Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer

Colorectal cancer (CRC) is a major public health issue worldwide, and novel tumor markers may contribute to its efficient management by helping in early detection, prognosis or surveillance of disease. The aim of our study was to identify new serum biomarkers for CRC, and we followed a phased biomarker discovery and validation process to obtain an accurate preliminary assessment of potential clinical utility. We compared colonic tumors and matched normal tissue from 15 CRC patients, using two-dimensional difference gel electrophoresis (2D-DIGE), and identified 17 proteins that had significant differential expression. These results were further confirmed by western blotting for heat shock protein (HSP) 60, glutathione-S-transferase Pi, α-enolase, T-complex protein 1 subunit β, and leukocyte elastase inhibitor, and by immunohistochemistry for HSP60. Using mAbs raised against HSP60, we developed a reliable (precision of 5–15%) and sensitive (0.3 ng·mL−1) immunoassay for the detection of HSP60 in serum. Elevated levels of HSP60 were found in serum from CRC patients in two independent cohorts; the receiver-operating characteristic curve obtained in 112 patients with CRC and 90 healthy controls had an area under the curve (AUC) of 0.70, which was identical to the AUC of carcinoembryonic antigen. Combination of serum markers improved clinical performance: the AUC of a three-marker logistic regression model combining HSP60, carcinoembryonic antigen and carbohydrate antigen 19-9 reached 0.77. Serum HSP60 appeared to be more specific for late-stage CRC; therefore, future studies should evaluate its utility for determining prognosis or monitoring therapy rather than early detection

Molecular Evolution of the Neuropeptide S Receptor

The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR

Rectocolite ulcéro-hémorragique (existe-t-il encore une place pour la conservation rectale ? Résultats comparatifs des anastomoses iléo-rectales et des anastomoses iléo-anales)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Valeur pronostique de la cytologie péritonéale dans les adénocarcinomes digestifs (protocole EVOCAP 2 : étude prospective multicentrique : analyse intermédiaire)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Traitement chirurgical coelioscopique de la pubalgie du sportif (série prospective à propos de 27 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Selection of patients and staging of peritoneal surface malignancies

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, thanks to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), has an important development. Due to its significant, but acceptable, morbidity and mortality, and high cost, this comprehensive management plan requires knowledgeable patient selection. Quantitative prognostic indicators are required to assess a patient’s eligibility. Large multicenter studies have identified several prognostic factors, which can be used for a better selection of patients who would benefit from the combination of cytoreductive surgery with HIPEC. Indications for treatment of PC with cytoreduction and HIPEC are now validated for several diseases: peritoneal mesothelioma, pseudomyxoma peritonei, PC from the appendix, and colorectal cancer. Indications are still under discussion for gastric and ovarian carcinomatosis. Computed tomography is the best radiological for staging the disease. The extent of peritoneal carcinomatosis is, however, difficult to evaluate preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with HIPEC for the treatment of peritoneal carcinomatosis should be performed for young patients with limited and resectable carcinomatosis, in specialized institutions involved in the management of peritoneal surface malignancies

Correction to: Postoperative ileus concealing intra-abdominal complications in enhanced recovery programs—a retrospective analysis of the GRACE database

International audienceWhen the original article was first published the given name and family names of Francophone Group for Enhanced Recovery After Surgery (GRACE) individually cited within the author list were inadvertently interchanged. The author list are correctly cited in this Correction

Enrichment of Circulating and Mucosal Cytotoxic CD8+ T Cells Is Associated with Postoperative Endoscopic Recurrence in Patients with Crohn's Disease

International audienceBACKGROUND AND AIMS: Evidence from mouse colitis models indicates that cytotoxic CD8+ T cells [CTL] play a key role in the initiation of gut lesions. We investigated whether changes in CD8+ CTL in blood or lamina propria [LP] of the neoterminal ileum were associated with postoperative endoscopic recurrence of Crohn's disease [CD]. METHODS: A total of 37 CD patients with ileocolonic resection were endoscopically followed up at 6 and 12 months post-surgery. CD8+ T cells were analysed by flow cytometry in blood and ileal LP. RESULTS: Granzyme B- and perforin-producing CD8+ T cells were significantly increased at 6 months in blood and in ileum LP in patients with endoscopic recurrence, as compared with those in remission. At a cutoff point of 45% of CD8+ CTL, the overall accuracies of the frequency of blood granzyme B+ or perforin+ CD8+ T cells to identify patients with postoperative endoscopic recurrence were 77% and 83%, respectively. Interestingly, patients with endoscopic recurrence at 12 months were those showing the highest mucosal CD8+ CTL frequency at 6 months, while still in remission. CONCLUSIONS: Enrichment of cytotoxic CD8+ T cells in blood and ileal mucosa coincides with CD postoperative endoscopic recurrence. This underscores that CD8 CTL may play a pathophysiological role in the initiation of gut lesions during CD

Intraoperative nasogastric tube during colorectal surgery may not be mandatory: a propensity score analysis of a prospective database

International audienceBACKGROUND: Avoiding the use of nasogastric tubes (NGTs) is recommended after colorectal surgery but there is no consensus on intraoperative gastric decompression using NGTs during colorectal surgery. The objective was to assess the effect of avoiding insertion of NGTs during colorectal surgery for the recovery of gastrointestinal (GI) functions. METHOD: 1561 patients undergoing colorectal surgery, for whom information on NGT use was available, were included in this retrospective analysis and propensity score analysis of the prospective GRACE Audit database. Patients who did and did not have an NGT during surgery were compared. RESULTS: Among the study population of 1561 patients, 696 patients were matched to correct baseline differences between groups. The no-NGT group significantly improved GI motility impairment (e.g., less postoperative nausea [OR = 0.59; CI 95%: 0.42-0.84] and a better tolerance of early feeding [OR = 2.07; CI 95%: 1.33-3.22]). Such an association was also highlighted for reduced postoperative morbidity [OR = 0.60; CI 95%: 0.43-0.83], and especially pulmonary complications [OR = 0.08; CI 95%: 0.01-0.59], or parietal complications [OR = 0.29; CI 95%: 0.09-0.87]. The risk of postoperative ileus was not significantly reduced in the no-NGT group [OR = 0.67; CI 95%: 0.43-1.06]. CONCLUSION: No NGT insertion during colorectal surgery is safe and could improve postoperative GI function recovery