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.

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.

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.

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.

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.

[Indications and complications of percutaneous endoscopic gastrostomy]. / Indikationen und Komplikationen der perkutanen endoskopischen Gastrostomie.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) plays an important role in maintaining enteral nutrition in patients with swallowing disorders of different etiologies. The aim of our study was to record indications and complications of PEG-placement in a one-year period. METHODS: All patients were investigated prospectively regarding indications, wound infections, other complications and mortality between 1999-10-01 and 2000-09-30. The exit site was examined daily, after 30 days a follow-up by telephone was carried out. RESULTS: The PEG-procedure was performed in 93 patients, one patient received a percutaneous endoscopic jejunostomy. The mean age of the patients was 65.4 years (range 7 months--92 years). The most frequent indications were neurological diseases (n = 61, 65%). 21 patients had a PEG-placement because of malignancies (22%), 9 patients following brain injury (10%) and 3 patients (3%) due to other benign swallowing disorders. 63 patients (67%) had no complications, 28 patients (30%) had wound infections, and in two patients hemorrhage was observed (small hematoma requiring no further intervention). One patient had laparotomy because of suspected perforation--however, laparotomy was negative. In 7 patients (7%) wound infections (n = 28) were mild and needed only local or no therapy. In 18 patients (19%) we found a relevant infection that required systemic antibiotic therapy. 2 patients had serious local infections that caused further interventions. One patient died from sepsis caused by wound infection. Patients receiving antibiotic therapy at the time of PEG-placement suffered from wound infections in 25%. Patients with malignant diseases more often had wound infections. 8 patients died after 7 days and 19 patients after 30 days (8% and 19%, respectively) from their underlying disease. CONCLUSIONS: PEG is regarded as a small intervention with low morbidity and mortality. However, our analysis of daily practice shows a remarkable rate of complications. The high mortality in our study reflects the seriousness of the comorbidities. Antibiotic therapy failed to prevent wound infection in 25% of our patients.