Endoscopic gallbladder drainage for acute cholecystitis: technical and clinical results.

BACKGROUND AND STUDY AIMS: Cholecystectomy is the standard treatment for acute cholecystitis while percutaneous drainage is reserved for high-risk patients. The aim of the present study was to assess the technical success rate and clinical efficacy of endoscopic gallbladder drainage in patients with acute cholecystitis. PATIENTS AND METHODS: A total of 35 consecutive patients with acute cholecystitis and without residual common bile duct obstruction were retrospectively identified. Patients were stratified according to the pathogenesis and stages of acute cholecystitis, and the morphology of the cystic duct and/or its insertion in the common bile duct. Primary outcomes were technical success and early and late clinical success. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) was performed within the first 72 hours in 19 patients (54%). Technical success was achieved in 29 patients (83%); drainage was nasocholecystic in 21 of these (72%), plastic stenting in 6 (21%), and a combined method in 2 (7%). The pathogenesis and stage of acute cholecystitis, and the morphology both of the cystic duct and its insertion in the common bile duct, did not influence technical success. Clinical success was achieved in 24 cases (83%) after a median of 3 days (range 2-12). Four patients (14%) died within 3 days due to septic complications, and one accidentally removed the nasocholecystic drain after 24 hours. Late results, available in 21 patients after a median follow-up of 17 months, showed relapse of acute cholecystitis in 2 (10%) (both with stents) and of biliary pain in 2 patients (10%), both of whom had nasocholecystic drainage. CONCLUSIONS: Endoscopic gallbladder drainage seems feasible and effective in resolving acute cholecystitis, but only as a temporary measure because of a 20% relapse rate in long-term follow-up. Prospective studies are necessary to identify which patients would benefit most from this endoscopic technique in the short and long term.

STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer.

A potential tumor suppressor gene, STK11 , encoding a serine threonine kinase, has recently been identified on chromosome 19p13. Germ-line mutations of this gene have been found in patients with Peutz-Jeghers syndrome (PJS). To further investigate the relevance of STK11 mutations in PJS, we analyzed its coding sequence in nine patients and identified two deletions and three missense mutations. Because intestinal carcinomas have been observed to develop in association with PJS, we analyzed tumors from 71 patients for allelic deletions (loss of heterozygosity) and STK11 gene mutations, to elucidate the etiological role of STK11 gene in sporadic colorectal cancer. Loss of heterozygosity, evaluated using the microsatellite D19S886, was observed in 10 of 52 informative cases. No somatic mutations were detected except for a missense alteration in one tumor. Our data indicate the heterogeneity of PJS and the infrequent involvement of the STK11 gene in colorectal cancer.

Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistance.

AIM: To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. METHODS: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1--0.2 mg.day/kg and adjusted in order to achieve levels of 5--10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. RESULTS: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. CONCLUSIONS: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials.

Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC).

BACKGROUND: Using data from a case-control study carried out in Italy 1989-1992, we estimated the odds ratios (OR) and the population attributable risks (AR) for inflammatory bowel diseases (IBD) in relation to smoking, oral contraception and breastfeeding in infancy. METHODS: The study focused on 819 cases of IBD (594 ulcerative colitis: UC; 225 Crohn's disease: CD) originating from populations resident in 10 Italian areas, and age-sex matched paired controls. RESULTS: Compared with non-smokers, former smokers were at increased risk of UC (OR = 3.0; 95% confidence interval [CI]: 2.1-4.3), whereas current smokers were at increased risk of CD (OR = 1.7; 95% CI: 1.1-2.6). Females who reported use of oral contraceptives for at least one month before onset of symptoms had a higher risk of CD (OR = 3.4; 95% CI: 1.0-11.9), whereas no significant risk was observed for UC. Lack of breastfeeding was associated with an increased risk of UC (OR = 1.5; 95% CI: 1.1-2.1) and CD (OR = 1.9; 95% CI: 1.1-3.3). Being a 'former smoker' was the factor with the highest attributable risk of UC both in males (AR = 28%; 95% CI: 20-35 %) and in females (AR = 12%; 95% CI: 5-18%). Smoking was the factor with the highest attributable risk for CD in males (AR = 31%; 95% CI: 11-50%). Lack of breastfeeding accounted for the highest proportion of CD in females (AR = 11%; 95% CI: 1-22%). Oral contraceptive use accounted for 7% of cases of UC and for 11% of cases of CD. CONCLUSIONS: Taken together, the considered factors were responsible for a proportion of IBD ranging from 26% (CD females) to 36% (CD males). It is concluded that other environmental and genetic factors may be involved in the aetiology of IBD.

[Behavior of the pressure of the lower esophageal sphincter after intravenous administration of domperidone in normal subjects]. / Comportamento della pressione dello sfintere esofageo inferiore (LES-P) dopo somministrazione intravenosa di domperidone in soggetti normali.

Manometric studies on the action of domperidone 10 mg and 20 mg i.v. on the lower esophageal sphincter pressure (LESP) have been carried on ten healthy volunteers. Domperidone inhibits dopamine receptors and results in an increase of LESP. A dose of 10 mg produces a significant increase in LESP which is rapid and prolonged for thirty minutes; a dose of 20 mg is less efficient. The stimulatory effect of domperidone on LESP suggests an important role for endogenous dopamine as an inhibitory neuromodulator of LES pressure. The use of domperidone in therapy for reflux esophagitis is suggested.

Femoral and sciatic nerves block (BiBlock) in orthopedic traumatologic lower limbs surgery in patients with multiple sclerosis.

Multiple sclerosis is a progressive demyelinating disease which affects large areas of the brain and of the spinal cord. Stressful events, surgical procedures, general anaesthesia and central blocks seem to be responsible for relapses, with worsening of the disease. So, when we scheduled 2 patients with multiple sclerosis for lower limbs orthopedic traumatologic surgery, we decided to use a peripheral block, and in particular a BiBlock. The patients' evaluation in the immediate postoperative course and 30 days after surgery has shown no relapses of the disease. In the literature, however, data about anaesthesia and multiple sclerosis are few and controversial, sometimes in contrast. Anyway, the use of peripheral blocks has neither anatomic, nor metabolic interferences with the lesion sites of multiple sclerosis. In conclusion, peripheral block is safe and it is the technique of choice for this type of patients, when surgery allows it.

Anaestethic problems in Sanfilippo syndrome. A rare case of adult patient.

The authors report the case of a female patient (41 years old) affected by mucopolysaccharidosis type III or Sanfilippo syndrome submitted to a gynecologic surgical procedure and describe the main anesthesiologic problems. A sub-arachnoid anesthesia with hyperbaric Bupivacain 0.5% was used. This technique proved to be safe and convenient without peri- and postoperative complications.

Evidence of small-bowel involvement in hereditary hemorrhagic telangiectasia: a capsule-endoscopic study.

BACKGROUND AND STUDY AIMS: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder leading to telangiectases and arteriovenous malformations of the skin, mucosa, and viscera. Telangiectases in the upper gastrointestinal tract are known, but data regarding possible small-bowel involvement are scarce due to the technical difficulty of exploring the entire gastrointestinal tract. The aim of the present study was to use capsule endoscopy (CE) to determine the prevalence of small-bowel telangiectases in HHT patients. PATIENTS AND METHODS: From December 2001 to September 2002, 20 consecutive adult HHT patients at an interdepartmental HHT center were prospectively evaluated. All patients underwent esophagogastroduodenoscopy (EGD) followed by CE within 24 h. The telangiectases were scored according to commonly accepted criteria by two endoscopists and two observers of the video-capsule images, who were blinded to each other's findings. RESULTS: EGD revealed gastric telangiectases in 15 of the 20 patients (75 %), while CE demonstrated small-bowel involvement in 10 of 18 patients (56 %; images were not recorded for two patients due to battery failure). No preferential site for telangiectasia was found between the jejunum and the terminal ileum. All patients who were positive on CE were also found to have gastric involvement at EGD. Patients with small-bowel telangiectases were significantly older than those without (62.5 years vs. 45 years; P < 0.02). CONCLUSIONS: This study established a 56 % prevalence of small-bowel telangiectases in patients with HHT. This new endoscopic technique will probably change the etiological diagnosis of occult bleeding in HHT patients (which is too often attributed only to epistaxis) and may also be able to alter treatment strategies in HHT patients with gastrointestinal bleeding.

Endoscopic treatment of postsurgical external pancreatic fistulas.

BACKGROUND AND STUDY AIMS: External pancreatic fistulas (EPFs) are managed primarily by conservative treatment with a success rate of 40-90%. Failures of conservative therapy have traditionally been dealt with using surgery; however, major morbidity and mortality are associated with operative treatment. The aim of this study was to evaluate the feasibility and effectiveness of endoscopic treatment in the closure of EPF. PATIENTS AND METHODS: A total of 16 consecutive patients with EPF (12 men, four women; median age 50, range 21-66) underwent an attempt at endoscopic management after failure of conservative therapy. Four patients had chronic pancreatitis. All patients had EPFs occurring after open abdominal surgery. The mean interval between the onset of the fistula and our intervention was 108 days (range 27-365 days). The mean output volume of the fistula was 205 ml/d (range 50-600 ml/ d). The aim of treatment was to lower the pancreatic duct pressure and to bypass the ductal disruption by placement of drains and/or stents to induce fistula healing. RESULTS: In all, 13 biliary and nine pancreatic sphincterotomies were performed in order to gain access to the pancreatic duct. Access through the minor papilla was required in one patient. Complete visualization of the main pancreatic duct as well as of the fistulous tract was obtained in 12 patients (75%). Treatment consisted of placement of a nasal pancreatic drain (NPD) across the pancreaticojejunal anastomosis in one patient after duodenopancreatectomy. In 11 of the remaining 15 patients (73%) a NPD could be placed in the pancreatic duct across the ductal leakage (n = 9) or nearby (n = 2). One patient died 24 hours after endoscopic treatment from severe sepsis and massive pulmonary embolism. Endoscopic drainage was effective in healing the EPF in all patients in whom NPDs had been successfully placed, except one. The fistula in this patient healed completely after insertion of an 8.5-Fr pancreatic stent. The mean interval between endoscopic treatment and fistula closure was 8.8 days (range 2-33 days). No complications related to the endoscopic treatment were recorded in this series. In the 12 successfully treated patients, fistulas did not recur in any of the 11 surviving patients after a mean follow-up of 24.7 months (range 3-63 months). CONCLUSIONS: Endoscopic pancreatic drainage, when feasible, is safe and effective for EPF and should be considered as a first-line therapy when EPFs do not respond to conservative therapy.

Oral tacrolimus (FK 506) in Crohn's disease complicated by fistulae of the perineum.

We describe the cases of two patients with Crohn's disease affected by severe perineal fistulae resistant to conventional therapies, successfully treated with FK 506, a new immunomodulatory drug. It is well absorbed from diseased bowel and preliminary experiences have indicated its short-term use in complicated Crohn's disease. The first patient was a 24-year-old male with perineal fistula and severe skin ulceration (8 cm of external opening diameter). He had undergone colectomy and ileostomy because of severe pancolitis refractory to medical treatment and had been treated with azathioprine and metronidazole. Two months after starting FK 506, a dramatic improvement made further surgical operation unnecessary. Local and general benefit was observed during the following 26 months, until FK 506 was withdrawn. The second patient was a 28-year-old male with a diagnosis of ulcerative pancolitis changed to Crohn's disease two months after the onset of a perineal fistula, recurring despite drainage procedures, steroid therapy, and total parenteral nutrition. FK 506 was administered for two months with a complete healing of fistula. Successively, it was stopped and corticosteroids (associated to enteral nutrition) were given because of recurrent rectal bleeding. Our experience encourages the use of oral FK 506 in complicated Crohn's disease and suggests the possibility of a long-term primary therapy other than the use as a "bridge" to other treatments.

Proliferative activity of gastric epithelium in progressive stages of Helicobacter pylori infection.

Helicobacter pylori (HP) infection is the main etiopathogenetic agent responsible for inflammatory and ulcerative changes in gastroduodenal mucosa and the basis for both intestinal and diffuse types of gastric carcinoma. In this latter case, intestinal metaplasia is the intermediary between gastritis and cancer. In this study we describe the proliferative activity of gastric epithelium in the progressive stages of HP infection. The expression of proliferating cell nuclear antigen (PCNA), which has proven to be a reliable method for this evaluation, was used as a marker. The study was performed on endoscopic biopsies of the gastric antrum of 40 patients, who were divided into five groups, eight in each group: normal histology and endoscopy, HP-; histological HP+ gastritis with normal endoscopy; histological HP+ gastritis with endoscopic evidence of chronic erosions; complete and incomplete intestinal metaplasia in a HP+ stomach. PCNA was detected by immunohistochemistry and expressed as labeling index, ie, percentage of positive nuclei either in the whole or upper third of foveolae. Our data show a progressive increase of epithelial proliferation in the successive stages of HP infection ranging from gastritis alone to the development of incomplete intestinal metaplasia, a well-known precancerous condition. The proliferative pattern tended to expand towards the upper foveolar third, which in normal conditions does not represent a site of epithelial renewal. These alterations may be related to the development of neoplastic transformations of gastric epithelium. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results indicate that the high epithelial turnover, expressed by PCNA LI, may be an indicator of increased risk of neoplastic changes in long-standing untreated HP+ chronic gastritis.

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.

Circadian rhythm of hepatic cytosolic and nuclear estrogen and androgen receptors.

Mammalian liver is a sex steroid-responsive tissue. The effects of these hormones presumably are mediated by hepatic estrogen receptors (ER) and androgen receptors (AR). Serum levels of sex hormones display circadian rhythms. Further, estrogens and androgens are commonly administered; administration of these agents is associated frequently with liver disease. Therefore, we investigated whether the cytosolic and nuclear sex steroid receptors also display a similar circadian rhythm, and whether variations occurred in the distribution of receptors between cytosolic and nuclear compartments. Animals were killed every 4 h from midnight till the following midnight; cytosolic and nuclear levels of both ER and AR were measured. Cytosolic ER reached a maximum level at 4 AM, and a minimum at 8 PM and midnight of both days. Nuclear ER was highest at 8 AM and lowest at 4 PM and 8 PM, a pattern which parallels variations in serum estradiol levels. Cytosolic AR was highest at 8 PM and lowest at midnight and 4 AM. Nuclear AR was highest at 4 AM and lowest at 4 PM and 8 PM. The highest level of nuclear AR does not correspond to the maximum serum testosterone level, which occurred at 4 PM. The total hepatic content of both ER and AR was not constant over the 24-h period, but varied considerably with time of day. These studies suggest that both ER and AR show a distinct circadian rhythm in subcellular compartmentalization, and that total hepatic content of ER and AR varies significantly during a 24-h period.

Sex hormone-related functions in regenerating male rat liver.

Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration.

Lupus nephritis improvement after anti-tumor necrosis factor alpha monoclonal antibody (infliximab) treatment for Crohn's disease: a case report.

Association between Crohn's disease (CD) and lupus nephritis is very rare and, to the best of our knowledge, it has been described only once. We report here a clinical case of CD occurred in a young woman 8 years after a diagnosis of lupus nephritis according to clinical, laboratory and histological criteria. CD was unresponsive to steroids and immunosuppressants and, therefore, the patient was treated with anti-tumour necrosis factor alpha monoclonal antibody (Infliximab). This therapy led to the remission of both CD (50% of Crohn's Disease Activity Index--CDAI--decrease) and lupus nephritis (disappearance of pyuria in absence of infection, significant increase of serum albumin and improvement of renal function tests). The immunological background of both diseases has to be taken into account to explain either the association of the two disorders or the therapeutic response. Moreover, this clinical case confirms and extends the concept that in patients with CD a more accurate detection of autoimmune associated disorders is required.

Effect of Helicobacter pylori eradication on gastric epithelial proliferation. Relationship with ras oncogene p21 expression.

BACKGROUND: Impaired changes in gastric epithelium proliferation have been described in Helicobacter pylori infection, and a progressive increase of proliferating cells has been shown with the progression of mucosal lesions. AIMS: Purpose of this investigation was to study the effect of eradication on bacterium-induced proliferative changes, evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS: This retrospective study was performed, before and after therapy, in five different groups of patients with progressive stages of Helicobacter pylori damage (N: normality; HG: histological gastritis with normal endoscopy; EHG: histological gastritis with endoscopic chronic erosions; CIM: complete intestinal metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after eradication, a normalization of PCNA LI was observed in the areas of gastritis, but not in those of intestinal metaplasia, which showed on unchanged type. Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only associated to intestinal metaplasia. The protein was also expressed in the cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest that the development of intestinal metaplasia may be associated with an alteration in the control of gastric epithelium proliferation and could represent an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes are necessary for a complete progression to neoplastic disease. A long-term follow-up on extension, type, proliferative situation and oncoprotein expression in areas of intestinal metaplasia may be helpful to explain whether the present data provide new information on the mechanism of Helicobacter pylori induced gastric carcinogenesis.