Infliximab for inflammatory bowel disease in Denmark 1999-2005: clinical outcome and follow-up evaluation of malignancy and mortality.

BACKGROUND & AIMS: Data on safety and long-term follow-up evaluation of population-based cohorts of inflammatory bowel disease (IBD) patients treated with infliximab are sparse. The aim of this article is to describe the use of infliximab in a national Danish population-based IBD cohort during 1999-2005. METHODS: Medical records of all infliximab-treated IBD patients were scrutinized to abstract information on patient demographics, treatment efficacy, and adverse events. RESULTS: A total of 651 patients (619 with Crohn's disease, 15 with ulcerative colitis, and 17 with colonic IBD type unclassified) received infliximab during 1999-2005. A total of 3351 infusions were administered, with a median of 3 infusions per patient. A positive clinical response was observed in 82.7% (95% confidence interval, 79.9-85.5) of patients. Infusion reactions were observed after 146 of 3351 infusions (4.4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95 patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2-1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0-3.2). Two deaths caused by infections were possibly related to infliximab. CONCLUSIONS: Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed.

Genetic and environmental factors as predictors of disease severity and extent at time of diagnosis in an inception cohort of inflammatory bowel disease, Copenhagen County and City 2003-2005.

BACKGROUND AND AIMS: The etiology of the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to investigate the influence of genetic, serological, and environmental factors on phenotypic presentation of IBD at diagnosis in a population-based Danish inception cohort from 2003-2005. METHODS: Three-hundred-forty-seven (62%) of 562 cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients answered a questionnaire concerning environmental factors with possible influence on IBD. RESULTS: Fourteen percent of CD patients vs. 11% of controls were positive for common CARD15 mutation (ns), whereas more CD patients than healthy controls were homozygous for the OCTN-TC haplotype (p=0.03). ASCA was more common in CD (22%) than UC (14%) (p=0.045) and was related to age and localization of CD. p-ANCA was more frequent in UC (p=0.00001) but was related to pure colonic CD (p=0.0001). Sugar consumption was significantly higher in CD patients than in UC patients (p=0.0001) and more CD patients than UC patients had undergone appendectomy prior to IBD diagnosis (p=0.03). A possible relation between tonsillectomy and disease severity in CD, and a relation between use of oral contraception and disease localization of UC to rectum/left-sided colon were found. CONCLUSIONS: In this cohort of unselected IBD patients we found a very low frequency of mutations in IBD susceptibility genes and observed a greater impact of ASCA and ANCA than of genetic factors on disease phenotypes. In addition, several environmental factors seemed to influence disease occurrence and disease presentation in both UC and especially CD.

Clinical practice and evidence in endoscopic treatment of bleeding peptic gastroduodenal ulcer.

OBJECTIVE: To investigate treatment practice in non-variceal upper gastrointestinal bleeding (NVUGIB) caused by gastroduodenal ulcer and how it adheres to the best evidence as documented in randomized studies and meta-analyses. MATERIAL AND METHODS: The literature was surveyed to identify appropriate practices, and a structured multiple choice questionnaire developed and mailed to all departments in Denmark treating UGIB. RESULTS: All 42 departments responded. All had therapeutic gastroscopes and equipment necessary for endoscopic haemostasis; 90% of departments had written guidelines. Adjuvant pharmacologic treatment included tranexamic acid in 38%. Proton-pump inhibitors (PPIs) were used by all departments, with 29% starting prior to endoscopic treatment. Eight departments (19%) used continuous PPI infusion, three of them starting with a bolus dose. In 50% of departments an anaesthesiologist was always present regardless of whether endotracheal intubation (routinely used by 10%) was used or not. Ten percent did not treat Forrest IIa and IIb ulcers, while IIc ulcers were treated by 36%. In 10% of departments clots were never removed, while in 2/3 attempts were made to remove resistant clots by mechanic means. Seven departments (17%) used monotherapy with epinephrine, while 59% always used dual therapy; 19% injected less than 10 ml. In rebleeding, 92% attempted endoscopic treatment before surgery, and used epinephrine in 79% of cases, while the remainder used epinephrine or polidocanol at the discretion of the endoscopist. Two out of three departments used high-dependency or intensive-care units for surveillance. Seventeen percent applied scheduled second-look gastroscopy. CONCLUSIONS: Practice is variable, even in areas with established evidence based on randomized controlled studies, such as dosage and way of administration and duration of PPI treatment, injection treatment used as monotherapy and the volume used, including ulcers with clots for treatment, and the use of scheduled second-look endoscopy. Since the rebleeding rate has remained unchanged for decades, and rebleeding implies increased surgery and mortality rates, appropriate practices must be promoted in order to improve results. Development and implementation of national guidelines may facilitate the process.

Initial clinical experience with oral manganese (CMC-001) for liver MR imaging.

Recently, a new oral liver-specific manganese-based MR agent (CMC-001) has been introduced. This contrast medium is delivered to the liver in high concentrations in the portal vein and very low doses in the hepatic artery, as only small amounts of manganese enter the general circulation. It is taken up by the hepatocytes and excreted in the bile. Our initial experience with the new MR contrast medium in a variety of patients is reported. A total of 20 patients (11 males and 9 females) were studied with MR imaging 2 h after oral ingestion of the contrast agent. Sixteen patients were referred for evaluation of focal liver lesion(s), whereas in the remaining four patients, evaluation of the biliary tract was requested. In the 17 patients without biliary obstruction, there was an increased signal intensity of the liver parenchyma, whereas in the three patients with biliary obstruction, the uptake was delayed. There was excellent visualization of the biliary system on the T1-weighted images in the 16 patients without biliary obstruction referred for evaluation of a focal liver lesion. In seven patients, the uptake was patchy. In patients with focal liver lesions or biliary tract diseases, it is possible to increase the signal intensity of the liver parenchyma after the oral intake of CMC-001. In patients without biliary tract obstruction, the biliary system is easily visualized. Oral manganese seems to be useful in hepatobiliary MRI. Further research is strongly warranted.

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005: a population-based study from the Danish Crohn colitis database.

OBJECTIVES: A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City. METHODS: All patients diagnosed with IBD during 2003-2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered. RESULTS: Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/10(5) for CD, 13.4/10(5) for UC, and 1.1/10(5) for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported. CONCLUSIONS: The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Curative resection for left-sided pancreatic malignancy.

BACKGROUND: Surgical technique in pancreatic cancer has seen significant developments, but much of the knowledge refers to pancreatic head carcinoma. Reports on the management of tumours of the body and tail have been less frequent. Current knowledge teaches that adenocarcinomas of the body and tail of the pancreas have a worse prognosis. The aim of this study is to report the short- and long-term outcome in 20 patients with left-sided pancreatic malignancy, where 'resection for cure' was done. PATIENTS AND METHODS: Retrospective study of demographic data, symptomatology, diagnostic methods, operative management, pathology report, postoperative morbidity and mortality. RESULTS: Postoperative complications were seen in 40% of patients. One patient died on day 5 from sepsis with multiple organ failure. Other complications were intra-abdominal bleeding, bleeding from the gastroentero-anastomosis, postoperative jaundice, pleural exudate, wound dehiscence and intra-abdominal abscess. The patients with ductal adenocarcinoma had a median survival of 14 months and a 5-year survival of 17%. The median survival for the whole group of patients was 17 months and the 5-year survival was 23%. One patient with malignant insulinoma and two patients with adenocarcinoma had a survival exceeding 5 years (98, 174 and 183 months, respectively). DISCUSSION: Selected patients with left-sided pancreatic adenocarcinoma may be operated on with results similar to pancreaticoduodenectomy (Whipple procedure) for cancer of the pancreatic head regarding postoperative morbidity and mortality as well as long-term survival. Thus, although left-sided pancreatic cancer generally appears at a more advanced stage, it seems true that treatment results are similar if radical excision can be achieved.

[Wandering spleen]. / Vandremilt.

The spleen is well fixed below the left side of the diaphragm. Wandering spleen is a rare condition of unknown pathogenesis. The wandering spleen is most often localized in the lower abdomen or pelvis. The diagnosis may be difficult if wandering spleen is not suspected. Often a wandering spleen can be palpated in the lower abdomen. In the rare cases of torsion of the splenic vascular pedicle, wandering spleen becomes symptomatic, and splenectomy should be performed. We report a case of a 20-year-old female treated with splenectomy because of torsion of the vascular pedicle.

[Diagnosis and treatment of complications during cholecystectomy]. / Diagnostik og behandling af komplikationer ved kolecystektomi.

The incidence of bile duct injury after laparoscopic cholecystectomy has been reduced to 0.6%. One factor contributing to such injuries is misidentification of the bile duct anatomy. During laparoscopic cholecystectomy the surgeon should follow the criteria for dissection of the triangle of Calot and dealing with bleeding. Immediate reconstruction over a T-tube may be possible, or a baby-feeding tube should be inserted into the proximal part of the bile duct and the patient should be transferred to a center with experience in bile duct reconstruction.

Resection of cancer of the body and tail of the pancreas.

BACKGROUND/AIMS: To report our results of resection of cancer in the body and tail of the pancreas and review the literature. METHODOLOGY: Thirteen patients with a median age of 62 years with cancer of the body and/or tail of the pancreas. The diagnosis was made by ultrasonography, computed tomography, endoscopic retrograde cholangiopancreatography and angiography. Eleven patients had distal or subtotal pancreatectomy and two patients total pancreatectomy. The surgical procedure included extensive dissection of lymph nodes and the connective tissue in the peripancreatic region. Main outcome measures were postoperative morbidity and mortality, median and 5-year survival rates. RESULTS: Ten of the resections were considered to be curative. Postoperative complications occurred in seven patients and one patient died in the postoperative period. The median survival time of operative survivors was 392 days. Two patients survived five years, and one was alive ten years after surgery. Eight patients died of recurrence. CONCLUSIONS: Long-term survival may be achieved in a quarter of the resectable patients.

[Ultrasound-guided radiofrequency ablation of malignant liver tumors]. / UL-vejledt radiofrekvensbehandling af maligne levertumorer.

INTRODUCTION: Radio frequency ablation (RFA) of malignant tumours is a new and promising treatment modality. The aim of this study was to evaluate the method in patients with non-resectable liver tumours. MATERIAL AND METHODS: RFA was performed under the guidance of ultrasonography and general anaesthesia in 37 patients from December 1998 to November 2001. Six patients had primary liver cancers, and 31 metastases from other cancer, often colorectal cancer. RESULTS: Eight patients could not be evaluated because of the short follow-up time. Twenty-four of 29 patients (83%) achieved a complete tumour response. Twelve patients (41%) are alive after 3-28 (median 16) months, without recurrence. Twelve patients (41%) are alive after 1-34 (median 14) months, with recurrence. Five patients (14%) died after 4-26 (median 11) months, because of recurrence in the liver and/or other organs. Four patients had minor complications and one a major complication. There was no postoperative mortality. DISCUSSION: RFA can be offered to patients with non-resectable liver tumours when it is technically possible. The treatment can be performed with few complications, requires only a short hospital stay, and is cheaper than other treatments. Prolonged survival is attained in 40-50% cent of the patients.

[Distribution of colonic surgery among surgeons in the city of Copenhagen]. / Fordeling af colonkirurgi på operatører i hovedstadsområdet.

INTRODUCTION: The outcome of some surgical procedures is related to the surgeon's experience. We examined how much experience surgeons in 12 hospitals in the region of Copenhagen gained in colon surgery in 1999. MATERIAL AND METHODS: The Ministry of Health identified the number of colon patients operated on in the region of Copenhagen in 1999. The departments were asked to validate the lists of patients and to fill in a questionnaire describing the surgeon's experience in that year. RESULTS: Eleven of 12 departments answered the questionnaire (92%). One hundred and two senior surgeons operated on 674 patients. Forty of the surgeons operated on one to four patients in 1999, and only five performed 15 or more operations. More than 50% of the surgical procedures were carried out by surgeons who performed fewer than 10 colon operations in 1999. Most of the low-volume surgeons' operations were performed during calls. DISCUSSION: Colon surgery in the region of Copenhagen was performed by a large number of surgeons in many hospitals in 1999. Hospital volume was not associated with surgeon volume.