B-cell non-Hodgkin lymphoma of the breast in Waldenström's macroglobulinemia: a case report.

Background: Non-Hodgkin lymphoma (NHL) of the breast is a rare disease and can occur amongst patients affected by Waldenström's Macroglobulinemia (WM). WM is an indolent B-cell lymphoproliferative disorder with an overall incidence of about 1/100,000 in Europe. Breast imaging is not specific to breast lymphoma that often mimics benign lesions. The diagnosis is based on breast biopsy, the presence of MYD88L265P somatic mutation and immunoglobulin M (IgM) paraprotein detectable in the setting of lymphoplasmacytic infiltration by bone marrow (BM) biopsy. Case Description: A 60-year-old woman with personal and familial history of monoclonal gammopathy of undetermined significance (MGUS) and a lump in her right breast was referred to our hospital. Standard imaging showed round mass with smooth edges. The lump was biopsied and the pathology examination showed lymphoplasmacytic lymphoma (LPL) of the breast which led to final the diagnosis of WM. Conclusions: Lymphoma of the breast is a rare disease, often misdiagnosed because of the lack of specific features at mammogram and ultrasound. Core biopsy is crucial to make diagnosis of breast lymphoma and early diagnosis of WM has been shown to improve overall survival (OS). A comprehensive approach is required in order to assess patients affected by blood disorders presenting with a new breast mass that can lead to diagnosis of breast lymphoma.

Is There Indication for the Use of Biological Mesh in Cancer Patients?

Up to 28% of all patients who undergo open surgery will develop a ventral hernia (VH) in the post-operative period. VH surgery is a debated topic in the literature, especially in oncological patients due to complex management. We searched in the surgical database of the Hepatobiliary Unit of the National Cancer Institute of Naples "G. Pascale Foundation" for all patients who underwent abdominal surgery for malignancy from January 2010 to December 2018. Our surgical approach and our choice of mesh for VH repair was planned case-by-case. We selected 57 patients that fulfilled our inclusion criteria, and we divided them into two groups: biological versus synthetic prosthesis. Anterior component separation was used in 31 patients (54.4%) vs. bridging procedure in 26 (45.6%). In 41 cases (71.9%), we used a biological mesh while a synthetic one was adopted in the remaining patients. Of our patients, 57% were male (33 male vs. 24 female) with a median age of 65 and a mean BMI of 30.8. We collected ventral hernia defects from 35 cm2 to 600 cm2 (mean 205.2 cm2); 30-day complications were present in 24 patients (42.1%), no 30-day mortality was reported, and 21 patients had a recurrence of pathology during study follow-up. This study confirms VH recurrence risk is not related with the type of mesh but is strongly related with BMI and type of surgery also in oncological patients.

Preoperative localisation of nonpalpable breast lesions using magnetic markers in a tertiary cancer centre.

BACKGROUND: We retrospectively evaluated safety and performance of magnetic seed localisation of nonpalpable breast lesions. METHODS: We reviewed records of patients with nonpalpable breast lesions preoperative localised by placing magnetic Magseed® marker between February 2019 and December 2020. During surgery, Sentimag® magnetic probe was used to localise the marker and guide surgery. Safety, lesion identification and excision with tumour with free margins and re-excision rate were assessed. RESULTS: A total of 77 Magseed® devices were placed into the breasts of 73 patients, 44 under ultrasound and 33 under stereotactic guidance (4 bilateral). All devices were retrieved as were the target lesions. Magnetic marker placement was successful in all cases without any adverse event. Intraoperative identification and excision of the localised lesion were successful in 77 of 77 of cases (100%). In three cases (all of them calcifications with the seed placed under stereotactic guidance), the seed did not reach the exact target position of the biopsy clip; thus, larger excision was needed, with localisation failure attributed to incorrect clip insertion (n = 1) or to clip dislocation (n = 2). Migration of the marker was negligible in all patients. Complete excision after the initial procedure with at least 1-mm disease-free margins was obtained in 74 out of 77 (96.1%) lesions. The re-excision rate was 3 out of 77 (4%). CONCLUSIONS: Magnetic marker localisation for nonpalpable breast lesions was safe, reliable, and effective in terms of lesion identification, excision with tumour-free margins and re-excision rate.

Radiomic and Artificial Intelligence Analysis with Textural Metrics Extracted by Contrast-Enhanced Mammography and Dynamic Contrast Magnetic Resonance Imaging to Detect Breast Malignant Lesions.

Purpose:The purpose of this study was to discriminate between benign and malignant breast lesions through several classifiers using, as predictors, radiomic metrics extracted from CEM and DCE-MRI images. In order to optimize the analysis, balancing and feature selection procedures were performed. Methods: Fifty-four patients with 79 histo-pathologically proven breast lesions (48 malignant lesions and 31 benign lesions) underwent both CEM and DCE-MRI. The lesions were retrospectively analyzed with radiomic and artificial intelligence approaches. Forty-eight textural metrics were extracted, and univariate and multivariate analyses were performed: non-parametric statistical test, receiver operating characteristic (ROC) and machine learning classifiers. Results: Considering the single metrics extracted from CEM, the best predictors were KURTOSIS (area under ROC curve (AUC) = 0.71) and SKEWNESS (AUC = 0.71) calculated on late MLO view. Considering the features calculated from DCE-MRI, the best predictors were RANGE (AUC = 0.72), ENERGY (AUC = 0.72), ENTROPY (AUC = 0.70) and GLN (gray-level nonuniformity) of the gray-level run-length matrix (AUC = 0.72). Considering the analysis with classifiers and an unbalanced dataset, no significant results were obtained. After the balancing and feature selection procedures, higher values of accuracy, specificity and AUC were reached. The best performance was obtained considering 18 robust features among all metrics derived from CEM and DCE-MRI, using a linear discriminant analysis (accuracy of 0.84 and AUC = 0.88). Conclusions: Classifiers, adjusted with adaptive synthetic sampling and feature selection, allowed for increased diagnostic performance of CEM and DCE-MRI in the differentiation between benign and malignant lesions.

Radiomics and Artificial Intelligence Analysis with Textural Metrics Extracted by Contrast-Enhanced Mammography in the Breast Lesions Classification.

The aim of the study was to estimate the diagnostic accuracy of textural features extracted by dual-energy contrast-enhanced mammography (CEM) images, by carrying out univariate and multivariate statistical analyses including artificial intelligence approaches. In total, 80 patients with known breast lesion were enrolled in this prospective study according to regulations issued by the local Institutional Review Board. All patients underwent dual-energy CEM examination in both craniocaudally (CC) and double acquisition of mediolateral oblique (MLO) projections (early and late). The reference standard was pathology from a surgical specimen for malignant lesions and pathology from a surgical specimen or fine needle aspiration cytology, core or Tru-Cut needle biopsy, and vacuum assisted breast biopsy for benign lesions. In total, 104 samples of 80 patients were analyzed. Furthermore, 48 textural parameters were extracted by manually segmenting regions of interest. Univariate and multivariate approaches were performed: non-parametric Wilcoxon-Mann-Whitney test; receiver operating characteristic (ROC), linear classifier (LDA), decision tree (DT), k-nearest neighbors (KNN), artificial neural network (NNET), and support vector machine (SVM) were utilized. A balancing approach and feature selection methods were used. The univariate analysis showed low accuracy and area under the curve (AUC) for all considered features. Instead, in the multivariate textural analysis, the best performance considering the CC view (accuracy (ACC) = 0.75; AUC = 0.82) was reached with a DT trained with leave-one-out cross-variation (LOOCV) and balanced data (with adaptive synthetic (ADASYN) function) and a subset of three robust textural features (MAD, VARIANCE, and LRLGE). The best performance (ACC = 0.77; AUC = 0.83) considering the early-MLO view was reached with a NNET trained with LOOCV and balanced data (with ADASYN function) and a subset of ten robust features (MEAN, MAD, RANGE, IQR, VARIANCE, CORRELATION, RLV, COARSNESS, BUSYNESS, and STRENGTH). The best performance (ACC = 0.73; AUC = 0.82) considering the late-MLO view was reached with a NNET trained with LOOCV and balanced data (with ADASYN function) and a subset of eleven robust features (MODE, MEDIAN, RANGE, RLN, LRLGE, RLV, LZLGE, GLV_GLSZM, ZSV, COARSNESS, and BUSYNESS). Multivariate analyses using pattern recognition approaches, considering 144 textural features extracted from all three mammographic projections (CC, early MLO, and late MLO), optimized by adaptive synthetic sampling and feature selection operations obtained the best results (ACC = 0.87; AUC = 0.90) and showed the best performance in the discrimination of benign and malignant lesions.

Debulking mastectomy with electrochemotherapy: a case report of no surgery approach to recurrent breast cancer.

Electrochemotherapy has been shown to be safe, effective and non-invasive loco-regional treatment for chest wall breast cancer recurrence. Electrochemotherapy is a palliative treatment offered to patients with cutaneous metastases from breast cancer, which are not eligible for resection and/or systemic therapy is ineffective or contraindicated. Electrochemotherapy combines the administration of bleomycin with electroporation of tumor cell, intraoperatively. Here we present the case of a women affected by multi-drug resistant metastatic synchronous solid cancers who refused radical mastectomy after being diagnosed with recurrent ulcerated right breast cancer. We first describe an extended indication to electrochemotherapy to treat breast cancer recurrence after previous breast conserving surgery. Electroporation-induced necrosis through electrochemotherapy replaced surgery and was delivered in 30 minutes at 5,000 Hz frequencies at 730 V by hexagonal needle under general anesthesia. The necrosis of the remaining breast resulted in a voluminous eschar that was easily removed few months after leaving the chest wall free from macroscopic disease turning in a "bladeless mastectomy". This kind of breakthrough application of electrochemotherapy might be considered to avoid palliative mastectomy in very selected patients. New technologies may help clinicians to find agreement between patient' will and the burden of treatment and might contribute in selected cases to give options to patients not keen on having surgery.

Intracystic papillary breast carcinoma with DCIS in a man: a case report.

Here we report a case of 50-mm lump within the left breast in a 56-year-old man. The patient underwent left total mastectomy and sentinel node biopsy. The pathology report showed low-grade intracystic papillary breast carcinoma surrounded by ductal carcinoma in situ. Sentinel node biopsy was negative. The patient was prescribed five years tamoxifen.

Angiosarcoma of the breast, the unknown-a review of the current literature.

Angiosarcoma of the breast is one of the rarest malignancies. Breast angiosarcoma can be classified into primary when arising de novo and secondary to chronic lymphoedema or breast irradiation. Molecular pathways involved in angiosarcoma development have not been described clearly, yet some gene point mutations and protein altered expression levels have been detected. So far, their management is based above all on surgery. Hence, further studies starting from the few known key points may help to develop more effective strategies based both on target therapies, together with surgery.

The Therapeutic Targets of miRNA in Hepatic Cancer Stem Cells.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide malignancy and the third leading cause of cancer death in patients. Several studies demonstrated that hepatic cancer stem cells (HCSCs), also called tumor-initiating cells, are involved in regulation of HCC initiation, tumor progression, metastasis development, and drug resistance. Despite the extensive research, the underlying mechanisms by which HCSCs are regulated remain still unclear. MicroRNAs (miRNAs) are able to regulate a lot of biological processes such as self-renewal and pluripotency of HCSCs, representing a new promising strategy for treatment of HCC chemotherapy-resistant tumors. In this review, we synthesize the latest findings on therapeutic regulation of HCSCs by miRNAs, in order to highlight the perspective of novel miRNA-based anticancer therapies for HCC treatment.

Inhibitory effect of (-)-epigallocatechin-3-gallate and bleomycin on human pancreatic cancer MiaPaca-2 cell growth.

BACKGROUND: Human pancreatic cancer is currently one of the deadliest cancers with high mortality rate. It has been previously shown that (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has showed suppressive effects on human pancreatic cancer cells. Bleomycin, (BLM), an anti-cancer chemotherapeutic drug that induces DNA damage, has antitumor effects by induction of apoptosis in several cancer cell lines and also in pancreatic cancer cells. The present study investigated for the first time, the inhibitory effect of EGCG and BLM on pancreatic cancer cell growth. METHODS: Using the pancreatic cancer cell lines MIA PaCa-2 cells the efficacy and synergism of EGCG and BLM were evaluated by in vitro tests. Inhibition of cell proliferation was determined by MTT assay. Mitochondrial depolarization was performed with JC-1 probe. Viability and apoptosis were determined by Flow Cytometry with annexin V, propidium iodide staining and DNA fragmentation assay. RESULTS: Cell proliferation assay revealed significant additive inhibitory effects with combination of EGCG and BLM at 72 h in a dose dependent manner. The combination of EGCG and BLM induced cell cycle S-phase arrest and mitochondrial depolarization. Viability, apoptosis and DNA fragmentation assay indicated that the combination of EGCG and bleomycin potentiated apoptosis. CONCLUSIONS: Our results indicate that EGCG and BLM have additive anti-proliferative effects in vitro by induction of apoptosis of MIA PaCa-2 cells. This combination could represent a new strategy with potential advantages for treatment of pancreatic cancer. To date, this is the first report published of the inhibitory effect of EGCG and BLM on human pancreatic cancer MIA Paca-2 cell growth.

Hepatocellular carcinoma and liver metastases: clinical data on a new dual-lumen catheter kit for surgical sealant infusion to prevent perihepatic bleeding and dissemination of cancer cells following biopsy and loco-regional treatments.

BACKGROUND: RFA is a safe and effective procedure for treating unresectable primary or secondary liver malignancies, but it is not without complications. The most common reported complications include abdominal hemorrhage, bile leakage, biloma formation, hepatic abscesses, and neoplastic seeding. The aim of this study is to evaluate the feasibility of percutaneous use of surgical sealant with a new coaxial bilumen catheter, to prevent the perihepatic bleeding and dissemination of cancer cells through the needle-electrode (neoplastic seeding) or along the needle track. METHODS: We designed a novel dual-lumen catheter to facilitate the optimal application of fibrin sealant after diagnostic and therapeutic percutaneous procedures. Percutaneous RFA has been performed using mask ventilation or neuroleptanalgesia. The main aims of this study, after the ablation procedure, in the treatment of unresectable liver cancer were to prevent major adverse events: a) the perihepatic bleeding; b) dissemination of cancer cells through the needle-electrode and or needle track. RESULTS: A total of 181 patients were evaluated for this study at National Cancer Institute of Naples from January 2012 to January 2014. The association of blood loss (≤1 g/dl; ≥1 g/dl) with age, gender, histological diagnosis were analyzed. No statistical significance was observed between bleeding and age (p = 0.840), gender (p = 0.607) and histological diagnosis (p = 0,571), respectively. CONCLUSIONS: This study demonstrated that fibrin sealant or other surgical sealant injection, after any locoregional procedure such as biopsy or ablation, could make adverse events even more rare.

Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma.

PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

Efficacy of a haemostatic matrix for the management of bleeding in patients undergoing liver resection: results from 237 cases.

BACKGROUND: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intraoperative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours. METHODS: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded. RESULTS: 105 women (age 61 +/- 9 years) and 132 men (age 61 +/- 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 +/- 1 min; this was significantly increased in patients with coagulopathy versus noncoagulopathic patients (4 +/- 1 vs. 2 +/- 1 min, p < 0.001). CONCLUSIONS: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intraoperative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.