Laparotomy for small-bowel obstruction: first choice or last resort for adhesiolysis? A laparoscopic approach for small-bowel obstruction reduces 30-day complications.

INTRODUCTION: Small-bowel obstruction (SBO) requiring adhesiolysis is a frequent and costly problem in the United States with limited evidence regarding the most effective and safest surgical management. This study examines whether patients treated with laparoscopy for SBO have better 30-day surgical outcomes than their counterparts undergoing open procedures. METHODS: Patients with a diagnosis of adhesive SBO were selected from the ACS National Surgical Quality Improvement Program database from 2005 to 2010. Cases were classified as either laparoscopic or open adhesiolysis groups using Common Procedural Terminology codes. Chi square and Student's t test were used to compare patient and surgical characteristics with 30-day outcomes, including major complications, incisional complications, and mortality. Factors with p < 0.1 were included in the multivariable logistic regression for each outcome. A propensity score analysis for probability of being a laparoscopic case was used to address residual selection bias. A two-sided p value <0.05 was considered significant. RESULTS: Of the 9,619 SBO included in the analysis, 14.9 % adhesiolysis procedures were performed laparoscopically. Patients undergoing laparoscopic procedures had shorter mean operative times (77.2 vs. 94.2 min, p < 0.0001) and decreased postoperative length of stay (4.7 vs. 9.9 days, p < 0.0001). After controlling for comorbidities and surgical factors, patients having laparoscopic adhesiolysis were less likely to develop major complications [odds ratio (OR) = 0.7, 95 % confidence interval (CI) 0.58-0.85, p < 0.0001] and incisional complications (OR = 0.22, 95 % CI 0.15-0.33, p < 0.0001). The 30-day mortality was 1.3 % in the laparoscopic group versus 4.7 % in the open group (OR = 0.55, 95 % CI 0.33-0.85, p = 0.024). CONCLUSIONS: Laparoscopic adhesiolysis requires a specific skill set and may not be appropriate in all patients. Notwithstanding this, the laparoscopic approach demonstrates a benefit in 30-day morbidity and mortality even after controlling for preoperative patient characteristics. Given these findings in more than 9,000 patients and consistent rates of SBO requiring surgical intervention in the United States, increasing the use of laparoscopy could be a feasible way of to decrease costs and improving outcomes in this population.

Postoperative pain control.

The effective relief of pain is of the utmost importance to anyone treating patients undergoing surgery. Pain relief has significant physiological benefits; hence, monitoring of pain relief is increasingly becoming an important postoperative quality measure. The goal for postoperative pain management is to reduce or eliminate pain and discomfort with a minimum of side effects. Various agents (opioid vs. nonopioid), routes (oral, intravenous, neuraxial, regional) and modes (patient controlled vs. "as needed") for the treatment of postoperative pain exist. Although traditionally the mainstay of postoperative analgesia is opioid based, increasingly more evidence exists to support a multimodal approach with the intent to reduce opioid side effects (such as nausea and ileus) and improve pain scores. Enhanced recovery protocols to reduce length of stay in colorectal surgery are becoming more prevalent and include multimodal opioid sparing regimens as a critical component. Familiarity with the efficacy of available agents and routes of administration is important to tailor the postoperative regimen to the needs of the individual patient.

Clinical response to primary letrozole therapy in elderly patients with early breast cancer: possible role for p53 as a biomarker.

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70-101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI - 34-72) and the median time to progression was 43 months (95% CI - 22-64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group.

Proteomic identification of predictive biomarkers of resistance to neoadjuvant chemotherapy in luminal breast cancer: a possible role for 14-3-3 theta/tau and tBID?

INTRODUCTION: Chemotherapy resistance is a major obstacle in effective neoadjuvant treatment for estrogen receptor-positive breast cancer. The ability to predict tumour response would allow chemotherapy administration to be directed towards only those patients who would benefit, thus maximising treatment efficiency. We aimed to identify putative protein biomarkers associated with chemotherapy resistance, using fresh tumour samples with antibody microarray analysis and then to perform pilot clinical validation experiments. MATERIALS AND METHODS: Chemotherapy resistant and chemotherapy sensitive tumour samples were collected from breast cancer patients who had received anthracycline based neoadjuvant therapy consisting of epirubicin with cyclophosphamide followed by docetaxel. A total of 5 comparative proteomics experiments were performed using invasive ductal carcinomas which demonstrated estrogen receptor positivity (luminal subtype). Protein expression was compared between chemotherapy resistant and chemotherapy sensitive tumour samples using the Panorama XPRESS Profiler725 antibody microarray containing 725 antibodies from a wide variety of cell signalling and apoptosis pathways. A pilot series of archival samples was used for clinical validation of putative predictive biomarkers. RESULTS: AbMA analysis revealed 38 differentially expressed proteins which demonstrated at least 1.8 fold difference in expression in chemotherapy resistant tumours and 7 of these proteins (Zyxin, 14-3-3 theta/tau, tBID, Pinin, Bcl-xL, RIP and MyD88) were found in at least 2 experiments. Clinical validation in a pilot series of archival samples revealed 14-3-3 theta/tau and tBID to be significantly associated with chemotherapy resistance. CONCLUSIONS: For the first time, antibody microarrays have been used to identify proteins associated with chemotherapy resistance using fresh breast cancer tissue. We propose a potential role for 14-3-3 theta/tau and tBID as predictive biomarkers of neoadjuvant chemotherapy resistance in breast cancer. Further validation in a larger sample series is now required.

Proteomic identification of putative biomarkers of radiotherapy resistance: a possible role for the 26S proteasome?

PURPOSE: We aimed to identify putative predictive protein biomarkers of radioresistance. EXPERIMENTAL DESIGN: Three breast cancer cell lines (MCF7, MDA-MB-231, and T47D) were used as in vitro models to study radioresistance. Inherent radiosensitivities were examined using a clonogenic survival assay. It was revealed that each cell line differed in their response to radiotherapy. These parental breast cancer cell lines were used to establish novel derivatives (MCF7RR, MDA-MB-231RR, and T47DRR) displaying significant resistance to ionizing radiation. Derivative cells were compared with parental cells to identify putative biomarkers associated with the radioresistant phenotype. To identify these biomarkers, complementary proteomic screening approaches were exploited encompassing two-dimensional gel electrophoresis in combination with mass spectrometry, liquid chromatography coupled with tandem mass spectrometry and quantitative proteomics using iTRAQ technology. RESULTS: A large number of potential biomarkers were identified, and several of these were confirmed using Western blot analysis. In particular, a decrease in the expression of the 26S proteasome was found in all radioresistant derivatives when compared with the respective parent cells. Decreased expression of this target was also found to be associated with radioresistant laryngeal tumors (P = .05) in a small pilot immunohistochemical study. CONCLUSIONS: These findings suggest that the 26S proteasome may provide a general predictive biomarker for radiotherapy outcome.