Clinical Behavior Research Articles

Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present

Recently, homologous recombination deficiency (HRD) has become a new target for hereditary cancers. Molecular-based approaches for hereditary cancers in the clinical setting have been reviewed. In particular, the efficacy of the PARP inhibitor has been considered by several clinical trials for various kinds of hereditary cancers. This indicates that the PARP inhibitor can be effective for any kind of BRCA mutated cancers, regardless of the organ-specific cancer. Homologous recombination deficiency (HRD) has become a new target for hereditary cancers, indicating the necessity to confirm the status of HRD-related genes. ARID1A, ATM, ATRX, PALB2, BARD1, RAD51C and CHEK2 are known as HRD-related genes for which simultaneous examination as part of panel testing is more suitable. Both surgical and medical oncologists should learn the basis of genetics including HRD. An understanding of the basic mechanism of homologous repair recombination (HRR) in BRCA-related breast cancer is mandatory for all surgical or medical oncologists because PARP inhibitors may be effective for these cancers and a specific strategy of screening for non-cancers exists. The clinical behavior of each gene should be clarified based on a large-scale database in the future, or, in other words, on real-world data. Firstly, HRD-related genes should be examined when the hereditary nature of a cancer is placed in doubt after an examination of the relevant family history. Alternatively, HRD score examination is a solution by which to identify HRD-related genes at the first step. If lifetime risk is estimated at over 20%, an annual breast MRI is necessary for high-risk screening. However, there are limited data to show its benefit compared with BRCA. Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.

Nodular fasciitis: a case series unveiling novel and rare gene fusions, including two cases with aggressive clinical behavior.

Nodular fasciitis is a benign myofibroblastic tumor characterized by rapid growth and spontaneous regression. While nodular fasciitis is typically an indolent process, rare cases with benign morphologic features have developed metastases. Conversely, nodular fasciitis with malignant histologic features and benign clinical course have also been reported. In this study, we present seven nodular fasciitis cases with novel USP6 gene fusion partners, in addition to two cases with rare fusions that displayed aggressive clinical behavior. The cohort comprised five females and four males with a median age of 36years (range 13-59). Tumors were located in the forearm (n = 3), thigh (n = 2), and shoulder, abdominal wall, chest wall, and oral cavity (one each), ranging from 1.4 to 24.0cm in size (median, 2.2cm). Except for the clinically aggressive cases, patients presented with painless masses of varying onset from days to months. Of the clinically aggressive cases, one patient presented with a slowly growing subfascial thigh/hip mass over nine years, leading to erosion of the femur and pelvis; the other presented with a painful subfascial thigh mass of several months' duration. Histologically, all cases, including the clinically aggressive ones, showed conventional nodular fasciitis features without nuclear pleomorphism or atypical mitotic figures; one case with aggressive clinical behavior exhibited focal infarction-type necrosis. Break-apart FISH analysis using USP6 flanking probes failed to detect USP6 rearrangement in two cases (false negatives) and was inconclusive in one case. Next-generation RNA sequencing identified USP6 fusions in all cases. The clinically aggressive cases showed fusions with COL1A1 (exon 1) and PPP6R3 (exon 1), while novel fusions were identified in the remaining cases including EIF4A1 (exon 1), FILIP1L (exon 2), NF1 (exon 33), OMD (exon 1), PFN1 (exon 1), RLIM (exon 1), and SETD5 (exon 1). Six patients underwent surgical resection; three were managed conservatively, with two experiencing spontaneous tumor resolution. Of the clinically aggressive cases, one patient had progression of the tumor with erosion of the underlying bone, and the second patient developed local recurrence at 14months and lung metastasis at 19months, ultimately dying of disease at 22months. The remaining patients showed no recurrence or metastasis. Our findings expand the spectrum of USP6 gene fusion partners in nodular fasciitis and, for the first time, report cases with conventional morphology exhibiting aggressive behavior, including death. These observations raise the question of whether a subset of deep lesions with conventional nodular fasciitis histology but unusual clinical features, such as large tumor size, represents malignant nodular fasciitis or alternatively a nodular fasciitis-like myofibroblastic sarcoma.

Acquiring a Comprehensive Awareness of the Current Insights on Pediatric Oral and Maxillofacial Malignancies

AbstractOrofacial tumors constitute a heterogeneous collection of pathological conditions characterized by distinct types of histology and clinical behaviors. Numerous accounts of craniofacial tumors in kids and young adults are being recorded globally. Within the pediatric population, leukemia, lymphoma, and nervous system tumors are the most common forms of pediatric cancer in developing nations; yet, when concentrating on specific anatomical regions, such as the head and neck, the incidence of malignant tumors is comparatively low. Additionally, the occurrence of oral and maxillofacial malignancy in pediatric populations is rare, varying from roughly 0.5 to 6%. The authors of this article conducted a comprehensive retrospective review of various cases and studies concerning oral and maxillofacial malignancies in the pediatric population, utilizing electronic databases, such as PubMed, Scopus, Web of Science, and Google Scholar to identify pertinent articles. We performed a narrative review on the current aspects and therapeutic procedures related to the four most prevalent oral and maxillofacial malignancies: Burkitt's lymphoma, mucoepidermoid carcinoma, rhabdomyosarcoma, and osteosarcoma.

Utility of p53 and p16 immunohistochemistry in the diagnosis of human papillomavirus-associated oral epithelial dysplasia: a retrospective study of 105 patients.

This study investigated the utility of combined p16 and p53 immunohistochemistry (IHC) for diagnosing high-risk human papillomavirus (HR HPV)-associated oral epithelial dysplasia (OED) and its associated clinical behaviour, including disease recurrence and transformation to malignancy. The expression of p53 was evaluated in 105 cases of HR HPV-positive oral cavity OED, of which 104 were scored as positive for p16. HPV status was confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for E6 mRNA or RNA in situ hybridization (ISH). Seven cases of p16-positive oral cavity OED with abnormal p53 expression and/or TP53 mutation and negative HPV RNA ISH were excluded. Most cases (93%) demonstrated classic HPV-associated basaloid morphology, and 7% were keratinizing. The most affected sites were the floor of the mouth/ventral tongue (61%), followed by the lateral tongue (18%) and gingiva (13%). p53 IHC showed that 76% of cases demonstrated a null-like / basal-sparing pattern, while 24% demonstrated a mid-epithelial/basal sparing pattern. Ten cases exhibited an invasive or suspicious for microinvasive component on biopsy. Dysplasia recurred in 14 cases, and a single case transformed to squamous cell carcinoma. The combination of p16 positivity and a basal-sparing pattern of p53 is predictive of HR HPV in OED, eliminating the need for further HPV-specific testing. Although HPV OED may co-occur with invasive squamous cell carcinoma on biopsy, the transformation to malignancy is low.

Myxoid liposarcoma: treatment outcomes, metastatic pattern and volumetric analysis.

Myxoid liposarcoma (MLPS) is arare subtype of soft tissue sarcoma. This entity has aspecific clinical behavior, characterized with adistinct pattern of hematogenous spread, as well as with aunique radiosensitivity and chemosensitivity. Oncologic results, metastatic patterns and treatment response after multimodal therapy were evaluated in aunicentric patient cohort. Patients with myxoid liposarcoma were retrospectively analyzed in asingle institution analysis (n = 31). Oncologic outcomes were evaluated in 28patients with localized MLPS treated with multimodal therapy in curative intent. Metastatic pattern was analyzed in additional 3patients with initially metastatic disease. In patients treated with concomitant MR-guided hyperthermia in the preoperative setting (n = 7), tumor size response was evaluated longitudinally during radio(-chemo)therapy in thermometry MRIs and before surgery (based on preoperative imaging). The median follow-up was 4.1 ± 1.0years. The most common anatomic localization was the lower extremity (78.6%). The 5‑year rates for oncologic outcomes in 28patients treated in curative intent were 91.7% (± 8.0%) for overall survival (OS), 77.4% (± 11.0%) for local control (LC), 60.1% (± 10.6%) for distant metastasis-free survival (DMFS) and 55.4% (± 11.1%) for disease free survival (DFS). Excellent 5‑year LC (94.7 ± 5.1%) was demonstrated for the cohort excluding 5patients treated for local recurrences. Most patients had good pathologic response (< 10% vital tumor tissue) following neoadjuvant treatment (82.4%, 14/17). However, this did not correlate with oncologic outcomes. Aspecific pattern of distant metastases has been observed, with predilection for soft tissues as the most common metastatic site. Furthermore, no isolated pulmonary metastases were observed. The MR analysis demonstrated asignificant tumor size reduction (≥ 25%) of the initial tumor volume in 85.7% (n = 6/7) patients. No local recurrences and no distant metastases were observed in patients with significant MR size reduction. Sequential MRIs during preoperative radiotherapy of myxoid liposarcoma show distinct patterns of the known size reduction of this specific subentity. Our analysis of metastatic patterns demonstrate mostly soft tissue metastases, no patient experienced isolated pulmonary metastases.

The paradoxical role of SERPINB5 in gastrointestinal cancers: oncogene or tumor suppressor?

SERPINB5, also known as Maspin, is a non-inhibitory member of the serine protease inhibitor superfamily. SERPINB5 exerts diverse effects on a variety of human cancers, including cell proliferation, angiogenesis, apoptosis, tumor invasion, and metastasis. SERPINB5 has traditionally been regarded as a tumor suppressor gene, but emerging evidences supports its oncogenic properties. We conducted a comprehensive review of the existing literature on SERPINB5 in gastrointestinal cancers, synthesizing data on its expression patterns, subcellular localization, epigenetic modifications, and clinical significance. Depending on its subcellular localization and epigenetic modifications, SERPINB5 demonstrate either protumor or antitumor activity in different gastrointestinal cancers, such as colorectal cancer, gastric cancer, pancreatic cancer, gallbladder cancer and liver cancer. We elucidate its potential as a predictive and prognostic biomarker, with a focus on its implications for diagnosis, prognosis, and therapeutic intervention, emphasizing its utility in early lesion detection and treatment. SERPINB5 plays a complex and context-dependent role in gastrointestinal cancers, highlighting further research to dissect the true significance of SERPINB5 expression and the molecular mechanisms underlying its divergent clinical behaviors in cancer.

IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread

IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course.

Chondrosarcoma in Japan: an analytic study using population-based National Cancer Registry.

Chondrosarcoma (CS) is a rare malignant bone tumor exhibiting diverse histological features and clinical behaviors. This study aimed to investigate the epidemiological characteristics, clinical features, prognostic factors, and subtype-specific differences of CS in Japan using National Cancer Registry data. We analyzed data from CS cases diagnosed between 2016 and 2019, calculating age-adjusted incidence, estimating overall survival, and identifying prognostic factors through multivariate analysis. The study identified 1015 CS cases with an age-adjusted incidence of 0.159 per 100 000 population and a mean overall survival of 1205.2days. Multivariate analysis revealed that female sex, younger age (15-39years), histological subtypes other than dedifferentiated CS, localized disease, and surgical treatment were associated with better prognoses. Conversely, male sex, older age (≥75years), dedifferentiated subtype, advanced stage, and non-surgical treatment were linked to a higher risk of death. Significant differences in sex distribution, age at diagnosis, tumor location, disease stage, and tumor differentiation were observed among CS subtypes. This comprehensive analysis provides valuable insights into CS epidemiology, prognostic factors, and subtype-specific characteristics in Japan. The identification of high-risk groups emphasizes the need for improved therapeutic strategies and supportive care. The observed heterogeneity among CS subtypes underscores the importance of individualized management approaches in treating this complex malignancy.

Evaluating an Early-Stage Psychosis Training Program for Interdisciplinary Mental Health Students and Trainees: A Mixed-Methods Pilot Study.

Identifying young people in the early stages of psychosis identification is critical, since a longer duration of untreated psychosis is associated with poorer recovery outcomes. However, many mental health students and trainees do not receive training in this area. The aim of this study was to pilot test the effectiveness of an early-stage psychosis training program for mental health students and trainees. A pre/post matched sample of interdisciplinary mental health students and trainees (N = 21) attended a 75-min early-stage psychosis training program, and completed measures related to stigma, clinical training outcomes, and knowledge. There were significant improvements in psychosis-related stigma, intended clinical behaviour and knowledge. There was also high satisfaction with the training program. This study suggests that a brief early-stage psychosis training program is acceptable to students and trainees and feasible to implement and may yield significant benefits regarding students and trainees' personal psychosis stigma, as well as improvements in clinical behaviour and psychosis knowledge.

Australian occupational therapists' perspectives about the management of driving safety concerns for older people with dementia and mild cognitive impairment.

Driving safety may be compromised in people with dementia or mild cognitive impairment (MCI). Occupational therapists assess and screen for driving safety in older people with cognitive impairment. However, little is known about their perspectives relating to these assessments. Aims included to (1) obtain perspectives from driver-trained and non-driver-trained occupational therapists about the management of driving safety concerns for older people with dementia and MCI; (2) understand factors influencing clinician's behaviour relating to driving assessment; and (3) gain perspectives regarding resources to support fitness-to-drive assessment. Semi-structured interviews were conducted with occupational therapists recruited from driving assessment services, hospitals, and community settings in Australia. Data were analysed inductively using content analysis, followed by a deductive approach with two authors mapping subcategories to the domains of the Theoretical Domains Framework and Capability, Opportunity and Motivation-Behaviour model. No consumers were involved in the design or study analysis. Participants (n = 17) reported inconsistencies in how the fitness-to-drive assessment is managed, with driving safety concerns often missed or avoided. Perceived barriers to fitness-to-drive assessment included: (i) clinician's capabilities: limited knowledge about fitness-to-drive assessment, and difficulties having complex discussions with patients with cognitive impairment; (ii) motivational factors: lack of confidence, fear of damaging therapeutic relationship with patients, and desire to maintain a sense of professional identity; and (iii) environmental factors: lack of processes to support health professionals with identifying cognitive concerns, lack of clarity of who takes responsibility for managing driving safety concerns, time constraints for completing in-office assessments and limited access to practical occupational therapy driving assessments. Participants expressed a desire for an evidence-based clinical pathway to improve the knowledge and communication skills of clinicians from non-driving specialist settings. Findings identify the need for an evidence-based pathway to support health professionals in managing driving safety concerns for people with dementia and MCI. Dementia and mild cognitive impairment (MCI) are brain conditions involving difficulty with memory and thinking, with dementia diagnosed when the changes are more severe. These conditions are not a normal part of getting older, but they are much more common in older people. Research has found that some, but not all, people with dementia and MCI show unsafe driving behaviours. As people with dementia and MCI are often unaware that their driving is unsafe, health professionals, such as doctors and occupational therapists, should be involved in deciding if, or when, they should stop driving. In this study, occupational therapists were asked to provide their opinions about how driving safety concerns for older people with dementia and MCI are managed by health professionals. Occupational therapists reported that there is variation in how concerns are managed, with driving problems often getting missed or avoided. They reported that this can happen because health professionals may not feel confident in their decision-making abilities, or they may feel that discussing driving concerns will cause the person to get upset or angry with them. They also reported that health professionals may not always know that a person has dementia or MCI, and if they do know, it is not always clear which health professional should take on the responsibility of considering the person's driving safety. The occupational therapists wanted a resource to support health professionals in providing more consistent care for patients relating to driving safety.

Clinical and genetic drivers of oligo-metastatic disease in colon cancer.

Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior. Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as ≤3 lesions per organ, each with a total diameter <70 mm and none exceeding 25 mm. Tumor DNA sequencing by NGS utilized the TruSight Oncology 500 kit. Overall survival (OS) was determined from metastasis diagnosis until death using Kaplan-Meier analysis. Multivariate Cox regression examined prognostic links between clinicopathological and genetic factors. Associations with metastatic patterns were evaluated using Chi-square. The analysis involved 104 patients (44 with OMD, 60 with PMD). OMD was more prevalent in males (P = 0.0299) and with single organ involvement (P = 0.0226). Multivariate analysis adjusted for age (>70 vs. <70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and RAS/BRAF variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.06-0.33; P<0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of BRAF p.V600E (P=0.0315) and KRAS mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (P=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: BRAF, SMAD4, RAF1, and mTOR) may prevent OMD occurrence. OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.

Patterns of metastatic spread and survival outcomes for stage IV left-sided colon vs. rectal cancers: A real-world analysis.

75 Background: A growing body of literature has reported differences in biology, metastatic potential, and outcomes among patients with colorectal cancer based on the sidedness of their primary tumor (right vs. left). Left-sided primary tumors have comprised both colon and rectal tumors, despite differences in venous and lymphatic drainage patterns and treatment paradigms. The present work sought to investigate patterns of metastases and survival outcomes among patients with left sided colon primary tumors and rectal primary tumors. We hypothesized that these two disease sites metastasize differently and exhibit different survival patterns based on metastatic site. Methods: The National Cancer Database (NCDB) was queried for all patients with a diagnosis of metastatic left-sided colon (splenic flexure, descending colon, rectosigmoid) or rectal adenocarcinoma with known primary site and known metastatic site(s) between 2010 and 2021 using parameters outlined in the NCDB Data Dictionary. Patients with left-sided colon primaries (LP) were compared to patients with rectal primaries (RP) along clinicodemographic parameters. Incidence of metastases to the liver, lungs, bone, brain, and non-regional lymph nodes were also compared. Multivariable survival analyses were performed to analyze differences in overall survival (OS). Results: Among 84,958 patients, 51,931 (61.1%) had LP while 33,027 (38.9%) had RP. Patients with RP were less likely to have liver metastases than those with LP (79.4% vs. 90.3%), but more likely to have lung (40.7% vs. 29.2%), bone (8.3% vs. 6.0%), and distant lymph node metastases (11.3% vs. 8.6%) (all p&lt;0.001). Compared to patients with LPs, patients with RP were less likely to undergo surgery to the primary tumor (25.1% vs. 46.3%) or any metastatic site (15.3% vs. 18.8%), more likely to receive chemotherapy for metastatic disease (80.8% vs. 75.2%), and more likely to receive radiation to the primary site (17.7% vs. 4.3%) (all p&lt;0.001). Additionally, patients with RP had longer median OS than those with LP (27.3 months vs. 26.4 months, p&lt;0.001). On multivariable analysis controlling for age, gender, tumor grade, RAS mutation status, MSI status, CEA level, clinical T and N category, and treatment details, patients with RP with liver metastases (HR 0.91, 95% CI 0.89-0.92), lung metastases (HR 0.85, 95% CI 0.82-0.87), and bone metastases (HR 0.89, 95% CI 0.84-0.95) (all p&lt;0.001) demonstrated improved OS compared to those with LP. Conclusions: Patterns of metastases, treatment regimens, and, in certain instances, survival outcomes, differ among patients with stage IV left-sided colon cancer and rectal cancer. Future work evaluating the implications of sidedness in colorectal cancer as well as future staging efforts should consider assessing left-sided colon cancer separately from rectal cancer, as these demonstrate distinct clinical behavior and outcomes.

Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive sarcoma subtypes.

Fibrosarcomas (FSA) are malignant mesenchymal tumors characterized by low chemo- and radiosensitivity. Development of novel treatment strategies for human adult FSA is hindered by the low incidence and the absence of suitable clinical models. Interestingly, aggressive FSA occur more frequently in domestic cats, hence potentially representing a clinically amenable model to assess novel therapies such as targeted imaging or theranostics. However, a lack of molecular characterization of FSA and adjacent normal tissue (NT) in both species hinders identification of tumor-specific targets and undermines the translational potential of feline FSA. Combining laser-capture microdissection, RNAsequencing and liquid chromatography-tandem mass spectrometry, we perform comprehensive profiling of 30 feline FSA and matched skeletal muscle, adipose and connective tissue. Clear inter-tissue differences allow identification of significantly upregulated and tumor-exclusive features that represent potential targets for diagnostic and therapeutic approaches. While feline FSA are characterized by hyperactive EIF2, TP53 and MYC signaling, immune-related and neuronal pathways emerge as modulators of tumor aggressiveness and immunosuppression. A high degree of molecular similarity with canine and adult FSA allows identification of tumor targets that are conserved across species. Significant enrichment in DNA repair pathways in feline FSA correlate with aggressive clinical behavior in human soft-tissue sarcoma. Finally, we leverage the molecular profiles to identify vulnerabilities, including sensitivity to ATR and PARP inhibition as potential treatment for feline FSA. In conclusion, this detailed landscape provides a rich resource to identify target candidates and therapeutic vulnerabilities within and across species and supports feline FSA as relevant models for the human disease.

Tertiary lymphoid structures in nasopharyngeal carcinoma: A multi-institutional study.

Tertiary lymphoid structures (TLSs) associate with prognosis of many malignancies. However, the clinical significance of TLSs is not well-elucidated in nasopharyngeal carcinoma (NPC) patients. In this whole population-based multicenter study, a total of 115 patients treated for NPC were included. The patients were treated at the five Finnish university hospitals. TLSs were assessed in routine hematoxylin and eosin (HE)-stained sections. Presence of TLSs associates significantly with improved survival in NPC. Absence of TLSs had a significant association with a poor disease-specific survival of NPC with a hazard ratio (HR) of 1.96 (95 % CI 1.09-3.53, P = 0.025) in the multivariable analysis. Similarly, absence of TLSs associated with worse overall survival with a HR of 1.68 (95 % CI 1.02-2.75, P = 0.040). TLSs seem to be associated with prognosis of NPC patients. Having TLSs in NPC tumors correlates with good survival. The assessment of TLSs could aid in understanding the clinical behavior and in planning the treatment of NPC.

THE EFFECT OF GLAZING AND THERMOCYCLING ON THE SURFACE ROUGHNESS OF DIFFERENT CAD/CAM MILLED CERAMIC LAMINATE VENEERS WITH SEM OBSERVATIONS

CAD/CAM technologies are one of the rapidly developing fields in digital restorative dentistry. The objective of this in vitro study was to evaluate the influence of glazing and thermocycling on the surface roughness values of four different types of milled CAD/CAM ceramic materials. Aim - to evaluate the effects of glazing and thermocycling on the surface roughness values of four different types of CAD/CAM ceramic veneers. This study hypothesized that there would be a statistically significant difference in surface roughness values between glazed and nonglazed CAD/CAM materials across the four tested ceramics. Materials and Methods - As part of the investigation,80 CAD/CAM ceramic veneer samples were milled using CAD/CAM system (inLab MC XL CEREC, Dentsply Sirona, Germany). The processing occurred after scanning of the first right typodont incisor of the upper jaw model prepared with the palatal chamfer preparation design without approximal involvement (KaVo, Germany) via an Omnicam scanner (CEREC, Dentsply Sirona, Germany). Four different CAD/CAM ceramic materials were evaluated in this study: lithium disilicate (IPS E.max CAD, Ivoclar, Germany), leucite-reinforced ceramic (IPS Empress CAD, Ivoclar, Germany), feldspathic ceramic (Cerec, CEREC, Dentsply Sirona, Germany), and hybrid ceramic (Cerasmart, GC, Japan). The 80 samples were categorized into four groups (20 in each, n=20), further divided into glazed and nonglazed subgroups (10 samples, n=10). All specimens underwent 10,000 thermal cycles.The surface roughness values were evaluated at three stages: post-milling, post-glazing, and post-thermocycling. Scanning electron microscope images (magnification 100x, 250x, 500x, 1000x) were captured for each material before glazingand after thermocycling. Results -Significant differences in surface roughness values were observed among materials after glazing and thermocycling. Surface roughness notably decreased following glazing. The Cerec group exhibited significantly higher surface roughness values after glazing compared to Cerasmart, Empress, and E.max groups (p &lt; 0.05). Analysis of the glazed surfaces after thermocycling also revealed significant differences among the groups (p &lt; 0.05). Tamhanes T2 post-hoc test showed that the Cerec groups average surface roughness values were significantly higher than those of Cerasmart, Empress, and E.max after thermocycling (p &lt; 0.05). For non-glazed samples, thermocycling similarly led to higher surface roughness values in the Cerec group compared to the other three groups (p &lt; 0.05). These findings highlight the effects of glazing and thermocycling on the surface roughness of CAD/CAM ceramic materials, reflecting their clinical behavior. Conclusion - Statistically significant differences were found between the glazed and non-glazed samples in terms of surface roughness. Among the tested materials, the Cerec group consistently showed higher roughness values compared to Cerasmart, Empress, and E.max (p &lt; 0.05). Glazing and thermocycling significantly influenced the surface roughness of all groups.

Long-Term Outcomes of Jugular Paragangliomas Undergoing Gamma Knife Radiosurgery: A Single Center Experience.

Jugular paragangliomas (JPG) pose a surgical challenge because of their vascularity and complex location. Stereotactic radiosurgery (SRS) offers a minimally invasive management for patients with JPG. Our aim was to evaluate outcomes of Gamma Knife radiosurgery (GKRS) for the treatment of JPG over the long term. We reviewed our 3.5-decade 17 800 patients' GKRS database. Clinical behavior, treatment parameters, tumor control, complications, and functional status were assessed. Forty patients (median = 56 years [range, 18-88], women = 24) with 40 JPG were included. There were 28 primary and 12 adjuvant GKRS. The median margin dose was 13.5 Gy (range, 12-18) delivered at 50% isodose line. Among patients with adjuvant GKRS, there were more staged-volume SRS (2 sessions) (n = 1 vs n = 3, P = .035) associated with larger tumor volume [3.5 cc (1.1-26.7) vs 10.2 cc (3.3-45.9), (P = .038) and increased V12Gy (P = .031). Better House-Brackmann grade (P = .008) and Gardner-Robertson hearing class (P < .001) before GKRS correlated with better facial nerve function and unchanged cochlear nerve function after treatment, respectively. During an overall median follow-up of 69.7 months (range, 6.0-339.3 months), symptom control and preserved functionality were achieved in 39 patients (97.5%). Tumor control was obtained in 38 patients (95%) (regression = 23, stable = 15) after SRS. The 5-, 10-, and 15-year progression-free survival rates were all 100% after primary GKRS and 91.7%, 83.3%, and 83.3% for adjuvant GKRS (P = .101). Larger (≥10 cc) tumor volumes (HR: 1.35 [95% CI: 1.11-1.70], P = .013) and mFisch Di2 (HR: 1.40 [95% CI: 1.18-1.64], P = .016) were associated with worse progression-free survival. One patient required a second GKRS after asymptomatic progression with no further growth. One patient with 2 failed surgical resections died 8 months after adjuvant GKRS related to tumor progression and hydrocephalus. As a minimally invasive management, GKRS proved to be a safe and effective treatment of JPG. GKRS should be considered both as an optimal primary management and as an early adjuvant strategy for residual or recurrent tumors after initial resection.

Immunohistochemical expression of Annexin A2 and Annexin A6 in a random sample group of Iraqi women with triple-negative breast cancer

Background: Breast cancer represents the most common and the first leading cause of cancer-associated deaths in Iraqi women. It is a heterogeneous disease with different subtypes; one of these subtypes is triple-negative (basal-like) breast cancer, which is characterized by a distinctive molecular profile, aggressive clinical behavior, and the absence of targeted therapies. Annexin A2 and Annexin A6 are part of the Annexin protein family; these proteins have a suggested role in the evolution and progression of many cancer types, including breast cancer. Evaluation of the immunohistochemical expression of Annexin A2 and Annexin A6 in triple-negative subtype) in a random sample group of Iraqi women patients and correlating the results with clinicopathological parameters, including tumor grade and stage.Methods: The current study was conducted in Baghdad /Iraq, in which forty paraffin-embedded blocks of breast tissue from women patients diagnosed with breast cancer were collected and selected to be triple-negative breast cancer. Immunohistochemical staining of Annexin A2 and Annexin A6 markers was performed for this sample with a correlation of the results with clinicopathological parameters, including tumor grade and stage.Results: The study demonstrates a significant association between Annexin A2 and Annexin A6 expression and a significant association between Annexin A2 expression and tumor grade and stage in triple-negative breast cancer in this group of Iraqi patients.Conclusions: This study displays the role of Annexin A2 and Annexin A6 in triple-negative breast cancer and suggests the role of Annexin A2 in the progression, metastasis, and prognosis of this special type of breast cancer by its association with advanced tumor grade and stage.Keywords: Annexin A2; Annexin A6; triple-negative; Breast cancer

NETest and Gastro-Entero-Pancreatic Neuroendocrine Tumors: Still Far from Routine Clinical Application? A Systematic Review

Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are the most prevalent subgroup among NETs and include heterogeneous tumors characterized by different clinical behavior and prognosis. The NETest is a tool based on real-time PCR combined with deep learning strategies to specifically identify tumors with a neuroendocrine genotype. Despite the promising results achieved regarding its utility in the field of GEP-NETs, the NETest has not yet entered into routine clinical practice. Methods: We performed a systematic review aimed at summarizing available evidence on the application of the NETest in both the diagnosis and the prognostic stratification of GEP-NETs. Results: We identified five studies evaluating the diagnostic role of the NETest and nine studies evaluating its prognostic value. The NETest emerged as a reliable biomarker for GEP-NET diagnosis with an accuracy higher than 90%, regardless of tumor stage and grade. However, according to some studies, the NETest showed a low specificity, mainly attributed to interferences with other gastro-intestinal malignancies. In terms of prognostic value, the NETest correlated with the detection of residual disease after surgery in six studies. The NETest was also associated with patients’ survival outcomes, namely progression-free survival (PFS) and overall survival (OS) in three studies. Conclusions: According to current systematic review, the value of the NETest both for diagnosis and for prognosis of GEP-NET emerged as robust across different studies. Further prospective analysis on larger GEP-NET series is encouraged to validate this tool, improving patients’ diagnosis, management, and follow-up.

Exploring the Role of FDG PET CT Scan in Detecting High Grade Diffuse Large B-Cell Lymphoma

Introduction. Diffuse B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. Currently, the standard method for evaluating patients at the initial stages of cancer diagnosis in Mashhad oncology centers involves computed tomography scans (CT scans), histopathological evaluation of tissue, bone marrow sampling, and cytogenetic studies, all of which are time-consuming and costly. It is worth mentioning that at present, the most recommended approach for determining lymphoma staging is the FDG-PET/CT scan, which combines labeled glucose with CT scan and offers a more accurate alternative. The objective of this study is to explore the potential of FDG-PET/CT scan as a tool for detecting high-grade lymphoma.Methods. In this study, patients with different types of DLBCL who underwent FDG-PET Scan for staging at Razavi Hospital, Mashhad, Iran between 2017 and 2021 were examined. The necessary clinical and paraclinical information, including the stage of the disease, the involved site at the time of diagnosis, the result of immunohistochemical examination, and the response to treatment were collected. FDG-PET Scan information including the extent of involvement and metabolic activity of the tumor before the start of treatment, pathological characteristics of the tumor, clinical behavior, and response to treatment in the form of response rate (RR), disease-free survival (DFS) and overall survival (OS) of the patients. Was also investigated. Aggressive histology in the present study was classified based on morphological characteristics and immunohistochemical staining, prognostic indicators, clinical behavior and response to treatment. Data were analyzed using SPSS software at a significance level of p&lt;0.05.Results. Comparing the two groups of patients with high grade histology (n=12) and NOS (n=14), the results showed that SUV max values in patients with aggressive lymphoma were 27.5 ± 15.6 (median 25.6) and in patients with NOS lymphoma was 15.4 ± 9.8 (median 14.4) (p=0.01). The overall survival of patients in the aggressive group was 10 months and in the non-aggressive group was 24 months (p=0.002). Also, the cut — off -point of 21.1 for SUV max has a sensitivity of 66 % and a specificity of 72 % in differentiating aggressive from non-aggressive types.Conclusion. The results revealed that FDG PET CT Scan can provide valuable insights into differentiating lymphomas with a more aggressive type from their usual types, as those with heightened metabolic activity (SUVmax) are often indicative of aggressive behaviors.

Principles of Surgical Treatment of Soft Tissue Sarcomas

Soft tissue sarcoma (STS) is a group of highly heterogeneous tumors of mesenchymal origin that have variable primary site locations and clinical behavior. Despite the broad diversity of STS, the standard of care involves surgical resection with or without radiation therapy (RT) to control local recurrence and systemic treatment in select cases. The complexities of STS require a critical understanding of the preoperative work-up process, surgical treatment, and postoperative management. Advanced imaging plays a vital role in the characterization of the soft tissue mass, preoperative biopsy planning, and disease staging. Surgical treatment prioritizes wide resection with negative margins, supported by newer margin classification systems for better prognosis. Further, advancements in surgical technique have enabled limb-salvage surgery to largely replace amputation in the management of these tumors. Additional surgical considerations, such as nerve preservation, vascular reconstruction, and complex tissue closure, further highlight the complexity of STS management. Lastly, postoperative follow-up is critical for the early detection of local or distant recurrences. For complex cases, such as unplanned excisions or invasive tumors, strategies like re-resection may be beneficial. Ongoing research into imaging, chemotherapy, and targeted therapies will further refine management strategies, especially in complex and recurrent cases. This review highlights the essential aspects of STS surgical management and underscores the need for coordinated, multidisciplinary care to enhance both survival and quality of life for affected patients.