Cardiovascular adverse events of antineoplastic monoclonal antibodies among cancer patients: real-world evidence from a tertiary healthcare system.

BACKGROUND: Antineoplastic monoclonal antibodies (mAbs), such as trastuzumab, bevacizumab, and pertuzumab have been the mainstay of therapy in cancer patients. Despite proven efficacy of the monoclonal antibodies, cardiovascular-induced adverse events such as heart failure, hypertension, ischemic heart disease, arrhythmias, thromboembolic events, and hemorrhage remain a major complication. The European society of cardiology address that concern with antineoplastic monoclonal antibodies issuing a guideline to manage and monitor chemotherapy-induced cardiotoxicity. There is limited evidence of the real-world prevalence of cardiovascular (CV) events induced by monoclonal antibodies among patients with cancer in Saudi Arabia. OBJECTIVE: To evaluate the prevalence of cardiovascular adverse events among patients with cancer treated with monoclonal antibodies in Saudi Arabia. METHODS: This is a retrospective study conducted in a tertiary care hospital, Riyadh, Saudi Arabia. Data were obtained from an electronic medical record of patients with cancer treated with one of the selected monoclonal antibodies, who met the inclusion criteria between January 2005 until June 2015 and have been followed up for at least one year. Patients were stratified into groups according to monoclonal antibodies treatment: trastuzumab, bevacizumab, pertuzumab, and combined mAbs. RESULTS: A total of 1067 patient were included in the study, within the pre-determined study period. The prevalence of cardiovascular disease among patients with cancer treated with monoclonal antibodies was 16.3%. The prevalence of heart failure was relatively higher in the trastuzumab group (46/626 patients, 7.3%). Among 418 patients treated with bevacizumab, hypertension was the most frequent adverse event, reported in 38 patients (9.1%), followed by thromboembolism reported in 27 patients (6.5%). Treatment discontinuation owing to cardiovascular adverse events was reported in 42/1,067 patients (3.9%). CONCLUSION AND RELEVANCE: Prevalence of antineoplastic monoclonal antibody induced cardiovascular adverse events among patients with cancer is substantially high in Saudi Arabia. There is an urgent need to streamline the practice for identifying high risk patients and flexible referral system for cardio-oncology care.

Patient outcomes after treatment with percutaneous cholecystostomy for biliary sepsis.

INTRODUCTION: Acute cholecystitis is among the most common general surgical presentations. There is a cohort of patients who develop systemic sepsis and complications of acute cholecystitis. These patients are often elderly and co-morbid. Conservative management with percutaneous cholecystostomy has been shown to be a safe and effective management option in the acute setting. However, there is currently no consensus for the further management of these patients. In particular, there is a paucity of data on readmission rates and subsequent operative or non-operative management. METHODS: A retrospective study was carried out of patients treated with a percutaneous cholecystostomy for biliary sepsis over a three-year period in a UK teaching hospital. Outcome measures were subsequent operative or conservative management, conversion rates, operative complications and readmission rates. RESULTS: Twenty-five patients had a percutaneous cholecystostomy for the treatment of acute biliary sepsis. The median follow-up duration was 35 months. Thirteen patients (52%) had operative treatment. In the operative group, 6/13 had a laparoscopic cholecystectomy, 2/13 had a planned open cholecystectomy, 2/13 had abandoned procedures and 3/13 had a converted procedure. Complications in the operative group included: postoperative mortality (1/13), common bile duct injury requiring drainage and endoscopic stenting (1/13) and one patient required readmission with recurrent pain. In the non-operative group, 5/12 patients were readmitted with biliary sepsis, 5/12 had no readmissions, 1/12 died in the community and 1/12 was readmitted with biliary colic. CONCLUSIONS: Percutaneous cholecystostomy is a recognised treatment modality for elderly, co-morbid patients with biliary sepsis. Nevertheless, the readmission rate in this group is relatively high at 5/12 (42%). Patients who undergo subsequent operative management have a conversion rate of 3/13 (23%) and a significant complication rate of 2/13 (15%). The further management of patients having undergone percutaneous cholecystostomy requires careful consideration on an individual case basis. The P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) may aid decision making.

Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review.

AIM: Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence. METHOD: A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared. RESULTS: Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret. CONCLUSION: The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.

Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity.

Increased eukaryotic translation initiation factor 4E (eIF4E) expression occurs in many cancers, and makes fundamental contributions to carcinogenesis by stimulating the expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis, and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and eIF4E-binding proteins (4E-BPs). Our hypothesis was that the combined analyses of these pathway components would allow insights into eIF4E activity and its influence on cancer. We have determined expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 within 424 breast tumours, and have carried out analyses to combine these and relate the product to patient survival, in order to estimate eIF4E activity. We show that this analysis gives greater prognostic insights than that of eIF4E alone. We show that eIF4E and 4E-BP expression are positively associated, and that 4E-BP2 has a stronger influence on cancer behaviour than 4E-BP1. Finally, we examine eIF4E, estimated eIF4E activity, and phosphorylated 4E-BP1 as potential predictive biomarkers for eIF4E-targeted therapies, and show that each determines selection of different patient groups. We conclude that eIF4E's influence on cancer survival is modulated substantially by 4E-BPs, and that combined pathway analyses can estimate functional eIF4E.

Practical advice on clinical decision making during neoadjuvant chemotherapy for primary breast cancer.

Neoadjuvant chemotherapy (NACT) is a useful approach in the treatment of many breast cancers. One of the main advantages of NACT is the possibility of breast conservation surgery in patients who would otherwise require a mastectomy. Most literature on NACT focuses on the effectiveness of different chemotherapy regimen and subsequent mastectomy rates. There is little guidance in the literature on aspects of individual patient management and decision making during NACT. This paper considers practical management advice where NACT is considered and adopted.

The potential role of ER beta isoforms in the clinical management of breast cancer.

The discovery of a second oestrogen receptor, ER beta, was a subject of much interest, as this suggested a means to improve the prognostic stratification of invasive breast cancer, better predict response to endocrine therapy, develop new chemotherapeutic/chemopreventative drugs and perhaps prevent inappropriate treatment. However, this has not proved to be straightforward with the discovery of five ER beta isoforms and numerous exon deletion variants. This review sets out to identify the present state of knowledge regarding the clinicopathological role of ER beta isoforms and discusses possible reasons for conflicting results arising from recent research findings.

Decreased sensitivity to self-inflicted pain.

There is anecdotal and incidental research evidence suggesting that self-inflicted injury is experienced as less painful than when the same injury is applied by another person. We tested the hypothesis that the sensitivity and the ability to tolerate pain differs depending on the person applying the painful stimulus. Self-selected healthy undergraduate students were obtained from the University of Stirling participant panel. None were suffering chronic pain or taking any form of analgesic drug. The participants applied a pressure algometer to themselves and to other participants. Depending on the type of trial, each was terminated when the participant experienced the algometer as either "painful" (for threshold reading) or "unbearable" (for tolerance reading). Both measures of pain, threshold and tolerance, were significantly higher when the algometer had been self-applied compared with when it was applied by another person. The mean difference for pain thresholds was 0.27MPa (95% confidence interval 0.10-0.44, P=0.002), and the mean difference for pain tolerance readings was 0.25MPa (95% confidence interval 0.03-0.48, P=0.028). An unexpected finding was that the mean tolerance score was less when females applied the algometer (P<0.01). When a painful stimulus was self-inflicted this resulted in significantly less pain and a greater ability to tolerate the pain compared with when the same stimulus was applied by another person. If the findings generalized to a clinical context, certain painful or discomforting procedures, such as mammography, removal of wound dressings and lancet withdrawal of blood, should be adapted for self-application by patients.

Clinicians' guide to microarrays.

Cancer is a heterogeneous disease with wide-ranging subsets of patients who have different prognoses and who respond differently to treatments. Accordingly, deciding the best treatment strategy has become a priority in cancer care. The development of microarray technology over the last decade has caused great excitement, with the promise that these new tools may provide molecular signatures to help predict patient outcome and direct therapeutic approaches. Here, we describe the different types of microarrays available and discuss their pros and cons from a clinical perspective, with respect to breast cancer.