Immunohistopathological Examination Research Articles

Gastrointestinal stromal tumor coexisting with disseminated peritoneal leiomyomatosis

BackgroundA case of gastrointestinal stromal tumor (GIST) coexisting with disseminated peritoneal leiomyomatosis (DPL) is rare. We report a case of GIST coexisting with DPL.Case presentationA 50-year-old woman underwent exploratory laparoscopy under a preoperative diagnosis of gastric GIST with an ovarian tumor or peritoneal dissemination in the pelvic space. Laparoscopy showed multiple peritoneal masses in the pelvic space. Intraoperative frozen sectioning of the pelvic tumors showed multiple spindle cells, suggesting leiomyomas or retroperitoneal tumors; however, it was difficult to rule out peritoneal dissemination from GIST. No disseminated lesion was noted near GIST, and hence, we believed that GIST and pelvic lesions had different origins. We achieved R0 resection by partial resection of the stomach, total hysterectomy, and bilateral salpingo-oophorectomy. The postoperative immunohistopathological examination confirmed the final diagnosis of GIST and DPL. The patient has been recurrence free for 10 years.ConclusionsImmunohistochemical examination is essential for correct diagnosis for GIST and DPL. R0 curative resection should be scheduled after immunohistochemical examination of specimens obtained from exploratory laparoscopy.

Ambrosin, a potent NF-κβ inhibitor, ameliorates lipopolysaccharide induced memory impairment, comparison to curcumin.

Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NF-κβ is a target for new therapeutics because it plays a pivotal role in the pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin, a sesquiterpene lactone which is a potent NF-κβ inhibitor, is scarcely studied in AD models. The current work aims to assess the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin. Memory impairment was induced in mice by single intraperitoneal injection of LPS (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κβp65 transcript and protein levels. Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNF-α, IL-1β, COX-2 and iNOS. BACE1 was inhibited, thereby reducing amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion, ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics.

Differential Hepatic Gene Expression and Antioxidant Activity in Male and Female Rats Induced by Subchronic Aflatoxicosis B1

Aflatoxin B1 (AFB1) is the most toxic mycotoxin that was proven to be deleterious to human and several animal species. Current work aimed at evaluating the sex-based differential hepatic genotoxic effect and the antioxidant activity as implications of subchronic aflatoxicosis B1. Albino rats were used that comprised two equal AFB1treated groups with AFB1 contaminated olive oil (50µg/kg) and a control group for each gender that received the vehicle only. Parts of animals’ livers were homogenized for gene expression assessment using quantitative RT-PCR and antioxidant activity analyses. Caspase-3 immunohistopathological examination was concomitantly undertaken. Results showed that AFB1 induced significant overexpression in cell cycle proliferation (ODC1), apoptosis (Aen), and antioxidant heme oxygenase (Hmox) genes in males alongside Bax (Bcl2- associated protein) under-expression. Meanwhile, female rats showed significant overexpression for (Hmox) and under-expression of Bax and Tnf (Tumor necrosis factor). Concomitant total hepatic antioxidant activity of liver homogenates showed a reduction in males, contrasting females. Degenerate vacuolated hepatocytes, polymorphic nuclei, cellular infiltration with concomitant Caspase-3 positive cells were profound findings in male rats. Hence, AFB1 is deferentially genotoxic at the given dose especially to male rats towards carcinogenicity, oxidative stress and apoptosis compared to a brief but compensated oxidative stress in females.

A previously undescribed cutaneous paraneoplastic syndrome in a cat with thymoma

Exfoliative dermatitis is a well-recognized cutaneous paraneoplastic syndrome (PNS) associated with thymoma in cats, of which the clinical and histopathological presentation has been well-characterized. To describe a novel clinical skin manifestation associated with thymoma in a cat. A 14-year-old neutered female domestic short hair cat. Physical, abdominal ultrasonographic, thoracic radiographic, ultrasonographic and computed tomographic examinations, histopathological assessment of the skin and mediastinal mass. The cat was presented with noninflammatory alopecia, with a dorsal multifocal distribution. Examination of the alopecic areas using a dermascope indicated an apparent lack of follicular ostia. Histopathological assessment of alopecic areas confirmed follicular and epidermal atrophy, trichilemmal keratinization and mild orthokeratotic hyperkeratosis. Diagnostic imaging revealed a mediastinal mass, which was surgically removed. Histopathological and immunohistopathological examination of the mass was consistent with a thymoma, associated with multiloculated cyst formation and multifocal cholesterol granulomas. Following surgery, hair re-growth was noted in the previously alopecic areas. The cat was euthanized 3.5months later because of recurrent chylothorax suspected to be a postoperative complication. The alopecic lesions had improved markedly. Thymoma-associated PNS might not always manifest as an exfoliative dermatitis and should be considered in the differential diagnosis of multifocal noninflammatory alopecia.

Possible role of angiogenesis suppression in rats model of non alcoholic fatty liver disease

Objective:to evaluate development of angiogenesis in rats of NAFLD and to determine the protective effects of antiangiogenic therapy (sorafenib) in preventing the progression of NAFLD. Methods: 45 Albino rats (200-300 g) were divided into 3 groups (15 rats for each): Group I: Control group fed on an ordinary diet. Group II: rats received high fat, high fructose diet (HFD,HFr) with DEN ( twice weekly for 8 weeks, ip). Group III: rats received HFD, HFr + DEN + sorafenib orally for 8 weeks. Biochemical, histopathologial, and immunohistopathological examination were studied. Results: high fat, high fructose diet with DEN resulted in a significant elevation in the serum cholesterol, TG, LDL, and AST, and ALT, significantly lower levels of HDL and Albumin together with a significant decrease in hepatic GSH, Histopathological examination revealed that liver of untreated rats showed severe fatty infilteration (grade3). Immunohistochemical examination of liver of untreated NAFLD rats showed strong staining reactions against VEGF, α- SMA, CD31, and Caspase3 antibodies. Oral administration of sorafenib alleviated all these parameters.

Bullous Systemic Lupus Erythematosus and Membranous Lupus Nephritis in a Filipino Child

Bullous eruptions are rare cutaneous manifestations of systemic lupus erythematosus. We report a case of an 8-year old Filipino girl with vesiculobullous systemic lupus erythematosus (SLE) and membranous lupus nephritis on kidney biopsy who presented with clinical nephrotic features of generalized edema, proteinuria, hypoalbuminemia and hyperlipidemia. The 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were met. Immunohistopathologic examination of the skin lesion revealed a sub-epidermal split with neutrophilic infiltrates along the dermo-epidermal junction, moderate perivascular, periadnexal and interstitial infiltrates composed of predominantly neutrophils with neutrophilic dusts, lymphocytes, plasma cells, rare eosinophils and increased dermal mucin. Direct immunofluorescence showed strong continuous linear IgG deposits along the basement membrane and weak linear IgM and IgA deposition along the basement membrane zone (BMZ). To our knowledge, this is the first report of vesiculobullous SLE in a Filipino child. This case is a rare form of cutaneous lupus in children. Bullous SLE (BSLE) should be considered in the differential diagnosis of children presenting with generalized bullous eruptions.

Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2.

Integrin ɑvβ3, an adhesion molecule overexpressed in neovascular endothelial cells, is involved in ocular angiogenesis. Integrin ɑvβ3-binding arginine-glycine-aspartic acid (RGD) peptide has been used to target and visualize new vessels. We explored the use of integrin ɑvβ3-targeted RGD peptide ([99mTc]IDA-D-[c(RGDfK)]2) for in vivo molecular imaging of choroidal neovascularization (CNV). To induce CNV in animals, the right eyes of C57BL/6 mice were treated with retinal argon laser photocoagulation. CNV formation was confirmed on immunohistopathological examination of retinal and choroidal tissues. To explore the association of integrin with angiogenesis, integrin mRNA expression in the retinal and choroidal tissues was measured using real-time reverse transcriptase-polymerase chain reaction. For in vivo imaging, mice were intravenously injected with [99mTc]IDA-D-[c(RGDfK)]2 and single-photon emission computed tomography (SPECT) images of [99mTc]IDA-D-[c(RGDfK)]2 were obtained before laser induction (baseline) and at 1, 3, 7, and 14days post-induction. CNV-induced regional alterations were measured using radiotracer uptake count. Immunohistopathological examination revealed that CNV lesions showed intense fluorescein isothiocyanate (FITC)-D-[c(RGDfK)]2 immunofluorescence, in contrast to the normal retina and choroid. Retinal integrin mRNA expression peaked at day 1 following CNV induction. On SPECT images using [99mTc]IDA-D-[c(RGDfK)]2, the radio-uptake count in eyes with CNV was significantly higher than in normal controls on days 1-7 (all p < 0.05), with a peak at day 3 representing the highest angiogenic activity. Our preclinical data demonstrated that [99mTc]IDA-D-[c(RGDfK)]2 can detect CNV and its associated angiogenesis in an animal model of CNV. SPECT imaging using an integrin ɑvβ3-targeted RGD peptide radiotracer may be a useful tool for in vivo functional molecular imaging of CNV.

Alpha-fetoprotein-producing rectal cancer successfully responded to preoperative chemoradiotherapy: case report

BackgroundAlpha-fetoprotein (AFP) is produced by some tumors, such as hepatocellular carcinoma and yolk sac tumors, leading to an increase in serum AFP level. However, AFP in colorectal cancer is extremely rare. Treatment for AFP-producing cancer is often performed according to conventional methods, but oncological outcomes of both surgery and chemotherapy are poor. We report a case of a patient with AFP-producing rectal cancer which successfully responded to preoperative chemoradiotherapy.Case presentationRectal tumor was diagnosed in a 68-year-old man referred to our hospital. Colonoscopy showed a type 2 tumor in the lower rectum, and biopsy revealed an adenocarcinoma with enteroblastic differentiation. Serum tumor marker levels were 8.8 ng/ml in carcinoembryonic antigen (CEA) and 28.3 ng/ml in AFP. Clinical diagnosis was stage IIIB (T3N1M0), and preoperative chemoradiotherapy was performed to prevent local recurrence. Effective tumor reduction was observed, and serum tumor marker levels decreased to normal range. Low anterior resection with temporary diverting ileostomy was performed, and histology revealed residual adenocarcinoma. Pathological diagnosis was stage I (T2N0M0). The tumor was found to be an AFP-producing adenocarcinoma on further immunohistopathological examination. The postoperative course was uneventful, and the patient received adjuvant chemotherapy for 3 months.ConclusionsThe outcomes of preoperative chemoradiotherapy against AFP-producing rectal cancer are reported here for the first time. Based on our experience with this patient, it appears preoperative chemoradiotherapy for patients with AFP-producing advanced rectal cancer is feasible.

Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.

Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). Patients who have HGPS exhibit ubiquitous progerin expression, accelerated aging and atherosclerosis, and die in their early teens, mainly of myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part, because of the lack of appropriate animal models. We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient (Apoe-/-) mice with LmnaG609G/G609G mice ubiquitously expressing progerin. To induce progerin expression specifically in macrophages or vascular smooth muscle cells (VSMCs), we crossed Apoe-/-LmnaLCS/LCS mice with LysMCre and SM22αCre mice, respectively. Progerin expression was evaluated by polymerase chain reaction and immunofluorescence. Cardiovascular alterations were determined by immunofluorescence and histology in male mice fed normal chow or a high-fat diet. In vivo low-density lipoprotein retention was assessed by intravenous injection of fluorescently labeled human low-density lipoprotein. Cardiac electric defects were evaluated by electrocardiography. Apoe-/-LmnaG609G/G609G mice with ubiquitous progerin expression exhibited a premature aging phenotype that included failure to thrive and shortened survival. In addition, high-fat diet-fed Apoe-/-LmnaG609G/G609G mice developed a severe vascular pathology, including medial VSMC loss and lipid retention, adventitial fibrosis, and accelerated atherosclerosis, thus resembling most aspects of cardiovascular disease observed in patients with HGPS. The same vascular alterations were also observed in Apoe-/-LmnaLCS/LCSSM22αCre mice expressing progerin specifically in VSMCs, but not in Apoe-/-LmnaLCS/LCSLysMCre mice with macrophage-specific progerin expression. Moreover, Apoe-/-LmnaLCS/LCSSM22αCre mice had a shortened lifespan despite the lack of any overt aging phenotype. Aortas of ubiquitously and VSMC-specific progerin-expressing mice exhibited increased retention of fluorescently labeled human low-density lipoprotein, and atheromata in both models showed vulnerable plaque features. Immunohistopathological examination indicated that Apoe-/-LmnaLCS/LCSSM22αCre mice, unlike Apoe-/-LmnaG609G/G609G mice, die of atherosclerosis-related causes. We have generated the first mouse model of progerin-induced atherosclerosis acceleration, and demonstrate that restricting progerin expression to VSMCs is sufficient to accelerate atherosclerosis, trigger plaque vulnerability, and reduce lifespan. Our results identify progerin-induced VSMC death as a major factor triggering atherosclerosis and premature death in HGPS.

IN VIVO ANTITUMOR ACTIVITY OF PHYTOCHEMICAL PITC-2 OBTAINED FROM TISSUE CULTURED PLANT PLUCHEA INDICA ON SARCOMA-180 SOLID TUMOR MICE MODEL

Objective: PITC-2 was isolated from the methanolic root extract of tissue cultured medicinal plant Pluchea indica (L.) Less. PITC-2 is a thiophene derivative which is 2-(Prop-1-ynyl)-5(5,6-dihydroxyhexa-1,3-diynyl)-thiophene. The main objective of the study is to evaluate the in vivo antitumor activity of PITC 2 against sarcoma-180 cancer cell in Swiss albino mice.Methods: The antitumor activity was evaluated by treatment with PITC-2 at a dose of 2.5 and 5 mg/kg b.w for 21 days on sarcoma-180 mice model. Cell viability was studied using 3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyl tetrazolium bromide assay and cell apoptosis, G1 cell cycle arrest and reduction in tumor cell proliferation were evaluated by histopathological analysis and Bcl-2, cyclic-D1, and Ki-67 protein expression through immunohistochemistry study.Results: Precisely, PITC-2 had a cytotoxic effect on various in vitro cancer cells. Significant decreases in solid tumor volume and weight along with increase lifespan also observed. The histopathological and immunohistopathological examination indicates that PITC-2 induces apoptosis, typical morphological changes and suppresses tumor cell proliferation along with G1 cell cycle arrest through the downregulation of the intratumoral expression of Bcl-2, cyclic D1, and Ki-67 and thus highlighting antiproliferative and apoptotic properties against sarcoma-180 in vivo solid tumor model.Conclusion: The present results clearly demonstrate that PITC-2 significantly inhibits sarcoma-180 cell growth in a dose-dependent manner in in vivo mice model. Besides this, the study reveals a comprehensive perception of the possible mechanism behind the antitumor activity of PITC-2 by significant changes in the morphological, hematological, biochemical parameters in sarcoma-180 cells.

Double pituitary adenomas associated with persistent trigeminal artery: a rare case report and the review of literature

Multiple pituitary adenomas are rare. We present a quite unique case of double pituitary adenomas associated with persistent trigeminal artery (PTA) treated by endoscopic surgery. To the best of our knowledge, this is the first report in the literature. A 64-year-old woman was referred to our hospital for suspicion of acromegaly. Preoperative magnetic resonance imaging revealed two separate intrasellar masses with intrasellar vascular structure. Right cerebral angiography showed medial-type PTA. The patient underwent endoscopic transsphenoidal surgery and both tumors were resected completely. Postoperative immunohistopathologic examination revealed two histologic types of adenoma: the first tumor was positive for growth hormone (GH), while the second was considered nonfunctioning. Postoperatively, the patient's serum levels of GH and insulin-like growth factor-1 returned to normal. We observed an extremely rare case of double pituitary adenomas associated with PTA. Preoperative neuroimaging and modern endoscopic surgery are valuable to confirm diagnosis of double pituitary adenomas and identify anatomical localization of PTA.

The protective role of tetramethylpyrazine against cisplatin-induced ototoxicity

ObjectivesThe aim of the present study was to investigate the protective effect of tetramethylpyrazine (TMP) on cisplatin-induced ototoxicity in rats. MethodsForty healthy, female, 24-week-old, Sprague-Dawley rats (n = 40) were randomly assigned to four groups as follows: group one (n = 10) received intraperitoneal (i.p.) physiological saline at daily doses of 3 mg/kg for seven days; group two (n = 10) received a single dose of i.p. 15 mg/kg cisplatin; group three (n = 10) received i.p. 140 mg/kg TMP daily for seven days plus a single dose of i.p. 15 mg/kg cisplatin on the fourth day; group four (n = 10) received i.p. 140 mg/kg TMP daily for seven days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements were obtained from the animals (40 rats, 80 ears) under general anesthesia before and after drug administration. The temporal bulla of animals were bilaterally removed for immunohistopathological examination. ResultsIn group two, DPOAE and ABR values were significantly deteriorated after drug administration, whereas there was no statistically significant difference between the pre- and posttreatment DPOAE and ABR values for all frequencies for groups one, three and four. The mean scores for external ciliated cells (ECCs), stria vascularis (SV) and spiral ganglion (SG) injuries in hematoxylin and eosin (H&E) staining, and also caspase-3 immunoreactivity were significantly higher in group two than in the other groups. ConclusionIn the present study, the protective effect of TMP on cisplatin ototoxicity was demonstrated through studies of electrophysiology and immunohistopathology. Co-administration of TMP may have potential protective effects against cisplatin-induced ototoxicity.

Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions.

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis.

リンパ節転移を認めた腫瘍径10mmの直腸Neuroendocrine tumorの1例

A 58-year-old woman visited our hospital with the complaint of bleeding on defecation. Colorectal endoscopy showed a 10-mm submucosal tumor with a slight central depression. Histopathological examination of biopsy specimens led to the diagnosis of rectal neuroendocrine tumor (NET) . Thoracoabdominal computed tomography did not reveal lymph node or distant metastasis. We performed endoscopic submucosal dissection. Immunohistopathological examination of the resected tumor led to the diagnosis of synaptophysin-positive, chromogranin-negative, CD56-positive grade 2 NET with a positive resection margin. Therefore, we additionally performed laparoscopic-assisted low anterior resection and lymphadenectomy. No remaining tumor was found in the resected ESD scar. Metastasis was identified in one (No. 251) of the 35 dissected lymph nodes. Her postoperative course was good, and she was discharged on the 12th hospital day. We report a case of a small rectal carcinoid tumor with lymph node metastasis with a literature review.

CD45 is a more sensitive marker than CD3 to diagnose lymphocytic myocarditis in the endomyocardium

To diagnose lymphocytic myocarditis (LM), immunohistopathological examination of endomyocardial biopsies (EMBs) is used with a cutoff value of at least 14 leukocytes per mm2, composed of CD3- and CD68-positive cells. We hypothesized that a more common leukocyte marker, CD45, instead of CD3 could increase the diagnostic sensitivity. Hearts of mice with acute viral myocarditis (n = 9) and of controls (n = 7) and the EMB sampling area of the left ventricular posterior wall (LVPW) obtained from autopsied hearts of patients diagnosed with LM (n = 18) and controls (n = 6) were stained with anti-CD68, anti-CD3, and anti-CD45. When applying the threshold of at least 14 leukocytes per mm2, 33% of the mice would be diagnosed with LM with the use of CD3+CD68 and 89% with the use of CD45+CD68. In the EMB sampling area of autopsied hearts, using the cutoff value of at least 14 leukocytes per mm2, CD3+CD68 could only confirm 17% of the diagnosis of LM, whereas CD45+CD68 could confirm 50% of the LM cases. Moreover, we compared inflammation in the EMB sampling area of the LVPW to the remaining myocardium of the LVPW and observed a significant increase of CD45+CD68 cells per mm2 in patients with LM. In conclusion, the use of the common leukocyte marker CD45 increases the sensitivity of the diagnosis of LM. Furthermore, the inflammatory infiltrate in the EMB sampling area is significantly increased compared with the remaining LVPW, indicating that the sampling area constitutes the highest chance for histological diagnosis of LM.

Poorly-differentiated signet-ring cell carcinoma of the ampulla of Vater: report of a rare malignancy.

Signet-ring cell carcinoma (SRCC) of the ampulla of Vater is a very rare clinical entity, which is infrequently reported in medical literature. A 78-year-old woman was admitted with jaundice, pruritus and postprandial vomiting. Abdominal ultrasound and computed tomography scanning demonstrated gross dilatation of the common bile and pancreatic ducts with gallbladder calculi. Endoscopic retrograde cholangiopancreatography suggested a duodenal tumour at the ampulla. The patient underwent Whipple's procedure with cholecystectomy. Immunohistopathological examination confirmed poorly-differentiated SRCC of the ampulla of Vater. The tumour had infiltrated the duodenal muscularis propria and pancreatic parenchyma, but local lymph nodes were clear (T3N0M0). The patient was disease-free at 6-month follow-up. We here report a case of poorly-differentiated SRCC of the Ampulla of Vater. The majority of patients with such tumours undergo pancreaticoduodenectomy, which affords good outcomes in early disease. However, owing to the rarity of cases, the exact prognosis of ampullary SRCC remains as yet undetermined.

Development of novel combined anticalcification protocols including immunologic modification for prolonged durability of cardiac xenograft: preclinical study using large-animal long-term circulatory models.

Cardiac xenografts are conventionally cross-linked with glutaraldehyde (GA) to impart tissue stability, reduce antigenicity, and maintain tissue sterility. However, GA-fixed xenografts are prone to calcification after long-term implantation in humans, because of phospholipids, free aldehyde groups, and residual antigenicity. We evaluated preclinical safety and efficacy using large-animal long-term circulatory models for our novel combined anticalcification protocol including immunological modification, which had been proven effective in small animal experiments. Bovine/porcine xenografts were treated with decellularization, immunological modification with α-galactosidase, GA fixation with organic solvent, and detoxification with glycine. Valve conduits made of these xenografts were transplanted into the pulmonary root of goats, and hemodynamic, radiological, immunohistopathological, and biochemical results were obtained for 12 months after implantation. Evaluation of echocardiography and cardiac catheterization demonstrated good hemodynamic status and function of the pulmonary xenograft valves. Durability of the xenografts was well preserved without calcification by specimen radiography and immunohistopathological examination. The calcium concentrations of the explanted xenografts were lower than the control xenografts. This preclinical study using large-animal long-term circulatory models demonstrated that our synergistic and simultaneous employment of multiple anticalcification therapies and novel tissue treatments, including immunological modifications, have promising safety and efficacy and should be examined further in future clinical studies.

Possible Involvement of Keratinocyte Growth Factor in the Persistence of Hyperpigmentation in both Human Facial Solar Lentigines and Melasma.

Possible Involvement of Keratinocyte Growth Factor in the Persistence of Hyperpigmentation in both Human Facial Solar Lentigines and Melasma.

Pseudoaneurysm Formation After Medtronic Freestyle Porcine Aortic Bioprosthesis Implantation: A Word of Caution

A growing literature describes aneurysmal deterioration after implantation of the stentless porcine aortic Medtronic Freestyle bioprosthesis (MFB; Medtronic Inc, Minneapolis, MN), with some suggesting inadequate tissue fixation with immune response as a cause. However, disjointed reports make the significance of these findings difficult to interpret. We address this concern by aggregating available data. We reviewed institutional data, the Food and Drug Administration's Manufacturer and User Facility Device Experience registry, and the medical literature for mention of aneurysm or pseudoaneurysm after MFB. Case details were aggregated, and the rate of aneurysmal deterioration was estimated. Immunohistopathologic examination of institutional explanted specimens was performed to elucidate a cause. We found 42 cases of aneurysmal deterioration with adequate detail for analysis; all occurred with full root replacement and valve sizes ranging from 23 to 29 mm. The rate of aneurysmal deterioration considering all data sources was 1.1% (9 of 851; 95% confidence interval, 0.5% to 2.0%) vs 4.7% (4 of 86; 95% confidence interval, 1.3% to 11.5%) at our institution, where yearly surveillance imaging is performed. Rate of aneurysmal deterioration appeared constant until 5 years after the operation; however, events are reported out to 10 years. Consistent with previous reports, histopathology demonstrated an immune cell infiltrate in areas of MFB wall breakdown. Aneurysmal deterioration is an increasingly described complication of MFB implantation as a full root, with an incidence as high as 4.7%. Given the observed immune reaction and lack of occurrence in smaller (19-mm and 21-mm) valve sizes, inadequate pressure fixation of larger valves is a potential etiology. Patients with MFB require annual surveillance imaging, and consideration of this complication should factor into preoperative decision making because treatment mandates redo root replacement, which may not be feasible in high-risk patients.

Hemorrhagic Brain Metastasis of Endometrial Stromal Sarcoma

High-grade endometrial stromal sarcoma is a rare uterine malignancy. The cells of these tumors resemble endometrial cells in the proliferation stage, with many small plexiform arterioles. Herein we present a patient with endometrial stromal sarcoma that metastasized to the brain, along with the CT and MRI findings and a discussion of the surgical and histopathological features of the metastatic tumor. Immunohistopathological examination of the metastatic tumor showed a high mitotic rate and strong immunopositivity for CD10 and vimentin (as a mesenchymal marker); therefore, the lesion was considered to be high-grade endometrial stromal sarcoma. Due to the rarity of reported cases of metastatic brain tumors of high-grade endometrial stromal sarcoma, there isn’t a standard treatment protocol; however, metastatic tumors of high-grade endometrial stromal sarcoma match the same general concepts of brain metastasis. In addition, endometrial stromal sarcomas may be associated with hemorrhagic metastasis to the brain due to their pathologic characteristics.