S100P immunostaining identifies a subset of peripheral‐type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas

Tsai J‐H, Huang W‐C, Kuo K‐T, Yuan R‐H, Chen Y‐L & Jeng Y‐M
(2012) Histopathology
S100P immunostaining identifies a subset of peripheral‐type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas Aims: S100P is a calcium‐binding protein that is frequently expressed in pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study was to investigate the pathological significance of the expression of S100P in peripheral intrahepatic cholangiocarcinoma (ICC). Methods and results: Immunohistochemical staining was used to investigate S100P expression in 112 cases of peripheral ICC. The results were compared with those for perihilar and extrahepatic cholangiocarcinomas. Patients with S100P‐positive peripheral ICC were more likely to have elevated serum levels of carcinoembryonic antigen (CEA) and CA19‐9 than those with S100P‐negative peripheral ICCs. All cases of peripheral ICC associated with intrahepatic lithiasis and all cases with intraductal/periductal growth patterns were positive for S100P. S100P‐positive peripheral ICCs were highly associated with ‘bile duct’ morphology rather than cholangiolar differentiation. Nearly all cases of perihilar and extrahepatic cholangiocarcinoma were positive for S100P. Similarly to perihilar and extrahepatic cholangiocarcinomas, S100P‐positive peripheral ICCs showed more frequent expression of CEA and MUC2, and were more likely to be N‐cadherin‐negative, than S100P‐negative cases. Notably, K‐RAS mutations were only detected in S100P‐positive peripheral ICCs, with a frequency similar to that in perihilar and extrahepatic cholangiocarcinomas. Patients with S100P‐positive peripheral ICC were more likely to have poor prognoses than those with S100P‐negative tumours. Conclusions: S100P immunostaining identifies a subset of peripheral ICC that probably originates from larger bile ducts. This subset of peripheral ICCs shares common morphological and molecular features with perihilar and extrahepatic cholangiocarcinomas.     

Additional benefit of combined therapy with melatonin and apoptotic adipose‐derived mesenchymal stem cell against sepsis‐induced kidney injury

This study tested whether combined therapy with melatonin and apoptotic adipose‐derived mesenchymal stem cells (A‐ADMSCs) offered additional benefit in ameliorating sepsis‐induced acute kidney injury. Adult male Sprague–Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal‐ligation and puncture (CLP), CLP‐melatonin, CLP‐A‐ADMSC, and CLP‐melatonin‐A‐ADMSC. Circulating TNF‐α level at post‐CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP‐melatonin than in CLP‐A‐ADMSC and CLP‐melatonin‐A‐ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper‐, cytoxic‐, and regulatory‐T cells at post‐CLP 72 hr exhibited the same pattern as that of circulating TNF‐α among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP‐melatonin than in CLP‐A‐ADMSC and CLP‐melatonin‐A‐ADMSC groups, and higher in CLP‐A‐ADMSC than in CLP‐melatonin‐A‐ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF‐1α, NF‐κB, MMP‐9, MIP‐1, IL‐1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF‐β) markers, reactive‐oxygen‐species (NOX‐1, NOX‐2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO‐1, NQO‐1+) were lowest in SC group and highest in CLP‐melatonin‐A‐ADMSC group, lower in CLP than in CLP‐melatonin and CLP‐A‐ADMSC groups, and lower in CLP‐melatonin‐ than in CLP‐A‐ADMSC‐tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A‐ADMSC was superior to A‐ADMSC alone in protecting the kidneys from sepsis‐induced injury.     

Microbial life at ?13 °C in the brine of an ice-sealed Antarctic lake

The permanent ice cover of Lake Vida (Antarctica) encapsulates an extreme cryogenic brine ecosystem (−13 °C; salinity, 200). This aphotic ecosystem is anoxic and consists of a slightly acidic (pH 6.2) sodium chloride-dominated brine. Expeditions in 2005 and 2010 were conducted to investigate the biogeochemistry of Lake Vida’s brine system. A phylogenetically diverse and metabolically active Bacteria dominated microbial assemblage was observed in the brine. These bacteria live under very high levels of reduced metals, ammonia, molecular hydrogen (H₂), and dissolved organic carbon, as well as high concentrations of oxidized species of nitrogen (i.e., supersaturated nitrous oxide and ∼1 mmol⋅L⁻¹ nitrate) and sulfur (as sulfate). The existence of this system, with active biota, and a suite of reduced as well as oxidized compounds, is unusual given the millennial scale of its isolation from external sources of energy. The geochemistry of the brine suggests that abiotic brine-rock reactions may occur in this system and that the rich sources of dissolved electron acceptors prevent sulfate reduction and methanogenesis from being energetically favorable. The discovery of this ecosystem and the in situ biotic and abiotic processes occurring at low temperature provides a tractable system to study habitability of isolated terrestrial cryoenvironments (e.g., permafrost cryopegs and subglacial ecosystems), and is a potential analog for habitats on other icy worlds where water-rock reactions may cooccur with saline deposits and subsurface oceans.     

Effects of Supraphysiological Testosterone Treatment and Orchiectomy on Ischemia/Reperfusion‐Induced Bladder Dysfunction in Male Rabbits

IntroductionThe roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages.AimTo elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery.MethodsMale New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 μg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries.Main Outcome MeasuresBladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers.ResultsI/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress‐related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor‐β and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries.ConclusionsTestosterone treatment or orchiectomy affected I/R‐induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.     

Erythema elevatum diutinum in systemic lupus erythematosus

Erythema elevatum diutinum (EED) is a rare chronic form of leukocytoclastic vasculitis with unknown etiology. EED has been described in association with hematological malignancies, infections and a number of rheumatological diseases. We report a patient with systemic lupus erythematosus (SLE) who presented with intermittent attacks of tender nodules and plaques on the shins and ankles for 6 months. Skin biopsy confirmed the diagnosis of EED. Treatment with dapsone resulted in complete resolution of the skin lesions. EED is rarely reported in SLE, and its presentation and treatment is reviewed.     

Interpretation and use of patient-reported outcome measures through a philosophical lens

Purpose

As patient-reported outcome measures (PROMs) increasingly become key outcome indicators in health care, there has been growing concern about the potential negative consequences that could result when interpretations are being made to inform clinical and policy decisions. Therefore, we explored theoretical issues, assumptions, and consequences of using PROMs from a philosophical point of view.

Methods

Our analysis of the literature was informed by Gadamerian hermeneutics, which emphasizes the dialectical processes that occur during interpretation, to provide insights as to how different users interpret and use standardized questions about health and quality of life.

Results

We structured our consideration according to three tenets of using PROMs: (1) the use of PROMs involves the interpretation of contextual elements; (2) interpretation of PROMs is an ongoing dialectical interaction; and (3) the use of PROMs involves openness and reflexivity. These findings suggest that hermeneutics provides a useful approach to examining the complexities of measuring patient-reported outcomes by attending to the perspectives of different users (e.g., patients, clinicians, administrators, and policy-makers) at the micro-, meso-, and macro-levels and the broader socio-historical and economic situation.

Conclusion

Because PROMs can have different meanings and are used for different purposes, we propose that hermeneutics be used as a lens to ask reflexive questions about the problems of measurement and open a pluralistic dialogue with respect to the way we use PROMs and the interpretations we make of the findings that derive from our studies.