Management of Intestinal Complications in Patients With Pelvic Radiation Disease

Lorenzo Fuccio, Alessandra Guido and H. Jervoise N. Andreyev

Clinical Gastroenterology and Hepatology Volume 10, Issue 12, Pages 1326-1334.e4 (December 2012)
DOI: 10.1016/j.cgh.2012.07.017

Copyright 2012 AGA Institute Terms and Conditions

Table 1. Incidence of Late GI Toxicity According to Different Radiation Techniques, 3-Dimensional Conformal Radiotherapy and IMRT, and Toxicity Scoring System

Tumor site

Radiotherapy technique 3D-CRT IMRT

Toxicity Late GI toxicity scoring system RTOG toxicity Grade 2, scoring system 15% Grade 2, 6% RTOG toxicity Grade 3, 3% scoring system Grade 3, 3.6% NCICTCAE Grade 3, 3% Grade 3, 7% Grade 3, 20% Grade 3, 9.5%

Prostate

Cervix

3D-CRT IMRT

Anus

3D-CRT IMRT

Rectum

Preoperative NCICTCAE chemotherapy + 3D-CRT Preoperative chemotherapy + IMRT

Figure 1

Source: Clinical Gastroenterology and Hepatology 2012; 10:1326-1334.e4 (DOI:10.1016/j.cgh.2012.07.017 ) Copyright 2012 AGA Institute Terms and Conditions

Type of treatment Thermal coagulation therapy (argon plasma coagulation; YAG laser; bipolar and heater probe) Formalin

Efficacy 76%100%

Complications Anal or rectal pain, abdominal bloating, cramping, vagal symptoms, rectal stricture, rectovaginal fistula, tenesmus, colonic gas explosion, perforation Rectal pain, incontinence, diarrhea, formalin-induced colitis, anal and rectal strictures, rectal ulceration, serum sickness, and perforation Rectal ulcer, perforation Radiofrequency ablation for rectal bleeding may be performed only in the setting of controlled clinical trials

48%100%

Cryoablation Radiofrequency ablation

70%100% Not available

Table 3. Endoscopic Treatments for Radiation-Induced Bleeding

Type of treatment Thermal coagulation therapy (argon plasma coagulation; YAG laser; bipolar and heater probe)

Efficacy 76%100%

Complications Anal or rectal pain, abdominal bloating, cramping, vagal symptoms, rectal stricture, rectovaginal fistula, tenesmus, colonic gas explosion, perforation Rectal pain, incontinence, diarrhea, formalininduced colitis, anal and rectal strictures, rectal ulceration, serum sickness, and perforation Rectal ulcer, perforation Radiofrequency ablation for rectal bleeding may be performed only in the setting of controlled clinical trials

Formalin

48%100%

Cryoablation Radiofrequency ablation

70%100% Not available

Table 2. Factors Associated With the Development of Radiation Pelvic Disease

Therapy-related factors Radiation dose Volume of bowel irradiated Time-dose-fractionation parameters Chemotherapy or biological therapy (antiangiogenic therapy) Patient-related factors Diabetes Tobacco smoking IBD Collagen vascular disease (scleroderma) History of previous pelvic or abdominal surgery BMI outside the normal range Polymorphisms

Supplementary Table 2. Possible Etiologic Factors for Radiation-Induced Diarrhea and Proposed Treatment Options

Possible etiologic factors SIBO

Diagnosis Culture of small-bowel contents Breath testing Bile-salt product determination in the blood

Treatment Minimally absorbed antibiotic (rifaximin 200 g, 2 tablets 2 or 3 times/d) or broad-spectrum oral antibiotics (ciprofloxacin or doxycycline) for 7 10 d or, when available, antibiotic treatment should be based on the duodenal aspirate result

Bile acid malabsorption

SeHCAT (selenium 75 homocholic acid conjugated with taurine) Breath testing Measurement of bile acid in serum or stool

Cholestyramine (48 g, 2 times/d) or colesevelam (625 mg, up to 6 times/d) bile acid sequestrants are more effective if taken with food, low-fat diets, or a combination of diet and medical therapy

Carbohydrate (lactose) malabsorption

Breath testing/exclusion diets

Diet

Changes in gastrointestinal transit

The investigation of small-bowel motility is of little clinical value Opioids taken 3060 min before meals In case of suspected pseudo-obstruction because of degeneration of the myenteric plexus, diagnosis is challenging and based on radiologic, endoscopic, and manometric findings

Large- or small-bowel strictures

Radiology Endoscopy (colonoscopy, enteroscopy) with histologic confirmation

Hyperbaric oxygen treatment is the treatment of choice together with fiber supplements (eg, sterculia) In highly selected cases, with short-segment stricture of the large intestine, endoscopic dilatation may be considered but carries a high risk of perforation Surgery rarely needed

Pancreatic insufficiency New-onset IBD

Determination of fecal elastase Endoscopy with histologic confirmation

Pancreatic enzyme supplementation Specific treatments

New neoplasia in the GI tract

Endoscopy with histologic confirmation

Specific treatments

SIBO

Culture of small-bowel contents Breath testing Bile-salt product determination in the blood

Bile acid malabsorption

SeHCAT (selenium 75 homocholic acid conjugated with taurine) Breath testing Measurement of bile acid in serum or stool

Minimally absorbed antibiotic (rifaximin 200 g, 2 tablets 2 or 3 times/d) or broad-spectrum oral antibiotics (ciprofloxacin or doxycycline) for 710 d or, when available, antibiotic treatment should be based on the duodenal aspirate result Cholestyramine (48 g, 2 times/d) or colesevelam (625 mg, up to 6 times/d) bile acid sequestrants are more effective if taken with food, low-fat diets, or a combination of diet and medical therapy Diet

Carbohydrate (lactose) malabsorption

Breath testing/exclusion diets

Changes in gastrointestinal transit

Large- or small-bowel strictures

Pancreatic insufficiency

The investigation of small-bowel motility is of Opioids taken 3060 min before meals little clinical value In case of suspected pseudo-obstruction because of degeneration of the myenteric plexus, diagnosis is challenging and based on radiologic, endoscopic, and manometric findings Radiology Hyperbaric oxygen treatment is the treatment Endoscopy (colonoscopy, enteroscopy) with of choice together with fiber supplements histologic confirmation (eg, sterculia) In highly selected cases, with short-segment stricture of the large intestine, endoscopic dilatation may be considered but carries a high risk of perforation Surgery rarely needed Determination of fecal elastase Pancreatic enzyme supplementation
Endoscopy with histologic confirmation Endoscopy with histologic confirmation Specific treatments Specific treatments

New-onset IBD

New neoplasia in the GI tract

Prevention

Drugs

Route of Type of evidence Acute Chronic Comments Supplementary Table 1. Medical Treatments for the Prevention of Radiation-Induced Intestinal Side Effects administration toxicity toxicity
IV or SC administration RCTs
X

Amifostine

Amifostine

Rectal administration RCTs

AngiotensinOral administration converting enzyme inhibitors Balsalazide Oral administration

Preclinical in vivo studies and 1 prospective study RCT

A dose of 340 mg/m IV or 500 SC administered during the whole period of treatment may prevent acute but not late-onset symptoms Nausea and vomiting are common side effects Intrarectal administration is feasible and seems safe A dose of 12 g/d administered during the whole period of treatment may prevent acute symptoms A dose of 2 g/d seems more effective than 1 g/d No systemic side effects reported No definitive data on long-term effect Large multicenter RCTs are warranted More prospective controlled studies are needed

Beclomethasone dipropionate Budesonide Elemental diet Mesalazine Misoprostol Octreotide

Rectal administration RCT Cost-effective analysis Rectal administration RCT Oral administration RCTs

X NA X X X X NA

NA NA

Daily dose of 6 capsules may reduce compliance to the preventive treatment in clinical practice Possible beneficial effect Large multicenter RCTs are warranted Possible preventive effect on late-onset rectal bleeding and costeffective preventive strategy The study is ongoing (http://clinicaltrials.gov) Oral elemental diets are unpalatable, thus strongly limiting compliance to the treatment No beneficial or even harmful effects on acute symptoms No beneficial effect on both acute and late-onset symptoms No beneficial effect on the prevention of radiation-induced diarrhea or on patient quality of life Trials for fibrosis after breast cancer suggest benefit Large multicenter trials in the GI tract are warranted Large multicenter RCTs are warranted More prospective controlled studies are needed

Oral or rectal RCTs administration Rectal administration RCTs Intramuscular injection RCTs Phase 2

NA
X X X ?

Pentoxifylline with Oral vitamin E Probiotics Oral administration Statin Oral administration

Sucralfate

Rectal or oral administration

RCTs Meta-analysis Preclinical in vitro and in vivo studies and 1 prospective study RCTs X Meta-analysis

No beneficial or even harmful effect as preventive agents on both acute and late-onset symptoms

Prevention

Drugs Amifostine

Route of administration IV or SC administration

Type of evidence RCTs

Acute toxicity

Chronic toxicity X

Amifostine

Rectal administration

RCTs