Acute pancreatitis caused by duodenal bezoar and treated with endoscopic procedures.

Background: Acute pancreatitis triggered by causative agents, including alcohol consumption, gallstones, dyslipidemia, drugs, and infection, is frequently addressed. However, reports of acute pancreatitis caused by duodenal bezoars are limited. Case Presentation: A 75-year-old man experiencing abdominal pain and frequent vomiting was transferred to our hospital. His medical records presented history of diabetes, hypertension, dyslipidemia, and gastric cancer surgery. Computed tomography of the abdomen indicated duodenal dilatation, enlarged pancreas, and fluid retention, with no bile duct stones present. Minor bleeding and duodenal bezoar were endoscopically detected with esophagogastroduodenoscopy (EGD). He was diagnosed with severe acute pancreatitis caused by a bezoar and admitted to the intensive care unit. The duodenal bezoar was dissected and removed with three repetitions of EGD, and the patient was discharged without any complications. Conclusion: Herein, we report a case showing that endoscopic procedures could be effective treatment options in severe pancreatitis caused by duodenal bezoars.

A Collaborative Study on the Classification of Silicone Oil Droplets and Protein Particles Using Flow Imaging Method.

In this study, we conducted a collaborative study on the classification between silicone oil droplets and protein particles detected using the flow imaging (FI) method toward proposing a standardized classifier/model. We compared four approaches, including a classification filter composed of particle characteristic parameters, principal component analysis, decision tree, and convolutional neural network in the performance of the developed classifier/model. Finally, the points to be considered were summarized for measurement using the FI method, and for establishing the classifier/model using machine learning to differentiate silicone oil droplets and protein particles.

Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.

Although the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, 'true' radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6-16 months after local X-ray (0.1-4 Gy) irradiation of the neck at 7 weeks of age. The gene expression profile in thyroid glands was comprehensively analyzed using RNA microarray. Subsequently, the expression levels of the genes of interest were verified using droplet digital PCR (ddPCR). The expression level of candidate genes as biomarkers for irradiated thyroid was examined in a randomized, controlled, double-blind validation study (n = 19) using ddPCR. The incidence of thyroid cancer increased in a dose- and time-dependent manner and was 33% at 16 months after irradiation with 4 Gy. The Ki-67 labeling index in non-tumorous thyroid was significantly higher in the exposed group than in the control. Comprehensive analysis identified radiation-dependent alteration in 3329 genes. Among them, ddPCR revealed a stepwise increase in CDKN1A expression from early pre-cancerous phase in irradiated thyroid compared to that in the control. The irradiated thyroids were accurately distinguished (positive predictive value 100%, negative predictive value 69%) using 11.69 as the cut-off value for CDKN1A/ß-actin. Thus, CDKN1A expression can be used as a biomarker for irradiated thyroid glands at the pre-cancerous phase.

[A case of elderly-onset myasthenia gravis mimicking stroke with dysarthria and left upper extremity paresis].

An 80-year-old woman presented with sudden-onset dysarthria and left-side dominant quadriparesis and transferred to our hospital. A neurologic examination revealed slurred speech, prominent left upper extremity weakness and mild weakness of the other extremities. Brain MRI revealed a history of right-side cerebral artery bypass surgery, but no new lesions indicative of stroke. Left upper extremity weakness had improved soon after admission, so a transient ischemic attack was suspected. After admission, the dysarthria fluctuated. The patient's respiratory condition deteriorated several days later and she required ventilation support. Assessment of the cause of the respiratory failure revealed positive muscle-specific kinase (MuSK) antibodies, which suggested myasthenia gravis (MG). The symptoms gradually improved with immunotherapy and we were able to completely withdraw her from the ventilator after a few months. There were some reports that dysphagia and dysarthria present suddenly like stroke without fluctuation of symptoms in elderly-onset MG. It is necessary to note that MG diagnosis may be difficult if elderly patients have multiple comorbidities and unclear diurnal fluctuations.

Immunofluorescence analysis of DNA damage response protein p53-binding protein 1 in a case of uterine dedifferentiated leiomyosarcoma arising from leiomyoma.

AIMS: Genomic instability has been indicated during the dedifferentiation process from leiomyoma (LM) to leiomyosarcoma (LMS). Previously, we have described that nuclear expression pattern of DNA damage response protein p53-binding protein 1 (53BP1), detected by immunofluorescence, reflects the magnitude of genomic instability during malignancy. Here, we present a case of LMS arising from LM with molecular analysis of 53BP1, which showed transitional magnitude of DNA damage response within a tumor. METHODS AND RESULTS: A fifty-year-old female with abdominal mass underwent hysterectomy. Histologically, the tumor consisted of LMS with highly atypical multinucleated giant cells as well as an LM component with transitional atypical spindle cells in the border area. LMS showed diffuse nuclear staining of 53BP1 expression, which has been previously described as high DNA damage response pattern. In contrast, the LM component lacked 53BP1 immunoreactivity and focal expression was observed in transitional lesion. Furthermore, double-labelled immunofluorescence revealed co-localization of 53BP1 with p53 and Ki-67 in the LMS component, which indicated abnormal DNA damage response in proliferative state. CONCLUSIONS: This study revealed that diffuse-type 53BP1 expression may be beneficial to estimate genomic instability during dedifferentiation from LM to DLMS.

Sublamina densa-type linear IgA bullous dermatosis with IgA autoantibodies specific for type VII collagen: a case report and clinicopathological review of 32 cases.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disorder characterized by linear deposits of IgA at the basement membrane zone(BMZ) and/or by circulating IgA anti-BMZ antibodies. Comparing with other immuno-bullous diseases, LABD represents a heterogeneous disease entitywith diversity of pathogenic IgA autoantibodies to different hemidesmosomal antigens and an association with malignancies and occasional drug use. We herein present an 82-year-old Japanese man with LABD, whose indirect immunofluorescence using 1M NaCl-split skin showed positive staining for IgA at the dermal side alone. Fluorescence overlay antigen mapping using laser scanning confocal microscopy (FOAM-LSCM) was employed to examine the in vivo bound patient's IgA, which was specific for type VII collagen (COL7), a prominent antigen of the sublamina densa. One year later, he developed malignant lymphoma, suggesting the diagnosis of paraneoplastic LABD. We reviewed 32 cases of sublamina-densa type LABD with anti-COL7 IgA antibodies thus far reported in the literature to compare the clinicopathological characteristics of this rare disease variant and emphasize that COL7 is the main autoantigen in sublamina densa disease.

Urologic Sequelae Following Phalloplasty in Transgendered Patients.

In recent years, the issues of the transgender population have become more visible in the media worldwide. Transgender patients at various stages of their transformation will present to urologic clinics requiring general or specialized urologic care. Knowledge of specifics of reconstructed anatomy and potential unique complications of the reconstruction will become important in providing urologic care to these patients. In this article, we have concentrated on describing diagnosis and treatment of the more common urologic complications after female-to-male reconstructions: urethrocutaneous fistulae, neourethral strictures, and symptomatic persistent vaginal cavities.

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin.

Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.

Tissue transfer techniques in reconstructive urology.

Tissue transfer techniques are an essential part of the reconstructive urologist's armamentarium. Flaps and graft techniques are widely used in genital and urethral reconstruction. A graft is tissue that is moved from a donor site to a recipient site without its native blood supply. The main types of grafts used in urology are full thickness grafts, split thickness skin grafts and buccal mucosa grafts. Flaps are transferred from the donor site to the recipient site on a pedicle containing its native blood supply. Flaps can be classified based on blood supply, elevation methods or the method of transfer. The most used flaps in urology include penile, preputial, and scrotal skin. We review the various techniques used in reconstructive urology and the outcomes of these techniques.

Robot-Assisted Ureteral Reconstruction Using Buccal Mucosa.

OBJECTIVE: To describe the technique of robotic buccal mucosa graft ureteroplasty as a minimally invasive alternative method of ureteral reconstruction for proximal or multifocal ureteral strictures not amenable to primary anastomosis. METHODS: Between October 2013 and May 2014, we performed robotic-assisted ureteral reconstruction using buccal mucosa grafts in four patients (mean age 41.5, range 23-67). The indication for surgery was a proximal or multifocal stricture not amenable to ureteroureterostomy or ureteropyelostomy. Buccal mucosa grafts were harvested to be the length of the strictured segment and 1 cm in width and placed in the ureter as an anterior or posterior onlay. Follow up was performed with diuretic renogram at least 3 months postoperatively and renal ultrasound as well as clinical assessment of symptoms. RESULTS: All 4 patients underwent successful robotic-assisted reconstruction of the ureter using buccal mucosa graft. There were no intraoperative complications. At a median follow up of 15.5 months (range 10.7-18.6), there has been 100% success. CONCLUSION: Robotic buccal mucosa graft ureteroplasty is a feasible option for reconstruction of proximal or multifocal ureteral strictures that are not amenable to primary anastomosis and it avoids the morbidity of alternative procedures.

Analytical and biological validation of a multiplex immunoassay for acute kidney injury biomarkers.

BACKGROUND: Acute kidney injury (AKI) is a dynamic process that can involve inflammatory, hypoxic, and structural changes to the kidney. We evaluated a multiplex panel of markers representing different AKI mechanisms as a tool to provide integrated assessment of AKI status in a single assay. METHODS: Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) were measured by multiplex electrochemiluminescence immunoassay. Analytical performance was compared to the biological and pathological variation of these markers in human samples. RESULTS: Linearity was established over a 3- to 4-log range for all markers, which spanned the reference ranges established from healthy donors. Imprecision was below 15%, comparing favorably with the observed biological variation of these markers. Control patients fell within donor-derived reference ranges for most markers, but a subset of patients showed CysC and KIM-1 elevations in the absence of documented AKI. CONCLUSION: The multiplex assay is reliable for simultaneous quantitation of CysC, IL-18, KIM-1 and NGAL in human urine, and performs at levels sufficient for clinical application. The observed differences in biological variability and baseline levels suggest that clinical strategies to detect AKI will need to vary depending upon the specific markers used.

Detection of miRNA in cell cultures by using microchip electrophoresis with a fluorescence-labeled riboprobe.

The analysis of a microRNA (miRNA), miR-222 isolated from the PC12 cell line, was performed by use of the ribonuclease (RNase) protection assay, cyanine 5 (Cy5)-labeled miR-222 riboprobe, and a Hitachi SV1210 microchip electrophoresis system, which can be used to evaluate the integrity of total RNA. The fluorescence intensity corresponding to the protected RNA fragment increased in a dose-dependent manner with respect to the complementary-strand RNA. More highly sensitive detection of miRNA by microchip electrophoresis than by conventional method using fluorescence-labeled riboprobe could be obtained in 180 s. An obvious increase in miR-222 expression induced by nerve growth factor in PC12 cells could be observed. These results clearly indicate the potential of microchip electrophoresis for the analysis of miRNA using RNase protection assay with a fluorescence-labeled riboprobe.

Accurate detection of carcinoma cells by use of a cell microarray chip.

BACKGROUND: Accurate detection and analysis of circulating tumor cells plays an important role in the diagnosis and treatment of metastatic cancer treatment. METHODS AND FINDINGS: A cell microarray chip was used to detect spiked carcinoma cells among leukocytes. The chip, with 20,944 microchambers (105 µm width and 50 µm depth), was made from polystyrene; and the formation of monolayers of leukocytes in the microchambers was observed. Cultured human T lymphoblastoid leukemia (CCRF-CEM) cells were used to examine the potential of the cell microarray chip for the detection of spiked carcinoma cells. A T lymphoblastoid leukemia suspension was dispersed on the chip surface, followed by 15 min standing to allow the leukocytes to settle down into the microchambers. Approximately 29 leukocytes were found in each microchamber when about 600,000 leukocytes in total were dispersed onto a cell microarray chip. Similarly, when leukocytes isolated from human whole blood were used, approximately 89 leukocytes entered each microchamber when about 1,800,000 leukocytes in total were placed onto the cell microarray chip. After washing the chip surface, PE-labeled anti-cytokeratin monoclonal antibody and APC-labeled anti-CD326 (EpCAM) monoclonal antibody solution were dispersed onto the chip surface and allowed to react for 15 min; and then a microarray scanner was employed to detect any fluorescence-positive cells within 20 min. In the experiments using spiked carcinoma cells (NCI-H1650, 0.01 to 0.0001%), accurate detection of carcinoma cells was achieved with PE-labeled anti-cytokeratin monoclonal antibody. Furthermore, verification of carcinoma cells in the microchambers was performed by double staining with the above monoclonal antibodies. CONCLUSION: The potential application of the cell microarray chip for the detection of CTCs was shown, thus demonstrating accurate detection by double staining for cytokeratin and EpCAM at the single carcinoma cell level.

Toxic epidermal necrolysis following allergic contact dermatitis caused by occupational exposure to ultraviolet-cured inks.

Erythema multiforme is a relatively common skin disorder; the most common cause is herpes simplex infection, but topical sensitivities reportedly also provoke this reaction. We report here a case that progressed to toxic epidermal necrolysis due to contact with ultraviolet (UV)-cured inks. The diagnosis was confirmed by patch tests to acrylates in the UV-cured inks, histopathological studies of the lesions, and positive patch test to 1,6-hexanediol diacrylate.

Malaria elimination in Isabel Province, Solomon Islands: establishing a surveillance-response system to prevent introduction and reintroduction of malaria.

BACKGROUND: The Solomon Islands National Malaria Programme is currently focused on intensified control and progressive elimination. Recent control efforts in Isabel Province have reduced their malaria incidence to 2.6/1,000 population in 2009 1 whereas most neighbouring provinces have much higher incidences. A malaria surveillance-response system that involves testing all travellers entering Isabel Province using rapid diagnostic tests (RDT) to prevent cases being imported had been proposed by local health authorities. This study provides information on the feasibility and acceptability of implementing a new approach of surveillance and response in the context of low levels of indigenous malaria transmission in Isabel Province. METHODS: A total of 13 focus group discussions (FGD) and 22 key informant interviews (KII) were conducted in Isabel Province, Solomon Islands. Key topics included: the travel patterns of people to, from and within Isabel Province; the acceptability, community perceptions, attitudes and suggestions towards the proposed surveillance programme; and management of suspected malaria cases. This information was triangulated with data obtained from port authorities, airlines and passenger ships travelling to and from Isabel Province in the preceding two years. RESULTS: Travel within Isabel Province and to and from other provinces is common with marked seasonality. The majority of inter-provincial travel is done on scheduled public transport; namely passenger ships and aircrafts. In Isabel Province there is a healthy community spirit as well as high concern regarding malaria and its importation and there is currently effective malaria passive case detection and management. Conducting malaria screening at ports and airports would be acceptable to the community. CONCLUSION: A robust surveillance-response system is essential when moving towards malaria elimination. Many factors contribute positively towards the feasibility of an RDT based malaria surveillance system in Isabel Province. Due to financial and logistical restraints local health authorities have concluded that a system of community-based vigilance to identify new arrivals in villages and direct them to have malaria testing is more feasible than formal screening at ports and airports. A surveillance response system to prevent introduction of malaria into Isabel Province can be integrated into the National Malaria Control Programme provided the operational steps are carefully planned with regards to human and financial resources.

Small renal masses: risk prediction and contemporary management.

The majority of kidney cancer tumors are small renal masses (SRMs). Partial nephrectomy is now established as the preferred treatment modality. In some patients the potential morbidity may outweigh the oncologic risk. Based on active surveillance studies, restriction of radical therapy to patients with aggressive tumors has been proposed. This has spurred renewed interest in development of radiologic and biopsy-based diagnostic techniques that can identify high-risk disease. This article discusses the natural history and pathologic features of SRMs, the evolving role of biopsy, and provides an overview of outcomes of various treatment approaches and current recommendations for management.

An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents.

The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy.

c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases.

The c-Met proto-oncogene encodes a receptor tyrosine kinase (TK) that promotes invasive tumor growth and metastasis. Recent studies show that the presence of c-Met gene amplification is predictive for selective c-Met TK inhibitors in gastric cancer and lung cancer. In this study, we utilized a highly quantitative PCR/ligase detection reaction technique to quantify c-Met gene copy number in primary colorectal cancer (CRC) (N=247), liver metastases (N=147), and paired normal tissues. We identified no differences in c-Met gene copy number between normal colonic mucosa and liver tissue. However, mean c-Met gene copy number was significantly elevated in CRC compared with normal mucosa (P<0.001), and in liver metastases compared with normal liver (P<0.001). Furthermore, a significant increase in c-Met was seen in liver metastases compared with primary CRC (P<0.0001). c-Met gene amplification was observed in 2% (3/177) of localized cancers, 9% (6/70) of cancers with distant metastases (P<0.02), and 18% (25/147) of liver metastases (P<0.01). Among patients treated by liver resection, there was a trend toward poorer 3-year survival in association with c-Met gene amplification (P=0.07). Slight increases in c-Met copy number can be detected in localized CRCs, but gene amplification is largely restricted to Stage IV primary cancers and liver metastases. c-Met gene amplification is linked to metastatic progression, and is a viable target for a significant subset of advanced CRC.

Ozone-induced cell death mediated with oxidative and calcium signaling pathways in tobacco bel-w3 and bel-B cell suspension cultures.

Ozone (O(3))-induced cell death in two suspension-cultured cell lines of tobacco (Nicotiana tabacum L.) derived from Bel-W3 (hyper-sensitive to O(3)) and Bel-B (highly tolerant to O(3)) varieties were studied. By exposing the newly prepared cell lines to the pulse of ozonized air, we could reproduce the conditions demonstrating the difference in O(3) sensitivity as observed in their original plants, depending on the exposure time. Since O(3)-induced acute cell death was observed in the dark, the requirement for photochemical reactions could be eliminated. Addition of several ROS scavengers and chelators inhibited the cell death induced by O(3), indicating that singlet oxygen ((1)O(2)), hydrogen peroxide (H(2)O(2)), hydroxyl radical and redox-active metals such as Fe(2+) play central roles in O(3)-induced acute damages to the cells. As expected, we observed the generation of (1)O(2) and H(2)O(2) in the O(3)-treated cells using chemiluminescent probes. On the other hand, an NADPH oxidase inhibitor, superoxide dismutase (SOD), and some SOD mimics showed no inhibitory effect. Thiols added as antioxidants unexpectedly behaved as prooxidants drastically enhancing the O(3)-induced cell death. It is noteworthy that some ROS scavengers effectively rescued the cells from dying even treated after the pulse of O(3) exposure, confirming the post-ozone progress of ROS-dependent cell death mechanism. Since one of the key differences between Bel-B and Bel-W3 was suggested to be the capacity for ROS detoxification by catalase, the endogenous catalase activities were compared in vivo in two cell lines. As expected, catalase activity in Bel-B cells was ca. 7-fold greater than that in Bel-W3 cells. Interestingly, Ca(2+) chelators added prior to (not after) the pulse of O(3) effectively inhibited the induction of cell death. In addition, increases in cytosolic Ca(2+) concentration sensitive to Ca(2+) chelators, ion channel blockers, and ROS scavengers were observed in the transgenic Bel-W3 cells expressing aequorin, suggesting the action of Ca(2+) as a secondary messenger initiating the oxidative cell death. The O(3)-induced calcium response in Bel-W3 cells was much greater than Bel-B cells. Based on the results, possible pathways for O(3)-dependent generation of the lethal level of ROS and corresponding signaling mechanism for induction of cell death were discussed.