General Gastro Flashcards
What is Lynch Syndrome?
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that is associated with a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome. Because patients with Lynch syndrome can have polyps, the term HNPCC has fallen out of favor.
Where in the colon does Lynch syndrome typically effect?
Two-thirds of colon cancers occur in the proximal colon
What are the genetics of Lynch Syndrome?
HNPCC is inherited in an autosomal dominant fashion
Screening for Lynch Syndrome?
Screening
Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.
Colon cancer
Colonoscopies are recommended as a preventative method of surveillance for individuals who have Lynch syndrome, or LS-associated genes. Specifically, it is recommended that colonoscopies begin at ages 20–25 for MLH1 and MSH2 mutation carriers and 35 years for MSH6 and PMS2 mutation carriers. Colonoscopic surveillance should then be performed at a 1-2 year interval for Lynch Syndrome patients.
Endometrial/Ovarian cancer
A transvaginal ultrasound with or without endometrial biopsy is recommended annually for ovarian and endometrial cancer screening. For women with Lynch syndrome, a yearly CA-125 blood test can be used to screen for ovarian cancer, however there is limited data on the efficacy of this test in reducing mortality.
Other cancers
There are also strategies for detecting other cancers early or reducing the chances of developing them that people with Lynch syndrome can discuss with their doctor, however their effectiveness is not clear. These options include:
Upper endoscopies to detect stomach and small bowel cancer every 3–5 years, starting at age 30 at the earliest (preferably in a research setting)
Annual urinalysis to detect bladder cancer, starting at age 30 at the earliest (preferably in a research setting)
Annual physical and neurological exams to detect cancer in the central nervous system (brain or spinal cord), starting at age 25 at the earliest
What is Celiacs disease? Histological findings?
Celiac disease, also called gluten-sensitive enteropathy, is an immune-mediated disease of the small intestine. While classically this disease has been diagnosed in childhood, changes to breastfeeding, environmental allergens (gluten), and consumption patterns as well as an increased awareness of the signs and symptoms of celiac disease have led to an increasing number of cases of late-onset diagnosis (age 10-40 years) as well as diagnosis of asymptomatic or mildly symptomatic cases. The disease is felt to be triggered by environmental allergens in people with a genetic predisposition. This theory is substantiated by a significant familial linkage and associations with HLA DR3-DQ2 and DR4-DQ8. The disease is found often in those of European ancestry, but is increasingly recognized in other ethnicities. Classic manifestations of celiac disease include foul-smelling, bulky stool; weight loss; anemia; and deficiencies in the B vitamins (sometimes resulting in neurological and dermatological sequelae), vitamin D, and calcium (resulting in osteopenia).
intestinal mucosa with flattened microvilli, which is characteristic of celiac disease. It is this villous atrophy that leads to the malabsorption of nutrients and many of the sequelae of the celiac disease
What is a Zenker Diverticulum? How do we diagnose? Treatment (for comlex only)
A barium swallow combined with dynamic continuous fluoroscopy is the best diagnostic test for a Zenker diverticulum (ZD). Patients with this diagnosis typically have a posterior midline diverticulum that is larger than 2 cm and that is just above the cricopharyngeus. A very large diverticulum can actually absorb all of the barium given for the study. Small diverticula can be missed if the study is not dynamic and if the patient is not rotated after swallowing.
Patients with a ZD usually present with esophageal dysphagia, voice changes, regurgitation of undigested food, and bad breath (halitosis).
The differential diagnosis of a ZD includes other causes of dysphagia. The first step in the workup of dysphagia is determining if it is due to oropharyngeal or esophageal dysphagia. Oropharyngeal dysphagia is often characterized by difficulty in initiating swallowing, concerns expressed by patients about their neck and jaw region, aspiration or nasopharyngeal regurgitation, drooling, dysarthria, food spillage, and choking or coughing during eating. Esophageal dysphagia is usually described as difficulty in swallowing several seconds after initiating swallowing or the sensation that foods or liquids are “stuck” in the chest (or both). Most patients feel this discomfort behind the sternum.
For patients with a symptomatic ZD, the optimal management is surgical repair. The details of possible surgical options are beyond the scope of the COMLEX examination.
Acute cholecystitis symptoms and testing?
his patient presents with the classic symptoms of acute cholecystitis. Right upper quadrant abdominal pain, fever, and leukocytosis suggest the diagnosis. A physical examination may reveal a Murphy sign (inspiratory arrest upon deep palpation of the right upper quadrant). Laboratory results generally show an elevated white blood cell count. Alkaline phosphatase and bilirubin are typically normal. The initial imaging modality of choice is an ultrasound because it is a rapid, safe, and cost-effective test. The sensitivity of ultrasound approaches 95%. When results of ultrasound are equivocal or negative for cholecystitis, cholescintigraphy (HIDA scan) is indicated in the presence of high clinical suspicion. Cholescintigraphy is a nuclear imaging procedure where a radioactive tracer, technetium-99m, is injected intravascularly. The tracer circulates to the liver and is excreted into the biliary system, and the flow of bile into the common bile duct, cystic duct, and gallbladder is studied. A normal study would reveal visualization of the gallbladder that fills with tracer material. A positive study that would support acute cholecystitis has no isotope accumulation visualized in the gallbladder, indicating an obstruction of the cystic duct. False positives may be seen in situations of severe liver disease, in patients on total parenteral nutrition, and in patients with hyperbilirubinemia or alcohol or opiate abuse. Cholescintigraphy has a sensitivity and specificity of approximately 95%. The negative predictive value of a normal exam in excluding acute cholecystitis is greater than 99%.
What is Melanosis coli?
melanosis coli, a benign disorder of pigmentation of the wall of the colon. It is often found incidentally on a colonoscopy and is caused by chronic use of anthraquinone laxatives, including senna extract, aloe, frangula, and cascara
What things are associated with Crohn’s disease?
This patient is presenting with classic symptoms concerning for the development of Crohn’s disease: abdominal pain, chronic diarrhea (>4 weeks), fatigue, and weight loss. Additionally, the presence of B12 deficiency (elevated MCV with anemia), skip lesions (intermittent normal mucosa), and colonic inflammation without rectal inflammation on endoscopy, smoking, and a family history of colon cancer make Crohn’s disease more likely. The B12 deficiency in this patient specifically points to Crohn’s disease as it most commonly affects the terminal ileum and proximal colon, the former of which absorbs vitamin B12. Smoking is also associated with a greater risk of developing Crohn’s disease. Ocular disease (anterior uveitis) is seen in IBD, but most commonly in Crohn’s disease (up to 10% of IBD patients). Eye disease can manifest at any time during the disease process, including times when bowel disease is quiescent. Eye disease can commonly be associated with erythema nodosum and arthralgias and if seen with sacroiliitis is often associated with positive HLA-B27.
Workup entails general laboratory evaluation for anemia and renal dysfunction, abdominal imaging, and endoscopy with biopsies. There are several extraintestinal complications of IBD including anterior uveitis, scleritis, primary sclerosing cholangitis, erythema nodosum, pyoderma gangrenosum, calcium oxalate renal stones, vitamin B12 deficiency, interstitial lung disease, and venous thromboembolism due to hypercoagulability. Crohn’s disease and ulcerative colitis can be differentiated by several factors as seen below:
What is Zollinger-Ellison? Pathophysiology? How do we diagnose?
Zollinger-Ellison syndrome is characterized by gastric acid hypersecretion resulting in severe, recurrent acid-related peptic ulcer disease and diarrhea. Zollinger-Ellison syndrome typically occurs secondary to the presence of a gastrinoma (gastrin-secreting tumor) in the duodenum or pancreas.
Gastrin is released by the G cells of the stomach antrum. Gastrin stimulates the release of gastric acid from the parietal cells of the stomach, and facilitates proliferation of the gastric epithelial cells. Abnormal gastrin production occurs in some clinical and diseased states, resulting in hypergastrinemia, and is defined by a gastrin level greater than 100–150 pg/ml. Chronic use of PPI’s results in hypersecretion of gastrin due to prolonged suppression of acid secretion and is one cause of a false positive result on a serum gastrin laboratory.
If gastric ulcers are severe and refractory to treatment, Zollinger-Ellison syndrome should be considered. Patients typically have a history of peptic ulcer disease and present with abdominal pain, heartburn, and diarrhea. A patient may present with jaundice if the gastrinomas compress the common bile duct.
The initial test that should be ordered is a fasting serum gastrin level. If elevated, it should be followed by a secretin infusion test. Somatostatin-receptor scintigraphy is the imaging test of choice as it detects for primary or metastatic lesions. Treatment includes intravenous (IV) proton pump inhibitors and surgical resection. Zollinger-Ellison syndrome is also associated with multiple endocrine neoplasia (MEN) type 1. MEN 1 is also known as Werner’s syndrome and presents with the 3 Ps: parathyroid tumors; pituitary tumors, including prolactinoma; and pancreatic endocrine tumors, including insulinomas, vipomas, glucagonomas, and Zollinger-Ellison syndrome.
How to stage and treat Crohn’s disease?
Crohn disease, which is an inflammatory bowel disease that most commonly affects the distal ileum, but may affect anywhere from the mouth to the anus, and should be treated with a tumor necrosis factor (TNF)-alpha inhibitor aka adalimumab. This patient is presenting with moderate to severe Crohn disease, given her systemic findings and weight loss.
Disease severity can be assessed using the Crohn’s Disease Activity Index (CDAI) or Harvey-Bradshaw Index. It is unlikely you will be required to know these for Step 3. You should, however, be aware that patients with mild Crohn disease would be ambulatory, tolerating an oral diet, with minimal (< 10 percent) weight loss and no systemic symptoms (tachycardia, fever, abdominal pain, obstruction, etc.). Moderate to severe disease would have the findings listed above, such as in this patient. Fulminant disease would be present if patients had persistent symptoms in the presence of glucocorticoids or biologic agents, or presented with severe complications such as abscess, obstruction, or severe systemic symptoms (many of these patients would require hospitalization).
The goal of treatment is to induce remission: symptom resolution and healing of mucosal damage. Many authors advocate for step-up therapy in patients with mild disease and step-down therapy in patients with moderate to severe or fulminant disease. Initial therapy for mild disease with TI and proximal colon involvement would include enteric-coated budesonide, a corticosteroid, oral prednisone, or 5-aminosalicylates (5-ASA) such as sulfasalazine, mesalamine, etc. It is generally considered that 5-ASA is inferior to budesonide. Patients with distal colonic involvement and mild disease would require oral steroids, as enteric steroids would not reach the distal colon intact.
Initial therapy for moderate to severe disease or fulminant disease would include the initiation of TNF-alpha inhibitors or other suitable biologic agents, with or without immune-modulating therapy, with a medication such as azathioprine, methotrexate, or 6-mercaptopurine. Trials have shown that the combination of TNF-alpha inhibitors and immunomodulators is superior to the single use of either agent alone in inducing remission. Many institutions will still use steroids as initial management inpatient and will not start biologic agents inpatient due to concerns about patients affording biologic agents outpatient. This is more of a social issue than anything. Guidelines show that for moderate to severe disease requiring admission, especially with fistula or abscess formation, that TNF-alpha inhibitors have strong evidence of efficacy in inducing remission.
Polyps found on colonoscopy and follow up screening recommendations?
The endoscopic appearance of a polyp is often not necessarily a good indicator of its histologic nature. Although as many as 70% of diminutive polyps (< 5 mm) may be adenomas, the risk of any particular polyp containing malignancy increases with the size of the polyp. The method chosen for polypectomy is often related to the appearance and size of the polyp. Polyps are usually described as being pedunculated, sessile, or flat. The risk of a polyp 2 cm in size or larger being malignant is greater than 10%.
Small rectal hyperplastic polyps 10 years after diagnosis
1-2 tubular adenomas with low-grade dysplasia < 1 cm 5-10 years after diagnosis
3-10 adenomas or an adenoma >1 cm or with high-grade features 3 years after diagnosis
> 10 adenomas < 3 years after diagnosis
Sessile adenomas removed in pieces 2-6 months after diagnosis
Personal history of colon cancer < 1 year after resection with a repeat at 3 years and, if normal, then repeated every 5 years
Family history of colon cancer:
In a first-degree relative < 60 or >2 first-degree relatives of any age Age 40 or 10 years prior to the age of immediate family case; repeat every 5 years
In a first-degree relative >60 or >2 second-degree relatives of any age Age 40; repeat every 10 years
When is colonoscopy contraindicated
Colonoscopy is contraindicated in acute diverticulitis cases due to the risk of increased inflammation and bowel perforation. Barium enema is also contraindicated, as it can cause barium peritonitis if it leaks into the abdominal cavity (or thoracic cavity if esophageal perforation).
