Feasibility of tumor testing for BRCA status in high-grade serous ovarian cancer using fresh-frozen tissue based approach.

OBJECTIVE: For many years, BRCA mutational status has only been considered as a predictor of ovarian cancer susceptibility and as a prognostic factor. Nonetheless, in the era of precision medicine, it has also become a predictive biomarker of response to platinum-based-chemotherapy and, more recently, to PARP-inhibitors, also in the frontline setting. We assessed the feasibility of a fresh frozen tissue-based-BRCA-screening workflow in a tertiary referral center. METHODS: We consecutively enrolled a series of 456 newly diagnosed FIGO-Stage IIIC-IV, high grade serous-ovarian cancer patients. All patients receiving tumor-biopsy underwent tBRCA-testing. RESULTS: Clinically relevant tissue-BRCA (tBRCA) variants were observed in 145 women (31.8%), particularly we recognized 89 (61.4%) patients with BRCA1-pathogenetic variants (PVs) and 56 women (38.6%) with BRCA2-PVs. Among 292 tBRCA wild-type (wt) patients, 88 cases were germline BRCA tested (gBRCA) and 86 (97.8%) were confirmed as gBRCAwt, while 1 (1.1%) had gBRCA variant of uncertain significance and 1 had gBRCA mutation (1.1%). The concordance of tumor test versus germline BRCA test was 86.3% (209/242). Large genomic rearrangements (LGRs) were suspected in 13/292 tBRCAwt patients (4.5%) by using bioinformatic algorithm and multiplex ligation-dependent probe amplification (MLPA) was performed, with evidence of PVs in only 1 case. CONCLUSIONS: Fresh-frozen tissue-based BRCA screening workflow is feasible and reliable. It allows to enlarge the BRCA mutated population that might receive PARPi with the greatest benefit, without missing cascade testing for family members and therefore, maintaining its preventive role.

Sentinel lymph node mapping procedure in T1 colorectal cancer: A systematic review of published studies.

OBJECTIVE: to investigate the role of sentinel lymph node mapping procedure in T1 Colorectal cancer. BACKGROUND: The incidence of T1 Colorectal cancer is increasing thanks to screening and awareness campaigns. The issue concerning T1 is when to consider a local treatment curative or when it is necessary a radical resection. The histopathological features of resected polyps are able to predict the nodal spread but the value of specificity is increasingly a problem of these predictors. The sentinel lymph node procedure could be a solution. METHODS: A systematic review was performed following PRISMA guidelines and using "sentinel node", "lymph nodes", and "colorectal cancer" as search terms in PubMed and Embase databases. References from included studies, review articles, and editorials were cross-checked. The risk of bias and quality of the included studies were assessed using the QUADAS-2 tool. The primary outcome was sentinel lymph node accuracy rate and the secondary outcome was sentinel lymph node detection rate for T1 Colorectal cancer. RESULTS: A total of 12 studies (108 patients) met inclusion and exclusion criteria, 8 were monocentric cohort studies and 4 were multicentric cohort studies. The rate of sentinel lymph node accuracy in T1 colorectal cancer varies from 89% to 100%. Only 1 false negative was found. In 7 of these 12 studies (71 patients) the detection rate of T1 colorectal cancer was reported and showed a variation from 92% to 100%. Even in this case, only 1 case of failed procedure was found. DISCUSSION: The literature on this topic agrees on that sentinel lymph node mapping, differently from breast cancer and melanomas should not be used for therapeutic purposes in colorectal cancer, but mainly to refine staging. The reason is the low sensitivity of this procedure with an accompanying high false negative rate. However, the data refers mainly to advanced stages of the disease because there are few data available on the earlier stages and in particular related to T1. Isolating the data related only to T1, the false negative rate seems to be very low. Additional studies are necessary, but a decisional role of sentinel lymph node mapping on the treatment of T1 Colorectal cancer is possible in the future.

Seriate cytology vs molecular analysis of peritoneal washing to improve gastric cancer cells detection.

BACKGROUND: Intraperitoneal malignant cells detection in patients with gastric cancer is associated with a significant decrease in overall survival. The overall accuracy of cytological examination of peritoneal lavages, however, is quite low, and intraperitoneal recurrence has been observed even in patients with negative cytology. Immunocytochemistry and molecular techniques have been investigated to improve high-risk patients' identification with variable results. The aim of this study was to compare the performance of different laboratory methods applied to peritoneal washing, to improve the cytological identification of malignant cells. METHODS: We prospectively evaluated 21 patients who underwent surgery and peritoneal lavage for gastric cancer. Among them, 18 had negative cytology and three were positive for malignant cells. For each patient, immunohistochemistry with BerEP4 antibody was performed on seriate sections of cellblock preparation at different levels, using the method reported for sentinel nodes in other types of cancer. Paired frozen quotes of washing fluids were evaluated by qRT-PCR with primer for mRNA of Ceacam5. RESULTS: In 4 of 18 patients with previous negative routine cytology, isolated neoplastic cells in seriate sections of the cellblock inclusion have been found. Results showed to be coherent with molecular analysis for CEA mRNA. CONCLUSION: The sensitivity and specificity of peritoneal washing analyses should be notably improved by immunohistochemistry applied to multilevel cellblock sectioning. The method is less expensive and more widely applicable than molecular analysis, in each laboratory setting. This approach allows detection of minimum peritoneal seeding in patients with gastric cancer.

O-Ring Protector in Prevention of SSIs in Laparoscopic Colorectal Surgery.

BACKGROUND: Surgical-site infections (SSIs) remain a serious complication of colorectal surgery, causing a significant financial burden to the health care system. The aim of this study is to investigate whether the use of an O-ring retractor can be effective in preventing the incidence of wound infections after elective laparoscopic colorectal surgery. METHODS: A retrospective case-control study from January 2014 to June 2018 was performed. Data were analyzed from a retrospective colorectal database. SSI was defined according to criteria published by the European Centre for Disease Prevention and Control and analyzed as a primary outcome. RESULTS: Three hundred twelve consecutive patients (n = 312) were enrolled in our study. Among them, 158 patients (Group A) in which an O-ring retractor device was used during surgery was compared with a control group of 154 patients (Group B) in which an O-ring retractor device was not used. Primary outcome was to determine SSIs rates among the 2 groups. No statistically differences were observed with regard to baseline characteristics between both groups. A total of 9 patients (5.69%) and 24 (15.58%) with SSIs were identified in Group A and B, respectively, and the difference was statistically significant (OR, 0.32; 95% CI, 0.14-0.72; P = .0045). The median postoperative hospital stay length was 6.7 days in group A and 7.6 days in group B (P ≤ .05). CONCLUSIONS: SSIs infections rates were significantly higher in patients in which an O-ring retractor device was not used. This study suggests that the use of a wound protector device can be considered for routine use in elective colorectal surgery.