The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Length of Stay: An Inappropriate Readout of the Success of Enhanced Recovery Programs

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are designed to reduce hospital length of stay by shortening the postoperative recovery period. The intended effect of an accelerated recovery on the length of stay may be frustrated by a delayed discharge. This study was designed to assess the influence of an ERAS program on the proportion, appropriateness, and extent of delay in discharge. METHODS: Patients who enrolled in the ERAS program (n = 121) between 2003 and 2006 were compared with 52 patients who were managed traditionally in 2001. RESULTS: Ninety percent of the pre-ERAS patients and 87% of the ERAS patients were not discharged on the day that discharge criteria were fulfilled. The additional stay of 59% of the pre-ERAS patients and 69% of the ERAS patients was inappropriate. Wound care (15% in the pre-ERAS and 3% of the ERAS group) and observation of any symptoms pointing to an anastomotic leakage (10% in both groups) were the most important reasons for a medical appropriate delay of discharge. The extent of delay in discharge decreased significantly from a median of two days in the pre-ERAS group to a median of 1 day in the ERAS group (p = 0.004). CONCLUSIONS: Reductions in length of stay up to a median of 2 days after start of an enhanced recovery program may relate to changes in organization of care and not to a shorter recovery period. Recovery statistics should replace or at least be added to the length of stay as outcome of enhanced recovery programs. AD - Department of Surgery, University Hospital Maastricht, PO Box 5800, 6202 AZ, Maastricht, the Netherlands. [email protected]

Tumor heterogeneity in neoplasms of breast, colon, and skin

<p>Abstract</p> <p>Background</p> <p>Different cell subpopulations in a single tumor may show diverse capacities for growth, differentiation, metastasis formation, and sensitivity to treatments. Thus, heterogeneity is an important feature of tumors. However, due to limitations in experimental and analytical techniques, tumor heterogeneity has rarely been studied in detail.</p> <p>Presentation of the hypothesis</p> <p>Different tumor types have different heterogeneity patterns, thus heterogeneity could be a characteristic feature of a particular tumor type.</p> <p>Testing the hypothesis</p> <p>We applied our previously published mathematical heterogeneity model to decipher tumor heterogeneity through the analysis of genetic copy number aberrations revealed by array CGH data for tumors of three different tissues: breast, colon, and skin. The model estimates the number of subpopulations present in each tumor. The analysis confirms that different tumor types have different heterogeneity patterns. Computationally derived genomic copy number profiles from each subpopulation have also been analyzed and discussed with reference to the multiple hypothetical relationships between subpopulations in origin-related samples.</p> <p>Implications of the hypothesis</p> <p>Our observations imply that tumor heterogeneity could be seen as an independent parameter for determining the characteristics of tumors. In the context of more comprehensive usage of array CGH or genome sequencing in a clinical setting our study provides a new way to realize the full potential of tumor genetic analysis.</p

In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes

EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 μM) or curcumin (10 μg ml−1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 μg ml−1). In response to TNF-α (25 ng ml−1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 μm for TNF-α (23.5%) and 15 μm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass

Psycho-education programme for temporomandibular disorders: a pilot study

BACKGROUND: Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care. The aim of this pilot study was to develop a simple, cost-effective management programme for TMDs using CD-ROM. 41 patients (age 18–70) participated in this study, patients were divided into three groups: the 1st group were involved in an attention placebo CD-ROM (contain anatomical information about the temporomandibular system), the 2nd group received information on CD-ROM designed to increase their control and self efficacy, while the 3rd group received the same programme of the 2nd group added to it an introduction to self-relaxing techniques followed by audio tape of progressive muscle relaxation exercises. Each of the groups was asked to complete a number of questionnaires on the day of initial consultation and six weeks afterwards. RESULTS: The two experimental groups (2nd & 3rd) were equally effective in reducing pain, disability and distress, and both were more effective than the attention placebo group (1st), however the experimental groups appeared to have improved at follow-up relative to the placebo-group in terms of disability, pain and depressed mood. CONCLUSION: This pilot study demonstrates the feasibility and acceptability of the design. A full, randomized, controlled trial is required to confirm the efficacy of the interventions developed here

Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients.</p> <p>Methods</p> <p>We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test.</p> <p>Results</p> <p>The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001).</p> <p>Conclusion</p> <p>Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.</p

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell

The correlation and level of agreement between end-tidal and blood gas pCO2 in children with respiratory distress: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>To investigate the correlation and level of agreement between end-tidal carbon dioxide (EtCO₂) and blood gas pCO₂in non-intubated children with moderate to severe respiratory distress.</p> <p>Methods</p> <p>Retrospective study of patients admitted to an intermediate care unit (InCU) at a tertiary care center over a 20-month period with moderate to severe respiratory distress secondary to asthma, bronchiolitis, or pneumonia. Patients with venous pCO₂(vpCO₂) and EtCO₂measurements within 10 minutes of each other were eligible for inclusion. Patients with cardiac disease, chronic pulmonary disease, poor tissue perfusion, or metabolic abnormalities were excluded.</p> <p>Results</p> <p>Eighty EtCO₂-vpCO₂paired values were available from 62 patients. The mean ± <smcaps>SD</smcaps> for EtCO₂and vpCO₂was 35.7 ± 10.1 mmHg and 39.4 ± 10.9 mmHg respectively. EtCO₂and vpCO₂values were highly correlated (r = 0.90, p < 0.0001). The correlations for asthma, bronchiolitis and pneumonia were 0.74 (p < 0.0001), 0.83 (p = 0.0002) and 0.98 (p < 0.0001) respectively. The mean bias ± <smcaps>SD</smcaps> between EtCO₂and vpCO₂was -3.68 ± 4.70 mmHg. The 95% level of agreement ranged from -12.88 to +5.53 mmHg. EtCO₂was found to be more accurate when vpCO₂was 35 mmHg or lower.</p> <p>Conclusion</p> <p>EtCO₂is correlated highly with vpCO₂in non-intubated pediatric patients with moderate to severe respiratory distress across respiratory illnesses. Although the level of agreement between the two methods precludes the overall replacement of blood gas evaluation, EtCO₂monitoring remains a useful, continuous, non-invasive measure in the management of non-intubated children with moderate to severe respiratory distress.</p