Background & Aims: Immunoglobulin (Ig)G4-associated cholangitis (IAC) is the biliary manifestation of a steroid-responsive multisystem fibroinflammatory disorder in which affected organs have a ...characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells. We describe clinical features, treatment response, and predictors of relapse in IAC and compare relapse rates in IAC with intrapancreatic vs proximal bile duct strictures. Methods: We reviewed clinical, serologic, and imaging characteristics and treatment response in 53 IAC patients. Results: IAC patients generally were older (mean age, 62 y) men (85%), presenting with obstructive jaundice (77%) associated with autoimmune pancreatitis (92%), increased serum IgG4 levels (74%), and abundant IgG4-positive cells in bile duct biopsy specimens (88%). At presentation, biliary strictures were confined to the intrapancreatic bile duct in 51%; the proximal extrahepatic/intrahepatic ducts were involved in 49%. Initial presentation was treated with steroids (n = 30; median follow-up period, 29.5 months), surgical resection (n = 18; median follow-up period, 58 months), or was conservative (n = 5; median follow-up period, 35 months). Relapses occurred in 53% after steroid withdrawal; 44% relapsed after surgery and were treated with steroids. The presence of proximal extrahepatic/intrahepatic strictures was predictive of relapse. Steroid therapy normalized liver enzyme levels in 61%; biliary stents could be removed in 17 of 18 patients. Fifteen patients treated with steroids for relapse after steroid withdrawal responded; 7 patients on additional immunomodulatory drugs remain in steroid-free remission (median follow-up period, 6 months). Conclusions: IAC should be suspected in unexplained biliary strictures associated with increased serum IgG4 and unexplained pancreatic disease. Relapses are common after steroid withdrawal, especially with proximal strictures. The role of immunomodulatory drugs for relapses needs further study.
Background & Aims Autoimmune pancreatitis (AIP) and pancreatic cancer (PaC) have similar presentations; a diagnostic strategy is needed to distinguish the 2 diseases. Methods We compared computed ...tomography images (for pancreas and other organ involvement), serum IgG4 levels, histology data, and the response to steroids between patients with AIP (n = 48) and those with PaC (n = 100). Results Pancreatic imaging findings stratified patients into 3 groups. Group 1 was highly suggestive of AIP, with diffuse pancreatic enlargement without group 3 features (n = 25, 100% AIP). Group 2 was indeterminate, with normal-sized pancreas or focal pancreatic enlargement without group 3 features (n = 20, 75% AIP). Group 3 was highly suggestive of PaC, with presence of >1 low-density mass, pancreatic duct cutoff, or upstream pancreatic atrophy (n = 103, 92% PaC). Although all patients in group 1 had AIP, only 20 of the 25 patients had increased serum IgG4 levels and/or other organ involvement. Of the patients in groups 2 and 3 who did not have cancer, all those with serum IgG4 levels >2-fold the upper limit of normal or a combination of increased serum IgG4 levels and other organ involvement (n = 15) had AIP. In AIP subjects without supportive serologic evidence or other organ involvement (n = 14), diagnosis required pancreatic core biopsy (n = 7), steroid trial (n = 5), or resection (n = 2). Conclusions PaC can be distinguished from AIP by pancreatic imaging, measurement of serum IgG4 levels, and determination of other organ involvement. However, a pancreatic core biopsy, steroid trial, or surgery is required for diagnosis in approximately 30% of patients with AIP. To view this article's video abstract, go to the AGA's YouTube Channel.
To assess the combination of scleral buckling (SB) and pars plana vitrectomy (PPV) versus PPV alone in the primary repair of rhegmatogenous retinal detachments (RRDs).
The current study was a ...retrospective, comparative, interventional, consecutive case series of 179 eyes of 174 patients who underwent primary RRD repair by five surgeons between January 1, 2008 and December 31, 2010, utilizing SB with PPV or PPV. Univariate and multivariate analyses were used to compare the efficacy of the two surgical strategies and assess for risk factors of proliferative vitreoretinopathy (PVR).
Single surgery anatomic success (SSAS) was similar (
=0.76) between the PPV group (112 of 132 eyes, 85%) and SB with PPV group (39 of 47 eyes, 83%). Final anatomic success was 100% in each group. There was no difference in rates of PVR formation (PPV 16% vs SB with PPV 19%,
=0.70). Final logarithm of the minimum angle of resolution acuity was 0.33 (20/43) in the PPV group and 0.37 (20/47) in the SB with PPV group (
=0.62). Postoperative anterior chamber fibrin was highly correlated with PVR formation (PVR 13% vs no PVR 0.7%,
=0.003; odds ratio =68.37,
=0.007). Separate analysis of medium- to high-complexity cases showed similar SSAS (PPV 86% vs SB with PPV 83%,
=0.45).
SB with PPV versus PPV alone were similarly efficacious for repair of primary RRDs of varying complexity. SSAS rates, PVR incidence, and final visual acuities were not significantly different.
Background & Aims: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and ...survival with histology, extent of resection, and duration of follow-up. Methods: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. Results: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23–75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). Conclusions: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete “curative” resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.
GASTROENTEROLOGY 2002;123:1500-1507
Background: We previously used a three-dimensional (3D) reconstituted basement membrane (rBM) assay to demonstrate that tumorigenic HMT-3522 T4–2 human breast cells can be induced to form ...morphologically normal structures (“reversion”) by treatment with inhibitors of β1 integrin, the epidermal growth factor receptor (EGFR), or mitogen-activated protein kinase (MAPK). We have now used this assay to identify reversion and/or death requirements of several more aggressive human breast cancer cell lines. Methods: Breast tumor cell lines MCF7, Hs578T, and MDA-MB-231 were cultured in 3D rBM and treated with inhibitors of β1 integrin, MAPK, or phosphatidylinositol 3-kinase (PI3K). MDA-MB-231 cells, which lack E-cadherin, were transfected with an E-cadherin cDNA. The extent of reversion was assessed by changes in morphology and polarity, growth in 3D rBM or soft agar, level of invasiveness, and tumor formation in nude mice. Results: All three cell lines showed partial reversion (MCF7 the greatest and Hs578T the least) of tumorigenic properties treated with a single β1 integrin, MAPK, or PI3K inhibitor. Combined inhibition of β1 integrin and either PI3K or MAPK resulted in nearly complete phenotypic reversion (MDA-MB-231, MCF7) or in cell death (Hs578T). E-cadherin-transfected MDA-MB-231 cells showed partial reversion, but exposure of the transfectants to an inhibitor of β1 integrin, PI3K, or MAPK led to nearly complete reversion. Conclusion: The 3D rBM assay can be used to identify signaling pathways that, when manipulated in concert, can lead to the restoration of morphologically normal breast structures or to death of the tumor cells, even highly metastatic cells. This approach may be useful to design therapeutic intervention strategies for aggressive breast cancers.
Chronic low back pain is a worldwide leading cause of pain and disability. Degenerative disc disease has been the presumptive etiology in the majority of cases of chronic low back pain (CLBP). More ...recent study and treatments have discovered that the vertebral endplates play a large role in CLBP in a term defined as vertebrogenic back pain. As the vertebral endplates are highly innervated via the basivertebral nerve (BVN), this has resulted in a reliable target in treating patients suffering from vertebrogenic low back pain (VLBP). The application of BVN ablation for patients suffering from VLBP is still in its early stages of adoption and integration into spine care pathways. BVN ablation is grounded in a solid foundation of both pre-clinical and clinical evidence. With the emergence of this therapeutic option, the American Society of Pain and Neuroscience (ASPN) identified the need for formal evidence-based guidelines for the proper identification and selection of patients for BVN ablation in patients with VLBP. ASPN formed a multidisciplinary work group tasked to examine the available literature and form best practice guidelines on this subject. Based on the United States Preventative Task Force (USPSTF) criteria for grading evidence, gives BVN ablation Level A grade evidence with high certainty that the net benefit is substantial in appropriately selected individuals. Keywords: back pain, vertebrogenic pain, lumbar degenerative disc, radiofrequency ablation, basivertebral nerve, guidelines
Abstract Background/Aims: We evaluated the impact of the initial intravenous fluid resuscitation rate within the first 24 h of presentation to the emergency room on important outcomes in severe acute ...pancreatitis. Methods: Patients presenting directly with a diagnosis of severe acute pancreatitis were identified retrospectively. Patients were divided into two groups — those who received ≥.33% (‘early resuscitation’) and <33% (‘late resuscitation’) of their cumulative 72-hour intravenous fluid volume within the first 24 h of presentation.The primary clinical outcomes were in-hospital mortality, development of persistent organ failure, and duration of hospitalization. Results: 17 patients were identified in the ‘early resuscitation’ group and 28 in the ‘late resuscitation’ group and there were no baseline differences in clinical characteristics between groups. Patients in the ‘late resuscitation’ group experienced greater mortality than those in the ‘early resuscitation’ group (18 vs. 0%,p<0.04) and demonstrated a trend toward greater rates of persistent organ failure (43 vs. 35%, p = 0.31). There was no difference in the total amount of fluid given during the first 72 h. Conclusions: Patients with severe acute pancreatitis who do not receive at least one third of their initial 72-hour cumulative intravenous fluid volume during the first 24 h are at riskfor greater mortality than those who are initially resuscitated more aggressively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The diagnosis of autoimmune pancreatitis can be difficult and often requires a larger specimen than can be provided by FNA alone to determine if the tissue sample obtained with EUS trucut biopsy ...(TCB) is sufficient to allow adequate histologic review to establish the diagnosis of autoimmune pancreatitis.
EUS TCB was performed in patients presenting with obstructive jaundice who were suspected of having autoimmune pancreatitis based on their clinical, laboratory and imaging studies. The charts were retrospectively reviewed to determine the feasibility of TCB.
Between August 2002 and June 2004, 3 patients with obstructive jaundice and suspected autoimmune pancreatitis (AIP) underwent EUS TCB. In each case, a diagnosis of pancreatic cancer also was considered, and surgical resection was the planned therapy before the patient underwent EUS TCB. Histologic review of the TCB specimens established the diagnosis of AIP in two patients and identified nonspecific changes of chronic pancreatitis in the third patient. EUS-guided FNA was performed in two of the 3 patients and failed to establish the diagnosis in either patient. Other than mild transient abdominal pain (n
=
1), no complications were identified.
This preliminary study suggests that EUS TCB can safely establish the diagnosis of AIP. Doing so helps guide management and may help to avoid unnecessary surgery. Prospective studies are needed to verify these findings and to more clearly define the role of EUS TCB in these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Clinical interventions targeting nonlipid risk factors are needed given the high residual risk of atherothrombotic events despite effective control of dyslipidemia. Dickkopf-1 (DKK1) plays a ...lipid-independent role in vascular pathophysiology but its involvement in atherosclerosis development and its therapeutic attractiveness remain to be established.
Patient data, in vitro studies and pharmacological intervention in murine models of atherosclerosis were utilized.
In patients' material (n = 127 late stage plaque specimens and n = 10 control vessels), DKK1 mRNA was found to be higher in atherosclerotic plaques versus control arteries. DKK1 protein was detected in the luminal intimal area and in the necrotic core of plaques. DKK1 was released from isolated primary human platelets (~12 - 21-fold) and endothelial cells (~1.4–2.5-fold) upon stimulation with different pathophysiological stimuli. In ApoE−/− and Ldlr−/− mice, plasma DKK1 concentrations were similar to those observed in humans, whereas DKK1 expression in different atheroprone arterial segments was very low/absent. Chronic treatment with a neutralizing DKK1 antibody effectively reduced plasma concentrations, however, plaque lesion area was not reduced in ApoE−/− and Ldlr−/− mice fed a western diet for 14 and 16 weeks. Anti-DKK1 treatment increased bone volume and bone mineral content.
Functional inhibition of DKK1 with an antibody does not alter atherosclerosis progression in classical murine models. This may reflect the absence of DKK1 expression in plaques and more advanced animal disease models could be needed to evaluate the role and therapeutic attractiveness of DKK1 in late stage complications such as plaque destabilization, calcification, rupture and thrombosis.
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•Dickkopf-1 (DKK1) was found to be present in human atherosclerotic plaques.•Human platelets and endothelial cells release DKK1 upon pathophysiological stimulation.•In murine models of atherosclerosis, DKK1 was present in plasma but not the vascular tissue.•Inhibition of DKK1 with a neutralizing antibody did not reduce atherosclerotic plaque development in mice.•More advanced animal models may be needed to evaluate the role and therapeutic attractiveness of DKK1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
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