Polyposis Syndromes
Familial Adenomatous Polyposis Syndrome
Diverticular Disease
Radiation Enteritis
Abdominal Trauma
Other IndicationsMedical and Surgical Management
SummaryT he formation of a fecal diversion is most frequently done for conditions such as colorectal cancer (CRC) or inflammatory bowel disease. However, several other disease states or patient conditions are associated with fecal ostomy formation. These conditions include intestinal polyposis syndromes, diverticular disease, radiation enteritis, abdominal trauma, and forms of intestinal obstruction (volvulus, intussusception, colonic inertia). Where the fecal diversion is located (colostomy vs. ileostomy) and the nature of its formation (temporary vs. permanent) are often related to the underlying pathology. CRC as an etiologic factor is discussed elsewhere; see Chapter 3.
Polyposis Syndromes
Several polyposis syndromes exist. The polyposis syndromes can usually be differentiated based on histologic and molecular characteristics of the polyps, involvement of different segments of the gastrointestinal (GI) tract, and alterations in other organs and tissues. Disease severity, cancer risks associated with the disorder, mode of inheritance, and underlying genetic aberration can also help distinguish the disorders (Lucci-Cordisco et al., 2013). However, some patients present with unexplained polyposis. A recent study of 38 patients in a polyposis registry demonstrated that only 17% (6 of 38) had their polyposis definitively identified. The challenge for optimal patient care is evident when geneticists, pathologists, and gastroenterologists cannot detect specific diagnostic criteria since care approaches differ for the various syndromes (Mongin et al., 2012). The focus of this discussion will be on more common conditions: familial adenomatous polyposis (FAP), Gardner’s syndrome, and the less common Peutz-Jeghers syndrome (PJS).
CLINICAL PEARL
Polyposis syndromes although somewhat rare, it is important for the patient and his or her family to be aware of the existing health risks associated with these disorders.
Familial Adenomatous Polyposis Syndrome
Familial (or familiar) Adenomatous Polyposis (FAP) Syndrome was the first polyposis syndrome recognized and is the best investigated. It is one of the CRCs that are known to be associated with familial genetic passage of mutated genes. These disorders include hereditary nonpolyposis colorectal cancer (HNPCC), FAP, PJS, juvenile polyposis syndrome (JPS), and MYH-associated polyposis (Centelles, 2012, p. 6).
Etiology
FAP is an autosomal dominant disorder caused by a mutation in the APC (adenomatous polyposis coli) gene located on chromosome 5q21-22 (Shah et al., 2013). APC is a tumor suppressor gene. On monoallelic mutation analysis (a form of genetic testing), more than 95% of FAP patients display an identifiable mutation (Centelles, 2012, p. 7). Accurate classification of FAP and other CRC syndromes is imperative given the associated risks, management strategies, and consequent risk to family relatives. The histologic analyses of colorectal polyps in FAP are predominantly adenomatous polyps (Jasperson, 2012, p. 328). FAP is estimated to occur in about 1 in 10,000 individuals usually occurring between 20 and 40 years. FAP accounts for approximately 1% of all CRC cases (Kastrinos & Syngal, 2011).
Clinical Presentation
The classic clinical presentation of FAP includes the occurrence of hundreds to thousands of adenomatous polyps in the colon and rectum. The sheer number of polyps present in FAP results in nearly a 100% lifetime risk of CRC in untreated persons. Generally, colorectal polyps begin to develop around age 16 years with CRC developing anywhere from 5 to 30 years later (mean age of 39 years) (Shah et al., 2013). Other cancer syndromes have substantial extracolonic manifestations, but when they occur in FAP, the most common scenario is upper GI tract polyps (Jasperson, 2012).
These intestinal adenomatous polyps are usually discovered during endoscopic evaluation for symptoms such as GI bleeding. Conversely, they may be identified during routine screening in people with a known family history. Clinical diagnosis of FAP requires at least 100 colorectal adenomatous polyps (Lucci-Cordisco et al., 2013).
Extraintestinal malignancies can be associated with FAP. They include central nervous system tumors (e.g., medulloblastomas), papillary thyroid cancer, and duodenal cancer. The risk of duodenal or periampullary carcinoma in patients with FAP is estimated to be 100 to 330 times greater than that in the general population, but the absolute risk is below 5% (Jasperson, 2012). The most common extracolonic finding in individuals with FAP is upper GI tract polyps (Jasperson, 2012). The extracolonic manifestations of FAP can be benign including duodenal adenomas, gastric fundic gland polyps, and desmoids (Lucci-Cordisco et al., 2013).
Although malignancy can occur in childhood and adolescence, malignant degeneration occurs typically by 40 to 50 years of age. The most common age of cancer diagnosis in classic FAP patients is 39 years. The most common cancer location is the rectum followed by the sigmoid and other colon segments (Popek & Tsikitis, 2011). Cancers in other body locations also increase risk. Periampullary cancer (occurring in the duodenum near the ampulla of Vater) and desmoid tumors represent the most common cause of death in FAP patients (Popek & Tsikitis, 2011). Though benign, desmoid tumors cause serious damage by local invasion and compression of adjacent body structures.
Medical Management
Genetic testing and counseling are the standard of care for individuals with classic FAP and for at-risk family members. Genetic evaluation begins with the affected person with the polyposis phenotype and full gene sequencing looking for the APC gene mutation.
For known gene mutation carriers, colorectal screening with flexible sigmoidoscopy or colonoscopy should begin at 10 to 12 years of age. Once polyps are identified, colon screening must be annual. A recent systematic review supports that registration and screening of FAP patients resulted in a reduction of the CRC incidence and mortality in this hereditary registry of patients (Barrow et al., 2013).
Because of extraintestinal manifestations, screening of the stomach and duodenum is also necessary. Upper endoscopy is recommended every 1 to 3 years (Kastrinos & Syngal, 2011). Since thyroid cancer is a possibility, health care providers should perform thyroid palpation and possibly thyroid ultrasonography annually.
Some literature has suggested a role for chemoprevention against polyps. For example, sulindac, a nonsteroidal anti-inflammatory drug, has been shown to cause regression of colorectal adenomas. However, the long-term benefits have been inconsistent; therefore, chemoprevention is not considered a reasonable alternative to surgery (Kastrinos & Syngal, 2011).
Research has also addressed the psychological issues of requisite surveillance for cancer degeneration in persons with FAP and other polyposis syndromes. A systematic review in 2012 (Gopie et al., 2012) analyzed 32 studies looking at psychological burden of hereditary cancer surveillance (breast, colon, colorectum, melanoma, etc.). For most hereditary cancer syndromes, surveillance was associated with good psychological outcomes. However, distress levels increased in those persons who were at high risk for developing multiple tumors.
Surgical Management
Despite frequent colonoscopies and polypectomy, the tumor burden or sheer number of polyps may preclude the continuing use of endoscopy. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred surgery. Total colectomy with removal of the rectal mucosa is the goal of therapy (to remove potentially diseased tissue). Total colectomy with ileorectal anastomosis does not offer as clear a benefit as does total colectomy with IPAA since rectal mucosa remains. Annual colonoscopy would be required to follow this retained tissue for polyp development.
Gardner’s Syndrome
At one time, Gardner’s syndrome was considered a separate disease from FAP. Today, Gardner’s syndrome is considered linked to FAP. Gardner’s syndrome is an inherited polyposis syndrome that is also associated with germline APC mutation. Gardner’s syndrome is thought to be a variation in the expressivity of APC mutations rather than being a distinct clinical entity from FAP (Jasperson, 2012). In fact, some authors suggest that Gardner’s syndrome is the full-blown manifestation of the FAP spectrum of clinical features due to the APC gene mutation (Ponti et al., 2013; Popek & Tsikitis, 2011).
CLINICAL PEARL
Gardner’s syndrome usually causes benign tumors to form in many different organs and causes a higher risk of developing CRC and other FAP-related cancers.
Etiology
Gardner’s syndrome shares characteristics with FAP in that it is due to a mutation in the APC gene. Notably, Gardner’s syndrome is also associated with formation of adenomatous polyps as opposed to hamartomas that occur in PJS (Omundsen & Lam, 2012). The APC gene of chromosome 5q21 is responsible for Gardner’s syndrome too. The gene encodes a protein that plays a substantive role in cell adhesion and signal transduction. In Gardner’s syndrome, the APC mutation goes beyond just effects on the colorectum and involves tissue growth in other body areas (hence the tumors and osteomas) (Ponti et al., 2013).
Clinical Presentation
Gardner’s syndrome has a clinical presentation that is distinct from FAP. In addition to colonic polyposis, Gardner’s syndrome is associated with osteomas, epidermoid cysts, soft tissue tumors, fibromas, and/or desmoid tumors (Jasperson, 2012; Ponti et al., 2013). In particular, skin manifestations of Gardner’s syndrome include epidermoid cysts, trichilemmal hybrid, or pilomatricomas developing on the face, scalp, or limbs of patients; something called a nuchal fibroma (diffuse induration and swelling of the back of the neck); and a “Gardner fibroma” area of thick collagen bundles and interspersed fibroblasts located mostly on the trunk (Ponti et al., 2013, pp. 244–245). Osteomas can arise on the mandible and skull. Dental lesions occur in almost 1/5 of patients including odontomas, absent, excess, or rudimentary teeth, or multiple caries (Ponti et al., 2013). Desmoid tumors do not have a malignant potential since they are locally invasive fibromatoses but can be highly aggressive in growth (Shah et al., 2013). They are associated with a higher mortality and morbidity because they can cause local destruction or tissue blockade. Intra-abdominal desmoid tumors can cause intestinal obstruction, blockage of the ureters, intestinal hemorrhage, or enterocutaneous fistulae (Kastrinos & Syngal, 2011).
Medical Management
Like other polyposis syndromes, endoscopic surveillance is required in Gardner’s syndrome. Panoramic dental radiographs may detect occult lesions in Gardner’s syndrome patients.
Prophylaxis regimens for Gardner’s syndrome have been proposed too. Celecoxib (a COX-2 NSAID) was recommended previously but is of questionable long-term safety due to associated cardiovascular events. Sulindac has also been tested but has a risk of adverse effects on the stomach. With appropriate medical management of GI toxicity (protective coating agents and use of H2 blockers and proton pump inhibitors), sulindac may be more tolerable in longer usage (Ponti et al., 2013). It should be noted that osteoma formation may precede the formation of colon polyps in Gardner’s syndrome. Persons with a family history should be screened for GI tract involvement if other extraintestinal lesions are identified (Ponti et al., 2013).
Surgical Management
Gardner’s syndrome is associated with the potential for multiple extraintestinal tissue growth. Consequently, total colectomy is not “curative” therapy. However, surgery may be required if polyps or desmoid tumors obstruct the intestine or if desmoids obstruct the ureters, kidneys, or other vital body systems.
A notable finding in both Gardner’s syndrome and FAP is the relationship of desmoid tumor formation and trauma. It is hypothesized that abdominal surgery can accelerate or precipitate desmoid formation and growth. The exact pathogenesis of this process is not understood (Popek & Tsikitis, 2011). When small bowel obstruction occurs related to desmoid tumors, several techniques are possible. Intestinal resection, bypass, and strictureplasty have all been used successfully (Xhaja & Church, 2013).
Peutz-Jeghers Syndrome
PJS is a polyposis syndrome characterized by the formation of hamartomatous polyps in the GI tract as opposed to adenomatous polyps. The hamartomatous syndromes like PJS are much less common than are adenomatous syndromes, approximately 1/10 the frequency (Omundsen & Lam, 2012).
PJS is a rare disease that has an autosomal dominant inheritance pattern. In addition, to the occurrence of hamartomatous polyps in the GI tract, there is usually a family history of PJS and a classical pigmentation finding. The hamartomatous polyps occur most frequently in the small bowel. The characteristic extraintestinal manifestation is mucocutaneous pigmentation (i.e., freckles) of the lips and buccal mucosa (Kastrinos & Syngal, 2011).
Etiology
Most PJS cases are due to a germ line mutation in the nuclear serine threonine kinase gene LKBI/STKII that regulates cell polarization, metabolism, and cell growth and is likely a tumor suppressor gene. The result of the mutation is a truncated protein with no kinase activity (Omundsen & Lam, 2012).
The hamartomas that occur in PJS are macroscopically large and pedunculated. The main histologic characteristic of Peutz-Jeghers polyps is the presence of a central core of bands of smooth muscle covered by mucosa similar to the body region with normal or hyperplastic glandular epithelium. A histologic description of a polyp with these characteristics can assist (along with demonstrable genetic findings) with the diagnosis of PJS (Lucci-Cordisco et al., 2013). They most commonly occur in the small bowel (jejunum most common) but can also occur in the stomach, colon, and, with much less frequency, in the bladder and lungs. They can also occur in the nose, uterus, and gallbladder. While polyps occur most commonly in the small intestine in PJS, the colon is the most frequent site for GI malignancy (Lucci-Cordisco et al., 2013; Omundsen & Lam, 2012).
Clinical Presentation
PJS usually presents around a median age of 11 years. Classic appearance is altered pigmentation in the form of dark blue to brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surface of the hands, and genitalia and perianally. It is from mucocutaneous melanin pigmentation (Jasperson, 2012). Notably, some patients have no pigmentary changes, but 95% of PJS patients have mucocutaneous pigmented lesions (Shah et al., 2013). When these pigmentary changes do occur, they usually start fading from the third decade onward (Omundsen & Lam, 2012).
Affected patients usually enter the health care system and begin surveillance after they present with an acute complication. The complications may include abdominal pain due to bowel obstruction, intussusception, volvulus, and rectal bleeding. Once identified, family members should be assessed as well. A definite diagnosis of PJS includes at least two of the following characteristics: (1) hyperpigmentation of the lips or buccal mucosa, (2) two or more hamartomatous polyps in the small bowel, or (3) a PJS family history (Kastrinos & Syngal, 2011).
Medical Management
Medical therapy involves ongoing intestinal endoscopic surveillance plus continuous screening for extraintestinal cancer (mammogram, PAP test, testicular ultrasound, etc.) (Kastrinos & Syngal, 2011). Endoscopy of both the upper and lower GI tract is recommended. Given PJS’s predilection for the small bowel, a small bowel series or capsule endoscopy is usually recommended starting around 8 years of age. Polyps can be removed endoscopically depending on the number of polyps. Surveillance endoscopy should be done every 2 to 3 years (Kastrinos & Syngal, 2011). Notably, the cancer risks associated with PJS are more significant after 30 years with GI tract cancers having the highest cumulative risk (Jasperson, 2012). Ideally, PJS is best managed by specialist centers with expert providers (Omundsen & Lam, 2012).
Surgical Management
Acute surgical intervention is sometimes required for intussusception, volvulus, and small bowel obstruction. CRCs associated with PJS should be managed like other CRCs with segmental resection. Prophylactic colectomy is not recommended for PJS given its location in multiple body sites (Omundsen & Lam, 2012). If polyps are above 1.5 cm in size or are suspicious for malignancy, they should be removed endoscopically or, if necessary, surgically (Omundsen & Lam, 2012).
Diverticular Disease
Diverticular disease is a disorder that represents a spectrum of clinical presentation varying from totally asymptomatic and uncomplicated to acute situations requiring emergency surgery with a diversion of fecal stream. Diverticulosis is the term used to describe the presence of colonic diverticula, that is, small sac-like outpouchings of the intestinal wall. Diverticulitis describes when one or more of these diverticula become inflamed. Diverticular disease includes both diverticulosis and diverticulitis. For most people, diverticulosis is discovered only incidentally at colonoscopy or barium enema testing. Diverticular disease is a very common GI disorder in the developed world with highest rates in the United States and Europe. By age 80, about 70% of Americans have diverticulosis (Boynton & Floch, 2013). Acute diverticulitis is the most common complication of diverticular disease affecting 10% to 25% of patients (Lahat et al., 2013).
Etiology
Diverticular disease has been noted to be a disease of aging, that is, acquired over time (Boynton & Floch, 2013; Gardiner, 2013) and is likely linked to diet. Specifically, diverticulosis is thought to be a “deficiency” disease of western civilization based on low intake of fiber (McQuaid, 2014). Painter and Burkitt (1971) originally hypothesized that low-fiber diets resulted in small-volume dry stools that required higher pressures for colonic transit.
Low fiber theoretically creates the higher luminal pressures that are thought to encourage the mucosa and submucosa to herniate through the bowel wall muscle at the sites where blood vessels perforate the muscle layer (points of greater weakness). Diverticula may develop more in the sigmoid colon because intraluminal pressures are highest in this region (McQuaid, 2014). The theory provides a logical explanation of why diverticulosis increases with age (Burgell et al., 2013; Peery & Sandler, 2013). Note that this etiologic fiber hypothesis has persisted for over 40 years largely without proof. A recent study by Peery et al. (2012) demonstrated that a high-fiber diet was associated with a higher prevalence of diverticula. Conversely, there is some evidence that a high-fiber diet may protect against diverticular disease (i.e., diverticulitis) (Burgell et al., 2013; Peery & Sandler, 2013).
In a cross-sectional colonoscopy-based study of 539 people with diverticulosis and 1,569 without it, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis (Peery et al., 2013). So findings continue to be mutually contradictory.
Another etiologic perspective relates to the effect of aging on colon tissue. Age-related changes in the connective tissue of the large bowel include an increase in collagen cross-linking and increased elastin; both may contribute to increased colon rigidity (Boynton & Floch, 2013).
Interestingly, when diverticulosis occurs in persons younger than 40 years of age, they tend to be obese and the cases are less likely to be complicated, however emergency operation rates are higher. The diagnosis of diverticulitis should be included in the differential diagnosis of younger obese patients with lower abdominal pain (Pilgrim et al., 2013). A cross-sectional study of 23 patients <50 years old demonstrated that risk factors for acute diverticulosis included obesity, male gender, and consumption of alcohol (Pisanu et al., 2013).
Notably, research has demonstrated that nuts and seeds do not increase the risk of diverticulitis or a diverticular bleed (Peery & Sandler, 2013). Though it was thought that nuts and seeds could obstruct the diverticula and cause a perforation, Strate and colleagues (2008) found no association.
Clinical Presentation
Diverticulosis remains asymptomatic in the majority of patients. However, about 20% will experience complications (Boynton & Floch, 2013). The two major recognized complications are acute episodes of bleeding and diverticulitis.
The symptom presentation in diverticulosis may be subtle and then more pronounced. Patients may report chronic vague GI symptoms including mild abdominal pain, bloating, constipation, and diarrhea or fluctuating bowel habits. Physical examination at this point is usually normal.
When acute diverticulitis strikes, the patient reports abdominal pain in the left lower abdominal quadrant. This presentation occurs because in almost all patients with diverticulosis the sigmoid and descending colon are involved (McQuaid, 2014).
Medical Management
Symptom management and medical management depend on the state of diverticular disease: diverticulosis versus diverticulitis. Though the fiber hypothesis is not fully supported by research, contemporary diverticulosis medical therapy still targets fiber. In asymptomatic disease that is discovered incidentally, the patient should be counseled to eat a high-fiber diet. Fiber supplements such psyllium or methylcellulose may also assist with less constipated stool movements.
Most diverticulitis patients can be managed conservatively. For those with mild symptoms and no signs of abdominal complications (e.g., peritoneal signs), they can be treated as outpatients via a clear liquid diet and broad-spectrum antibiotics covering anaerobes, for example, metronidazole 500 mg three times daily or amoxicillin/clavulanate 875/125 mg twice daily plus either ciprofloxacin 500 mg twice daily or trimethoprim–sulfamethoxazole 160/800 mg twice daily for 7 to 10 days or until the patient is afebrile for 72 hours (McQuaid, 2014). A recent retrospective review supported that outpatient treatment for acute uncomplicated diverticulitis was feasible and safe in 118 patients (Unlu et al., 2013).
If symptoms worsen (increasing pain, high fevers, increased white blood cell counts, or peritoneal signs e.g., rebound tenderness), patients should be hospitalized. Patients should be NPO, be placed on IV fluids, and be given antibiotics covering anaerobic and gram-negative bacteria usually for 5 to 7 days before converting to oral therapy. Commonly used agents include cefoxitin, piperacillin–tazobactam, or ticarcillin–clavulanate (McQuaid, 2014).
The degree of complexity of diverticulitis can be described using something called the modified Hinchey classification. Based on diagnostic testing and operative findings, the diverticulitis complexity can be placed into one of four stages: stage 1, pericolonic abscess; stage 2, pelvic abscess; stage 3, purulent peritonitis; and stage 4, fecal peritonitis (Hinchey et al., 1978; Wexner & Moscovitz, 2000). The higher the stage, the more likely a multistage surgery will be used and the higher the associated morbidities (Turley et al., 2013). If an abscess is developed related to the diverticulitis, a higher risk of surgical intervention is noted (Van De Wall et al., 2013).
Surgical Management
Surgical management is usually reserved for those individuals who have had diverticulitis with complications. For persons who have had multiple episodes of diverticulitis, an elective bowel resection of the worst affected parts may be done to ameliorate the likelihood of future attacks. However, prophylactic bowel resection is being questioned for its efficacy in prevention (Lutwak & Dill, 2013). Elective surgery for uncomplicated diverticulitis should be done on a case by case basis considering patient-specific factors like age, computed tomography (CT)-graded severity, and patients’ medical condition (Turley et al., 2013).
For persons who develop acute diverticulitis with complications (e.g., peritonitis, abscess), emergency surgery will be performed. Most commonly, a temporary colostomy and a Hartmann’s procedure will be done. This approach leaves the anus and rectal stump inside the body closed over with surgical staples. The proximal part of the bowel exits the body in the left lower quadrant as a stoma. When the sepsis resolves (usually 12 to 16 weeks later), the two segments can be reconnected. This approach is usually reserved for patients who are more severely toxic.
Some surgeons do not use the two-step Hartmann’s surgery but rather complete it in one step. The diseased segment is removed, the two open bowel ends are cleansed with irrigation, and a primary anastomosis is completed. Both one-stage and Hartmann’s procedures can be done laparoscopically (Turley et al., 2013). A recent systematic review by Gaertner et al. (2013) suggests that elective laparoscopic colon resection for diverticular disease is associated with better outcomes and less complications than open colectomy.
Radiation Enteritis
Radiation enteritis, sometimes called radiation enteropathy, is a rare complication of radiation therapy for pelvic malignancy, mainly prostate, rectal, and gynecological cancers. Tissue injury to the GI tract especially the small intestine may occur during treatment or at a variable time following therapy. As more patients survive cancer and radiation is included in multiple cancer care pathways, the incidence of radiation-related GI complications continues to increase. Recently, “pelvic radiation disease” has been suggested as the preferred nomenclature for the disorder (Hogan et al., 2013; Li et al., 2013).
CLINICAL PEARL
Due to the nature of the treatment, radiotherapy can affect tissue and other organs in the pelvic region. Although they may be called “late effects,” some symptoms may occur at anytime from during treatment to many years later.
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