Osseointegration potential of boron-coated titanium alloy pedicle screw in rabbit spine model.

BACKGROUND: Spinal implants' longevity is crucial, but titanium alloys, while advantageous, lack strong bone integration. This study aimed to achieve better osseointegration rates by utilizing the ability of boron compounds to transform stem cells in the vertebra into osteoblasts. METHOD: Twenty male albino rabbits were divided into control (n = 10) and experimental (n = 10) groups. Control group received titanium alloy pedicle screws, while experimental group received boron-coated titanium alloy screws. Under general anesthesia, screws were inserted into the L6 and L7 lumbar spines. After 16 weeks, all animals were euthanized for histological examination. Vertebra samples underwent decalcification and H&E staining. Microscopic examination assessed osseointegration, necrosis, fibrosis, and vascularization using a triple scoring system by two blinded observers. RESULT: In the boron-coated titanium alloy group, all subjects exhibited osseointegration, with 50% showing focal, 40% moderate, and 10% complete osseointegration. In the titanium alloy group, 90% showed osseointegration (70% focal, 10% moderate, and 10% complete).The differences between the groups were not statistically significant (p = 0.302). Focal necrosis rates were similar between groups, with 50.0% in the titanium alloy and 60.0% in the boron-coated group (p = 0.653).Fibrosis was absent in the titanium alloy group but present in the boron-coated group, albeit with lower rates of focal fibrosis (20.0%). However, the difference was not statistically significant (p = 0.086).Vascularization patterns showed no significant difference between groups. CONCLUSION: Boron-coated titanium alloy pedicle screws provided osseointegration rates comparable to standard titanium screws and exhibited acceptable levels of necrosis and fibrosis. With stronger biomechanical properties, they could be a better alternative to currently used titanium screws.

Comparison of Pathologist and Artificial Intelligence-based Grading for Prediction of Metastatic Outcomes After Radical Prostatectomy.

Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning-based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin-stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence-based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell's C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence-assigned GG was 0.77 (95% confidence interval [CI]: 0.73-0.81), compared with 0.77 (95% CI: 0.73-0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73-0.82). PATIENT SUMMARY: Artificial intelligence-enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.

Can the Briganti 2019 nomogram be modified to predict lymph node metastasis risk in patients with prostate cancer detected with in-bore biopsy?

OBJECTIVES: We aimed to modify the Briganti 2019 nomogram and to test whether it is valid for patients who were diagnosed with prostate cancer through in-bore prostate biopsies. METHODS: Data for 204 patients with positive multiparametric prostate MRI and prostate cancer identified either by mpMRI-cognitive/software fusion or in-bore biopsy and who underwent robot-assisted radical prostatectomy and extended pelvic lymph node dissection between 2012 and 2023 were retrospectively analyzed. The Briganti 2019 nomogram was applied to the mpMRI-cognitive/software fusion biopsy group (142 patients) in the original form, and then, two modifications were tested for the targeted component. Original and modified scores were compared. These modifications were adapted for the in-bore biopsy group (62 patients). The final histopathologic stage was regarded as the gold standard. RESULTS: Nodal metastases were identified in 18/142 (12.6%) of mpMRI-cognitive/software fusion biopsy patients and 8/62 (12.9%) of the in-bore biopsy patients. In the mpMRI-cognitive/software fusion biopsy group, tumor size/core size (%) of targeted biopsy cores and positive core percentage on systematic biopsy were significant parameters for lymph node metastasis based on univariate logistic regression analyses (p < 0.05). With the modifications of these parameters for the in-bore biopsy group, V1 modification of the Briganti 2019 nomogram provided 100% sensitivity and 31.5% specificity (AUC:0.627), while V2 modification provided 75% sensitivity and 46.3% specificity (AUC:0.645). CONCLUSIONS: Briganti 2019 nomogram may be modified by utilizing tumor size/core size (%) for targeted biopsy cores instead of positive core percentage on systematic biopsy or by not taking both parameters into consideration to detect node metastasis risk of patients diagnosed with in-bore biopsies.

Natural history of histologically benign PIRADS 4-5 lesions in multiparametric MRI: Real-life experience in an academic center.

INTRODUCTION: The follow-up findings of patients who underwent prostate biopsy for prostate image reporting and data system (PIRADS) 4 or 5 multiparametric magnetic resonance imaging (mpMRI) findings and had benign histology were retrospectively reviewed. METHODS: There were 190 biopsy-naive patients. Patients with at least 12 months of follow-up between 2012 and 2023 were evaluated. All MRIs were interpreted by two very experienced uroradiologists. Of the patients, 125 had either cognitive or software fusion MR-targeted biopsies with 4 + 8/10 cores. The remaining 65 patients had in-bore biopsies with 4-5 cores. Prostate-specific antigen (PSA) levels below 4 ng/mL were defined as PSA regression following biopsy. PIRADS 1-3 lesions on new MRI images were classified as MRI regression. RESULTS: Median patient age and PSA were 62 (39-82) years and six (0.4-33) ng/mL, respectively, at the initial work-up. During a median follow-up period of 44 months, 37 (19.4%) patients were lost to follow-up. Of the remaining 153 patients, 82 (53.6%) had persistently high PSA. Among them, 72 (87.8%) had repeat mpMRI within 6-24 months which showed regressive findings (PIRADS 1-3) in 53 patients (73.6%) and PIRADS 4-5 index lesion persistence in 19 cases (26.4%). The latter group was recommended to have rebiopsy. Of these 19 patients, 16 underwent MRI-targeted rebiopsy. Prostate cancer was diagnosed in six (37.5%) patients and of these four (25%) were clinically significant (>Grade Group 1). Totally, clinically significant prostate cancer was detected in 4/153 (2.6%) patients followed up. CONCLUSION: Patients should be warned against the relative relaxing effect of a negative biopsy after identification of PIRADS 4-5 index lesion. While PSA decrease was observed in many patients during follow-up, persistent MRI findings were present in nearly a quarter of patients with persistently high PSA. A rebiopsy is warranted in these patients, with significant prostate cancer diagnosed in a quarter of patients with rebiopsy.

The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy.

BACKGROUND: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. METHODS: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. RESULTS: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. CONCLUSION: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.

Molecular Pathology of Prostate Cancer.

Molecular profiling studies have shed new light on the complex biology of prostate cancer. Genomic studies have highlighted that structural rearrangements are among the most common recurrent alterations. In addition, both germline and somatic mutations in DNA repair genes are enriched in patients with advanced disease. Primary prostate cancer has long been known to be multifocal, but recent studies demonstrate that a large fraction of prostate cancer shows evidence of multiclonality, suggesting that genetically distinct, independently arising tumor clones coexist. Metastatic prostate cancer shows a high level of morphologic and molecular diversity, which is associated with resistance to systemic therapies. The resulting high level of intratumoral heterogeneity has important implications for diagnosis and poses major challenges for the implementation of molecular studies. Here we provide a concise review of the molecular pathology of prostate cancer, highlight clinically relevant alterations, and discuss opportunities for molecular testing.

Large Language Models as a Rapid and Objective Tool for Pathology Report Data Extraction.

Medical institutions continuously create a substantial amount of data that is used for scientific research. One of the departments with a great amount of archived data is the pathology department. Pathology archives hold the potential to create a case series of valuable rare entities or large cohorts of common entities. The major problem in creation of these databases is data extraction which is still commonly done manually and is highly laborious and error prone. For these reasons, we offer using large language models to overcome these challenges. Ten pathology reports of selected resection specimens were retrieved from electronic archives of Koç University Hospital for the initial set. These reports were de-identified and uploaded to ChatGPT and Google Bard. Both algorithms were asked to turn the reports in a synoptic report format that is easy to export to a data editor such as Microsoft Excel or Google Sheets. Both programs created tables with Google Bard facilitating the creation of a spreadsheet from the data automatically. In conclusion, we propose the use of AI-assisted data extraction for academic research purposes, as it may enhance efficiency and precision compared to manual data entry.

Fusion of old and new: Employing touch imprint slides for next generation sequencing in solid tumors.

BACKGROUND: Cytomorphological evaluation of tissue touch imprints during rapid on-site evaluation or intraoperative pathology consultation has crucial value. However, literature on their utility for molecular testing is limited. In this study, we emphasize a further benefit of touch imprint slides and scrutinize our institutional experience on their use in molecular testing, specifically next generation sequencing (NGS). MATERIALS AND METHODS: NGS-based reports (2019-2023) of Koç University Hospital were retrospectively analyzed and circumstances in which sequencing was conducted on touch imprint slides were retrieved (n = 18). Type/location of the biopsy, diagnosis, results, and quality metrics were recorded. RESULTS: Touch imprints were addressed when they harbored more neoplastic cells compared with permanent biopsies, when suboptimal fixation mitigated deoxyribonucleic acid/ribonucleic acid (DNA/RNA) yield in resections or when the sample was obtained from bone and required decalcification. Diagnoses were diverse, namely non-small-cell lung cancer, gastric adenocarcinoma, glial tumor, Ewing sarcoma, and carcinoma of unknown primary. The percentage of tumor cells on slides stretched between 15% and 70%. Molecular findings ranged from KRAS mutations to TRIM1::NTRK2 and EWSR::FLI1 fusions. For five cases, sequencing did not yield any alteration, one study was not completed because it did not yield high-quality RNA. CONCLUSION: Touch imprint slides provide a reliable alternative, especially when neoplastic cells are scarce in permanent biopsies or decalcification deters nucleic acid quality. Based on our experience, we suggest making touch imprints on a routine basis, especially for every bone biopsy. Once digitally scanned duplicates are made, original slides can be safely used for DNA-/RNA-based molecular studies.

Novel ALK immunohistochemistry assay (clone OTI1A4, Dako) is a sensitive, reliable marker for identifying ALK rearrangements in lung adenocarcinomas: A validation study.

OBJECTIVES: We present the first study validating the recent Dako ALK assay (clone OTI1A4, in vitro diagnostic) for detecting ALK rearrangements in lung adenocarcinoma. METHODS: Lung adenocarcinoma cases between 2011 and 2023 were retrospectively collected to create a cohort of 203 samples. Cases were stained with Dako ALK OTI1A4 and Ventana ALK D5F3 and reviewed by 3 pathologists independently. Correlation between assays, including their sensitivity and specificity, was evaluated. RESULTS: The cohort (n = 203) consisted of resections, core needle biopsies, and cell blocks. Agreement between Dako ALK OTI1A4 and Ventana ALK D5F3 assays was "almost perfect," with κ = 0.89. The sensitivity and specificity of the Dako ALK OTI1A4 assay were 93.3% and 96%, respectively, in a subgroup of 55 molecularly confirmed cases (n = 30 with and n = 25 without ALK rearrangement). CONCLUSIONS: Immunohistochemistry-based assays provide a valid and reasonably priced alternative, especially in settings where molecular confirmatory tests are neither offered nor accessible. Given high interassay and molecular concordance, we propose that the novel Dako OTI1A4 assay can be reliably used to identify cases with ALK rearrangement.

Pathological perspectives in pilocytic astrocytomas: Extent of resection as the sole critical factor for recurrence-free survival, and the challenge of evaluating conclusions derived from limited data.

Introduction: Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. Materials and Methods: We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. Results: Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p <0.001). Conclusion: Multivariate analysis was able to identify extent of resection as the only significant variable to influence recurrence-free survival. We did not find a statistically significant association between age, NF1 status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival.

Intraoperative Frozen Section via Neurosafe During Robotic Radical Prostatectomy in the Era of Preoperative Risk Stratifications and Primary Staging With mpMRI and PSMA-PET CT: Is There a Perfect Candidate?

BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.

Predicting Prostate Cancer Molecular Subtype With Deep Learning on Histopathologic Images.

Microscopic examination of prostate cancer has failed to reveal a reproducible association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H&E)-stained whole slide images (WSI) may outperform the human eye and help to screen for clinically-relevant genomic alterations. We created deep-learning algorithms to identify prostate tumors with underlying ETS-related gene (ERG) fusions or PTEN deletions using the following 4 stages: (1) automated tumor identification, (2) feature representation learning, (3) classification, and (4) explainability map generation. A novel transformer-based hierarchical architecture was trained on a single representative WSI of the dominant tumor nodule from a radical prostatectomy (RP) cohort with known ERG/PTEN status (n = 224 and n = 205, respectively). Two distinct vision transformer-based networks were used for feature extraction, and a distinct transformer-based model was used for classification. The ERG algorithm performance was validated across 3 RP cohorts, including 64 WSI from the pretraining cohort (AUC, 0.91) and 248 and 375 WSI from 2 independent RP cohorts (AUC, 0.86 and 0.89, respectively). In addition, we tested the ERG algorithm performance in 2 needle biopsy cohorts comprised of 179 and 148 WSI (AUC, 0.78 and 0.80, respectively). Focusing on cases with homogeneous (clonal) PTEN status, PTEN algorithm performance was assessed using 50 WSI reserved from the pretraining cohort (AUC, 0.81), 201 and 337 WSI from 2 independent RP cohorts (AUC, 0.72 and 0.80, respectively), and 151 WSI from a needle biopsy cohort (AUC, 0.75). For explainability, the PTEN algorithm was also applied to 19 WSI with heterogeneous (subclonal) PTEN loss, where the percentage tumor area with predicted PTEN loss correlated with that based on immunohistochemistry (r = 0.58, P = .0097). These deep-learning algorithms to predict ERG/PTEN status prove that H&E images can be used to screen for underlying genomic alterations in prostate cancer.

STRN-ALK rearranged malignant peritoneal mesothelioma-Presenting with bilateral extensive pelvic masses in a young woman: Mimicking low-grade serous ovarian carcinoma.

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

Fluorescence-guided extended pelvic lymphadenectomy during robotic radical prostatectomy.

We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.

Senior Moments Are Never-ending Times When You Are Old (Are They?): First Step of Turquoise Project.

Introduction: The number of dementia patients in Turkey is increasing, as well as all over the world. However, we do not know how much society knows about dementia. The aim of this study is to evaluate people's concept of dementia, their awareness of dementia research and treatment, whether dementia and forgetfulness are considered normal in old age, and whether having dementia is associated with a lack of mental abilities. Methods: A Dementia Awareness Questionnaire was created in the form of a self-report questionnaire, consisting of 20 questions and using a five-point Likert-type answering method in order to question participants' information about dementia. In addition, we asked for demographic information such as age, gender, occupation, education level of the participants, as well as whether they have had relatives diagnosed with a neurodegenerative disease. The surveys were administered online. Results: A total of 1551 participants from 53 cities were included in the study. Approximately half of the participants did not know the definition of dementia, 20.9% thought that dementia and Alzheimer's disease were the same; 50.4% considered forgetfulness, and 55.2% considered dementia as a natural consequence of aging. While 34.5% of the participants thought that dementia patients could be dangerous, 10.3% thought they could not continue living as a part of society. While 38.5% of healthcare professionals do not know the definition of dementia, 18.5% of them say that dementia and Alzheimer's disease are the same, 58.5% think that dementia patients are not fit to make their own decisions, 40.6% believe that dementia patients have criminal liability. 15.8% of healthcare professionals thought that dementia is only seen in elderly people; 21.4% thought that dementia, and 49.2% thought that forgetfulness was a result of normal aging. Conclusion: Our study confirms that dementia is still an unknown concept in society and among healthcare professionals. It is widely believed that forgetfulness and dementia are part of normal aging, and there is no cure for dementia. This study, which we have done in order to understand the level of dementia awareness in Turkish society, reveals the necessity for research on dementia and studies on how to increase dementia awareness.

Towards Development of a Standard Terminology of the World Health Organization Classification of Tumors of the Central Nervous System in the Turkish Language, and a Perspective on the Practical Implications of the WHO Classification for Low and Middle Income Countries.

In our manuscript, we propose a common terminology in the Turkish language for the newly adopted WHO classification of the CNS tumors, also known as the WHO CNS 5th edition. We also comment on the applicability of this new scheme in low and middle income countries, and warn about further deepening disparities between the global north and the global south. This division, augmented by the recent COVID-19 pandemic, threatens our ability to coordinate efforts worldwide and may create significant disparities in the diagnosis and treatment of cancers between the "haves" and the "have nots".

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

Impact of the Amyotrophic Lateral Sclerosis Disease on the Biomechanical Properties and Oxidative Stress Metabolism of the Lung Tissue Correlated With the Human Mutant SOD1G93A Protein Accumulation.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, and ALS incidence is increasing worldwide. Patients with ALS have respiratory failure at the disease's end stages, leading to death; thus, the lung is one of the most affected organs during disease progression. Tissue stiffness increases in various lung diseases because of impaired extracellular matrix (ECM) homeostasis leading to tissue damage and dysfunction at the end. According to the literature, oxidative stress is the major contributor to ECM dysregulation, and mutant protein accumulation in ALS have been reported as causative to tissue damage and oxidative stress. In this study, we used SOD1G93A and SOD1WT rats and measured lung stiffness of rats by using a custom-built stretcher, where H&E staining is used to evaluate histopathological changes in the lung tissue. Oxidative stress status of lung tissues was assessed by measuring glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR), glutathione s-transferase (GST), catalase (CAT), and superoxide dismutase 1 (SOD1) levels. Western blot experiments were performed to evaluate the accumulation of the SOD1G93A mutated protein. As a result, increased lung stiffness, decreased antioxidant status, elevated levels of oxidative stress, impaired mineral and trace element homeostasis, and mutated SOD1G93A protein accumulation have been found in the mutated rats even at the earlier stages, which can be possible causative of increased lung stiffness and tissue damage in ALS. Since lung damage has altered at the very early stages, possible therapeutic approaches can be used to treat ALS or improve the life quality of patients with ALS.