Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Randomised clinical trial: low-volume bowel preparation for colonoscopy - a comparison between two different PEG-based formulations.

BACKGROUND: Low-volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso-osmotic sulphate-free formulation of PEG-Citrate-Simethicone (PEG-CS) in combination with bisacodyl has been recently developed. AIM: To compare the quality of bowel cleansing with PEG-CS with bisacodyl vs. PEG-Ascorbate (PEG-ASC) in adult out-patients undergoing colonoscopy. METHODS: Randomised, observer-blind, parallel group study in adult out-patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2-4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG-CS at 20:00 hours or 2 L of PEG-ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as 'clinical success'), and mucosal visibility according to a 3-point scale. Tolerability, acceptability and compliance were also evaluated. RESULTS: Four hundred and eight patients were randomly allocated to PEG-CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG-ASC (n = 204, male patient 51%, age 59.4 years). In the planned per-protocol analysis, the rate of successful preparation was 79.1% following PEG-CS with bisacodyl, and 70% following PEG-ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG-CS and bisacodyl and 46.3% in the PEG-ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG-ASC group discontinued the study because of AE. CONCLUSIONS: Polyethylene glycol-Citrate-Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG-ASC for out-patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low-volume bowel preparations were similar.

Use of macrogol 4000 in chronic constipation.

BACKGROUND: Chronic constipation is a common functional disorder of the gastrointestinal tract, affecting up to 35% of the general population, and especially the elderly. However, its definition as perceived by the patient can vary, making it difficult to understand the problem and find appropriate therapeutic measures. The approach to chronic constipation, thus, needs a thorough understanding of the patient's complaint and the main pathophysiological mechanism requiring treatment. Lifestyle changes do not usually meet with complete patient satisfaction. Other treatments include different types of laxatives. Of these, osmotic laxatives appear one of the most effective and are, therefore, frequently prescribed. DESIGN: This review will cover the topic of osmotic laxatives, specifically focusing on polyethylene glycol (PEG/macrogol 4000) in chronic constipation and as a key agent for bowel cleansing prior to colonoscopy. PEG formulations, including macrogol 4000, are safe, effective treatments for constipation, even in children and elderly patients. Macrogol 4000 may well be more palatable than combined formulations (macrogol 3350 with electrolytes), which could help improve adherence to the long-term treatment required for chronic constipation. CONCLUSIONS: PEG/macrogol is also recommended as an effective option for bowel cleansing prior to colonoscopy. The improved cost-effectiveness of macrogol over other commonly prescribed laxatives, such as lactulose, should be taken into consideration.

Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett's esophagus: a translational approach.

AIM: Human epidermal growth factor receptor (HER2) protooncogene, overexpressed/ amplified in preneoplastic lesions and in adenocarcinoma (ADC) of the esophagus, can be considered a target for treatment of esophageal dysplasia/ADC. The aim of this study was to evaluate the therapeutic role of the anti-HER2 monoclonal antibody, trastuzumab, in the management of ADC originating from HER2-positive Barrett's esophagus (BE). METHODS: Two patients with high-grade dysplasia and ADC of the esophagus after esophageal mucosectomy and no metastatic disease were studied. Patients were not eligible for radical surgery or chemo-radiotherapy because of age and comorbidities. HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. Additional immunohistochemical analyses were performed. The whole panel was analysed at baseline, after treatment and at follow-up. RESULTS: At baseline, the two patients showed HER-2 overexpression/amplification in all areas of dysplasia and ADC but not in BE. Six months after treatment no significant differences in terms of endoscopical and histological patterns of the disease were found. HER-2, EGFR, TOPOII-alpha and anti-ssDNA analysis demonstrated a down-regulation of these markers and increased apoptosis. CONCLUSION: This study demonstrates that this treatment is feasible. No clear evidence of dysplasia regression was observed. However, HER2 and TopoII-alpha downregulation and induction of apoptosis occurring 6 months after treatment encourages further investigation.

Screening for and surveillance of Barrett's esophagus is clinically indicated.

Barrett's esophagus (BE) is a complication of chronic gastroesophageal reflux disease (GERD) and is the precursor of esophageal adenocarcinoma (EA), through a progression from intestinal metaplasia (IM), through high-grade dysplasia (HGD). Although the progression from BE to EA seems to be infrequent (0.5% per year), endoscopic and bioptic surveillance would play a significant role in the evaluation of HGD and the detection of EA in early, curable stage, improving survival rates after treatments. The severity and the duration of GERD could be helpful in the assessment of the risk for BE and to enroll these subjects into screening protocols to detect any dysplastic or neoplastic change. The benefits of screening-surveillance programs could be furthermore enhanced by an improvement in diagnostic methods, such as high-resolution endoscopic techniques and the use of biomarkers for the histological examination seems to play a primary role in the cancer risk stratification; in such way, endoscopic resection techniques (mucosal resection and submucosal dissection) can be considered as a helpful method to stage dysplastic changes in BE.

COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasia-carcinoma progression in Barrett's esophagus.

BACKGROUND: Immunohistochemical changes associated with development of cancer in Barrett's esophagus offer potential areas of intervention to prevent and manage esophageal cancer. AIMS: To assess the role of cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2/cyclin-dependent kinase 1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. PATIENTS AND METHODS: Specimens from 46 patients with Barrett's esophagus (39% without dysplasia, 33% with dysplasia and 28% with adenocarcinoma) were stained for cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2. RESULTS: Cyclooxygenase 2: No expression differences between groups were found, except for adenocarcinomas (p=0.04). Caudal-type homeobox transcription factor 2: Nuclear positivity decreased from Barrett's esophagus without dysplasia (71.6%), to Barrett's esophagus with low grade dysplasia (35.3%), to Barrett's esophagus with high grade dysplasia (17.14%); in adenocarcinoma these percentages were intermediate between high and low grade dysplasia (30.5%). Cell division cycle 2: Expression on deeper glandular structures was 40% in Barrett's esophagus without dysplasia, 55.47% in Barrett's esophagus with dysplasia, and 63.84% in adenocarcinoma, with no statistical differences between groups. Concerning cells of the superficial layer, Barrett's esophagus with low grade dysplasia expressed focal positivity (p=0.0001 vs. no dysplasia); Barrett's esophagus with high grade dysplasia displayed diffuse positivity (p=0.0001 vs. no dysplasia and low grade dysplasia). A diffuse positivity was found in Barrett's esophagus with adenocarcinoma (p=0.0001 vs. no dysplasia and low grade dysplasia). CONCLUSIONS: Further evaluation of cyclooxygenase 2, cell division cycle 2 and caudal-type homeobox transcription factor 2, in association with morphology, might help to improve the accuracy of diagnosis and be useful for the clinical-pathological assessment of patients with Barrett's esophagus.

Immunological markers anti-saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: a helpful diagnostic tool.

AIM: Nowadays the diagnosis of inflammatory bowel disease (IBD) and the differentiation between Crohn disease (CD) and ulcerative colitis (UC) is still based on morphological changes identified at endoscopy, radiology, and histopathology. In 5-15% of cases this differentiation is not possible (diagnosed with indeterminate colitis). METHODS: We evaluated if recently developed commercial kits for the determination of anti-Saccharomyces Cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) are useful in differentiating cases of UC from CD diseases with a consequent reduced number of undefined colitis and improved clinical management. Sera from 56 consecutive patients with a clinical diagnoses of IBD were evaluated in a blinded fashion for the presence of ASCA IgA and IgG and ANCA IgG with 2 different diagnostic methods: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). RESULTS: In our cases we observed good agreement between histopathological examination and laboratory results and the combined use of ASCA and ANCA yielded a correct diagnosis in 93% of patients with CD and in 97% of the UC patients. CONCLUSIONS: We confirm the value of the test for the diagnosis of CD and UC and the differentiation from other forms of colitis.

Endoscopic features of celiac disease in children.

BACKGROUND: Endoscopic abnormalities have been described in adult patients with celiac disease that may suggest the diagnosis, especially when the presentation is atypical. METHODS: The duodenum of 140 children undergoing EGD for various different indications was evaluated macroscopically and histologically. RESULTS: Histology revealed total villous atrophy in 80 patients, 79 of whom had celiac disease. Among these, 100% had a mucosal mosaic pattern in the duodenum (sensitivity 98.7%, specificity 96.7%, positive predictive value 97.5%, negative predictive value 98.3%), 70% had scalloped duodenal folds (sensitivity 68.7%, specificity 98.3%, positive predictive value 98.2%, negative predictive value 70.2%), 15% had visible vasculature, and 6% had reduction of duodenal folds. Sensitivity and specificity of endoscopic findings were not modified by chromoendoscopy. Except for the mosaic pattern, the frequency of endoscopic abnormalities increased with age; reduction of duodenal folds was never seen in children with celiac disease who were less than 5 years of age. CONCLUSIONS: The frequency and diagnostic value of endoscopic abnormalities are different in children with celiac disease compared with adults with this disease. Because indications for endoscopy, such as abdominal pain, dyspepsia, and unexplained anemia, can be manifestations of celiac disease, and villous atrophy may have a patchy distribution, awareness of these endoscopic abnormalities is important in the diagnosis of celiac disease in children.

Dilated intercellular spaces as markers of reflux disease: histology, semiquantitative score and morphometry upon light microscopy.

BACKGROUND AND AIMS: A recent electron microscopy study suggested that dilated intercellular spaces (DIS) are specific for acid reflux-damaged esophageal epithelium. Electron microscopy is, however, expensive and difficult to apply to routine biopsies. The aims of this study are to establish a method for assessing DIS on light microscopy of esophageal biopsies and to estimate its association with current clinicopathological parameters of esophagitis. MATERIALS AND METHODS: 21 patients with reflux symptoms were investigated. Light microscopy biopsies were assessed for DIS size by a semiquantitative method and computer-assisted, static morphometry. A DIS score accounting for DIS size and distribution was assigned to each patient and its association with 30 clinicopathological variables investigated by univariate and multivariate logistic regression. RESULTS: Both the semiquantitative method and static morphometry identified 4 different classes of DIS size. The DIS score was significantly and independently associated with the esophageal symptoms score, the histological score of esophagitis and the relevant morphometry data. CONCLUSIONS: DIS may be efficiently assessed during light microscopy of routine esophageal biopsies. Since correlation with both the histology and the symptoms of esophagitis, the DIS score may be considered a novel parameter of esophagitis and is suggested for the routine evaluation of esophageal biopsies in patients with reflux disease.

Evidence of Epstein-Barr virus infection in ulcerative colitis.

BACKGROUND AND AIM: The aetiology of ulcerative colitis is still controversial, however, recent studies have emphasised the possible role of infectious agents or ingested substances and their breakdown products, which might activate immune-mediated mechanisms eventually leading to tissue damage. Aim of this investigation was to ascertain the occurrence and the potential role of Epstein-Barr virus infection in large bowel mucosa of ulcerative colitis patients. PATIENTS AND METHODS: Twenty-three biopsies and six total colectomies from 17 patients were analysed for the expression of Epstein-Barr virus proteins and RNAs. Polymerase chain reaction experiments were also carried out to detect Epstein-Barr virus DNA. For comparison, ten biopsies from patients with Crohn's disease, ten biopsies from patients with different types of colitis, seven biopsies and five surgical margins of normal colonic mucosa from the small and large bowels were studied (controls). RESULTS: Six biopsies and four colectomies from seven ulcerative colitis patients showed scattered lymphocytes expressing nuclear EBER 1-2 and harbouring polymerase chain reaction-amplifiable Epstein-Barr virus-DNA. In some cases, linear viral DNA (typical of lytic Epstein-Barr virus infection) was also found. Epithelial cells were invariably negative in all cases. All control tissues from non-ulcerative colitis patients were also invariably non-reactive. CONCLUSION: Evidence of Epstein-Barr virus infection in the mucosal inflammatory cells of ulcerative colitis patients suggests a possible role of this virus in the chronicity of ulcerative colitis.

Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC).

BACKGROUND & AIMS: The clinical importance of portal hypertensive gastropathy (PHG) as a source of gastrointestinal bleeding in patients with cirrhosis is poorly defined. We investigated the natural history of this condition in a large series of patients. METHODS: All patients with cirrhosis seen at 7 hospitals during June and July 1992 were followed up with clinical and endoscopic examinations every 6 months for up to 3 years. Gastropathy was classified according to the classification of the New Italian Endoscopic Club. RESULTS: The prevalence of gastropathy was 80% and was correlated with the duration of disease, presence and size of esophagogastric varices, and a previous history of endoscopic variceal sclerotherapy. During 18+/-8 months of follow-up, gastropathy was stable in 29% of patients, deteriorated in 23%, improved in 23%, and fluctuated with time in 25%. The evolution of gastropathy with time was identical in patients with and without previous or current sclerotherapy. Acute bleeding from gastropathy occurred in 8 of 315 patients (2.5%). The bleeding-related mortality rate was 12.5%. Chronic bleeding occurred in 34 patients (10.8%). CONCLUSIONS: PHG is common in patients with cirrhosis, and its prevalence parallels the severity of portal hypertension. Gastropathy can progress from mild to severe and vice versa or even disappear completely. Bleeding from this lesion is relatively uncommon and rarely severe. Sclerotherapy of esophageal varices does not seem to influence the natural history of this condition.

Incidental renal cell carcinoma-age and stage characterization and clinical implications: study of 1092 patients (1982-1997).

OBJECTIVES: To compare the epidemiologic, clinical, and pathologic characteristics of incidental and symptomatic renal cell carcinoma in a large series of patients, with emphasis on age distribution and its potential impact in defining groups of patients that may benefit from early detection programs. METHODS: Records of 1092 patients with renal tumors from 1982 to 1997 were reviewed. Age, clinical presentation, and pathologic stage and grade were analyzed. Special attention was given to the age distribution and its relationship to the incidental or symptomatic diagnosis. RESULTS: The overall mean age and proportion of patients older than 65 gradually increased (from 57 to 62.6 years and from 24.7% to 48.7%, respectively) from 1982 to 1997. The mean age in the incidental group rose steadily higher than in the symptomatic group. A progressive increase of incidental tumors from 13.0% in 1982 to 1983 to 59.2% in 1996 to 1997 was observed. A lower stage (74.3% versus 49.1%), grade (75.5% versus 56.9%), and percentage of metastases at presentation (10.4% versus 19.6%) were registered in the incidentally found neoplasms than in the symptomatic neoplasms. Eighty-two (80.4%) of 102 patients who underwent conservative surgery had incidental renal cell carcinoma. CONCLUSIONS: Our data confirm a rapid and dramatic change in the epidemiologic and clinical characteristics of renal cancer, with an increasing number of incidentally found tumors presenting with lower stage, grade, and percentage of metastases. An unexpected but significantly higher rate of renal neoplasms was observed in older patients. The stage, grade, and patient age observed in our series of incidentally found tumors raises the question of whether to leave the current diagnostic approach unaltered, thus benefiting a subgroup of patients with clinically unrecognized and possibly indolent renal cell carcinoma, or to extend early detection programs to younger patients with potentially more aggressive tumors.

[Intestinal brushing. Technical-cytological contribution in the pathological study of Vater's ampulla, common bile duct, and pancreatic system]. / Il brushing intestinale. Apporto tecnico-citologico nello studio della patologia della papilla di Vater, della via biliare principale e del sistema pancreatico.

OBJECTIVE: This experience shows the effectiveness of the cytological examination in the diagnosis of biliary and pancreatic neoplasm on samples obtained from Vater's papilla through endoscopic intestinal brushing. STUDY DESIGN: From June 1997 to October 1998, 28 patients, suffering from suspicious neoplasm of Vater's papilla or biliary system, were studied. Each sample was obtained through intestinal brushing during an Endoscopic Retrograde Colangio-Pancreatography (ERCP) and processed with the technique of direct smear stained with Papanicolaou's method. The sample was followed by the corresponding biopsy in 16 cases and by surgical specimens in 8 cases. RESULTS: 27 patients out of 28 were correctly classified by the intestinal brushing. The method carried out a positive predictive value of 100% and a sensitivity of 93%. The sensitivity of biopsy turned out to be 80%. CONCLUSIONS: The intestinal brushing is an effective method of diagnosis, which turned out to be relevant as a support and, in several cases, as a substitute of the biopsy. We think, therefore, that the brushing should be carried out whenever a lesion of the Vater's papilla or of the biliary system is suspected during an ERCP.

Ranitidine bismuth citrate (RBC) based triple therapy for 7 days is more effective than RBC plus clarithromycin for 14 days in dyspeptic patients with Helicobacter pylori infection. H. Pylori Lombardy Group.

BACKGROUND: Ranitidine bismuth citrate (RBC) in co-prescription with clarithromycin for 2 weeks has been shown to be effective for the eradication of Helicobacter pylori. Moreover, several studies have reported good H. pylori eradication rates with RBC plus two antibiotics for 1 week. AIM: To compare the H. pylori eradication rates and safety of two different RBC co-prescription regimens. METHODS: Patients undergoing endoscopy for upper gastrointestinal symptoms were randomized to open treatment with either RBC 400 mg b.d. plus clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 1 week (RbcCT) or RBC 400 mg b.d. plus clarithromycin 500 mg b.d. (RbcC) for 2 weeks. H. pylori infection was detected by CLO-test on antral biopsy and confirmed by histology on antral and corpus biopsies and by 13C-urea breath test (UBT). A further UBT was performed at least 4 weeks after the end of treatment to assess the H. pylori eradication. H. pylori eradication was calculated for an intention-to-treat (ITT) population (all H. pylori-positive patients who received at least one treatment dose) and for an all-patients-treated (APT) population (patients of the ITT population assessed for H. pylori at least 4 weeks after the end of treatment). RESULTS: Two hundred and ninety-five patients (142 males, 153 females, mean age 48 years) were recruited to the study. Of these, 239 had H. pylori infection confirmed by all three tests required by the protocol. The two treatment groups were similar with respect to all the demographic data. H. pylori ITT eradication rates were 85% (104/123) for RbcCT and 67% (78/116) for RbcC. APT eradication rates were 92% (104/113) for RbcCT and 76% (78/103) for RbcC. A significant statistical difference was found between the two treatments, irrespective of the population analysis (P = 0.001). Adverse events occurred in 7% of patients on RbcCT and in 13% on RbcC. No serious adverse events were reported. CONCLUSIONS: The 1-week treatment with RBC plus clarithromycin and tinidazole yielded higher eradication rates than the 2-week treatment with RBC plus clarithomycin. Both treatments were well tolerated.

[Flow cytometry sutdy of DNA and cell kinetics in the adenoma- carcinoma sequence in the large intestine]. / Studio citofluorimetrico del DNA e della cinetica cellulare nella sequenza adenoma-carcinoma del grosso intestino.

UNLABELLED: The quantitation of DNA and growth fraction in the different step from dysplastic to neoplastic process in large bowel is the aim of this study. 70 colonic polyps were studied. The fresh specimens were processed and DNA analysis was carried out using a Partec CA II flow cytometer and the growth fraction was tested with KI-67 monoclonal antibody. The percentage of S-phase cells has been calculated with the Multicycle program. Our results demonstrated that 7 adenomas were tubulo-villous with mild dysplasia, 39 with mild-moderate dysplasia, 1 with severe dysplasia, 5 were polypoid carcinomas, 2 juvenile polyps, 1 polypoid leiomyoma, 1 inflammatory fibroid polyps. DNA analysis showed a diploid DNA content in non adenomatous polyps, in all adenomas with mild dysplasia, in 37 with mild-moderate dysplasia, in 8 cases with moderate-severe dysplasia and 1 cancer. Aneuploidy was discovered in 2 cases with mild-moderate dysplasia, in 6 cases with moderate-severe dysplasia, in the case of severe dysplasia and in 4 cases of carcinomas. Best indexes of linear correlation (Pearson's r) has been found between S-phase and DNA index (r = .75) and between S-phase and KI-67 (r = .82). IN CONCLUSION: 1) No relationship was found between DNA content and age, sex, size and location of polyps. 2) Aneuploidy is strictly related to moderate-severe grade of dysplasia therefore it is an important element in the development of adenomacarcinoma sequence. 3) DNA-index, S-phase and KI-67 are strictly related.

[Intracavitary brachytherapy in esophageal neoplasms. Experience at the Radiology Institute of Brescia]. / La brachiterapia endocavitaria nelle neoplasie esofagee. L'esperienza dell'istituto del Radio di Brescia.

We investigated the role of brachytherapy in the management of esophageal cancer. From March, 1990, to December 1994, seventy patients, with biopsy-proved esophageal carcinoma, were treated with brachytherapy +/- external beam radiotherapy. According to the TNM staging system, 24 patients were graded as T1, 24 as T2, 10 as T3, 9 as T4, and 3 as Tx. Median Karnofsky score was 80. Dysphagia was the major symptom in 68% of cases. Treatment consisted of low dose rate first, and then high dose rate brachytherapy, with progressive optimization of doses and fractions, up to total doses of 15-30 Gy in low dose rate and 7-21 Gy in high dose rate. When associated, external beam radiotherapy was delivered with conventional schedules. Tolerance to treatment was good with slight acute toxicity. Symptoms were markedly improved, with reduction of dysphagia in 100% of cases. Overall survival was 75%, 47%, 23% and 18% at 6, 12, 24, 36 months; no significant difference was found between low and high dose rate groups. Furthermore, no difference was shown in the overall survival of the group treated with brachytherapy alone and the one with associated external beam radiotherapy. Late toxicity occurred in 10% of patients and was managed by endoscopic procedures in all cases. In our opinion, brachytherapy appears to be an effective palliative treatment; its role as radical treatment remains to be defined.

Portal hypertensive gastropathy: reproducibility of a classification, prevalence of elementary lesions, sensitivity and specificity in the diagnosis of cirrhosis of the liver. A NIEC multicentre study. New Italian Endoscopic Club.

OBJECTIVE: To classify elementary endoscopic lesions of portal hypertensive gastropathy, assess their reproducibility, prevalences, sensitivity and specificity in the diagnosis of cirrhosis of the liver. METHODS: 1) A classification of portal hypertensive gastropathy elementary lesions was defined. 2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3) Fifteen centres enrolled consecutive patients with or without cirrhosis of the liver and recorded portal hypertensive gastropathy pattern according to its location. RESULTS: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal hypertensive gastropathy prevalence was higher in patients with cirrhosis of the liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was 0.83. Portal hypertensive gastropathy was tentatively classified as mild or severe when mosaic-like pattern alone or red marks of any kind were present, respectively; this classification led to a further improvement in reproducibility. CONCLUSIONS: Our results suggest that a sufficient degree of agreement can be achieved in recording portal hypertensive gastropathy. Therefore, the New Italian Endoscopic Club classification should be used to evaluate the natural history of this condition.

Digestive endoscopy and portal hypertension. North Italian Endoscopic Club.

Improved knowledge of pathophysiology of portal hypertension and technological progress have contributed to development of new endoscopic techniques and pharmacological approaches to treatment of this condition. To put the role of endoscopy in the right perspective, it is important to consider that liver transplantation has greatly modified prognosis of cirrhosis. Because of the increase of indications for transplantation, these complications are no longer regarded as the last, but rather as an intermediate stage before a possible transplantation. We have reviewed some pathophysiologic, diagnostic and therapeutic aspects on portal hypertension, especially the role of endoscopy in diagnosis, natural history and therapeutic options for complications of cirrhosis. In addition to sclerotherapy, new endoscopic methods have been developed, with a low complication rate and possibility of being applied for treatment of gastric varices, i.e. injection of tissue adhesives and rubber band ligation. Besides oesophageal varices, gastric varices and portal hypertensive gastropathy (and portal colopathy) are important findings in cirrhosis. Further information is needed on natural history and treatment of these conditions. Digestive haemorrhage is the most important consequence of portal hypertension, so treatment should be aimed at controlling acute bleeding, rebleeding and, more important, at preventing first haemorrhagic episode. Good results will probably be obtained using a combination of drugs, a combination of endoscopic methods or a combination of both. All will need evaluation in randomised, controlled trials. These considerations renew interest in strategies for diagnosis and treatment of portal hypertension and a multidisciplinary approach may be necessary, involving gastroenterologists, endoscopists, interventionist radiologists and surgeons, ideally in a departmental environment.

Different neurotransmitter systems are involved in the development of esophageal achalasia.

Clinical and pharmacological evidence suggests that several neurotransmitters are involved in the control of the esophageal motility; in fact, besides the well known cholinergic and sympathetic innervation, Vasoactive Intestinal Polypeptide (VIP)-containing fibers as well as dopamine (DA)-containing nerve endings have been identified within the esophageal wall. Lower Esophageal Sphincter (LES) achalasia is a neuromuscular disorder characterized by the absence of peristalsis in the body of the esophagus and by the failure of the LES to relax in response to swallowing. Stimulation of both VIP receptors and D-2 DA receptors induce a decrease in LES pressure, while D-1 receptors mediates LES contractions. In the present study we show that both VIP and DA system is disregulated in LES achalasia. In particular, this disease is associated not only with the lack of VIP nerves in the LES, but also with a failure in the responsiveness of postsynaptic receptors to VIP stimulation. Furthermore, we demonstrate a selective functional loss of the D-2 DA receptor component, without changes in the D-1 DA receptor mediated responses.