Photodynamic therapy with polyhematoporphyrin for malignant biliary obstruction: A nationwide retrospective study of 150 consecutive applications.

BACKGROUND: Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction. OBJECTIVE: The objective of this article is to assess the feasibility and safety of this technique. METHODS: In this nationwide, retrospective study of prospectively collected clinical data, all patients treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013 were included. Feasibility, adverse events, stent patency and mortality rates were investigated. RESULTS: Eighty-eight patients (54 male, 34 female, median age 69 years) underwent 150 PDT procedures at seven Austrian referral centers for biliary endoscopy. The predominant underlying disease was Klatskin tumor (79/88). All PDT procedures were feasible without technical issues. Cholangitis was the most frequent adverse event (21/88). Stent patency was 246 days (95% CI 203-289) median and was significantly longer for metal than for plastic stents (269 vs. 62 days, p < 0.01). The median survival was 12.4 months (95% CI 9.7-14.9 m) calculated from first PDT and 15.6 months (95% CI 12.3-18.7 m) calculated from initial diagnosis. In patients suffering from biliary tract cancer, Cox regression revealed the number of PDT treatment sessions as the only independent predictor of survival at a multivariate analysis (p = 0.048). CONCLUSION: PDT using polyhematoporphyrin was feasible and safe in this nationwide analysis. Survival data suggest a benefit of PDT in this unselected real-life patient population. Prospective trials comparing PDT to other palliative treatments will help to define its role in the management of malignant biliary obstruction. The study is registered at ClinicalTrials.gov number: NCT02504957.

Sex is a stronger predictor of colorectal adenoma and advanced adenoma than fecal occult blood test.

Due to high costs and limited availability of screening colonoscopy, some screening programs require a positive fecal occult blood test (FOBT) before screening colonoscopy is remunerated. As male sex is a strong predictor of adenoma and advanced adenoma, we evaluated whether a positive FOBT or male sex is a stronger risk factor for adenoma and advanced adenoma. FOBT and screening colonoscopy results from 18.665 consecutive patients participating in a "national health check program" between 2009 and 2011 were included in this cohort study. Age-corrected adenoma detection rates (ADR), advanced adenoma detection rates (AADR) and carcinoma detection rates were calculated for men and women according to FOBT result separately. ADR and AADR in FOBT-positive men (34.6 and 11.8 %) and FOBT-negative men (29.1 and 7.6 %) were higher than ADR and AADR in FOBT-positive women (20 and 6.9 %) and in FOBT-negative women (17.6 and 4.4 %), (p = 0.0003). Men with negative FOBT were at higher risk of having an adenoma and advanced adenoma than women with positive FOBT (p < 0.0001). Odds ratios of a positive FOBT for ADR and AADR were 1.3 (1.1-1.5) (p = 0.0047) and 1.6 (1.2-2.1) (p < 0.0001), respectively. Odds ratios of male sex to predict ADR and AADR were significantly higher with 1.9 (1.8-2.1) and 1.8 (1.6-2), respectively (p < 0.001). Male sex is a stronger predictor for colorectal adenoma and advanced adenoma than positive FOBT. These results should be taken into account analyzing FOBT-based screening programs.

Clinical presentation of venous thromboembolism in inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE), but data on frequency, site of thrombosis and risk factors are limited. We sought to determine prevalence, incidence as well as location and clinical features of first VTE among IBD patients. METHODS: We evaluated a cohort of 2811 IBD patients for a history of symptomatic, objectively confirmed first VTE, recruited from 14 referral centers. Patients with VTE before IBD diagnosis or cancer were excluded. Incidence rates were calculated based on person-years from IBD diagnosis to first VTE or end of follow-up, respectively. RESULTS: 2784 patients (total observation time 24,778 person-years) were analyzed. Overall, of 157 IBD patients with a history of VTE, 142 (90.4%) had deep vein thrombosis (DVT) and/or pulmonary embolism (PE), whereas 15 (9.6%) had cerebral, portal, mesenteric, splenic or internal jugular vein thrombosis. The prevalence and incidence rate of all VTE was 5.6% and 6.3 per 1000 person years, respectively. Patients with VTE were older at IBD diagnosis than those without VTE (34.4±14.8years vs 32.1±14.4years, p=0.045), but did not differ regarding sex, underlying IBD and disease duration. 121 (77.1%) VTE were unprovoked, 122 (77.7%) occurred in outpatients and 78 (60.9%) in patients with active disease. Medication at first VTE included corticosteroids (42.3%), thiopurines (21.2%), and infliximab (0.7%). CONCLUSION: VTE is frequent in IBD patients. Most of them are unprovoked and occur in outpatients. DVT and PE are most common and unusual sites of thrombosis are rare.

Quality assessment of endoscopic retrograde cholangiopancreatography: results of a running nationwide Austrian benchmarking project after 5 years of implementation.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) has a high risk of various complications. The aim of this study is to report the main ERCP outcome, that means complications and success rates, on the basis of the pooled data of a national continuous quality assessment program. METHODS: This study is an uncontrolled prospective survey and provides data from both academic and community-based endoscopy centers with varying case volumes and expertise. Data were collected within a nationwide voluntary ERCP benchmarking project that was initiated by the Austrian Society of Gastroenterology and Hepatology. RESULTS: In total, 42 sites participated in this program for varying periods (1 month up to 5 years) and reported 13 513 procedures within 5 years. The overall complication rate in nonselected patients was 10.1%. Post-ERCP pancreatitis occurred in 4.2%, bleeding in 3.6% (0.4% clinically relevant), cholangitis in 1.4%, cardiopulmonary complications in 1.2%, perforation in 0.6%, and procedure-related deaths in 0.1% of procedures. The overall therapeutic and diagnostic target was achieved in 80.3% (2009-2011) to 84.8% (2006/2007) of procedures. The desired duct was visualized in 90.7% and cannulated in 88.8% of procedures. CONCLUSION: The aim of the running benchmarking project in ERCP is to improve patient care in Austria. The survey reflects the general effectiveness and safety of ERCP. The overall complication and success rates are consistent with the available literature data. It sets an example as a benchmarking program that might result in international or even pan-European projects in high-risk endoscopic procedures.

Sedation in screening colonoscopy: impact on quality indicators and complications.

OBJECTIVES: Quality indicators including cecal intubation rate (CIR) and adenoma detection rate (ADR) are established. Sex differences of quality indicators are observed, but the influence of sedation has not been investigated so far. The objective of this study is to assess the impact of sedation on quality indicators, including CIR and ADR, according to sex. METHODS: We analyzed data of 52,506 screening colonoscopies performed by 196 endoscopists between November 2007 and April 2011 according to the Austrian "quality management for colon cancer prevention" program. RESULTS: Sedation did not affect polyp detection rate (women P=0.7972, men P=0.3711) or ADR for both sexes (women P=0.2773, men P=0.8676). ADR was not significantly influenced by sedation (P=0.1272), but by age and sex (both P<0.0001), when the executing endoscopist was considered. Although women were more often sedated than men (90.70 vs. 81.83%; P<0.0001), CIR was slightly lower in women than in men (94.69 vs. 96.58%; P<0.0001). Sedation improved the CIR in women by 2.95% (94.96 vs. 92.01%; P<0.0001), whereas in men it was just by 1.28% (96.81 vs. 95.53%; P<0.0001). Sedated women only reached the CIR of unsedated men (94.96 vs. 95.53%; P=0.1005). Accounting for the intra-observer influence of the endoscopist, the overall CIR was influenced by the interaction of sex and age (P=0.0049), but not by sedation (P=0.1435). CONCLUSIONS: Sedation does not increase adenoma or polyp detection, although it leads to an increase in CIR in men and women. This effect is more pronounced in women, yet CIR of men remains higher compared with women. Quality indicators are mainly influenced by the patient's age, sex, and the endoscopists' individual performance, rather than the endoscopists' subspeciality or procedural experience.

Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study.

Wilson disease (WD), a disorder of copper metabolism is caused by mutations in the ATP7B gene, a copper transporting ATPase. In the present study we describe a novel mutation in exon 9 of the ATP7B gene. The ATP7B gene was analyzed for mutations by denaturing HPLC and direct sequencing. DNA from 100 healthy blood donors from the same geographic area was examined as control. Sixteen (7.4%) out of the 216 patients diagnosed with WD in Austria carried the newly identified R816S(c.2448G>T) point mutation in exon 9 (4 male, age: 19 (6-30) years, median (range)). One patient was homozygous for R816S(c.2448G>T). Thirteen patients were compound heterozygotes (p.H1069Q(c.3207C>A)/R816S(c.2448G>T) (N=6), P539L/R816S(c.2448G>T) (N=3), each one G710S/R816S(c.2448G>T), P767P(2299insC)/R816S(c.2448G>T), W779G/R816S(c.2448G>T), T1220M/R816S(c.2448G>T)). In two patients no second mutation was identified. Interestingly, all but three of the patients originated within a distinct geographical area in Austria. Eleven patients presented with hepatic disease, 3 patients with neurological disease and 2 were asymptomatic sisters of an index case. A liver biopsy was available in 14 patients. Three patients showed advanced liver disease with liver transplantation for acute hepatic failure in two. The remaining patients had only mild histological changes, most commonly steatosis. Chronic hepatitis was described in five patients. Kayser-Fleischer ring was present in five patients. None of the 100 healthy controls carried the mutation. We describe a novel mutation in the ATP7B gene, occurring in patients originated from a distinct geographical area in Austria associated with a variable course of the disease.

Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD. METHODS: We assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006-December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE. RESULTS: Overall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8-45.0 vs 21.7%; 95% CI: 18.8-24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4-4.2; P = .001). CONCLUSIONS: Patients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members.

BACKGROUND AND AIMS: Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members. METHODS: Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene. RESULTS: Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs. CONCLUSION: This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers.

Quantitative autonomic testing in the management of botulism.

Even with mild neurological signs, patients with botulism frequently complain of autonomic symptoms. This study aimed at the evaluation of sudomotor and cardiovascular reflex functions by quantitative autonomic testing (QAT), which may identify patients with autonomic involvement but otherwise benign clinical presentation. Five patients with food-borne botulism were subjected to a structured questionnaire on autonomic symptoms, cardiac and neurological examination, and QAT after a median of 2 weeks (baseline) and 12 weeks (follow-up) post intoxication. For calculation of haemodynamic and cardiovascular autonomic parameters, we used the Task Force((R)) Monitor (Version 2.1, CNSystems, Graz, Austria). Cardiovagal function was assessed by Ewing's test battery. Autonomic complaints were more pronounced than neurological symptoms. Baseline tests revealed widely abnormal sudomotor function and marked impairment of heart rate variation and blood pressure response to standing. Prominent features of cardiovascular failure were high resting heart rate, supine hypertension, orthostatic hypotension, and impaired baroreflex function. Three patients reported inability to keep up with their routine amount of physical work. Based on the baseline QAT results, these three patients were instructed to engage in physical activity but avoid physical strain until there was considerable improvement. On follow-up, fatigue was the most frequent residual complaint, sympathetic skin responses were present, and cardiovascular QAT results were significantly improved and did not differ from those of ten control subjects. QAT identified autonomic involvement in botulism patients with otherwise benign neurological presentation. Comprehensive evaluation of autonomic failure may provide useful information for the management of botulism.

Concomitant manifestation of pyoderma gangrenosum and colorectal carcinoma.

Pyoderma gangrenosum is an ulcerative skin disease of unknown origin and is commonly associated with inflammatory bowel disease, arthritis or lymphoproliferative disorders. Only sporadic cases of pyoderma gangrenosum in combination with malignant disease of the gastrointestinal tract have been reported until now. We report on a 53-year-old patient who suffered injury to the right scapula while gardening. Initially, the patient had only a superficial wound of the upper skin but in the subsequent weeks the lesion developed into an ulcerative defect and pyoderma gangrenosum was diagnosed. Laboratory test results, ultrasound of the abdomen and computed tomography of the chest and abdomen were normal. Immunosuppressive therapy with prednisolone and azathioprine was initiated. Four months later the patient was admitted to the gastroenterology department for further examination because of chronic fatigue, subfebrile temperature and a positive fecal occult blood test. Colonoscopy showed a semicircular carcinoma of the sigmoid colon measuring 3-4 cm. A left-sided hemicolectomy was performed. Microscopic examination revealed an adenocarcinoma (T3, N2, G3) and consequently the patient was given adjuvant chemotherapy. Nine months later the patient was asymptomatic and the pyoderma gangrenosum had recovered. Pyoderma gangrenosum is not only associated with inflammatory bowel disease or lymphoproliferative disorders. This case report demonstrates that colorectal carcinoma must also be considered as a possible differential diagnosis. The fast and complete remission of pyoderma gangrenosum following surgical treatment of colorectal carcinoma emphasizes a causal relationship.

[The frequency of wound infections after PEG-placement and utilization of glycogel wound dressing: a randomized controlled trial]. / Häufigkeit von Wundinfektionen bei Verwendung eines Glycogelverbandes nach PEG-Anlage: Ergebnisse einer kontrollierten Studie.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the method of choice for long- term artificial enteral feeding. Standardized wound management such as daily dressing changes and local disinfection of the exit site helps to keep complication rates low. New bacteriostatic glycogel wound dressing has not yet been tested. We compared glycogel dressing to the usual method of wound aftercare with regard to wound infections. METHODS: The standard wound management was compared to glycogel dressing. 100 consecutive patients were investigated in a prospective randomized trial from Aug. 2004 to Jan. 2006 regarding wound infections. We also compared indications for PEG placement, complications other than wound infection, and mortality. The exit site was examined and scored daily using a specific wound scoring system. After 30 days, the patients were followed up by phone calls to determine if any infection had occurred after discharge. RESULTS: During our study, 98 out of 100 patients had a successful PEG procedure performed. Out of these 98 patients, 48 patients received standard wound dressing care and 50 patients used glycogel dressing. The indications for PEG placement were not significantly different between the two groups. A total of 88% of patients (n = 42) with standard wound care had no relevant infection (50%, n = 24 with score 0 or 1; 38%, n = 18 had score 2), 10% (n = 5) presented with serious local infection (score 3) and one patient (2%) had severe infection necessitating PEG removal (score 4). In the group using glycogel dressing, 88% of the patients (n = 44) did not show any relevant sign of infection (54%, n = 27 with score 0 or 1; 34%, n = 17 had score 2), 8% (n = 4) had serious local infection (score 3), 2% (n = 1) had severe infection (score 4) and 2% (n = 1) were lost to follow up. CONCLUSION: Regarding wound infection rates after PEG placement, glycogel wound dressing was found to be as effective as standard wound dressing. Thus, omitting daily changes of regular wound dressings by using glycogel dressing instead may be advantageous for patients and generally help to decrease overall cost.

A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.

OBJECTIVE: Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey. METHODS: Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator. RESULTS: 6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients; using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH. CONCLUSION: This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy.

Long-term outcome following placement of percutaneous endoscopic gastrostomy in younger and older patients.

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is the method of choice in maintaining enteral nutrition in patients with swallowing and nutritional disorders of different etiology. The aim of this study was to assess the long-term outcome of patients following placement of a PEG. MATERIAL AND METHODS: All patients who received a PEG between October 1999 and September 2000 were included in this prospective study. Long-term function, replacement or removal of the PEG, complications and survival of the patients were analyzed in group A (younger than 75 years) and group B (75 years or older). RESULTS: The indications for PEG placement in group A (54 patients, mean age 54.5 years) were neurological (66.7%) and malignant (31.5%) disorders, whereas in group B (40 patients, mean age 81 years) the indications were predominantly neurological diseases (87.5%). The majority of patients (91 of 94 patients; 96.8%) could be followed long term or until death. In group A, 46 patients (85.2%) had uncomplicated long-term function of their PEG and interventions were necessary in only 8 patients. Removal of the PEG was possible during the course in 17 patients (31.5%). In group B, uncomplicated long-term function was observed in 34 patients (85%) and interventions were required in only 6 patients. Removal of the PEG was not possible in group B. Survival rates for 1-, 2- and 5 years in group A were 73.9%, 61.8% and 43.9%, respectively, and in group B 41.4%, 31.9% and 15.9%, respectively; the difference was statistically significant (p=0.002). CONCLUSIONS: Excellent long-term function of PEG was seen in this study of 94 consecutive patients, and interventions were necessary only in a minority of patients. The prognosis for older patients was worse; however, the 2-year survival rate of 32% justified the PEG insertion.

ERCP is safe and effective in patients 80 years of age and older compared with younger patients.

BACKGROUND: Biliary disease frequently occurs in the elderly, but there are limited data on ERCP in the elderly population. PATIENTS: A total of 502 patients (group A, 97; group B, 405) underwent 724 ERCP procedures. MAIN OUTCOME MEASUREMENTS: All consecutive ERCPs performed between 2000 and 2002 at a single center were retrospectively reviewed for patients >/=80 years old (group A) and patients <80 years old (group B) to evaluate endoscopic findings, interventions, complications, and mortality related to complications. RESULTS: The number of important chronic concomitant diseases was significantly higher in the older group (average per patient 1.08 vs 0.57, P < .001). Successful cannulation was achieved in 88% in group A versus 86% in group B, and endoscopic sphincterotomy was performed in 63.2% versus 51.4%. Periampullary diverticulum was found significantly more often in patients of group A (39.2%) than of group B (14.1%, P < .001). Stents were used in 24.1% of ERCP procedures in group A and in 22.9% in group B. There was no significant difference in the complication rate between group A (6.8%) and group B (5.1%) and in early mortality (1.03% vs 0.25%), respectively. CONCLUSION: ERCP is a safe and effective intervention in the elderly because complication and early mortality rates are comparable to those of younger patients, although comorbidity is significantly higher.

Colorectal cancer in geriatric patients: endoscopic diagnosis and surgical treatment.

AIM: To investigate the prevalence of colorectal cancer in geriatric patients undergoing endoscopy and to analyze their outcome. METHODS: All consecutive patients older than 80 years who underwent lower gastrointestinal endoscopy between January 1995 and December 2002 at our institution were included. Patients with endoscopic diagnosis of colorectal cancer were evaluated with respect to indication, localization and stage of cancer, therapeutic consequences, and survival. RESULTS: Colorectal cancer was diagnosed in 88 patients (6% of all endoscopies, 55 women and 33 men, mean age 85.2 years). Frequent indications were lower gastrointestinal bleeding (25%), anemia (24%) or sonographic suspicion of tumor (10%). Localization of cancer was predominantly the sigmoid colon (27%), the rectum (26%), and the ascending colon (20%). Stage Dukes A was rare (1%), but Dukes D was diagnosed in 22% of cases. Curative surgery was performed in 54 patients (61.4%), in the remaining 34 patients (38.6%) surgical treatment was not feasible due to malnutrition and asthenia or cardiopulmonary comorbidity (15 patients), distant metastases (11 patients) or refusal of operation (8 patients). Patients undergoing surgery had a very low in-hospital mortality rate (2%). Operated patients had a one-year and three-year survival rate of 88% and 49%, and the survival rates for non-operated patients amounted to 46% and 13% respectively. CONCLUSION: Nearly two-thirds of 88 geriatric patients with endoscopic diagnosis of colorectal cancer underwent successful surgery at a very low perioperative mortality rate, resulting in significantly higher survival rates. Hence, the clinical relevance of lower gastrointestinal endoscopy and oncologic surgery in geriatric patients is demonstrated.

[Natural therapy instead of chemistry? Probiotics in gastroenterology]. / Natur statt Chemie? Einsatzgebiete für Probiotika in der Gastroenterologie.

Probiotics are living microorganisms that upon ingestion exert health benefits. The impact of probiotics on gut flora represents a new and interesting therapeutic approach in a number of diseases of the gastrointestinal tract. According to actual publications and guidelines of medical societies, the clinical relevance of probiotics can be described as follows: (a) In the case of ulcerative colitis, available data demonstrate benefits of probiotic therapy. (b) The available data regarding pouchitis are limited, but the therapeutic effect seems to be excellent. (c) In the case of Crohn's disease, the role of probiotics is not clearly defined, thus the results of new trials have to be awaited before probiotic therapy is recommended. (d) Further indications such as antibiotic-associated diarrhea, acute pancreatitis or irritable bowel syndrome have been reported recently. The results of these clinical trials have been encouraging, but they often included only a small number of patients and therefore a clear-cut assessment seems difficult at the moment.