Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia.

BACKGROUND: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. METHODS: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAF(c.1799T>A) mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. RESULTS: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15-2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27-2.58; P=0.001), and BRAF(c.1799T>A) mutation (HR 2.16; 95% CI 1.25-3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09-5.75; P=0.77). CONCLUSION: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells. RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours. CONCLUSION: Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cancer.

Hydroxy-propyl-methyl-cellulose is a safe and effective lifting agent for endoscopic mucosal resection of large colorectal polyps.

BACKGROUND: Endoscopic mucosal resection (EMR) is today the treatment of choice for flat and sessile colorectal lesion, the only concern being completeness of resection. One of the major issues is the choice of the infiltrating substance to enable a long-lasting cushion under the lesion. The aim of this study was to prospectively evaluate safety and efficacy of hydroxy-propyl-methyl-cellulose (HPMC) injection for this purpose. PATIENTS: All flat and sessile lesions of the colon and rectum larger than 20 mm and considered suitable for EMR were included. In all cases 0.8% HPMC solution was injected through a 23G needle, in quantity according to the endoscopist's indication. Primary endpoints of the study were: (1) ability to perform en bloc resection of the lesions by using this new injection means, (2) complete resection rate, and (3) early and late complication rate. RESULTS: We resected 27 flat, sessile, or laterally spreading lesions up to 60 mm (28 mm average). Mean dose of HPMC injected was 10.2 ml (range 8-40 ml). Median procedure time was 32 min (range 15-105 min). En bloc resection was achieved in up to 21 cases (78%). Histologically detected complete tumour removal was achieved in 23 lesions, whereas lateral margins could not be properly evaluated in 4 cases due to coagulation artefacts. No perforation was observed. Procedural spurting bleeding was managed by epinephrine injection in one case and clip application in the remaining. Two case of local recurrence of adenomatous tissue were observed at 3 and 12 months, and treated by EMR. No complication related to the use of HPMC was observed. CONCLUSIONS: Injection of HPMC for EMR resulted safe and effective, allowing en bloc resection in the majority of cases with a limited number of complications. Continued progress in the field will include more outcomes research and techniques simplification.

Humanoid assessing rehabilitative exercises.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "New Methodologies for Patients Rehabilitation". BACKGROUND: The article presents the approach in which the rehabilitative exercise prepared by healthcare professional is encoded as formal knowledge and used by humanoid robot to assist patients without involving other care actors. OBJECTIVES: The main objective is the use of humanoids in rehabilitative care. An example is pulmonary rehabilitation in COPD patients. Another goal is the automated judgment functionality to determine how the rehabilitation exercise matches the pre-programmed correct sequence. METHODS: We use the Aldebaran Robotics' NAO humanoid to set up artificial cognitive application. Pre-programmed NAO induces elderly patient to undertake humanoid-driven rehabilitation exercise, but needs to evaluate the human actions against the correct template. Patient is observed using NAO's eyes. We use the Microsoft Kinect SDK to extract motion path from the humanoid's recorded video. We compare human- and humanoid-operated process sequences by using the Dynamic Time Warping (DTW) and test the prototype. RESULTS: This artificial cognitive software showcases the use of DTW algorithm to enable humanoids to judge in near real-time about the correctness of rehabilitative exercises performed by patients following the robot's indications. CONCLUSION: One could enable better sustainable rehabilitative care services in remote residential settings by combining intelligent applications piloting humanoids with the DTW pattern matching algorithm applied at run time to compare humanoid- and human-operated process sequences. In turn, it will lower the need of human care.

Endoclipping for gastric perforation secondary to second session of EMRC in locally residual early gastric cancer: a case report.

A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap-fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic follow-up at 1 and 3 months after the procedure. By the third month of follow up, biopsies of a slightly depressed scar area showed an high grade epithelial dysplasia. For this reason a second endoscopic resection (ER) was performed using the oblique soft cap. A perforation in the site of endoscopic resection was immediately observed. The complication was treated successfully by the application of seven clips.