Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30–40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

Aims To determine the clinicopathological features of colorectal cancer (CRC) in Crohn's disease (CD).Methods and results All histological slides from surgical specimens with inflammatory bowel disease-related colorectal neoplasia examined in our hospital between 1990 and 2005 were reviewed. We identified 18 CRCs in 16 patients with CD and compared them with 57 CRCs in 41 patients with ulcerative colitis (UC). We also studied 25 patients with dysplasia without cancer (CD 2, UC 23). When CD and UC were compared, the median age at diagnosis of cancer (CD 52 years, UC 51 years), the frequency of mucinous adenocarcinoma (CD 16.7%, UC 17.5%) and the frequency of dysplasia adjacent to and distal from cancer (CD 56.3 and 37.5%, UC 65.8 and 39%, respectively) were similar. All neoplastic lesions occurred in areas affected by inflammatory bowel disease.Conclusions CRC complicating CD and UC shares many clinicopathological features, in particular similar frequencies of dysplasia, both adjacent and distal, with cancer. Thus, surveillance for patients with Crohn's colitis should be similar to that for patients with UC. Consideration should be given to a more extensive UC-like surgical approach instead of segmental resection of the involved area.

Schistosomiasis, also known as bilharziasis, is an infection caused by trematodes of the genus schistosoma. Three schistosomal species cause most human infections, namely: S japonica , S haematobium , and S mansoni . Intestinal schistosomiasis classically associates with S mansoni , which is endemic in Africa, central south American countries, and in the Middle East.1 Infected persons complain of abdominal pain, diarrhoea, and bloody stools. Most lesions affect the rectum and the left colon. Patients’ tissues tend to be examined only when patients present with intussusception, mass lesions, or strictures that cause intestinal obstruction.2 We report a case of recurrent sigmoid volvulus in a patient incidentally found to have colonic schistosomiasis. A 40 year old man, a native of Angola who had immigrated to France five years previously, was referred to our hospital for treatment of a recurrent sigmoid volvulus. The resected colonic segment showed a dilated lumen of the greatly oedematous wall, with a 4 mm red sessile polyp located 2 cm from one edge. This polyp …

HistopathologyVolume 49, Issue 5 p. 533-536 Myxoid perineal tumour in a 25-year-old woman N Mourra, N Mourra Departments of Pathology, RadiologySearch for more papers by this authorC Hoeffel, C Hoeffel Departments of Pathology, RadiologySearch for more papers by this authorS Gaujoux, S Gaujoux Surgery, Hôpital Saint-Antoine, AP-HP, ParisSearch for more papers by this authorJ-M Coindre, J-M Coindre Institut Bergonie, Bordeaux, FranceSearch for more papers by this authorJ-F Flejou, J-F Flejou Departments of Pathology, RadiologySearch for more papers by this author N Mourra, N Mourra Departments of Pathology, RadiologySearch for more papers by this authorC Hoeffel, C Hoeffel Departments of Pathology, RadiologySearch for more papers by this authorS Gaujoux, S Gaujoux Surgery, Hôpital Saint-Antoine, AP-HP, ParisSearch for more papers by this authorJ-M Coindre, J-M Coindre Institut Bergonie, Bordeaux, FranceSearch for more papers by this authorJ-F Flejou, J-F Flejou Departments of Pathology, RadiologySearch for more papers by this author First published: 26 October 2006 https://doi.org/10.1111/j.1365-2559.2006.02526.xCitations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Angervall L, Kindblom LG, Merck C. Myxofibrosarcoma. A study of 30 cases. Acta Pathol. Microbiol. Scand. (A) 1977; 85; 127–140. 2 Mentzel T, Calonje E, Wadden C et al. Myxofibrosarcoma. Clinico-pathologic analysis of 75 cases with emphasis on the low-grade variant. Am. J. Surg. Pathol. 1996; 20; 391–405. 3 Weiss SW, Goldblum JR. Fibrosarcoma. In Enzinger and Weiss's soft tissues tumors, 4th edn. St Louis: Mosby 2001. 4 Steeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum. Report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm. Am. J. Surg. Pathol. 1983; 7; 463–475. 5 Kaur A, Makhija PS, Vallikad E, Padmashree V, Indira HS. Multifocal aggressive angiomyxoma: a case report. J. Clin. Pathol. 2000; 53; 798–799. 6 McCluggage WG. A review and update of morphologically bland vulvovaginal mesenchymal lesions. Int. J. Gynecol. Pathol. 2004; 24; 26–38. 7 Graadt Van Roggen JF, Unnik JAM, Briaire-de Bruijn IH, Hogendoorn PCW. Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up. Virchows Arch. 2005; 446; 157–163. 8 Siassi RM, Papadopoulos T, Matzel KE. Metastasizing aggressive angiomyxoma. N. Engl. J. Med. 1999; 341; 1772. 9 Blandamura S, Cruz J, Vergara LF, Puerto IM, Ninfo V. Aggressive angiomyxoma: a second case of metastasis with patient's death. Hum. Pathol. 2003; 34; 1072–1074. 10 Huang HY, Lal P, Qin J, Brennan MF, Antonescu CR. Low-grade myxofibrosarcoma: a clinicopathologic analysis of 49 cases treated of a single institution with simultaneous assessment of the efficacy of 3-tier and 4-tier grading systems. Hum. Pathol. 2004; 35; 612–621. Citing Literature Volume49, Issue5November 2006Pages 533-536 ReferencesRelatedInformation

Barrett's oesophagus is a premalignant condition that predisposes to the development of oesophageal adenocarcinoma. It is detected on endoscopy and confirmed histologically by the presence in the lower oesophagus of a metaplastic mucosa, the so-called specialised epithelium, which resembles incomplete intestinal metaplasia in the stomach. These similarities with incomplete intestinal metaplasia are present on histology, mucin histochemistry, and immunohistochemistry with various differentiation markers (cytokeratins and MUC antigens). On morphology, the carcinogenetic process of Barrett's mucosa progresses through increasing grades of epithelial dysplasia. Dysplasia, a synonym of intraepithelial neoplasia, is the only marker that can be used at the present time to delineate a population of patients at high risk of cancer. Among the numerous molecular events that have been shown to play a role in the neoplastic transformation of Barrett's mucosa, only changes in DNA ploidy, increased proliferation, and alterations of the p53 gene have been suggested to be of potential help in the surveillance of patients.

We read with great interest the well designed study of Couvelard et al ( Gut 2001; 49 :761–6). In agreement with other studies,1–3 the authors reported that cytokeratin (CK) 7 and 20 immunoreactivity in the specialised intestinal metaplasia found in Barrett’s oesophagus differs from the intestinal metaplasia found in the stomach. The specific pattern of CK7/CK20 expression, so-called Barrett’s type, is characterised by strong CK7 staining of both superficial and deep glands together with a strong superficial CK20 stain. The authors report that both clinical and endoscopic findings support this differentiation. The origin and development of intestinal metaplasia at the gastro-oesophageal junction have been a matter for debate. There are findings suggesting that intestinal metaplasia of the cardia has an immunophenotype similar to Barrett’s oesophagus3 while others suggest that it is similar to the rest of the gastric mucosa.1 We evaluated the CK7/CK20 pattern of gastric cardia with intestinal metaplasia and compared it with Barrett’s oesophagus, corpus, and antrum metaplasia in 68 endoscopic biopsies and selected surgical specimens.4 Immunostaining was performed using the same monoclonal antibodies for CK7 and CK20 as in the study of Couvelard et al for all specimens of Barrett’s (n=17), cardia metaplasia (n=15), corpus metaplasia (n=14), and antrum metaplasia (n=22). We found three patterns of CK7/CK20 immunostaining and identified them as IM-1, IM-2, and IM-3. IM-1 is characterised by strong diffuse CK7 staining in both superficial and deep …

BACKGROUND:Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens.METHODS:Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2-5 (OAAz). Eradication was confirmed by urea breath test 4-6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure.RESULTS:The eradication rate with OAAz was 38% (95% CI, 25.6-49.4) on intention-to-treat analysis, which was lower (P < 0.05) than with the other regimens [OCM, 61% (50.0-72.8); OBC, 65% (54.0-76.5); OAC, 72% (61.8-81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant.CONCLUSIONS:OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.

Rats transgenic for HLA-B27/human beta2-microglobulin develop a spontaneous multisystem inflammatory disorder that closely mimics human spondyloarthropathies. Prominent features of this disorder are gut inflammation that predominates in the colon, and arthritis. Several mediators such as IFN-gamma, IL-1beta, TNF-alpha, and inducible nitric oxide synthase (iNOS) have been found increased in the inflamed colonic mucosa. In the colon of HLA-B27 transgenic rats, iNOS is predominantly expressed by epithelial cells, and iNOS transcripts are detected in the hip cartilage of those rats, but not in nontransgenic littermates. The role of iNOS in this disorder was evaluated by administering the corticosteroid dexamethasone, or the NOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL) to HLA-B27 transgenic rats with established disease. Treatment with dexamethasone attenuated some aspects of gut inflammation, although it had no effect on iNOS expression. In contrast, treatment with L-NIL effectively inhibited iNOS activity, and resulted in an increase in colitis. Cytokine transcripts in the colon were modified by these treatments: IFN-gamma and IL-1beta were decreased after dexamethasone treatment, whereas administration of L-NIL resulted in decreased IFN-gamma, and TNF-alpha. A trend towards increased IL-1b expression was observed which could have contributed to the L-NIL pro-inflammatory effect. These results suggest that iNOS exerts a protective effect on colitis, in the inflammatory disorder of HLA-B27 transgenic rats.

Rats transgenic for HLA-B27/human beta (2)-microglobulin develop a spontaneous multisystem inflammatory disorder that closely mimicks human spondyloarthropathies Prominent features of this disorder are gut inflammation that predominates in the colon, and arthritis. Several mediators such as IFN-gamma, IL-1 beta, TNF-alpha, and inducible nitric oxide synthase (iNOS) have been found increased in the inflamed colonic mucosa, In the colon of HLA-B27 transgenic rats, iNOS is predominantly expressed by epithelial cells, and iNOS transcripts are detected in the hip cartilage of those rats, but not in nontransgenic littermates. The role of iNOS in this disorder was evaluated by administering the corticosteroid dexamethasone, or the NOS inhibitor L-N-6-(1-iminoethyl)lysine (L-NIL) to HLA-B27 transgenic rats with established disease. Treatment with dexamethasone attenuated some aspects of gut inflammation, although it had no effect on iNOS expression. In contrast, treatment with L-NIL effectively inhibited iNOS activity, and resulted in an increase in colitis. Cytokine transcripts in the colon were modified by these treatments: IFN-gamma and IL-1 beta were decreased after dexamethasone treatment, whereas administration of L-NIL resulted in decreased IFN-gamma, and TNF-alpha, A trend towards increased IL-1 beta expression was observed which could have contributed to the L-NIL pro-inflammatory effect. These results suggest that iNOS exerts a protective effect on colitis, in the inflammatory disorder of HLA-B27 transgenic rats.

Granular cell tumor of the esophagus is an unusual tumor. It presents usually as a small and well limited lesion, localized in the mucosa or the submucosa. We report two cases of granular cell tumor of the esophagus, remarkable for their infiltrative growth. The tumor invaded the esophageal muscularis propria in one case and went through the adventitia in the other. There was no recurrence 1 year and 7 years after surgery, despite an incomplete resection in the second case. Thirteen cases of infiltrative granular cell tumors of the esophagus have been published. They are usually responsible for dysphagia. They can invade the muscularis propria and the adventitia as well as the periesophageal organs. There is no recurrence, even after an incomplete resection. The infiltrative feature of the granular cell tumors of the esophagus, by itself, cannot be considered as a malignant feature. The diagnosis of malignant granular cell tumor of the esophagus lies on the discover of metastases.

BACKGROUND Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Objectives - Chromosomal deletions are the most frequent genetic alterations observed in hepatocellular carcinoma. Loss of heterozygosity on chromosome 4q has been observed in 40% of hepatocellular carcinomas suggesting the presence of a tumor suppressor gene which has not yet been identified.Methodology - We developed a semi-automated quantitative genotyping method which allowed us to characterize 119 hepatocellular carcinomas with 22 fluorescent microsatellite markers distributed on chromosome 4q.Results - 4q loss was observed in 40% of cases. Among these deletions, 19 cases of partial or interstitial loss made it possible to define two common minimal regions of deletion of 25.1 and 37.6 centimorgans localized between markers D4S414 and D4S430 and between markers D4S3033 and D4S408, respectively.Conclusion - This work represents the first step towards the identification and characterization of new genes involved in hepatic carcinogenesis.