Mesenteric inflammatory veno-occlusive disease: a rare cause of intestinal ischemia. The first description of recurrent disease.

BACKGROUND: Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischemia of unknown etiology. Histologically, MIVOD is characterized by extended thrombophlebitis and fibrous organized thrombosis of multiple veins. The arteries are by definition not involved. Management includes surgery in all cases described. Recurrence has not been described until now. METHODS: We describe the case of a 64-year-old woman operated with the suspicion of intestinal ischemia. Clinical and histopathological characteristics are reported. RESULTS: The patient underwent a right hemicolectomy and segmental resection of the terminal ileum 15 months later for a recurrence. The histological examination of the resected specimen confirmed the diagnosis of MIVOD and a recurrence thereof. CONCLUSION: MIVOD is a rare cause of colonic ischemia. Recurrence of the disease, which is described here for the first time, is unusual after surgical resection.

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

Helicobacter pylori and gastric erosions. Results of a prevalence study in asymptomatic volunteers.

BACKGROUND/AIMS: Helicobacter pylori is considered to be the primary cause of most forms of gastritis, but its role as a causative agent in gastric erosions is unclear. The aim of this study was to estimate the prevalence of gastric erosions and H. pylori infection in asymptomatic volunteers. METHODS: 175 asymptomatic subjects underwent upper gastrointestinal endoscopy. Antral biopsies were taken for bacterial cultures, histology and quick urease (CLO) test. A (13)C-urea breath test was performed after endoscopy. NSAID intake, alcohol consumption and smoking habits were also recorded in each subject. RESULTS: 33 (19%) of 175 asymptomatic volunteers had macroscopic lesions on upper gastrointestinal endoscopy, 7 were H. pylori positive, 26 were H. pylori negative. Gastric erosions occurred in 8% (14 subjects) of all volunteers. 10 subjects were H. pylori negative and 4 H. pylori positive. In 11 volunteers, gastric erosions were restricted to the prepyloric antrum. Only 1 of 14 subjects had a history of NSAID intake and 6 subjects were alcohol abstainers. CONCLUSION: We conclude that gastric erosions occur in a considerable amount of asymptomatic volunteers. They are predominantly localized in the prepyloric antrum and are most likely not associated with H. pylori infection, NSAID intake, smoking or alcohol consumption.

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Expression of transforming growth factor beta1, beta2, and beta3 in multinodular goiters and differentiated thyroid carcinomas: a comparative study.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.

Inhibition of iodine organification and regulation of follicular size in rat thyroid tissue in vitro.

The factors mediating the accumulation of thyroglobulin are of great importance to the understanding of the pathogenesis of human and experimentally induced colloid goiters. To elucidate further the underlying cellular mechanism, thyroid fragments from newborn rats were incorporated into semisolid alginate beads and were cultured as three-dimensional organoids for up to 21 d. In five parallel cultures, the medium contained either no supplements (group A), Nal (group B), thyroid-stimulating hormone (TSH) (group C), Nal plus TSH in the same concentrations as B and C (group D), or Nal and TSH (as in group D) plus methimazole (MMI, group E). The thyroid organoids maintained morphological integrity, functional activity, and ability to proliferate in vitro. Addition of iodine to the cultures significantly increased mean (+/-SEM) follicular diameters from 19.5 +/- 0.7 microm in controls to 33.9 +/- 2.2 microm (p < 0.0001) when NaI was added alone (group B), and 30.4 +/- 1.7 microm (p < 0.0001) when combined with TSH (group D). The effect of NaI on follicular size was abolished by MMI (group E, follicular diameter 23.5 +/- 1.3 microm). The results presented support the recent finding, using a rat colloid goiter model, that not only TSH but also iodine organification or its inhibition are important factors in modulating follicular morphology.

Risk factor assessment of endoscopically removed malignant colorectal polyps.

BACKGROUND: Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. AIMS: To determine the significance of histological findings of patients with malignant polyps. METHODS: Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). RESULTS: Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. CONCLUSION: As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.

[Intestinal paralysis in long-term diabetes mellitus]. / Darmparalyse bei langjährigem Diabetes mellitus.

A 74 year old patient with diabetes mellitus was hospitalized because of nausea, recurrent vomiting and increasing fatigue. Shortly before admittance the patient had diarrhea. He also reported a recent onset of aversion against meat consumption. Clinical investigation revealed a possible right-sided paraumbilical abdominal tumor, normal bowel sounds, a vascular bruit and a normal white blood count with increased band forms. During hospitalisation the general condition of the patient deteriorated rapidly with fever and increasing numbers of immature granulocytes. The patient finally died under the symptoms of a paralytic ileus with hypotonia and hypoglycemia. Autopsy revealed a fist-sized stenosing tumor in the cecum with the histology of a mainly well differentiated, cylindrocellular adenocarcinoma. As immediate cause of death a bilateral paracentral lung embolism with pulmonary edema was found, the latter probably as immediate consequence of preterminal heart failure.

[Severe chronic iron deficiency in a 17-year-old student]. / Schwerer chronischer Eisenmangel bei 17jährigem Schüler.

A 17 year old male suffered from iron deficiency of undetermined cause for 2 years. Iron substitution was able to correct it for short periods. With the exception of fatigue and recurring abdominal pain attributed to oral iron therapy no further symptoms were present. The physical status on admission was unremarkable. The laboratory detected intestinal disorders, an anemia of the chronic type without evidence for malignancy or renal failure suggested an inflammatory gastro-intestinal disorder. In spite of a twice negative noninvasive test for gluten-intolerance the clinician favored in his differential diagnosis non tropical sprue over inflammatory bowel disease (IBD, Crohn's disease, Whipple's disease). Histopathology of small bowel specimens did not indicate sprue. An ileo-colonoscopy revealed severe ulcerating ileitis and mild chronic colitis. The histologic specimen revealed a severe ileal inflammation with cosinophilia and the colon specimens epitheloid microgranuloma. These findings are highly compatible with the diagnosis of Crohn's disease. Iron deficiency anemia is common in Crohn's disease. In the current case it is due to disturbed iron uptake. Iron deficiency anemia as sole symptom of Crohn's disease is extremely rare.

Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue.

The extracellular matrix (ECM) and basement membranes (BM, a specialized form of ECM) greatly influence proliferation, differentiation, and function of cells and the structure of tissues. While a considerable amount of information is available on thyroid cellular proliferation, differentiation and function, much less is known about thyroid ECM and BM. In this study the presence of the ECM/BM components fibronectin, collagen IV, alpha1, beta1, gamma1 laminin, several laminin variants, osteonectin, and perlecan was demonstrated in cryosections of nonadenomatous and toxic adenoma human thyroid tissue. Also, positive immunohistochemical staining for collagen IV, laminin, perlecan, and fibronectin was obtained in sections of human thyroid tissue cultured in a three-dimensional (alginate) culture system. The present study provides methods and data that will facilitate the investigation of the interaction between cells and ECM in thyroid tissue.

[Gastric leiomyoblastoma: literature review and report of a case]. / Léiomyoblastome gastrique: revue de la littérature et à propos d'un cas.

Leiomyoblastoma is a rare, smooth muscle tumor of the stomach that occurs chiefly in the antrum. We present the case of a 51 year old man suffering from asthenia and mild upper abdominal pain. Investigations showed a big exculcerated tumor of the lesser gastric curvature. He underwent a subtotal gastrectomy for a non-metastasizing leiomyoblastoma, grade 1. But already 5 months later, he developed an invasive non-resectable local recurrence of high grade malignancy and died 3 month after a second look. Those tumors affect middle-aged patients who present usually upper gastrointestinal bleeding or peptic ulcer-like symptoms. Although the large majority of leiomyoblastoma are benign, malignancy occurs in up to 10% of cases. A large surgical resection of the tumor (including the total thickness of the gastric wall) or a partial gastrectomy is recommended.

High coincidence of Mirizzi syndrome and gallbladder carcinoma.

BACKGROUND: Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied. METHODS: Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study. RESULTS: Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation. CONCLUSIONS: There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.

Carcinoid of the pancreas: clinical characteristics and morphological features.

The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its diagnosis may puzzle physicians and pathologists. Here, 29 previously published cases of pancreatic carcinoid tumours, including one new case, are reviewed. Literature research was done using MedLine from 1966 to 1995. Pancreatic carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in only 34%. The main symptom was pain, followed by diarrhoea and weight loss. Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid tumour is based on the typical endocrine histological features together with increased serotonin metabolism. Generally, the slow growth rate and late invasion of adjacent organs render local resection possible, but the high incidence of distant metastases (69%) prevents long-term survival in the majority of patients. The possible role of the Octreoscan, a new radionuclide imaging technique, is discussed with regard to this tumour entity.

[Nonsteroidal antirheumatic drugs and acetylsalicylic acid: adverse effects distal to the duodenum]. / Nichtsteroidale Antirheumatika und Azetylsalizylsäure: Nebenwirkungen distal des Duodenums.

An increasing number of case reports and controlled trials have drawn attention to NSAID-induced side effects in the lower gastrointestinal tract. In this review we also report 9 cases of colonic ulcers and 7 cases of diaphragm disease of the ascending colon, most of them associated with the long-term intake of slow release diclofenac. NSAIDs not only can exacerbate preexisting conditions such as inflammatory bowel disease or diverticular disease, but may also induce de novo enteropathy, colitis, collagenous colitis ulcers and strictures. Complications such as bleeding, perforation or bowel obstruction may require surgery. From the literature and our own experience we conclude that the use of slow release formulations has shifted the toxicity of NSAIDs from the upper to the lower gastrointestinal tract. This must be considered in differential diagnosis and checked by endoscopy if appropriate.

[Long-term course of medullary thyroid gland carcinoma]. / Langzeitverlauf des medullären Schilddrüsenkarzinomes.

UNLABELLED: To obtain information on the outcome of medullary thyroid carcinoma (MTC) in the Berne area, a retrospective analysis of the 28 MTCs diagnosed by the Institute of Pathology of the University of Berne in the 25-year period between 1969 and 1994 was done. These 28 MTCs represented 2.4% of all thyroid malignancies diagnosed at the Bernese Institute of Pathology in the 25-year period mentioned above. 25 MTCs were sporadic and 3 associated with a multiple endocrine neoplasia (MEN) syndrome. Follow-up data were available from 27 of the 28 MTC patients. After a follow-up period of between 2 and 275 months 7 of these 27 patients had died form the MTC (among them all 4 patients with T4 tumors) and two were alive with tumor. 18 patients, including all 14 patients with T1 or T2 tumors without lymph node or distant metastases at the time of diagnosis, were alive and without evidence of tumor at the end of the follow-up period. CONCLUSIONS: MTCs are rare malignant tumors and comprise only a small fraction of all thyroid carcinomas in the Berne area. Most MTCs were sporadic, only a small minority was associated with a MEN syndrome. The TNM stage was the most important prognostic factor for patient survival. These data are in accordance with the results of similar MTC surveys done in other areas.

[Congenital cystic duplication of the stomach--a rare surgical disease]. / Die congenitale cystische Duplikatur des Magens--eine seltene chirurgische Erkrankung.

Duplication of the stomach is a rare congenital disease of the childhood. We report the exceptional manifestation in two adults. The clinical presentation and developmental theory is discussed by reviewing the literature. Today the therapy of choice is resection of the duplication with removal of the adjacent wall of the stomach.

Subcutaneous periumbilical metastasis of a gallbladder carcinoma after laparoscopic cholecystectomy.

The frequency of gallbladder carcinoma is 1.2 to 7.4% of all cholecystectomy specimens. In open cholecystectomy for gallstone disease, undetected gallbladder carcinoma is found postoperatively in the histological examination in 0.3%. Tumor cells of these clinically inapparent gallbladder carcinomas can be implanted at the trocar sites during laparoscopic cholecystectomies. We report a case with subcutaneous tumor seeding at the navel trocar insertion site in a 65-year-old woman.