting with

the patient awake or in a minor procedure room under in-

travenous sedation. Seow-Choen et al

reported their ini-

tial experience with 8 patients with hemorrhagic radiation

proctitis. There were 7 women and 1 man, with a median

age of 68 years. The median duration of symptoms before

treatment was 8 months, with a median number of units of

blood transfusion of 4 (range, 2 to 32). Bleeding resolved

in 7 patients after 1 application, and 1 patient had an ad-

ditional treatment at 2 weeks. No blood transfusion was re-

quired during a mean follow-up of 4 months.

Chautems et

reported their experience with 13 patients who presented

with hemorrhagic radiation-induced proctitis over a 10-year

period. All of the patients were followed up to 1 year after

treatment. In 8 patients, the bleeding resolved after the ﬁrst

application, and in 4 patients it required between 2 and 4 ap-

plications. One patient developed a mild asymptomatic rec-

tal stricture.

Lee et al

reported their experience with a 4%

formalin application. The mean duration of symptoms at

presentation was 15.6 months. Improvement in symptoms

and resolution of the bleeding were noted in the majority

of patients after 1 treatment.

An additional study from Po-

land reported the outcome of 4% formalin application in 20

patients with radiation proctitis.

Most patients required

an average of 2 treatments (range, 1–5). After the ﬁrst ap-

plication, 50% of the patients had complete resolution of

the symptoms. In the remainder of patients, an additional

formalin instillation, argon therapy, and/or 5-aminosalicylic

acid suppositories were used to achieve remission.

The

Cleveland Clinic Florida reported its experience with 4%

formalin instillation for the treatment of radiation procti-

tis in 21 patients.

Bleeding stopped after the ﬁrst treatment

in 17 patients. The adverse effects noted were rectal pain in

4 patients, fecal incontinence in 2, and colitis in 1 patient.

Haas et al

reported their results with topical application of

10% buffered formalin. A total of 100 patients underwent

the treatment. Cessation of bleeding was noted in 93% of the

patients following a mean of 3.5 applications at 2- to 4-week

intervals. Patients with severe proctitis and those on aspirin

therapy required on average 1.5 additional treatments. Re-

current bleeding was noted in 8 patients, and all responded

to additional formalin applications.

Luna-Pérez et al

re-

ported their experience in 20 women with radiation proc-

titis refractory to topical steroids and/or mesalamine. A 4%

formalin solution was used in 17 patients, and the bleeding

resolved after the ﬁrst application. Three patients needed re-

peat applications, with an overall success rate of 90% during

a median follow-up of 20 months. Two patients developed

rectovaginal ﬁstula requiring colostomy with 1 subsequent

abdominoperineal resection.

Sucralfate retention enemas are a moderately effective

treatment for rectal bleeding resulting from CRP. Grade

of Recommendation: Strong recommendation based on

low-quality evidence, 1C.

In 1991, a prospective randomized, double-blind con-

trolled trial of sucralfate enemas (2 g in 20 mL of water,

twice daily) and oral sulfasalazine (1 g, 3 times daily) ver-

sus prednisolone enemas (20 mg in 20 mL of water, twice

daily) and oral placebo, in 37 patients with symptomatic

CRP, demonstrated clinical improvement in 94% and

53% of patients.

A subsequent study of 26 patients, all

of whom were treated with a 10% sucralfate suspension in

water administered twice daily, resulted in a signiﬁcant de-

crease in rectal bleeding after 4 weeks of therapy, including

negligible or complete cessation of bleeding in 23 patients

(88%) after 16 weeks of therapy and no recurrent bleed-

ing in 71% patients who were followed for a median of

45 months (range, 5–72 mo).

Two more recent studies,

with 9 and 8 patients, who were treated with sucralfate en-

ema (2 g in 20–50 mL of water or saline), demonstrated

rectal ulcer with healing or alleviation of bleeding in 89%

and 100% of patients.

24,25

In a recent study of 23 patients,

a 6-week course of sucralfate paste enemas (2 g of sucral-

fate mixed with 4.5 mL of water, twice daily) resulted in

PAQUETTE ET AL: TREATMENT OF CHRONIC RADIATION PROCTITIS

1138

a partial improvement in a composite score of radiation

proctitis symptoms (ie, bleeding, urgency, frequency, and

cramping) in 41% and complete resolution of all symp-

toms in 32%.

Short chain fatty acid enemas are not effective in prevent-

ing or treating chronic hemorrhagic radiation proctitis

and are not recommended. Grade of Recommendation:

Weak recommendation based on moderate-quality evi-

dence, 1B.

There has been some interest in short chain fatty acids such

as butyrate to treat radiation proctitis. The limited studies

in treating chronic hemorrhagic proctitis have not been

conclusive. Although some studies have demonstrated no

clear beneﬁt,

27,28

1 randomized controlled trial showed

superior symptom relief and mucosal healing compared

with placebo.

However, the enema treatments needed to

be given for 5 weeks to achieve this result, and the ben-

eﬁcial effects dissipated once the treatment was ceased.

Short chain fatty acids have been studied with reasonable

clinical improvements in acute radiation proctitis, but

have not been shown to decrease the incidence of chronic

hemorrhagic radiation proctitis.

14,30,31

Alternative treatments such as mesalamine, ozone

therapy, and metronidazole have not been adequately

evaluated in treating radiation proctitis and are not rec-

ommended. Grade of Recommendation: Strong recom-

mendation based on low-quality evidence, 1C.

Many alternative treatments, such as mesalamine,

32,33

ozone

therapy,

and metronidazole,

have been described in the

treatment of radiation proctitis. These treatments have

not been thoroughly evaluated and are not recommended

in the treatment of CRP.

Interventional Treatments

Endoscopic argon beam plasma coagulation is a safe

and effective treatment for rectal bleeding induced by

CRP. Grade of Recommendation: Strong recommen-

dation based on moderate-quality evidence, 1B.

In patients with rectal bleeding from CRP, endoscopic ar-

gon beam plasma coagulation (APC) therapy results in

cessation or a meaningful decrease in bleeding in 79% to

100% of patients.

36–43

A median of 2 APC sessions (range,

1–5) is typically required to control rectal hemorrhage. A

randomized trial of APC versus topical formalin applica-

tion conducted in 30 patients with bleeding CRP dem-

onstrated control of bleeding in 94% and 100% (p value

not signiﬁcant) and no difference in relief of other CRP

symptoms.

Rectal pain, mucus discharge, and rectal ul-

cerations commonly occur after APC but infrequently re-

quire intervention and are most often self-limited. Severe

complications, including rectovaginal ﬁstula and rectal

stricture, occur infrequently, with ≈3% of patients affect-

ed.

39,41–43

The effectiveness of APC for the relief of fecal

urgency and frequency in patients with CRP is limited, but

2 prospective studies have demonstrated improvement of

these symptoms,

36,44

and another showed no beneﬁt or

harm.

Despite rare reports of colonic explosion with per-

foration during APC after retrograde enema preparation

of the rectum,

the use of retrograde enema, complete

antegrade bowel preparation, or no bowel preparation, all

appear to be safe for rectal APC procedures.

38,40,43

In most

studies, argon ﬂow of 1 to 2 L per minute, at a power of 40

to 60 watts, and application to the rectal mucosa in pulses

of 1 to 2 seconds have been described.

Hyperbaric oxygen therapy is an effective treatment

modality to reduce bleeding in patients with CRP. Grade

of Recommendation: Strong recommendation based on

moderate-quality evidence, 1B.

Hyperbaric oxygen therapy (HBOT) has emerged as an

effective treatment for nonhealing wounds from various

etiologies including traumatic, postoperative, diabetic

related, or radiation induced.

The impact of HBOT on

tissue healing is postulated through improving tissue oxy-

genation and possible angiogenic and antibacterial effects.

Woo et al

evaluated 18 patients with CRP. Of 13 patients

with rectal bleeding, 4 patients had complete resolution

and 3 had some improvement.

Kitta et al

from Japan

reported the outcome of 4 patients with radiation proc-

titis after treatment of prostate cancer. Although patients

had a signiﬁcant reduction in degree of bleeding, 1 patient

relapsed 3 months after completion of therapy, 1 contin-

ued to have minor rectal bleeding, and 1 continued to

have persistent proctalgia with no rectal bleeding.

An-

other study examined the outcome of 10 patients, includ-

ing 3 men and 7 women, with CRP treated by HBOT.

HBOT was well tolerated, and 9 of the 10 patients com-

pleted the full course of 40 treatments. During a median

follow-up period of 25 months, rectal bleeding stopped in

4 patients and improved in 3 others. There was symptom-

atic improvement in bleeding, diarrhea, and rectal pain in

the majority of patients. Only 2 of the 10 patients had no

response.

Similarly, Oscarsson et al

conducted a pro-

spective cohort study to assess the effectiveness of HBOT

in patients with CRP. Thirty-nine patients (35 men and

4 women, mean age of 71 y) were evaluated. The mean

number of treatment was 36 sessions. The symptoms of

CRP were alleviated in 89% of the patients.

A random-

ized, controlled, double-blind crossover trial was conduct-

ed by Clarke et al

to assess the long-term effectiveness of

HBOT in patients with refractory radiation proctitis. The

patients were randomly assigned to HBOT (100% oxygen

at 2.0 atmospheres, group 1) versus air (21% oxygen at

1.1 atmospheres, group 2). Patients in group 2 were sub-

sequently crossed to group 1. Symptoms were assessed at

DISEASES OF THE COLON & RECTUM VOLUME 61: 10 (2018)

1139

3 and 6 months and then at year 1 to 5. Of 150 patients

enrolled in the study, 120 patients were evaluable. The

amount of improvement was nearly twice as great in group

1, which had a greater portion of responders (88.9% vs

62.5%; p = 0.009). In group 2, the differences were abol-

ished after crossover.

Virginia Mason Medical Center re-

ported its experience with HBOT for patients treated for

prostate cancer with radiotherapy. Over a 5-year period,

27 patients received HBOT (average of 36 sessions; range,

29 to 60 sessions). Complete resolution of bleeding was

noted in 48% of patients, and 28% reported fever bleeding

episodes. Fecal urgency resolved in 50% of the patients. Of

patients with rectal ulcers on endoscopy, complete resolu-

tion was noted in 21%, and 29% had some improvement.

In this study, only 33% of the patients had no response.

Although there is a clear beneﬁt to HBOT in patients with

CRP, it is an expensive therapy that requires specialized

equipment and several weeks of treatment sessions; thus,

it is not widely available.

Endoscopic bipolar electrocoagulation, radiofrequency

ablation, Nd-YAG laser, and cryotherapy are alternative

treatments of rectal bleeding from CRP that have been

insufﬁciently evaluated and are thus not recommended.

Grade of Recommendation: Strong recommendation

based on low-quality evidence, 1C.

A recent randomized prospective trial of bipolar elec-

trocoagulation or APC for the treatment of rectal bleed-

ing attributed to CRP demonstrated equal efﬁcacy in

bleeding control (92% vs 93%) but signiﬁcantly more

complications in the bipolar electrocoagulation group

(87% vs 33%).

Endoscopic radiofrequency ablation is

an emerging technology that, in 2 retrospective studies,

resulted in control of CRP rectal bleeding in 94% and

100% of patients.

53,54

Despite limited evidence in sup-

port of the use of endoscopic Nd-YAG laser

or cryo-

therapy,

uncertainty of the efﬁcacy and safety of these

techniques should preclude their routine use in patients

with bleeding CRP.

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