Endoscopic submucosal dissection in a European setting. A multi-institutional report of a technique in development.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technique for "en bloc" resection of superficial tumors of the gastrointestinal tract. In France, experience with this technique is still limited. We wanted to assess the development of ESD in France, with special attention to short term outcomes. PATIENTS AND METHODS: Members of the Société Française d'Endoscopie Digestive (SFED) who declared performing ESD reported their cases prospectively on a voluntary basis. Demographic, clinical, and technical data, and the results of immediate complications were collected. Case reports were completed prospectively by each investigator before pooled analysis. RESULTS: A total of 188 consecutive case reports were collected from 16 centers. The median case mix per center was 6 patients (range 1-43). The lesion sites treated by ESD were the stomach (n = 75), esophagus (n = 27), duodenum (n = 1), cecum (n = 2), right colon (n = 3), transverse colon (n = 5), sigmoid (n = 3), and rectum (n = 72). The median size of the lesions was 26 mm (range 2-150 mm). En bloc resection was achieved in 77.1% of cases, with complete R0 resection in 72.9%. Histopathology results showed high grade dysplasia or superficial cancer in 71.2%. The median duration of ESD was 105 minutes (range 20-450 minutes). The short term morbidity was 29.2% including 34 cases of perforation (18.1%), and 21 hemorrhages (11.2%) during the 24 hours following ESD, 89% of which were managed conservatively or endoscopically. CONCLUSION: In this early experience, the feasibility of ESD appeared to be good but R0 resection and complication rates did not match those reported by Japanese authors and must be improved by an extended practice.

Accuracy of computed tomographic colonography in a nationwide multicentre trial, and its relation to radiologist expertise.

OBJECTIVE: Reports on the accuracy of computed tomographic colonography (CTC) mainly involve series from expert institutions. The aims of this study were to assess CTC accuracy in a nationwide population and to relate it to radiologist performance in their initial training. DESIGN: Nationwide multicentre trial. SETTING: Twenty-eight radiologists, working in 26 mostly academic clinical units, were involved in the study after having attended a formal specialised 2-day training session on CTC. They worked through a training set of 52 cases with automatic feedback after an attempt at each case. PATIENTS: The study enrolled 845 patients with average and high risk of colorectal cancer, 737 of whom had both complete CTC and videocolonoscopy data, which constituted the dataset. INTERVENTIONS: Patients underwent same-day CTC followed by videocolonoscopy with segmental unblinding of CTC results. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive and negative predictive values for detection of polyps ≥ 6 mm in per-patient and per-lesion analyses of CTC without computer-aided detection. RESULTS: Sensitivity, specificity and positive and negative predictive values for patients with polyps ≥ 6 mm were 69% (95% CI 61% to 77%), 91% (95% CI 89% to 94%), 67% (95% CI 59% to 74%) and 92% (95% CI 90% to 94%), respectively. Univariate analysis showed that the detection rate for polyps ≥ 6 mm was linked to neither radiologist case volume nor number of polyps, but was related to sensitivity achieved in the training set. Pooled sensitivity was 72% (95% CI 63% to 80%) versus 51% (95% CI 40% to 60%) for radiologists achieving above and below median sensitivity in the training set (61%), respectively. Multivariate analysis showed that sensitivity for polyps ≥ 6 mm in the training set was the only remaining significant predictive factor for subsequent performance. CONCLUSIONS: Radiologist sensitivity CTC for detection of polyps ≥ 6 mm in training was the sole independent predictor for subsequent sensitivity in detection of such polyps.

Primary chemotherapy with or without colonic stent for management of irresectable stage IV colorectal cancer.

AIM: Management of patients with irresectable stage IV colorectal cancer is controversial. Since 2000, we have favoured primary chemotherapy with stent insertion in case of obstructive tumor. Our aim was to report the results of this strategy in an unselected consecutive series of patients. PATIENTS AND METHODS: From 2000 to 2007, 68 of 115 consecutive patients admitted with stage IV colorectal cancer were considered irresectable. Data were collected prospectively. Feasibility and outcomes were analysed in an intention to treat basis. RESULTS: Of 68 patients, 37 received the intended primary chemotherapy, with stent insertion in 19, 13 required surgery as initial management and 18 patients received supportive care only. Twelve patients in the primary chemotherapy group developed local complication, including bowel obstruction in 9, successfully managed by stent in 6 of them. In patients requiring surgery at presentation, mortality and morbidity were 31% and 77%, respectively. Overall, 41 patients received chemotherapy, of whom, 6 were downstaged to undergo curative resection. Median survival was 6.7 and 15.4 months for the whole series and patients treated by primary chemotherapy, respectively (p<0.0001). On multivariate analysis, age, CEA level, primary chemotherapy and secondary curative resection were independently associated with survival. CONCLUSION: In unselected patients with irresectable stage IV colorectal cancer, primary chemotherapy with or without stent is feasible in more than 50% of cases and is associated with a low rate of secondary surgery for complicated primary tumor. This strategy may represent the best palliation in these patients for both duration and quality of survival.

Association between entero-hepatic Helicobacter species and Crohn's disease: a prospective cross-sectional study.

BACKGROUND: The pathogenesis of Crohn's disease (CD) involved microbial factors. Some Helicobacter species, the so-called entero-hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans. Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies. METHODS: Two groups of patients were included prospectively in a multicentre cross-sectional study: CD patients with an endoscopic post-operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis. RESULTS: In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age-adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04-6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis. CONCLUSION: Crohn's disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.

Fibrin glue sealing in the treatment of a recto-urethral fistula in Crohn's disease: a case report.

Recto-urethral fistulas in Crohn's disease are rare, and managing them is difficult. The various surgical techniques are not reliably effective and are associated with a significant risk of morbidity. The rectal mucosal transposition flap technique, which is used most frequently, requires the rectal mucosa to be in a healthy condition. We report here on a case where treatment was by injecting fibrin glue into a complex fistula with a single anorectal point of origin but combining a median recto-urethrocutaneous tract with two deep lateral rectoperineal tracts. The patient had presented with active rectal Crohn's disease. This treatment produced complete closure, verified by MRI, of all the fistula tracts, which was still maintained after three years, and with normal anal continence. When confronted with this type of fistula, and particularly when the condition of the rectal mucosa is poor, the specialist should be encouraged by this good result to consider the injection of fibrin glue, a technique without risk of morbidity, as a first course of action.

Chemotherapy has also an effect on primary tumor in colon carcinoma.

BACKGROUND: This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors. METHODS: Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface. Tumor regression grade (TRG) was determined by the amount of residual tumor cells and was graded from 1 to 5. RESULTS: No patient had complete histological response. Major histological tumor regression (TRG2) was observed in 70% of patients treated by CT and none of the not treated patients (P < 0.0001). Fibrosis, acellular necrosis, and surface changes were significantly increased in the CT group. TRG in the primary was comparable to the TRG in the corresponding liver metastases for 7/9 patients who underwent both colonic and hepatic resection after CT. CONCLUSION: CT induces major histological response in 70% of colon cancers. Response to CT in the primary and the corresponding liver metastases are correlated. These results support a policy of initial CT management for stage IV colon cancer and may warrant future studies of neoadjuvant CT in locally advanced colon carcinomas.

High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas.

BACKGROUND AND AIMS: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. METHODS: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. RESULTS: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. CONCLUSIONS: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs.

[Haemolytic uremic syndrome and acute mesenteric ischemia caused by interferon-alpha-2b in the treatment of Kaposi's sarcoma in an AIDS patient]. / Syndrome hémolytique et urémique et ischémie mésentérique aiguë lors d'un traitement par interféron alpha-2b pour une maladie de Kaposi associée au VIH.

BACKGROUND: Interferon alpha is approved for the treatment of Kaposi's sarcoma in HIV infected patients. Hemolytic and uremic syndrome (HUS) is a rare side-effect of interferon alpha and has been reported primarily in chronic myelogenous leukemia. CASE REPORT: A 44-year-old HIV-infected woman from Cameroon was admitted for treatment of cutaneous Kaposi's sarcoma. Two days later, she presented severe HUS. Abdominal pains subsequently revealed non-occlusive mesenteric ischemia. The patient rapidly improved after interferon withdrawal. DISCUSSION: To our knowledge this is the first case of HUS induced by interferon alpha given for Kaposi's sarcoma. Further, no cases of acute mesenteric ischemia have been reported with interferon alpha. It is possible that the condition may have been induced or aggravated by HUS or a low infusion rate. Interferon can exert vascular toxicity on both the mesenteric vessels and the renal vessels in a setting of microangiopathy.

[Portal vein thrombosis associated with a myeloproliferative disorder, prothrombin G20210A mutation, antiphospholipid syndrome, with repermeation during anticoagulant therapy]. / Thrombose portale récente régressive sous anticoagulants secondaire à un syndrome myéloprolifératif latent, une mutation G20210A du gène de la prothrombine et un syndrome des antiphospholipides.

Portal vein thrombosis, except in hepatocellular carcinoma and severe cirrhosis, is due to one or several prothrombotic disorders with or without a local precipitating factor. We report a case of a portal and splenic vein thrombosis, without cavernoma and varices which occurred in a 72-year-old man with abdominal pain and weakness. Three prothrombotic states including latent myeloproliferative disorder, antiphospholipid syndrome, and factor II G202101 mutation, were observed. Anticoagulant treatment resulted in complete repermeation of the portal and splenic veins without a hemorrhagic event. This illustrates that several prothrombotic states may occur in a single patient with portal vein thrombosis. Early anticoagulant therapy, in recent portal vein thrombosis, can result in repermeation.