PubMed Health⌕ Search

Biomedical subjects

R Willén

Publications and source records attributed to R Willén.

At least 19 recordsLinked to original sources

Mucosal assessment for dysplasia and cancer in the ileal pouch mucosa in patients operated on for ulcerative colitis--a 30-year follow-up study.

PURPOSE: Sporadic reports of epithelial dysplasia and the occasional development of adenocarcinoma in the ileal pouch mucosa have recently appeared in the literature, pointing toward yet another long-term complication of the continent ileostomy and the pelvic pouch. The incidence of dysplasia and the risk for developing cancer has not been critically evaluated, however, and the reports are contradictory, with most having short observation times. The purpose of this study was to report long-term mucosal adaptation patterns and the incidence of dysplasia in Kock pouches after a mean follow-up of 30 years for patients previously operated on for ulcerative proctocolitis. METHODS: Two sets of two pathologists each (in Gothenburg, Sweden, and Manchester, United Kingdom) examined sequential, small-intestinal biopsy specimens from 40 patients with Kock pouch to observe long-term epithelial changes, with particular reference to the presence of dysplasia. RESULTS: There was full agreement between the two groups regarding the absence of high-grade dysplasia and invasive carcinoma (Categories 4 and 5 of the Vienna classification). There was, however, significant disagreement in reporting the frequency of low-grade and indefinite categories of dysplasia (Categories 2 and 3, of the Vienna classification). No attempt was made to report the differences within each set of pathologists. CONCLUSION: Because no case of high-grade dysplasia or invasive carcinoma was found in this study after a mean follow-up of 30 years, we conclude that it is very unlikely for invasive carcinoma to be a complication in ileal pouch mucosa.

Adenocarcinoma↗

Dysplasia in the ileoanal pouch.

Formation of an ileo-anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch-anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a 'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long-term safety of the ileo-anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long-term follow-up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long-term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo-anal pouch.

Journal Article↗

Nasopharyngeal glioma in a new-born girl.

Nasal gliomas are uncommon tumours of neurogenic origin that occur sporadically. They are diagnosed with MRI and a preoperative biopsy, and surgery is the treatment of choice. Most of the gliomas emerge from the nasal cavity, but only a few cases of nasopharyngeal gliomas have been reported. We present one case of a nasopharyngeal glioma and two cases of nasal gliomas.

Female↗

Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer.

Components of the urokinase plasminogen activator (u-PA) system are involved in the metastatic process, and have accordingly been associated with clinical outcome in a variety of malignant tumours. We investigated the prognostic importance of u-PA and plasminogen activator inhibitor type 1 (PAI-1) in endometrial cancer, analysed with luminometric immunoassay (LIA) and enzyme-linked immunosorbent assay (ELISA), respectively. Two different cut-off levels were used: the median and the 80th percentile-the latter because of the low progression rate for patients with early stage (I-II) endometrial cancer. After a median follow-up time of 6.8 years, univariate analysis of patients with stage I-II disease (n=188) showed that high u-PA and high PAI-1 content was associated with a shorter progression-free survival (PFS), but at different cut-off levels, uPA at the median (P=0.003), and PAI-1 at the 80th percentile (P<0.001). Among the other factors, DNA ploidy status was most strongly correlated to PFS, followed by age (continuous), International Federation of Gynaecology and Obstetrics (FIGO) grade of differentiation, S-phase fraction and progesterone receptor (PgR) status. Bivariate analyses, including ploidy and one of the factors u-PA or PAI-1, showed that both add significant prognostic information. We conclude that u-PA and PAI-1 are promising prognostic factors in early stage endometrial cancer.

Adult↗

Familial occurrence of microscopic colitis: a report on five families.

BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. METHODS: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. RESULTS: Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.

Adult↗

Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas.

The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.

Adult↗

Inhibition of Helicobacter pylori infection by bovine milk glycoconjugates in a BAlb/cA mouse model.

The attachment of Helicobacter pylori to the human gastric mucosa is a complex process involving several specific structures recognised by the cell surface receptors. Sialylated multivalent high mol. wt glycoproteins have been shown to inhibit H. pylori sialic acid-specific haemagglutination. This study explored whether sialylated glycoconjugates from bovine milk could inhibit an experimental H. pylori infection in a mouse model. BALB/cA mice (6-8 weeks old) were inoculated with a mouse-passaged H. pylori strain 317p. Four weeks after infection the mice were given lactoferrin (iron-free LF or 20% iron-saturated LF) or bovine milk fat globule membrane fractions (MFGM or defatted MFGM) orally (400 mg/kg body weight) once daily for 10 days and then killed to examine for bacterial colonisation and gastritis. Mice treated with iron-free LF, 20% iron-saturated LF, MFGM or defatted MFGM showed 30%, 10%, 20% or 20% healing rates, respectively, when compared with the H. pylori-infected control. Gastric colonisation by H. pylori was remarkably decreased in all mice treated with bovine milk glycoconjugates and the inflammation score was also significantly lower in treated mice than in infected control animals. The fact that there was no significant difference between iron-free LF and iron-saturated LF or MFGM and defatted MFGM suggested that iron is not crucial for inhibition of H. pylori by lactoferrin and that the lipid part of MFGM is not important for anti-H. pylori activity. In conclusion, bovine milk glycoconjugates showed potencies to inhibit H. pylori infection in this mouse model and, therefore, could be considered as candidates for non-antibiotic strategies against H. pylori infection in man.

Animals↗

Comparative study of Helicobacter pylori infection in guinea pigs and mice - elevation of acute-phase protein C3 in infected guinea pigs.

Eighteen Dunkin-Hartley guinea pigs and 50 NMRI mice were inoculated with Helicobacter pylori and the infection followed by culture, histopathology, antibody response, and plasma levels of the acute-phase proteins albumin, C3, and transferrin for up to 7 weeks. The immune response to H. pylori surface proteins was studied by an enzyme immunoassay (EIA) and Western immunoblot and the plasma levels of albumin, C3, and transferrin were analyzed by single radial immunodiffusion. Guinea pigs had a more severe gastritis and a higher EIA immune response than NMRI mice. Serum C3 levels were elevated in infected guinea pigs after 3 and 7 weeks indicating a systemic inflammatory response and a possible link between H. pylori infection and extragastric manifestations such as vasculitis associated with atherosclerosis. Serum cholesterol levels were analyzed in guinea pigs at 7 weeks and indicated a higher level in H. pylori-infected than in control animals, but this difference was not statistically significant.

Acute-Phase Reaction↗

High intake of selenium, beta-carotene, and vitamins A, C, and E reduces growth of Helicobacter pylori in the guinea pig.

PURPOSE: Helicobacter pylori is a human gastroduodenal pathogen associated with type-B gastritis and gastric cancer. Low gastric tissue antioxidant levels are believed to increase the risk of developing gastric cancer. We investigated whether dietary antioxidant levels protect against infection and type-B gastritis in H. pylori-infected guinea pigs. METHODS: Dunkin-Hartley guinea pigs infected for 6 weeks with H. pylori were fed diets with various antioxidant levels. Stomach specimens were cultured, and gastritis was graded from 0 to 3. RESULTS: Supplementation with vitamins A, C, and E and with selenium yielded H. pylori recovery from 17% of challenged animals, compared with 43% of those fed a control diet. Gastritis was scored at 0.33 and 0.93, respectively. Supplementation with only vitamin C or astaxanthin had less effect on gastritis and recovery rate. In a second experiment, gastritis score in a group given vitamins A, C, E, and selenium and beta-carotene was 2.25 and in a control group, it was 2.57. The H. pylori recovery rate was 75 and 100%, respectively, with fewer colonies from animals given antioxidant supplementation (P < 0.05). CONCLUSIONS: A combination of antioxidants can protect against H. pylori infection in guinea pigs. In animal studies, antioxidant intake should be low to optimize development of H. pylori-associated disease. Furthermore we established that H. pylori causes severe gastritis in guinea pigs.

Animals↗

Intestinal permeability in humans is increased after radiation therapy.

PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.

Aged↗

Modes of adherence of Helicobacter pylori to gastric surface epithelium in gastroduodenal disease: a possible sequence of events leading to internalisation.

We have investigated various modes of adherence of Helicobacter pylori to the human gastric epithelium, using transmission electron microscopy, in biopsies from nine patients with peptic ulcer disease and from four patients with chronic active gastritis. H. pylori was demonstrated in abundance in all cases within the surface mucous layer. In all ulcer- and in one out of four gastritis patients H. pylori was shown in close proximity to the gastric epithelium, with concurrent alterations in the configuration of microvilli and the apical cytoplasmic region of gastric cells. Previously described modes of H. pylori adherence were confirmed, such as loose attachment with fibrillar-like strands, firm attachment with pedestal formation, invasion in the intercellular spaces, and invagination with "cup" formation. Moreover, in many cases a fusion between the bacterial outer layer and gastric cell membranes was evident. In four cases (31%; three with active and one with past ulcer disease) viable H. pylori was found in the cytoplasm of gastric mucous cells. Our results support the hypothesis that the different modes of adherence of H. pylori represent a stepwise, possibly sequential, process which in a significant number of cases leads to internalisation of the organism. The invariable occurrence of adhesion and more frequent internalisation of H. pylori in ulcer patients may suggest a link with the pathogenesis of peptic ulcer disease.

Adult↗

Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice.

Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of carotenoids and vitamin C has been proposed to prevent development of gastric malignancies. The aim of this study was to explore if the microalga Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks postinoculation mice were treated orally once daily for 10 days (i) with different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively), (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the cessation of treatment, and the other five animals were sacrificed 10 days after the cessation of treatment. Culture of H. pylori and determination of the inflammation score of the gastric mucosae were used to determine the outcome of the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Lipid peroxidation was significantly decreased in mice treated with the astaxanthin-rich algal meal and vitamin C compared with that of animals not treated or treated with the control meal. Both astaxanthin-rich algal meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.

Agar↗

Morphologic conversion of Helicobacter pylori from spiral to coccoid form. Scanning (SEM) and transmission electron microscopy (TEM) suggest viability.

Helicobacter pylori is a pathogen associated with type B gastritis, peptic ulcer disease, gastric atrophy, and stomach cancer. H. pylori exists in two morphological forms, spirals and coccoids. The latter has been described as viable but non-cultivable. The role of the coccoid form in the pathogenesis of gastric disease is disputed. Some authors consider the coccoid form to be a degenerative or dead form of H. pylori, while others consider it a resting but still metabolically active form. This study reports the conversion from spiral to coccoid form ultrastructurally. Dense material is accumulated in the periplasmic space, the spiral bacteria bend and the outer membrane is separated from the inner cell wall layer. Remodeling of inner structures takes place, ending in the coccoid form of the bacteria with preserved light polyphosphate areas. Reduction of surface takes place by production of surface membrane vesicles, which later are squeezed off. The finding of preserved subcellular structures and intact double membranes in combination with degenerative forms suggests that some of the coccoids are viable. Scanning electron microscopy (SEM) demonstrates coccoid form of bacteria with slightly ruffled surfaces but no spiral forms.

Culture Media↗

Screening for oesophageal adenocarcinoma: an evaluation of a surveillance program for columnar metaplasia of the oesophagus.

BACKGROUND: Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs. METHODS: One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed. RESULTS: The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US$ 37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus). CONCLUSIONS: Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.

Adenocarcinoma↗

Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes.

Helicobacter pylori is a gram-negative bacterium affecting about half of the world population, causing chronic gastritis type B dominated by activated phagocytes. In some patients the disease evolves into gastric ulcer, duodenal ulcer, gastric cancer or MALT lymphoma. The pathogenesis is in part caused by the immunological response. In mouse models and in human disease, the mucosal immune response is characterized by activated phagocytes. Mucosal T-lymphocytes are producing IFN-gamma thus increasing mucosal inflammation and mucosal damage. A low dietary intake of antioxidants such as carotenoids and vitamin C may be an important factor for acquisition of H. pylori by humans. Dietary antioxidants may also affect both acquisition of the infection and the bacterial load of H. pylori infected mice. Antioxidants, including carotenoids, have anti-inflammatory effects. The aim of the present study was to investigate whether dietary antoxidant induced modulation of H. pylori in mice affected the cytokines produced by H. pylori specific T-cells. We found that treatment of H. pylori infected mice with an algal cell extract containing the antioxidant astaxanthin reduces bacterial load and gastric inflammation. These changes are associated with a shift of the T-lymphocyte response from a predominant Th1-response dominated by IFN-gamma to a Th1/Th2-response with IFN-gamma and IL-4. To our knowledge, a switch from a Th1-response to a mixed Th1/Th2-response during an ongoing infection has not been reported previously.

Animals↗

Cloacogenic adenocarcinoma of the vulva.

Primary adenocarcinoma of the vulva is rare, and cloagocenic adenocarcinoma of the vulva is extremely rare. Here we report a vulvar tumor characterized by columnar cells with prominent brush border and the presence of goblet cells and endocrine cells, presenting the tubulovillous pattern and mucin histochemistry of enteric adenocarcinoma. Electron microscopy verified a colon-like pattern. We suggest that cloacogenic carcinoma of the vulva arises from embryonic tissue, normally present in the vulvar introital area. In our case, a wide local excision was sufficient for radical cure.

Adenocarcinoma↗

Bladder augmentation with different forms of intestinal grafts: an experimental study in the pig.

OBJECTIVE: To create an experimental animal model to examine changes in bladder volume and histology after bladder augmentation in growing individuals and from the model, evaluate a method using demucosalized intestinal grafts and short-term bladder drainage. MATERIALS AND METHODS: The study comprised 21 piglets: in group 1, seven underwent a sham operation; in group 2, seven piglets underwent bladder augmentation with full-thickness caecum after a major bladder resection; in group 3 seven underwent the same procedure but with demucosalized caecum. The bladder volume and area of the intestinal segment were measured peroperatively and when the animals were killed 2 months later. Bladder specimens were taken for histological examination. RESULTS: The mean preoperative bladder volumes were similar among the groups; in the control group, volumes increased from 58 to 165 mL and in group 2 from 63 to 255 mL, with an increase in area of the intestinal segment from 59 to 138 cm2. In group 3 the volume was unchanged, from 63 to 71 mL, with a decrease in area from 58 to 5 cm2. Control bladders showed normal urothelium with neutral mucins and sialomucins. In group 2, there was metaplasia in the border between urothelium and colonic epithelium, with enhancement of sialo- and sulphomucins. Demucosalization resulted in extensive fibrosis, with a monolayer of urothelial cells showing metaplasia. CONCLUSIONS: The experimental model was successful; the observed changes in bladder volume correlated well with the fate of the intestinal implant, because the bladder resection was major. This is essential, as the bladder remnant has some growth potential. Full-thickness grafts grew faster than the normal bladder. Mechanical demucosalization, including submucosa, results in shrinkage despite short-term drainage. Glandular metaplasia, with production of sialomucins and sulphomucins, occurs at the junction between bladder and colon, irrespective of mucosal removal.

Animals↗