Radiologic and histopathologic effects of favipiravir and hydroxychloroquine on fracture healing in rats.

Fracture healing is a process in which many factors interact. In addition to many treatments, physical and biological therapy methods that affect different steps of this process, there are many biological and chemical agents that cause fracture union delay. Although the number of studies on fracture healing is increasing day by day, the mechanism of fracture healing, which is not fully understood, still attracts the attention of all researchers. In this study, we aimed to investigate the effects of favipiravir and hydroxychloroquine used in the treatment of COVID-19. In this study, 48 male Wistar rats weighing 300 ± 50 g were used. Each group was divided into eight subgroups of six rats each to be sacrificed at the 2nd and 4th weeks and evaluated radiologically and histologically. Favipiravir (group 1), hydroxychloroquine (group 2), favipiravir + hydroxychloroquine (group 3), and random control (group 4) were used. A statistically significant difference was observed between the 15th day histological scoring averages of the groups (p < 0.05). Although there was no statistically significant difference between the 15th day radiological score distributions of the groups (p > 0.05), we obtained different results in terms of complete bone union distributions and radiological images of the fracture line. Although favipiravir has a negative effect on fracture union in the early period, favipiravir may have a positive effect on fracture union in the late period. We did not find any effect of hydroxychloroquine on fracture union.

Metastatic Melanoma of the Common Bile Duct Presented with Dyspepsia.

Malignant melanoma (MM) is an aggressive tumor that can metastasize to any organ, but biliary tract metastasis is scarce. We describe a very rare case of MM metastasis to the common bile duct (CBD), presented with only dyspeptic symptoms. The patient had mildly elevated alkaline phosphatase and gamma-glutamyl transferase levels. Magnetic resonance cholangiopancreatography demonstrated a dilated common bile duct with a distal stricture. The MM diagnosis was established with the ampulla of Vater biopsy specimens obtained by endoscopic retrograde cholangiopancreatography (ERCP), and the patient's symptoms were resolved after biliary stenting. Both primary CBD cancer and other cancer types like MM that metastasize to CBD can cause obstruction and can be manifested only by dyspeptic symptoms. MM metastasis to CBD can cause obstruction manifested only by dyspeptic symptoms without obstructive jaundice. ERCP can be employed as a promising option for treatment and diagnosis. New-onset dyspeptic symptoms in patients with a history of MM should be investigated thoroughly, especially in the context of biliary metastasis.

Investigation of the effects of pentoxifylline and alpha tocopherol treatment on recovery in rats with Achilles tendon rupture.

Although the Achilles tendon is the largest and strongest tendon in the body, healing of the Achilles tendon is the most common injury, and this process is difficult due to poor tendon circulation; moreover, the underlying mechanism has not been fully elucidated. In our study, we aimed to investigate the effects of pentoxifylline and alpha-tocopherol administered separately or in combination on rats with Achilles tendon injury. Forty-eight male Wistar rats weighing 230 ± 30 g were used in the study. The rats were randomly divided into eight groups of six animals each. Tendons were evaluated histopathologically and biomechanically. According to the statistical analysis, the vascularity density in the pentoxifylline group on day 14 was significantly greater than that in the other groups (p < 0.05). The collagen arrangement in the pentoxifylline and alpha-tocopherol groups on day 14 was found to be firmer and smoother than that in the control group (p < 0.05). The collagen arrangement in the pentoxifylline group on day 28 was greater than that in the other groups (p < 0.05). The biomechanical results were significantly greater in all groups (p < 0.05). Pentoxifylline contributed to tendon healing both through neovascularization in the early period and by improving collagen orientation in the late period, while alpha-tocopherol had a positive effect on collagen orientation in the early period. No beneficial effects were observed when pentoxifylline and alpha-tocopherol were used together. We believe that further research is needed to understand the effects of this combination therapy on tendon healing.

Receptor Tyrosine Kinase Pathway and Infiltrating Urothelial Carcinoma.

Receptor tyrosine kinase pathway is frequently searched for cancer causing mutations in tumors. Emerging targeted therapies are gleam of hope for them. Infiltrating urothelial carcinoma can have many morphological aspects according to their differentiation/variants. To evaluate KRAS, BRAF, and PIK3CA mutations and HER2, EGFR, and p16 expression, we divided urothelial carcinomas into two groups: differentiated/variants (n = 12) and conventional (n = 12). We compared results with clinical, demographic, histopathologic features and survival rates. No statistically significant results could be obtained in the comparison of histopathologic properties/survival rates with mutation analysis and EGFR, HER2, and p16 status. Differentiated/variants urothelial carcinoma showed higher EGFR expression (P < 0.001). Glandular differentiation was the most frequent type, followed by squamous and sarcomatoid differentiation. We observed the most common mutation at KRAS with a propensity for urothelial carcinoma with glandular differentiation. More than one mutation/high protein expression was seen in some tumors. Targeted therapies for KRAS mutation can be effective at urothelial carcinoma with glandular differentiation. Heterologous expression of relevant proteins and genes can be a cause for targeted treatment obstacle. The determination of the molecular characters of tumors is a guide in creating targeted treatment algorithms and in choosing the patient.

STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival?

Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.

CD123 immunoexpression in cutaneous lupus erythematosus, polymorphous light eruption, pityriasis rosea, and mycosis fungoides.

INTRODUCTION: CD123-positive plasmacytoid dendrocytes are prominent in the infiltrate of cutaneous lupus erythematous. AIM: To determine the significance of the CD123 immunostain, which labels plasmacytoid dendritic cells (PDC), in cutaneous lupus erythematous (CLE), polymorphous light eruption (PLE), pityriasis rosea (PR) and mycosis fungoides (MF). MATERIAL AND METHODS: A total of 76 cases, including MF (n = 27), CLE (n = 19), PR (n = 19), and PLE (n = 11), were included in the study after reviewing their diagnostic clinical features and pathologic findings. The primary antibody against CD123 was performed in all cases. RESULTS: CD123+ immunostaining in PDCs was positive in all cases. The highest mean percentage was noted in CLE (15.2%), followed by PLE (15%), PR (8.8%), and MF (2%). Besides, the clustering of CD123-positive cells was significant in CLE and PLE compared to MF and PR. CONCLUSIONS: PDC may have an important role in the aetiology of PLE and CLE cases. CD123 is a useful marker for differentiating CLE and PLE from MF and PR.

Analysis of HPV Genotypes and Liquid-Based Cervical Cytology: Results from a Tertiary Academic Center in Northwestern Turkey.

High-risk human papilloma virus (hrHPV) plays an important role in cervical cancer. The aim of this study was to investigate the distribution of HPV genotypes in the region and to correlate it with liquid-based-cytology (LBC) and colposcopic biopsy results. Furthermore, the potential relationship between HPV infections and bacterial vaginosis (BV) was investigated. HPV genotypes were determined using real-time PCR. LBC, biopsies, and BV examinations were performed by the Pathology and Cytology. Consecutive cervical specimens of 409 women who underwent both cytology and HPV-DNA tests were included in the study. A total of 172 (42.1%) patients were positive for HPV-DNA; of these, 107 (26.2%) had hrHPV. The most common HPV genotypes were HPV 59, 16, 33, 52, and 51, at 16.6%, 15.9%, 13.4%, 13.4%, and 8.9%, respectively. Epithelial cell abnormality was detected in 11.5% of LBC test results. The genotypes of HPV 33, 56, 66, and 68 were found at a higher rate in patients with epithelial cell abnormalities than in those with no detected abnormalities. Bacterial vaginosis was found in 24 patients (5.9%). HPV-DNA positivity was observed to be statistically higher in patients with BV than in those without BV.

BRAF mutation, TERT promoter mutation, and HER2 amplification in sporadic or neurofibromatosis-related neurofibromas and malignant peripheral nerve sheath tumors: do these molecules have a signature in malignant transformation?

Peripheral nerve sheath tumors may occur sporadically or related to neurofibromatosis (NF). Unless the mechanisms of tumorigenesis in NF related malignant peripheral nerve sheath tumors (MPNST) are better understood, it remained unclear in sporadic cases. We aimed to investigate the genetic route for malignancy in both individuals with NF-1 and sporadic ones to open a way for targeted therapies in the future. We investigated the role of HER2 with Dual ISH DNA Probe Cocktail test, BRAF mutation (exon 15) and TERT promoter mutation frequency with Sanger sequencing method in respectively 25 sporadic neurofibromas, 25 NF-1 related neurofibromas and 25 MPNST cases from two institutes. Categorical data were analyzed and summarized as frequency and percentage. Statistical analysis was done with SPSS v.22 statistical package, and the statistical significance level was considered as 0.05. We identified TERT promoter mutation only in one sporadic MPNST (4%) and no BRAF mutation in any case. HER2 amplification is found in 10/25 (40%) MPNST cases. No mutations or gene amplification detected in neurofibromas (p < 0.001). MPNSTs are sarcomas with poor prognosis and limited treatment options. TERT promoter mutations and HER2 amplification may play a putative role in therapeutic purposes.

KRAS, BRAF, PIK3CA mutation frequency of radical prostatectomy samples and review of the literature.

OBJECTIVE: The molecular basis of prostate cancer is highly heterogeneous. Our study aimed to perform the mutation analysis of KRAS, BRAF, PIK3CA, and immunohistochemical (IHC) evaluation of EGFR, HER2, p16, and PTEN to demonstrate new areas for targeted therapies. METHODS: A total of 24 prostatectomy samples diagnosed with adenocarcinoma were analyzed by microarray hybridization. Also, these samples were IHC stained for EGFR, HER2, P16, and PTEN. The cases were divided into two groups based on low and high Gleason scores. All findings were compared with the clinicopathological parameters of the patients. RESULTS: While KRAS mutation was in 3/24 (12.5%) of our cases, BRAF and PIK3CA mutations were not detected. There was no significant difference between the groups in terms of KRAS mutation frequency. HER2 was immunohistochemically negative in all samples. There was no correlation between EGFR, P16 immunopositivity, and clinicopathological features. CONCLUSION: KRAS mutation frequency is similar to those in Asian populations. BRAF and PIK3CA mutation frequencies have been reported in the literature in the range of 0-15% and 0-10.4%, respectively, consistent with our study findings. HER2 immunoexpression is a controversial issue in the literature. EGFR and p16 expressions may not correlate with the stage.

Retrospective analysis of clinicopathological features of solid pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm that accounts for 2-3% of all primary pancreatic neoplasms. This study aimed to characterize clinicopathological features associated with SPNs and to retrospectively evaluate the relationship of these features with predictive parameters associated with aggressive behavior. We reviewed 16 cases of SPN of the pancreas that had been diagnosed between 2005 and 2014 at our pathology department. A total of 16 cases, 15 female and one male, were evaluated in this study. The patient age ranged from 13 years to 63 years with a median of 35.70 years. The mean tumor diameter ranged from 2 cm to 18 cm with a mean diameter of 5.90 cm. We identified a significant association between the presence of clear cells and perineural invasion (p=0.019), which was considered to be a predictive factor for aggressive behavior. Other features (i.e., localization, nuclear grooves, central hyalinization, myxoid stroma, eosinophilic bodies, foamy histiocyte aggregates, multinucleated cells, and calcification) were not significantly associated with predictive factors for aggressive behavior. One patient died as a result of a pancreatic fistula that developed as a postoperative complication. The remaining 15 patients are alive and have not demonstrated any signs of recurrence or metastasis. The current study suggested that the presence of clear cells might serve as a possible prognostic indicator of perineural invasion, which is a predictive parameter associated with aggressive behavior in SPN.