A standardized care plan is associated with shorter hospital length of stay in patients undergoing pancreaticoduodenectomy.

BACKGROUND: In this retrospective review, we evaluate a standardized care plan (SCP) for patients undergoing pancreaticoduodenectomy, which included selective placement of feeding jejunostomy tubes (FJTs) and a perioperative fast-track recovery pathway (FTRP). METHODS: A review of 242 patients undergoing pancreaticoduodenectomy was completed. Patients treated pre- and post-SCP implementation were compared. Univariate comparison followed by multivariable linear regression were performed to identify predictors of hospital length of stay (HLOS). RESULTS: SCP patients (n = 100) were slightly older but otherwise similar to pre-SCP patients (n = 142). FJT placement occurred less frequently in SCP patients (38 versus 94%, P < 0.001). All SCP patients were initiated on the FTRP. Among SCP patients, an oral diet was introduced earlier (5 versus 8.5 d, P < 0.001) and HLOS was shorter (11 versus 13 d, P = 0.015). Readmission rates were similar. Following adjustment with linear regression, we confirmed SCP status as a predictor of HLOS. To assess SCP components, HLOS was evaluated separately based on FTRP status and FJT placement. Although both were highly associated with HLOS, neither was independently predictive in multivariable analysis. CONCLUSIONS: Implementation of an SCP resulted in shorter HLOS without an increase in readmissions. Future studies are necessary to identify specific components of SCPs that most influence outcomes.

The role of clinical care pathways: an experience with distal pancreatectomy.

BACKGROUND: Previous studies have indicated that clinical pathways may shorten hospital length of stay (HLOS) among patients undergoing distal pancreatectomy (DP). Here, we evaluate an institutional standardized care pathway (SCP) for patients undergoing DP. MATERIALS AND METHODS: A retrospective review of patients undergoing DP from November 2006 to November 2012 was completed. Patients treated before and after implementation of the SCP were compared. Multivariable linear regression was then performed to identify independent predictors of HLOS. RESULTS: There were no differences in patient characteristics between SCP (n=50) and pre-SCP patients (n=100). Laparoscopic technique (62% versus 13%, P<0.001), splenectomy (52% versus 38%, P=0.117), and concomitant major organ resection (24% versus 13%, P=0.106) were more common among SCP patients. Overall, important complication rates were similar (24% versus 26%, P=0.842). SCP patients resumed a normal diet earlier (4 versus 5 d, P=0.025) and had shorter HLOS (6 versus 7 d, P=0.026). There was no increase in 30-d resurgery or readmission. In univariate comparison, SCP, cancer diagnoses, intraductal papillary mucinous neoplasm diagnoses, neoadjuvant therapy, operative technique, major organ resection, and feeding tube placement were associated with HLOS; however, after multivariable adjustment, only laparoscopic technique (-33%, P=0.001), concomitant major organ resection (+38%, P<0.001), and feeding tube placement (+68%, P<0.001) were independent predictors of HLOS. CONCLUSIONS: Implementation of a clinical pathway did not improve HLOS at our institution. The increasing use of laparoscopy likely accounts for shorter HLOS in the SCP cohort. In the future, it will be important to identify clinical scenarios most likely to benefit from implementation of a clinical pathway.

Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme.

Cloretazine (VNP40101M) is a newly synthesized alkylating agent belonging to a novel class of alkylating agents called 1,2-bis(sulfonyl)hydrazines. Agents that belong to this class do not produce vinylating and chloroethylating species, and hence this class of alkylating agents is thought to have minimal systemic toxicity. Cloretazine produces two short-lived active species: 1,2-bis(methylsulfonyl)-1-(2-chloroethyl) hydrazine (a chloroethylating species) and a thiophilic carbamoylating methylisocyanate species. The chloroethylating species preferentially produces lesions at the O(6) position of guanine. The methylisocyanate species may inhibit O(6)-alkylguanine-DNA alkyltransferase, an important mechanism of resistance against alkylating agents. The purpose of this study was to determine the efficacy and tolerability of Cloretazine in patients with recurrent glioblastoma multiforme. The basis for the determination of efficacy was the proportion of patients alive without evidence of disease progression six months after initiation of treatment. Patients with recurrent glioblastoma multiforme received Cloretazine (300 mg/m(2)) intravenously every six weeks. Radiographic response, survival data, and toxicity were assessed. Thirty-two patients were enrolled. Median age was 56 years; 24 patients (75%) were men. At six months, two patients were alive and progression free, so the six-month progression-free survival (PFS) was 6%. The median PFS was 6.3 weeks. There were no objective radiographic responses. Twelve patients had stable disease for at least one cycle, but only two patients received more than three cycles. Nine patients experienced grade 4 thrombocytopenia and three patients experienced grade 4 neutropenia. Cloretazine administered every six weeks was relatively well tolerated, although this schedule has insignificant activity for patients with recurrent glioblastoma multiforme.

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.

Gefitinib (Iressa, ZD1839) and tyrosine kinase inhibitors: the wave of the future in cancer therapy.

Targeted therapies are one of the latest innovative trends in cancer therapy. The epidermal growth factor receptor (EGFR) is a target found in high concentrations in several solid tumors including lung, breast, colorectal, and brain. Tyrosine kinase inhibitors, such as gefitinib (Iressa, ZD1839), block the EGFR. As a result, there is inhibition of cellular proliferation, promotion of apoptosis, and inhibition of anti-angiogenesis. Gefitinib has demonstrated significant efficacy in non-small-cell lung cancer (NSCLC), leading to FDA approval for treatment of this refractory disease. Phase 2 trials with gefitinib for platinum refractory NSCLC reported disease response and symptom improvement. Early results of phase 2 studies of gefitinib, combined with standard chemotherapy in colorectal cancer, showed a 75% response rate compared with 55% with standard therapy alone. Gefitinib, combined with flutamide, produced an additive growth inhibition in prostate cancer. A phase 2 trial of gefitinib in first-relapse glioblastoma multiforme demonstrated median overall survival from treatment start of 39.4 weeks compared with 40 weeks with standard chemotherapy. Gefitinib is an oral agent with a mild toxicity profile, and thus, may be an optimal addition to chemotherapeutic regimens for some solid tumors. Gefitinib is potentially a vital and useful weapon in the arsenal of cancer therapies.

The Role of the Advanced Practice Nurse in the Academic Setting.

OBJECTIVES: To explore how advanced practice nurses implement practice change in academic medical centers to support optimal patient and staff outcomes. DATA SOURCES: Published peer reviewed literature, web-based resources, and professional society materials. CONCLUSION: Cancer care is rapidly evolving and advanced practice nurses can shape the future of how care is delivered as well as the setting it is delivered in. IMPLICATIONS FOR NURSING PRACTICE: Advanced practice oncology nurses (Nurse Practitioners and Clinical Nurse Specialists) have an opportunity to significantly shape the patient experience by implementing programmatic changes across the continuum of care by engaging stakeholders in project design. Knowledge of change management and implementation science is critical to success.

Using evidence in central catheter care.

OBJECTIVES: To discuss a project that identified the causes of central venous catheter infections, implemented corrective interventions, and evaluated the effectiveness of interventions. DATA SOURCES: Research studies, review articles, data collection, and personal experience. CONCLUSIONS: An educational intervention and individual demonstration improved sterile technique during catheter care, decreased infection rates, and decreased length of hospital stay. IMPLICATIONS FOR NURSING PRACTICE: Education has a significant impact on patient care and outcomes. Nurses can provide optimal catheter care for lowering infection risks.

Feeding jejunostomy tube placement in patients undergoing pancreaticoduodenectomy: an ongoing dilemma.

BACKGROUND: Concomitant placement of feeding jejunostomy tubes (FJT) during pancreaticoduodenectomy is common, yet there are limited data regarding catheter-specific morbidity and associated outcomes. This information is crucial to appropriately select patients for feeding tube placement and to optimize perioperative nutrition strategies. METHODS: A review of all patients undergoing pancreaticoduodenectomy with FJT placement was completed. Patients were grouped by the occurrence of FJT-related morbidity. Multivariable logistic regression was performed to identify predictors of FJT morbidity; these complications were then further defined. Finally, associated postoperative outcomes were compared between groups. RESULTS: In total, 126 patients were included, of which 18 (14 %) had complications directly related to their FJT, including pericatheter infection (n = 6), pneumatosis intestinalis (n = 4), severe tube feed intolerance (n = 3), and primary catheter malfunction (n = 7). Following adjustment with logistic regression, preoperative hypoalbuminemia was identified as the only independent predictor of FJT complications (OR 2.23, p = 0.035). Patients with FJT complications were more likely to be initiated on total parenteral nutrition (TPN; 55.6 vs. 7.4 %, p -0.035) and to require TPN at discharge (16.7 vs. 0%, p = 0.003). Correspondingly, these patients resumed an oral diet later (14 vs. 8 days, p = 0.06). Both reoperation (50.0 vs. 6.5%, p < 0.001) and readmission (50.0 vs. 22.4%, p = 0.041) rates were higher among patients with FJT complications. CONCLUSIONS: FJT-related morbidity is common among patients undergoing pancreaticoduodenectomy and is associated with inferior outcomes and other performance metrics. Preoperative malnutrition appears to predict FJT complications, creating an ongoing dilemma regarding FJT placement. In the future, it will be important to better define criteria for FJT placement during pancreaticoduodenectomy.

Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.

TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this study was to define the MTD and dose limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients with recurrent malignant brain tumors. Twenty patients were enrolled in the study and doses were escalated from 25 ng/mL to 100 with a 40 mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. The overall median survival after TP-38 for all patients was 23 weeks whereas for those without radiographic evidence of residual disease at the time of therapy, the median survival was 31.9 weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy, have demonstrated radiographic responses and one patient with a complete response and has survived greater than 83 weeks.