Immunotherapy for Esophageal Cancers: What Is Practice Changing in 2021?

The prognosis of advanced esophageal cancer is dismal, and treatment options are limited. Since the first promising data on second-line treatment with checkpoint inhibitors in esophageal cancer patients were published, immunotherapy was surmised to change the face of modern cancer treatment. Recently, several studies have found this to be true, as the checkpoint inhibitors nivolumab and pembrolizumab have achieved revolutionary response rates in advanced as well as resectable settings in esophageal cancer patients. Although the current results of large clinical trials promise high efficacy with tolerable toxicity, desirable survival rates, and sustained quality of life, some concerns remain. This review aims to summarize the novel clinical data on immunotherapeutic agents for esophageal cancer and provide a critical view of potential restrictions for the implementation of these therapies for unselected patient populations.

Subcutaneous progesterone versus vaginal progesterone for luteal phase support in in vitro fertilization: A retrospective analysis from daily clinical practice

Objective: Progesterone application for luteal phase support is a well-established concept in in vitro fertilization (IVF) treatment. Water-soluble subcutaneous progesterone injections have shown pregnancy rates equivalent to those observed in patients receiving vaginal administration in randomized controlled trials. Our study aimed to investigate whether the results from those pivotal trials could be reproduced in daily clinical practice in an unselected patient population.Methods: In this retrospective cohort study in non-standardized daily clinical practice, we compared 273 IVF cycles from 195 women undergoing IVF at our center for luteal phase support with vaginal administration of 200 mg of micronized progesterone three times daily or subcutaneous injection of 25 mg of progesterone per day.Results: Various patient characteristics including age, weight, height, number of oocytes, and body mass index were similar between both groups. We observed no significant differences in the clinical pregnancy rate (CPR) per treatment cycle between the subcutaneous (39.9%) and vaginal group (36.5%) (p=0.630). Covariate analysis showed significant correlations of the number of transferred embryos and the total dosage of stimulation medication with the CPR. However, after adjustment of the CPR for these covariates using a regression model, no significant difference was observed between the two groups (odds ratio, 0.956; 95% confidence interval, 0.152–1.786; p=0.888).Conclusion: In agreement with randomized controlled trials in study populations with strict selection criteria, our study determined that subcutaneous progesterone was equally effective as vaginally applied progesterone in daily clinical practice in an unselected patient population.

Effect of Microfluidic Sperm Separation vs. Standard Sperm Washing Processes on Laboratory Outcomes and Clinical Pregnancy Rates in an Unselected Patient Population

A prospective, multicenter, randomized, sibling oocyte study was conducted with 86 couples to evaluate if a microfluidic sperm separation device improved ICSI sperm selection and subsequent cycle outcomes of fertilization, blastocyst utilization, ploidy, and clinical pregnancy rate when applied to a general patient population. Patients with at least 10 metaphase II oocytes were enrolled in the study and sibling oocyte groups were split in half. One half of the oocytes underwent ICSI with the control processed sperm and the other half were injected with sperm sorted by the ZyMōt microfluidic sperm separation device. Fertilization rate was recorded and resulting blastocysts were biopsied and evaluated for ploidy status with NGS. Euploid, non-mosaic embryos were randomly selected for single embryo transfer. A total of 787 oocytes were evaluated in the ZyMōt group and 777 in the control group. No statistical differences were observed between ZyMōt and control processing methods in any of the study outcomes evaluated. It is possible that the selection of normal, progressive sperm for ICSI, and the repair capacity of oocytes are sufficient to promote normal embryonic development in the general infertility population.

Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

Unibody bifurcated aortic endograft: device description, review of the literature and future perspectives

The unibody (Powerlink/AFX/AFX2) Endovascular AAA device (Endologix Inc., CA, USA) presents a unique design with its long main body and two innate limbs. The device is designed to be deployed and sits on the native aortoiliac bifurcation and represents the only one-piece bifurcated endograft designed to use anatomical fixation for endograft stabilization. According to published literature, the unibody device seems to represent a valid choice in the treatment of abdominal aortic aneurysms. This particular device would seem to satisfactorily perform even in the treatment of more compressed aneurysms (also in off-label association with parallel grafts) and in occlusive pathologies. Ongoing studies will provide new real-life data in a large and unselected patient population to better understand the device’s advantages and limitations.

Patients undergoing urgent trans-aortic valve implantation suffer from an increased mortality rate

Introduction Information on the outcome of urgent Transcatheter valve implantations (TAVI) is scarce, but available data suggest that it could be a reasonable option for the treatment of decompensated severe aortic valve stenosis. The prospects of an all-comer urgent population, however, are unknown. Here we report our experience with clinically indicated urgent TAVI implantation in an unselected patient population with severe aortic valve stenosis (AS). Purpose To compare the outcome of patients undergoing urgent or elective TAVI and to identify potential predictors of outcome. Methods A retrospective, single centre study of AS patients undergoing femoral or apical TAVI between 01. 01.2013 and 30.09.2018 was performed. Demographic information, medical history, clinical and procedural data were collected from the local electronic database. Urgent implantation was defined as accelerated, in-hospital patient preparation and urgent device placement following an acute admission. Survival was investigated with Kaplan-Meier survival analysis and log-rank test. Regression analysis was performed to identify possible predictors of mortality. Results During the study period TAVI was performed in 631 patients, of whom 53 (8.4%) underwent urgent TAVI. In the case of urgent procedures, the median admission-to-procedure time was 18 [10–29] days. Age, gender and the prevalence of diabetes mellitus, chronic obstructive lung disease (COPD) and a glomerular filtration rate of ≤30ml/min was comparable among the groups. Patients in the urgent group had a lower BMI (26 [23–28] vs. 27 [24–30]; p<0.05), had more frequently an ejection fraction <30% (30% vs 4%p<0.001) and a higher Euroscore II (5.3 [3.4–10.9]% vs 2.9 [1.7–4.5]%; p<0.001). The rate of apical implantation and post-operative stroke, pacemaker implantation and renal failure did not differ between the groups. Urgent patients, however, needed longer post-procedural hospitalization (6 [4–9] vs 4 [3–6] days; p<0.001) and had higher in-hospital (11.3% vs 3,1%; <0.001) and one-year mortality rates (28.3% vs 8.5%; p<0.001). Urgency was an independent predictor of overall one-year mortality (HR 3.0, p=0.001) and worsened the survival of the individuals who were discharged from the hospital (out-of-hospital mortality at one-year; HR 2.8, p=0.011), but had no effect on in-hospital mortality. In-hospital mortality was mainly determined by apical access (OR 3.1; p=0.016) and major post-operative stroke (OR 8.8.; p=0.006), with both worsening overall 1-year survival too (HR 1.8 for apical access and 4.8 for stroke; p<0.05). Mortality after a successful hospital discharge was increased not only by urgency (HR 2.8, p=0.011), but by COPD (HR 2.1; p=0.04) and prolonged post-operative hospitalization (HR 1.05/day; p=0.001) as well. Conclusion Stabilizing AS patients can mitigate the effect of urgency on peri-procedural survival. Urgency remains, however, an important determinant of one-year TAVI outcome. Funding Acknowledgement Type of funding source: None

Screening and Brief Intervention

Screening and brief interventions for alcohol and other drugs are recommended by many expert guidelines. This is often followed by referral to treatment for those with a moderate–severe substance use disorder (SBIRT). Screening begins with asking about alcohol and other drug use; a number of instruments can help with this process. Brief intervention is a motivational process of assessing drug use, giving feedback, setting goals, arriving at a strategy for change, and providing a plan for follow-up. Research on SBIRT has yielded mixed results, with some evidence of efficacy, particularly for nondependent at-risk drinkers. Assessing an individual’s stage of change can help inform the approach to helping initiate recovery. Engaging and building rapport helps promote change by offering hope and encouragement, as well as treatment options. Relapse is a time for both patient and clinician to learn from mistakes and to correct them by strengthening treatment. Drug testing has limited utility for screening in unselected patient populations, but it can be useful in certain clinical situations and for monitoring individuals in treatment.

Lower gastrointestinal symptoms and symptoms-based triaging systems are poor predictors of clinical significant disease on colonoscopy

IntroductionLower gastrointestinal symptoms (LGS) are a common cause of referral to the gastroenterology service. International guidelines are available to prioritise referrals. Some studies have reported that symptoms alone are a poor marker of clinically significant disease (CSD) but symptoms remain the main way to prioritise referrals in routine clinical practice.Aims/backgroundTo correlate LGS with colonoscopy findings in an unselected patient cohort and to investigate whether using National Institute for Health and Care Excellence (NICE) guidelines improve risk stratification.MethodColonoscopy data over a 2-year period were obtained from our endoscopy database. Only patients with assessment of symptoms as their primary indication for colonoscopy were included. Patient records were retrospectively reviewed. Exclusion criteria: known inflammatory bowel disease (IBD), familial cancer syndromes, polyp and colorectal cancer (CRC) surveillance, and prior colonoscopy within 5 years. Demographics, symptoms and colonoscopy findings were recorded and analysed.Results1116 cases were reviewed; 493 (44%) males, age 54.3 years (16–91). CSD occurred in only 162 (14.5%); CRC 19 (1.7%), high-risk adenoma 40 (3.6%), inflammation 97 (8.7%) (IBD 65 (5.8%), microscopic colitis 9 (0.8%) and indeterminate-inflammation 23 (2%)), angiodysplasia 6 (0.5%). Diarrhoea gave the highest diagnostic yield for CSD of 5.3% (OR 3.15, 95% CI 2.2 to 4.7, p<0.001), followed by PR bleeding, 2.9% (OR 1.9, 95% CI 1.24 to 2.9, p=0.003). Weight loss gave the lowest diagnostic yield of 0.4%; (OR 0.79, 95% CI 0.28 to 2.24, p=0.65). 592 (53%) and 517 (46%) fitted the NICE guidelines for CRC and IBD, respectively. Using NICE positivity improved detection but overall yield remained low 3% vs 0.4% (OR 7.71, 95% CI 1.77 to 33.56, p=0.0064) for CRC, and 9% vs 2.8% (OR 3.5, 95% CI 1.99 to 6.17, p<0.0001) for IBD.ConclusionsThe overall prevalence of CSD in our unselected symptomatic patients is low (14.5%). A holistic approach including combining symptoms and demographics with novel tools including stool biomarkers and minimally invasive colonoscopy alternatives should be applied to avoid unnecessary colonoscopy.