Neoplasms of the Gastrointestinal System

The most common benign liver tumors include hepatic hemangiomas, focal nodular hyperplasia, and hepatic adenomas. These tumors are mostly asymptomatic and/or found incidentally on abdominal imaging. While these tumors are benign, large lesions can cause symptoms such as upper abdominal pain, or produce complications such as bleeding. Malignant potential is a concern for hepatic adenoma, depending on risk factors. The diagnosis is based on imaging studies, with characteristic findings defining the tumor. Biopsy generally is reserved for equivocal cases. Management is observation for most small, asymptomatic, and non-growing tumors. However, high-risk factors, symptoms, increasing tumor size, and complications dictate the need for surgical intervention.

Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Diagnosis is made by genetic testing of the index patient and their family members. Management consists of an earlier screening of individuals with defective MMR genes, as well as total colectomy if colorectal neoplasia is discovered. Prophylactic hysterectomy plus salpingo-oophorectomy are recommended for women beyond reproductive age.

Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Common causes of functional dysphagia include achalasia, scleroderma, and diffuse esophageal spasm (DES). Mechanical causes of dysphagia include esophageal rings, webs, strictures, and cancer. Oropharyngeal dysphagia may be due to structural abnormalities or abnormal neuromuscular function and coordination. The diagnostic workup depends on the patient’s presenting symptoms, but may include manometry, barium esophagram, or direct visualization with nasopharyngeal laryngoscopy or endoscopy. Treatment varies depending on the underlying cause.

Colorectal cancer (CRC) is the 2nd-leading cause of cancer-related death in the United States. Almost all cases of CRC are adenocarcinoma and the majority of lesions come from the malignant transformation of an adenomatous polyp. As most CRCs are asymptomatic, screening is essential in detecting early disease. Screening is recommended to start at the age of 45 years, utilizing various screening tools available with colonoscopy, flexible sigmoidoscopy, and fecal tests among them. For high-risk individuals, earlier and more frequent screening is recommended. Other stool-based strategies and visualization tests are also available for CRC screening.

Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (also called MALToma, MALT lymphoma, and pseudolymphoma) is a group of non-Hodgkin’s lymphomas that have historically been grouped together because they appear to arise from postgerminal center marginal zone B cells and share a similar immunophenotype. MALT lymphoma is thought to arise in the setting of chronic immune stimulation, which is usually due to bacterial, viral, or autoimmune stimuli. MALT lymphomas present with symptoms due to localized involvement of glandular epithelial tissues in the specific site where they develop. Diagnosis of MALT lymphoma is made by morphologic, immunophenotypic, and genetic analysis of biopsy samples. Helicobacter pylori–positive gastric MALT lymphoma is treated with H. pylori eradication therapy, and H. pylori–negative gastric MALT lymphoma is treated with radiation therapy. Nongastric MALT lymphoma is treated based on the involved area and extent of disease. MALT lymphoma patients have a good prognosis, with a median survival of > 10 years.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. These syndromes are caused by mutations in specific genes associated with tumor suppression or cell cycle regulation. All patients with FAP will develop colon cancer by age 35–40 years if left untreated. Management is with a surveillance program and colectomy.

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. The syndromes are caused by mutations in specific genes associated with tumor-suppression or cell-cycle regulation. Peutz-Jeghers syndrome is caused by disruptions in the STK11 gene and is associated with colonic (colorectal) and noncolonic (pancreatic, gastric, breast, uterine, cervical, lung, ovarian, and testicular) cancers. Management is with close surveillance and surgery.

Familial juvenile polyposis, also known as juvenile polyposis syndrome, is an autosomal dominant condition characterized by the growth of hyperplastic, hamartomatous polyps in the colon. Polyposis syndromes are a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, and are associated with other extracolonic features. These syndromes are caused by mutations in specific genes associated with tumor suppression or cell cycle regulation. Familial juvenile polyposis is commonly associated with mutations in the SMAD4 (chromosome 18q) and BMPR1A (chromosome 10q) genes. Diagnosis is made by visualizing 5 or more polyps on colonoscopy, or any number plus a positive family history. Management is surgical in order to reduce the likelihood of GI bleeding and obstruction.

Although hepatocellular carcinoma (HCC) is by far the most common malignant liver tumor, there are several rare malignant tumors that are important to keep in mind when making a differential diagnosis. These tumors include cholangiocarcinoma; hepatoblastoma and mesenchymal tumors, such as epithelioid hemangioendothelioma (EHE); and angiosarcoma. While these conditions differ in their etiology and pathology, they often present similarly, with nonspecific symptoms such as fatigue, weight loss, and abdominal discomfort. Diagnosis is by imaging, which can be supported by a biopsy. Surgical excision is the only curative approach for these tumors.

Pancreatic cancer, consisting mostly of invasive pancreatic ductal adenocarcinoma (PDAC), arises from the ductal cells of the exocrine pancreas and is the 4th leading cause of cancer-related deaths in the United States. Pancreatic cancer has the highest mortality rate among the major cancers, with a 5-year survival rate of only 8%–10%. Clinical presentation includes symptoms of abdominal pain, jaundice, and weight loss. Diagnosis is made by CT, MRI, and endoscopic ultrasonography (EUS). Management by surgical resection, usually with neoadjuvant or adjuvant chemotherapy, provides the only chance for cure in the 15%–20% of patients who have resectable disease at the time of diagnosis. Other rare malignant tumors arising from the exocrine pancreas are acinar cell carcinoma and pancreatoblastoma.

Pancreatic neuroendocrine tumors (PanNETs) arise from the endocrine pancreas (islet cells) and represent 2%–5% of primary pancreatic neoplasms; the other 95%–98% of pancreatic neoplasms are from the exocrine pancreas. The majority of PanNETs are nonfunctional (50%–75%), while others that are functional may be benign or malignant. Benign or malignant PanNETs include insulinomas, gastrinomas, malignant pancreatic neuroendocrine carcinomas, and very rare tumors named glucagonomas, somatostatinomas, and VIPomas, after the hormones they secrete. Diagnosis is made clinically, with lab testing for hormone secretion, as well as imaging or upper endoscopy. Management is surgical or with newer molecularly targeted therapies.

Gastric acid medications include proton pump inhibitors (PPIs) and H₂ receptor antagonists (also known as H₂ blockers). The drugs work through different mechanisms to suppress acid secretion by parietal cells in the stomach. The most common indications include peptic ulcer disease, GERD, and dyspepsia. Adverse effects of PPIs include malabsorption, acute interstitial nephritis, and an increased risk of Clostridioides difficile infection. Adverse effects of H₂ blockers include CNS effects, bradycardia/hypotension, gynecomastia, and galactorrhea. Both classes are associated with drug interactions related to the cytochrome P450 system.

Colon polyps are growths of mucosal tissue in the colon, the most common site of polyps in the GI tract. Polyps can be classified as neoplastic or nonneoplastic and may be associated with genetic syndromes. Hyperplastic polyps are nonneoplastic and are the most common type overall, whereas adenomas are the most common type of neoplastic polyp and have the potential to progress to cancer. For most people without hereditary syndromes, colon cancer screening should begin at age 50 (at age 45 for Black individuals) and in adolescence for those with the rare familial adenomatous polyposis (FAP) syndrome. Diagnosis is by biopsy, and management includes frequent surveillance in people with adenomatous polyps or screening every 10 years in the general population until age 75.

The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. The pancreas is covered with a very thin connective tissue capsule that extends inward as septa, partitioning the gland into lobules. This organ has both exocrine and endocrine tissue. The exocrine portion is organized in grape-like clusters of acini, which are small sacs surrounding the terminal ends of pancreatic ducts. The cells lining the acini and ducts secrete products that make up pancreatic juices, which play a major role in digestion. The endocrine portion of the gland consists of circular islets interspersed between acini, which secrete glucagon, insulin, and somatostatin.

The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. On a microscopic level, the stomach wall has several layers, including a mucosa, submucosa, muscularis, and serosa. The stomach is filled with glands that secrete a variety of substances involved in the digestive process. The arterial supply to the stomach is primarily from vessels originating from the celiac trunk.

The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. The colon also contains many mucus-secreting glands to lubricate the stool passing through it. The colon receives its blood supply from colic branches of the superior and inferior mesenteric arteries, which form an important anastomosis along the transverse colon. The colon is regulated by the ANS and receives both sympathetic (inhibitory) and parasympathetic (stimulatory) input.

Carcinoid tumors are small, well-differentiated, slow-growing neuroendocrine tumors (NET). Carcinoid syndrome describes the signs and symptoms associated with unregulated vasoactive hormone production by neuroendocrine tumors. Carcinoid tumors are most commonly found in the GI and bronchopulmonary tracts. Vasoactive substances produced by NET of the GI tract do not cause carcinoid syndrome until the tumors metastasize to the liver. Symptoms of carcinoid syndrome include flushing, diarrhea, and wheezing. Treatment consists primarily of surgical tumor resection and therapy with somatostatin analogs. Prognosis depends on the tumor location, aggressiveness, and overall disease burden.

Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Almost all cases of CRC are adenocarcinoma, and the majority of lesions come from the malignant transformation of an adenomatous polyp. Since most CRC cases are asymptomatic, screening colonoscopy or stool tests are generally recommended in patients ≥ 50 years of age. Along with screening, diagnosis is reached by colonoscopy, which allows visualization as well as tissue sampling. Treatment is primarily surgical, with chemotherapy reserved for advanced disease.

Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). This condition may eventually lead to inflammation (esophagitis), metaplasia (Barrett’s esophagus), and progression to esophageal cancer. Uncomplicated GERD can be managed with lifestyle changes and over-the-counter medications. Sometimes, however, stronger medications or surgery may be required to ease symptoms and prevent complications.

Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. The most common etiologies for gastritis are Helicobacter pylori infection and autoimmune disease. Chronic gastritis is a risk factor for gastric cancer. Management involves the use of proton pump inhibitors with antibiotics (in case of H. pylori infection), avoidance of offending agents, and replacement of associated deficiencies.

Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Hereditary syndromes, pernicious anemia, and prior partial gastrectomy are among the endogenous risk factors. When symptoms such as epigastric fullness, vomiting, and weight loss occur, it is likely that the cancer is in the advanced stage. Diagnosis is confirmed with esophagogastroduodenoscopy and biopsy. Imaging studies and laparoscopy aid in determining the cancer stage. Consequently, staging dictates the management approach. Management consists of gastrectomy and chemoradiotherapy. Most cases are diagnosed in late stages, indicating a generally poor prognosis.

Esophageal cancer is 1 of the most common causes of cancer-related deaths worldwide. Nearly all esophageal cancers are either adenocarcinoma (commonly affecting the distal esophagus) or squamous cell carcinoma (affecting the proximal two-thirds of the esophagus). Major risk factors for adenocarcinoma include smoking, obesity, and Barrett’s esophagus. For squamous cell carcinoma, risk factors include smoking, alcohol consumption, and certain dietary factors. Early-stage cancer is often asymptomatic, with dysphagia and weight loss presenting as the disease progresses. Diagnosis is by endoscopic biopsy or image-guided biopsy of the metastatic site. Management depends on the disease stage. Options include surgical resection, chemotherapy, and radiation. For unresectable esophageal cancers, palliative measures are provided for symptom relief and to prolong survival.