Histopathological Methods Research Articles

The effect of ionizing radiation on the fetal bone development in pregnant rats: Role of melatonin.

Radiation has been widely used in many business sectors over the last century. Our study investigated the possible teratogenic effects of radiation on the bones of rat fetuses and the protective effect of melatonin against these effects. In this study, 15 pregnant female Wistar albino rats were used. These rats were divided into four groups: the control group, melatonin group (10 mg/kg/day), radiation group (0.5 gray), radiation (0.5 gray) + melatonin group (10 mg/kg/day), and sham group (1 mm hanks/day). The skeletal system development of fetuses was examined with double skeletal and scanning electron microscope (SEM), histopathological methods. In our study, fetal weight, placental weight, and fetal morphometric values were found to be statistically significantly decreased in the radiation group compared to the control group (p < .05). In immünohistochemistry (IHC) analysis, alkaline phosphatase, and tartrate-resistant acid phosphatase) concentrations were found to be significantly lower in the radiation group compared to the other groups. In the SEM analysis, it was observed that the amount of calcium and sodium decreased when the radiation group was compared with the other groups. As a result, when exposed to ionizing radiation during pregnancy, melatonin has a protective feature against the negative effects of radiation on the bone development of fetuses. RESEARCH HIGHLIGHTS: In our study, fetuses obtained from pregnant rats exposed to ionizing radiation were examined. In this study, the effect of melatonin on bone development in fetuses exposed to gray ionizing radiation was investigated. There are few studies on our subject in the literature. We believe that our findings will contribute to other planned studies.

COVID-19 Associated Rhino-Orbital-Cerebral Mucormycosis: Clinical Features, Antifungal Susceptibility, Management and Outcome in a Tertiary Hospital in Iran.

Despite the unprecedented surge in the incidence of mucormycosis in the COVID-19 era, the antifungal susceptibility patterns (ASPs) of COVID-19 associated mucormycosis (CAM) isolates have not been investigated so far and it is unclear if the high mortality rate associated with CAM is driven by decreased susceptibility of Mucorales to antifungal drugs. To describe the clinical, mycological, outcome and in vitro ASPs of CAM cases and their etiologies from Iran. A prospective study from January 2020 to January 2022 at a referral tertiary hospital in Tehran, Iran was conducted for screening mucormycosis through histopathology and mycological methods. The identity of Mucorales isolates was revealed with ITS-panfungal PCR& sequencing and MALDI-TOF. The AS for amphotericin B, itraconazole, isavuconazole and posaconazole was cleared according to the EUCAST antifungal susceptibility testing protocol. A total of 150 individuals were diagnosed with CAM. Males constituted 60.7% of the population. The mean age was 54.9years. Diabetes was the leading risk factor (74.7%). The median interval between diagnosis of COVID-19 and CAM was 31days. The recovery rate of culture was as low as 41.3% with Rhizopus arrhizus being identified as the dominant (60; 96.7%) agent. Amphotericin B (MIC50 = 0.5µg/ml) demonstrated the highest potency against Mucorales. Majority of the cases had either diabetes, history of corticosteroid therapy or simultaneously both conditions. Accordingly, close monitoring of blood glucose should be considered. The indications for corticosteroids therapy are recommended to be optimized. Also, an anti Mucorales prophylaxis may be necessitated to be administrated in high risk individuals. Although amphotericin B was the most active agent, a higher rate of resistance to this antifungal was noted here in comparison with earlier studies on mucormycetes from non-CAM cases.

Initial assessment of “Gissell's stain”: A novel histopathological method for the identification of Helicobacter pylori

Introduction and ObjectivesThe histopathological identification of Helicobacter pylori using the routine method (haematoxylin–eosin) is not only very difficult but also has low sensitivity. Giemsa staining is often used in addition, but different protocols do not produce homogeneous results. Furthermore, the Gold Standard recommended by the European Helicobacter Pylori Study Group has been applied in very few studies, thus resulting in uncertain outcomes. Therefore, a new staining method is required to overcome these limitations. The aim of this study was to evaluate the diagnostic capacity and inter-observer agreement of “Gissell's stain”. Material and MethodsA cross-sectional study evaluated 99 gastric paraffin blocks from a private laboratory. Three sections were prepared from each block, and haematoxylin–eosin (HE), Giemsa and “Gissell's stain” methods were applied. The kappa statistics, sensitivity, specificity, and predictive values were calculated. Results“Gissell's stain” obtained the highest inter-observer agreement (kappa=0.87) compared to the other two methods (HE, kappa=0.51; Giemsa, kappa=0.83). It also obtained the best sensitivity and negative predictive value (97.1% and 98.3%, respectively) compared with the other two methods (HE: 68.6% and 85.1%, respectively; Giemsa: 88.6% and 93.9%, respectively). ConclusionsGiven its unique characteristics (fast, cheap, accessible, and easy to use), in addition to its statistical reliability, “Gissell's stain” has great potential for routine use in the identification of H. pylori.

Siyatik sinir yaralanması oluşturulan ratlarda Andız (Juniperus sp) kökü ekstraktının ve B12 vitamininin sinir iyileşmesi üzerine etkisinin karşılaştırılması

The self-repair capacity of peripheral nerves is limited, and the repair of severely damaged or significantly flawed nerves is challenging. For preclinical investigations on peripheral nerve regeneration, the sciatic nerve injury model is the most often used experimental model. In rats, sciatic nerve injury is the most frequently used model in studies related to peripheral nerve regeneration.&#x0D; Material and Methods: In this study, 32 rats were subjected to sciatic nerve injury, and applications of B12 vitamin and Andız root extract were performed. After the applications, the rats were sacrificed on the 21st day, and samples of the sciatic nerve tissue were taken. The collected samples were examined using histopathological and immunofluorescence methods.&#x0D; Results: The examination revealed that B12 vitamin and Andız root extract, when applied separately to the rats, provided limited and similar benefits histopathologically, while the group that received combined treatment showed more effective positive effects compared to all other groups. Additionally, when assessing S100 and GFAP expression through immunofluorescence, it was observed that individual applications provided similar benefits, while the group that received combined treatment contributed more effectively compared to all other groups.&#x0D; Conclusion: In conclusion, in the rat model of sciatic nerve injury, it was determined that Andız root extract and B12 vitamin, when applied separately, had limited and similar effects compared to the control group in determining the levels of recovery. However, when applied together, they exhibited a synergistic effect, providing a greater contribution to nerve regeneration compared to all other groups.

A histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolution neural network.

Histopathological image analysis plays an important role in the diagnosis and treatment of cholangiocarcinoma. This time-consuming and complex process is currently performed manually by pathologists. To reduce the burden on pathologists, this paper proposes a histopathological image classification method for cholangiocarcinoma based on spatial-channel feature fusion convolutional neural networks. Specifically, the proposed model consists of a spatial branch and a channel branch. In the spatial branch, residual structural blocks are used to extract deep spatial features. In the channel branch, a multi-scale feature extraction module and some multi-level feature extraction modules are designed to extract channel features in order to increase the representational ability of the model. The experimental results of the Multidimensional Choledoch Database show that the proposed method performs better than other classical CNN classification methods.

Eccrine Poroma: Pathogenesis, New Diagnostic Tools and Association with Porocarcinoma-A Review.

Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene studies have revealed gene fusions as key incidences resulting in oncogenetic pathways. It often presents as a solitary, firm papule, mostly asymptomatic, located on the soles or palms. Due to its clinical and dermoscopic variability, it is characterized as the great imitator. We performed a literature review, aiming to summarize current data on the pathogenetic mechanisms, new dermoscopic features, and novel diagnostic tools that may aid in early diagnosis and proper management of this rare adnexal tumor. Furthermore, we reviewed the possible pathogenetic associations between EP and its malignant counterpart, namely eccrine porocarcinoma. This systematic approach may aid in understanding the pathogenetic mechanisms and how to use novel histopathologic markers and imaging methods to overcome the diagnostic dilemma of this rare tumor.

The Correlation of Tissue’s Endotype Biomarkers and Dominant Inflammation Cell in Chronic Rhinosinusitis

Background and Objectives This study analyzes the relationship between endotype biomarkers and the type of tissue inflammation in chronic rhinosinusitis (CRS) in order to obtain a more accurate division of disease groups and appropriate therapy.Subjects and Method We carried out a cross-sectional study involving 33 samples of CRS patients. We conducted enzyme-linked immunosorbent assay to examine endotype biomarkers and histopathology methods to examine tissue inflammation.Results Statistical analysis with an independent t-test showed significant differences with respect to eosinophil cationic protein (ECP) between the eosinophilic and neutrophilic groups (p&lt;0.05), whereas there were no significant differences between the two groups (p&gt;0.05) with respect to Charcot-Leyden crystal (CLC), interleukin-5 (IL-5), interferon gamma (IFN-γ), interleukin- 17A (IL-17A), and oncostatin M (OSM). The Spearman test showed also showed that ECP, CLC, IL-5, IL-17A, IFN-γ and OSM had no significant correlation with the two groups (p&gt;0.05). The receiver operating characteristics analysis showed the optimal cut-off value of ECP of 342.22 pg/mL with sensitivity and specificity of 72.7% for determining the inflammation type (area under cover=0.78, p=0.009).Conclusion The higher level of ECP was more likely to be found in the eosinophilic tissue inflammation. Consequently, we propose using ECP as the main biomarker to identify the CRS type 2. Further research with a larger sample size is required for cut-off points of ECP in order to determine the endotype of CRS.

Molecular Diagnosis and Application of Combined Alternative Treatment in Lesions Developing in the Oral Region due to Orf Virus in Sheep and Goats

Background: Orf virus (ORFV) is a zoonotic pathogen that infects sheep and goats, causing significant economic losses. The infection results in proliferative and self-limiting crustal lesions, commonly seen on the skin of the lips and around the nostrils of sheep and goats and occasionally on their feet and teats. ORFV infection is prevalent worldwide and endemic in regions where sheep and goats are raised. Vaccines are widely used to protect against ORFV-induced ecthyma in these animals. However, the disease has become increasingly prevalent throughout the year in small ruminants, necessitating the development of new approaches to treat it. Methods: Crust samples were taken from ORFV lesions in the mouth (lips, gingiva) of 29 sheep and 29 goats aged two years or older from various barns in Burdur-Center and its districts. Conventional polymerase chain reaction was used to investigate the presence of the ORFV genome in the samples, using seven different types of primers (GIF/IL-2, PPP1-PPP4, Orf1-Orf2, VIR1-VIR2, vIL-10-3, vIL-10-4, B2L and Alpha tubulin). Additionally, samples from oral mucosa lesions were examined using histopathological and immunohistochemical methods. As an alternative treatment approach, PAPILENDTM,®cream was applied and Ivermectin was administered subcutaneously twice every 15 days, along with 10 grams of AlquermoldTM premix powder daily for 10 days to all animals with a detected ORFV viral genome. Result: The presence of viral genomes was determined in 10 (34.48%) of 29 sheep and 14 (48.28%) of 29 goats using 7 different types of primers, which have been detected intensively in our region before. In sheep the GIF/IL-2, PPP1-PPP4 and B2L primers detected viral genome (10/29 positive) while in goats Orf1-Orf2 and B2L primers (14/29 positive). Histopathological examination showed epidermal hyperplasia, hyperkeratosis, parakeratosis and crust formations at the epidermal layer. Both epithelial and dermal cells expressed orf virus antigen throughout the immunohistochemical investigation. The alternative treatment of PAPILENDTM,®cream + Ivermectin + AlquermoldTM premix powder triple combination applied to sheep and goats with ORFV genome determined was successful in treating oral lesions caused by ORFV. PCR tests provide rapid and reliable results in the diagnosis of ORFV. The use of triple combined alternative treatments, in addition to ORFV preventive vaccinations in sheep and goats, was found to be successful in treating ORFV infections. The animals showed recovery or regression within a range of 5 to 21 days.

Validity of Cell Block Histopathology and Fine Needle Aspiration Cytology in the Diagnosis of Lymphoma

Introduction: Lymphoma, a type of cancer affecting the lymphatic system, requires accurate diagnostic methods for effective treatment. This study aimed to evaluate the validity of Cell Block Histopathology and Fine Needle Aspiration Cytology (FNAC) in the diagnosis of lymphoma. Methods: A total of 30 patients with clinically suspected lymphoproliferative disorder were included in the study. Both Cell Block Histopathology and FNAC were used to diagnose lymphoma in these patients. The results were then compared with the final diagnosis based on histopathology, immunochemistry, and clinical follow-up, which was considered the gold standard. Result: The study included 30 patients with clinically suspected lymphoproliferative disorder. The Cell Block Histopathology method diagnosed 12 patients (40%) as lymphoma positive, 11 patients (36.67%) as lymphoma negative, and 7 cases (23.33%) were inconclusive. The Fine Needle Aspiration Cytology (FNAC) method diagnosed 13 patients (43.33%) as lymphoma positive, 12 patients (40%) as lymphoma negative, and 5 cases (16.67%) were inconclusive.When compared with the final diagnosis based on histopathology, immunochemistry, and clinical follow-up, the sensitivity, specificity, and accuracy of Cell Block Histopathology were 91.67%, 90.91%, and 93.33% respectively. The positive predictive value (PPV) and negative predictive value (NPV) were both 91.67%. The FNAC method demonstrated a sensitivity, specificity, and accuracy of 92.31%, 91.67%, and 93.33% respectively. The PPV and NPV were 92.31% and 91.67% respectively. Conclusion: This study concludes that both Cell Block Histopathology and FNAC are valid and effective diagnostic tools for lymphoma. They can be used independently or in conjunction with one another to enhance diagnostic accuracy. The findings contribute to the growing body of evidence supporting the use of these methods in lymphoma diagnosis.

Immunohistochemical Diagnostic Characteristics of Parvovirus Infection in Dogs

Abstract Thе current study goal was to compare the results from the histopathological and immunohistochemical findings in dogs that have previously been clinically diagnosed with parvovirus infection. The Canine parvovirus enteritis (PVE) is a highly contagious disease mostly affecting dogs below six months of age. The canine parvovirus (CPV) belongs to the parvoviridae family within the feline parvovirus sub group of the genus Parvovirus. This investigation was performed on twenty dogs 2 to 12 months old with previous clinical diagnosis for PVE, and it included necropsy, histopathology, and immunohistochemistry. The necropsy findings included severe hemorrhagic enteritis and enlarged mesenteric lymph nodes as most frequent and prominent changes. The histopathological changes were also most significant in these organs in the form of villus atrophy and lymphoid depletion, respectively. These areas revealed the highest expression of CPV antigen. The histopathological and immunohistochemical methods provide strong base for a reliable CPV diagnosis.

Clinical Characteristics of Chronic Rhinosinusitis With Nasal Polyp According to Histopathological Endotypes and Staining Method for Neutrophilic Polyp Classification and Its Clinical Implication

Background and Objectives There are various methods used to histologically assess the cell count of neutrophils in nasal polyps. With various classification of neutrophilic nasal polyps, determining the appropriate staining techniques and criteria is deemed important for the diagnosis of neutrophilic nasal polyps by assessing neutrophil cell counts. In this study, we tried to optimize different methods of neutrophil counting and staining by comparing clinical outcomes.Subjects and Method We studied 207 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis with nasal polyp from August 2014 to September 2018. Patients’ nasal polyp were taken to make following three slide sections: hematoxylin and eosin, human neutrophil elastase (HNE), myeloperoxidase. After staining, microscope picture (×400) was taken and neutrophils were counted. Neutrophil polyp (NP) was classified either by the tissue neutrophil count (20/HPF) or by the neutrophil percentage (1%/total cell) for clinical outcome comparison.Results Two groups were made after HNE staining: the NP and the non-NP groups. The L-K scores and delta showed significant differences between each group while neutrophil was defined based on 20 counts/HPF (&lt;i&gt;p&lt;/i&gt;&lt;0.001). By Kaplan-Meier estimation, there was no statistical meaning between the two groups. But the NP group had a tendency to recur more than the non-NP group while 20 counts/HPF definition was used (&lt;i&gt;p&lt;/i&gt;&gt;0.05).Conclusion HNE staining and 20 counts/HPF were the most specific for neutrophil counting. Analyzing the nasal polyp into two groups due to histologic types showed that the NP group had worse prognosis than the non-NP group. In conclusion, neutrophils in the nasal polyp might be considered seriously for clinical outcomes.

Wide-field optical coherence tomography for microstructural analysis of key tissue types: a proof-of-concept evaluation.

Introduction: The presence of positive margins following tumor resection is a frequent cause of re-excision surgery. Nondestructive, real-time intraoperative histopathological imaging methods may improve margin status assessment at the time of surgery; optical coherence tomography (OCT) has been identified as a potential solution but has not been tested with the most common tissue types in surgical oncology using a single, standardized platform. Methods: This was a proof-of-concept evaluation of a novel device that employs wide-field OCT (WF-OCT; OTIS 2.0 System) to image tissue specimens. Various cadaveric tissues were obtained from a single autopsy and were imaged with WF-OCT then processed for permanent histology. The quality and resolution of the WF-OCT images were evaluated and compared to histology and with images in previous literature. Results: A total of 30 specimens were collected and tissue-specific microarchitecture consistent with previous literature were identified on both WF-OCT images and histology slides for all specimens, and corresponding sections were correlated. Application of vacuum pressure during scanning did not affect specimen integrity. On average, specimens were scanned at a speed of 10.3s/cm2 with approximately three features observed per tissue type. Conclusion: The WF-OCT images captured in this study displayed the key features of the most common human tissue types encountered in surgical oncology with utility comparable to histology, confirming the utility of an FDA-cleared imaging platform. With further study, WF-OCT may have the potential to bridge the gap between the immediate information needs of the operating room and the longer timeline inherent to histology workflow.

Quantitative multiphoton imaging of cell metabolism, stromal fibers, and keratinization enables label-free discrimination of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) features atypical clinical manifestations and a low 5-year survival rate (< 5% in many developing countries where most of the disease occurs). Precise ESCC detection and grading toward timely and effective intervention are therefore crucial. In this study, we propose a multidimensional, slicing-free, and label-free histopathological evaluation method based on multispectral multiphoton fluorescence lifetime imaging microscopy (MM-FLIM) for precise ESCC identification. To assess the feasibility of this method, comparative imaging on fresh human biopsy specimens of different ESCC grades is performed. By constructing fluorescence spectrum- and lifetime-coded images, ESCC-induced morphological variations are unveiled. Further quantification of cell metabolism and stromal fibers reveals potential indicators for ESCC detection and grading. The specific identification of keratin pearls provides additional support for the early detection of ESCC. These findings demonstrate the viability of using MM-FLIM and the series of derived indicators for histopathological evaluation of ESCC. As there is an increasing interest in developing multiphoton endoscopes and multiphoton FLIM systems for clinical use, the proposed method would probably allow noninvasive, label-free, and multidimensional histological detection and grading of ESCC in the future.

The Utility of Mitochondrial Detection Methods Applied as an Additional Tool for the Differentiation of Renal Cell Tumors.

The precise differentiation of renal cell tumors (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods, especially for those with eosinophilic features. It has been suggested that the vast overabundance of mitochondria, as a well-known hallmark of eosinophilic cytoplasm, and could be a characteristic of distinct tumor types with opposing clinical outcomes. Thus, we intended to explore the associations between mitochondrial distribution patterns in different RCTs, including 43 cell renal cell carcinomas (ccRCCs), 15 papillary renal cell carcinomas (pRCCs), 20 chromophobe renal cell carcinomas (chRCCs), and 18 renal oncocytomas (ROs). Tumor samples were stained with two anti-mitochondrial antibodies (mitochondrial antibody Ab-2, clone MTC02; prohibitin, II-14-10, MA5-12858), applying immunohistochemistry and immunofluorescence to define mitochondrial distribution patterns (coarse scanty, moderate granular, and diffuse granular). Our results revealed significantly different expression patterns among the investigated RCTs (p < 0.001). The majority of ccRCCs exhibited coarse scanty mitochondrial staining, while all chRCCs had moderate granular expression. Nevertheless, all ROs, all pRCCs, and two cases of ccRCC presenting with higher nuclear grade and eosinophilic cytoplasm had diffuse granular mitochondrial expression. Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p < 0.001). Here we present a strategy that utilizes fast and easy mitochondrial detection to differentiate RO from chRCC, as well as other eosinophilic variants of RCC with high accuracy.

A Case-Based Review of Free-living Amebic Human Infections and Diagnosis

Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba species are free-living amebae that are ubiquitously found in soil and water and can opportunistically cause invasive, deadly infections in humans. In this review, we present four patient cases due to free-living amebae and review the epidemiology and clinical significance of the diseases they cause. Specifically, primary amebic encephalitis due to N. fowleri, granulomatous amebic encephalitis due to B. mandrillaris and Acanthamoeba spp., keratitis due to Acanthamoeba spp., and non-central nervous system systemic infections (due to B. mandrillaris and Acanthamoeba spp.) are reviewed, and the clinical utility of microbiologic and histopathologic methods for diagnosing infections due to free-living amebae are compared.

Post-mortem pulmonary tuberculosis: comparison of available diagnostic methods.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a serious public health threat with the World Health Organisation (WHO) reporting 5.8 million cases and 1.3 million deaths in the year 2020 due to TB. TB can be diagnosed by imaging, histopathological and bacteriological methods with culture remaining the gold standard. This study was performed to look at the sensitivity and specificity of post-mortem computed tomography (PMCT) imaging when compared to culture in diagnosing pulmonary tuberculosis. This was a retrospective comparative study looking at post mortem cases where lung tissue samples sent for TB culture at Hospital Kuala Lumpur were compared against PMCT imaging. Exclusion criteria included contaminated samples, decomposed cases, immunocompromised subjects and those below 18 years of age. Subjects included 80 medico-legal autopsy cases at the National Institute of Forensic Medicine, Hospital Kuala Lumpur, Malaysia who had whole body PMCT done in accordance with the Institute's protocol and tissue samples sent for bacteriology culture for tuberculosis. PMCT findings were positively associated with acid-fast organisms in 23.5 out of 33 cases (71.2%). Our study also showed that PMCT had a sensitivity of 71.3% and specificity of 54.3% (95% CI: 39.5-68.4) in diagnosing TB based on the protocol set in this study. This study showed that there was relatively good agreement between radiological PMCT findings and bacterial culture, suggesting that radiological examination is a relatively reliable tool for preliminary screening and possible diagnosis of TB prior to a postmortem examination which would be beneficial in reducing the risk of transmission of TB to health workers during autopsy.

Three-dimensional histological electrophoresis enables fast automatic distinguishment of cancer margins and lymph node metastases.

Tissue diagnosis is important during surgical excision of solid tumors for margin evaluation. Conventional histopathologic methods rely heavily on image-based visual diagnosis by specialized pathologists, which can be time-consuming and subjective. We report a three-dimensional (3D) histological electrophoresis system for rapid labeling and separation of the proteins within tissue sections, providing a more precise assessment of tumor-positive margin in surgically resected tissues. The 3D histological electrophoresis system uses a tumor-seeking dye labeling strategy to visualize the distribution of tumor-specific proteins within sections and a tumor finder that automatically predicts the tumor contour. We successfully demonstrated the system's capability to predict the tumor contours from five murine xenograft models and distinguish the tumor-invaded region of sentinel lymph nodes. Specifically, we used the system to accurately assess tumor-positive margins from 14 patients with cancer. Our 3D histological electrophoresis system serves as an intraoperative tissue assessment technology for more accurate and automatic pathologic diagnosis.

Enhanced osseointegration of drug eluting nanotubular dental implants: An in vitro and in vivo study

Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The invivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.

Histopathological Spectrum of Gallbladder Lesions and Outcome Of Routine Histopathological Examination Of Cholecystectomy Specimens

Abstract Background: Cholecystectomy specimens are very frequently examined in a surgical pathology practice and reveal a myriad of lesions. Cholelithiasis is a major risk factor for most of the gallbladder diseases. Gallbladder is one of the most common organs where the incidental carcinoma is commonly reported in published literature. This study was intended to evaluate the histopathological spectrum of gallbladder lesions and to assess the utility of histopathological examination of cholecystectomy specimens to diagnose the incidental carcinoma. Materials and Methods: This observational and descriptive study was carried out on a total 400 cholecystectomy specimens by conventional histopathological methods. Results: Cholecystectomy specimens comprised of 4.70% all surgical pathology specimens. The mean age of patients was 41.84 ± 13.74 years. A striking female preponderance (F: M = 3.49:1) was noted. Most cases were associated with gallstones (83.5%). Non-neoplastic and neoplastic lesions comprised 97.5%, and 2.5% respectively. Chronic cholecystitis was the most frequent pathology (67.5%). Adenocarcinoma was observed in 2.25% cases and 88.89% of all malignant lesions were reported as an incidental finding. Conclusion: Gallstones are consistently observed in both neoplastic as well as non-neoplastic lesions of gallbladder. Many premalignant and malignant lesions may masquerade as chronic cholecystitis; both on clinical and radiological parameters and so, histopathology proves to be a gold standard tool for the correct diagnosis. This study affirms the importance of routine histopathological examination of each and every cholecystectomy specimen; as incidental detection of gallbladder carcinoma is very high. Key words: Histopathology, Cholecystectomy, Gallstones, Cholecystitis, Adenocarcinoma

#5863 A NOVEL SELF-SEALING DIALYSIS PORT EVALUATION

Abstract Background and Aims There are several complications associated with hemodialytic vascular that arise from the incorrect cannulation, including aneurysms, infection, vessel damage, and uncontrolled bleeding. These risks severely limit treatment opportunities for self-cannulation by patients, which is necessary step for home hemodialysis. To improve quality of life and reduce complications, we developed a novel access port, called Safe Entry Port for AV fistuLae (SEAL), that integrates with fistulae, guides cannulation, and uses an internal colinear valve to prevent aneurysms with minimal risk of back-bleeding and infections (Figure 1A-C). Method The device was additively manufactured using direct metal laser sintering of FDA-approved Ti-6Al-4V. It was then polished and coated with silver-doped titanium nitride (TiN/Ag). The operation of the valve was tested in a mock circulation system using a peristaltic pump and Tyvek tubing to produce a pulsatile hydrostatic pressure gradient. The antimicrobial properties of the valve coating were evaluated in vitro against biofilm formation using standard assays for bacterial spreading area and turbidity. A custom computer-controlled robotic cannulation system was created to fatigue test the port as well as to determine the needle force required to open the valve. Finally, the device was implanted subdermally on a mature brachiocephalic arteriovenous fistula of an adult sheep and cannulated biweekly for six weeks. Device integration and host tissue reaction were evaluated using standard histopathological methods and micro-CT scanning. Results SEAL is engineered to integrate directly over a fistula via a Ti matrix (a mesh of small holes covering the sides of the device for interaction with host tissue). No fluid leaked through the valve during in vitro testing even under physiologically high circulatory pressure. In repeated cannulations of the device during ex vivo simulations with 14G dialysis needles, the peak force required to engage the valve recorded in our dialysis fatigue cycling simulation was 160.5 $ \pm $ 0.02 mN (Figure 1D, E). The device withstood cannulation cycles equivalent to 14 years of dialysis. Furthermore, the colinear valve smoothly opened for continuous flow through the needle guide (Figure 1F-I) and closed automatically under the tensile force similar to that of subcutaneous tissue. Antimicrobial TiN/Ag coating showed significant reduction in bacterial growth in both biofilm assays (Figure 1J,K). In preclinical trials, no signs of infection or backbleeding were observed during the continuous six-week cannulation period; vascular access was continuous with no resistance or complications. Conclusion We show that SEAL nearly eliminates backbleeding risk both in vitro and in vivo. The TiN/Ag coating of the colinear valve significantly limits bacterial biofilm formation ex vivo. Preclinical studies in the sheep model show that the device implanted on a mature fistula can easily be cannulated twice a week without any infection, cannulation complications, or backbleeding for an extensive period. SEAL has the potential to change the future of dialysis treatments, improve the quality of life for patients due the reduction of complications, and allow improved access to home hemodialysis.