Mario Del Piano

Endoscopy or surgery for malignant GI outlet obstruction

BACKGROUND The treatment of gastroduodenal outflow obstruction (GOO) caused by malignant diseases represents a significant challenge. Open surgical gastrojejunostomy (GJ) has been the treatment of choice, but it has high morbidity and mortality rates. More recently, endoscopic placement of self-expanding metallic stents (SEMS) has been proposed and the results of small, preliminary studies are encouraging. This study compared technical and clinical success, morbidity, mortality, and hospital stay in patients undergoing endoscopic and surgical treatment of GOO. METHODS Medical records of 60 consecutive patients with GOO seen between April 1997 and November 2002 were retrospectively reviewed. Because of extremely short life expectancy, 13 patients were treated by insertion of a double-lumen nasogastric-jejunal tube. The remaining 47 patients (28 men, 19 women; mean age 73.5 years, range 48-92 years) with unresectable pancreatic (33), gastric (7), metastatic lymph nodal (4), papillary (2), and biliary (1) tumors were treated by placement of a SEMS (24) or open surgical GJ (23). RESULTS The technical success rates were similar, but clinical success was lower in the GJ group (92% vs. 56%, p = 0.0067). The SEMS group had a shorter length of hospital stay (3.0 [1.4] days vs. 24.1 [10.3], p < 0.001). Thirty-day mortality was 30% in the GJ group, and 0% in the SEMS group ( p = 0.004). Morbidity was higher in the GJ compared with the SEMS group (61% vs. 17%, p = 0.0021). Mean survival was longer in the SEMS group (96.1 [9.6] days vs. 70.2 [36.2] days, p = 0.0165 for a single test of hypothesis; Bonferroni correction for a multiple testing removes this significance), consequently, out-of-hospital survival was longer for the SEMS group (93.2 [9.3] days vs. 46.0 [31.5] days, p < 0.001). None of the endoscopic procedures required the assistance of an anesthesiologist or the use of an operating room. CONCLUSIONS The results of this retrospective study suggest that SEMS insertion is better than surgical GJ for palliation of patients with GOO in terms of clinical success, morbidity, and mortality. Technical success rates were similar. SEMS placement should be proposed as the first-line treatment for relief of GOO. However, a randomized, comparative, prospective study of SEMS vs. laparoscopic GJ is needed.

Predicting Mortality in Non-Variceal Upper Gastrointestinal Bleeders: Validation of the Italian PNED Score and Prospective Comparison With the Rockall Score

OBJECTIVES:We sought (i) to validate a new prediction rule of mortality (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to compare the accuracy of the Italian PNED score vs. the Rockall score in predicting the risk of death.METHODS:We conducted prospective validation of analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008. Outcome measure was 30-day mortality. All the variables used to calculate the Rockall score as well as those identified in the Italian predictive model were considered. Calibration of the model was tested using the χ2 goodness-of-fit and performance characteristics with receiver operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of the two predictive models.RESULTS:Over a 16-month period, data on 1,360 patients were entered in a national database and analyzed. Peptic ulcer bleeding was recorded in 60.7% of cases. One or more comorbidities were present in 66% of patients. Endoscopic treatment was delivered in all high-risk patients followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six patients died (mortality 4.85%; 3.54–5.75). The PNED score showed a high discriminant capability and was significantly superior to the Rockall score in predicting the risk of death (AUC 0.81 (0.72–0.90) vs. 0.66 (0.60–0.72), P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk score >8 was 16.05.CONCLUSIONS:The Italian 10-point score for the prediction of death was successfully validated in this independent population of patients with non-variceal gastrointestinal bleeding. The PNED score is accurate and superior to the Rockall score. Further external validation at the international level is needed.

Digestive Endoscopy Is Not a Major Risk Factor for Transmitting Hepatitis C Virus

Context Controversy persists regarding the risk for transmission of hepatitis C virus (HCV) as a result of digestive-tract endoscopy. Contribution This prospective study of HCV-negative patients who underwent gastroscopy with the same endoscopes as HCV-positive patients showed no transmission of infection on follow-up 6 months later. Biopsy with reusable or disposable forceps did not increase the risk for HCV infection. Blood donors who were HCV negative without endoscopic exposure showed a few conversions to infected status an average of 2.5 years later. Implications The risk for HCV transmission by endoscopy is extremely low when standard instrument-cleaning techniques are used. The Editors Health carerelated procedures have been implicated in the transmission of a consistent proportion of contemporary hepatitis C virus (HCV) infections. The role of major surgical operations, such as cardiovascular, gynecologic, and orthopedic procedures, is well established. However, the role of less invasive procedures, such as digestive endoscopy, remains a matter of debate. A claim from a retrospective French study (1) that digestive endoscopic procedures are a major cause of HCV transmission among blood donors has not been substantiated by other authors (2, 3); acquisition of HCV through endoscopy has in fact been rarely reported in recent years (4, 5). Nevertheless, endoscopy as a vehicle for HCV transmission has been suspected since 1996, when blood banks in France and Italy suspended donors who reported a history of recent digestive endoscopy from donating blood for 6 months and up to 1 year, respectively. It is therefore important to establish whether digestive endoscopy represents a real risk and, if so, to define its magnitude. We conducted a prospective study among outpatients referred to 3 endoscopic units in northwestern Italy from 1999 to 2002. The patients entering the study were tested for antibody to HCV (anti-HCV) at baseline and 6 months after endoscopy. The incidence of HCV infection in this cohort was compared with that in blood donors recruited in the same area and during the same time period; these donors had not undergone any digestive endoscopic procedure. Methods Endoscopy Cohort Between January 1999 and December 2002, all of the outpatients referred for upper digestive endoscopy to 3 endoscopic units in northwestern Italy (1 secondary referral center and 2 tertiary referral centers) were asked to participate in this study. Eligibility criteria were age older than 18 years and indication for gastroscopy. We restricted the procedure to gastroscopy in order to obtain a high rate of invasive procedures (for example, gastric biopsy). We excluded patients if they were hospitalized, had previously undergone endoscopic procedures, were known anti-HCV carriers, or had to undergo additional endoscopic procedures other than gastroscopy. However, to identify the potentially infective population, we retrospectively looked for known HCV carriers who underwent gastroscopy in the 3 centers between January 1999 and December 2002. Of 11348 patients fulfilling the inclusion criteria, 9188 (81.0%) agreed to participate and gave written consent. They completed a questionnaire about risk factors for HCV infection during the past 6 months, and a serum sample was obtained from each immediately before endoscopy. Mild sedation with midazolam and hyoscine butylbromide was administered to each patient by using disposable syringes and vials. Gastroscopies were done by using various types of endoscopes, including fiberscopes and video endoscopes (Olympus GIF-Q20, GIF-Q30, GIF-IT30, GIF-IT140, Olympus Europe, Hamburg, Germany). Biopsies were performed with disposable biopsy forceps (Radial Jaw 3, Boston Scientific Microvasive, Natick, Massachusetts) in one center and reusable biopsy forceps (FB-24U-1, Olympus Europe) in another center; the third center used reusable forceps (EN-62143, Pescetto, Genova, Italy) in 1999 and disposable forceps (Max Capacity, Boston Scientific Microvasive) after 1999. Each patient was invited to attend a follow-up visit 6 months after endoscopy in order to obtain a serum sample for determining anti-HCV; at this visit, the patient was asked to complete the HCV questionnaire again. To reduce the risk for false-negative results, potentially immunodeficient patients (those undergoing hemodialysis or receiving immunosuppressive treatment) were also tested for HCV RNA by polymerase chain reaction (PCR). All patients who did not attend the follow-up visit were recontacted by telephone. Among patients in the endoscopy cohort, we identified an at-risk subset of patients: Overall, 912 endoscopic procedures (732 gastroscopies performed on known HCV carriers and 180 gastroscopies performed on newly discovered HCV carriers) were considered potentially infective. When we considered that each endoscope was used 3 times during the endoscopic session and assumed that the anti-HCVpositive patient was the first, second, or third at random, the number of exposed patients per HCV-infectedpatient-day was 0, 1, or 2, with equal probability (the mean of those numbers is 1). Blood Donors Cohort Using a computerized database, we retrospectively identified all 51645 consecutive blood donors at 2 transfusion centers in Torino and Pinerolo between January 1999 and December 2002 who were negative for HCV. Of these, 415 (0.8%) reported previous digestive endoscopy; the blood bank database did not record invasive procedures performed during endoscopy (such as biopsy and polypectomy). These 415 donors were asked to repeat the serologic and virologic HCV tests: 329 (79.3%) agreed, and 86 declined. Of the 51230 blood donors who did not undergo endoscopic procedures during the observation period, 38 280 (74.7%) were tested again after a mean of 2.49 years (range, 6 months to 4 years); the remaining 12 950 blood donors could not be contacted by telephone for retesting or declined to be retested. Retested blood donors found to be newly positive for anti-HCV completed a structured questionnaire aimed at investigating risk factors for HCV infection, including endoscopic procedures, travel history, sexual activity, and potential parenteral exposures to blood or blood products (previous blood, platelet, or plasma transfusions; administration of coagulation factor concentrates; intravenous drug use; tattooing; acupuncture therapy; ear piercing; and major or minor surgery). Cleaning and Disinfection Method The instruments used for the known HCV carriers were not handled differently from those used for the HCV-negative patients; they were not removed from the general instrument pool, were disinfected in the same way as the others, and were then used promptly to perform endoscopy on the HCV-negative patients. Moreover, endoscopic procedures in known HCV carriers were not postponed at the end of the session but were performed according to the list of scheduled appointments. All units participating in this study adhered to the international guidelines for cleaning and disinfection practices in digestive endoscopy (6-10) and reprocessing endoscopic accessories (11); written protocols were available in each center. The staff involved in disinfection procedures consisted of trained nurses who were unaware of the ongoing study. At the end of the endoscopic procedure, the staff manually cleaned the instrument, including brushing the channels; each internal channel was flushed with detergent, rinsed with water, and blown through with air. The endoscopic units used 3 different automated washer-disinfectors (DSD-91E, Medivators, Minneapolis, Minnesota; Circlean MC-12, Shoei, Tokyo, Japan; and ETD2, Olympus Europe), but the reprocessing cycle was similar: 1) The units were immersed in 2% glutaraldehyde for 20 minutes, and internal channels were flushed with the same solution; 2) the units were rinsed internally and externally with drinking-quality water to remove all traces of disinfectant; and 3) the units were dried externally and each channel was flushed with air. Before the first endoscopy of each day, all endoscopes were disinfected in a washer-disinfector. After use, reusable biopsy forceps were immersed in enzymatic detergent solutions; next, they were cleaned first manually and then by a medical-grade ultrasonic cleaner. After rinsing and drying, the forceps were sterilized by autoclave at 134 C for at least 5 minutes. Finally, the sterilized devices were stored in sterile packaging in a closed cupboard where they were protected from dust, humidity, and temperature fluctuations. Laboratory Methods We tested for anti-HCV by using a third-generation enzyme immunoassay (Ortho HCV EIA-3, Ortho Diagnostic Systems, Raritan, New Jersey). Anti-HCV immunoreactivity was confirmed with a third-generation immunoblot assay (RIBA-3, Chiron Corp., Emeryville, California, and Ortho Diagnostic Systems). We measured HCV RNA by using PCR (Cobas Amplicor 2.0, Roche Diagnostic Systems, Branchburg, New Jersey); the sensitivity of this assay was 1000 copies/mL. Statistical Analysis We estimated person-years of observation and incidence rates of anti-HCV seroconversion for both cohorts. We used the difference between the incidence rates to compare the 2 cohorts. For the endoscopy cohort, we also measured the risk for anti-HCV seroconversion 6 months after the procedure, using the number of persons as denominators. Further analyses were limited to subgroups of the endoscopy cohort: 1) 6132 patients who underwent biopsy (biopsy cohort) and 2) 912 patients who underwent endoscopy later in the same day as and with the same instruments used in HCV-positive patients (at-risk cohort). Because we could not identify with certainty each patient in the at-risk cohort, we estimated that number with a rough but conservative approach. If we assume that each endoscope was used approximately 3 times during an ordinary endoscopic session and that at least 1 HCV carrier would be seen at

Evaluation of the intestinal colonization by microencapsulated probiotic bacteria in comparison with the same uncoated strains.

Background Beneficial findings concerning probiotics are increasing day by day. However, one of the most important parameter which affects the probiotic activity of a microorganism is its survival during the gastroduodenal transit. Some microencapsulation techniques could be applied to bacterial cells to improve this parameter. Methods A comparison between the intestinal colonization by microencapsulated bacteria and the same not microencapsulated strains has been conducted in a double blind, randomized, cross-over study. The study (April to July 2005) involved 44 healthy volunteers. In particular, participants were divided into 2 groups: group A (21 participants) received a mix of probiotic strains Lactobacillus plantarum LP01 (LMG P-21021) and Bifidobacterium breve BR03 (DSM 16604) in an uncoated form, group B (23 participants) was given the same strains microencapsulated with a gastroresistant material. The not microencapsulated strains were administered at 5×109 colony forming units/strain/d for 21 days, whereas the microencapsulated bacteria were given at 1×109 colony forming units/strain/d for 21 days. At the end of the first period of treatment with probiotics a 3 weeks washout phase has been included in the study protocol. At the end of the washout period the groups were crossed: in detail, group A had the microencapsulated and group B the uncoated bacteria. The administered amounts of each strain were the same as the first treatment. The quantitative evaluation of intestinal colonization by strains microencapsulated or not microencapsulated was made by fecal samples examination at the beginning of the clinical trial, after 10 and 21 days of each treatment period. In particular, fecal heterofermentative Lactobacilli and Bifidobacteria have been counted. Results A statistically significant increase in the fecal amounts of Lactobacilli and Bifidobacteria was recorded in both groups at the end of each treatment compared with d0 or d42 (P<0.0001 and P<0.0001 at d21, P<0.0001 and P<0.0001 at d63 for Lactobacilli and Bifidobacteria, respectively), confirming the ability of the 2 strains to colonize the human gut, either in a gastroprotected form or not. Participants treated with the microencapsulated bacteria reported a kinetics of intestinal colonization quite similar to participants who received not coated strains. Conclusions Probiotics are able to exert many different beneficial effects on the human host. These effects are mediated by the number of viable cells which reach the gut. The microencapsulation techique used in this study is a valid strategy to significantly improve gastroresistance of strains, thus enhancing their probiotic activity and allowing the use of a 5 times lower amount.

The use of probiotics in healthy volunteers with evacuation disorders and hard stools: A double-blind, randomized, placebo-controlled study

Background Evacuation disorders and hard stools are common in industrialized countries, affecting on average 12% to 17% of the adult healthy population at any age. Dietary supplementation with probiotic microorganisms may be useful in reducing the disorder. Methods We performed a double-blind, randomized, placebo-controlled study to evaluate the effectiveness of 2 different probiotic blends, either mixed Lactobacillus plantarum LP01 (LMG P-21021) and Bifidobacterium breve BR03 (DSM 16604) or Bifidobacterium animalis subspecies lactis BS01 (LMG P-21384), in the management of evacuation disorders and intestinal discomfort. In a period of 5 years (2003 to 2008), the study involved 300 healthy volunteers (151 males and 149 females; age 24 to 71 y) with evacuation disorders and hard stools. In particular, subjects were divided into 3 groups: 80 subjects in the group A received placebo, 110 subjects in the group B received mixed L. plantarum LP01 and B. breve BR03 (2.5×109 colony-forming units/d of each strain), and 110 subjects in the group C received B. animalis subsp. lactis BS01 (5×109 colony-forming units/d) for 30 days. At the beginning of the observational study, the healthy status of volunteers was evaluated by a complete, laboratory and ultrasound study of the abdomen. The physical examination was repeated after 15 and 30 days. In particular, the main troubles typically associated with evacuation disorders and hard stools as well as abdominal bloating were considered as parameters of interest. Exclusion criteria were items of gastrointestinal diseases and antibiotics intake. Results Subjects treated with the mixed probiotic strains L. plantarum LP01 and B. breve BR03 or B. animalis subsp. lactis BS01 reported a significant improvement in the number of weekly bowel movements and in the main troubles associated with evacuations, particularly consistency of feces and ease of expulsion. Discomfort items such as abdominal bloating and anal itching, burning, or pain also registered a relevant improvement in the active groups receiving probiotics. Conclusions The intake of an effective amount of mixed L. plantarum LP01 and B. breve BR03 or B. animalis subsp. lactis BS01 for 30 days is able to significantly relieve the evacuation disorders and hard stools, thus providing a useful tool for the management of such condition, which is particularly widespread in industrialized countries at any age.

Is microencapsulation the future of probiotic preparations? The increased efficacy of gastro-protected probiotics

In a recent publication we assessed the kinetics of intestinal colonization by microencapsulated probiotic bacteria in comparison with the same strains given in an uncoated form. It’s well known, in fact, that microencapsulation of probiotics with specific materials is able to confer a significant resistance to gastric juice, thus protecting the cells during the gastric and duodenal transit and enhancing the probiotic efficacy of any supplementation. In any case, this was the first study reporting the fecal amounts of probiotics administered in a coated, protected form compared with traditional, uncoated ones. Here we discuss additional in vitro data of resistance of the same bacteria to gastric juice, human bile and pancreatic secretion and correlate them with the results of in vivo gut colonization. .

Mortality from nonulcer bleeding is similar to that of ulcer bleeding in high-risk patients with nonvariceal hemorrhage: A prospective database study in Italy

BACKGROUND Nonulcer causes of bleeding are often regarded as minor, ie, associated with a lower risk of mortality. OBJECTIVE To assess the risk of death from nonulcer causes of upper GI bleeding (UGIB). DESIGN Secondary analysis of prospectively collected data from 3 national databases. SETTINGS Community and teaching hospitals. PATIENTS Consecutive patients admitted for acute nonvariceal UGIB. INTERVENTIONS Early endoscopy, medical and endoscopic treatment as appropriate. MAIN OUTCOME MEASUREMENTS Thirty-day mortality, recurrent bleeding, and need for surgery. RESULTS A total of 3207 patients (65.8% male), mean (standard deviation) age 68.3 (16.4) years, were analyzed. Overall mortality was 4.45% (143 patients). According to the source of bleeding, mortality was 9.8% for neoplasia, 4.8% for Mallory-Weiss tears, 4.8% for vascular lesions, 4.4% for gastroduodenal erosions, 4.4% for duodenal ulcer, and 3.1% for gastric ulcer. Frequency of death was not different among benign endoscopic diagnoses (overall P = .567). Risk of death was significantly higher in patients with neoplasia compared with benign conditions (odds ratio 2.50; 95% CI, 1.32-4.46; P < .0001). Gastric or duodenal ulcer significantly increased the risk of death, but this was not related to the presence of high-risk stigmata (P = .368). The strongest predictor of mortality for all causes of nonvariceal UGIB was the overall physical status of the patient measured with the American Society of Anesthesiologists score (1-2 vs 3-4, P < .001). LIMITATIONS No data on the American Society of Anesthesiologists class score in the Prometeo study. CONCLUSIONS Nonulcer causes of nonvariceal UGIB have a risk of death, similar to bleeding peptic ulcers in the clinical context of a high-risk patient.

Fluorescence in situ hybridisation in the cytological diagnosis of pancreatobiliary tumours

Aims: To assess the sensitivity, specificity, positive and negative predictive values of fluorescence in situ hybridisation (FISH) and conventional cytology in identifying bile duct stricture malignancies. Methods: Brushing samples were collected from 64 patients by means of endoscopic retrograde cholangiopancreatography, and assessed cytologically and by means of a multi-probe FISH set. The cytological diagnoses were: positive, negative and suspicious, whereas criteria for FISH positivity were: more than five polysomic cells or more than 10 trisomic cells for chromosomes 3 or 7. Results: Forty-eight of the 64 patients showed histological or clinical signs of malignancy. The sensitivity of cytology was high (77%) if suspicious cases were considered positive, but was significantly lower than that of FISH if suspicious cases were considered negative (58% versus 90%; p < 0.05). The specificity of cytology was 81% (positive and suspicious) or 100% (negative and suspicious), and the specificity of FISH was 94% (p = 1). FISH yielded one false negative result (isolated chromosome 7 trisomy). FISH allowed a definite diagnosis of 9/12 cytologically inconclusive cases. Conclusions: Our findings suggest using FISH in the case of bile duct strictures cytologically negative or inconclusive; a FISH diagnosis of malignancy should only be made in the presence of polysomic pattern.

In vitro sensitivity of probiotics to human pancreatic juice.

Background The resistance of gut flora with probiotic activity to pancreatic juice is usually tested with artificial pancreatic fluid. Previous studies evaluated the sensitivity of diverse probiotics to human gastric and biliary secretion; none tested the resistance of probiotics to human pancreatic juice. As most bacteria sensitive to artificial pancreatic fluid in vitro have a high rate of isolation from feces, the resistance to human pancreatic juice could be higher. Aim The aim of this study was to compare the sensitivity of different strains of probiotics to artificial and human pancreatic juice. Materials and Methods The viability of 8 strains of Lactobacillus and 4 strains of Bifidobacterium was tested with standard artificial and human pancreatic juice withdrawn from 16 patients during endoscopic retrograde cholangiopancreatography procedure. The mortality rate (%) of various bacteria was measured after 5, 30, and 60 minutes contact time. The results were normalized for mortality rate induced by hypotonic condition and time exposure to 37°C. Results When incubated with artificial and human pancreatic juice, the mortality rate of all strains of Lactobacillus at 5, 30, and 60 minutes was 10.1 versus 7.6, 20.5 versus 19.7, and 28.6 versus 29.8, respectively; whereas the mortality rate of all strains of Bifidobacterium was 8.0 versus 9.2, 33.3 versus 28.9, and 42.2 versus 44.4, respectively. Conclusions All the tested strains were sensitive to artificial and human pancreatic juice depending on time contact. Bifidobacterium strains seem to be more sensitive than Lactobacillus strains in particular at higher time contact. There is no significant difference between sensitivity to simulated and human pancreatic juice. For this reason, probiotics activity may be tested with artificial pancreatic fluid using a standardized, easier, and less costly procedure.

Clinical experience with probiotics in the elderly on total enteral nutrition.

Background: Recent data support that after 2 years of age, intestinal microflora remains relatively constant over time, except in elderly people, who harbor fewer bifidobacteria and a higher population of fungi and enterobacteria than young adults. Diet supplementation with probiotics may improve the nutritional status and reduce the impaired immunity associated with aging. The goal of this study was to establish the effect on bifidobacteria fecal counts, and some clinical parameters, of bifidobacteria supplementation to elderly patients in total parenteral nutrition. Methods: Thirteen patients (6 men and 7 women; mean age, 69 years; range, 65–76 years) affected by permanent vegetative status (PVS) and fed by total enteral nutrition (TEN) were studied. Bifidobacteria and clostridia were investigated by microbiologic and molecular biology methods in stool specimens collected twice at basal time (T–2 and T0) and after 12 and 15 days (T12 and T15, respectively). Seven patients with basal bifidobacteria counts less than 10−7 were supplemented with Bifidobacterium longum W 11 for 12 days. The remaining 6 patients were used as control subjects. For 1 month diarrhea and fever episodes, use of antibiotics, and nutritional status (BMI) were assessed. Results: In the 7 patients with bifidobacteria counts less than 107, the administration of B. longum W 11 resulted in a 1 log increase in 6 of 7 patients at T12. No statistically significant difference in episodes of fever or diarrhea, use of antibiotics, or BMI was observed between the treatment and control groups. Conclusion: The administration of B. longum W11 in PVS patients fed by TEN is effective in increasing the population of bifidobacteria. Larger studies with longer follow-up could demonstrate the influence of these microbiologic changes in a clinical setting.