Preoperative metopic forehead contours varied significantly from postoperative contours. Cranial reconstructions approximated the foreheads of normal controls, and reconstructions were stable at more than 1-year follow-up.
Cholecystocolic fistula (CCF), a connection between the gallbladder and neighboring colon, is a rare entity with little consensus as to the optimal surgical management. Existing case reports have described both open and laparoscopic repairs. We describe the first reported case of a successful robotic repair of a CCF in a 50-year-old woman diagnosed with cholangitis 5 years prior to surgery. The patient had a longitudinal follow-up by a single surgeon, allowing for early diagnosis and repair. This case also includes radiographic imaging over 5 years during the index hospitalization and preoperative workup. This allows for a glimpse into the natural pathogenesis of this disease. After robotic surgery, the patient made a complete recovery with no postoperative complications.
Background
The calcium-sensing receptor (CaSR) has been localized and characterized in numerous tissues throughout the body. In the mammalian gastrointestinal tract, the CaSR is known to act as a nutrient sensor and has recently been found to play a role in intestinal fluid and electrolyte balance. This study aims to demonstrate the functionality of the CaSR as a modulator of fluid secretion and absorption along the small intestine.
Methods
Small intestine regions (proximal, middle, and distal) were isolated from Sprague Dawley rats and loaded into an
ex vivo
intestinal perfusion device that provides independent intraluminal and extraluminal (serosa/basolateral) perfusion. The regions were perfused with 5 and 7 mM of Ca
2+
, both in the presence and absence of forskolin (FSK), a potent secretagogue. Control experiments were conducted with intraluminal perfusate containing standard Ringer-HEPES buffer with a physiological concentration of Ca
2+
(1 mM). A second set of comparison experiments was performed with intraluminal perfusates containing AC-265347, a CaSR activator and agonist, in the presence of FSK. In all experimental conditions, the intraluminal perfusate contained fluorescein isothiocyanate (FITC)-inulin, a nonabsorbable fluorescent marker of secretion and/or absorption. Intraluminal fluorescence signal was utilized as a measure of water movement at the start of the experiment and every 15 min for 90 min.
Results
Under physiological conditions, increasing the concentration of Ca
2+
in the luminal perfusate reduced intestinal fluid secretion in all regions. At a Ca
2+
concentration of 7 mM, net fluid absorption was observed in all regions. In the presence of FSK, 5 mM Ca
2+
significantly decreased fluid secretion and 7 mM Ca
2+
abolished FSK-induced fluid secretion. Intraluminal perfusion with 5 mM Ca
2+
was as effective as AC-265347, in reducing secretagogue-induced fluid hypersecretion in the proximal and middle regions.
Conclusion
This study concludes that apical CaSR is active along the small intestine. Its activation by Ca
2+
and/or calcimimetics reduces fluid secretion in a dose-dependent manner, with higher Ca
2+
concentrations, or application of a calcimimetic, leading to fluid absorption. We furthermore show that, in the presence of FSK, receptor activation abates FSK secretagogue-induced fluid secretion. This presents a new therapeutic target to address secretory diarrheal illnesses.
This is the first study to examine the mechanisms of glucocorticoid, serum- and glucocorticoid-inducible kinase 1, and nongenomic kinase signaling of CFTR in the native intestine. We identified unique and druggable intestine-specific factors of the pathway that are targets for treating stress-induced diarrhea.
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