Papillary Injury Research Articles

Relationship of endoscopic lesions of the renal papilla with type of renal stone and 24\u2009h urine analysis

BackgroundOur purpose was to study the relationship of the 3 different types of endoscopic calcifications of the renal papilla (Randall’s plaque, intratubular calcification, papillary crater) with the type of stone and urine analysis.MethodsThis prospective study examined 41 patients (age range: 18 to 80 years) who received retrograde intrarenal surgery (RIRS) for renal lithiasis (mean stone size: 15.3 ± 7.2 mm). The renal papilla injuries were endoscopically classified as Randall’s plaque, intratubular calcification, or papillary crater. Calculi were classified as uric acid, calcium oxalate monohydrate (COM; papillary and cavity), calcium oxalate dihydrate (COD), or calcium phosphate (CP). A 24 h urine analysis of calcium, oxalate, citrate, phosphate, and pH was performed in all patients. The relationship of each type of papillary injury with type of stone and urine chemistry was determined. Fisher’s exact test and Student’s t-test were used to determine the significance of relationships, and a p value below 0.05 was considered significant.ResultsThe most common injury was tubular calcification (78%), followed by Randall’s plaque (58%), and papillary crater (39%). There was no significant relationship of Randall’s plaque with type of stone. However, endoscopic intratubular calcification (p = 0.025) and papillary crater (p = 0.041) were more common in patients with COD and CP stones. There were also significant relationships of papillary crater with hypercalciuria (p = 0.036) and hyperoxaluria (p = 0.024), and of Randall’s plaque with hypocitraturia (p = 0.005).ConclusionsThere are certain specific relationships between the different types of papillary calcifications that were endoscopically detected with stone chemistry and urine analysis. COD and CP stones were associated with endoscopic tubular calcifications and papillary craters. Hypercalciuria was associated with tubular calcification, and hypocitraturia was associated with Randall’s plaque.

Intraoperative real-time three-dimensional transesophageal echocardiography as a precise navigator for a successful complicated postoperative left ventricular pseudoaneurysm repair: a case report

BackgroundLeft ventricular pseudoaneurysm (LV-PAN) formation is a rare complication after cardiac surgery and mainly occurs after mitral valve surgery. Echocardiography plays a critical role in the assessment of rupture location, orifice geometry, and anatomical relationship with surrounding structures.Case presentationA 56-year-old man presented with LV-PAN formation 1 year after aortic root replacement combined with aortic replacement despite the lack of direct manipulation of the rupture site in the procedure and postoperative myocardial infarction. Intraoperative real-time three-dimensional transesophageal echocardiography (RT 3-D TEE) during surgical repair of the LV-PAN facilitated understanding of the shape of the LV-PAN orifice and the exact anatomical relationship between the rupture site and the posteromedial papillary muscle. Information sharing with surgeons contributed to avoiding direct papillary muscle injury and thus mitral valve deformation.ConclusionLV-PAN formation after cardiac surgery can present without direct manipulation of the rupture site and major coronary lesion. Intraoperative RT 3-D TEE can facilitate better understanding of the anatomical relationship between the rupture site and the posteromedial papillary muscle and allow for information sharing to avoid complications during surgical repair.

A Surgical Perspective on Ischemic Mitral Regurgitation: Tethering or Prolapse? Going Back to Papillary Muscles Anatomy. What the Surgeons Really Need to Know

More than one third of patients with ischemic mitral regurgitation (IMR) present a valve prolapse whose mechanism is subtended by a papillary injury. The recent literature is pointing at a regional ventricular injury or wall motion abnormality rather than a global LV dysfunction as responsible for IMR and the presence of localized valve prolapse related to papillary dysfunction is additionally supporting this idea. Leaflet tethering or prolapse in these patients is subtended by lesion of the papillary muscle (PM) per se rather than its dysfunction secondary to regional and global ventricle enlargement. Identification of this type of lesion is difficult and can be overlooked. Morphological characteristics and anatomical variability of the papillary muscles determine their different susceptibility ischemic damage and dysfunction. Pioneering work in mitral anatomy shows a range of morphological diversity of PM anatomy and leads to an anatomical classification with important implications in IMR surgery. New methods of investigation, as multidetector computed tomography or magnetic resonance provide a very accurate and proper identification of the morphological pattern of the subvalvular apparatus, which is crucial for a long-lasting and successful surgical correction. The involvement of PM in the pathophysiology of IMR not only in terms of their functional anomaly, but also of their effective anatomical aspects and characteristics is increasingly emerging. The modern advancements of imaging techniques can guide the preoperative surgical planning and the surgeon needs to be aware of morphological features of the subvalvular apparatus and combine these findings with echographic functional parameters before embarking in complex mitral repairs.

Is the Balloon Dilation Duration in Endoscopic Papillary Balloon Dilation (EPBD) Related to the Occurrence of Post-EPBD Pancreatitis?

See Twenty-Second versus Sixty-Second Dilation Duration in Endoscopic Papillary Balloon Dilation for the Treatment of Small Common Bile Duct Stones: A Prospective Randomized Controlled Multicenter Trial by Byoung Wook Bang, Tae Hoon Lee, Tae Jun Song, et al., on page 59-65 Endoscopic papillary balloon dilation (EPBD) was proposed as an alternative to endoscopic sphincterotomy (EST) for opening the bile duct orifice to allow stone extraction with functional preservation of the biliary sphincter. Since its introduction in 1982,1 EPBD has been widely performed because it is associated with lower bleeding and perforation risks compared to EST.2,3,4,5,6 However, EPBD is more likely to cause pancreatitis than EST, resulting in an increased mortality rate.7,8 Therefore, EPBD is reserved for selective patients with a bleeding diathesis or altered anatomy, especially in Western countries. The reported incidence of post-EPBD pancreatitis varies greatly, ranging from 0% to 15.4%.9,10,11,12,13 This disparity may be explained by differences in the stone size, bile duct size, balloon diameter, and balloon dilation duration (BDD). Although the mechanism is unknown, post-EPBD pancreatitis has been associated with papillary edema or spasm resulting from balloon dilation and papillary trauma during stone extraction through an insufficiently dilated sphincter. Therefore, papillary injury resulting in increased post-EPBD pancreatitis may frequently occur in cases with relatively large stones in small bile ducts and balloon diameters larger than the stone size or bile duct diameter. BDD was found to correlate with post-EPBD pancreatitis in previous studies, although the results were conflicting. In a prospective randomized trial,14 the risk of pancreatitis was higher with a 1-minute BDD (15.1%, 13/86) than with a 5-minute BDD (4.8%, 4/84; p=0.038). In a systemic review of randomized trials that compared EPBD and EST,15 short EPBD (≤1 minute) had a higher risk for pancreatitis (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.08 to 13.84) compared to EST, but long EPBD (>1 minute) did not pose a higher risk than EST (OR, 1.14; 95% CI, 0.56 to 2.35). A longer BDD may achieve greater loosening of the sphincter of Oddi and cause less papillary damage during stone extraction, resulting in a lower pancreatitis rate. In contrast, however, an initial 2-minute BDD was modified to 15 seconds during the later period of a retrospective study.16 A lesser tendency toward post-EPBD pancreatitis was observed in the modified group (4%, 13/324) relative to the initial group (7.4%, 24/324; p=0.063). A shorter BDD may be less traumatic to the papilla, thus reducing post-EPBD pancreatitis. Bang et al.17 evaluated the risk of pancreatitis after EPBD with a 20- or 60-second BDD in patients with relatively small bile duct stones (≤12 mm) while using balloon diameters (6 to 10 mm) selected according to the stone size and bile duct diameter. The authors also used a prophylactic pancreatic stent in patients at a high risk of post-ERCP pancreatitis. As a result, all factors that might affect the occurrence of post-EPBD pancreatitis were well controlled except for the BDD. However, they observed no difference in the occurrence of post-ERPD pancreatitis between the 20- and 60-second BDD groups (6.4%, 7/109 vs. 7.5%, 9/119). Bang and colleague17 proposed that EPBD could be adequately performed with a 20-second BDD in carefully selected patients because the BDD had little effect on the incidence of post-EPBD pancreatitis, a difficult finding to accept when compared with previous EPBD studies. Although this study may not appear to make sense, new approaches and data have made us rethink the best approach for bile duct stone removal. Therefore, we continue to seek the safest and most effective bile duct stone removal method.

Post-ERCP Pancreatitis: Mechanisms, Risk Factors, and Prevention

Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), occurring in up to 30 to 40% of high risk patients. The most prominent theories of post-ERCP pancreatitis (PEP) pathogenesis include mechanical trauma to the papillary orifice, hydrostatic injury, and enzymatic injury from activated proteolytic enzymes introduced from the duodenum. Investigators have proposed a number of patient-related, procedure-related, and physician-related risk factors for PEP. However, when evaluated in large prospective trials, the role of these factors in increasing risk of PEP is inconsistent. Placement of a pancreatic duct stent and administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) are the two interventions with the greatest body of evidence supporting efficacy in PEP prevention.

Toxicogenomic biomarkers for renal papillary injury in rats

Renal papillary injury is a common side effect observed during nonclinical and clinical investigations in drug development. The present study aimed to identify genomic biomarkers for early and sensitive detection of renal papillary injury in rats. We hypothesized that previously identified genomic biomarkers for tubular injury might be applicable for the sensitive detection of papillary injury in rats. We selected 18 genes as candidate biomarkers for papillary injury based on previously published studies and analyzed their expression profiles by RT-PCR in each kidney region, namely the cortex, cortico-medullary junction, and papilla in various nephrotoxicity models. Comparative analysis of gene expression profiles revealed that some genes were commonly upregulated or downregulated in the renal papilla, reflecting papillary injuries induced by 2-bromoethylamine hydrobromide, phenylbutazone, or n-phenylanthranilic acid. By applying receiver operator characteristics analysis, six candidate biomarkers were identified and their usefulness was confirmed by using an independent data set. The three top-ranked genes, Timp1, Igf1, and Lamc2, exhibited the best prediction performance in an external data set with area under the curve (AUC) values of greater than 0.91. An optimized support vector machine model consisting of three genes achieved the highest AUC value of 0.99. In conclusion, even though definitive validation studies are required for the establishment of their usefulness and reliability, these identified genes may prove to be the most promising candidate genomic biomarkers of renal papillary injury in rats.

POD-08.01: Randall's Plaque and Papillary Injury

POD-08.01: Randall's Plaque and Papillary Injury

Bovine polymerized hemoglobin (hemoglobin-based oxygen carrier-201) resuscitation in three swine models of hemorrhagic shock with militarily relevant delayed evacuation—Effects on histopathology and organ function*

To test our hypothesis that hemoglobin-based oxygen carrier (HBOC)-201 resuscitation in hemorrhagic shock (HS) will not lead to increased organ injury and dysfunction. Three swine HS models simulating military-relevant delayed evacuation: a) moderate controlled HS, b) severe controlled HS, and c) severe uncontrolled HS. Military research laboratory. Swine. Swine were anesthetized/intubated and instrumented. To induce HS, in two controlled hemorrhage experiments, 40% (moderate controlled HS) or 55% (severe controlled HS) of blood volume was withdrawn; in an uncontrolled HS experiment, the liver was crushed/lacerated. During a 4-hr "prehospital phase," pigs were resuscitated with HBOC-201 (HBOC) or Hextend (HEX) or were nonresuscitated (NON). Upon "hospital arrival," liver injury was repaired (severe uncontrolled HS), blood or saline was infused, hemodynamics were monitored, and blood was collected. Upon animal death and/or 72 hrs, necropsy was followed by histopathologic evaluation of organ injury (hematoxylin and eosin, electron microscopy) and immunohistochemistry of oxidative potential (3-nitrotyrosine). Significance (p < .05) was assessed by Kruskal-Wallis, analysis of variance/Bonferroni, and mixed procedure tests. Survival was significantly higher with HBOC than HEX only with severe uncontrolled HS (p = .002). Myocardial necrosis/fibroplasia, fluid requirements, cardiac output, and cardiac enzymes were generally similar or lower in HBOC than HEX pigs, but creatine kinase-MB (but not creatine kinase-MB/creatine kinase ratio) was higher with HBOC in moderate controlled HS. Alveolar/interstitial pulmonary edema was similar with HBOC and HEX, but Po2 was higher with HBOC in severe uncontrolled HS. Jejunal villar epithelial and hepatocellular necrosis were similarly minimal to moderate in all groups. Minimal biliary changes occurred exclusively with HBOC. Aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were generally higher with HBOC than HEX. Mild renal papillary injury occurred more frequently with HBOC, but consistent patterns for urine output, blood urea nitrogen, and creatinine, were not seen. The 3-nitrotyrosine staining intensity was not different. In comparison with hetastarch, HBOC-201 resuscitation of swine with HS increased survival (with severe HS), did not increase evidence of oxidative potential, and had histopathologic and/or functional effects on organs that were clinically equivocal (myocardium, lungs, hepatic parenchyma, jejunum, and renal cortex/medulla) and potentially adverse (hepatobiliary and renal papilla). The effects of HBOC-201-resuscitation in HS should be corroborated in controlled clinical trials.

Papillary Muscle Rupture After Blunt Chest Trauma

We report a case of anterolateral papillary muscle rupture in a 22-year-old man who had blunt chest trauma caused by a car accident. Transesophageal echocardiography revealed severe mitral regurgitation caused by the rupture. He successfully underwent emergency mitral valve replacement and was discharged 9 days after the surgical correction.

Clinical and echocardlographic spectrum of mitral valve and papillary muscle injury as a complication related to percutaneous transvenous mitral commissurotomy with inoue balloon catheter: experience from 6,800 patients

Clinical and echocardlographic spectrum of mitral valve and papillary muscle injury as a complication related to percutaneous transvenous mitral commissurotomy with inoue balloon catheter: experience from 6,800 patients

Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells.

Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2). After dehydration, the maintenance of normal renal function becomes particularly dependent upon PG synthesis. The present studies were designed to examine the potential link between medullary COX1 and COX2 expression in hypertonic stress. In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs). Water deprivation also increases renal NF-kappaB-driven reporter expression in transgenic mice. NF-kappaB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea. RMIC COX2 expression was also induced by driving NF-kappaB activation with a constitutively active IkappaB kinase alpha (IKKalpha). Conversely, introduction of a dominant-negative IkappaB mutant reduced COX2 expression after hypertonicity or IKKalpha induction. RMICs failed to survive hypertonicity when COX2 was downregulated using a COX2-selective antisense or blocked with the selective nonsteroidal anti-inflammatory drug (NSAID) SC58236, reagents that did not affect cell survival in isotonic media. In rabbits treated with SC58236, water deprivation induced apoptosis of medullary interstitial cells in the renal papilla. These results demonstrate that water deprivation and hypertonicity activate NF-kappaB. The consequent increase in COX2 expression favors RMIC survival in hypertonic conditions. Inhibition of RMIC COX2 could contribute to NSAID-induced papillary injury.

Sulfur‐containing amino acids that increase renal glutathione protect the kidney against papillary necrosis induced by 2‐bromoethylamine

Papillary necrosis was observed in the kidneys of rats, 72 h after receiving a single injection of bromoethylamine (BEA). This effect was associated with renal glutathione (GSH) depletion 1 h after the administration of BEA. Stimulation of renal GSH synthesis by pretreatment of the animals either with glutamine + glycine + cystine or N-acetyl-L-cysteine was attempted. Low doses of these precursors administered previously to BEA, respectively, decreased or abolished the GSH depletion. Nevertheless, both pretreatments failed to modify the magnitude of renal papillary necrosis. High doses of these precursors did not modify the BEA-induced GSH depletion, but they significantly increased GSH levels 24 h after BEA administration. At this time, although a smaller intensity of renal papillary necrosis was observed with the amino acid mixture pretreatment, N-acetyl-L-cysteine pretreated rats showed no papillary necrosis. It is suggested that the observed protective effects against BEA-induced renal papillary injury may be ascribed in some measure, to a mechanism independent of GSH.

Natriuretic effect of atriopeptin III in rats with papillary necrosis

This study compared the effects of atriopeptin III (AP III) on sodium excretion and renal interstitial hydrostatic pressure (RIHP) in control rats and in rats pretreated with 2-bromoethylamine (BEA) to produce papillary necrosis. In control rats, infusion of AP III (100 ng.kg-1.min-1) increased sodium excretion from 2.2 +/- 0.7 to 6.4 +/- 0.9 microeq.min-1.g kidney wt-1 and RIHP from 6.8 +/- 0.7 to 8.7 +/- 0.9 mmHg, whereas glomerular filtration rate and renal blood flow were unaltered. Similar results were obtained in rats pretreated with BEA 48 h before the experiment. In rats studied 6 wk after BEA treatment, the papilla was absent and there was atrophy of juxtamedullary nephrons. AP III did not alter sodium excretion or RIHP in this group of rats. These results indicate that 1) an intact renal papilla and/or juxtamedullary nephron population may be required for the natriuretic effect of AP III; 2) the papillary injury 48 h after BEA is not sufficient to abolish the natriuretic response to AP III; and 3) elevations in RIHP may play a role in the natriuretic response to AP III.

Healed experimental renal papillary necrosis and cortical scarring in the rat from 2-bromoethylamine hydrobromide

Male Sprague-Dawley rats were each given a single subcutaneous injection of an aqueous solution of bromoethylamine hydrobromide (BEA) at dose levels of 80 mg/kg (16 rats), 125 mg/kg (15 rats) and 250 mg/kg (16 rats) or a single subcutaneous injection of water (controls, 15 rats). The dose levels were chosen so as to cause renal papillary injury varying from minor necrotic foci to necrosis and subsequent sloughing of the entire papilla. The animals were killed after 5 months and the kidneys were weighed and examined macroscopically and microscopically for the presence of RPN and cortical scarring. Macroscopically evident RPN occurred in 18 of 43 surviving BEA-treated rats, bilaterally in 16 and unilaterally in 2. Bilateral asymmetry of the extent of sloughing was evident. All kidneys with macroscopic RPN exhibited cortical scarring. Asymmetry of the extent of atrophy and scarring in some animals resulted in a significant unilateral reduction in renal weight and a significant contralateral compensatory hypertrophy. Twenty-three of the 25 BEA-treated rats without macroscopically evident RPN exhibited minor, histologically visible lesions of the renal papillae including necrosis of loops of Henle in the presence of intact collecting ducts. Only 2 of these animals exhibited tiny, unilateral cortical scars, and renal weights did not differ significantly from those of controls. It may therefore be concluded, contrary to certain published proposals: that experimental RPN may be followed by severe renal cortical scarring, reduction in renal size and (in the presence of asymmetrical lesions) compensatory renal hypertrophy, and that necrosis of thin limbs of loops of Henle does not appear to lead to frequent or severe cortical scarring.

Pathology of analgesic nephropathy: Australian experience

Analgesic nephropathy was first studied in Switzerland and Scandinavia, and most observers thought that papillary necrosis, a feature of the pathology, was the result of chronic interstitial nephritis, the other principal feature. From 1962, reports indicated a high incidence of analgesic nephropathy in Australia and suggested that papillary changes preceded cortical damage. Later, associated uroepithelial carcinoma was noted. Early papillary lesions consist of necrosis of elements around groups of collecting ducts. Necrosis extends upward through the medulla from the papilla and gradually intensifies to total papillary destruction. Fat and calcium accumulation and changes in matrix mucopolysaccharide are markers of papillary injury. Cortical atrophy is dependent upon collecting duct obstruction and is proportional to the degree of obstruction. Infection may complicate late pathologic changes. It is suggested that in the early stages the disease represents an injury to "concentrating columns" in the medulla.

Behavior of dental and surrounding structures following dental papillary injury--a histologic study in rats.

Recent studies of rat incisors, in which the dental papilla has suffered different intensities of injury, showed several pathological alterations of the continuously developing teeth. FERGUSON & LAWTON [1] verified a well localized reaction of the dental pulp and cessation of growth for 48 hours after injury of rats' lower incisors at the dental papilla level. After rats' upper incisors luxation [2], there were hyperemic vessels and quick recovery of the dental pulp. On the other hand, the tissue necrosis, enamel organ atrophy and tooth germs at the dental apical third could be seen after replanting and transplanting upper incisors of rats [3, 4]. These tooth germs, dental alveolus ankylosis and mineralized masses were related by DALLESTINI, OKAMOTO, CASTRO and SANTOS-PINTO [5], following dental fractures in rats.The purpose of the present study is to verify histologically the behavior of the rat dental pulp and papilla, faced with a more intense injury in comparison with that cited by FERGUSON & LAWTON [1]. Likewise, the clinical aspects of the gingival mucosa, dental crown, and growth of the same teeth are studied.