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Medical Management of Microscopic Colitis
American Gastroenterological Association Institute Guideline on the Medical Management of Microscopic Colitis
Microscopic colitis presents as chronic watery diarrhea, is diagnosed by mucosal biopsy, and consists of the subtypes lymphocytic colitis and collagenous colitis. Management of the subtypes is similar. This new guideline from the AGA provides medical treatment recommendations and was published online November 13, 2015
Key Recommendations:
For symptomatic microscopic colitis, use budesonide as first-line therapy over mesalamine for induction of remission, and use budesonide for maintenance. During maintenance of remission, budesonide is typically tapered to the lowest effective dose. When budesonide therapy is not feasible, treat patients with mesalamine, bismuth salicylate, or prednisone for induction of remission. For induction of remission, do not treat patients with probiotics or Boswellia serrata, and do not add cholestyramine to mesalamine monotherapy.
Recommendations:
- In patients with symptomatic microscopic colitis, the AGA recommends treatment with budesonide over no treatment for the induction of clinical remission.
- In patients with symptomatic microscopic colitis, the AGA recommends treatment with budesonide over mesalamine for the induction of clinical remission.
- In patients with symptomatic microscopic colitis in whom budesonide therapy is not feasible, the AGA suggests treatment with mesalamine over no treatment for the induction of clinical remission.
- In patients with symptomatic microscopic colitis in whom budesonide therapy is not feasible, the AGA suggests treatment with bismuth salicylate over no treatment for the induction of clinical remission.
- In patients with symptomatic microscopic colitis in whom budesonide therapy is not feasible, the AGA suggests treatment with prednisolone (or prednisone) over no treatment for the induction of clinical remission.
- In patients with symptomatic microscopic colitis, the AGA suggests against combination therapy with cholestyramine and mesalamine over mesalamine alone for the induction of clinical remission.
- A single randomized clinical trial failed to show benefit from the addition of cholestyramine to mesalamine therapy. The AGA considered not only the uncertain balance between benefits and harms but also the feasibility of taking cholestyramine, which can interfere with the administration of other medications, especially in an older population in which polypharmacy is commonplace.
- In patients with symptomatic microscopic colitis, the AGA suggests against treatment with Boswellia serrata over no treatment for the induction of clinical remission.
- In patients with symptomatic microscopic colitis, the AGA suggests against treatment with probiotics over no treatment for the induction of clinical remission.
- For patients with recurrence of symptoms following discontinuation of induction therapy for microscopic colitis, the AGA recommends budesonide for maintenance of clinical remission.
Summary
The recommendations for the medical management of microscopic colitis are intended to reduce practice variation and promote high-value care. The evidence supports the first-line use of budesonide for induction and, when appropriate, maintenance therapy. Because the technical review and guideline focused on treatments assessed in clinical trials, it did not address the full armamentarium of therapies currently used in practice. The effectiveness of lower-cost alternatives such as antidiarrheal agents (eg, loperamide) and cholestyramine monotherapy were not addressed and the role of combination therapies has yet to explored. Due to the absence of clinical trial data, this guideline did not address medical treatment of corticosteroid-refractory microscopic colitis. The guideline suggests that immunosuppressants such as azathioprine and anti–tumor necrosis factor agents may benefit these patients.
http://www.gastro.org/guidelines
http://www.gastrojournal.org/article/S0016-5085(15)01625-X/abstract
http://www.gastrojournal.org/article/S0016-5085(15)01625-X/fulltext
American Gastroenterological Association Institute Guidelines on the Management of Acute Diverticulitis
The American Gastroenterological Association (AGA) Institute has issued updated guidelines regarding the management of acute diverticulitis. Routine use of antibiotics in uncomplicated diverticulitis is not recommended, and selective use is more appropriate. Patients who have not had a recent colon exam require colonoscopy after an episode of acute diverticulitis to rule out the possibility of malignancy.
Patients with a history of acute diverticulitis may benefit from a fiber-rich diet or fiber supplementation, and do not need to avoid nuts, seeds, and popcorn. Patients with a history of acute diverticulitis may safely take aspirin but should avoid non-aspirin NSAIDs. Mesalamine, rifaximin, and probiotics all have no proven benefit after an episode of acute diverticulitis. Patients should be advised to exercise.
Recommendations
The AGA suggests:
- that antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis.
- that colonoscopy be performed after resolution of acute diverticulitis in appropriate candidates to exclude the misdiagnosis of a colonic neoplasm if a high-quality examination of the colon has not been recently performed.
- against elective colonic resection in patients with an initial episode of acute uncomplicated diverticulitis. The decision to perform elective prophylactic colonic resection in this setting should be individualized.
- a fiber-rich diet or fiber supplementation in patients with a history of acute diverticulitis.
- against routinely advising patients with a history of diverticulitis to avoid consumption of seeds, nuts, and popcorn.
- against routinely advising patients with a history of diverticulitis to avoid the use of aspirin.
- advising patients with a history of diverticulitis to avoid the use of nonaspirin NSAIDs if possible.
- against the use of mesalamine after acute uncomplicated diverticulitis.
- against the use of rifaximin after acute uncomplicated diverticulitis.
- against the use of probiotics after acute uncomplicated diverticulitis.
- advising patients with diverticular disease to consider vigorous physical activity.
Important discussion points:
- Antibiotics:
Until recently, antibiotics have been the cornerstone of treatment of patients with acute diverticulitis. The emerging belief that acute diverticulitis may be more inflammatory than infectious, as well as increasing concerns about the overuse of antibiotics have led to the recommendation of selective and individualized antibiotic use. The current data are of low quality, and recommendations could change as further studies are performed. These recommendations should not be generalized to complicated patients (ie, those with abscesses or fistulas), those with signs of severe infection or sepsis, immunosuppressed patients, or patients with other significant comorbidities.
Furthermore, outpatient management without antibiotics has not been studied. - Colonoscopy:
Observational studies of patients with imaging-proven diverticulitis who subsequently underwent colonoscopy detected a small number of colorectal cancers (15/1000 patients) and advanced adenomas (38/1000 patients). Absence of a mass lesion on CT scan does not exclude the possibility of an underlying colonic neoplasm. Evidence of alternative, non-neoplastic explanations for the index presentation, such as inflammatory bowel disease or ischemic colitis, was either infrequently identified or not reported. Although an increased risk of recurrent diverticulitis or colonic perforation is a concern in patients undergoing colonoscopy after an episode of acute diverticulitis, this was not reported as an adverse event. - Elective Colonic Resection:
Approximately 20% of patients with acute uncomplicated diverticulitis experience a recurrent episode of diverticulitis in the following 5 years. The risk of future diverticular complications and need for emergency surgery among patients treated medically without colonic resection is low (<5%). Approximately 10% of patients with elective sigmoid resection after an episode of acute diverticulitis experience short-term complications of surgery, including wound infection, anastomotic leak, and cardiovascular/thrombotic events. Such postoperative risks are increased in patients older than 65 years of age. Long-term complications of abdominal distention, cramping, altered defecation, and fecal incontinence are reported in 25% of patients after elective surgery. The rates of recurrent diverticulitis appear to be higher in younger patients and the operative risks are lower, but the data do not support elective surgery in this subgroup when presenting with acute uncomplicated diverticulitis.
In conclusion, the AGA states that the management of acute diverticulitis has undergone meaningful changes over the past decade, including more judicious use of antibiotics and surgery as well as preliminary and ongoing investigations into medical therapies to decrease symptoms and reduce recurrence.
http://www.gastro.org/guidelines
http://www.gastrojournal.org/article/S0016-5085(15)01432-8/abstract
http://www.gastrojournal.org/article/S0016-5085(15)01432-8/fulltext
Canadian Guidelines for the Medical Management of Ulcerative Colitis in Nonhospitalized Patients
- In patients with mild to moderate active ulcerative proctitis, rectal 5-ASA, at a dosage of 1 g daily, is recommended as first-line therapy to induce symptomatic remission.
- In patients with mild to moderate active left-sided UC, 5-ASA enemas, at a dosage of at least 1 g daily, are recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, an oral 5-ASA preparation, at dosages between 2.0 and 4.8 g/day, is recommended as an alternative first-line therapy to induce complete remission.
- In patients with mild to moderate active UC of any disease extent beyond proctitis, the combination of a rectal and an oral 5-ASA preparation over oral 5-ASA alone is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to oral/rectal 5-ASA induction therapy in 4 to 8 weeks to determine the need to modify therapy.
- In patients with oral or rectal 5-ASA–induced complete remission of mild to moderate active left-sided UC or proctitis, the same therapy shall be continued to maintain complete remission.
- In patients with oral 5-ASA–induced complete remission of mild to moderate active UC of any disease extent, continued oral therapy of at least 2 g/day is recommended to maintain complete remission.
- In selected 5-ASA–naive patients with UC who have achieved symptomatic remission on oral corticosteroids, an oral 5-ASA preparation of at least 2 g/day is recommended while being assessed for corticosteroid-free complete remission.
- In patients with UC who have failed to respond to oral 5-ASA, switching to another oral 5-ASA formulation to induce remission is not recommended.
- When using oral 5-ASA to induce or maintain complete remission of UC, once-daily dosing is preferred over more frequent dosing.
- In patients with moderate to severe active UC, oral corticosteroids are recommended as first-line therapy to induce complete remission.
- In patients with mild to moderate active UC who fail to respond to 5-ASA therapy, oral corticosteroids are recommended as second-line therapy to induce complete remission.
- In patients with mild to moderate active left-sided UC or proctitis who fail to respond to rectal 5-ASA therapy, rectal corticosteroids are suggested as second-line therapy to induce complete remission.
- In patients with UC, oral corticosteroids are not recommended to maintain complete remission because they are ineffective for this indication and their prolonged use is associated with significant adverse effects.
- In patients with mild to moderate UC of any disease extent, oral budesonide MMX is suggested as an alternative first-line therapy to induce complete remission.
- It is recommended that patients with UC be evaluated for lack of symptomatic response to corticosteroid induction therapy within 2 weeks to determine the need to modify therapy.
- In patients with UC, the use of thiopurine monotherapy to induce complete remission is not recommended.
- In selected patients with UC who have achieved symptomatic remission on oral corticosteroids, thiopurine monotherapy is suggested as an option to maintain complete corticosteroid-free remission.
- In patients with UC, the use of methotrexate monotherapy is not recommended to induce or maintain complete remission.
- In patients with UC who fail to respond to thiopurines or corticosteroids, anti-TNF therapy is recommended to induce complete corticosteroid-free remission.
- Anti-TNF therapy should be combined with a thiopurine or methotrexate rather than used as monotherapy to induce complete remission.
- In patients with UC who are corticosteroid dependent, anti-TNF therapy is recommended to induce and maintain complete corticosteroid-free remission.
- It is recommend that patients with UC be evaluated for lack of symptomatic response to anti-TNF induction therapy in 8 to 12 weeks to determine the need to modify therapy.
- In patients with UC who respond to anti-TNF induction therapy, continued anti-TNF therapy is recommended to maintain complete remission.
- In patients with UC who have a suboptimal response to anti-TNF induction therapy, dose intensification is recommended to achieve complete remission.
- In patients with UC who lose response to anti-TNF maintenance therapy, optimizing dose is recommended to recapture complete remission.
- Dose optimization for patients with UC thjrough therapeutic drug monitoring is recommended.
- In patients with primary failure to an anti-TNF therapy, switching to vedolizumab is recommended over switching to another anti-TNF therapy to induce complete corticosteroid-free remission.
- In patients with secondary failure to an anti-TNF therapy, switching to another anti-TNF therapy or vedolizumab is recommended based on therapeutic drug monitoring results to induce complete corticosteroid-free remission.
- In patients with moderate to severe active UC who fail to respond to corticosteroids, thiopurines, or anti-TNF therapies, vedolizumab is recommended to induce complete corticosteroid-free remission.
- Patients with UC shall be evaluated for lack of symptomatic response to vedolizumab induction therapy in 8 to 14 weeks to determine the need to modify therapy.
- In patients with UC who respond to vedolizumab, continued vedolizumab therapy is recommended to maintain complete corticosteroid- free remission.
- Fecal microbial transplant to induce or maintain complete remission in patients with UC is not recommended outside the setting of a clinical trial.
- In patients with UC, probiotics to induce or maintain complete remission outside the setting of a clinical trial are not recommended.
- 5-ASA failure: Inability of the patient to achieve and maintain complete corticosteroid-free remission despite optimal treatment with oral, rectal, or combination 5-ASA therapy
- Thiopurine failure: Inability of the patient to maintain corticosteroid-free complete remission despite dose optimization
- Biologic failure:
- Primary failure: Inability of the patient to achieve corticosteroid-free complete remission despite dose optimization
- Secondary failure: Inability of the patient to maintain corticosteroid-free complete remission after achieving a symptomatic response
- High disease activity (in acute setting)
- Frequency of hospitalization
- Need for surgery
- Inability to work or participate in leisure activities
- Failure to respond to medication
- Complete remission: Both symptomatic remission and endoscopic healing as defined below
- Endoscopic healing: Normal mucosa, vascular blurring, or chronic changes (eg, inflammatory polyps, scarring) without friability
- Symptomatic remission: Normal stool frequency ( 3/day) and no blood in the stool
- Symptomatic response: Meaningful improvement in symptoms as judged by both the patient and physician in the absence of remission; response should not be considered a desirable final outcome but is useful to assess early response to treatment
- Disease Extent
- The extent of endoscopic disease was categorized as
- proctitis (distal to the rectosigmoid junction or within 18 cm of the anal verge)
- left-sided colitis (extending anywhere from the sigmoid to the splenic flexure), or
- extensive colitis (extending beyond the splenic flexure).
- The extent of endoscopic disease was categorized as
- Disease Activity
- Disease activity is best determined by clinical symptoms and an objective assessment of disease activity through endoscopy. Yet is often necessary to make clinical decisions based on symptoms alone. Ideally, a formal scoring tool such as the Mayo score or a similar disease activity score should be used to determine disease activity in patients with UC. The Mayo score includes 4 measures: stool frequency, rectal bleeding, endoscopic findings, and the physician’s global assessment. Although such a scoring system is desirable for accurate and consistent assessment of disease activity, it is often necessary to make management decisions in the absence of endoscopic information while considering the subjective aspects of disease presentation not captured by the full Mayo score. In such circumstances, the partial Mayo score (which omits the endoscopic subscore) can be informative.
- 0 – Normal number of stools for this patient
- 1 – 1–2 stools more than normal
- 2 – 3–4 stools more than normal
- 3 – 5 or more stools more than normal
- 0 – No blood seen
- 1 – Streaks of blood with stool less than half the time
- 2 – Obvious blood with stool most of the time or more
- 3 – Blood passed alone
- 0 – Normal or inactive disease
- 1 – Mild disease (erythema, decreased vascular pattern, mild friability)
- 2 – Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
- 3 – Severe disease (spontaneous bleeding, ulceration)
- 0 – Normal (there are no symptoms of colitis, the patient feels well, and the flexible proctosigmoidoscopy score is 0) (stool frequency = 0; rectal bleeding = 0; patient’s functional assessment = 0; flexible proctosigmoidoscopy findings = 0)
- 1 – Mild disease (mild symptoms and proctoscopic findings that were mildly abnormal) (the subscores should be mostly 1: stool frequency = 0 or 1; rectal bleeding = 0 or 1; patient’s functional assessment = 0 or 1; flexible proctosigmoidoscopy findings = 0 or 1)
- 2 – Moderate disease (more serious abnormalities and proctosigmoidoscopic and symptom scores of 1 or 2) (the subscores should be mostly 2: stool frequency = 1 or 2; rectal bleeding = 1 or 2; patient’s functional assessment = 1 or 2; flexible proctosigmoidoscopy findings = 1 or 2)
- 3 – Severe disease (the proctosigmoidoscopic and symptom scores are 2 to 3 and the patient probably requires corticosteroid therapy and possibly hospitalization) (the subscores should be mostly 3: stool frequency = 2 or 3; rectal bleeding = 2 or 3; patient’s functional assessment = 2 or 3; flexible proctosigmoidoscopy findings = 2 or 3)
- 0 – Generally well
- 1 – Fair
- 2 – Poor
- 3 – Terrible
Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes
- A family history of cancer and premalignant GI conditions that provides sufficient information to develop a preliminary determination of the risk of a familial predisposition to cancer should be obtained for all patients being evaluated in outpatient gastroenterology and endoscopy practices.
- Essential elements of a family history include presence and type of cancer diagnoses in first- and second-degree relatives, and presence and (ideally) type of polyps in first-degree relatives; age and lineage should be noted for each diagnosis.
- All newly diagnosed colorectal cancers (CRCs) should be evaluated for mismatch repair deficiency.
- Analysis may be done by immunohistochemical testing for the MLH1/MSH2/MSH6/PMS2 proteins and/or testing for microsatellite instability. Tumors that demonstrate loss of MLH1 should undergo BRAF testing or analysis for MLH1 promoter hypermethylation.
- Individuals who have a personal history of a tumor showing evidence of mismatch repair deficiency (and no demonstrated BRAF mutation or hypermethylation of MLH1), a known family mutation associated with LS, or a risk of ≥5% chance of LS based on risk prediction models should undergo genetic evaluation for LS.
- Genetic testing of patients with suspected LS should include germline mutation genetic testing for the MLH1, MSH2, MSH6, PMS2, and/or EPCAM genes or the altered gene(s) indicated by immunohistochemical (IHC) testing.
- Individuals who have a personal history of >10 cumulative colorectal adenomas, a family history of one of the adenomatous polyposis syndromes, or a history of adenomas and FAP-type extracolonic manifestations (duodenal/ampullary adenomas, desmoid tumors (abdominal>peripheral), papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium ((CHRPE), epidermal cysts, osteomas) should undergo assessment for the adenomatous polyposis syndromes.
- Genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analysis.
- Individuals with perioral or buccal pigmentation and/or two or more histologically characteristic gastrointestinal hamartomatous polyp(s) or a family history of PJS should be evaluated for PJS.
- Genetic evaluation of a patient with possible PJS should include testing for STK11 mutations.
- Individuals with five or more juvenile polyps in the colorectum or any juvenile polyps in other parts of the GI tract should undergo evaluation for JPS.
- Genetic evaluation of a patient with possible JPS should include testing for SMAD4 and BMPR1A mutations.
- Individuals with multiple gastrointestinal hamartomas or ganglioneuromas should be evaluated for Cowden syndrome and related conditions.
- Genetic evaluation of a patient with possible Cowden syndrome should include testing for PTEN mutations.
- Individuals who meet at least one of the following criteria have the clinical diagnosis of serrated polyposis syndrome (SPS):
- at least 5 serrated polyps proximal to the sigmoid colon with ≥2 of these being >10 mm;
- any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative (FDR) with serrated polyposis; and
- >20 serrated polyps of any size, distributed throughout the large intestine.
- A clear genetic etiology has not yet been defined for SPS, and therefore genetic testing is currently not routinely recommended for SPS patients; testing for MUTYH mutations may be considered for SPS patients with concurrent adenomas and/or a family history of adenomas.
- Individuals should be considered to be at risk for familial pancreatic adenocarcinoma if they
- have a known genetic syndrome associated with pancreatic cancer, including hereditary breast-ovarian cancer syndrome, familial atypical multiple melanoma and mole syndrome (FAMMM), PJS, LS, or other gene mutations associated with an increased risk of pancreatic adenocarcinoma; or
- have two relatives with pancreatic adenocarcinoma, where one is a FDR;
- have three or more relatives with pancreatic cancer; or
- have a history of hereditary pancreatitis.
- Genetic testing of patients with suspected familial pancreatic cancer should include analysis of BRCA1/2, CDKN2A, PALB2, and ATM. Evaluation for PJS, LS, and hereditary pancreatitis-associated genes should be considered if other component personal and/or family history criteria are met for the syndrome.
- Individuals with
- ≥2 cases of diffuse gastric cancer, with at least one diagnosed at <50 years;
- ≥3 cases of documented diffuse cancer in first- or second degree relatives independent of age of onset;
- diffuse gastric cancer diagnosed at <40 years;
- a personal or family history of diffuse gastric cancer and lobular breast cancer with one diagnosed at <50 years should be evaluated for HDGC.
- Genetic testing of individuals who fulfill HDGC clinical criteria should include analysis of CDH1 mutations.
- In individuals at risk for or affected with LS, screening for colorectal cancer by colonoscopy should be performed at least every 2 years, beginning between ages 20 and 25 years. Annual colonoscopy should be considered in confirmed mutation carriers.
- Colectomy with ileorectal anastomosis (IRA) is the preferred treatment of patients affected with LS with colon cancer or colonic neoplasia not controllable by endoscopy. Segmental colectomy is an option in patients unsuitable for total colectomy if regular postoperative surveillance is conducted.
- Hysterectomy and bilateral salpingo-oophorectomy should be offered to women who are known LS mutation carriers and who have finished child bearing, optimally at age 40–45 years.
- Screening for endometrial cancer and ovarian cancer should be offered to women at risk for or affected with LS by endometrial biopsy and transvaginal ultrasound annually, starting at age 30 to 35 years before undergoing surgery or if surgery is deferred.
- Screening for gastric and duodenal cancer can be considered in individuals at risk for or affected with LS by baseline esophagogastroduodenoscopy (EGD) with gastric biopsy at age 30–35 years, and treatment of H.pylori infection when found. Data for ongoing regular surveillance are limited, but ongoing surveillance every 3–5 years may be considered if there is a family history of gastric or duodenal cancer.
- Screening beyond population-based recommendations for cancers of the urinary tract, pancreas, prostate, and breast is not recommended unless there is a family history of the specific cancers.
- Although data suggest that daily aspirin may decrease the risk of colorectal and extracolonic cancer in LS, currently the evidence is not sufficiently robust or mature to make a recommendation for its standard use.
- In individuals at risk for or affected with the classic AP syndromes, screening for colorectal cancer by annual colonoscopy or flexible sigmoidoscopy should be performed, beginning at puberty. In families with attenuated familial adenomatous polyposis (AFAP) or MAP, surveillance should be by colonoscopy.
- Absolute indications for immediate colectomy in FAP, AFAP, and MAP include: documented or suspected cancer or significant symptoms. Relative indications for surgery include the presence of multiple adenomas >6 mm, a significant increase in adenoma number, and inability to adequately survey the colon because of multiple diminutive polyps.
- Screening for gastric and proximal small bowel tumors should be done using upper endoscopy including duodenoscopy starting at age 25–30 years. Surveillance should be repeated every 0.5–4 years depending on Spigelman stage of duodenal polyposis: 0=4 years; I=2–3 years, II=1–3 years, III=6–12 months, and IV=surgical evaluation. Examination of the stomach should include random sampling of fundic gland polyps. Low-grade dysplasia is common in fundic gland polyps, and surgery should be reserved for high-grade dysplasia or cancer.
- Annual thyroid screening by ultrasound should be recommended to individuals affected with FAP, MAP, and attenuated polyposis.
- Biannual screening should be offered to affected infants until age 7 years with α-fetoprotein and ultrasounds.
- Postsurgical surveillance should include yearly endoscopy of rectum or ileal pouch, and examination of an ileostomy every 2 years.
- Surveillance in affected or at-risk PJS patients should include monitoring for colon, stomach, small bowel, pancreas, breast, ovary, uterus, cervix, and testes cancers. Risk for lung cancer is increased, but no specific screening has been recommended. It would seem wise to consider annual chest radiograph or chest computed tomography (CT) in smokers.
- Surveillance of the gastrointestinal (GI) tract in affected or at-risk JPS patients should include screening for colon, stomach, and small bowel cancers.
- Colectomy and ileorectal anastomosis or proctocolectomy and ileal pouch-anal anastomosis is indicated for polyp-related symptoms, or when the polyps cannot be managed endoscopically.
- Cardiovascular examination for and evaluation for hereditary hemorrhagic telangiectasia should be considered for SMAD4 mutation carriers.
- Surveillance in affected or at-risk Cowden syndrome patients should include screening for colon, stomach, small bowel, thyroid, breast, uterine, kidney, and skin (melanoma) cancers.
- Patients with serrated polyposis should undergo colonoscopies every 1–3 years with attempted removal of all polyps >5 mm diameter.
- Indications for surgery for serrated polyposis syndrome (SPS) include an inability to control the growth of serrated polyps, or the development of cancer. Colectomy and ileorectal anastomosis is a reasonable option given the risks of metachronous neoplasia.
- There is no evidence to support extracolonic cancer surveillance for SPS at this time. Screening recommendations for family members are currently unclear pending further data and should be individualized based on results of baseline evaluations in family members.
- Surveillance of individuals with a genetic predisposition for pancreatic adenocarcinoma should ideally be performed in experienced centers utilizing a multidisciplinary approach and under research conditions. These individuals should be known mutation carriers from hereditary syndromes associated with increased risk of pancreatic cancer (Peutz-Jeghers, hereditary pancreatitis, familial atypical multiple melanoma and mole syndrome (FAMMM)) or members of familial pancreatic cancer kindreds with a pancreatic cancer affected first-degree relative. Because of a lower relative risk for pancreatic adenocarcinoma development in BRCA1, BRCA2, PALB2, ATM, and LS families, surveillance should be limited to mutation carriers with a first or second-degree relative affected with pancreatic cancer.
- Surveillance for pancreatic cancer should be with endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) of the pancreas annually starting at age 50 years, or 10 years younger than the earliest age of pancreatic cancer in the family. Patients with PJS should start surveillance at age 35 years.
- Because of the increased risk for pancreatic cancer development when compared with a pancreatic cyst in the sporadic setting, cystic lesion(s) of the pancreas detected during surveillance of a hereditary pancreatic cancer-prone family member requires evaluation by centers experienced in the care of these high-risk individuals. Determining when surgery is required for pancreatic lesions is difficult and is best individualized after multidisciplinary assessment.
- Management for patients with hereditary diffuse gastric cancer should include:
- prophylactic gastrectomy after age 20 years (>80% risk by age 80);
- breast cancer surveillance in women beginning at age 35 years with annual mammography and breast MRI and clinical breast examination every 6 months; and
- colonoscopy beginning at age 40 years for families that include colon cancer.
- At least three relatives with colorectal cancer (CRC); all of the following criteria should be present:
- One should be a first-degree relative of the other two;
- At least two successive generations must be affected;
- At least one of the relatives with CRC must have received the diagnosis before the age of 50 years;
- Familial adenomatous polyposis should be excluded;
- Tumors should be verified by pathologic examination.
- At least three relatives must have a cancer associated with Lynch syndrome (colorectal, cancer of the endometrium, small bowel, ureter, or renal-pelvis); all of the following criteria should be present:
- One must be a first-degree relative of the other two;
- At least two successive generations must be affected;
- At least one relative with cancer associated with Lynch syndrome (LS) should be diagnosed before age 50;
- Familial adenomatous polyposis should be excluded in the CRC case(s) (if any);
- Tumors should be verified whenever possible.
- Tumors from individuals should be tested for microsatellite instability (MSI) in the following situations:
- CRC diagnosed in a patient who is younger than 50 years of age
- Presence of synchronous, or metachronous, colorectal or other LS-related tumors, regardless of age
- CRC with MSI-high histology diagnosed in a patient who is younger than 60 years of age
- CRC diagnosed in a patient with one or more first-degree relatives with an LS-related cancer, with one of the cancers being diagnosed under age 50 years
- CRC diagnosed in a patient with two or more first- or second-degree relatives with LS-related cancer regardless of age
- Do you have a first-degree relative (mother, father, brother, sister, or child) with any of the following conditions diagnosed before age 50?
- Colon or rectal cancer
- Cancer of the uterus, ovary, stomach, small intestine, urinary tract (kidney, ureter, bladder), bile ducts, pancreas, or brain
- Have you had any of the following conditions diagnosed before age 50 years?
- Colon or rectal cancer
- Colon or rectal polyps
- Do you have three or more relatives with a history of colon or rectal cancer? (This includes parents, brothers, sisters, children, grandparents, aunts, uncles, and cousins)
- Lynch syndrome-related cancers include colorectal, endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma), small intestinal cancers, as well as sebaceous gland adenomas and keratoacanthomas.
- Presence of tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucionous/signet-ring differentiation, or medullary growth pattern.
- Information on the specific genetic mutation(s) or genomic variant(s) being tested, including whether or not the range of risk associated with the variant will affect medical care.
- Implications of positive and negative results.
- Possibility that the test will not be informative.
- Options for risk estimation without genetic or genomic testing.
- Risk of passing a genetic variant to children.
- Technical accuracy of the test, including, where required by law, licensure of the testing laboratory
- Fees involved in testing and counseling and, for direct to consumer testing, whether the counselor is employed by the testing company.
- Psychological implications of test results (benefits and risks).
- Risks and protections against genetic discrimination by employers or insurers.
- Confidentiality issues, including, for direct-to-consumer testing companies, polices related to privacy and data security.
- Possible use of DNA testing samples in future research.
- Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing.
- Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information.
- Plans for follow-up after testing.
Spigelman Duodenal adenomatosis staging system
Polyps 1 Point 2 Points 3 Points
Number <4 5–20 >20
Size 0-4mm 5-10mm >10
Histology Tubular Tubulovillous Villous
Dysplasia Mild Moderate Severe
Recommended duodenal surveillance frequency
Spigelman stage Total points Frequency of surveillance
0 0 Every 4 years
I ≤4 Every 2–3 years
II 5-6 Every 1–3 years
III 7-8 Every 6–12 months
IV 9-12 Expert surveillance every 3- 6 months
Surgical evaluation, complete mucosectomy or duodenectomy or Whipple procedure if
duodenal papilla is involved
Management of Colon Ischemia
The American College of Gastroenterology published an excellent guideline on the management of Colon Ischemia in December 2014. This important topic was summarized by Utah Gastroenterology. For detailed information, please review the excellent guideline paper.
Abbreviations:
- AMI – acute mesenteric ischemia
- IRCI – isolated right colon ischemia
- SMA – superior mesenteric artery
- IMA – inferior mesenteric artery
Colonic Ischemia Recommendations and Best Practice Summary Statements
Clinical Presentation
- The diagnosis of CI is usually established in the presence of symptoms including sudden cramping, mild, abdominal pain; an urgent desire to defecate; and passage within 24 h of bright red or maroon blood or bloody diarrhea.
- A diagnosis of non-isolated right colon ischemia (non-IRCI) should be considered when patients present with hematochezia.
Imaging of CI
- CT with intravenous and oral contrast should be the first imaging modality of choice for patients with suspected CI to assess the distribution and phase of colitis.
- The diagnosis of CI can be suggested based on CT findings (e.g., bowel wall thickening, edema, thumbprinting).
Multiphasic CTA should be performed on any patient with suspected IRCI or in any patient in whom the possibility of acute mesenteric ischemia (AMI) cannot be excluded. - CT or MRI findings of colonic pneumatosis and porto-mesenteric venous gas can be used to predict the presence of transmural colonic infarction.
- In a patient in whom the presentation of CI may be a heralding sign of acute mesenteric ischemia (AMI) (e.g., isolated right colon ischemia (IRCI), severe pain without bleeding, atrial fibrillation), and the multiphasic CT is negative for vascular occlusive disease, traditional splanchnic angiography should be considered for further assessment.
Colonoscopy in the Diagnosis of CI
- Early colonoscopy (within 48 h of presentation) should be performed in suspected CI to confirm the diagnosis.
- When performing colonoscopy on a patient with suspected CI, the colon should be insufflated minimally.
- In patients with severe CI, CT should be used to evaluate the distribution of disease. Limited colonoscopy is appropriate to confirm the nature of the CT abnormality. Colonoscopy should be halted at the distal most extent of the disease.
- Biopsies of the colonic mucosa should be obtained except in cases of gangrene.
- Colonoscopy should not be performed in patients who have signs of acute peritonitis or evidence of irreversible ischemic damage (i.e., gangrene and pneumatosis).
Severity and Treatment of CI
- Most cases of CI resolve spontaneously and do not require specific therapy.
- Surgical intervention should be considered in the presence of CI accompanied by hypotension, tachycardia, and abdominal pain without rectal bleeding; for IRCI and pan-colonic CI; and in the presence of gangrene.
- Antimicrobial therapy should be considered for patients with moderate or severe disease.
Risk Factors
- Comorbid cardiovascular disease and diabetes mellitus should increase consideration of CI in patients with typical clinical features.
- A history of IBS and constipation should be sought in patients suspected to have CI.
- Selective cardiology consultation is justified in patients with CI, particularly if a cardiac source of embolism is suspected.
- Chronic kidney disease is associated with increased mortality from CI.
- Evaluation for thrombophilia should be considered in young patients with CI and all patients with recurrent CI.
- Surgical procedures in which the inferior mesenteric artery (IMA) has been sacrificed, such as abdominal aortic aneurysm repair and other abdominal operations, should increase consideration of CI in patients with typical clinical features.
- In patients suspected of having CI, a history of medication and drug use is important, especially constipation-inducing medications, immunomodulators, and illicit drugs.
Clinical Presentation
- IRCI is associated with higher mortality rates compared with other patterns of CI.
Laboratory Tests in CI
- Laboratory testing should be considered to help predict CI severity.
- Decreased hemoglobin levels, low serum albumin, and the presence of metabolic acidosis can be used to predict severity of CI.
Severity and Treatment of CI
- When considering mortality risk for patients undergoing surgical intervention for acute CI, the Ischemic Colitis Mortality Risk (ICMR) factors should be utilized.
Detailed Data Summary
1.Risk factors
- Comorbid cardiovascular disease and diabetes mellitus should increase consideration of CI in patients with typical clinical features.
- A history of irritable bowel syndrome (IBS) and constipation should be sought in patients suspected to have CI.
- Selective cardiology consultation is justified in patients with CI, particularly if a cardiac source of embolism is suspected.
- Chronic kidney disease and chronic obstructive pulmonary disease are associated with increased mortality from CI.
- Evaluation for thrombophilia should be considered in young patients with CI and in all patients with recurrent CI.
- Surgical procedures in which the inferior mesenteric artery (IMA) has been sacrificed, such as abdominal aortic aneurysm repair and other abdominal operations, should increase consideration of CI in patients with typical clinical features.
- In patients suspected of having CI, a history of medication and drug use should be sought, especially constipation- inducing medications, immunomodulators, and illicit drugs.
2. Medical conditions and surgical history independently associated with colon ischemia in multivariate analyses of case–control studies
- Atherosclerosis
- Atrial fibrillation
- Chronic obstructive pulmonary disease
- Congestive heart failure
- Diarrhea
- Irritable bowel syndrome
- Diabetes
- Dyslipidemia
- Rheumatoid arthritis
- Systemic rheumatologic disorders
3a. Drugs proposed to predispose to CI and postulated pathogenesis (moderate evidence)
- Constipation-inducing drugs (Predicted CI in patients with abdominal pain)
- All drugs: C-CS; increased risk 0.68 (0.62–1.27)
- Opioids: C-CS; increased risk 1.96 (1.43–2.67)
- Nonopioids: C-CS; increased risk 1.75 (1.25–2.44)
- Reduced blood flow, increased intraluminal pressure
- All drugs: C-CS; increased risk 0.68 (0.62–1.27)
- Immunomodulator drugs
- Antitumor necrosis factor-α inhibitors for rheumatoid arthritis
- Type 1 interferon-α for hepatitis C
- Type 1 interferon-β for multiple sclerosis)
- Cytokines affecting thrombogenesis
- Illicit drugs
- Amphetamines
- Cocaine
- Vasoconstriction, hypercoagulation, direct endothelial injury
- Multiple Classes
- Antibiotics
- Appetite suppressants
- Bitter orange
- Hydroxycut
- Ma huang
- Phentermine
- Xenadrine (bitter orange, ma huang, caffeine, salicin)
- Vasoconstriction
- Chemotherapeutic drugs
- R-CHOP
- Taxanes
- Vinorelbine/cisplatin
- Direct epithelial toxicity, inhibited repair of vascular injury
- Decongestants
- Pseudoephedrine
- Phenylephrine
- Vasoconstriction
- Diuretics
- Extracellular volume deficit, lower peripheral vascular resistance, vasoconstriction
- Ergot alkaloids (often combined with caffeine)
- Vasoconstriction
- Hormonal therapies
- Predominance of women among young patients
- Female hormones
- Oral contraceptives
- Estrogen replacement
- Hypercoagulability, endothelial injury
- Laxatives
- Osmotic agents
- Bisacodyl
- Bisacodyl/polyethylene glycol
- Lubiprostone
- Increased motility or rapid intravascular volume deficit, reduced perfusion
- Psychotropic drugs (hypotension, constipation)
- Serotoninergic drugs
- 5-Hydroxytryptamine1 receptor agonists
- 5-hydroxytryptamine3 receptor antagonist
- 5-hydroxytryptamine4 partial agonist
- For 5-hydroxytryptamine1 receptor agonists vasoconstriction; for other agents various factors
- Mulitple Classes
- Digitalis
- Kayexalate
- NO-Xplode
- NSAIDs
- Statins
- Vasopressors
- Vasoconstriction
4. Clinical Presentation
- The diagnosis of CI is usually established because of symptoms including sudden cramping, mild, abdominal pain; an urgent desire to defecate; and passage within 24 h of bright red or maroon blood per rectum or bloody diarrhea.
- A diagnosis of non-IRCI should be considered when patients present with hematochezia.
- CI isolated to the right colon (IRCI) is associated with higher mortality rates compared with other patterns of CI.
5. Laboratory Testing
- Laboratory testing should be considered to help predict CI severity.
- Decreased hemoglobin levels, low serum albumin, and the presence of metabolic acidosis can be used to predict severity of CI.
- Recommended initial serology and stool studies for suspected colon ischemia (CI):
- Blood tests
- Albumin
- Amylase
- Complete blood count
- Comprehensive electrolyte panel
- Creatine kinase (CK)
- Lactate
- Lactate dehydrogenase (LDH)
- Stool tests
- Clostridium difficile toxin assay
- Culture
- Ova and parasite
- Blood tests
6. Imaging of CI
- CT with intravenous and oral contrast should be ordered as the imaging modality of choice for patients with suspected CI, to assess the distribution and phase of colitis.
- The diagnosis of CI can be suggested based on CT findings (e.g., bowel wall thickening, edema, and thumbprinting)
- Multiphasic CT angiography (CTA) should be performed on any patient with suspected IRCI or in any patient in whom the possibility of AMI cannot be excluded.
- CT or magnetic resonance imaging (MRI) findings of colonic pneumatosis and portomesenteric venous gas can be used to predict the presence of transmural colonic infarction.
- In a patient in whom the presentation of CI may be a heralding sign of acute mesenteric ischemia (AMI; e.g., IRCI, severe pain without bleeding, and atrial fibrillation), and the multiphasic CT is negative for vascular occlusive disease, traditional splanchnic angiography should be considered for further assessment.
7. Classification of disease severity and management
- Mild
- Typical symptoms of CI with a segmental colitis not isolated to the right colon and with none of the commonly associated risk factors for poorer outcome that are seen in moderate disease.
- Observation
- Supportive care
- Typical symptoms of CI with a segmental colitis not isolated to the right colon and with none of the commonly associated risk factors for poorer outcome that are seen in moderate disease.
- Moderate
- Any patient with CI and up to three of the following factors:
- Male gender
- Hypotension (systolic blood pressure <90mmHg)
- Tachycardia (heart rate >100beats/min)
- Abdominal pain without rectal bleeding
- BUN >20mg/dl
- Hgb <12g/dl
- LDH >350U/l
- Serum sodium <136mEq/l (mmol/l)
- WBC >15 cells/cmm (×109/l)
- Colonic mucosal ulceration identified colonoscopically
- Correction of cardiovascular abnormalities (e.g., volume replacement)
- Broad-spectrum antibiotic therapy
- Surgical consultation
- Any patient with CI and up to three of the following factors:
- Severe
- Any patient with CI and more than three of the criteria for moderate disease or any of the following:
- Correction of cardiovascular abnormalities (e.g., volume replacement)
- Broad-spectrum antibiotic therapy
- Peritoneal signs on physical examination
- Pneumatosis or portal venous gas on radiologic imaging
- Gangrene on colonoscopic examination
- Pancolonic distribution or IRCI on imaging or colonoscopy
- Emergent surgical consultation (treatment is likely to be surgical)
- Transfer to intensive care unit
- Correction of cardiovascular abnormalities (e.g., volume replacement)
- Broad-spectrum antibiotic therapy
- Any patient with CI and more than three of the criteria for moderate disease or any of the following:
8. Predictors of disease severity (factors from multiple studies that are significantly associated with the requirement for surgery and/or mortality)
- Epidemiologic factors
- Antibiotic treatment
- Chronic obstructive pulmonary disease
- Chronic kidney disease
- Hepatitis C positivity
- History of cancer
- Male gender
- Warfarin use
- Presentation of disease
- Abdominal pain without rectal bleeding
- Nonbloody diarrhea
- Peritoneal signs
- Symptom onset after admission
- Vital signs
- Pulse >90-100beats/min
- Systolic blood pressure <90mmHg
- Serology
- Hemoglobin <12mg/dl
- Na <136mEq/l (mmol/l)
- LDH >450U/l
- BUN >28.0 mg/dl
- Colonoscopic finding
- Ulceration
- Distribution of disease
- Bilateral or right-side disease distribution
- Isolated right colon involvement
9. Colonoscopy in the diagnosis of CI
- Early colonoscopy (within 48 h of presentation) should be performed in suspected CI cases to confirm the diagnosis.
- When performing colonoscopy on a patient with suspected CI, the colon should be insufflated minimally.
- In patients with severe CI, CT should be used to evaluate the distribution of disease. Limited colonoscopy is appropriate to confirm the nature of the CT abnormality. The endoscopic procedure should be stopped at the distal-most extent of the disease.
- Biopsies of the colonic mucosa should be obtained except in cases of gangrene.
- Colonoscopy should not be performed in patients who have signs of acute peritonitis or evidence of irreversible ischemic damage.
10. Severity and treatment CI
- Most cases of CI resolve spontaneously and do not require specific therapy.
- Surgical intervention should be considered in the presence of CI accompanied by hypotension, tachycardia, and abdominal pain without rectal bleeding; for IRCI and pancolonic CI; and in the presence of gangrene.
- Antimicrobial therapy should be considered for patients with moderate or severe disease.
- When considering the mortality risk for patients undergoing surgical intervention for acute CI, Ischemic Colitis Mortality Risk (ICMR) factors should be utilized.
11. Indications for surgery in colonic ischemia
- Acute indications
- Peritoneal signs
- Massive bleeding
- Universal fulminant colitis with or without toxic megacolon
- Portal venous gas and/or pneumatosis intestinalis on imaging
- Deteriorating clinical condition
- Subacute indications
- Failure of an acute segmental ischemic colitis to respond to treatment within 2–3 weeks with continued symptoms or a protein-losing colopathy
- Apparent healing but with recurrent bouts of sepsis
- Chronic indications
- Symptomatic colon stricture
- Symptomatic segmental ischemic colitis
12. Risk factors for perioperative mortality
- Low output heart failure (e.g., cardiac ejection fraction <20% on echocardiogram)
- Acute kidney injury
- Subtotal or total colectomy
- Lactate >2.5mmol/l
- Pre- and intraoperative catecholamine administration
- Risk factors = Mortality
- 0 = 10.5%
- 1 = 28.9%
- 2 = 37.1%
- 3 = 50.0%
- 4 = 76.7%
- 5 = 100.0%
- Risk factors = Mortality
ACG Clinical Guideline: Epidemiology, Risk Factors, Patterns of Presentation, Diagnosis, and Management of Colon Ischemia (CI)
Am J Gastroenterol 2015; 110:18–44
http://gi.org
http://gi.org/clinical-guidelines/
http://gi.org/clinical-guidelines/clinical-guidelines-sortable-list/
http://gi.org/guideline/epidemiology-risk-factors-patterns-of-presentation-diagnosis-and-management-of-colon-ischemia/
http://gi.org/wp-content/uploads/2015/01/ACG_Guideline_Colon-Ischemia_January_2015.pdf
Management of Benign Anorectal Disorders – ACG Clinical Guidelines
- Patient education – explain to patients that they unconsciously squeeze their anus when they are trying to defecate and this holds the stool in the rectum.
- Simulated defecation training – for patients who do not increase intraabdominal pressure during simulated defecation, the use of feedback on rectal balloon pressure teaches them to tighten their abdominal wall muscles and lower their diaphragm to push stool out.
- Training to relax pelvic floor muscles while simulating defecation — for patients who paradoxically contract their pelvic floor muscles during simulated defecation, provide visual feedback on anal canal pressure or averaged EMG activity from the anal canal to teach this skill.
- Practicing simulated defecation – patients practice defecation of a lubricated, inflated balloon while the therapist gently pulls on the catheter to assist them. Remind the patient to relax the pelvic floor muscles, increase abdominal pressure using abdominal wall muscles, and concentrate on the sensations produced by balloon passage.
- Anal sphincter weakness
- Traumatic: obstetric, surgical (e.g., fistulotomy, internal sphincterotomy)
- Nontraumatic: scleroderma, internal sphincter degeneration of unknown etiology
- Neuropathy: peripheral (e.g., pudendal) or generalized (e.g., diabetes mellitus)
- Disturbances of pelvic floor: rectal prolapse, descending perineum syndrome
- Inflammatory conditions: radiation proctitis, Crohn’s disease, ulcerative colitis
- Central nervous system disorders: dementia, stroke, brain tumors, multiple sclerosis, spinal cord lesions
- Diarrhea: irritable bowel syndrome, post-cholecystectomy diarrhea Other: fecal retention with overflow, behavioral disorders
Guidelines for Follow-up of Colorectal Cancer Patients
- Which evaluations (eg, colonoscopy, computed tomography [CT], carcinoembryonic antigen [CEA], liver function, complete blood count [CBC], chest x-ray, history, and physical examination) should be performed for surveillance for recurrence of cancer?
- What is a reasonable frequency of these evaluations for surveillance?
- Which symptoms and/or signs potentially signify a recurrence of CRC and warrant investigation?
- What are the common and/or significant long-term and late effects of CRC treatment?
- On what secondary prevention measures should CRC survivors be counseled?
- The target population for these guidelines included CRC survivors (adult patients who have completed primary treatment for stage II or III CRC and who are without evidence of disease). Whether these recommendations are extrapolated to stage I patients or a patient with metastatic CRC who underwent metastatectomy and is currently without evidence of disease, is left to the discretion of the health care provider.
- The target audience for these guidelines include clinicians (eg, medical oncologist, radiation oncologist, surgeon, advanced practice nurse, physician assistant, primary care provider [family physician, nurse practitioner, family practice nurse]) involved in the delivery of care for CRC patients, families of patients who have survived CRC, and health care organizations and system leaders responsible for offering, monitoring, or providing resources for CRC survivorship protocols.
- Surveillance should be guided by presumed risk of recurrence and functional status of patient where early detection would lead to aggressive treatment including surgery. It is especially important in the first 2 to 4 years, when the risk of recurrence is the greatest.
- A medical history, physical examination, and CEA testing should be performed every 3 to 6 months for 5 years. The frequency of visits and testing should be driven by the data showing that 80% of recurrences occur in the first 2 to 2.5 years from date of surgery and 95% occur by 5 years. Patients at a higher risk of recurrence should be considered for testing in the more frequent end of the range.
- Abdominal and chest imaging using a CT scan is recommended annually for 3 years. For high-risk patients, it is reasonable to consider imaging every 6 to 12 months for the first 3 years. Outside of a clinical trial, PET scans are not recommended for surveillance.
- For patients with rectal cancer, a pelvic CT is also recommended. Clinician judgment, considering risk status, should be used to determine the frequency of pelvic scans (eg, annually for 3 to 5 years). For those patients who have not received pelvic radiation, a rectosigmoidoscopy should be performed every 6 months for 2 to 5 years.
- A surveillance colonoscopy should be performed approximately 1 year after the initial surgery. The frequency of subsequent surveillance colonoscopies should be dictated by the findings of the previous one, but they generally should be performed every 5 years if the findings of the previous one are normal. If a complete colonoscopy was not performed before diagnosis, a colonoscopy should be done as soon as reasonable after completion of adjuvant therapy and not necessarily at the 1-year time point.
- Any new and persistent or worsening symptoms warrant the consideration of a recurrence.
- Despite the lack of high-quality evidence on secondary prevention in CRC survivors, it is reasonable to counsel patients on maintaining a healthy body weight, being physically active, and eating a healthy diet.
- A treatment plan from the specialist should be sent to the patient’s other providers, particularly the primary care physician, and it should have clear directions on appropriate follow-up.
- If a patient is not a surgical candidate or a candidate for systemic therapy because of severe comorbid conditions, surveillance tests should not be performed.
The ASCO Panel wants to highlight that the recommendations are primarily for patients with stage II or III cancer. There are insufficient data to provide guidance for follow-up for stage I patients or patients with resected metastatic disease with no evidence of disease. The ASCO Panel emphasizes that surveillance tests should only be performed in patients in whom the results will change treatment decisions. If a patient is not a surgical candidate or a candidate for systemic therapy because of severe co-morbid conditions, surveillance tests should not be performed.
Fecal Incontinence
Introduction:
Fecal incontinence is a difficult yet seldom talked about problem. The impaired ability to control gas or stool ranges from mild (difficulty with gas) to severe (loss of control of liquid and formed stools); symptoms can be continuous or recurrent. Nearly 18 million U.S. adults – about one in 12 – suffer from fecal incontinence. This number is likely underestimated as patients are reluctant to discuss this disabling problem. Incontinence causes emotional distress, loss of dignity, embarrassment, shame, frustration, anger, depression as well as social isolation. Perianal skin irritation may lead to pain, itching, and ulcers which may require medical or surgical treatments.
Causes of fecal incontinence include:
- diarrhea
- constipation
- muscle or nerve damage (due to constant straining, spinal cord injury, stroke)
- childbirth related trauma (episiotomy, forceps)
- anal operations
- traumatic injuries
- rectocele (a weakness of the recto-vaginal septum allows rectal tissue to bulge into the vagina. Rectoceles are uncommon in men as the prostate gland provides structural support)
- rectal prolapse
- inflammation (colitis)
- radiation
- tumors
- diseases such as diabetes, multiple sclerosis
- dementia (the prevalence of fecal incontinence is estimated at 47% for nursing home residents )
- aging (the prevalence of fecal incontinence is estimated at 15% in those 70 or older)
Other risk factors further include:
- poor general health
- physical disabilities
- chronic obstructive pulmonary disease
- irritable bowel syndrome
- urinary incontinence
- colectomy
- chronic diarrhea
- fecal impaction
- depression
Anorectal function and continence depend on factors such as stool volume, stool consistency, colonic transit, rectal distensibility, anal sphincter function, anorectal sensation and intact anorectal reflexes. Anatomical structures which help preserve continence include the rectum, the internal and external anal sphincter muscles, and the pubo-rectalis muscle. Defecation is initiated when stool enters the rectum, leading to rectal distention with reflex relaxation of the internal anal sphincter. The urge to defecate increases as more stool passes into the rectum. During defecation the anorectal angle is straightened and abdominal pressure is increased; pelvic floor descent, rectal contraction, and external anal sphincter relaxation then lead to emptying of stool.
Workup:
To better understand incontinence, a detailed history, physical exam and supplemental studies are required.
The clinical history should assess for onset of disease, duration, frequency, severity, precipitating events, and look for a history of difficult or traumatic vaginal delivery, anorectal surgery, pelvic irradiation, diabetes, and neurologic diseases.
A physical exam should include inspection of the perianal area which may reveal dermatitis (suggesting chronic incontinence), fistulizing disease, prolapsing hemorrhoids, or even rectal prolapse. Perianal sensation should be tested, with the absence of an anal wink reflex suggesting nerve damage. A digital rectal exam may provide information about the resting anal sphincte tone and may detect obvious anal pathology such as masses or fecal impaction . Inspection of the anus, rectum and large intestine via anoscopy, flexible sigmoidoscopy or colonoscopy may help to exclude mucosal inflammation, masses, or other pathology.
Anorectal manometry measures resting anal pressures, amplitude and duration of squeeze pressures, the rectoanal inhibitory reflex, threshold of conscious rectal sensation, rectal compliance, and anal rectal pressures during straining. Rectal sensation can be assessed by balloon inflation. Pudendal nerve terminal latency may assess potential nerve damage.
Endorectal ultrasound and magnetic resonance imaging are helpful to define structural abnormalities of the anal sphincters, the rectal wall, and the puborectalis muscle.
Defecography assesses anorectal anatomy at rest and during defecation; it assesses the anorectal angle, pelvic descent and may detect occult or overt rectal prolapse.
Intervention:
Three treatment approaches are commonly used for fecal incontinence:
- medical therapy such as dietary changes (i.e. avoidance of sphincter relaxing foods), constipating medications (treatment of diarrhea) and bulking agents (to enhance stool control)
- biofeedback and muscle strengthening exercises
- surgery, such a surgical sphincter muscle repair or implantation of an artificial anal sphincter
Medical therapy should be aimed at reducing stool frequency and improving stool consistency. Specific treatment for the underlying cause of diarrhea should be implemented, as formed stool is easier to control than liquid stool. While stool consistency can be improved with bulking agents (i.e. fiber supplements, bile binders), this may exacerbate incontinence in patients with decreased rectal compliance (i.e. in radiation proctitis or rectal stricture).
Stool frequency can be reduced with antidiarrheals such as loperamide (Imodium®) or diphenoxylate (Lomotil®); anticholinergic agents i.e. hyoscyamine (Levsin®, NuLev®, Anaspaz®, Levsinex®, Levbid®) may help with postprandial leakage if taken before meals.
Patients with fecal impaction should be disimpacted and treated with a bowel training regiment to prevent recurrent impaction.
Pelvic floor exercise and biofeedback may help retrain pelvic floor and abdominal wall musculature and may enhance the ability to sense rectal distention, thereby improving sensory as well strength components required for continence. Pelvic floor exercises involve squeezing and relaxing pelvic floor muscles 50-100 times a day. A health care provider can help with proper technique. Biofeedback therapy may help to perform these exercises properly and may improve anorectal sensation. Biofeedback uses special anal and rectal pressure sensors, as well as rectal balloons to produce graded sensations of rectal fullness. Measurements are displayed on a video screen and are used to modify or change abnormal function. Success depends on the cause of fecal incontinence, its severity, and the person’s ability to follow instructions; the role of biofeedback in the management of fecal incontinence is still debated, as the optimal protocol, equipment, and duration of treatment are undefined.
Surgical approaches to fecal incontinence include direct sphincter repair, plication of the posterior part of the sphincter, anal encirclement, implantation of an artificial sphincter, and muscle transfer procedures with or without electrical stimulation. Patients with a sphincter tear (obstetric trauma, fistula surgery) can be cured with a sphincteroplasty. It is the most common fecal incontinence surgery and reconnects the ends of a torn sphincter muscle.
A synthetic sphincter device or magnetic anal sphincter may be available in highly specialized centers. The Acticon (TM) neosphincter, consisting of an occlusive cuff (implanted around the anal canal), a pressure-regulating balloon (implanted in the prevesical space) and a control pump (implanted in the labium or scrotum) enables users to squeeze the control pump to permit defecation.
Sacral nerve electrical stimulation may restore continence in patients with structurally intact muscles. This approach appears to be effective in patients with neurologic disorders. The FDA approved the sacral nerve stimulator (InterStim®, Medtronics) for the treatment of chronic fecal incontinence in patients who have failed or are not candidates for more conservative treatments.
Injectable materials allow augmentation of the function of the internal anal sphincter. Injection of dextranomer-hyaluronic acid (Solesta®), used for the treatment of urinary incontinence, has also been approved for patients with fecal incontinence.
Anal plugs have been studied as a possible treatment for fecal incontinence. Fecal incontinence improved only in a minority of patients, anal plugs were poorly tolerated and their usefulness is thereby limited.
In extreme cases patients may need a colostomy to improve quality of life as a colostomy may be the only option for patients with intractable symptoms who are not candidates for any other therapy, or in whom other treatments have failed.
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Guidelines for the management of Lynch syndrome (HNPCC) are summarized and adapted from recommendations of US and European experts.
Introduction
Although a family history of colon cancer increases an individual’s risk of colon cancer by two-to-threefold, some families have a very significantly increased cancer risk due to proven genetic mutations. While most patients with a family history of colon cancer may be surveilled with a 5-yearly screening protocol (typically starting at age 40 or 10 years before the index relative’s disease), these special families require a much closer surveillance interval and consideration for multiple other cancers. Two major genetic conditions to be considered are Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS).
Lynch syndrome (LS), also called hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant disorder caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. It is the most common inherited colon cancer susceptibility syndrome, accounting for approximately 1–3% of all colorectal cancers (CRC). The name HNPCC can be misleading as this disorder predisposes to multiple cancers:
- colon cancer (risk ~25–70%)
- endometrial cancer (EC) (risk ~30–70%)
- stomach cancer
- ovarian cancer
- bladder cancer
- upper urologic tract cancers (renal pelvis, ureter)
- small bowel cancer
- biliary/pancreatic cancer
- skin cancer (sebaceous adenomas, carcinomas and keratoacanthomas)
- brain cancers
- possible prostate cancer
The frequency of extracolonic cancers in LS varied from 2-20%. LS is responsible for about 2 percent of all endometrial cancers. There is some debate whether even breast cancers may be part of the LS.
Clinical features/genetics
Early age of onset and multiplicity of cancers have been considered hallmarks of LS. 7-10% of LS patients have more than one cancer at diagnosis (i.e. synchronous CRC), metachronous CRC are also common (developing another CRC after an initial resection if a subtotal colectomy is not performed). The overall CRC rate appears moderately higher for men than women. LS is an autosomal dominant disorder caused by a defect in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2.
- MLH1 (MutL homolog 1), located on chromosome 3p21
- MSH2 (MutS homolog 2), located on chromosome 2p16
- MSH6 (MutS homolog 6), located on chromosome 2p16
- PMS1 and PMS2 (postmeiotic segregation 1 and 2), located on chromosomes 2q31 and 7p22, respectively
These gene defects lead to a loss of MMR function and result in an accumulation of microsatellite mutations. These microsatellite instabilities (MSI) refer to an expansion or contraction of short repetitive DNA sequences (microsatellites) due to loss of DNA mismatch repair. These mutations lead to alterations in cancer related genes, likely driving the process of carcinogenesis. The overall cancer risk (~80%) and the colorectal cancer risk (50-70%) are similar in MLH1 and MSH2 families, but the risks of endometrial and other extracolonic cancers appear to be substantially higher in MSH2 families. Families with MSH6 and possibly PMS2 mutations appear to have an attenuated cancer phenotype (later age of cancer diagnosis and lower penetrance) compared to MLH1 and MSH2 families. Homozygous or compound heterozygous carriers of MLH1, MSH2, MSH6, or PMS2 often develop hematologic and brain malignancies during childhood. Most had a family history of LS on both the maternal and paternal sides of their families.
The term Lynch syndrome should only be used in individuals and families known to have a detectable MMR gene mutation. Individuals without gene testing are no longer labeled as having LS even if Amsterdam criteria are met.
Amsterdam criteria have been used to identify patients and families at risk for LS.
- “3-2-1 rule”: 3 affected members, 2 generations, 1 under age 50 – (3 or more relatives with LS-associated cancers (colorectal, endometrial or small bowel cancers, transitional cell carcinoma of the ureter or renal pelvis), one being a first degree relative of the other two, involvement of at least two generations, one or more cancers diagnosed before the age of 50).
Bethesda guidelines identify individuals with LS-associated cancers who should be tested for microsatellite instability (and MMR gene testing in those with MSI-H tumors). LS is suggested in colon cancer patients if certain characeristics are present such as young age and strong familial clustering of colon cancer. LS cancers appear to evolve from adenomas, tend to be larger, flatter, more proximal, and have high-grade dysplasia and/or villous histology, with a more rapid progression of the adenoma-carcinoma sequence. Cancers are more proximal, poorly differentiated , and often mucinous. Histologic features such as tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucin/signet ring cell differentiation, and medullary growth pattern can be used to select patients who might have LS. These patients should have their colon cancers tested for microsatellite instability (if positive, proceed with germline MMR gene testing).
- Benefits of genetic testing in high risk families including a more accurate diagnosis and risk assessment as well as better implementation of surveillance protocols.
- Family members who do not need intensive surveillance can also be better identified; these members without high risk mutations carry a similar cancer risk as the general population and do not need heightened surveillance.
- Once high risk individuals are identified, germline testing is recommended in the affected individual. If possible, gene testing should be performed on the family member most likely to have the syndrome (i.e. the youngest family member with colorectal cancer).
- Practitioners should ensure that patients received appropriate counseling. Informed consent should include a general description of the test, the disorder to be tested for, the meaning of positive and negative results, and the level of certainty that a positive or negative test is a predictor of disease. Counseling about benefits of early cancer detection and prevention or treatment modalities should be offered.
Muir-Torre and Turcot Syndrome
Two variants of Lynch syndrome had been considered distinct entities: Muir-Torre (Lynch syndrome with associated sebaceous tumors, cutaneous keratoacanthomas, and visceral carcinomas) and Turcot syndrome (Lynch syndrome with associated brain tumors, typically gliomas). These families with extracolonic cancers (brain, sebaceous tumors, skin acanthomas, and visceral carcinomas) are considered part of the spectrum of LS.
General cancer surveillance in LS
Analysis of all causes of cancer deaths in LS revealed that 61% of cancer deaths were associated with non-CRC non-EC cancers. Testing of all patients (<70 years) with CRC or EC for loss of MMR function by means of MSI or immunohistochemistry has been recommended, as testing remains one of the first steps to identify individuals who are at increased risk for LS.
CRC surveillance
- Colorectal surveillance by regular colonoscopy is the only surveillance protocol proven to be effective. Due to advanced CRC in LS detected between 2 and 3 years after surveillance colonoscopy, an interval of 1-2 years is recommended. Colonoscopy is recommended to begin at age 20-25, or 10 years prior to the earliest age of colon cancer in the family (whichever comes first). In families with MSH6 mutations, surveillance starts at age 30, since onset of colon cancer is seen later in these families. Since the risk of developing a second CRC after partial colectomy for primary CRC is estimated at approximately 16% after 10 years (despite following close surveillance), more extensive surgery(total or subtotal colectomy) for the primary CRC might be considered.
EC surveillance
- Although the value of surveillance for EC is unclear, routine annual surveillance (gynecological exam, transvaginal ultrasound, biopsy starting at age of 35–40, or 5-10 years earlier than the earliest age of diagnosis of these cancers) may lead to early detection of premalignant disease or cancers and should be offered to mutation carriers. A CA 125 may be of benefit. Hysterectomy and bilateral oophorectomy prevents the development of endometrial and ovarian cancer and could be discussed with patients after the age of 35-40, who have completed their family planning. If CRC surgery is scheduled, prophylactic hysterectomy and bilateral oophorectomy at the same time should be considered.
Gastric cancer surveillance
- The cumulative risk of developing gastric cancer in LS by the age of 70 is approximately 5%. Most gastric cancers in LS are of the intestinal type, so regular EGDs may be of benefit. Given the relatively low risk of gastric cancer and the lack of established surveillance benefit, European guidelines advise against surveillance for gastric cancer.
Small bowel cancer surveillance
- The risk of developing small bowel cancer in carriers of an MLH1 or MSH2 mutation is approximately 5%. Currently European guidelines advise against surveillance for small bowel cancer, but inspection of the distal duodenum during upper endoscopy and ileum during colonoscopy (if performed) is recommended. Evaluation of the small bowel in patients with unexplained abdominal complaints or iron deficiency anemia has been suggested.
Urinary tract cancer surveillance
- Increased risks of bladder cancer as well as urothelial cancers of the upper urinary tract in LS have been demonstrated. Given lack of evidence of surveillance benefits for urinary tract cancer, European guidelines advise against surveillance for urinary tract cancer in LS.
Prostate cancer surveillance
- European guidelines do not recommend increased surveillance for prostate cancer in LS families outside of appropriate research studies.
Pancreatic cancer surveillance
- Recent studies have revealed an increased risk of developing pancreatic cancer in LS. Still, the benefit of surveillance for pancreatic cancer in high-risk groups is unknown and European guidelines advise against surveillance for this cancer in LS families.
Breast cancer surveillance
- Whether breast cancer is part of the tumor spectrum of LS is controversial. The cumulative risk by the age of 70 years may be 14% in all female carriers, with the highest risk in MLH1 carriers (MLH1: 17%; MSH2: 14.4%; MSH6: 11%). At present, female carriers of an MMR gene mutation should be advised to participate in population screening programs for breast cancer (biannual mammography from the age of 45 or 50) as per European guidelines. Since most patients with Lynch syndrome who develop breast cancer do so after the age of 50 years, standard screening approaches for breast cancer are likely appropriate.
In summary
As a practical expert opinion approach to surveillance strategies in LS, the reviewers for UpToDate® suggest annual colonoscopy starting at age 20-25 (or 10 years prior to the earliest age of colon cancer in a given family), annual screening for EC with endometrial biopsy and ovarian cancer with CA 125 as well as transvaginal ultrasound beginning at age 30-35 (or 5 to 10 years earlier than the earliest age of first diagnosis of these cancers, whichever is earlier), discussion of prophylactic hysterectomy and salpingo-oophorectomy at the end of childbearing, annual urinalysis beginning at age 25-35, annual skin surveillance and periodic upper endoscopy.
Colonoscopy Surveillance
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy:
A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer
Often patients ask the important question when they should have a repeat colonoscopy done. The US Multi-Society Task Force (MSTF) guidelines attempt to address this important question and warrant a review on this education blog. When doing so one must recall that these guidelines do not apply to patients with a family history of colon cancer, or other genetic syndromes such as FAP or HNPCC.
In general a simple rule applies to surveillance colonoscopies:
- If no polyps are found at the initial exam, then a 10 year follow-up is appropriate.
- If small (<10 mm) rectal or sigmoid colonic hyperplastic polyps are found at the initial exam, then a 10 year follow-up is appropriate.
- If 1-2 small (<10 mm) tubular adenomas are found at the initial exam, then a 5-10 year follow-up is appropriate.
- If 3 or more tubular adenomas are noted at the initial exam, if a tubular adenoma is larger that 10mm, or if a villous component is noted on histology, then a 3 year follow-up is appropriate.
- If more than 10 adenomas are noted at the initial exam, then a less than 3 year follow-up may be advised.
- If an adenoma with high-grade dysplasia was noted at the initial exam and complete excision has been accomplished, then a 3 year follow-up is appropriate.
- Serrated lesions are followed according to these above discussed principles.
- Sessile serrated polyp(s) <10 mm with no dysplasia: 5 year follow-up is appropriate.
- Sessile serrated polyp(s) >10 mm or a sessile serrated polyp(s) with dysplasia or a traditional serrated adenoma: 3 year follow-up is appropriate.
- A serrated polyposis syndrome requires a more aggressive surveillance protocol with likely yearly colonoscopies (i.e. similar to aFAP – attenuated familial adenomatous polyposis)
Current guidelines factor in that important lesions may be missed at baseline colonoscopy. While the risk of having an advanced adenoma on the initial screening colonoscopy is estimated at 4-10%, several prospective studies have shown that the risk of having advanced adenomas within 5 years after a negative screening colonoscopy is low at 1.3–2.4%. This evidence supports the 10-year interval recommendation after a negative screening colonoscopy for average-risk individuals, as long as the baseline colonoscopy was complete, thorough and with a good bowel preparation. Evidence suggests that size (>10 mm), histology (tubular adenoma, sessile serrated polyp, villous histology, high-grade dysplasia) and location (proximal to the sigmoid colon) are risk factors that might be associated with higher risk of CRC.
Ongoing surveillance after the first follow-up colonoscopy
The appropriate ongoing follow-up interval after the initial screening colonoscopy and first follow-up surveillance colonoscopy is being better defined. Data suggest that the detection of an advanced adenoma is an important risk factor for finding further advanced adenomas at the next examination. Otherwise, if patients had no adenomas or only a low-risk lesion, the risk of advanced neoplasia at the next examination is low. Patients with only a low-risk lesion at baseline and no adenomas at the first follow-up surveillance colonoscopy appear to have a very low risk (2.8%- 4.9%) of having advanced adenomas at the second surveillance examination 3–5 years later.
It is therefore recommended that patients with a negative or low risk baseline study and a negative study at the first surveillance interval study can have their next surveillance examination at 10 years.
Patients with high risk lesions at any examination appear to remain at high risk and should have shorter follow-up intervals for surveillance.
Age specific guidelines: When should surveillance stop?
Given considerable evidence of increased procedural risk of colonoscopy (complications) at an advanced age, surveillance and screening should not be continued if the risk outweighs the benefit.
- The United States Preventive Services Task Force (USPSTF) does not recommend screening after age 85.
- Patients with high risk lesions may still benefit from surveillance, given the higher risk for developing advanced neoplasia.
- The USPSTF recommends against routine screening for patients aged 75–85 years but allows for individualization. The US Multi-Society Task Force (MSTF) recognizes that this age group (75–85) may benefit from surveillance, depending on life expectancy.
How about the question of a poor prep, guaiac positive stool or a new symptom – what to do?
- Given that a poor-quality bowel preparation may obscure visualization of the colon and allow for missed lesions, the MSTF recommends that the examination be repeated within 1 year.
- If a positive fecal occult test, positive guaiac test, or positive fecal immunochemical test is obtained before the scheduled surveillance colonoscopy, no change in interval appears needed, as long as patients have had an adequate baseline colonoscopy. The MSTF recommends against interval fecal testing within the first 5 years after a colonoscopy, as the likelihood of a false-positive test is high, resulting in unnecessary early colonoscopies.
- If a patient develops new symptoms during the surveillance interval (i.e. minor rectal bleeding, diarrhea, constipation), a colonoscopy should only be repeated if the colonoscopy would answer important clinical questions (i.e. IBD, ischemic colitis, microscopic colitis etc.). The likelihood of finding significant pathology (regarding colon cancer risk) after a prior adequate colonoscopy is low.
Utah Gastroenterology Blog 