Background and Objectives: Electrochemotherapy is effective in treatment of various cutaneous tumors and could be translated into treatment of deep-seated tumors. With this aim a prospective pilot study was conducted to evaluate feasibility, safety, and efficacy of intraoperative electrochemotherapy in the treatment of colorectal liver metastases. Methods: Electrochemotherapy with bleomycin was performed during open surgery, by insertion of long needle electrodes into and around the tumor according to the individualized pretreatment plan. Results: A 29 metastases in 16 patients were treated in 16 electrochemotherapy sessions. No immediate (intraoperative) and/or postoperative serious adverse events related to electrochemotherapy were observed. Radiological evaluation of all the treated metastases showed 85% complete responses and 15% partial responses. In a group of seven patients that underwent a second operation at 6-12 weeks after the first one, during which electrochemotherapy was performed, the histology of resected metastases treated by electrochemotherapy showed less viable tissue (P ¼ 0.001) compared to non-treated ones. Conclusions: Electrochemotherapy of colorectal liver metastases proved to be feasible, safe, and efficient treatment modality, providing its specific place in difficult to treat metastases, located in the vicinity of major hepatic vessels, not amenable to surgery or radiofrequency ablation.

BackgroundTo overcome obstacles within the Slovenian organised cervical cancer screening programme, a randomised pilot study of human papillomavirus (HPV) self-sampling among non-attenders was performed, aiming to assess three different screening approaches.Participants and methodsNon-attenders aged 30–64 years from two Slovenian regions were randomised to two HPV self-sampling groups–the opt-in (I1, n = 14.400) and the opt-out (I2, n = 9.556), with a control group (P, n = 2.600). Self-collected samples were analysed using the Hybrid Capture 2 assay. HPV-positive women were invited to a colposcopy. The overall and type-specific intention-to-screen response rates and histological outcomes with a positive predictive value (PPV) according to the women’s age, the screening approach, the level of protection resulting from previous screening history, and the region of residence were assessed.ResultsOf the 26.556 women enrolled, 8.972 (33.8%) responded with self-sample for HPV testing and/or traditional cytology within one year of enrolment. Response rates were 37.7%, 34.0% and 18.4% (p < 0.050) for opt-out, opt-in and control groups. Cervical intraepithelial neoplasia (CIN)2+ was diagnosed in 3.9/1.000, 3.4/1.000, and 3.1/1.000 women (p > 0.050), respectively. PPV of the HPV self-sampling was 12.0% and 9.6% for CIN2+ and CIN3+. The highest PPV was obtained in non-attenders in screening programme for more than 10-years and concordant results of HPV testing with 40.8% for CIN2+ and 38.8% for CIN3+.ConclusionsThe results of our study show that a high response to HPV self-sampling can be achieved also in an opt-in approach, if women are encouraged to choose between self-sampling at home and screening with gynaecologist. In addition, clinically important risk difference for a high-grade cervical lesion exists in the case of a positive result of HPV testing on self-collected samples, depending on the length of the interval since last screening. Stratified management of these women should be strongly considered. Women who were not screened with cytology for at least 10 years should be referred to immediate colposcopy for histology verification instead to delayed re-testing.

Background: For hepatocellular carcinoma (HCC), effective therapeutic approaches are lacking. As aberrant gene methylation is a major contributor to HCC development, demethylating drugs such as 5-azacytidine (5-Aza) have been proposed. As most 5-Aza mechanisms of action are unknown, we investigated its phenotypic/molecular effects. Methods: 5-Aza effects were examined in the human HCC cell lines JHH-6/HuH-7 and in the rat cell-line N1-S1. We also employed a xenograft mouse model (HuH-7), a zebrafish model (JHH-6), and an orthotopic syngeneic rat model (N1-S1) of HCC. Results: 5-Aza downregulated cell viability/growth/migration/adhesion by upregulating miR-139-5p, which in turn downregulated ROCK2/cyclin D1/E2F1 and increased p27kip1, resulting in G1/G0 cell accumulation. Moreover, a decrease in cyclin B1 and an increase in p27kip1 led to G2/M accumulation. Finally, we observed a decrease in MMP-2 levels, a stimulator of HCC cell migration. Aza effects were confirmed in the mouse model; in the zebrafish model, we also demonstrated the downregulation of tumor neo-angiogenesis, and in the orthotopic rat model, we observed impaired N1-S1 grafting in a healthy liver. Conclusion: We demonstrate for the first time that 5-Aza can impair HCC development via upregulation of miR-139-5p, which in turn impairs the ROCK2/cyclin D1/E2F1/cyclin B1 pro-proliferative pathway and the ROCK2/MMP-2 pro-migratory pathway. Thus, we provide novel information about 5-Aza mechanisms of action and deepen the knowledge about the crosstalk among ROCK2/cyclin D1/E2F1/cyclin B1/p27kip1/MMP-2 in HCC.

Intraosseous hibernoma is a rare finding that has only recently come to light in the literature. We report a case of intraosseous hibernoma in the sacrum identified as an incidental finding in a 40 year-old female with chronic lower back pain. The tumor was characterized with all routine imaging modalities. In the review of the literature we correlate the imaging findings with previously reported cases. With increasing number of radiologic investigations it is expected to discover more intraosseous hibernomas and the radiologists should consider intraosseous hibernoma as differential diagnosis of the sclerotic bone lesion.

Chronic lymphocytic leukemia (CLL) typically pursues a prolonged course. Its transformation into a more aggressive lymphoma occurs in 2-8% of all patients. Most commonly, diffuse large B-cell lymphoma develops. Transformation into a classical Hodgkin's lymphoma (cHL) occurs in <1%. Plasmablastic transformation has been only rarely reported. Cases of synchronous divergent transformation of CLL into a composite lymphoma are exceedingly rare. We describe the unique occurrence of the transformation of a long-standing CLL into a synchronous clonally related cHL as well as plasmablastic lymphoma (PBL) in an 85-year-old female patient. After 10 years of asymptomatic CLL, our patient was treated with a rituximab-chlorambucil scheme in combination with pegfilgrastim for recurrent infections and the development of B symptoms. Five cycles (of six planned) were administrated with no adverse effects. After the fifth cycle, lymphadenopathy with pronounced B symptoms appeared. Histology showed the presence of cHL in the lymph node, while the bone marrow was infiltrated by PBL. Our patient died in sepsis not receiving further specific oncologic treatment due to her poor general condition. Additional cytogenetic and molecular studies showed that this was a case of mutated CLL with trisomies of chromosomes 12, 3, and 18 (a rare specific +12 plus other-non+19 CLL subgroup). The presence of trisomy 12 has also been proved in plasmablasts and in cHL cells. BM specimen. This differential diagnosis can easily be abandoned by morphology of PBL-T cells in comparison to CLL cells and their proliferative rate, PBL-T showing a high proliferative activity while it does not exceed a few percent in CLL. ConclusionIn conclusion, herein we described the unique case of a long-standing CLL in an 85-year-old patient in the very rare specific +12 plus other-non+19 CLL subgroup with co-existing trisomies 3 and 18 and transformation into a composite lymphoma, namely cHL and PBL-T. Considering the trisomies observed, it is very likely that both of them are clonally related to the CLL clone. To the best of our knowledge, such a case has never been previously described. Statement of EthicsThis case study was approved by the Medical Ethics Committee of the Institute of Oncology, Ljubljana, Slovenia. Informed consent for publication is not applicable. The patient died, and she has not had any living relatives.

BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers. We present a case of a patient with BAP1 cancer syndrome who developed a metastatic breast cancer with loss of BAP1 demonstrated on immunohistochemistry. She carried a germline BAP1 likely pathogenic variant (c.898_899delAG p.(Arg300Glyfs*6)). In addition, tumor tissue sequencing identified a concurrent somatic variant in BAP1 (partial deletion of exon 12) and a low tumor mutational burden. As her triple negative tumor was shown to be PD-L1 positive, the patient was treated with combination of atezolizumab and nab-paclitaxel. She had a complete and sustained response to immunotherapy even after discontinuation of nab-paclitaxel. This case strengthens the evidence for including breast cancer in the BAP1 cancer syndrome tumor spectrum with implications for future cancer prevention programs. It also indicates immune checkpoint inhibitors might prove to be an effective treatment for BAP1-deficient breast cancer.

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Erythroblastic sarcoma (ES) is an extremely rare extramedullary solid tumor of immature erythroid cells, with around a dozen human cases to our knowledge presented so far in the english literature, none of the cases presenting as pleural effusion. Here we describe a case of ES in a thoracic wall diagnosed by cytological examination of pleural effusion with histologic correlation in a 53-year-old patient with a 10month history of myelodysplastic syndrome/myeloproliferative neoplasm with grade III reticulin myelofibrosis.