ECCO Topical Review on Biological Treatment Cycles in Crohn’s Disease

There are now a growing number of licensed biological therapies for patients with Crohn’s disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side-effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by re-treatment with the same biological agent. Therefore, a concept has emerged in which cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden—ensuring decreased exposure to biological therapy but still enabling appropriate disease control.Currently, there remains uncertainty about the benefit–risk balance for using cycles of biological treatment for patients with Crohn’s disease. Accordingly, an expert panel was convened by the European Crohn’s and Colitis Organisation [ECCO] to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of probable relapse or remission, safety, patient preferences, and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualized, to enable shared decision-making by patients with their clinicians

Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is over-expressed in 70–75% of colorectal adenocarcinomas (CRC). The anti-EGFR monoclonal antibody cetuximab has been approved for the treatment of metastatic CRC, however tumor response to cetuximab has not been found to be associated with EGFR over-expression by immunohistochemistry (IHC). The aim of this study was to explore EGFR and the downstream effector phosphatase and tensin homologue deleted on chromosome 10 (PTEN) as potential predictors of response to cetuximab.</p> <p>Methods</p> <p>CRC patients treated with cetuximab by the Hellenic Cooperative Oncology group, whose formalin-fixed paraffin-embedded tumor tissue was available, were included. Tissue was tested for EGFR and PTEN by IHC and fluorescence in situ hybridization (FISH).</p> <p>Results</p> <p>Eighty-eight patients were identified and 72 were included based on the availability of tissue blocks with adequate material for analysis on them. All patients, except one, received cetuximab in combination with chemotherapy. Median follow-up was 53 months from diagnosis and 17 months from cetuximab initiation. At the time of the analysis 53% of the patients had died. Best response was complete response in one and partial response in 23 patients. In 16 patients disease stabilized. Lack of PTEN gene amplification was associated with more responses to cetuximab and longer time to progression (p = 0.042).</p> <p>Conclusion</p> <p>PTEN could be one of the molecular determinants of cetuximab response. Due to the heterogeneity of the population and the retrospective nature of the study, our results are hypothesis generating and should be approached with caution. Further prospective studies are needed to validate this finding.</p

Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

<p>Abstract</p> <p>Background</p> <p>Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.</p> <p>Methods</p> <p>Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m²daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.</p> <p>Results</p> <p>Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.</p> <p>Conclusion</p> <p>Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.</p> <p>Trial registration</p> <p>NCT00953394</p

A Pichia anomala Strain (P. anomala M1) Isolated from Traditional Greek Sausage is an Effective Producer of Extracellular Lipolytic Enzyme in Submerged Fermentation

Ayeast isolate, selected for its lipolytic activity from a meat product, was characterized as Pichia anomala. Lipolytic activity, determined on p-NPA as esterase, was maximum at 28 °C, pH 6.5, and induced by the short chain triglyceride tributyrin. Fermentations in 2 L and 10 L stirred tank bioreactors, with 20 and 60 g/L glucose respectively, showed that in the second case lipolytic activity increased 1.74-fold, while the biomass increased 1.57-fold. Under otherwise identical aeration conditions, improved mixing in the 10 L reactor maintained higher dissolved oxygen levels which, along with the elevated glucose concentration, resulted in significant increase of specific rates of lipolytic activity (51 vs. 7 U/g/L), while specific rates of growth and glucose consumption maintained lower. The Crabtree-negative yeast (glucose insensitive growth) exhibited a Pasteur effect at lower dissolved oxygen concentrations while elevated glucose prevented ethanol formation under oxygen saturation. The particular physiological traits can be exploited to obtain significant lipolytic activity in a scalable aerobic process

ECCO Topical Review on Biological Treatment Cycles in Crohn's Disease

There are now a growing number of licensed biological therapies for patients with Crohn's disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by retreatment with the same biological agent. Therefore, a concept has emerged where cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low-risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden - ensuring decreased exposure to biological therapy but still enabling appropriate disease control. Currently, there remains uncertainty about the benefit-risk balance for using cycles of biological treatment for patients with Crohn's disease. Accordingly, an expert panel was convened by the European Crohn's and Colitis Organisation (ECCO) to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of likely relapse or remission, safety, patient preferences and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualised, to enable shared decision-making by patients with their clinicians.</p

Correction to: Molecular, biochemical and kinetic analysis of a novel, thermostable lipase (LipSm) from Stenotrophomonas maltophilia Psi‑1, the first member of a new bacterial lipase family (XIX)

We have recently (8th February 2018) published our article entitled “Molecular, biochemical and kinetic analysis of a novel, thermostable lipase (LipSm) from Stenotrophomonas maltophilia Psi-1, the first member of a new bacterial lipase family (XVIII)” [1]. While our manuscript was going through the final stages of publication, an article by Samoylova et al. [2] was published (12th January 2018) in the journal Extremophiles, entitled “Cloning, expression and characterization of the esterase estUT1 from Ureibacillus thermosphaericus which belongs to a new lipase family XVIII”. Since we could not have known of the work of Samoylova et al. [2] when we submitted our manuscript, and in order to avoid confusion in the scientific community, we propose to reclassify LipSm as the first characterized member of the new bacterial lipase family XIX. Therefore throughout our article [1] “lipase family XVIII” should read “lipase family XIX” (title included)