Kyrillus S. Shohdy

Gastric antral vascular ectasia in systemic sclerosis: Where do we stand?

Gastric antral vascular ectasia (GAVE) continues to be a challenge in both diagnosis and treatment. GAVE has a diverse group of associations and presumed causes, including cirrhosis, chronic renal failure and autoimmune connective tissue diseases. However, in most occasions, the management plan of GAVE itself is the same whatever the underlying disease by using Argon plasma coagulation (APC). Herein, we will discuss three cases of systemic sclerosis‐associated GAVE presenting with either acute or chronic gastrointestinal bleeding showing variable responses to APC. Anemia and telangiectasia may be the first striking presentation of systemic sclerosis (SSc). Renal artery stenosis, aortic stenosis, widespread cutaneous and mucosal telangiectasia and hypertension seem to be associated with poor prognosis and should prompt rapid intervention and careful follow‐up. Moreover, the hunt for molecular underpinnings of the broad array of vascular lesions in SSc has to include von Willebrand factor and endoglin. Eventually, we will review the recent alternatives that can be effective in SSc‐GAVE, such as band ligation, hematopoietic stem cells transplantation and immunotherapy.

Fatigue, alopecia and stomatitis among patients with breast cancer receiving cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta-analysis.

ABSTRACT Background: Cyclin-dependent kinase (CDK) inhibitors emerge as efficacious agents in hormone positive metastatic breast cancer with more acceptable toxicity profiles than cytotoxic chemotherapy. However, some adverse effects such as fatigue, alopecia and stomatitis, vastly concern patients. Methods: The search was conducted in PubMed, American Society of Clinical Oncology meeting library, European Society for Medical Oncology meeting abstract, and the San Antonio meeting abstract databases. We identified phase 2 or 3 trials recruiting patients with breast cancer, randomized to receive hormonal treatment plus either CDK4/6 inhibitors or placebo. We considered studies providing incidence of fatigue, alopecia and stomatitis relevant. Results: One thousand records were screened. 34 studies were considered relevant. Four studies were found to be eligible for meta-analysis with a total of 2007 patients. The relative risk for all grade fatigue was 1.34 [95% CI: 1.17–1.54, p < 0.0001], for all grade alopecia was 2.14 [95% CI: 1.23–3.73, p = 0.007], and for all grade stomatitis 4.87 [95% CI: 2.11–11.24, p = 0.0002]. In addition, the relative risk for high grade fatigue was 2.40 [95% CI: 1.10–5.26, p = 0.03]. Conclusion: CDK4/6 inhibitors were associated with an increased risk of fatigue, alopecia and stomatitis. Further studies with self-reported questionnaires may elucidate the impact of the increased risk of these selected adverse effects on the patients’ quality of life.

Leprosy Masquerading as Systemic Rheumatic Diseases.

AbstractRheumatologic manifestations not only are encountered in leprosy but also can be the first and even the sole presenting manifestation. The hallmark of leprosy is skin and peripheral nerve affection; however, it can affect a wide range of other organs, with the joints being the commonest. We have searched PubMed with the key words leprosy, arthritis, vasculitis, rheumatic diseases, and autoantibodies in a proper combination. Relevant studies were retrieved from scanning of their abstracts. The relevant references provided in these articles were also selected and reviewed. We summarize the clinical and laboratory manifestations that make leprosy masquerade as a systemic rheumatic disease. Moreover, we report 4 Egyptian patients who presented with rheumatologic manifestations, namely, arthritis and vasculitis that turned out to be leprosy related.

Gastrointestinal adverse effects of cyclin-dependent kinase 4 and 6 inhibitors in breast cancer patients: a systematic review and meta-analysis

Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12–1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09–2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07–1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19–1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29–4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25–7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87–18.37, p = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44–3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

Alopecia Universalis Associated with Ulcerative Colitis and The Role of Azathioprine

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection.

Abiraterone acetate/androgen deprivation therapy combination versus docetaxel/androgen deprivation therapy combination in advanced hormone-sensitive prostate cancer: a network meta-analysis on safety and efficacy

Abstract Background: A major, yet precisely studied, shift has occurred in the treatment of advanced hormone-sensitive prostate cancer (HSPC) by the addition of docetaxel to androgen deprivation therapy (ADT) in the first line. Recently, two landmark trials showed that abiraterone acetate (AA) can be an effective alternative along with ADT in the same setting. We implemented a network meta-analysis to compare the safety and efficacy of the two combinations. Methods: PubMed database, ASCO and ESMO meeting library databases of all results published until June 2017 were searched using the keywords: “prostate cancer” AND “docetaxel” OR “abiraterone acetate”. Efficacy endpoints including progression-free survival (PFS) and overall survival (OS), and safety endpoints (including treatment related deaths and selected adverse events) were assessed. Results: Twenty relevant studies were retrieved and assessed for eligibility. Of those trials, eight were found potentially eligible. Inconsistent reporting of efficacy outcomes limited our analysis to M1 HSPC. The pooled hazard ratios (HRs) of OS and PFS of the direct comparison of abiraterone acetate plus ADT versus ADT were 0.63 (95% CI: 0.545–0.717) and 0.38 (95% CI: 0.34–0.43), respectively. Meanwhile, in the trials of docetaxel plus ADT the pooled HRs of OS and PFS were 0.75 (95% CI: 0.65–0.86) and 0.634 (95% CI: 0.57–0.70), respectively. The indirect comparison showed that the HRs of OS and PFS in DOC + ADT in comparison to AA + ADT were 1.2 (95% CI: 0.98–1.46) and 1.65 (1.40–1.94), respectively. The pooled RR of treatment-related mortality in docetaxel + ADT versus AA + ADT was 1.438 (95% CI: 0.508–4.075). Conclusion: Patients with metastatic HSPC (mHSPC) who received abiraterone acetate with ADT had better PFS and less toxicity compared to those receiving docetaxel with ADT. A trend towards superior OS and fewer treatment-related deaths was also observed, but was statistically non-significant. In view of lacking clear OS advantage, the choice between docetaxel and AA should include a discussion with the patient about the potential toxicities and impact on quality of life of each regimen.

Safety of Vinflunine in patients with advanced urothelial carcinoma refractory to platinum-based chemotherapy: a prospective pilot study

BACKGROUND Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. METHODS This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. RESULTS The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. CONCLUSION The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

Optimal regimen of cisplatin in squamous cell carcinoma of head and neck yet to be determined

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target receptors expressed on surface of T-lymphocytes and tumor cells, those receptors such as programmed death receptor-1 (PD-1), and the programmed death-ligand 1 (PD-L1) mediate an immunosuppressive state characterized by T cell anergy that enables institution of tumorigenesis.

Would the skyrocketed advances of immune checkpoint inhibitors over chemotherapy be stumbled by the safety issues

Immune checkpoint inhibitors (ICIs) have inaugurated a new era in the treatment of advanced malignancies. It is not only associated with higher progression-free survival and overall-survival but also a durable response that reached to 10 years in certain subsets of patients (1). This superiority over conventional chemotherapy regimens guaranteed an approval for ICIs in second and even first lines in treatment of non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma. Of those molecularly defined immune targeting, PD-1 and PD-L1 pathways are influential in suppressing effector immune response against tumor. That’s why anti-PD-1 and PD-L1 monoclonal antibodies (mAbs) could induce sustainable anti-tumor immune response. Unfortunately, this immune system manipulation may lead to emergence of autoimmune manifestations, usually reported as immune-related adverse effects.

Addition of 3-day aprepitant to ondansetron and dexamethasone for prophylaxis of chemotherapy-induced nausea and vomiting among patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy

BACKGROUND Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness. PURPOSE To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy. METHODS This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication. RESULTS Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant. CONCLUSION This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.