The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue.

Intestinal invasion by the protozoan parasite Entamoeba histolytica is characterized by remodelling of the extracellular matrix (ECM). The parasite cysteine proteinase A5 (CP-A5) is thought to cooperate with human matrix metalloproteinases (MMPs) involved in ECM degradation. Here, we investigate the role CP-A5 plays in the regulation of MMPs upon mucosal invasion. We use human colon explants to determine whether CP-A5 activates human MMPs. Inhibition of the MMPs' proteolytic activities abolishes remodelling of the fibrillar collagen structure and prevents trophozoite invasion of the mucosa. In the presence of trophozoites, MMPs-1 and -3 are overexpressed and are associated with fibrillar collagen remodelling. In vitro, CP-A5 performs the catalytic cleavage needed to activate pro-MMP-3, which in turn activates pro-MMP-1. Ex vivo, incubation with recombinant CP-A5 was enough to rescue CP-A5-defective trophozoites. Our results suggest that MMP-3 and/or CP-A5 inhibitors may be of value in further studies aiming to treat intestinal amoebiasis.

Newly visualized fibrillar collagen scaffolds dictate Entamoeba histolytica invasion route in the human colon.

The extracellular matrix (ECM) and its role in the outcome of infectious diseases have been poorly investigated. In this study, we determined the impact of the collagen fibres architecture on the invasive process of the enteric parasite Entamoeba histolytica. The behaviour of E. histolytica wild-type and silenced for the cysteine protease A5 (CP-A5) were compared on a three-dimensional collagen matrix and within human colon fragments for fibrillar collagen cleavage and migration. The interstitial collagen fibres within the connective tissue of the human colon, visualized by multiphoton and second harmonic generation signals imaging, presented a dense scaffold at the subepithelial level and a loose meshwork within the chorion. To penetrate the tissue, E. histolytica migrated on the dense scaffold that remained intact, reached the crypt of Lieberkhün, migrated along and then disorganized the loose scaffold to escape into the mucosa. Interestingly, in vitro, CP-A5 was not required for collagenase activity and migration through the matrix but was necessary within the tissue environment for collagen meshwork remodelling and subsequent invasion. The data point out that further step of invasion relay with ECM destruction that requires human components induced or activated in the presence of CP-A5.

An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis.

Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.

[Intrabiliary metastasis in colorectal cancer]. / Métastase endobiliaire métachrone de cancer colique.

Endobiliary metastasis of colorectal cancers are rare. We report a 36 years-old patient, operated on 5 years ago for a left colon cancer with a left colectomy. He consulted for pain in the upper right quadrant without fever nor jaundice. Ultra-sound, CTscan, RMI and PET led to the diagnosis of endobiliary metastasis and the patient underwent a right hepatectomy. A review of the literature of the endobiliary metastasis follows this case-report. These tumours can mimic intrahepatic cholangiocarcinoma in clinical presentation, imaging or even histological examinations. The main goal of the imaging explorations is to establish the resecability of such tumours. Patients with endobiliary metastasis seem to have better survival than patients with intrahepatic metastasis.

Surgical treatment of rectal cancer: results of a strategy for selective preoperative radiotherapy.

AIM: The indications for preoperative adjuvant therapy in rectal cancer are still a subject of debate. The objective of this study was to analyze the results of surgical resection and selective radiotherapy in a group of high-risk patients (Dukes B and C) taken from a series of 148 consecutive patients with rectal cancer. METHODS: All patients with rectal cancer considered for resection during the period 1994-2004 were prospectively included. The policy was to deliver preoperative radiotherapy in cases of fixed or tethered tumors or when imaging predicted T3 tumors with positive circumferential margins. Other tumors were resected without neoadjuvant therapy. All resections were done using the total mesorectal excision (TME) technique. RESULTS: One hundred and forty-eight consecutive patients underwent rectal resection during the study period. A sphincter-saving technique was carried out in 134 patients (90%). No patient was excluded from the analysis. The perioperative mortality was 2/148 (1.5%). Curative surgery was obtained in 135 patients. The 94 patients with a Dukes B or C tumor formed the high-risk group that was the basis of our study. The mean follow-up in this group was 58 months (range 24-120). Twenty patients (21%) received preoperative radiotherapy (PRT) and 74 (79%) underwent surgical resection alone. A positive circumferential margin, defined as one that was < or =1 mm, was found in seven of the 85 patients (8.2%) for whom this measure was available. The actuarial five-year overall survival was 74%. Local recurrence developed in eight patients (8.4%): four in the PRT group (20%), and four in the non-PRT group (5.4%). Only two patients developed an isolated local recurrence. CONCLUSIONS: Preoperative adjuvant therapy can be safely omitted in patients who demonstrate clear circumferential margins on preoperative imaging, provided that adequate surgery is subsequently performed.

[Cytomegalovirus enterocolitis: a rare cause of gastrointestinal ischemia and bleeding]. / L'entérocolite a cytomégalovirus: une cause rare d'ischémie et d'hémorragie digestive.

Cytomegalovirus (CMV) infections are frequent in patients with severe immunodeficiency. We report a case of isolated digestive localization in a young woman initially non-immunocompromised. Initially, she was admitted in the intensive-care unit for a severe post-operative shock secondary to a respiratory distress syndrome. She then developed severe enterocolitis which was initially unexplained. Outcome was favorable but digestive perforations required multiple surgical digestive resections. The histological diagnosis was confirmed by immunofluorescence staining and the antigenemia and specific antibodies kinetics. We emphasize the various characteristics of this pathology and point out the risk of missing this unusual cause of digestive perforation and severe bleeding.

Functional results after the Orr-Loygue transabdominal rectopexy for complete rectal prolapse.

PURPOSE: The aim of this study was to assess functional results after Orr-Loygue transabdominal rectopexy for complete rectal prolapse. METHODS: Thirty-one consecutive patients operated on for complete rectal prolapse between 1995 and 1998 were evaluated preoperatively and postoperatively with regard to anal incontinence, constipation, evacuation difficulties, and overall satisfaction with a standardized questionnaire. Anal continence assessment was based on a clinical scoring system. RESULTS: After a mean follow-up of 28 +/- 13 (range, 12-57) months, no prolapse recurred. Preoperative and postoperative rates of incontinence were 81 percent (25/31) and 55 percent (17/31), respectively (P < 0.03). Continence improved in 24 (96 percent) of the 25 patients who were incontinent before surgery. The mean incontinence score decreased from 11.7 +/- 7.8 preoperatively to 3.2 +/- 4.2 postoperatively (P < 0.001). The self-reported constipation rate was 61 percent (19/31) before surgery and 71 percent (22/31) after surgery (P = nonsignificant). Constipation appeared or worsened in 16 patients (52 percent), whereas it disappeared or improved in 8 (26 percent; P = nonsignificant). Evacuation difficulties increased significantly after surgery from 23 percent (7/31) to 61 percent (19/31; P < 0.003). Ninety-seven percent of patients reported good or very good satisfaction. CONCLUSIONS: Transabdominal Orr-Loygue rectopexy resulted in improved continence and a high satisfaction level. Despite a significant postoperative increase in evacuation difficulties, only a 10 percent (nonsignificant) increase in the self-reported constipation rate was observed.

[Aerobilia: a rare consequence of anaerobic acute cholecystitis: a case report]. / L'aérobilie: une conséquence rare de la cholécystite aiguë à germes anaérobies.

Acute acalculous cholecystitis is rare in non critically ill or postoperative patients. We report a case of acute acalculous cholecystitis with secondary bile infection with Clostridium perfringens. Ultrasound and tomodensitometry revealed diffuse aerobilia. The germ in this case report is atypical and contrasts with the very discrete clinical findings. Aerobilia, secondary to the development of bacteria in the biliary tract falsely suggested a bilio-digestive fistula. Treatment included a simple cholecystectomy associated with 7 days of antibiotherapy.