Standardization of surgical care in a high-volume center improves survival in resected pancreatic head cancer.

BACKGROUND: Durable clinical gains in surgical care are frequently reliant on well-developed standardization of practices. We hypothesized that the standardization of surgical management would result in improved long-term survival in pancreatic cancer. METHODS: Seventy-seven consecutive, eligible patients representing all patients who underwent pancreaticoduodenectomy and received comprehensive, long-term postoperative care at the University of Florida were analyzed. Patients were divided into prestandardization and poststandardization groups based on the implementation of a pancreatic surgery partnership, or standardization program. RESULTS: Standardization resulted in a reduction in median length of stay (10 vs 12 days; P = .032), as well as significant gains in disease-free survival (17 vs 11 months; P = .017) and overall survival (OS; 26 vs 16 months; P = .004). The improvement in overall survival remained significant on multivariate analysis (hazard ratio = .46, P = .005). CONCLUSIONS: Standardization of surgical management of pancreatic cancer was associated with significant gains in long-term survival. These results suggest strongly that management of pancreatic head adenocarcinoma be standardized likely by regionalization of care at high performing oncologic surgery programs.

Circulating Estrogens and Postmenopausal Ovarian Cancer Risk in the Women's Health Initiative Observational Study.

BACKGROUND: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). METHODS: We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years. RESULTS: Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors. CONCLUSIONS: Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers. IMPACT: These findings further support the heterogeneous etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 648-56. ©2016 AACR.

Comorbidity, age, and mortality among adults treated intensively for acute myeloid leukemia (AML).

INTRODUCTION: Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. METHODS: We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002 to 2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. RESULTS: In this series, 144 patients were ≥ 60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, P<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non-diabetic patients, p=0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6-15.2) times. DISCUSSION: Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.

New primary malignancy masquerading as metastatic prostate adenocarcinoma.

In the management of patients with prostate cancer, the development of new radiographic findings can mimic progression of the disease, thereby triggering changes in treatment. Typically, clinicians evaluate additional parameters, such as symptoms and prostate specific antigen (PSA) levels, for further evidence of disease progression. In the absence of additional findings, for example, elevated PSA, the possibility of an additional malignancy should be considered and evaluated. We present three cases of patients undergoing treatment for prostate adenocarcinoma and discovered on imaging to have findings suggestive of disease progression, but ultimately found to be a new primary malignancy. Our cases suggest that, in patients with prostate cancer, the appearance of new lymphadenopathy or bone lesions cannot be assumed to solely represent progression of the prostate cancer and warrant further investigation, especially in the presence of stable PSA levels.

Multidisciplinary neoadjuvant management for potentially curable pancreatic cancer.

Pancreatic adenocarcinoma remains the fourth leading cause of cancer mortality in the U.S. Despite advances in surgical technique, radiotherapy technologies, and chemotherapeutics, the 5-year survival rate remains approximately 20% for the 15% of patients who are eligible for surgical resection. The majority of this group suffers metastatic recurrence. However, despite advances in therapies for patients with advanced pancreatic cancer, only surgery has consistently proven to improve long-term survival. Various combinations of chemotherapy, biologic-targeted therapy, and radiotherapy have been evaluated in different settings to improve outcomes. In this context, a neoadjuvant (preoperative) treatment strategy offers numerous potential benefits: (1) ensuring delivery of early, systemic therapy, (2) improving selection of patients for surgical therapy with truly localized disease, (3) potential downstaging of the neoplasm facilitating a negative margin resection in patients with locally advanced disease, and (4) providing a superior clinical trial mechanism capable of rapid assessment of the efficacy of novel therapeutics. This article reviews the recent trends in the management of pancreatic adenocarcinoma, with a particular emphasis on a multidisciplinary neoadjuvant approach to treatment.

Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).

The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy. We collected data on age, gender, race, Charlson comorbidity index (CCI), cytogenetics, type of treatment, complete remission (CR), complete remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and Cox proportional hazards models. Frontline response rate (CR + CRi) was 26.5 %, and median overall survival (OS) was 3.4 months (95 % CI 1.3-7.4), with 18 % alive at 1 year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6 versus 26.5 %, p = 0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 months (CI 4.8-10.3). In the consolidation cohort, OS was 13.8 months (CI 8.0-21.6) with one patient in remission more than 30 months from diagnosis. These data suggest that prior cytotoxic therapy decreases marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over 1 year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.

Bevacizumab-induced bowel perforation.

Bevacizumab has shown efficacy in many different malignancies and is approved by the US Food and Drug Administration for advanced colon and lung cancers. As bevacizumab use is expanding, the number of reports of serious adverse effects from the drug are growing. Bowel perforation is a rare but often fatal event that leads the list of dangerous adverse effects. It has been frequently reported in ovarian cancer trials, with early closure of some trials because of the high incidence of bowel perforation. Physicians should be familiar with not only the presentation of bowel perforation, but also with the risk factors, considerations for surgery, and management of perforation in selected patient populations. The authors review the current knowledge on bevacizumab-induced bowel perforation.

Methotrexate-induced Hodgkin disease in a patient with systemic lupus erythematosus.

Methotrexate sodium use in the management of various immunologic disorders has increased--as have the number of reported adverse effects associated with this therapy. While methotrexate has helped combat various autoimmune and cancerous disorders, the paradoxical risk of causing an often fatal malignancy may still occur as a result of the drug's effect on suppressing immune function. We present a case of methotrexate-induced Hodgkin disease in a 48-year-old man with a history of systemic lupus erythematosus (SLE). Discontinuation of methotrexate facilitated Hodgkin disease reversal. In addition, we review other lymphoproliferative hematologic malignancies caused by methotrexate.