While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m2 of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd step). 90Y doses of 2.22-2.96 GBq/m2 were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m2. Tumour mass reduction (>25%-100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from 90Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m2, allowing the injection of 90Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies.

In selected cases, NSM with ELIOT of NAC has so far permitted good local control of the disease and satisfactory cosmetic results. Wider surgical experience is required to minimise the risk of leaving tumor cells in the region of the spared NAC and a longer follow up is necessary to evaluate the long term tumor recurrence rate at the NAC.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted. Cancer Cytopathol 2020;0:2-10.

Epithelial ovarian carcinoma (EOC) arises from the ovarian surface epithelium (OSE), a monolayer of poorly differentiated epithelial cells that lines the ovary. The molecular mechanisms underlying EOC invasion into the surrounding stroma and dissemination to the peritoneum and to retroperitoneal lymph nodes are still unclear. Here, we analyzed the expression and the functional role of the cell adhesion molecule L1 during EOC development. In patient-derived samples, L1 was expressed both in OSE and in a subset of EOC, in the latter being mostly restricted to the invasive areas of the tumors. The expression of L1 correlated significantly with poor outcome and with unfavorable clinicopathologic features of the disease. The peculiar expression pattern of L1 in normal OSE and invasive EOC raised the possibility that this adhesion molecule serves a different function in nontransformed versus neoplastic ovarian epithelial cells. Indeed, we showed that in OSE cells L1 supports cell-cell adhesion and enhances apoptosis, whereas it has no effect on cell proliferation and invasion. In contrast, L1 inhibits cell-cell adhesion and apoptosis in ovarian carcinoma cells, where it promotes malignancy-related properties, such as cell proliferation, Erk1/2-dependent and phosphoinositide 3-kinase-dependent invasion, and transendothelial migration. Interestingly, a crosstalk with the fibroblast growth factor receptor signaling is implicated in the promalignant function of L1 in tumor cells. Our findings point to L1 as an EOC biomarker correlating with poor prognosis, and highlight a switch in L1 function associated to the neoplastic transformation of ovarian epithelial cells, thus implicating L1 as a potential therapeutic target.