Navid Sadeghi

Metformin Use Is Associated with Better Survival of Diabetic Patients with Pancreatic Cancer

Purpose: Accumulating evidence suggests that metformin has antitumor activity. The aim of this study was to determine whether metformin use has a survival benefit in patients with pancreatic cancer. Experimental Design: We conducted a retrospective study of patients with diabetes and pancreatic cancer treated at The University of Texas MD Anderson Cancer Center (Houston, TX). Information on diabetes history, including treatment modalities and clinical outcome of pancreatic cancer, was collected using personal interviews and medical record review. Survival analysis was carried out using a Kaplan–Meier plot, log-rank test, and Cox proportional hazards regression models. Results: Among the 302 patients identified, there were no significant differences in demographic or major clinical characteristics between the patients who had received metformin (n = 117) and those who had not (n = 185). The 2-year survival rate was 30.1% for the metformin group and 15.4% for the non-metformin group (P = 0.004; χ2 test). The median overall survival time was 15.2 months for the metformin group, and 11.1 months for the non-metformin group (P = 0.004, log-rank test). Metformin users had a 32% lower risk of death; the HR (95% confidence interval) was 0.68 (0.52–0.89) in a univariate model (P = 0.004), 0.64 (0.48–0.86) after adjusting for other clinical predictors (P = 0.003), and 0.62 (0.44–0.87) after excluding insulin users (P = 0.006). Metformin use was significantly associated with longer survival in patients with nonmetastatic disease only. Conclusions: Our finding that metformin use was associated with improved outcome of patients with diabetes and pancreatic cancer should be confirmed in independent studies. Future research should prospectively evaluate metformin as a supplemental therapy in this population. Clin Cancer Res; 18(10); 2905–12. ©2012 AACR.

A Bayesian model for triage decision support.

OBJECTIVE To compare triage decisions of an automated emergency department triage system with decisions made by an emergency specialist. METHODS In a retrospective setting, data extracted from charts of 90 patients with chief complaint of non-traumatic abdominal pain were used as input for triage system and emergency medicine specialist. The final disposition and diagnoses of the physicians who visited the patient in Emergency Department (ED) as reflected in the medical records were considered as control. Results were compared by chi(2)-test and a binary logistic regression model. RESULTS Compared to emergency medicine specialist, triage system had higher sensitivity (90% versus 64%) and lower specificity (25% versus 48%) for patients who required hospitalization. The triage system successfully predicted the Admit decisions made in the ED whereas the emergency medicine specialist decisions could not predict the ED disposition. Both triage system and emergency medicine specialist properly disposed 56% of cases, however, the emergency medicine specialist in this study under-disposed more patients than the triage system considering Admit disposition (p=0.004) while he appropriately discharged more patients compared to the triage system (p=0.017). CONCLUSION The triage system studied here shows promise as a triage decision support tool to be used for telephone triage and triage in the emergency departments. This technology may also be useful to the patients as a self-triage tool. However, the efficiency of this particular application of this technology is unclear.

Determinants of operative mortality following primary coronary artery bypass surgery

BACKGROUND The purpose of this study was to determine the factors which can help to predict operative mortality before performing the operation, and afterwards. METHODS The study population consisted of 504 patients (91 women and 413 men) who underwent primary isolated coronary artery bypass surgery from December 1997 to September 1999 by the same surgeon in a referral center in Tehran, Iran. Perioperative data were gathered and analyzed both in a univariate and multivariate model. RESULTS After the operation patients spent 7.3 +/- 4.0 days in hospital. The total operative morbidity was 20.5%. Arrhythmias were the most common complication, with atrial fibrillation as the predominant feature. Major complications of the operation were: low cardiac output (4.2%); prolonged ventilatory support (2.4%); hemorrhage and exploratory reoperation (2.0%); postoperative myocardial infarction (1.4%); postoperative renal failure in (1.4%); and postoperative cerebrovascular accident (0.8%). Operative mortality rate in this study was 2.98%. Factors associated with high operative mortality in univariate analysis were: recent myocardial infarction, low ejection fraction, non-elective operation, left main coronary artery disease and prolonged cardiopulmonary bypass time. CONCLUSION Our data suggest that prior to operation, operative mortality can be best predicted by urgency of operation and left ventricle ejection fraction. After performing the operation, prognostic factors include preoperative LVEF < or = 35%, non-elective operation, and prolonged cardiopulmonary bypass time. Further study is required to assess the generalization of our findings to Iranian patients.

Mitral valve recurrence of a left atrial myxoma.

Recurrence of intracardiac myxoma is unusual, and heart valves are extremely rare locations for this tumor to originate, either as the primary site or the site of recurrence. We present a case of non-familial cardiac myxoma, which after successful resection of the tumor mass from the left atrium, recurred in the atrial surface of anterior leaflet of the mitral valve, along with a review of similar cases in the literature. Myxoma was originally believed to recur due to inadequate resection, but recent data suggest the multicentric disease to be the reason. Mitral valve myxoma mainly presents with symptoms of embolization and appears to affect women more often. It involves both leaflets with the same frequency and usually originates from the atrial side. Transesophageal echocardiography is the gold standard for non-invasive diagnosis and localization. Operative resection of the tumor along with the underlying tissue followed by suture repair of the valve and annuloplasty is recommended as the most appropriate treatment option. Long-term follow-up of patients by echocardiography is advised for early detection of any recurrence.

Targeting the PI3K pathway for cancer therapy

The PI3K pathway plays an important role in key cellular functions such as cell growth, proliferation and survival. Genetic and epigenetic alterations in different pathway components lead to aberrant pathway activation and have been observed in high frequencies in various tumor types. Consequently, significant effort has been made to develop antineoplastic agents targeting different nodes in this pathway. Additionally, PI3K pathway status may have predictive and prognostic implications, and may contribute to drug resistance in tumor cells. This article provides an overview of our current knowledge of the PI3K pathway with an emphasis on its application in cancer treatment.

Things We Do For No Reason: Neutropenic Diet

For several decades, providers have routinely restricted the diets of neutropenic cancer patients by eliminating foods that might harbor pathogenic microbes to reduce infection rates. These diets, known as neutropenic or low-bacteria diets, are prescribed across the country with little uniformity in the extent or content of prescription. These diets are difficult to follow and force patients to omit fresh fruits and vegetables and limit dairy and meat products from their diet. These dietary omissions compromise nutritional intake in patients who are already at high risk of malnutrition. Randomized trials have shown that these restrictive diets are not superior in preventing infections than more liberalized diets. Evidence shows that adherence to the Safe Food-Handling guidelines issued by the Food and Drug Administration, a mandate for all hospital kitchens, provides adequate protection against food-borne infection, precluding the need for the neutropenic diet. Thus, routine use of the neutropenic diet should be abandoned.

Primary effusion lymphoma: current concepts and management

Purpose of review To summarize the current epidemiology, management, and outcomes of primary effusion lymphoma (PEL) and highlight possible future research efforts. Recent findings Cyclophosphamide, doxorubicin, vincristine, prednisone-based chemotherapy regimens alone or in combination with immunomodulatory agents (e.g., lenalidomide), or proteasome inhibitors (e.g., bortezomib), or targeted therapies, are commonly used to treat PEL. Highly active antiretroviral therapy should be continued or initiated in patients with HIV infection. Randomized controlled trials are lacking. Prognosis remains grim and there exists a need for further investigation into optimal treatment strategies. Summary PEL is an aggressive mature B-cell neoplasm primarily seen in young to middle aged men with HIV, though immunosuppression related to age and comorbidities such as cirrhosis or organ transplantation also predisposes to PEL. Classic cavitary PEL presents as an effusion in the pleural, pericardial, or peritoneal space. Human herpes virus-8/Kaposis sarcoma herpes virus) is classically detected. Given its rarity, randomized controlled trials evaluating optimal treatment regimens are lacking, and cyclophosphamide, doxorubicin, vincristine, prednisone-based chemotherapy has been the mainstay of treatment. Advancement in knowledge of the oncogenic signaling pathways involved in Kaposis sarcoma herpes virus-induced tumorigenesis may pave the way to develop targeted therapies. Video abstract http://links.lww.com/COPM/A19

Reducing Wait Time Between Admission and Chemotherapy Initiation

PURPOSE Reducing the length of stay is a high-priority objective for all health care institutions. Delays in chemotherapy initiation for planned preadmissions lead to patient dissatisfaction and prolonged length of stay. PATIENTS AND METHODS A multidisciplinary team was formed as part of the ASCO Quality Training Program. We aimed to reduce the time to initiation of chemotherapy from patient arrival at Parkland Hospital from a median of 6.2 hours at baseline to 4 hours over a 6-month period (35% reduction). The team identified inconsistency in blood work requirements, poor communication, and nonstandard patient arrival times as key causes of delay in the process. Plan-Do-Study-Act (PDSA) cycles were implemented based on identified improvement opportunities. The outcome measure was time from arrival to chemotherapy start. Data were obtained from time stamps in the electronic health record. RESULTS The first PDSA cycle included patient reminders to arrive at specific times, improved communication using a smartphone secure messaging application, and preadmission notes by oncology fellows detailing whether fresh blood work were needed on admission. Baseline data from 36 patients and postimplementation data from 28 patients were analyzed. Median time from admission to chemotherapy initiation preprocess change was 6.2 hours; it was 3.2 hours postchange. A sustained shift in the process was apparent on a control chart. CONCLUSION Delays in initiation of chemotherapy can be prevented using classic quality improvement methodology and a multidisciplinary team. We aim to further refine our PDSA cycles and ensure sustainability of change.

Sacral bone cyst treatment resulting in paraplegia

A 50-year-old man with a stage 1 solitary right sacral plasmacytoma complained of a sharp, burning lower back pain with radiation into his right lower extremity which worsened with movement. He had initially undergone localised radiation therapy, but the pain did not resolve. Postradiation CT-guided biopsy showed persistence of malignant plasma cells, and he then underwent seven cycles of VRD (dexamethasone, lenalidomide and bortezomib) chemotherapy. After chemotherapy, an 18-fluorodeoxyglucose-positron emission tomography/CT scan showed a new area of uptake in the right sacral ala near the initial plasmacytoma. A subsequent CT-guided biopsy was non-diagnostic, and repeat imaging at the time of presentation showed no interval growth. The lesion was believed to be a residual cyst with inflammatory changes from radiotherapy. Examination revealed no neurological deficits. The patient’s pain was thought to be secondary to the cyst (figure 1) and was not relieved with physical therapy, duloxetine or …

Utility and proposed algorithm of CSF flow cytometry in hematologic malignancies

In patients with hematologic malignancies, multiparameter flow cytometry (FCM) offers greater sensitivity than cytology in detecting malignant cells in the initial cerebrospinal fluid (CSF) specimen. However, the role of FCM in assessment of subsequent specimens is unclear. We developed an algorithm to reduce the number of low-yield FCM tests without significant impact on clinically meaningful results. Patients with hematologic malignancies were studied in a derivation cohort, and the following algorithm was developed: (1) cytology and FCM on all initial samples, (2) cytology on all subsequent samples, and (3) FCM on subsequent samples only if previous FCM was positive. A separate population served as the validation cohort. The derivation cohort included 197 patients representing 1157 cytology and 543 FCM samples. Common malignancies were B-Cell ALL (25.3%), diffuse large B cell lymphoma (29.4%), and Burkitt lymphoma (7.7%). In the derivation cohort, the algorithm yielded a sensitivity of 90.0% (95% CI, 81.2–95.6%) and a specificity of 100% (95% CI, 98.9–100.0%). The validation cohort included 132 patients with 563 cytology and 602 FCM samples. In the validation cohort, the testing algorithm yielded a sensitivity of 87.5% (95% CI, 75.9–94.8%) and a specificity of 100% (95% CI, 99.1–100.0%). Of the 15 samples that were missed by the algorithm, FCM findings did not impact patients’ management because of known CNS disease (seven patients) or they were responding to treatment (eight patients). CSF testing in hematologic malignancies using the proposed algorithm presents an evidence-based approach to reduce the number of unnecessary FCM tests of CSF without compromising patient care.