Management of postoperative ileus: focus on alvimopan

Postoperative ileus (POI) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication. Ileus causes a variety of symptoms including bloating, pain, nausea, and vomiting, but particularly delays tolerance of oral diet and liquids. Thus POI is a primary determinant of hospital stay after surgery. ‘Fast-track’ recovery protocols, opioid sparing analgesia, and laparoscopic surgery reduce but do not eliminate postoperative ileus. Alvimopan is a mu opioid receptor antagonist that blocks the effects of opioids on the intestine, while not interfering with their centrally mediated analgesic effect. Several large randomized clinical trials have demonstrated that alvimopan accelerates the return of gastrointestinal function after surgery and subsequent hospital discharge by approximately 20 hours after elective open segmental colectomy. However, it has not been tested in patients undergoing laparoscopic surgery and is less effective in patients receiving nonsteroidal anti-inflammatory agents in a narcotic sparing postoperative pain control regimen. Safety concerns seen with chronic low dose administration of alvimopan for opioid bowel dysfunction have not been noted with its acute use for POI

Alvimopan for the Management of Postoperative Ileus After Bowel Resection: Characterization of Clinical Benefit by Pooled Responder Analysis

BACKGROUND: A pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection. METHODS: Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. The proportion of responders and numbers needed to treat (NNT) were examined on postoperative days (POD) 3-8 for GI-2 recovery (first bowel movement, toleration of solid food) and hospital discharge order (DCO) written. RESULTS: Alvimopan significantly increased the proportion of patients with GI-2 recovery and DCO written by each POD (P \u3c 0.001 for all). More patients who received alvimopan achieved GI-2 recovery on or before POD 5 (alvimopan, 80%; placebo, 66%) and DCO written before POD 7 (alvimopan, 87%; placebo, 72%), with corresponding NNTs equal to 7. CONCLUSIONS: On each POD analyzed, alvimopan significantly increased the proportion of patients who achieved GI-2 recovery and DCO written versus placebo and was associated with relatively low NNTs. The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection

Observation of Low Energy Raman Modes in Twisted Bilayer Graphene

Two new Raman modes below 100 cm^-1 are observed in twisted bilayer graphene grown by chemical vapor deposition. The two modes are observed in a small range of twisting angle at which the intensity of the G Raman peak is strongly enhanced, indicating that these low energy modes and the G Raman mode share the same resonance enhancement mechanism, as a function of twisting angle. The 94 cm^-1 mode (measured with a 532 nm laser excitation) is assigned to the fundamental layer breathing vibration (ZO (prime) mode) mediated by the twisted bilayer graphene lattice, which lacks long-range translational symmetry. The dependence of this modes frequency and linewidth on the rotational angle can be explained by the double resonance Raman process which is different from the previously-identified Raman processes activated by twisted bilayer graphene superlattice. The dependence also reveals the strong impact of electronic-band overlaps of the two graphene layers. Another new mode at 52 cm^-1, not observed previously in the bilayer graphene system, is tentatively attributed to a torsion mode in which the bottom and top graphene layers rotate out-of-phase in the plane.Comment: 12 pages, 5 figures, 14 supp. figures (accepted by Nano Lett

Preoperative Rectal Cancer Management: Wide International Practice Makes Outcome Comparison Challenging: Reply

In a letter to the editor Dr. Hottenrott provides valuable comments on our survey describing international preoperative rectal cancer management. In our opinion, three key messages are derived from our survey: First, most surgeons agree to neoadjuvant treatment when there is an increased risk of finding histologically positive circumferential margins. In addition, we found more than 40 other indications for neoadjuvant treatment (see our Table 4). This emphasizes the need for an international agreement, as different indications for neoadjuvant treatment will select noncomparable groups of patients in outcome studies. Second, we have shown (see our Table 6) that multidisciplinary team (MDT) meetings significantly influence several important decisions in preoperative rectal cancer management. Interestingly, centers with regular MDT have a higher rate of using magnetic resonance imaging (MRI) (Odds Ratio [OR] = 3.62) and consider a threatened circumferential resection margin (CRM) as indication for neoadjuvant treatment (OR = 5.67). We believe that MDT improves preoperative management of rectal cancer by increasing adherence to national guidelines. Similar discussions in international rectal cancer societies are needed aiming towards an international consensus statement. Finally, our survey revealed sparse use (35% of all cases) of MRI. The goal for the radiologic examination in rectal cancer is to explore the tumor’s relation to nearby anatomical structures. This evaluation will conclude with TNM staging, important for chemoradiotheraphy, surgical treatment, and prognosis. Magnetic resonance imaging has a central role in this evaluation and should be the first choice radiologic modality. Not only is MRI crucial in detection of TNM stage but also plays a central role in determination of the tumor’s distance to the mesorectal fascia and the CRM. Magnetic resonance imaging has moderate sensitivity on T1 and T2 tumors, and should be supplemented with rectal ultrasound

Attenuated CSF-1R signalling drives cerebrovascular pathology

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood-brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor-1 receptor (CSF-1R) in an ultra-rare autosomal dominant condition termed adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p-Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF-1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). Here, we show that depletion in CSF-1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF-1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf-1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF-1R signalling causes re-modelling of BBB-associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's-like dementias

Laparoscopic versus open colectomy for colon cancer in an older population: a cohort study

<p>Abstract</p> <p>Background</p> <p>Laparoscopic colectomy for colon cancer has been compared with open colectomy in randomized controlled trials, but these studies may not be generalizable because of strict enrollment and exclusion criteria which may explicitly or inadvertently exclude older individuals due to associated comorbidities. Previous studies of older patients undergoing laparoscopic colectomy have generally focused on short-term outcomes. The goals of this cohort study were to identify predictors of laparoscopic colectomy in an older population in the United States and to compare short-term and long-term outcomes.</p> <p>Methods</p> <p>Patients aged 65 years or older with incident colorectal cancer diagnosed 1996-2002 who underwent colectomy within 6 months of cancer diagnosis were identified from the linked Surveillance, Epidemiology, and End Results-Medicare database. Laparoscopic and open colectomy patients were compared with respect to length of stay, blood transfusion requirements, intensive care unit monitoring, complications, 30-day mortality, and long-term survival. We adjusted for potential selection bias in surgical approach with propensity score matching.</p> <p>Results</p> <p>Laparoscopic colectomy cases were associated with left-sided tumors; areas with higher population density, income, and education level; areas in the western United States; and National Cancer Institute-designated cancer centers. Laparoscopic colectomy cases had shorter length of stay and less intensive care unit monitoring. Although laparoscopic colectomy patients (n = 424) had fewer complications (21.5% versus 26.3%), lower 30-day mortality (3.3% versus 5.8%), and longer median survival (6.6 versus 4.8 years) compared with open colectomy patients (n = 27,012), after propensity score matching these differences disappeared.</p> <p>Conclusions</p> <p>In this older population, laparoscopic colectomy practice patterns were associated with factors which likely correlate with tertiary referral centers. Although short-term and long-term survival are comparable, laparoscopic colectomy offers shorter hospitalizations and less intensive care.</p

International Preoperative Rectal Cancer Management: Staging, Neoadjuvant Treatment, and Impact of Multidisciplinary Teams

BACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods