Liposomal bupivacaine addition versus standard bupivacaine alone for colorectal surgery: a randomized controlled trial.

Aim: This study evaluated use of liposomal bupivacaine (LB) versus standard bupivacaine (SB) alone in quadratus lumborum (QL) blocks for laparoscopic colorectal surgery. Materials & methods: In this prospective, randomized controlled trial, patients received QL1 blocks with either LB (40 ml 0.125% SB plus 20 ml of LB) or SB (60 ml of 0.25% SB) with 30 ml per side. Opioid usage, pain scores, side effects and other medications were recorded. Results: For 78 patients (38 LB; 40 SB), all parameters were similar between groups, except that the LB group had a higher 48 h need for metoclopramide. Conclusion: LB provided no analgesic benefit over SB alone for QL blocks. Clinical Trials registration number: NCT03702621.

Lay abstract This study evaluated use of extended release bupivacaine (LB) versus standard bupivacaine (SB) alone in nerve blocks for laparoscopic colorectal surgery. Patients undergoing colorectal surgery received nerve blocks with either LB combined with SB, or SB alone. Opioid usage, pain scores, side effects and other medications were recorded. For 78 patients (38 LB + SB; 40 SB), all parameters were similar between groups, except that the LB group had a higher 48 h need for anti-nausea medication. LB provided no pain control benefit over SB alone for nerve blocks in colorectal surgery.

Perioperative Management of Patients with Colovesical Fistula.

BACKGROUND: Colovesical fistula (CVF) is an uncommon complication of diverticulitis. Substantial heterogeneity exists in the perioperative management of this condition. We seek to evaluate the role of bladder leak testing, closed suction drainage, prolonged bladder catheter usage, and routine postoperative cystogram in the management of CVF. STUDY DESIGN: This is a retrospective study from a single academic health center investigation patients undergoing operation for diverticular CVF from 2005 to 2015 (n = 89). RESULTS: Patients undergoing operative repair for diverticular CVF resection had a mortality of 4% and overall morbidity of 46%. Intraoperative bladder leak test was performed in 36 patients (40%) and demonstrated a leak in 4 patients (11%). No patients with a negative intraoperative bladder leak test developed a urinary leak. Overall, five (6%) patients developed postoperative bladder leak. Three were identified by elevated drain creatinine and two by cystogram. The diagnostic yield of routine cystogram was 3%. All bladder leaks were diagnosed between postoperative day 3 and 7. Of patients with a postoperative bladder leak, none required reoperation and all resolved within 2 months. CONCLUSIONS: There is significant variability in the management of patients undergoing operation for CVF. Routine intraoperative bladder leak test should be performed. Cystogram may add cost and is low yield for routine evaluation for bladder leak after operation for CVF. Urinary catheter removal before postoperative day 7 should be considered.

Contemporary Management of Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is an uncommon cause of bowel obstruction that is historically associated with high morbidity and mortality. The objective of this study was to evaluate contemporary management of sigmoid volvulus and the safety of primary anastomosis in patients with sigmoid volvulus. METHODS: The National Surgical Quality Improvement Project from 2012 to 2015 was queried for patients with colonic volvulus who underwent left-sided colonic resection. A propensity score-matched analysis was performed to compare patients with sigmoid volvulus undergoing colectomy with primary anastomosis without proximal diversion to colectomy with end colostomy. RESULTS: Two thousand five hundred thirty-eight patients with sigmoid volvulus were included for analysis. Patients had a median age of 68 years (interquartile range, 55-80) and 79% were fully independent preoperatively. Fifty-one percent of operations were performed emergently. One thousand eight hundred thirteen (71%) patients underwent colectomy with anastomosis, 240 (10%) colectomy with anastomosis and proximal diversion, and 485 (19%) colectomy with end colostomy. Overall, 30-day mortality and morbidity were 5 and 40%, respectively. After propensity score matching, mortality, overall morbidity, and serious morbidity were similar between groups. CONCLUSIONS: Sigmoid volvulus occurs in elderly and debilitated patients with significant morbidity, mortality, and lifestyle implications. In selected patients, anastomosis without proximal diversion in patients with sigmoid volvulus results in similar outcomes to colectomy with end colostomy.

Bowel Preparation Is Associated with Reduced Morbidity in Elderly Patients Undergoing Elective Colectomy.

BACKGROUND: Bowel preparation in elderly patients is associated with physiologic derangements that may result in postoperative complications. The aim of this study is to determine the impact of bowel preparation on postoperative outcomes in elderly patients. METHODS: Patients age 75 years and older who underwent elective colectomy were identified from the 2012-2014 American College of National Surgical Quality Improvement Program (ACS-NSQIP database). Patients were grouped into no bowel preparation, mechanical bowel preparation (MBP), oral antibiotic preparation (OABP), or combined MBP + OABP. Logistic regression modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There were 4829 patients included in the analysis. Morbidity was 34.3% in no bowel prep, 32.4% in MBP, 24.8% in OABP, and 24.6% in MBP + OABP groups (p < 0.001). The MBP + OABP group compared with no bowel prep was associated with reduced rates of anastomotic leak, ileus, superficial surgical site infection (SSI), organ space SSI, respiratory compromise, and reduced length of stay. There was no difference in the rate of acute kidney injury between the groups. CONCLUSION: MBP + OABP was associated with reduced morbidity compared with no bowel preparation in elderly patients undergoing elective colorectal resection. MBP alone was not associated with differences in outcomes compared with no bowel preparation. The use of MBP + OABP is safe and effective in elderly patients undergoing elective colectomy.

Dimethylamino parthenolide enhances the inhibitory effects of gemcitabine in human pancreatic cancer cells.

INTRODUCTION: Gemcitabine is standard treatment for pancreatic cancer but has limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF-κB) can promote chemoresistance and is therefore an attractive therapeutic target. We hypothesize that NF-κB suppression with the novel, orally bioavailable inhibitor dimethylamino parthenolide (DMAPT) will sensitize pancreatic cancer cells to gemcitabine. METHODS: BxPC-3, PANC-1, and MIA PaCa-2 human pancreatic cancer cell lines were treated with gemcitabine and/or DMAPT. Effects on the NF-κB pathway were determined by electrophoretic mobility shift assay, ELISA, or Western blot. Proliferation and apoptosis were measured by cell counts and ELISA, respectively. The effect of gemcitabine in vivo was determined using a MIA PaCa-2 heterotopic xenograft model. RESULTS: Gemcitabine induced NF-κB activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased the level of the NF-κB inhibitor IκBα in BxPC-3 and PANC-1 cells. DMAPT prevented the gemcitabine-induced activation of NF-κB. The combination of DMAPT/gemcitabine inhibited pancreatic cancer cell growth more than either agent alone. Gemcitabine also induced intratumoral NF-κB activity in vivo. CONCLUSIONS: DMAPT enhanced the anti-proliferative effects of gemcitabine in association with NF-κB suppression in pancreatic cancer cells in vitro. Furthermore, gemcitabine induced NF-κB activity in vivo, thus supporting the evaluation of NF-κB-targeted agents to complement gemcitabine-based therapies.

Effect of celecoxib and the novel anti-cancer agent, dimethylamino-parthenolide, in a developmental model of pancreatic cancer.

OBJECTIVES: Cancer of the exocrine pancreas is the fourth leading cause of cancer-related deaths in the United States. The efficacy of a novel bioavailable anticancer agent, dimethylamino-parthenolide (DMAPT), and the cyclooxygenase 2 inhibitor, celecoxib, was evaluated in a carcinogen-induced developmental model of pancreatic cancer. METHODS: Syrian golden hamsters were injected with N-nitrosobis(2-oxopropyl)amine, once weekly for 6 weeks. Upon the first injection, hamsters were randomized as follows: placebo, low-/high-dose DMAPT (20 and 40 mg/kg per day), low-/high-dose celecoxib (10and 50 mg/kg per day), or combination DMAPT/celecoxib (low/low, high/high). RESULTS: The 32-week trial showed that 40 mg/kg DMAPT alone significantly decreased the size of gross pancreatic cancers relative to placebo. No significant difference in gross tumor number was observed between the treatment groups and placebo with the exception of 50 mg/kg celecoxib with a higher tumor incidence; this group also exhibited lower lymphotactin levels suggestive of decreased immune surveillance. Tumor invasion into adjacent organs and metastasis were not observed in the DMAPT/celecoxib treatment groups. Drug targets including prostaglandin E2, prostaglandin E2 metabolite and activated nuclear factor kappaB were significantly decreased. CONCLUSIONS: Dimethylamino-parthenolide and celecoxib have the potential to be novel chemotherapeutic agents for pancreatic cancer; however, further optimization or the use of other modalities may be required for chemoprevention.

The role of nuclear factor kappaB in pancreatic cancer and the clinical applications of targeted therapy.

Pancreatic cancer is one of the leading causes of cancer mortality in the United States. Current therapy for pancreatic cancer involves surgery, chemotherapy, and radiation therapy; however, the 5-year survival rate remains less than 5%. New strategies for treating pancreatic cancer include targeting intracellular signaling that provides survival advantages to cancer cells. One of these targets is the transcription factor nuclear factor (NF) kappaB, which is activated by a variety of mechanisms. Data demonstrate that increased NF-kappaB activity can promote growth and tumorigenesis, inhibit apoptosis, promote angiogenesis, promote invasion and metastasis, and promote chemoresistance in pancreatic cancer. This review explores the roles of NF-JB in these processes and examines the evidence that different NF-kappaB-inhibiting drugs can improve the treatment of pancreatic cancer.

Pancreatic cancer cell genetics and signaling response to treatment correlate with efficacy of gemcitabine-based molecular targeting strategies.

INTRODUCTION: Pancreatic cancer is a deadly cancer with limited sensitivity to gemcitabine. Molecular targeting of critical signaling pathways [nuclear factor kappa-B (NF-kappaB), PI3K/AKT, and mitogen-activated protein kinase (MAPK)] in combination with gemcitabine may improve sensitivity. We hypothesize that pancreatic cancer cell genetics and signaling response to treatment correlate with efficacy of gemcitabine-based molecular targeting strategies. MATERIALS AND METHODS: PANC-1, PaCa-2, and BxPC-3 cells were treated with curcumin, LY294002, or PD325901 alone or in combination with gemcitabine. Proliferation was measured by cell counts and enzyme activity by Western blot and electrophoretic mobility shift assay. RESULTS: Each agent dose-dependently decreased proliferation. All cells decreased NF-kappaB activity with curcumin(24 h) except PaCa-2, MEK activity with PD325901(24 h), and PI3Kinase with LY294002(3 h). However, PI3K rebounded to(PaCa-2) or above (Panc-1,BxPC-3) basal in LY294002-treated cells (24 h). Combinations with gemcitabine resulted in at least additive effects on proliferative inhibition. For PANC-1, curcumin + gemcitabine was nearly synergistic, correlating with gemcitabine-induced NF-kappaB activity. LY294002 + gemcitabine was nearly synergistic in PaCa-2 cells, which showed a lower induction of PI3Kinase activity with LY294002. Finally, gemcitabine + PD325901 was only effective in BxPC-3, which exhibited increased MEK activity with gemcitabine. CONCLUSIONS: These results demonstrate differences in treatment efficacy, which correlate with the cell's signaling response to treatment. Signaling profiles of each tumor may be necessary to determine an optimal chemotherapy for pancreatic cancer.

Adults' knowledge and behaviors related to human papillomavirus infection.

BACKGROUND: Our objective was to assess adults' knowledge, risk behaviors, and preference for information about human papillomavirus (HPV). METHODS: A cross-sectional study using a self-administered questionnaire given in 3 locations (a university health service and 2 community family practice offices); 289 people completed the questionnaire. The primary outcome measure was a knowledge score calculated from the responses on specific items in the questionnaire. This knowledge score was developed by other investigators and has acceptable psychometric properties. RESULTS: Knowledge about HPV was low, with an average knowledge score of 5.50 (possible scores ranged from 0 to 14) and a mode of 0. Knowledge scores were significantly higher in women (P =.001) and married adults (P =.001). Knowledge scores were inversely related to age (P =.004) and positively correlated with years of education (P =.001) and self-assessment of knowledge (P <.001). Knowledge scores were positively correlated with condom use (P =.05) but not significantly associated with other risk behaviors. The most frequently desired time to receive information about HPV was before becoming sexually active. CONCLUSIONS: Adults seen in a typical family physician's office have limited knowledge of HPV. One tool family physicians can use to identify those with the least amount of knowledge is to ask patients how informed they are about HPV. The preferred time to receive information about HPV was before a patient became sexually active. However, it remains unclear whether educational intervention or knowledge changes risky behaviors.