Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Tuberculous Pericarditis Mimicking a Malignant Pericardial Tumor: A Case Report.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

15-Prostaglandin Dehydrogenase Inhibition Enhances Colon Cancer Metastasis by Up-regulation of Epithelial-to-Mesenchymal Transition Genes.

BACKGROUND/AIM: Most deaths from colon cancer are due to metastasis. Recently, PGE2 was found to influence colon cancer invasion and metastasis. 15-PGDH, an enzyme that metabolizes PGE2, is known as a tumor suppressor in colonic carcinogenesis. This study investigated the effect of 15-PGDH on colon cancer metastasis. MATERIALS AND METHODS: 15-PGDH expression by immunohistochemical staining, clinicopathologic features, and 5-year cancer-specific survival were investigated in colon cancer patients. Liver metastasis was examined by assaying 15-PGDH activity in an animal model. Changes in PGE2, proliferation, migration, and invasion of the colorectal cancer cell line HCT116, were examined using a 15-PGDH inhibitor (SW033291) or enhancer (CDDO-ME). The expression of genes involved in the epithelial-to-mesenchymal transition (EMT) was also studied. RESULTS: The absence of 15-PGDH expression significantly correlated with advanced-stage, lymph node metastasis, and decreased cancer-specific survival in colon cancer patients. Inhibition of 15-PGDH increased colon cancer liver metastasis in the animal model. The 15-PGDH inhibitor, SW033291, increased PGE2 and decreased 15-PGDH expression on HCT116. However, treatment with CDDO-ME, a substance that enhances 15-PGDH, showed the opposite results. Inhibition of 15-PGDH increased cell proliferation, migration, and invasion, but activation of 15-PGDH showed the opposite effect. Inhibition of 15-PGDH also affected the EMT markers, N-cadherin, Snail, and Twist2. CONCLUSION: 15-PGDH inhibition increased colon cancer metastasis by inducing changes in EMT-related genes via an increase in PGE2 expression and could be a promising biomarker for anticancer treatment.

Retropharyngeal chordoma extending to the spinal cord, mimicking a neurogenic tumor: a case report and literature review.

Chordomas are rare, locally aggressive bone malignancies with poor prognoses. However, those with minimal or no bone involvement are more easily resectable because of their well-delineated margins and thus have better prognoses. Such extraosseous chordomas of the spine are localized both intradurally and extradurally. Only a few case reports have focused on extraosseous, extradural spinal chordomas. Radiologically, this type of chordoma has a dumbbell shape; however, dumbbell-shaped spinal tumors are traditionally thought to be neurogenic tumors (i.e., schwannomas or neurofibromas). We herein report a unique case involving a woman with a dumbbell-shaped extraosseous chordoma protruding predominantly into the retropharyngeal space. A 44-year-old woman presented for evaluation of a left submandibular mass. A T2-hyperintense, gadolinium-enhancing mass was found in her cervical spinal canal, protruding through the C2/3 neural foramen into the retropharyngeal space with minimal vertebral involvement. The initial diagnosis was a neurogenic tumor, most likely a schwannoma. After subtotal removal, the pathologic diagnosis was a chordoma. Because chordomas and schwannomas have significantly different prognoses, caution is warranted when a dumbbell-shaped tumor is identified in the spine with minimal or no vertebral deterioration on radiology. This report also provides the first thorough review of extraosseous dumbbell-shaped intraspinal-extraspinal chordomas.

15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury.

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.

Enlightening the Immune Mechanism of the Abscopal Effect in a Murine HCC Model and Overcoming the Late Resistance With Anti-PD-L1.

PURPOSE: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study. METHODS AND MATERIALS: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) ß expression was confirmed through polymerase chain reaction. RESULTS: After investigation, the intratumoral transcription of type Ⅰ IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8+ T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance. CONCLUSIONS: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model.

Inhibition of 15-PGDH prevents ischemic renal injury by the PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A receptors.

In the present study, we demonstrated the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia-reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. PGE2 is vasodilatory in the kidney, but it is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury scores and tubular apoptosis and markedly reduced biomarkers of renal injury that included blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high-mobility group box 1, and malondialdehyde. Protective effects of SW033291 were mediated by PGE2 signaling, as they could be blocked by pharmacological inhibition of PGE2 synthesis. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 receptors and cAMP, along with other vasodilatory effectors, including AMP, adenosine, and the adenosine A2A receptor. The protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Inhibition of 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.

An Animal Model of Colorectal Cancer Liver Metastasis With a High Metastasis Rate and Clonal Dynamics.

BACKGROUND: Various animal models have been introduced into the study of liver metastasis of colorectal cancer, but they have not been compared under the same conditions. The aim of this study was to identify an optimized mouse model that showed a high rate of hepatic metastasis and expression of clonal dynamics. MATERIALS AND METHODS: Athymic nude mice (n=30) were divided into two equal groups for the creation of a splenic injection model (SIM) and surgically orthotopic implantation model (SOIM) of liver metastasis of colorectal cancer using HCT116 cells. Hepatic metastasis was confirmed by gross and microscopic examinations. Expression of MET transcriptional regulator MACC1 (MACC1) in colon cancer cell lines and metastatic tumors in the group with a higher liver metastasis rate was confirmed by quantitative reverse-transcription-polymerase chain reaction. RESULTS: The observation time was significantly shorter for SIM than for SOIM (33.0±6.8 vs. 41.2±7.2 days, p<0.001). The rate of hepatic metastasis was significantly higher in SIM than in SOIM (76.9% vs. 38.4%, p=0.038). MACC1 was expressed in Colo201, HCT116, HT29, LS513, SW620, and WiDr cells but not in SW480 cells. All hepatic metastases in SIM mice expressed MACC1, and metastatic HCT116 cells had significantly greater expression than did the original HCT116 cells (p<0.001). CONCLUSION: With a higher rate of hepatic metastasis with clonal dynamics in a shorter observation time than the SOIM, SIM appears to be a good animal model for identifying new targets and in drug development for colorectal cancer liver metastasis. SOIM should also be considered for the study of the full steps of metastasis.

Activation of the alternative complement pathway predicts renal outcome in patients with lupus nephritis.

OBJECTIVES: The aims of this study were to clarify the activation of complement pathways in patients with lupus nephritis (LN), and to elucidate the association between these complement activation types and clinical outcomes. METHODS: We enrolled 115 patients with biopsy-proven LN from 2003 to 2016 from the lupus cohort at the Busan Paik Hospital and the Jeju National University Hospital in Korea. The patients were divided into two groups based on the patterns of glomerular complements deposits. The presence of C1q, C4 and/or C3 deposits in the glomerulus was considered evidence for the activation of the classical pathway with or without alternative pathway activation (group 1, N = 93), and glomerular C3 deposition without C1q and C4 deposits was considered as a marker for the alternative pathway limited activation (group 2, N = 22). The study end point was progression of kidney disease defined as a ≥50% reduction in estimated glomerular filtration rate from baseline values or advancement to end-stage renal disease. RESULTS: The mean estimated glomerular filtration rate and median urine protein-to-creatinine ratio of the patients were 85.7 ± 32.4 mL/min/1.73 m2 and 3.1 g/g, respectively, at the time of kidney biopsy. Forty-nine patients (43%) had nephrotic range of proteinuria. Compared to group 1 patients, those in group 2 were older, were more likely to be males and were more hypertensive. In addition, plasma C3 and C4 levels were significantly lower in group 1 patients compared to those in group 2. Moreover, anti-dsDNA concentration was significantly higher in group 1 patients compared to those in group 2. The mean follow-up time was 5.4 ± 3.4 years. The rates of response to one-year immunosuppressive treatment were poorer in group 2 patients compared to those in group 1. During the follow-up time, the progression of kidney disease was significantly higher in group 2 than in group 1 patients. CONCLUSION: This study showed that there was alternative complement pathway limited activation in the renal tissue in a small number of patients with LN, and these patients had worse renal outcomes compared to patients with glomerular classical complement pathway activation with or without alternative pathway activation.

Two separate nodules of Merkel cell carcinoma occurring concomitantly on one cheek.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroectodermal carcinoma arising from mechanoreceptor Merkel cells. Multiple MCCs are even rarer. We report a case of two independent MCCs simultaneously present in the cheek of a patient, which were effectively and esthetically treated using a cheek flap. Punch biopsy performed in a 60-year-old woman admitted with a chief complaint of two skin-colored hard nodules in her left cheek, accompanied by an itching sensation, was suggestive of MCC. Accordingly, we performed sentinel lymph node biopsy through the modified Blair incision under general anesthesia, in cooperation with the head and neck surgery department. The defect was covered with a cheek flap by slightly extending the existing incision following wide excision with a safety margin of 1 cm. This paper is significant in that it introduces an effective reconstruction technique that maintains function using a cheek flap for the management of this rare case. In addition, this paper is the first to classify multiple MCCs according to the time of onset. We believe that this paper presents an effective alternative reconstruction technique with sentinel node biopsy through the modified Blair incision.

Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study.

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Morphologic pattern analysis of submucosal deformities identified by endoscopic ultrasonography for predicting the depth of invasion in early gastric cancer.

BACKGROUND: The aims of this study are to evaluate the usefulness of submucosal deformity pattern analysis with endoscopic ultrasonography (EUS) for predicting the depth of invasion in early gastric cancer (EGC) and the treatment results of endoscopic submucosal dissection (ESD). METHODS: The endoscopic and EUS parameters of 345 patients with endoscopically suspected EGC who underwent endoscopic or surgical resection between July 2012 and May 2017 were retrospectively reviewed. All patients were classified into three categories as follows according to the morphologic type of submucosal deformity identified by EUS: (1) no submucosal deformity, (2) wedge-shaped deformity, and (3) arch-shaped deformity. The presence of an arch-shaped submucosal deformity on EUS and an active endoscopic ulcer or surrounding mucosal fold convergence/clubbing on conventional endoscopy were defined as suggestive of deep submucosal cancer invasion (SCI). RESULTS: Upper location (p = 0.034) and the presence of an arch-shaped submucosal deformity on EUS (p < 0.001) were significant predictors of deep submucosal invasion, with the presence of an arch-shaped submucosal deformity showing the highest predictive value (odds ratio of 26.27). The overall diagnostic accuracy of EUS for predicting deep SCI was 83.5%, with a sensitivity of 84.0% and a specificity of 83.3%, which were significantly higher than those of conventional endoscopy. A larger lesion size and the presence of an arch-shaped submucosal deformity were significant factors associated with noncurative resection after ESD. CONCLUSIONS: Submucosal deformity pattern analysis with EUS can provide more accurate information than conventional endoscopy for predicting deep SCI. The presence of an arch-shaped submucosal deformity on EUS was an effective predictor of deep SCI and noncurative resection.

Overexpression of peroxiredoxin-3 and -5 is a potential biomarker for prognosis in endometrial cancer.

Endometrial cancer is the sixth most common cancer in women worldwide. Peroxiredoxins (PRDXs) are antioxidant enzymes that serve important roles in cell differentiation, proliferation, and apoptosis. In the present study, the potential associations between PRDX expression and endometrial cancer were investigated. The expression levels of various PRDX mRNAs were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in endometrial cancer tissues (n=26) and normal endometrial tissues (n=10). Additionally, the expression of PRDX isoforms was immunohistochemically examined in endometrial cancer tissues and adjacent normal endometrial tissues from 42 patients. Finally, the associations between high PRDX expression levels and clinicopathological features were examined in patients with endometrial cancer. Analysis of PRDX expression in endometrial cancer tissues and normal endometrial tissues by semi-quantitative RT-PCR showed that all PRDX isoforms had increased expression in the endometrial cancer tissues compared with that in the normal endometrium, and the differences in the expression levels of PRDX1 and PRDX3 between cancer and normal tissues were statistically significant (P=0.0015 and P=0.0134, respectively). Additionally, analysis of PRDX expression in endometrial cancer and paired normal endometrial tissues by immunohistochemistry showed strong cytoplasmic staining of PRDX3 and PRDX5 in cancer tissues, with high PRDX3 (25/42, 59.5%) and PRDX5 (32/42, 76.2%) appearing more frequently in endometrial cancer than in normal endometrial tissues (P=0.0001 and P=0.0023, respectively). Furthermore, high expression of PRDX5 was associated with advanced-stage endometrial cancer (P=0.0399). Although the 5-year survival rate was marginally higher in patients with low expression of PRDX3 and PRDX5, this result was not statistically significant. In summary, PRDX3 and PRDX5 are highly expressed in endometrial cancer and could be associated with advanced stage and poor prognosis. Therefore, these proteins may potentially be used as prognostic markers for endometrial cancer.

Collision Tumor Associated with Sarcomatoid Eccrine Porocarcinoma and Basal Cell Carcinoma.

A 'collision' tumor refers to the existence of two different neoplasms within the same tumor. Sometimes, the term 'biphasic tumor' is also used. However, a 'collision' tumor is defined as the occurrence of two neoplasms within proximity of each other yet maintaining distinctly defined, separate boundaries. In contrast, a 'biphasic' tumor demonstrates two or more phenotypically distinct neoplastic cell populations merging within the same space. Here, we report a case of collision tumor associated with sarcomatoid eccrine porocarcinoma and basal cell carcinoma arising in a 57-year-old male patient.

Simultaneous Development of Three Different Neoplasms of Trichilemmoma, Desmoplastic Trichilemmoma and Basal Cell Carcinoma Arising from Nevus Sebaceus.

Nevus sebaceus is a hamartoma of the sebaceous gland that occurs congenitally, from which various secondary tumors can arise with a prevalence of 5%-6%. Benign neoplasms commonly arise from nevus sebaceous, but they have a very low malignant potential. Two neoplasms may occasionally arise within the same lesion, but it is rare for three or more neoplasms to occur in a nevus sebaceus simultaneously. A 61-year-old male patient was admitted to our hospital for a 4 cm×2.5 cm growing tumor in a verrucous form arising within a periauricular nevus sebaceus in the post auricle of the left ear that had developed 30 years earlier. The nodule was diagnosed as 3 different types of tumors: trichilemmoma, desmoplastic trichilemmoma, and basal cell carcinoma. To our knowledge, this is the first report of the coexistence of three different tumors arising from nevus sebaceous. It contain malignant neoplasm also. Surgeons should be aware of the need for close monitoring and early complete surgical excision of sebaceous nevus in order to improve patient outcomes.

The Significance of VSIG4 Expression in Ovarian Cancer.

OBJECTIVES: The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage protein with the capacity to inhibit T-cell activation, has a potential role in cancer. Here we suggest its possibility as a therapeutic target and prognostic biomarker of ovarian cancer. METHODS: Between January 2011 and June 2015, tumor tissues and peripheral blood samples were obtained during surgery from 10 patients with benign ovarian tumors and 22 patients with ovarian cancers. Messenger RNA and protein expression levels of VSIG4 in benign tumor and cancer tissues were examined by the reverse transcription polymerase chain reaction and Western blot, respectively. Soluble VSIG4 concentrations were measured by an enzyme-linked immunosorbent assay. The correlation between VSIG4 expression and the prognosis of ovarian cancer was analyzed according to the patients' clinicopathologic characteristics. RESULTS: VSIG4 messenger RNA and protein expression levels in ovarian cancer tissues were higher than those in benign ovarian tumors (P = 0.0013 and 0.0001, respectively). Soluble VSIG4 concentrations were increased in patients with ovarian cancer compared with that in patients with benign ovarian tumors (P = 0.0452). Moreover, soluble VSIG4 levels were significantly increased in advanced-stage and recurrent ovarian cancer (P = 0.0244 and 0.0288, respectively). High VSIG4 expression of cancer tissue and low VSIG4 expression of plasma (soluble VSIG4) were associated with a longer disease-free interval (P = 0.0246 and 0.0398, respectively). CONCLUSIONS: VSIG4 is overexpressed in ovarian cancers compared with that in benign tumors. This finding supports VSIG4 being used as a potential therapeutic target for ovarian cancer. Furthermore, soluble VSIG4 levels are associated with the progression and recurrence of ovarian cancer, indicating that soluble VSIG4 may be used as a potential biomarker for predicting tumor prognosis.

Effect of Porcine Chondrocyte-Derived Extracellular Membrane (CDECM) on Postoperative Wound Healing in an Experimental Rabbit Model of Glaucoma Filtration Surgery.

PURPOSE: We investigated whether a chondrocyte-derived extracellular membrane (CDECM) could reduce postoperative scar formation in an experimental rabbit model of glaucoma filtration surgery. METHODS: Thirty-six male New Zealand white rabbits underwent experimental glaucoma filtration surgeries on the right eye and were randomly divided into the following two treatment groups: the CDECM group was treated with subconjunctival injections of 0.1ml CDECM (25 mg/ml; n = 18 eyes), and the operation (OP) group was treated with subconjunctival injections of 0.1 ml balanced salt solution (n = 18 eyes). The left eyes were used as controls (n = 36 eyes). The effects of the CDECM on the experimental rabbit model were investigated using histopathological, immunochemical analyses and Western blotting analyses of the inflammation, fibrosis and angiogenesis. RESULTS: On the 14th postoperative day, the eyes of the CDECM group displayed reduced vascularity and fibrosis compared with the OP group. The vascular endothelial growth factor (VEGF), CD31 and TNFß immunostaining were also reduced in the CDECM group. The level of TNFα mRNA was increased in the OP group. On the 28th postoperative day, the eyes of the CDECM group also exhibited reduced vascularity and less inflammation and fibrosis than those of the OP group. The expressions of VEGF, CD31, macrophage, TNFß and NF-κB p65 were also decreased in the CDECM group. The levels of TNFα mRNA significantly differ, and the level of matrix metallopeptidase 9 (MMP9) was increased in the OP group. To determine the specific upstream pathway that was associated with NF-κB activation due to glaucoma filtration surgery, we measured Akt, PKCs and MAPKs signaling. The phosphorylation of p38 MAPK was increased in the OP group, whereas this expression was decreased by CDECM treatment. CONCLUSIONS: CDECM seems to suppress angiogenesis, inflammation and fibrosis, which were related to wound healing in the experimental rabbit model of glaucoma filtration surgery. This effect, resulting from the inhibition of NF-κB expression, may be the blocking of the p38 MAPK signaling pathway.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites.

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach-Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

NecroX-5 prevents breast cancer metastasis by AKT inhibition via reducing intracellular calcium levels.

A major goal of breast cancer research is to prevent the molecular events that lead to tumour metastasis. It is well-established that both cytoplasmic and mitochondrial reactive oxygen species (ROS) play important roles in cell migration and metastasis. Accordingly, this study examined the molecular mechanisms of the anti-metastatic effects of NecroX-5, a mitochondrial ROS scavenger. NecroX-5 inhibited lung cancer metastasis by ameliorating migration in a mouse model. In human cancer cells, the inhibition of migration by NecroX-5 is cell type-dependent. We observed that the effect of NecroX-5 correlated with a reduction in mitochondrial ROS, but mitochondrial ROS reduction by MitoQ did not inhibit cell migration. NecroX-5 decreased intracellular calcium concentration by blocking Ca2+ influx, which mediated the inhibition of cell migration, AKT downregulation and the reduction of mitochondrial ROS levels. However, the reduction of mitochondrial ROS was not associated with supressed migration and AKT downregulation. Our study demonstrates the potential of NecroX-5 as an inhibitor of breast cancer metastasis.

The Colonoscopist's Expertise Affects the Characteristics of Detected Polyps.

BACKGROUND/AIMS: The influence of the endoscopist on the polyp detection rate (PDR) is underappreciated in clinical practice. Moreover, flat lesions or lesions of the proximal colon are more difficult to detect. Here, we evaluated the differences in the PDR and the characteristics of detected polyps according to the experience of the colonoscopist. METHODS: We collected data on 2,549 patients who underwent screening colonoscopy performed by three fellows. The PDR was calculated according to the percentage of patients who had at least one polyp (method A) and according to the percentage of detected lesions (method B). The primary outcome included the change in the PDR, and the secondary outcome included the change in the characteristics of the detected polyps with increasing experience of the colonoscopist. RESULTS: No proportional correlation was found between the PDR and increasing experience in colonoscopy with method A; however, with method B, the PDR increased after 400 colonoscopies (p=0.0209). With method B, the detection rates of small polyps (<5 mm) (p=0.0015) and polyps in proximal sites (p=0.0050) increased after 300 colonoscopies. CONCLUSIONS: Our study demonstrated that the quality of a colonoscopy, measured by using the PDR, may increase when performed by experienced fellows.