Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in colorectal cancer cells.

12(S)-Lipoxygenase (LOX) and its product 12(S)-hydroxyeicosatetraenic (HETE) acid have been implicated in angiogenesis and tumour invasion in several tumour types while their role in colorectal cancer progression has not yet been studied. We have analysed 12(S)-LOX expression in colorectal tumours and found gene expression up-regulated in colorectal cancer specimens for which the pathology report described involvement of inflammation. Using cell line models exposed to 12(S)-HETE or over-expressing 12(S)-LOX malignant cell growth as well as tumour cell migration was found to be stimulated. Specifically, Caco2 and SW480 cells over-expressing 12(S)-LOX formed fewer colonies from sparse cultures, but migrated better in filter-migration assays. SW480 LOX cells also had higher anchorage-independent growth capacity and a higher tendency to metastasise in vivo. Knock-down or inhibition of 12(S)-LOX inhibited cell migration and anchorage-independent growth in both 12(S)-LOX transfectants and SW620 cells that express high endogenous levels of 12(S)-LOX. On the cell surface E-cadherin and integrin-ß1 expression were down-regulated in a 12(S)-LOX-dependent manner disturbing cell-cell interactions. The results demonstrate that 12(S)-LOX expression in inflammatory areas of colorectal tumours has the capacity to induce an invasive phenotype in colorectal cancer cells and could be targeted for therapy.

[First manifestation of a leucocytoclastic vasculitis in the colon: case report and differential diagnostic aspects]. / Erstmanifestation einer leukozytoklastischen Vaskulitis im Dickdarm: Fallbericht und differenzialdiagnostische Überlegungen.

This report presents a female patient suffering from chronic diarrhea, who developed palpable purpura on the lower extremities 8 weeks after onset of the gastrointestinal symptoms. Biopsies obtained from the colon and skin showed leukocytoclastic vasculitis. Possible triggers or underlying diseases could not be found, and the patient recovered without specific treatment for vasculitis. Possible differential diagnoses and the difficulties in classifying vasculitides are discussed in the present report.

Fibroblast growth factor receptor 3-IIIc mediates colorectal cancer growth and migration.

BACKGROUND: Deregulation of fibroblast growth factor receptor 3 (FGFR3) is involved in several malignancies. Its role in colorectal cancer has not been assessed before. METHODS: Expression of FGFR3 in human colorectal tumour specimens was analysed using splice variant-specific real-time reverse transcriptase PCR assays. To analyse the impact of FGFR3-IIIc expression on tumour cell biology, colon cancer cell models overexpressing wild-type (WT-3b and WT3c) or dominant-negative FGFR3 variants (KD3c and KD3b) were generated by either plasmid transfection or adenoviral transduction. RESULTS: Although FGFR3 mRNA expression is downregulated in colorectal cancer, alterations mainly affected the FGFR3-IIIb splice variant, resulting in an increased IIIc/IIIb ratio predominantly in a subgroup of advanced tumours. Overexpression of WT3c increased proliferation, survival and colony formation in all colon cancer cell models tested, whereas WT3b had little activity. In addition, it conferred sensitivity to autocrine FGF18-mediated growth and migration signals in SW480 cells with low endogenous FGFR3-IIIc expression. Disruption of FGFR3-IIIc-dependent signalling by dominant-negative FGFR3-IIIc or small interfering RNA-mediated FGFR3-IIIc knockdown resulted in inhibition of cell growth and induction of apoptosis, which could not be observed when FGFR3-IIIb was blocked. In addition, KD3c expression blocked colony formation and migration and distinctly attenuated tumour growth in SCID mouse xenograft models. CONCLUSION: Our data show that FGFR3-IIIc exerts oncogenic functions by mediating FGF18 effects in colorectal cancer and may constitute a promising new target for therapeutic interventions.

Coexpression of the melatonin receptor 1 and nestin in human breast cancer specimens.

Activation of the G-protein-coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue-Quest software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER-2 status. Nestin was located together with MT1 in myoepithelial cells in 38 NCa specimens (total n = 42) and in 18 Ca specimens with intact milk ducts. Quantitative evaluation of selected 16 NCa and Ca samples revealed that MT1 levels were higher in invasive Ca sections than in NCa specimens in eight and lower in six cases. Specimens from higher tumor stages (TII/III) with a higher risk of relapse were associated with MT1/nestin co-staining in more than 10% of tumor cells, whereas a lack of co-staining correlated with lower tumor stages. Abundant expression of MT1 and, particularly, coexpression of MT1 with nestin in invading tumor cells in more advanced tumors suggest an important role for this GPCR in the pathogenesis of breast cancer.

Hepatic resection for metastases from colorectal carcinoma--a survival analysis.

Between 1 January 1984 and 31 December 1992, 66 patients with hepatic metastases from colorectal carcinomas underwent liver resection. 40 of these patients had synchronous hepatic metastases, and liver resection was carried out simultaneously with radical resection of the primary tumour; in 26 cases metachronous metastases in the liver were surgically removed. 25 patients had an anatomical resection and the remainder underwent atypical resections. The postoperative mortality rate was 4.5% and the major complication rate was 19.7%. Univariate and subsequently multivariate analyses were used to predict the influence of various clinical, histopathological and surgical variables. The observed 5-year survival rate was 29.6% and the 5-year disease-free survival rate 13.9%. Furthermore, the observed median survival time was 24.7 months and the mean disease-free survival time was 16.7 months. Multivariate analysis showed that stage of primary (pTN) (P = 0.043), tumour grading (P = 0.013) and site of primary (P = 0.007) were factors which independently influenced 5-year disease-free survival whereas stage of primary (pTN) (P = 0.008), tumour grading (P = 0.004) and type of resection (P = 0.035) were identified as having independent influence on 5-year observed survival. We consider liver resection to be an effective form of treatment for patients with resectable liver metastases from colorectal carcinoma, although the overall chances for cure are generally not very promising. It appears that the biological behaviour of the primary tumour, in terms of tumour stage and grading, has the greatest influence on survival.

Anti-carcinoembryonic antigen immunoscintigraphy (technetium-99m-monoclonal antibody BW 431/26) and serum CEA levels in patients with suspected primary and recurrent colorectal carcinoma.

This study comprises a total of 141 patients with suspected primary and recurrent colorectal carcinomas, in whom immunoscintigraphy with 99mTc-Mab BW 431/26 was performed. Whole-body scans were done 5.5 hr and SPECT imaging of the abdominal region was done at 6 and 24 hr postinjection of 1100 MBq 99mTc-labeled Mab (1 mg). In the course of primary tumor identification (n = 65), sensitivity of anti-CEA immunoscintigraphy was 95%, specificity 91%. In the diagnosis of early recurrences (n = 76), immunoscintigraphy was the method of choice to clarify the problem (sensitivity 94%; specificity 86%). Overall sensitivity of immunoscintigraphy in patients with suspected colorectal carcinomas and early recurrences was 95%, specificity 88%. Human anti-mouse antibodies were found in 29% (80% predominantly anti-isotypic, 20% predominantly anti-idiotypic). In contrast to anti-CEA immunoscintigraphy, the results of serum CEA levels were rather disappointing. Only 18 out of the 43 surgically verified primary colorectal carcinomas and 17 out of 32 patients with recurrences showed elevated serum CEA levels. In our clinical experience with this 99mTc-labeled anti-CEA antibody, immunoscintigraphy can play an important role in the identification of early colorectal recurrences and in postoperative colorectal cancer patients it should be performed in cases with unclear transmission computed tomography.

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Multivariate karyometric approach in differential diagnosis of follicular thyroid neoplasms. A study of 31 cases.

A retrospective analysis of 19 follicular adenomas, 12 minimally invasive follicular carcinomas and 3 widely invasive follicular carcinomas of the thyroid was performed on 5-microm-thick Feulgen-stained paraffin sections by means of a semiautomatic system for picture analysis. The major aim was to assess the potential of multiparameter karyometry for separation of the first two tumour types. Sixteen planimetric and densitometric features were defined in each case on 200-300 randomly selected nuclei and processed by a number of uni- and multivariate statistical methods. Despite predominantly significant ANOVA results a substantial overlap between tumour groups limited the practical usefulness of any karyometric feature alone. Factor and cluster analyses indicated independence of planimetric and densitometric parameters from each other, which was of crucial importance in finding an optimal subset of variables for discriminant analysis. The classification rule derived from the latter procedure was checked by the "jack-knife" method, by classification of 3 widely invasive cancers and by hierarchical tumour clustering. Sensitivity and specificity of the model for detection of malignancy were 100% and 94.7%, respectively. A multivariate karyometric approach, when applied correctly, can be a useful tool for differentiation between follicular adenomas and minimally invasive follicular carcinomas of the thyroid.

Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer.

Tumour-associated macrophages (TAM) are involved in tumour angiogenesis and anti-tumour immune response. In colorectal cancer (CRC), an association of high microvascular density (MVD) and unfavourable prognosis has been reported by some investigators. However, heterogeneous patient groups were studied. We, therefore, analysed the correlation between TAM and MVD and the prognostic relevance of MVD, TAM and T lymphocyte infiltration for long-term survival in a homogeneous group of 70 patients with moderately differentiated cancers of the International Union Against Cancer (UICC) stages II and III, who did not receive chemotherapy. MVD was evaluated using immunohistochemistry with antibodies against CD34 and von Willebrand factor (vWF). TAM and T lymphocytes were visualised with antibodies against CD68 and CD3, respectively. Statistical analysis did not reveal a significant correlation between TAM and T lymphocyte numbers and MVD. Multivariate analysis of immunohistochemical data from all CRC patients and the subgroup of patients with UICC stage-II CRC identified TAM- and vWF-positive microvessel numbers as prognostically relevant markers. Low numbers of TAM- and high numbers of vWF-positive microvessels were associated with an unfavourable prognosis. In conclusion, TAM- and vWF-positive microvessel numbers may serve as independent prognostic markers for patients with UICC stage-II and -III CRC and may help to identify patients with an unfavourable prognosis.

Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution.

Recent molecular studies have suggested that hyperplastic duct lesions of the pancreas are potential precursors of pancreatic ductal carcinoma. This study examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancreases from 140 patients were screened for the presence of mucinous cell hypertrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyperplasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples were analyzed for K-ras codon 12 mutations by polymerase chain reaction amplification of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 showed duct lesions. The lesions were evenly distributed throughout the pancreas. They were more common beyond the age of 40. MHT was present in 68%, DPH in 36%, ADH in 40%, and SQM in 36% of the cases. K-ras mutations were found in 19 samples from 15 out of 79 pancreases (18%), including all types of duct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positive specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/metaplastic duct changes of the pancreas increase with age, but their distribution pattern in the pancreas differs from that of ductal carcinomas.

Neuroendocrine tumours in various organ systems in a ten-year period.

Neuroendocrine cells are present in various organ systems. These widely distributed cells as well as their histogenetically related tumours can produce various peptides and peptide hormones. From 1984 to 1993, 349 neuroendocrine tumours were found among 511,382 histological diagnoses at the Institute of Pathology of the Medical School of the Karl Franzens University in Graz. In 30% carcinoid of the appendix was diagnosed, in 16% carcinoid of the colorectum, in 9% carcinoid of the small intestine and in 2% duodenal carcinoid. Carcinoid of the stomach was detected in 14%. Seven of these cases showed microcarcinoidosis and five of them were combined with an adenocarcinoma. Carcinoid of the oesophagus was present in 1%, neuroendocrine pancreatic tumours in 6%. Neuroendocrine tumours of the bronchial system were found in 12%, medullary thyroid cancer in 5%. In 1% a Merkel-cell tumour was diagnosed. Other more rare localizations of neuroendocrine tumours were the uterus, ovary, breast, testes, epididymis, anal region and the upper respiratory tract.

Long-term results of radical surgery for rectal cancer: multivariate analysis of prognostic factors influencing survival and local recurrence.

AIMS: To evaluate consistent radical surgery performed over a 13-year period for rectal cancer in terms of local tumour control and long-term survival. METHODS: Radical surgical procedure principally using total mesorectal excision (TME) for middle and lower rectal tumours, high ligation of the inferior mesenteric artery and sphincter-saving resections (SSR) whenever possible, has been performed prospectively since January 1984. RESULTS: Tumour resection was possible in 98.8% (636/644), potentially curative resections (UICC/AJCC R0 resection) in 85.7% (552/644) and sphincter preservation in 71.7% (462/644). Five- and 10-year observed survival rates, surgical mortality not excluded, for all patients were 49.2% and 37.4%. Tumour-adjusted 5- and 10-year survival rates were 60.5% and 55.3%. For curatively operated patients (UICC/AJCC R0) 5- and 10-year observed survival rates were 56.3% and 42.6% and tumour-adjusted survival rates were 68.6% and 62.7%. The 5- and 10-year local recurrence rates for R0 resected patients were 12.0% and 12.6%. Post-operative hospital mortality was 3.1%. CONCLUSIONS: Multivariate analysis using Cox's model identified increasing pT category and pN category, old age and low tumour location as detrimental factors having independent influence on survival. For local tumour failure only pT and pN category as well as adjuvant radiation therapy were identified in the Cox model as having an independent detrimental influence.

Experience with a high speed biopsy gun in breast cancer diagnosis.

Pre-operative determination of histology and receptor status is important in optimizing the management of breast cancer. The purpose of our study was to evaluate the high speed biopsy gun in 109 patients with palpable breast tumours. High speed biopsies were performed using the system BIP High Speed Multi 22 with 16-gauge-needles at a speed of 30 m/s. All biopsies could be used for frozen sections and for determination of receptor status. In 81 patients (74.3%) malignant breast tumours were diagnosed, and three patients (2.8%) had highly suspicious lesions. The oestrogen receptor status was negative in 32%, progesterone receptor status negative in 41%. In one patient (0.9%) a high grade non-Hodgkin's lymphoma of B-cell-type was diagnosed. In 21.1% benign tumours were found. In one patient a malignant tumour was missed at biopsy (0.9% false-negative). It was concluded that high speed biopsy is a reliable and simple method for preoperative sampling of breast lesions.

Mutant p53 expression and DNA analysis in human breast cancer comparison with conventional clinicopathological parameters.

Scientific research evaluates the prognostic importance of 53 expression and DNA flow cytometry controversially. To evaluate the prognostic relevance of mutant p53 protein overexpression and DNA flow cytometry in primary breast cancer we correlated these factors with the common prognostic parameters such as tumor size, lymph node status, grading, menopausal status and receptor status. Human breast cancer specimens from 180 previously untreated patients were collected and deep frozen. On each specimen DNA-analysis by Geohde's technique (Partec PAS II) and immunohistochemical evaluation of mutant p53 protein (PAb 1801 and 240, Novocastra Lab., Great Britain) were performed. Besides TNM- and histological classification, estrogen (ER)- and progesterone (PgR) receptor content was recorded. Overexpression of mutant p53 protein was found in 34 (19%) of all specimens. All these 34 tumors were aneuploid (p = 0.007), 86% of them were receptor negative (p 0.0001), 79% had a high tumor grade (p 0.0001), 73% a high S-phase-fraction (SPF) (p = 0.045) and 53% were premenopausal (p 0.0001). Tumor size and node status did not correlate significantly with p53 expression. 27 (15%) out of 180 carcinomas were diploid. There was a significant correlation between ploidy and the tumor grade (p = 0.003) and SPF (p 0.0001), but not correlation between ploidy and tumor size (p = 0.21), node status (p = 0.33) or receptor status (p = 0.18). A low SPF was predominantly found in tumors less than 2 cm in diameter (p 0.0001); no significant correlation was found between SPF, receptor status, tumor grade, node and menopausal status. Mutant p53 protein expression and DNA analysis in combination with common prognostic parameters might help to detect prognostically unfavourable subgroups of breast cancer patients.

Concomitant point mutation of tumor suppressor gene p53 and oncogene c-N-ras in malignant neuroendocrine pancreatic tumor.

Activation by point mutation of ras family genes as well as point mutations of the p53 tumor suppressor gene are found in many tumors. Here we describe a rare case of malignant neuroendocrine pancreatic tumor with multiple metastases in different organs showing strong positivity for synaptophysin, glucagon-like peptide 1, pan-cytokeratin, moderate positivity for chromogranin, Phe-5 and calcitonin and weak positivity for vasointestinal peptide. We found a point mutation at codon 61 of the c-N-ras oncogene, and point mutations in the p53 tumor suppressor gene in the primary tumor as well as in its metastases in liver. The mutation in the c-N-ras gene was a cytosine to adenine transversion, resulting in the amino-acid lysine. Allele specific hybridization showed that the mutation involved one of two c-N-ras alleles as the oligonucleotide for the normal codon also hybridized to amplified tumor DNA. Concomitant mutation of the p53 tumor suppressor gene at codons 248 and 249 was found. The mutation in codon 248 was a cytosine to guanine transversion resulting in the amino-acid glycine. The mutation in codon 249 was a third base, G- > T, transversion leading to a change from arginine to serine. This is the first time that concomitant point mutations in c-N-ras and p53 have been found in a neuroendocrine pancreatic tumor. Based upon these and our previous results, we concluded that these genetic changes may play a role in the development of this particular pancreatic tumor.

Differentiation of lymph-node metastases by anti-CEA immunoscintigraphy in a patient with follicular thyroid and breast cancer.

Supraclavicular lymph node metastases appeared in a female patient six years after thyroidectomy, radioiodine therapy and external radiation for a follicular thyroid carcinoma and four years after mastectomy and lymphadenectomy for an invasive ductal breast cancer. It was not possible either by conventional imaging methods or by serological methods, to assign the metastases to one of the two primary tumors. Anti-CEA immunoscintigraphy and SPECT of the cervicothoracic region showed a circumscribed pathological uptake of 99mTc-labeled anti-CEA antibodies in the area of the supraclavicular lymph nodes. The preoperative suspicion of lymph-node infiltration by CEA-expressing breast cancer cells was confirmed histologically after surgical removal of the lymph nodes.

[Therapeutic relevance of the classification of gastritis]. / Therapeutische Relevanz der Gastritis-Klassifikation.

The histological gastritis classification according to the Sydney system is a standardisation of different classification systems used so far. It is based on the principles of etiology, topography and course of the disease, as well as morphological changes of the gastric mucosa in gastritis. Histological examination represents the practical gold standard of Helicobacter pylori detection and can be used on routinely formaldehyde-fixed biopsy material and hematoxylin-eosin stained slides. Histology is therefore also of practical diagnostic value for the control of the eradication therapy of Helicobacter pylori. The sensitivity of histological Helicobacter detection is on average higher than that of other methods including microbiology. Nevertheless, additional bacterial cultures are useful in cases of therapy resistant Helicobacter pylori infections. For routine diagnosis histological Helicobacter pylori detection is often combined with the so-called rapid urease test, which can be used in the endoscopy outpatient department, frequently offering an interim diagnosis of Helicobacter pylori infection. Furthermore, histological examination enables not only exact gastritis classification with Helicobacter pylori detection, but also the diagnosis of precancerous lesions and gastric carcinomas, as well as primary gastric lymphomas. Biopsy material for histological examination can be taken during the routinely necessary gastroscopic examination of patients with gastric symptoms without much additional burden.

[Pathologic findings in colorectal cancers and discussion of their significance for tumor therapy according to stage]. / Der pathologische Befund bei kolorektalen Karzinomen und Diskussion seiner Bedeutung für die stadiengerechte Tumortherapie.

The histological degree of differentiation is a valuable determinant of the malignancy of colorectal carcinomas. It correlates well with the tumour stage and has a prognostic relevance similar to the Dukes stages. Well and moderately well differentiated colorectal carcinomas showed significantly lower lymph node metastasis (35% and 45% of the cases, respectively) than the poorly differentiated tumours (70%). Among 20 carcinomas limited to mucosa and submucosa, only one poorly differentiated carcinoma produced lymph node metastases. The histological degree of differentiation of a given tumours assessed consecutively in biopsy and surgical material was identical in 81%. The degree of differentiation had to be corrected from moderate to well in only 9% of cases and in 8% from well to moderate. These corrections were without prognostic relevance. The prognostically important correction from moderate to poor histological degree of differentiation had to be made in only 2% of the cases. Therefore, the histological degree of differentiation can be accepted as an important preoperative criterium for the selection of adequate tumour therapy. An increased risk of tumour infiltration of resection margins was found only in cases with resection distances less than 1 cm from the tumour, whereas tumour infiltration of resection margins was minimal (below 1%) for distances of more than 1 cm. Consideration of the histological degree differentiation, clinical stage of tumour and sufficient distances of resection margins from tumours should lead to increased numbers of resections with preservation of sphincter function despite radical surgery.

[76-year-old patient with adenocarcinoma of the rectum and fibrolamellar hepatocellular 2d carcinoma. Case report with literature review of hepatocellular carcinoma of the fibrolamellar type]. / 76jähriger Patient mit einem Adenokarzinom des Rektums und fibrolamellärem hepatozellulärem Zweitkarzinom. Kasuistik mit Literaturübersicht über das hepatozelluläre Karzinom von fibrolamellären Typ.

This paper presents the case report of the coincidental presence of an adenocarcinoma of the rectum and fibrolamellar hepatocellular carcinoma in a 76 year-old man. The tumours were successfully removed by simultaneous resection. The characteristics of hepatocellular carcinoma of the fibrolamellar type are discussed in detail on the basis of the presented case and a survey of the literature. This variant of hepatocellular carcinoma is predominantly found in younger patients. It appears in non-cirrhotic livers and is preferentially localized in the right lobe. Histologically, fibrolamellar hepatocellular carcinoma is characterized by large eosinophilic tumour cells. The cells show trabecular or solid arrangement separated by fibrous septa. Cytoplasmic globules are often found in the tumour cells. In the literature, fibrinogen, CEA, alpha-1-antitrypsin, copper binding protein and copper have been demonstrated in the tumour cells by immunohistochemistry and histochemistry. The fibronectin content is increased in the tumour and seems to correlate with a higher degree of differentiation, as well as a better prognosis. The serum alpha-fetoprotein levels of patients with fibrolamellar carcinomas are normal, in contrast to those in patients with other types of hepatocellular carcinomas. The serum vitamin B12 binding-capacity, as well as neurotensin concentrations are increased. Patients with fibrolamellar carcinomas have a much better prognosis than patients with ordinary hepatocellular carcinomas because of the earlier onset of symptoms, slower tumour progression with late metastasis, and better operability. Two-year survivals of 82% and five-year survivals of 63% have been reported. The prognosis is also better after total hepatectomy followed by liver transplantation.

[Hypersensitivity vasculitis causing an acute abdomen]. / Hypersensitivitätsvaskulitis als Ursache eines akuten Abdomens.

The members of a family of four persons suffered acute gastroenteritis after eating a meal consisting of chicken. While three of them recovered rapidly, the 18-year old son developed an acute abdomen which had to be treated surgically and led to a complicated stay at the intensive care unit. Intraoperatively, a mild insignificantly inflamed appendix and an obscure segmental inflammatory process of the small bowel with local peritonitis were seen; this required an appendectomy and a peritoneal lavage. The development of bacterial peritonitis with multiple organ dysfunction required several surgical revisions with an open abdominal toilet treatment. Histological examination of the resected appendix specimen showed a severe primary fibrinoid necrotizing vasculitis with epitheloid-granulomatous reaction. Diseases such as Panenteritis nodosa, Wegener's disease and Churg-Strauss's syndrome were excluded by negative serology. By a process of exclusion, a hypersensitivity vasculitis was diagnosed and treated successfully with a high-dose cortisone regime.