Cyclin E expression is associated with high levels of replication stress in triple-negative breast cancer

Replication stress entails the improper progression of DNA replication. In cancer cells, including breast cancer cells, an important cause of replication stress is oncogene activation. Importantly, tumors with high levels of replication stress may have different clinical behavior, and high levels of replication stress appear to be a vulnerability of cancer cells, which may be therapeutically targeted by novel molecularly targeted agents. Unfortunately, data on replication stress is largely based on experimental models. Further investigation of replication stress in clinical samples is required to optimally implement novel therapeutics. To uncover the relation between oncogene expression, replication stress, and clinical features of breast cancer subgroups, we immunohistochemically analyzed the expression of a panel of oncogenes (Cyclin E, c-Myc, and Cdc25A,) and markers of replication stress (phospho-Ser33-RPA32 and γ-H2AX) in breast tumor tissues prior to treatment (n = 384). Triple-negative breast cancers (TNBCs) exhibited the highest levels of phospho-Ser33-RPA32 (P < 0.001 for all tests) and γ-H2AX (P < 0.05 for all tests). Moreover, expression levels of Cyclin E (P < 0.001 for all tests) and c-Myc (P < 0.001 for all tests) were highest in TNBCs. Expression of Cyclin E positively correlated with phospho-RPA32 (Spearman correlation r = 0.37, P < 0.001) and γ-H2AX (Spearman correlation r = 0.63, P < 0.001). Combined, these data indicate that, among breast cancers, replication stress is predominantly observed in TNBCs, and is associated with expression levels of Cyclin E. These results indicate that Cyclin E overexpression may be used as a biomarker for patient selection in the clinical evaluation of drugs that target the DNA replication stress response

Hybrid endoscopic mucosal resection and full-thickness resection for large colonic polyps harboring a small focus of invasive cancer: a case series

Endoscopic treatment of large laterally spreading tumors (LSTs) with a focus of submucosally invasive colorectal cancer (T1 CRC) can be challenging. We evaluated outcomes of a hybrid resection technique using piecemeal endoscopic mucosal resection (pEMR) and endoscopic full-thickness resection (eFTR) in patients with large colonic LSTs containing suspected T1 CRC. Six hybrid pEMR-eFTR procedures for T1 CRCs were registered in a nationwide eFTR registry between July 2015 and December 2019. In all cases, the invasive part of the lesion was successfully isolated with eFTR; with eFTR, histologically complete resection of the invasive part was achieved in 5/6 patients (83.3%). No adverse events occurred during or after the procedure. The median follow-up time was 10 months (range 6-27), with all patients having undergone >= 1 surveillance colonoscopy. One patient had a small adenomatous recurrence, which was removed endoscopically. In conclusion, hybrid pEMR-eFTR is a promising noninvasive treatment modality that seems feasible for a selected group of patients with large LSTs containing a small focus of T1 CRC.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

‘Albania: €1’ or the story of ‘big policies, small outcomes’: how Albania constructs and engages its diaspora

Since the fall of the communist regime in the early 1990s, Albania has experienced one of the most significant emigrations in the world as a share of its population. By 2010 almost half of its resident population was estimated to be living abroad – primarily in neighbouring Greece and Italy, but also in the UK and North America. This chapter discusses the emergence and establishment of the Albanian diaspora, its temporal and geographical diversity, and not least its involvement with Albania itself. Albania’s policymaking and key institutions are considered, with a focus on matters of citizenship; voting rights; the debate on migration and development; and not least the complex ways in which kin-state minority policies – related to ethnic Albanians living in Kosovo, Montenegro, southern Serbia, Macedonia and Greece – are interwoven with Albania’s emigration policies

Surgical management of children with intractable functional constipation; experience of a single tertiary children's hospital

Children with intractable functional constipation (FC) may eventually require surgery. However, guidelines regarding the surgical management of children with intractable FC are lacking. The aim of this study was to describe the surgical management of FC in children. A retrospective chart review was performed of children with FC (according to the Rome III criteria) who underwent ileostomy, colostomy or (sub)total colectomy at a tertiary hospital. Treatment success was defined as no longer fulfilling the Rome III-FC-criteria or having a functional ostomy. In addition, a self-developed questionnaire was administered to parents by telephone to assess postsurgical satisfaction (yes-no question and rated on a scale of 1-10). Thirty-seven patients (68% female) were included; median age at first surgery was 12 years (range 1.6-17.6). The initial surgical procedure consisted of ileostomy (n=21), colostomy (n=10), sigmoid resection (n=5) and subtotal colectomy (n=1). Success criteria were fulfilled by 85% of the patients. Postsurgical satisfaction of parents was 91% with a median postoperative satisfaction score of 8 (range 2-10), and 97% would opt for the same procedure(s) if necessary. Thirty patients (81%) experienced stoma problems, with 12 patients (32%) requiring stoma-revisions. Other complications occurred in 16 patients (43%). Surgery can improve symptoms in children with intractable FC. Despite morbidity and complications, parental satisfaction is high. Prospective, high-quality research is necessary to develop guidelines for the diagnostic work-up and surgical management in children with intractable F

Remittances, return, diaspora: framing the debate in the context of Albania and Kosova

This paper is an introduction to the special issue and is in five parts. The first part provides a brief overview of post-1990 migration from Albania as a route out of poverty and a quest for freedom and self-realization for Albanians. The Kosovan migration has a different history: labour migration in the 1960s and early 1970s, refugee flight in the 1990s. Then the authors outline a theoretical framework for migration's contribution to development. Third, this framework is applied to the cases of Albania and Kosova, drawing on findings from the papers in this issue and other literature. The fourth section of the paper revisits the migration-development nexus from a policy perspective, examining in turn remittances, return migration and host- and home-country government responsibilities. Finally, we speculate on the global economic crisis that started in mid-2008 and its impact on the region and its migrants

Surgical management of children with intractable functional constipation; experience of a single tertiary children's hospital

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The intersection of gender and generation in Albanian migration, remittances and transnational care

The Albanian case represents the most dramatic instance of post-communist migration: about one million Albanians, a quarter of the country's total population, are now living abroad, most of them in Greece and Italy, with the UK becoming increasingly popular since the late 1990s. This paper draws on three research projects based on fieldwork in Italy, Greece, the UK and Albania. These projects have involved in-depth interviews with Albanian migrants in several cities, as well as with migrant-sending households in different parts of Albania. In this paper we draw out those findings which shed light on the intersections of gender and generations in three aspects of the migration process: the emigration itself, the sending and receiving of remittances, and the care of family members (mainly the migrants' elderly parents) who remain in Albania. Theoretically, we draw on the notion of `gendered geographies of power and on how spatial change and separation through migration reshapes gender and generational relations. We find that, at all stages of the migration, Albanian migrants are faced with conflicting and confusing models of gender, behavioural and generational norms, as well as unresolved questions about their legal status and the likely economic, social and political developments in Albania, which make their future life plans uncertain. Legal barriers often prevent migrants and their families from enjoying the kinds of transnational family lives they would like

Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registry

Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions Methods Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. Results Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), reresection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9%). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4%) and full-thickness resection in 288 (83.2%). The median diameter of resected specimens was 23mm. Overall adverse event rate was 9.3% (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. Conclusion eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed