Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?

Purpose: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes. Methods: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS). Results: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour >= 10 cm in diameter. Conclusion: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Efficacy of Trabectedin in Patients with Advanced or Metastatic Alveolar Soft-Part Sarcoma

Background: Alveolar soft-part sarcoma (ASPS) is a rare sarcoma often occurring in young patients that is characterized by the unbalanced translocation der(17)t(X;17) (p11;q25). Although itusuallyshowsan indolent clinical course, the prognosis is usually poor in advanced disease. Since standard chemotherapy regimens used in soft-tissue sarcomas lack efficacy in ASPS, new therapeutic options are needed. We investigated the efficacy of trabectedin, which has demonstrated activity in a variety of cancer types including some of the most prevalent translocation-related sarcomas. Patients and Methods: 7 patients with metastatic or advanced ASPS treated with trabectedin in the Sarcoma Center Berlin-Brandenburg and the University Hospital of Greifswald were analyzed for median progression-free survival (mPFS), overall survival (OS), and therapy-related toxicity. Results: In 6 patients with documented disease progression, disease stabilization was reached with trabectedin; only 1 patient experienced progressive disease. The mPFS and OS were 7 months and 21 months, respectively, since the start of trabectedin treatment. Overall, no severe Common Toxicity Criteria (CTC) grade 3 or 4 toxicity was observed. Conclusions: The poor prognosis of patients with ASPS has so far been due to the unavailability of effective systemic treatments. Trabectedin can be considered the only currently registered drug with clinical activity in this disease

Delivering public services in the mixed economy of welfare : perspectives from the voluntary and community sector in rural England

The voluntary and community sector in England is playing an increasingly important role in the delivery of public services to older adults and in doing so they rely on unpaid volunteers. In this article, we draw on the findings of a recent qualitative study of the impact on the voluntary and community sector of delivering ‘low-level’ public services that promote independent living and wellbeing in old age. The fieldwork focused on services that help older adults aged 70+ living in remote rural communities across three English regions. Those charged with service delivery, which is increasingly the voluntary and community sector, face particular challenges, such as uncertain funding regimes and reliance on volunteer labour

Fibrinogen-like protein 2 in gastrointestinal stromal tumour

Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2. FGL2 expression was associated with small GIST size, low mitotic counts and low tumour-infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence-free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2-negative GIST appeared to benefit most from long duration of adjuvant imatinib. We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.Peer reviewe

Analysis of TCR activation kinetics in primary human T cells upon focal or soluble stimulation.?

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Gemcitabine and Docetaxel for Epithelioid Sarcoma: Results from a Retrospective, Multi-Institutional Analysis

Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients' median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy

Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation

Implantation of the fertilized egg into the maternal uterus depends on the fine balance between inflammatory and anti-inflammatory processes. Whilst regulatory T cells (Tregs) are reportedly involved in protection of allogeneic fetuses against rejection by the maternal immune system, their role for pregnancy to establish, e.g., blastocyst implantation, is not clear. By using 2-photon imaging we show that Foxp3(+) cells accumulated in the mouse uterus during the receptive phase of the estrus cycle. Seminal fluid further fostered Treg expansion. Depletion of Tregs in two Foxp3.DTR-based models prior to pairing drastically impaired implantation and resulted in infiltration of activated T effector cells as well as in uterine inflammation and fibrosis in both allogeneic and syngeneic mating combinations. Genetic deletion of the homing receptor CCR7 interfered with accumulation of Tregs in the uterus and implantation indicating that homing of Tregs to the uterus was mediated by CCR7. Our results demonstrate that Tregs play a critical role in embryo implantation by preventing the development of a hostile uterine microenvironment.DFG grants: (ZE526/4-2, SFB854TP7), Wilhelm Sander Stiftung Germany grant: (2009.022.1), Helmholtz Alliance for Immunotherapy, FCT, Medical Faculty Otto-von-Guericke University PhD grant

The timing of pregnancies after bariatric surgery has no impact on children’s health—a nationwide population-based registry analysis

Purpose Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children’s outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12–24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied. Materials and Methods A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring’s data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months. Results Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval. Conclusion Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children.publishedVersio

Quality of Life and Utility in Patients with Metastatic Soft Tissue and Bone Sarcoma: The Sarcoma Treatment and Burden of Illness in North America and Europe (SABINE) Study

The aim of the study was to assess health-related quality of life (HRQoL) among metastatic soft tissue (mSTS) or bone sarcoma (mBS) patients who had attained a favourable response to chemotherapy. We employed the EORTC QLQ-C30, the 3-item Cancer-Related Symptoms Questionnaire, and the EQ-5D instrument. HRQoL was evaluated overall and by health state in 120 mSTS/mBS patients enrolled in the SABINE study across nine countries in Europe and North America. Utility was estimated from responses to the EQ-5D instrument using UK population-based weights. The mean EQ-5D utility score was 0.69 for the pooled patient sample with little variation across health states. However, patients with progressive disease reported a clinically significant lower utility (0.56). Among disease symptoms, pain and respiratory symptoms are common. This study showed that mSTS/mBS is associated with reduced HRQoL and utility among patients with metastatic disease