Association between lesion enhancement and breast cancer in contrast-enhanced spectral mammography

Background Contrast-enhanced spectral mammography (CESM) may help to determine the malignancy potential of lesions according to the degree of enhancement. Purpose To investigate the correlation between the degree of contrast enhancement of the lesions in contrast-enhanced spectral mammography (CESM) and the final histopathological diagnosis in patients with BI-RADS 4 and 5 lesions. Material and Methods CESM was performed in 128 patients who had BI-RADS 4 and 5 lesions on mammography and underwent histopathological examination. A total of 128 index lesions were scored using a 4-point scale regarding the degree of contrast enhancement (0 = no contrast enhancement, 1 = minimal, 2 = moderate, 3 = marked), a score of 2 and 3 was accepted as suggestive of malignancy. The study was approved in our institutional scientific committee. Results In total, 76 (59.4%) of the lesions had benign histopathological results, whereas 52 of them had malignant results. Contrast enhancement was not observed in 22.7% of the lesions while 24.2% had minimal enhancement, 18.8% had moderate enhancement, and 34.4% had marked enhancement in CESM. The sensitivity of the degree of contrast enhancement in CESM was 98.1%, when the specificity was 77.6%, positive predictive value was 75%, negative predictive value was 98.3%, and accuracy was 85.9%. Conclusion This study demonstrated that the degree of contrast enhancement of the lesions in CESM may be used in daily practice with easily performing a visual scale in predicting the malignancy potential of the lesions.

Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring

Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) HSPA1 and HSP90AA1 expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. HSPA1 and HSP90AA1 were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. HSPA1 and HSP90AA1 are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.

New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma via Comprehensive Bioinformatic Analysis and Validation

Skin cutaneous melanoma (SKCM) is the most aggressive and fatal type of skin cancer. Its highly heterogeneous features make personalized treatments difficult, so there is an urgent need to identify markers for early diagnosis and therapy. Detailed profiles are useful for assessing malignancy potential and treatment in various cancers. In this study, we constructed a co-expression module using expression data for cutaneous melanoma. A weighted gene co-expression network analysis was used to discover a co-expression gene module for the pathogenesis of this disease, followed by a comprehensive bioinformatics analysis of selected hub genes. A connectivity map (CMap) was used to predict drugs for the treatment of SKCM based on hub genes, and immunohistochemical (IHC) staining was performed to validate the protein levels. After discovering a co-expression gene module for the pathogenesis of this disease, we combined GWAS validation and DEG analysis to identify 10 hub genes in the most relevant module. Survival curves indicated that eight hub genes were significantly and negatively associated with overall survival. A total of eight hub genes were positively correlated with SKCM tumor purity, and 10 hub genes were negatively correlated with the infiltration level of CD4+ T cells and B cells. Methylation levels of seven hub genes in stage 2 SKCM were significantly lower than those in stage 3. We also analyzed the isomer expression levels of 10 hub genes to explore the therapeutic target value of 10 hub genes in terms of alternative splicing (AS). All 10 hub genes had mutations in skin tissue. Furthermore, CMap analysis identified cefamandole, ursolic acid, podophyllotoxin, and Gly-His-Lys as four targeted therapy drugs that may be effective treatments for SKCM. Finally, IHC staining results showed that all 10 molecules were highly expressed in melanoma specimens compared to normal samples. These findings provide new insights into SKCM pathogenesis based on multi-omics profiles of key prognostic biomarkers and drug targets. GPR143 and SLC45A2 may serve as drug targets for immunotherapy and prognostic biomarkers for SKCM. This study identified four drugs with significant potential in treating SKCM patients.

Medulloblastoma in Adulthood

Defined as a tumour with increased malignancy potential in childhood, medulloblastoma was first reported in the literature by Percival Bailey and Harvey Cushing in 1925. Scientific studies over the years have shown that this type of tumour represents about 20% of all intracranial tumours encountered in childhood, their percentage decreasing with advancing age. The genetic factor plays an important part in the appearance of medulloblastoma; there are certain diseases, in the patient’s history, that can be associated with this type of tumour. Here, we can specify Turcot syndrome (an autosomal recessive disease, rarely encountered) or basal cell carcinoma syndrome. This article presents the case of a young patient (41-year-old) suffering from a cerebellar tumour formation that turned out to be, after histopathological examination, a medulloblastoma. In practice we can find several types of medulloblastoma (desmoplastic or nodular, anaplastic, classical or undifferentiated). In what follows I will try to highlight a few aspects of a classic medulloblastoma.

In prostatic transition zone lesions (PI-RADS v2.1): which subgroup should be biopsied?

Background The study aimed to compare the diagnostic performance of T2-weighted imaging (T2WI) score 3 transition zone (TZ) lesions between Prostate Imaging and Reporting Data System (PI-RADS) v2.1 and modified PI-RADS v2.1-B. Results Among TZ lesions (n = 78), 47 (60.0%) had T2WI score of 3, and 16 of the 47 (34.0%) were malignant. The rate of malignancy was 8.8% in PI-RADS category 3A, 100% in PI-RADS category 3B, and 100% in PI-RADS category 4. The apparent diffusion coefficient value of PI-RADS category 3B (0.934 ± 0.158 × 10−3 mm2/s) showed significant difference with that of PI-RADS category 3A (1.098 ± 0.146 × 10−3 mm2/s) but none with PI-RADS category 4 (0.821 ± 0.091 × 10−3 mm2/s). There was no significant difference in the sensitivity and negative predictive value of PI-RADS v2.1 and PI-RADS v2.1-B. Specificity and positive predictive value of modified PI-RADS v2.1-B were much higher than those of PI-RADS v2.1 for both readers (p < .001). The area under the receiver operating characteristic curve tended to be higher with PI-RADS v2.1-B than with PI-RADS v2.1. Conclusion Biopsy for PI-RADS 3B lesion is necessary due to its superior malignancy potential than that of PI-RADS 3A lesion.

Von Meyenburg Complexes and Malignancy: A Systematic Review

Von Meyenburg Complexes (VMC) are benign lesions secondary to ductal plate malformations. These are relatively rare in adults and are often asymptomatic, with many lesions being diagnosed on imaging. Despite these benign characteristics, VMC have the potential to undergo malignant changes leading to conditions such as cholangiocarcinoma and other cancers. The objective of the review is to report and analyze the cases of biliary hamartomas which were associated with malignancy. We performed a structured systematic review of literature and identified 31 cases of biliary duct hamartomas associated with malignancy. The mean age at onset was 61 years +/- 13 (min 19 to max 88) with the majority of the patients being male (64.5%). Of all cases, 41.9% reported symptoms (13/31 cases) with the most common symptom being abdominal pain (32.3%). Biopsies reported malignancy in 77.4% of cases (24/31 cases) with the most common reported associated malignancy being cholangiocarcinoma 54.8% (17/31). 93.3% of the cases underwent surgical intervention (28/30 cases). VMC are an important entity with malignancy potential which is under-reported. Presence of red flag symptoms such as weight loss and obstructive jaundice in patients with diagnosed biliary hamartomas should prompt an evaluation for malignancy. Key-words: Von meyenburg complexes; cholangiocarcinoma; malignancy; biliary hamartomas

Correlation of endoscopic ultrasonography features with mitotic index in 2–5 cm gastric gastrointestinal stromal tumors

Background: Predicting the malignancy potential of gastrointestinal stromal tumor (GIST) before resection could improve patient management strategies, as gastric GISTs with a low malignancy potential can be safely treated endoscopically, but surgical resection is required for those tumors with a high malignancy potential. This study aimed to evaluate endoscopic ultrasound (EUS) features of 2–5 cm gastric GISTs that might be used to predict their mitotic index using surgical specimens as the gold standard. Patients and Methods: Forty-nine patients (30 females and 19 males; mean age 55.1 ± 12.7 years) who underwent EUS examinations, followed by surgical resections of 2–5 cm gastric GISTs were retrospectively reviewed. Results: The mean tumor size was 3.44 ± 0.97 cm (range 2.1–5.0 cm). A univariate analysis revealed no significant differences in age, sex, and tumor location in the low mitotic index and high mitotic index groups (all P > 0.05). In terms of EUS features, there were no significant differences in the mitotic indexes with respect to the shape, surface lobulation, border regularity, echogenicity, homogeneity, growth patterns, presence of mucosal ulceration, hyperechogenic foci, anechoic spaces, and hypoechoic halos (all P > 0.05). However, the tumor size was larger in the high mitotic index group than in the low mitotic index group (3.97 ± 1.05 vs. 3.27 ± 0.9 cm, P = 0.03). Conclusion: Conventional EUS features are not reliable for predicting the mitotic index of 2–5 cm gastric GISTs. Further modalities for predicting the mitotic index are needed to prevent unnecessary surgical resections in patients with a low risk of malignancy.

Immediate results of spleen-preserving distal subtotal pancreatic resection

Aim. To assess the possibility of open spleen-preserving distal subtotal pancreatic resection for tumors of the body and tail of the pancreas.Material and methods. A retrospective comparative analysis of the immediate results of the spleen-preserving interventions in 41 patients was carried out. Mainly benign tumors or tumors with a low malignancy potential of the corpus and (or) the tail of the pancreas were detected. Distal subtotal pancreatectomy with splenectomy was performed in 53 patients with pancreatic tumors of different histogenesis with low malignancy potential (control group).Results. The duration of spleen-preserving distal subtotal pancreatectomy was 12 minutes shorter, compared with the distal subtotal pancreatectomy with splenectomy group (p = 0.180). Significantly lower volume of intraoperative blood loss during spleen-preserving procedure was noted – by 460 ml (p = 0.0001). The level of postoperative complications in the spleen-preserving pancreatectomy group was 15 (37%), while in the group of distal subtotal pancreatectomy with splenectomy was 26 (49%) (p = 0.227), respectively. External pancreatic fistula after spleenpreserving pancreatectomy was noted in 13 (32%) patients, in the other group in 21 (40%; p = 0.429). The duration of hospital stay did not statistically significantly differ in the compared groups and amounted to: 18.6 ± 6.9 and 20.3 ± 5.4 days (p = 0.123), respectively.Conclusion. Open spleen-preserving pancreatectomy is a relatively safe type of surgical treatment for patients with benign tumors and tumors with a low potential for malignancy of the body and/or tail of the pancreas. The surgery is shorter in time, accompanied by a lower level of complications, significantly less intraoperative blood loss, compared with a similar procedure involving splenectomy.