Comparison of Task-Layered Clinical Orientation to Traditional Orientation in a RN Residency Program.

OBJECTIVE: The purpose of this study was to compare outcomes of using a task-layered clinical orientation when compared with the original patient-layering approach. BACKGROUND: Use of task-layering to orient new graduate nurses to the clinical world of nursing has been theorized to provide a decrease in cognitive load and allow for more streamlined clinical orientation. METHODS: The method of this study was a nonrandomized, comparative design to measure the outcomes of length of orientation, new graduate perceptions about level of confidence/comfort with professional nurse responsibilities/skills, stress, satisfaction, and perceptions about orientation. RESULTS: Analysis revealed no statistical significance between the 2 groups. However, the task-layered clinical orientation group completed orientation earlier than the traditional patient-layered group. CONCLUSIONS: The task-layered approach to clinical orientation provided as good of outcomes as traditional orientation strategy and may result in cost savings due to decrease in total clinical orientation days.

Psychological and sexual distress in rectal cancer patients and partners.

BACKGROUND: Rectal cancer (RC) patients experience unique sources of distress, including sexual dysfunction and body image concerns, which can also cause distress among partners. This preliminary study investigated patterns of psychological distress, sexual functioning, sexual distress, and relationship satisfaction among RC patient-partner couples at pivotal points during cancer treatment. METHODS: Twenty couples participated (N = 40). Patients and partners completed a series of validated measures of psychological distress (ET), sexual functioning (FSFI; IIEF), sexual distress (GMSEX; Sexual Distress Scale) and relationship satisfaction (GMREL) at time of diagnosis, 3 weeks after radiation, 4 weeks post-surgery, and after chemotherapy and surgery for ostomy closure. Descriptive statistics, t-tests, and repeated-measures ANOVA were used to analyze scores over time, first for patients and partners, and then by sex. RESULTS: Relationship satisfaction remained elevated over time. In this sample, 55% of patients and 78.9% of partners reported clinically significant rates of psychological distress at diagnosis, which decreased to 23% and 46% respectively at the last assessment. Sexual satisfaction and distress worsened for patients and partners between baseline and surgery for ostomy closure. Both male and female participants reported statistically significant declines in sexual function from baseline to end of treatment (p < 0.05). DISCUSSION: Relative to relationship satisfaction, psychological and sexual health outcomes seem more vulnerable to the effects of RC treatment during the first year after diagnosis, both for patients and partners and for men and women. Results support the need for psychosocial care and sexual education/counseling for couples coping with RC.

Generalization of skills between operant control and discrimination of EEG alpha.

While biofeedback is often said to increase self-control of physiological states by increasing awareness of their subjective correlates, relatively few studies have analyzed the relationship between control (standard biofeedback) and awareness (a discrimination paradigm). We hypothesized that the two skills would generalize and facilitate each other for 8-12Hz EEG amplitude (alpha). Participants were given 7 sessions of training to either control or discriminate Pz alpha followed by 3 sessions of the other paradigm. Another group was given 7 sessions with time divided equally between the two types of training. The control-training first group showed significant generalization of skills to the discrimination task. However, the reverse was not true, and the combined task group did no better in either task than the other two groups. These results provide ambivalent support for the role of awareness in biofeedback, and suggest possible improvements in the discrimination paradigm.

Educating the surgeon-scientist: A qualitative study evaluating challenges and barriers toward becoming an academically successful surgeon.

BACKGROUND: The advancement of surgical science relies on educating new generations of surgeon-scientists. Career development awards (K Awards) from the National Institutes of Health, often considered a marker of early academic success, are one way physician-scientists may foster skills through a mentored research experience. This study aimed to develop a conceptual framework to understand institutional support and other factors leading to a K Award. METHODS: A national, qualitative study was conducted with academic surgeons. Participants included 15 K Awardees and 12 surgery department Chairs. Purposive sampling ensured a diverse range of experiences. Semistructured, in-depth telephone interviews were conducted. Interviews were audio recorded and transcribed verbatim, and 2 reviewers analyzed the transcripts using Grounded Theory methodology. RESULTS: Participants described individual and institutional factors contributing to success. K Awardees cited personal factors such as perseverance and team leadership skills. Chairs described the K Awardee as an institutional "investment" requiring protected time for research, financial support, and mentorship. Both K Awardees and Chairs identified a number of challenges unique to the surgeon-scientist, including financial strains and competing clinical demands. CONCLUSION: Institutional support for surgeons pursuing K Awards is a complex investment with significant initial costs to the department. Chairs act as stewards of institutional resources and support those surgeon-scientists most likely to be successful. Although the K Award pathway is one way to develop surgeon-scientists, financial burdens and challenges may limit its usefulness. These findings, however, may better prepare young surgeons to develop career plans and identify new mechanisms for academic productivity.

Biomarkers and targeted therapeutics in colorectal cancer.

The development of colorectal cancer is characterized by a multitude of molecular events that can occur through the pathways of loss of heterozygosity, microsatellite instability, and CpG-island methylation. The accumulation of these molecular events ultimately results in polyps formed from previously normal mucosa to develop the fundamental characteristics of cancerization: uncontrolled proliferation, growth, and invasion. Advances in the understanding of molecular events leading to colorectal cancer have led to the development of biomarkers, patient-specific and tumor-specific molecular signatures that have potential as tools for accurate risk assessment, personalized treatment planning, development of targeted agents, and evaluation of treatment response.

Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy.

Focal adhesion kinase (FAK) increasingly has been implicated in cancer growth and progression. 1,2,4,5-Benzenetetraamine tetrahydrochloride (Y15) is a small molecule FAK inhibitor that blocks the Y397 autophosphorylation site. FAK inhibitor, Y15 decreased Y397 FAK in different colon cancer cells lines in a dose-dependent manner. In addition, Y15 decreased phosphorylated Src in SW480 and SW620 cells. Y15 decreased cell viability, increased detachment, and increased apoptosis in SW480 and SW620 cells in vitro. Combination of FAK inhibitor Y15 and Src inhibitor PP2 decreased colon cancer cell viability more effectively than each agent alone. In addition, when combined with 5-FU, oxaliplatin or 5-FU and oxaliplatin, colon cancer viability was decreased further, demonstrating that dual and triple therapy synergistically inhibits cell viability. In vivo, Y15 decreased subcutaneous SW620 tumor growth by 28%. Combination of oral Y15 with 5-FU/or oxaliplatin decreased tumor growth by 48% more effectively than each inhibitor alone. Finally, tumors treated with Y15 expressed less Y397 phosphorylation, Src phosphorylation and had greater apoptosis than controls. Thus, the small molecule FAK inhibitor, Y15, inhibits cell growth in vitro and in vivo and enhances the efficacy of chemotherapy, demonstrating that it can be an effective therapeutic inhibitor for treating colon cancer.

Soft tissue tumors of the anorectum: rare, complex and misunderstood.

Anorectal soft tissue tumors are uncommon and often present both diagnostic and therapeutic challenges. Although many of these tumors are identified with imaging performed for unrelated reasons, most present with nonspecific symptoms that can lead to a delay in diagnosis. Historically, radical surgery (abdominoperineal resection) has been the mainstay of treatment for both benign and malignant anorectal soft tissue tumors. However, a lack of proven benefit in benign disease along with changes in technology has called this practice into question. In addition, the role of radiation and/or chemotherapy remains controversial. In this manuscript, we review the history and current status of anorectal soft tissue tumor management, with a particular focus on challenges in optimizing survival.

Management of bowel obstruction in patients with stage IV cancer: predictors of outcome after surgery.

BACKGROUND: Patients with stage IV cancer and bowel obstruction (BO) present a complicated management problem. We sought to determine if specific parameters could predict outcome after surgery. METHODS: Records of patients with stage IV cancer and BO treated from 1991 to 2008 were reviewed. For surgical patients, 30-day morbidity and 90-day mortality were assessed using exact multivariable logistic regression methods. RESULTS: Of 198 patients, 132 (66.7%) underwent surgery, 66 medical treatment alone, and demographics were similar. A total of 41 patients (20.7%) were diagnosed with stage IV cancer and BO synchronously, all treated surgically; the remaining presented metachronously. Medically managed patients were more likely to have received chemotherapy in the 30 days prior to BO (45 of 66 [68.2%] vs 40 of 132 [30.3%], p < .01). In the surgical group, 30-day morbidity was 35.6%, while 90-day mortality was 42.3%. Median overall survival for synchronous patients was 14.1 months (95% confidence interval [95% CI] 7.6-23.2), and 3.7 months (95% CI 2.5-5.2) and 3.6 months (95% CI 1.5-5.2) for metachronous patients treated surgically and medically, respectively. A multivariate model for 90-day surgical mortality identified low serum albumin, metachronous presentation, and ECOG > 1 as predictors of death (p < .05). A model for 30-day surgical morbidity yielded low hematocrit as a predictive factor (p < .05). CONCLUSIONS: This cohort identifies characteristics indicative of morbidity and mortality in stage IV cancer and BO. Low serum albumin, ECOG > 1, and metachronous presentation predicted for 90-day surgical mortality. These data suggest factors that can be used to frame treatment discussion plans with patients.

FAK and HAS inhibition synergistically decrease colon cancer cell viability and affect expression of critical genes.

Focal adhesion kinase (FAK), hyaluronan (HA), and hyaluronan synthase-3 (HAS3) have been implicated in cancer growth and progression. FAK inhibition with the small molecule inhibitor Y15 decreases colon cancer cell growth in vitro and in vivo. HAS3 inhibition in colon cancer cells decreases FAK expression and activation, and exogenous HA increases FAK activation. We sought to determine the genes affected by HAS and FAK inhibition and hypothesized that dual inhibition would synergistically inhibit viability. Y15 (FAK inhibitor) and the HAS inhibitor 4-methylumbelliferone (4-MU) decreased viability in a dose dependent manner; viability was further inhibited by treatment with Y15 and 4-MU in colon cancer cells. HAS inhibited cells treated with 2 µM of Y15 showed significantly decreased viability compared to HAS scrambled cells treated with the same dose (p < 0.05) demonstrating synergistic inhibition of viability with dual FAK/HAS inhibition. Microarray analysis showed more than 2-fold up- or down-regulation of 121 genes by HAS inhibition, and 696 genes by FAK inhibition (p < 0.05) and revealed 29 common genes affected by both signaling. Among the genes affected by FAK or HAS3 inhibition were genes, playing role in apoptosis, cell cycle regulation, adhesion, transcription, heatshock and WNT pathways. Thus, FAK or HAS inhibition decreases SW620 viability and affects several similar genes, which are involved in the regulation of tumor survival. Dual inhibition of FAK and HAS3 decreases viability to a greater degree than with either agent alone, and suggests that synergistic inhibition of colon cancer cell growth can result from affecting similar genetic pathways.

Postoperative adjuvant chemotherapy use in patients with stage II/III rectal cancer treated with neoadjuvant therapy: a national comprehensive cancer network analysis.

PURPOSE: Practice guidelines recommend that patients who receive neoadjuvant chemotherapy and radiation for locally advanced rectal cancer complete postoperative adjuvant systemic chemotherapy, irrespective of tumor downstaging. PATIENTS AND METHODS: The National Comprehensive Cancer Network (NCCN) Colorectal Cancer Database tracks longitudinal care for patients treated at eight specialty cancer centers across the United States and was used to evaluate how frequently patients with rectal cancer who were treated with neoadjuvant chemotherapy also received postoperative systemic chemotherapy. Patient and tumor characteristics were examined in a multivariable logistic regression model. RESULTS: Between September 2005 and December 2010, 2,073 patients with stage II/III rectal cancer were enrolled in the database. Of these, 1,193 patients receiving neoadjuvant chemoradiotherapy were in the analysis, including 203 patients not receiving any adjuvant chemotherapy. For those seen by a medical oncologist, the most frequent reason chemotherapy was not recommended was comorbid illness (25 of 50, 50%); the most frequent reason chemotherapy was not received even though it was recommended or discussed was patient refusal (54 of 74, 73%). After controlling for NCCN Cancer Center and clinical TNM stage in a multivariable logistic model, factors significantly associated with not receiving adjuvant chemotherapy were age, Eastern Cooperative Oncology Group performance status ≥ 1, on Medicaid or indigent compared with private insurance, complete pathologic response, presence of re-operation/wound infection, and no closure of ileostomy/colostomy. CONCLUSION: Even at specialty cancer centers, a sizeable minority of patients with rectal cancer treated with curative-intent neoadjuvant chemoradiotherapy do not complete postoperative chemotherapy. Strategies to facilitate the ability to complete this third and final component of curative intent treatment are necessary.

Anorectal melanoma: diagnosis and treatment.

An increase in the incidence of anorectal melanoma has recently been noted in the United States. Anorectal melanoma is an uncommon and lethal condition, with a median survival of <20 months. Unfortunately, nonspecific symptoms also attributable to common and benign conditions (eg, hemorrhoids) cause significant delay in its diagnosis. Although it has not been validated by clinical trials, abdominoperineal resection has historically been the treatment of choice for this disease. However, for the past 2 decades, a lack of clear survival benefit has led to a shift toward less-mutilating wide local excisions. Controversy still exists regarding the benefit of radiation therapy and chemotherapy. Furthermore, the value of nodal surgery in anorectal melanoma is unclear. In this article, we review the history and current status of management of anorectal melanoma, with a particular focus on surgical controversies and challenges in optimizing survival.

Hypoglycemia with intensive insulin therapy after cardiac surgery: predisposing factors and association with mortality.

BACKGROUND: Intensive insulin therapy has become a major therapeutic target in cardiac surgery patients. It has been associated, however, with an increased risk of hypoglycemia compared with conventional insulin therapy. Our study sought to identify the factors predisposing to hypoglycemia with intensive insulin therapy and investigate its effect on early clinical outcomes after cardiac surgery. METHODS: A concurrent cohort study of 2,538 consecutive patients undergoing cardiac surgery (coronary artery bypass grafting, valve, or bypass grafting and valve surgery) from January 2005 to March 2010 was carried out. Multivariable logistic regression analysis and propensity score matching were used (1) to identify the risk factors for developing hypoglycemia (blood glucose < 60 mg/dL) after cardiac surgery and (2) to compare major morbidity, operative mortality, and actuarial survival between patients in whom hypoglycemia developed (n = 77) and those in whom it did not (n = 2461). The propensity score-adjusted sample included 61 patients in whom hypoglycemia developed and 305 patients in whom it did not (1 to 5 matching). RESULTS: Risk factors for hypoglycemia included female gender (odds ratio [OR] = 2.3, 95% confidence intervals [CI] = 1.4-3.7; P < .001), diabetes (OR = 2.8, CI = 1.7-4.5; P < .001), hemodialysis (OR = 3.0, CI = 1.3-6.8; P = .009), intraoperative blood product transfusion (OR = 2.0, CI = 1.2-3.4; P = .010), and earlier date of surgery (years of surgery, 2005-2007; OR = 2.1, CI = 1.2-3.7; P = .007) . Hypoglycemia increased the risk for operative mortality in univariate (hypoglycemic 10% vs normoglycemic patients 2%; P < .001) but not in propensity score- adjusted analysis (OR= 2.5, 0.9-6.7; P = .11). The propensity score-adjusted analysis demonstrated a significant increase in hemorrhage-related reexploration (P = .048), pneumonia (P < .001), reintubation (P < .001), prolonged ventilatory support (P < .001), hospital length of stay (P < .001), and intensive care unit length of stay (P < .001) for the hypoglycemic compared with normoglycemic patients. Five-year actuarial survival was similar in the compared patient groups (hypoglycemic 75% vs normoglycemic 75%; P = .22). CONCLUSIONS: Hypoglycemia with intensive insulin therapy is independently associated with increased risk for respiratory complications and prolonged hospital and intensive care unit lengths of stay after cardiac surgery. In our study, hypoglycemia was not independently associated with increased risk of death.

Metastasectomy for stage IV colorectal cancer.

Metastatic colorectal cancer traditionally has been considered incurable. Over the past 3 decades, however, resection of low-volume hepatic disease has been recognized as beneficial in some cases. More recently, resection of isolated pulmonary metastases has been shown to offer long-term survival in carefully selected patients. Resection of metastases to more unusual sites (ovary, brain, peritoneal cavity) is more controversial; nevertheless, retrospective data suggest that a few patients may be cured with resection of these tumors. In this article, we review the history and current status of metastasectomy in stage IV colorectal cancer.

Inhibition of hyaluronan synthase-3 decreases subcutaneous colon cancer growth in mice.

PURPOSE: Hyaluronan and hyaluronan synthases have been implicated in cancer progression. Hyaluronan synthase-3 is up-regulated in metastatic colon cancer cells (SW620), and its expression mediates cellular growth in vitro. We hypothesized that inhibition of hyaluronan synthase-3 would decrease tumor formation and/or alter the pattern of metastasis in mouse models of colon cancer growth. METHODS: Hyaluronan synthase-3 was inhibited in SW620 cells by transfection with small interfering RNA (silenced cells); a scrambled sequence served as a negative control. To study primary tumor growth, transfected cells were injected into the flanks of BALB/c nude mice. To study metastasis, an orthotopic model was used. Metastases were confirmed histologically. Student t test and Fisher exact probability test were used for statistical analysis. RESULTS: Inhibition of hyaluronan synthase-3 significantly decreased subcutaneous tumor growth; tumor weight was 0.94 +/- 0.17 g in the hyaluronan synthase-3-silenced group vs 1.70 +/- 0.26 g in the control scrambled group (P < .01). In contrast, metastases were similar in both groups: liver metastases were present in 22% of the silenced group vs 11% of the scrambled group; lung metastases were present in 6% of the silenced group vs 0% of the scrambled group (P = not significant). CONCLUSION: Inhibition of hyaluronan synthase-3 expression in SW620 colon cancer cells decreases subcutaneous tumor growth in mice, but has less of an effect on lung and liver metastases. This observation suggests that hyaluronan synthase-3 may enhance primary colon cancer growth.

Retrorectal tumors.

Retrorectal or presacral tumors are rare and can be challenging to diagnose and treat. Because the retrorectal space contains multiple embryologic remnants derived from various tissues, the tumors that develop in this space are heterogeneous. Most lesions are benign, but malignant neoplasms are not uncommon. Lesions are classified as congenital, neurogenic, osseous, inflammatory, or miscellaneous. Although treatment depends on diagnosis and anatomic location, most retrorectal lesions will require surgical resection.

Evolving therapies and FAK inhibitors for the treatment of cancer.

Despite advances in medical and surgical therapy, cancer kills more than half a million people in the United States annually, and the majority of these patients succumb to metastatic disease. The traditional approach to treating systemic disease has been the use of cytotoxic chemotherapy. However, chemotherapy is rarely curative and toxicity is often dose limiting. In addition, the effects of chemotherapy are nonspecific, targeting both malignant and normal tissues. As a result, recent efforts increasingly have focused on developing agents that target specific molecules in tumor cells in order to both improve efficacy and limit toxicity. This review summarizes the history and current use of targeted molecular therapy for cancer, with a special emphasis on recently developed inhibitors of Focal Adhesion Kinase (FAK).

Anastomotic sinuses after ileoanal pouch construction: incidence, management, and outcome.

PURPOSE: This study was designed to analyze the incidence, management, and outcome of pouch sinuses after ileal pouch-anal anastomosis at one institution. METHODS: We identified 282 ileal pouch-anal anastomosis patients between 1992 and 2002 who had a pouchogram before planned ileostomy closure. The management and outcome of patients with pouchograms revealing pouch sinuses were reviewed. RESULTS: Twenty-two patients (7.8 percent) had a pouch sinus at pouchogram. Nineteen patients were observed and underwent repeat pouchogram. Of these, ten had sinus resolution (mean, 3.6 months) and underwent successful ileostomy closure. Eight patients underwent examination under anesthesia +/- sinus debridement. Six of these patients had subsequent pouchograms with five showing sinus resolution. The patient without resolution was not reversed. Of the eight patients who underwent examination under anesthesia +/- debridement, seven underwent ileostomy closure (mean, 4.9 months), with healing in six and pelvic sepsis in one. Four patients underwent successful ileostomy takedown despite persistent sinus. Overall, 21 of the 22 pouch sinus patients underwent ileostomy closure and only 1 had postoperative pelvic sepsis. CONCLUSIONS: Pouch sinuses after ileal pouch-anal anastomosis with ileostomy are uncommon. Most heal within six months. The majority of patients with sinuses eventually undergo successful ileostomy closure. Pelvic septic complications are rare but can occur despite sinus healing on pouchogram.

Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer?

OBJECTIVE: To assess whether TNODS is an independent prognostic factor after adjusting for the lymph node ratio (LNR). SUMMARY BACKGROUND DATA: The medical literature has suggested that the TNODS is associated with better survival in stage II and III colon cancer. Thus TNODS was endorsed as a quality measure for patient care by American College of Surgeons, National Quality Forum. There is, however, little biologic rationale to support this linkage. METHODS: : A total of 24,477 stage III colon cancer patients were identified from Surveillance, Epidemiology, and End Results cancer registry and categorized into 4 groups, LNR1 to LNR4, according to LNR interval: <0.07, 0.07 to 0.25, 0.25 to 0.50, and >0.50. Patients were also stratified according to TNODS into high TNODS (> or = 12) and low TNODS (<12) groups. The method of Kaplan-Meier was used to estimate the 5-year survival and the log-rank test was used to test the survival difference among the different groups. RESULTS: Patients with high TNODS have better survival compared with those with low TNODS (5-year survival 51.0% vs. 45.0%, P < 0.0001). However, after stratifying by LNR status, there was no significant survival difference between patients with high TNODS and those with low TNODS within strata LNR2 (5-year survival 56.3% vs. 56.0%, P = 0.26). Ironically, patients with high TNODS had significantly worse survival than those with low TNODS within strata LNR3 (5-year survival 41.2% vs. 47.4%, P = 0.0009) and LNR 4 (5-year survival 22.0% vs. 32.1%, P < 0.0001). CONCLUSIONS: The previously reported prognostic effect of TNODS on node-positive colon cancer was confounded by LNR. This observation calls into question the use of TNODS as a quality measure for colon cancer patients' care.