Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance.

Triple negative breast cancer (TNBC) displays a high aggressive behavior, tendency to relapse and early metastasize, leading to poor prognosis. The lack of estrogen receptors, and human epidermal growth factor receptor 2, prevents the use of endocrine or molecular targeted therapy, being therapeutical options for TNBC managements mostly limited to surgery, radiotherapy and mainly chemotherapy. While an important number of TNBCs initially responds to chemotherapy, they are prone to develop chemoresistance over the time. Thus, there is an urgent need to identify novel molecular targets to improve the outcome of chemotherapy in TNBC. In this work we focused on the enzyme paraoxonase-2 (PON2) which has been reported to be overexpressed in several tumors contributing to cancer aggressiveness and chemoresistance. Through a case-control study, we analyzed PON2 immunohistochemical expression in breast cancer molecular subtypes Luminal A, Luminal B, Luminal B HER2+, HER2 + and TNBC. Subsequently, we evaluated the in vitro effect of PON2 downregulation on cell proliferation and response to chemotherapeutics. Our results showed that the PON2 expression levels were significantly upregulated in the infiltrating tumors related to the subtypes Luminal A, HER2+ and TNBC compared to the healthy tissue. Furthermore, PON2 downregulation led to a decrease in cell proliferation of breast cancer cells, and significantly enhanced the cytotoxicity of chemotherapeutics on the TNBC cells. Although further analyses are necessary to deeply understand the mechanisms by which the enzyme could participate to breast cancer tumorigenesis, our results seem to demonstrate that PON2 could represent a promising molecular target for TNBC treatment.

Close and positive margins in non-melanoma skin malignancies of the head and neck. What to do in patients over 75 years of age? A preliminary study.

BACKGROUND: The incidence of non-melanoma skin cancer (NMSC) of the head and neck is increasing among older adults where it is credited to have a poorer prognosis also because the radicality of the surgery is often missed for a too conservative approach. An assessment of the amount of tumor regrowth and its prognostic consequences, in patients with surgical margins close or involved and older than 75 years, seems thus worth to be pursued in order to provide the best therapeutic strategy. METHODS: 91 cases of basal cell carcinomas (BBC) and squamous cell carcinomas (SCC), in patients older than 75 years of age, were followed from a minimum of one year to up to ten years. 15 patients had close margins at histology while 30 patients turned out to have positive margins. The other 46 patients had clear histologic margins and were considered as a control group. Several parameters were also considered like the site of occurrence, morphology, grading, size, thickness, type of margin involved (lateral, deep or both) and the status of the neck, for the SCC. A cut-off follow-up of two years (less than two years and more than two years) was adopted. RESULTS: Among the BCCs there was one recurrence in the clear margin subgroup (1/23-4.3%) and two in the positive margin subgroup (2/20-10%). For the SCCs there was only one recurrence in the group of positive margins (1/10-10%). Hence the observed rate of recurrence was much lower than reported in the literature. CONCLUSIONS: In the authors' opinion the low tendency to recur that NMSC shows in people older than 75 years might validate, at least in this age group, an "economic" surgical approach and a watchful attitude. Larger numbers are needed to assess and possibly validate this strategy, especially for the SCCs.

Stylet slow-pull vs. standard suction technique for endoscopic ultrasound-guided fine needle biopsy in pancreatic solid lesions using 20 Gauge Procore™ needle: A multicenter randomized trial.

BACKGROUND: Standard suction and slow-pull techniques have been utilized during endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions, but the correct sampling technique remains unclear. New needles designed to obtain samples suitable for histological evaluation have become available. We performed a study comparing the two sampling methods during endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in patients with pancreatic solid lesions. METHODS: We performed EUS-FNB with a 20 Gauge FNB needle using slow-pull or standard suction techniques in a prospective, randomized, multicenter study. The primary aim was bloodiness of the collected specimens. Secondary aims were technical success and performance of the two techniques. RESULTS: 110 patients were included (55 per group). No difference in blood contamination was observed (slow-pull 80% vs. suction 74%, p = 0.917). Technical success was 95% (96% vs. 94%, p = 0315). Sensitivity (96% vs. 93%), specificity (100% vs. 100%), positive likelihood ratio (NA), negative likelihood ratio (0.04 vs. 0.07), diagnostic accuracy (96 vs. 93%) did not differ between the two groups. CONCLUSION: EUS-FNB with slow-pull and standard suction techniques are comparable in terms of blood contamination providing similar high diagnostic sensitivity and accuracy in pancreatic solid lesions. The use of the new generation FNB needle allows to reach such high level of diagnostic adequacy regardless of the technique utilized.

Endoscopic Ultrasound-Guided Fine Needle Aspiration of a PET/CT-Positive Small Hilar Lymph Node for the Diagnosis of Metastatic Merkel Cell Carcinoma.

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EUS-guided sampling with 25G biopsy needle as a rescue strategy for diagnosis of small subepithelial lesions of the upper gastrointestinal tract.

BACKGROUND AND STUDY AIMS: This study was designed to evaluate the impact of additional tissue obtained with endoscopic ultrasound (EUS)-guided 25-gauge core biopsy needle (25G-PC) following an unsuccessful fine-needle biopsy (FNB) performed with larger-bore needles for the characterization of gastrointestinal subepithelial lesions (GI-SELs). PATIENTS AND METHODS: We prospectively collected and retrospectively analyzed information in our database from January 2013 to June 2017 for all patients with GI-SELs who received a EUS-guided FNB (EUS-FNB) with 25G-PC during the same procedure after failure of biopsy performed with larger-bore needle. Diagnostic yield, diagnostic accuracy and procedural complications were evaluated. RESULTS: Sixteen patients were included in this study, 10 men and 6 women, median age 67.8 (range 43 to 76 years). Five patients were found to have a SEL localized in the distal duodenum, five in the gastric antrum, two in the gastric fundus and four in the gastric body. The mean size of the lesions was 20.5 mm (range 18 - 24 mm). EUS-FNB with 25G-PC enabled final diagnosis in nine patients (56.2 %). Regarding the subgroup of duodenal lesions, the procedure was successful in four of five (80 %). Final diagnoses with EUS-guided sampling were GIST (n = 6), leiomyoma (n = 2) and metastatic ovarian carcinoma (n = 1). No procedure-related complications were recorded. CONCLUSION: In patients with small GI-SELs, additional tissue obtained with 25G-PC could represents a "rescue" strategy after an unsuccessful procedure with larger-bore needles, especially when lesions are localized in the distal duodenum.

Biliary plastic stent does not influence the accuracy of endoscopic ultrasound-guided sampling of pancreatic head masses performed with core biopsy needles.

OBJECTIVE: While the presence of biliary stent significantly decreases the accuracy of endoscopic ultrasound (EUS) for pancreatic head cancer staging, its impact on the EUS-guided sampling accuracy is still debated. Furthermore, data on EUS-fine needle biopsy (EUS-FNB) using core biopsy needles in patients with pancreatic mass and biliary stent are lacking. The aim of this study was to evaluate the influence of biliary stent on the adequacy and accuracy of EUS-FNB in patients with pancreatic head mass. METHODS: All patients who underwent EUS-guided sampling with core needles of solid pancreatic head masses causing obstructive jaundice were retrospectively identified in a single tertiary referral center. Adequacy, defined as the rate of cases in which a tissue specimen for proper examination was achieved, with and without biliary stent, was the primary outcome measure. The diagnostic accuracy and complication rate were the secondary outcome measures. RESULTS: A total of 130 patients with pancreatic head mass causing biliary obstruction were included in the study: 74 cases of them were sampled without stent and 56 cases with plastic stent in situ. The adequacy was 96.4% in the stent group and 90.5% in the group without stent (p=0.190). No significant differences were observed for sensitivity (88.9% vs. 85.9%), specificity (100% for both groups), and accuracy (89.3% vs. 86.5%) between those with and without stent, respectively. The accuracy was not influenced by the timing of stenting (<48h or ≥48h before EUS). No EUS-FNB related complications were recorded. CONCLUSION: The presence of biliary stent does not influence the tissue sampling adequacy, the diagnostic accuracy and the complication rate of EUS-FNB of pancreatic head masses performed with core biopsy needles.

IgG4-related sclerosing disease: an emerging entity frequently misdiagnosed.

IgG4-related sclerosing disease, a multiorgan system disease that has been identified in the last 10 years, is a fibroinflammatory condition with a marked propensity to manifest itself as mass forming lesions characterized by three main histological features (sclerosis, obliterative phlebitis and lymphoplasmacytic infiltrate) and by the presence of abundant IgG4+ plasma cells, frequent elevation of serum IgG4 and a dramatic initial response to steroid therapy. The aim of this mini-review is to increase the capacity to identify the characteristic features of IgG4-related sclerosing disease in specific organs and in two newly proposed entities (urethral caruncle and paratesticular fibrous pseudotumor) using biopsy specimens and methods of counting IgG4. In addition we examine the relationship between IgG4-related sclerosing disease and malignancy. In fact, an increased ability to recognize the characteristic features of IgG4-related sclerosing disease would play an extremely important role in avoiding unnecessary surgery in favor of initiating corticosteroid therapy.