In-house colorectal laparoscopic preceptorship: a model for changing a unit’s practice safely and efficiently

Purpose  There has been steady increase in demand for laparoscopic colonic resection as benefits are manifold compared to open and include smaller incisions, less pain, quicker recovery and convalescence, reduced morbidity and reduced analgesic demands. We devised a preceptorship programme with the aim of all four coloproctologists in our unit becoming proficient colorectal laparoscopic surgeons over a period of 12 months. Method  The surgeon in the unit with significant experience of laparoscopic colorectal surgery acted as a preceptor to the remaining three. A prospective database was set up to allow analysis of the impact of the preceptorship on the units’ elective practice and outcomes from January 2006. Results  Results were analysed 106 cases to assess the success of this novel method and were more than encouraging. During this period, 57 laparoscopic resections were performed compared 49 open resections. The proportion of patients undergoing laparoscopic resection had risen from 20% to 80% (p = 0.000). This was associated with a significant drop in post-operative stay from 14 to 4 days (p = 0.000). Analysis of patient demographics, pathology and type of resection found there to be no significant difference between the open and laparoscopic groups. The conversion rate was acceptably low (10.5%) and there were no re-admissions. Conclusions  For hospitals with the facilities and an appropriately experienced preceptor, we offer this as a patient-safe, cost-neutral method of significantly increasing a units’ laparoscopic practice over a relatively short period of time.     

A Culturally Tailored Navigator Program for Colorectal Cancer Screening in a Community Health Center: A Randomized, Controlled Trial

Background  Minority racial/ethnic groups have low colorectal cancer (CRC) screening rates. Objective  To evaluate a culturally tailored intervention to increase CRC screening, primarily using colonoscopy, among low income and non-English speaking patients. Design  Randomized controlled trial conducted from January to October of 2007. Setting  Single, urban community health center serving a low-income, ethnically diverse population. Patients  A total of 1,223 patients 52-79 years of age overdue for CRC screening, randomized to intervention (n = 409) vs. usual care control (n = 814) groups. Intervention  Intervention patients received an introductory letter with educational material followed by phone or in-person contact by a language-concordant “navigator.” Navigators (n = 5) were community health workers trained to identify and address patient-reported barriers to CRC screening. Individually tailored interventions included patient education, procedure scheduling, translation and explanation of bowel preparation, and help with transportation and insurance coverage. Rates of colorectal cancer screening were assessed for intervention and usual care control patients. Results  Over a 9-month period, intervention patients were more likely to undergo CRC screening than control patients (27% vs. 12% for any CRC screening, p < 0.001; 21% vs. 10% for colonoscopy completion, p < 0.001). The higher screening rate resulted in the identification of 10.5 polyps per 100 patients in the intervention group vs. 6.8 in the control group (p = 0.04). Limitations  Patients were from one health center. Some patients may have obtained CRC screening outside our system. Conclusions  A culturally tailored, language-concordant navigator program designed to identify and overcome barriers to colorectal cancer screening can significantly improve colonoscopy rates for low income, ethnically and linguistically diverse patients. ClinicalTrials.gov registration number: NCT00476970     

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer.
DESIGN: Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score–matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions.
SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used.
PARTICIPANTS: Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship.
MEASUREMENTS: The outcome was colon cancer–specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery.
RESULTS: All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups.
CONCLUSION: These findings have important clinical and policy implications for the risk–benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.     

结肠靶向定位滴丸克癌素的提取工艺研究

目的建立结肠靶向滴丸克癌素的提取工艺方法。方法采用碱溶酸沉法从槐米中提取芦丁,再进行酸水解得到槲皮素;采用传统乙醇回流法从姜黄中提取总姜黄素,以姜黄中的总姜黄素含量为指标,通过正交表分析确定最佳提取工艺。结果槲皮素的提取条件为:碱性pH8～9,酸性pH3～5条件下提取芦丁;得到精制芦丁加100倍量的2%硫酸酸水解90min。姜黄的最佳提取工艺为:85%乙醇回流提取3次,每次1h;得浸膏上硅胶柱收集氯仿洗脱部分得总姜黄素。结论该工艺可行,可为结肠靶向滴丸克癌素的生产提供参考。     

Histamine receptors and cancer pharmacology

Considerable evidence has been collected indicating that histamine can modulate proliferation of different normal and malignant cells. High histamine biosynthesis and content together with histamine receptors have been reported in different human neoplasias including melanoma, colon and breast cancer, as well as in experimental tumours in which histamine has been postulated to behave as an important paracrine and autocrine regulator of proliferation. The discovery of the human histamine H₄ receptor in different tissues has contributed to our understanding of histamine role in numerous physiological and pathological conditions revealing novel functions for histamine and opening new perspectives in histamine pharmacology research. In the present review we aimed to briefly summarize current knowledge on histamine and histamine receptor involvement in cancer before focusing on some recent evidence supporting the novel role of histamine H₄ receptor in cancer progression representing a promising molecular target and avenue for cancer drug development.

LINKED ARTICLES

BJP has previously published a Histamine themed issue (2009). To view this issue visit http://dx.doi.org/10.1111/bph.2009.157.issue-1     

Assessment of the in‐vivo drug release from pellets film‐coated with a dispersion of high amylose starch and ethylcellulose for potential colon delivery

Objectives The aim of this study was to test the ability of a colon targeting system comprising pellets film‐coated with a dispersion of high amylose starch (Hylon VII) and ethylcellulose (Surelease) (1 : 2 w/w) to deliver a model drug (5‐aminosalicylic acid; 5‐ASA) in vivo into the colon of rabbits. An uncoated pellet formulation was used as a control. Methods Six New Zealand female rabbits, approximately 2 kg, were randomly divided into two groups. Pellet formulations containing 50 mg/kg of 5‐ASA were filled into hard gelatin capsules size 4, and were administered orally using a cannula. The rabbits were fasted for 12 h before, and throughout, the study but had free access to water. Blood samples were collected, through a catheter inserted into the marginal vein of the ear, at pre‐determined times and the plasma analysed by a validated HPLC method with fluorescence detection. Results Analysis of the 5‐ASA plasma levels following administration of the uncoated pellets showed a C_max of 2.38 ± 0.49 μg/ml at 2 h post administration confirming that this system released the drug at an unspecific site, most likely in the rabbits' stomach and proximal small intestine. On the other hand, the coated formulation showed a delayed drug absorption (C_max 0.22 ± 0.19 μg/ml and t_max of 8 h), suggesting that the coating is able to prevent drug release in the stomach and small intestine, but allowing drug release in the colon. The coated pellets were retrieved from the rabbits' faeces after the 24‐h study. They had a drug content of < 40%, suggesting that the film‐coating had been digested by the bacterial amylases of the colon and the drug was released specifically in the colon of the rabbits. Conclusions Results from this study showed that the proposed drug delivery system has the potential to deliver drugs specifically into the colon.     

Transient receptor potential vanilloid 1-immunopositive neurons in the mouse are more prevalent within colon afferents compared to skin and muscle afferents

Previous studies in our laboratories found that isolectin B(4)(IB(4))-positive polymodal nociceptors in the mouse do not express transient receptor potential vanilloid 1 (TRPV1), nor does deletion of TRPV1 compromise the ability of these afferents to detect thermal stimuli. Considering that IB(4)-positive afferents account for over 70% of cutaneous nociceptors and that 30-50% of all mouse primary afferents express TRPV1, it is highly likely that many TRPV1-positive fibers project to non-cutaneous structures. To investigate this issue, Alexa Fluor-conjugated wheat germ agglutinin (WGA) or IB(4) was injected into the nerves innervating quadriceps muscle (femoral) or hindlimb skin (saphenous) of male C57Bl/6 mice. Similarly, Alexa Fluor-conjugated cholera toxin-beta was injected subserosally into the distal colon. Spinal ganglia at the appropriate level (L2-3 for saphenous and femoral nerves; L6 for colon) were processed for TRPV1, calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NHF) and IB(4) visualization and examined on a confocal microscope. Colon afferents contained the highest percentage of both TRPV1- and CGRP-positive neurons, followed by femoral (WGA) and saphenous afferents (WGA and IB(4)). In contrast, NHF staining was more prevalent among femoral afferents, followed by saphenous (WGA) and colon afferents. IB(4) binding was observed in very few colon or saphenous (WGA) afferents, with no femoral afferents binding or transporting IB(4). Considering that the largest percentages of TRPV1-positive neurons observed in this study were within visceral and muscle afferent populations (neurons that typically are not subject to noxious temperatures), these results suggest that TRPV1 may not function primarily as a temperature sensor but rather as a detector of protons, vanilloid compounds or through interactions with other membrane proteins.