This study determined whether a progesterone (P) receptor (PR)-mediated mechanism regulates morphological characteristics associated with prepartum cervix remodeling at term and with preterm birth. With focus on the transition from a soft to ripe cervix, the cervix stroma of untreated controls had reduced cell nuclei density/area and less organized extracellular collagen, while the density of macrophages/area, but not neutrophils, increased just 2 days before birth (day 17 vs day 15 or 16.5 postbreeding). Preterm birth was induced within 24 hours of treatment on day 16 postbreeding with PR antagonist or ovariectomy (Ovx). Pure or mixed PR antagonists increased the density of macrophages in the cervix within 8 hours (day 16.5 postbreeding), in advance of preterm birth. However, neither PR antagonists nor P withdrawal after Ovx affected the densities of cell nuclei and neutrophils or extracellular collagen compared to the same day controls-an indication that the cervix was sufficiently remodeled for birth to occur. To block the effect of systemic P withdrawal, Ovx pregnant mice were given a PR agonist, either pure or mixed. These treatments forestalled preterm birth and prevented further morphological remodeling of the cervix. The resulting increase in macrophage density in cervix stroma following Ovx was only blocked by a pure PR agonist. These findings support the hypothesis that inflammatory processes in the prepartum cervix that include residency of macrophages, cellular hypertrophy, and extracellular collagen structure are regulated by genomic actions of PR in a final common mechanism both at term and with induced preterm birth.
INTRODUCTION:
Livers from donation after circulatory death (DCD) donors have a higher incidence of poor functional status and ischemic cholangiopathy as highlighted in our case report below.
CASE DESCRIPTION/METHODS:
Here we present a case of a 64 year old male with end stage liver disease due to Hepatitis C cirrhosis complicated by HCC, with three episodes of TACE with a pretransplant MELD-Na 28 who underwent OLT from DCD donor with replaced left and right hepatic arteries. He presented with worsening liver enzymes on post-operative day (POD) 19. Initial labs suggested a hepatocellular liver injury pattern with total bilirubin 0.7 mg/dl, aspartate aminotransferase 116 U/L, alanine aminotransferase 286 U/L, and alkaline phosphatase 473 U/L. A post-transplant ultrasound indicated nonvascular hypoechoic areas in the right hepatic lobe possibly representing abscesses or areas of infarction. A vascular scan indicated decreased resistive indices and elevated systolic rise time in the right hepatic artery indicating hepatic arterial stenosis. A CT scan showed mild intrahepatic biliary ductal dilation with decompressed distal common bile duct (CBD) representing a possible anastomotic stricture. The liver biopsy showed minimal-mild portal infiltrates, without venulitis or ductulitis with mild lobular disarray and focal, mild cholestasis. Rare necrotic and degenerating hepatocytes, with focal drop-out were noted which showed active hepatitis. An ERCP was performed on POD 20. Necrotic and denuded biliary mucosa with a distal CBD stricture (Figure 1) was noted on cholangioscopy. Fluoroscopic images showed multiple intrahepatic strictures and cystic dilatation of several intrahepatic biliary ducts (Figure 2). Given the tightness of the stricture, only a A 7Fr x 7 cm plastic biliary stent could be placed across the stricture. Angiogram showed severe focal stenosis of the proximal right hepatic artery, just distal the anastomosis related to “kinking” of the vessel. Percutaneous Transluminal balloon Angioplasty resulted in wide patency after balloon dilation and placement of a 4 mm × 15 mm stent within the vessel (Figure 3). The middle and left hepatic arteries were patent.
DISCUSSION:
This case of DCD OLT complicated by ischemic cholangiopathy resulted in intrahepatic and CBD strictures requiring biliary stenting. What is unique in this case is the additionally stenosis of right hepatic artery, the inciting trigger which was re-perfused with a vascular stent and resulted in the stabilization of liver function.
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