Plecanatide, a uroguanylin analog, activates the guanylate cyclase C receptors in the epithelial lining of the gastrointestinal tract in a pH-dependent fashion initiating (1) the conversion of intracellular guanosine triphosphate to cyclic guanosine monophosphate, which increases the activity of the cystic fibrosis transmembrane conductance regulator to increase chloride and bicarbonate secretion into the intestinal lumen and (2) a decrease in activity of the sodium-hydrogen ion exchanger. The resulting ionic shifts cause an increase in lumenal fluid to facilitate digestion. Plecanatide has been approved by the FDA for use in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. This manuscript is a critical assessment of the therapeutic efficacy and potential risks associated with the use of plecanatide in CIC. The discussion of CIC as a clinical and investigative disorder focuses on the importance of this problem as well and the difficulties involved in clinical management and scholarly investigation of a symptom arising from multiple pathophysiologic mechanisms. Clinical data from studies of recently approved drugs for CIC are utilized to construct a platform for thoughtful understanding of CIC and of how changes in investigation guidelines influence the interpretation of study data and guide symptom management. Plecanatide is a safe and effective medication for the management of adults with CIC.
Question: A 56-year-old Native American man with a history of hepatitis C infection presented with worsening eye pain, double vision, rapidly progressive loss of visual acuity, and exophthalmos with ophthalmoplegia in his right eye. Physical examination findings were suggestive of liver cirrhosis. Cross-sectional imaging of the head and neck showed large extra-axial mass lesion involving the sphenoid wing of the right orbit, anterior cranial fossa, middle cranial fossa, sinus, and temporal fossa (Figure A). Thyroid function tests were within normal limits. What is the diagnosis? Look on page 1258 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Fine needle aspiration of the lesion showed pleomorphic cells with abundant granular cytoplasm and transgressing vessels (Figure B) with intracellular bile (Figure C). Follow-up imaging of the liver showed liver cirrhosis, with a 6.8-cm mass with arterial enhancement and washout (Figure D), compatible with hepatocellular carcinoma. Orbital metastases are rare, and account for 3%–7% of all orbital neoplasms.1Font R.L. Ferry A.P. Carcinoma metastatic to the eye and orbit. III. A clinicopathologic study of 28 cases metastatic to the orbit.Cancer. 1976; 38: 1326-1335Crossref PubMed Scopus (216) Google Scholar Hepatocellular carcinoma very rarely metastasizes to the orbits, and interestingly favors the right orbit. This diagnosis carries very high rate of morbidity and mortality.2Font R.L. Maturi R.K. Small R.G. Garcia-Rojas M. Hepatocellular carcinoma metastatic to the orbit.Arch Ophthalmol. 1998; 116: 942-949Crossref PubMed Scopus (33) Google Scholar, 3Machado-Netto M.C. Lacerda E.C. Heinke T. et al.Massive orbital metastasis of hepatocellular carcinoma.Clinics. 2006; 61: 359-362Crossref PubMed Google Scholar The patient was started on palliative radiation therapy for control of symptoms.
