Squamous-cell carcinoma developing within anal lichen planus

AIM: We present a case of squamous-cell carcinoma developing within perianal lichen planus. This is a chronic or recurrent cutaneous and/or mucosal dermatosis affecting less than 1 percent of the population. Neoplastic degeneration of cutaneous lichen planus is rare; only one case of squamous-cell carcinoma developing within perianal lichen planus has been described up until now in the international literature. CASE REPORT: Our case involved a 68-year-old woman with chronic, long-term lichen planus spreading all over the vulva and perianal region and the mucosa of the anal canal, where squamous-cell carcinoma developed within the perianal lichen planus. Treatment consisted of wide, circular excision of the perianal skin and mucosectomy of the anal canal up to as far as 1 cm above the dentate line. Reconstruction was performed by means of two V-Y bilateral subcutaneous flaps. CONCLUSION: Wide excision was performed not only to remove the squamous-cell carcinoma but also the lichen planus to prevent recurrence of metachronous or synchronous squamous-cell carcinoma. Follow-up at one year after surgery showed no local recurrence of either lichen planus or squamous-cell carcinoma, which suggests that surgical removal should be the therapy of choice for long-term, chronic perianal lichen planus that has proved to be resistant to medical therapy.     

Adenosine affects expression of membrane molecules,cytokine and chemokine release,and the T-cell stimulatory capacity of human dendritic cells

Dendritic cells (DCs) express functional purinergic type 1 receptors, but the effects of adenosine in these antigen-presenting cells have been only marginally investigated. Here, we further characterized the biologic activity of adenosine in immature DCs (iDCs) and lipopolysaccharide (LPS)-matured DCs (mDCs). Chronic stimulation with adenosine enhanced the macropinocytotic activity and the membrane expression of CD80, CD86, major histocompatibility complex (MHC) class I, and HLA-DR molecules on iDCs. Adenosine also increased LPS-induced CD54, CD80, MHC class I, and HLA-DR molecule expression in mDCs. In addition, adenosine dose-dependently inhibited tumor necrosis factor alpha and interleukin-12 (IL-12) release, whereas it enhanced the secretion of IL-10 from mDCs. The use of selective receptor agonists revealed that the modulation of the cytokine and cell-surface marker profile was due to activation of A(2) adenosine receptor. Functionally, adenosine reduced the allostimulatory capacity of iDCs, but not of mDCs. More important, DCs matured in the presence of adenosine had a reduced capacity to induce T helper 1 (Th1) polarization of naive CD4(+) T lymphocytes. Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDCs. In aggregate, the results provide initial evidence that adenosine diminishes the capacity of DCs to initiate and amplify Th1 immune responses.     

TIPS for acute and chronic Budd-Chiari syndrome: a single-centre experience

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a technically challenging but feasible treatment for Budd-Chiari syndrome (BCS). However, information about the outcome, particularly in patients with liver failure, is scarce. We report our experience of TIPS for BCS. METHODS: Fifteen patients with BCS underwent TIPS. Eight had hepatic failure and seven underwent TIPS for BCS uncontrolled by medical treatment. RESULTS: Fourteen out of 15 had successful TIPS placement. Out of the eight hepatic failure patients, four died soon after TIPS: one liver rupture, one portal vein rupture, one liver failure and one pulmonary oedema. Another patient had a significant intrahepatic haematoma, which resolved with conservative management. TIPS was successfully placed in all of the seven patients with chronic BCS, in whom there was an average follow-up of 20 months. Ascites resolved and liver function improved in all. One patient died after 18 months from the original hepatic metastatic disease. Four patients have had evidence of TIPS dysfunction requiring three balloon dilatations and one restenting. No patient has required liver transplantation. CONCLUSIONS: TIPS should be the first line treatment for BCS uncontrolled by medical therapy. However, mortality in BCS with hepatic failure is high and liver transplantation could be a better option.     

Effect of Anti-TNF Therapy and Vitamin D Derivatives on the Proliferation of Peripheral Blood Mononuclear Cells in Crohn's Disease

Infliximab treatment demonstrated clinical and endoscopic benefits in active refractory and fistulizing Crohn's disease. The aim of this research was to investigate the proliferative response of peripheral blood mononuclear cells (PBMC) obtained from patients with active and fistulizing Crohn's disease treated with infliximab therapy. PBMC proliferation and VDR protein levels were also studied when 1,25(OH)2D3 or its analogues (EB 1089, KH 1060) were added to cells cultures. At day 5 of culture, the proliferation of PBMC obtained from patients responsive to the therapy showed a remarkable decrease (about 60%) at T6 (after two infusions) with respect to T0 (before the first infusion). On the contrary, in the unresponsive patient, the proliferative response was four times higher at T6 in comparison with T0. Vitamin D derivatives induced a decrease in cell proliferation higher in responsive patients than in the unresponsive one. Increased VDR levels during therapy were registered only in the unresponsive patient. Our results indicate that PBMC proliferation and VDR expression may be useful indicators to predict the response of patients with Crohn's disease to the infliximab therapy.     

Recurrent aortic aneurysms following thoracic aortic stent-graft repair in a patient with Cogan syndrome.

PURPOSE: To report the need for multiple surgical interventions to treat recurrent aortic aneurysms in a patient with Cogan syndrome. CASE REPORT: A 17-year-old Chinese man with clinical Marfanoid features had a left common carotid artery pseudoaneurysm electively repaired with an autologous saphenous vein graft. Four months later, he presented with acute chest pain. Computed tomography (CT) revealed a 1-cm pseudoaneurysm at the mid descending aorta; a 24 x 100-mm Talent stent-graft was implanted to exclude the pseudoaneurysm. He was also found to have increasing left-sided hearing loss. A month later, the patient was re-admitted with vertigo and keratitis, which were treated appropriately. Nine months following stent-graft insertion, he was admitted with acute hemoptysis. Urgent CT showed a rupture at the proximal end of the stent-graft, with hemorrhage into the lung parenchyma. In an emergent procedure, the stent-graft was removed, and the descending thoracic aorta was repaired. Intraoperatively, a large pseudoaneurysm was found arising from the proximal part of the stented aorta, which appeared thickened. His postoperative recovery was uneventful. Nine months after the thoracotomy, a routine CT revealed an aneurysm at the distal descending thoracic aorta. On re-thoracotomy, a de novo saccular aneurysm was found 2.5 cm from the distal anastomosis. The affected segment was replaced with a Dacron graft. The distal aorta appeared thickened and edematous; histology confirmed aortitis. The patient was subsequently diagnosed with Cogan syndrome and given corticosteroids and methotrexate. There is no evidence of recurrence at nearly 2 years after the last intervention. CONCLUSION: This case highlights the pitfalls of stent-graft repair in a patient with presumed connective tissue disease.     

SRC homology-2-containing protein tyrosine phosphatase-1 restrains cell proliferation in human medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells, where, in the inherited form, constitutive activation of the RET protooncogene is responsible for unrestrained cell proliferation. We previously demonstrated that somatostatin (SRIF) reduces cell growth in the human MTC cell line TT, which expresses all SRIF receptor (SSTR) subtypes and responds differently to selective SSTR agonists. The antiproliferative mechanism of SRIF and its analogs in MTC is still unclear. Src homology-2-containing protein tyrosine phosphatase-1 (SHP-1), a cytoplasmic protein tyrosine phosphatase (PTP), is activated by somatotropin release-inhibiting factor and reduces mutated RET autophosphorylation in a heterologous system. In this study, we explore the role of PTP activation, in particular of SHP-1, in TT cells, where RET is constitutively activated. In TT cells, SRIF stimulated the PTP activity of SHP-1, which was associated with proliferation inhibition and with reduction in the MAPK pathway activation. Blockade of PTP activity with sodium orthovanadate induced cell proliferation and MAPK phosphorylation and blunted the inhibitory effects of SRIF. Moreover, SHP-1 associates with SSTR2 depending on its activation. By using a MAPK kinase inhibitor, we demonstrated that TT cell growth depends on MAPK pathway activation. Furthermore, in TT cells overexpressing SHP-1, cell proliferation and MAPK signaling were strongly down-regulated, whereas in TT cells transfected with a dominant negative form of SHP-1, cell proliferation and MAPK signaling were markedly induced. Our data demonstrate that SRIF inhibitory effects on TT cell proliferation are mediated, at least in part, by SHP-1, which acts through a MAPK-dependent mechanism.     

Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome

Introduction and objectives

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.

High-Value,Cost-Conscious Care Attitudes in the Graduate Medical Education Learning Environment: Various Stakeholder Attitudes That Residents Misjudge

BackgroundTraining residents in delivering high-value, cost-conscious care (HVCCC) is crucial for a sustainable healthcare. A supportive learning environment is key. Yet, stakeholders’ attitudes toward HVCCC in residents’ learning environment are unknown.ObjectiveWe aimed to measure stakeholders’ HVCCC attitudes in residents’ learning environment, compare these with resident perceptions of their attitudes, and identify factors associated with attitudinal differences among each stakeholder group.DesignWe conducted a cross-sectional survey across the Netherlands between June 2017 and December 2018.ParticipantsParticipants were 312 residents, 305 faculty members, 53 administrators, and 1049 patients from 66 (non)academic hospitals.Main MeasuresRespondents completed the Maastricht HVCCC Attitude Questionnaire (MHAQ), containing three subscales: (1) high-value care, (2) cost incorporation, (3) perceived drawbacks. Additionally, resident respondents estimated the HVCCC attitudes of other stakeholders, and answered questions on job demands and resources. Univariate and multivariate analyses were used to analyze data.Key ResultsAttitudes differed on all subscales: faculty and administrators reported more positive HVCCC attitudes than residents (p ≤ 0.05), while the attitudes of patients were less positive (p ≤ 0.05). Residents underestimated faculty’s (p < 0.001) and overestimated patients’ HVCCC attitudes (p < 0.001). Increasing age was, among residents and faculty, associated with more positive attitudes toward HVCCC (p ≤ 0.05). Lower perceived health quality was associated with less positive attitudes among patients (p < 0.001). The more autonomy residents perceived, the more positive their HVCCC attitude (p ≤ 0.05).ConclusionsAttitudes toward HVCCC vary among stakeholders in the residency learning environment, and residents misjudge the attitudes of both faculty and patients. Faculty and administrators might improve their support to residents by more explicitly sharing their thoughts and knowledge on HVCCC and granting residents autonomy in clinical practice.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06261-8) contains supplementary material, which is available to authorized users.KEY WORDS: attitudes, graduate medical education, high-value, cost-conscious care, learning environment, job characteristics