Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the TOPICOP score.

BACKGROUND: Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries. METHODS: This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire. RESULTS: A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country. CONCLUSIONS: The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.

Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer.

Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.

What's new in atopic eczema? An analysis of systematic reviews published in 2012 and 2013. Part 1. Epidemiology, mechanisms of disease and methodological issues.

This review provides a summary of key findings from nine systematic reviews on atopic eczema (AE) published over the 2-year period from January 2012 to 31 December 2013, focusing on epidemiology, mechanisms of disease and methodological issues. There is now reasonable evidence to suggest that antibiotic exposure in early life is associated with increased incidence of AE, but delivery by caesarean section is not. The prevalence of AE is increasing in Africa, eastern Asia, western Europe and parts of northern Europe. Autoimmunity may play a part in the development and subsequent severity of AE. For researchers conducting clinical trials and other prospective studies involving patients with AE, the two best-validated scales for capturing objective clinical signs of AE are the Eczema Assessment Severity scale (EASI) and the objective SCORing Atopic Dermatitis scale (objSCORAD). For the assessment of quality of life in children aged 0-3 years, the Infant Dermatitis Quality of Life scale (IDQoL) is reasonably well validated. A standardized definition of an incident case of AE for use in prevention studies is still required.

What's new in atopic eczema? An analysis of systematic reviews published in 2012 and 2013. Part 2. Treatment and prevention.

This review provides a summary of key findings from 22 systematic reviews on atopic eczema (AE) published over the 2-year period from January 2012 to 31 December 2013, focusing on prevention and treatment of AE. For an update of systematic reviews on the epidemiology, mechanisms of disease and methodological issues, see Part 1 of this update. Based on current systematic review evidence, the most promising intervention for the prevention of AE is the use of probiotics (and possibly prebiotics) during the late stages of pregnancy and early life. Exposure to household pets, especially dogs, may also be protective, but exclusive breastfeeding for up to 7 months does not confer benefit. The role of vitamin D in preventing AE is currently unclear. Very few of the systematic reviews provided additional evidence for the use of specific treatments for AE. Further research is required to establish the role of desensitization, Chinese herbal medicines, homeopathy and specialist clothing. Nevertheless, there is now clear evidence that evening primrose oil and borage oil are not effective for the treatment of AE. There have been no randomized controlled trials on the use of H1 anti-histamines as monotherapy for the treatment of AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2010-11.

This review provides a summary of key findings from 24 systematic reviews of atopic eczema (AE) published or indexed between 1 August 2010 and 31 December 2011, updating published summaries from previous years. Epidemiological evidence points to the protective effects of early daycare, endotoxin exposure, consumption of unpasteurized milk, and early exposure to dogs, but antibiotic use in early life may increase the risk for AE. With regard to prevention of AE, there is currently no strong evidence of benefit for exclusive breastfeeding, hydrolysed protein formulas, soy formulas, maternal antigen avoidance, omega-3 or omega-6 fatty-acid supplementation, or use of prebiotics or probiotics. With respect to AE treatments, the most compelling new systematic review evidence was for proactive treatment with topical anti-inflammatory agents (topical corticosteroids and topical calcineurin inhibitors) for the prevention of AE flares in patients with moderate to severe AE. A meta-analysis of 4 trials confirmed the superiority of tacrolimus 0.1% over pimecrolimus for the treatment of AE, and a review of 17 trials found that tacrolimus (0.1% or 0.03%) was broadly similar in efficacy to mild/moderate topical corticosteroids. Evidence for the role of education in the management of AE was less conclusive, with evidence from randomized controlled trials showing mixed results. Further work is needed in this area to conduct high-quality trials of educational interventions that are clearly described and reproducible. There is no clear evidence for the efficacy of homeopathy, botanical extracts or Chinese herbal medicine in the treatment of AE, as large well-designed trials are lacking in these areas.

Chronic treatment with a glucokinase activator delays the onset of hyperglycaemia and preserves beta cell mass in the Zucker diabetic fatty rat.

AIMS/HYPOTHESIS: Glucokinase activators (GKAs) are currently being developed as new therapies for type 2 diabetes and have been shown to enhance beta cell survival and proliferation in vitro. Here, we report the effects of chronic GKA treatment on the development of hyperglycaemia and beta cell loss in the male Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes with severe obesity. METHODS: Cell protection by GKA was studied in MIN6 and INS-1 cells exposed to hydrogen peroxide. Glucose homeostasis and beta cell mass were evaluated in ZDF rats dosed for 41 days with Cpd-C (a GKA) or glipizide (a sulfonylurea) as food admixtures at doses of approximately 3 and 10 mg kg(-1) day(-1). RESULTS: Incubation of MIN6 and INS-1 832/3 insulinoma cell cultures with GKA significantly reduced cell death and impairment of intracellular NADH production caused by exposure to hydrogen peroxide. Progression from prediabetes (normoglycaemia and hyperinsulinaemia) to overt diabetes (hyperglycaemia and hypoinsulinaemia) was significantly delayed in male ZDF rats by in-feed treatment with Cpd-C, but not glipizide. Glucose tolerance, tested in the fifth week of treatment, was also significantly improved by Cpd-C, as was pancreatic insulin content and beta cell area. In a limited immunohistochemical analysis, Cpd-C modestly and significantly enhanced the rate of beta cell proliferation, but not rates of beta cell apoptosis relative to untreated ZDF rats. CONCLUSIONS/INTERPRETATION: These findings suggest that chronic activation of glucokinase preserves beta cell mass and delays disease in the ZDF rat, a model of insulin resistance and progressive beta cell failure.

IgE antibodies to omega-5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children.

BACKGROUND: Gliadins have been implicated in immunoglobulin E (IgE)-mediated allergy to ingested wheat and omega-5-gliadin is known to represent a major allergen in wheat-dependent exercise-induced anaphylaxis. Less known is whether omega-5-gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to omega-5-gliadin (sIgE-omega-5-gliadin-ab) could be used as a marker for oral wheat challenge outcome in wheat-sensitized children. A secondary objective was to study whether the level of sIgE-omega-5-gliadin was related to symptom severity in children with a positive challenge test. METHODS: Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE-omega-5-gliadin-ab was related to a physician's diagnosis of wheat allergy and challenge symptoms. RESULTS: The mean concentration of sIgE-omega-5-gliadin-ab was 7.25 kU(A)/l in patients with wheat allergy and 1.08 kU(A)/l in patients with no wheat allergy (P < 0.01). sIgE-omega-5-gliadin-ab was only detected in 12 of the non-wheat allergic children and 11 of them had a specific IgE to wheat below 1.30 kU(A)/l. Children reacting with severe symptoms upon challenge (n = 8) had increased levels of sIgE-omega-5-gliadin-ab compared to children with moderate, mild or no symptoms (P < 0.001). CONCLUSIONS: The presence of sIgE-omega-5-gliadin-ab is related to the reaction level to wheat challenge outcome in wheat-sensitized children. The sIgE-omega-5-gliadin-ab was found to be associated with a strong convincing history of wheat allergy also in those cases when oral food challenge was avoided. The sIgE-omega-5-gliadin-ab level may serve as a marker for clinical reactivity in wheat-sensitized individuals.

Relapse of neonatal herpes simplex virus infection.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. Recurrence of skin vesicles is common. OBJECTIVE: To determine the features of relapse and identify the factors related to relapse. DESIGN: Thirty two surviving patients with neonatal herpes virus infections were enrolled. All patients received acyclovir treatment. Clinical and virological data were analysed and compared between relapsed and non-relapsed cases. RESULTS: Thirteen (41%) had either local skin or central nervous system relapse between 4 and 63 days after completing the initial antiviral treatment. Nine patients exhibited local skin relapses, and four developed central nervous system relapses. In one skin and two central nervous system relapse cases, neurological impairment later developed. Type 2 virus infection was significantly related to relapse (odds ratio 10.4, 95% confidence interval 1.1 to 99.0). Patients with relapse had worse outcomes than those without relapse. CONCLUSION: Neonates with HSV type 2 infections have a greater risk of relapse. Relapsed patients have poorer prognoses.

Detection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients.

Peritoneal recurrence after curative resection of malignant tumor with negative cytology is considered to be caused by microscopic dissemination of the exfoliated cancer cells from primary tumors to serosal surfaces at the time of operation, not detectable with conventional diagnostic tools. We applied the reverse transcriptase-polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK 20) to detect micrometastatic foci in the peritoneal cavity of colon cancer patients. Cytological samples taken by peritoneal lavage from a series of 79 colon cancer patients were analyzed microscopically, for CEA levels, and by RT-PCR analysis using nested primers for CEA and CK 20. Cases with both CEA and CK 20 signals were defined as PCR-positive. This RT-PCR method proved both sensitive (1 tumor cell/10(6) non-tumor cells on preparation of serial colorectal cancer cell dilutions) and specific (no false positive results, 0/23 tested in our control experiment). Intraperitoneal micrometastatic cells were detected in peritoneal lavage 7.6% by cytology, 17.7% by CEA levels, and 24.1% by RT-PCR (significantly higher than by cytology: p=0.0046). RT-PCR detection rate increased in parallel with pathological depth of tumor invasion, and also a pathological stage-dependence was suggested according to the tumor-node-metastasis classification of the International Union Against Cancer. Our results suggest that CEA and CK 20 mRNA identification by RT-PCR appeared to be reliable and may be useful for early diagnosis in peritoneal dissemination of colon cancer.

Malolactomycin D, a potent inhibitor of transcription controlled by the Ras responsive element, inhibits Ras-mediated transformation activity with suppression of MMP-1 and MMP-9 in NIH3T3 cells.

To search for anti-cancer agents, a screening system for Ras signal inhibitors was developed using a NIH3T3 cell line with an introduced reporter gene which is controlled by the Ras-responsive element (RRE). With this screening system, malolactomycin D was identified as a selective inhibitor of transcription from the RRE. This compound was found to preferentially inhibit the anchorage-independent growth rather than the anchorage-dependent growth of Ras-transformed NIH3T3 cells. The expression of matrix metalloproteinases MMP-1 and MMP-9, which have RRE in their promoters, were reduced by treatment with malolactomycin D at the translational and transcriptional levels. Analysis of the activity of mitogen-activated protein (MAP) kinases, which play important roles in transduction of the Ras signal, showed that malolactomycin D inhibits the activation of p38 MAP kinase and Jun N-terminal-kinase (JNK) but not extracellular signal-regulated kinase 1 or 2 (ERK1 or 2). These findings suggest that by inhibiting the pathway that leads to the activation of p38 MAP kinase and JNK, malolactomycin D suppresses the expression of MMPs. Since MMPs play important roles in metastasis and maintenance of the microenvironment of tumor cells, both of which facilitate tumor growth, the inhibition of MMPs by malolactomycin D is believed to contribute to its ability to inhibit Ras-mediated tumorigenesis.

A simple method for classification of cell death by use of thin layer collagen gel for the detection of apoptosis and/or necrosis after cancer chemotherapy.

To assess the efficacy of cancer chemotherapy, an important index is apoptosis of the target cells, which can usually be confirmed by electron microscopy (EM). We established a new experimental technique, whereby cancer cells (MKN45) were distributed in thin collagen gel as one or two cell layers, and cultured with anti-cancer drugs (5-FU and CDDP). The cells were stained with fluorescent Hoechst 33258 (Ho) and photographed, then with hematoxylin and eosin (H&E) and again photographed, and processed for EM. This approach allowed us to characterize the patterns of death of single cells in detail. There were six patterns of cell damage: two patterns of apoptosis, early peripheral condensation of chromatin and late apoptotic bodies, two patterns of necrosis, cytoplasmic swelling and washed-out images, and two further patterns, with morphological features of both apoptosis and necrosis, neither classified into necrosis nor apoptosis. The results show that cell death patterns can be mostly determined by combining observations of Ho and H&E-stained cells without the necessity for EM observation.

[Preparation of a gel-forming ointment base applicable to the recovery stage of bedsore and clinical evaluation of a treatment method with different ointment bases suitable to each stage of bedsore].

A novel ointment base suitable for the treatment of bedsore at the recovery stage was developed by the use of hydroxypropyl methylcellulose (HM-HPMC) modified on the basis of the hydrophobicity. A considerable sustained release of drug (minocycline hydrochloride) formulated to the ointment (T50 of 170 min) was attained with a macrogol ointment (MO) mixed with the HM-HPMC and Carbopol (CP) of the formulating ratio of 3:7. It was also found that a change in the formulating ratio of HM-HPMC and CP lead to a change in the drug release rate. The water absorption property of the ointment base, required to absorb on exudative solution in applying to the bedsore treatment, was as high as that of an ointment base containing hydroxypropyl cellulose (HPC) and CP reported in our previous paper. We clinically evaluated the effectiveness of the bedsore treatment, in which different ointment bases were applied to patients at different stages of the bedsore. A total of 22 cases were divided into two categories for applying to the different treatments. One category comprised of 11 subjects was treated with a povidone-iodine sugargel, which was the conventional method in our hospital, while the other 11 subjects were treated by the use of the newly developed ointment bases in consideration for the different stages of the bedsore. In comparison of the clinical results with the healing index, we ascertained that the latter method was significantly more efficacious (p < 0.01-0.05) than the conventional one. The effectiveness was emphasized in treating the intractable bedsore classified into the grades IV and V. Therefore, we confirmed that the newly developed ointment base formulation is useful in treating bedsore at each stage.

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

Congenital balloon digits in two neonates caused by constriction rings.

Balloon digits were found in two neonates with congenital constriction ring syndrome. The affected digits were the right long finger and right great toe. They were surgically treated at the age of 10 and 9 days, respectively. Morphologic improvement was dramatic after surgery. In cases with extensive enlargement, severe cyanosis, redness, and no subsidence of edema within several days after birth, early operative treatment may be necessary to maintain digit viability and prevent autoamputation due to circulatory embarrassment. It can also be helpful to prevent fibrosis of the subcutaneous tissue. Pathologic examination revealed marked proliferation of fibrous tissue and lymphatic vessels.

Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers.

Members of the recently identified family of Homo sapiens Aurora / Ipl1-related kinases (HsAIRKs), homologous to chromosome segregation kinases, fly Aurora and yeast Ipl1, are highly expressed during M phase, and have been suggested to regulate centrosome function, chromosome segregation, and cytokinesis. In the present study, immunohistochemical analyses were performed of HsAIRK1 and HsAIRK3 expression in 78 primary colorectal cancers and 36 colorectal adenomas as well as 15 normal colorectal specimens. In normal colon mucosa, some crypt cells showed weak positive staining in 10 and 12 out of 15 cases for HsAIRK1 and HsAIRK3, respectively, the remaining cases being negative. Elevated expression of HsAIRK1 was observed in 53 (67.9%) of the colorectal cancers, and of HsAIRK3 in 40 (51.3%). Furthermore, colorectal adenomas showed high expression of HsAIRK1 and HsAIRK3 in 11 (30.6%) and 7 (19.4%) cases, respectively, thus being intermediate between colorectal cancers and normal colorectal mucosa. Interestingly, HsAIRK1 overexpression was significantly associated with pT (primary tumor invasion) and p53 accumulation in colorectal cancers. There was no significant correlation between proliferating cell nuclear antigen-labeling index (PCNA-LI) and the levels of these proteins. The results suggest that overexpression of HsAIRK1 and HsAIRK3 might be involved in tumorigenesis and / or progression of colorectal cancers.

Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers.

BACKGROUND/AIMS: In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22-24. The aim of the present study was to determine the type of alterations in primary rectal cancers as well as colon cancers and the correlation between these alterations and clinicopathological data. METHODS: Mutation analyses of the PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit (Huntington elongation A subunit TOR (HEAT) repeats 11-15) and partial binding sites of the regulatory B subunit were carried out on cDNA samples from 30 primary colorectal cancer specimens and corresponding normal tissues using a combination of the polymerase chain reaction and subsequent direct DNA sequencing. RESULTS: Five missense mutations producing amino acid substitutions were detected in the four colon cancer cases (13.3%; four of 30 colorectal cancers): (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine (ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)valine (GTA) to glycine (GGA), and (365)serine (TCT) to proline (CCT). Of these five mutations, three (60%) were located in HEAT repeat 13 and four (80%) showed T to other nucleotide substitutions. In addition, a normal polymorphism, (478)leucine, was found. No correlation was found between these mutations and clinicopathological data. CONCLUSION: Our results suggest that the PPP2R1B gene is one of the true targets at 11q23, and its inactivation is involved in the development of all types of colorectal cancers.

Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection.

OBJECTIVE: To analyze the clinical value of reverse transcriptase-polymerase chain reaction (RT-PCR) recognition of mRNA coding for carcinoembryonic antigen (CEA) and cytokeratin 20 in blood obtained from patients with colorectal carcinoma. SUMMARY BACKGROUND DATA: RT-PCR has been applied to identify very small numbers of tumor cells. Molecular detection is thought to provide useful information for the clinical management of perioperative prophylaxis of tumor cell implantation or postoperative adjuvant therapy regimens. METHODS: From 52 patients with colorectal cancer, peripheral blood specimens were obtained before and after surgical manipulation; also, a specimen of mesenteric venous blood draining the colorectal tumor was obtained just before tumor resection. Using cDNA primers specific for CEA and cytokeratin 20, RT-PCR was performed to detect tumor cells. Subsequently, the 52 patients were divided into two groups, a group positive for both CEA and cytokeratin 20 and a group negative for CEA, cytokeratin 20, or both. RESULTS: On the basis of 450 days of follow-up data, the PCR-positive group had a significantly shorter overall survival than the PCR-negative group only with the mesenteric venous blood specimens. Multivariate analysis indicated that detection of the simultaneous presence of CEA and cytokeratin 20 mRNA in mesenteric venous blood is a potent prognostic factor independent of the traditional pathologic parameters. Of the eight peripheral blood specimens found to be PCR-positive, five showed a change of PCR from negative to positive during surgery, and liver metastases developed 11 months later in one of these five patients. CONCLUSIONS: Molecular detection of both CEA and cytokeratin 20 mRNA in mesenteric venous blood may be of prognostic value for patients with colorectal carcinoma. Molecular detection in the peripheral blood at surgery suggests that hematogenic tumor cell dissemination is a common and early event and that surgical manipulation enhances this release of tumor cells into the circulation.