[What Must the (Abdominal) Surgeon Know about Experimental Medicine (?) - Translational Research in General (Abdominal) Surgery(Viszeral-)Chirurg & experimentelle Medizin]. / Was muss der (Viszeral-)Chirurg von experimenteller Medizin wissen (?) - translationale Forschung in der (Viszeral-)Chirurgie.

Experimental medicine has evolved tremendously in the last few years. In particular, the introduction of novel techniques, in-vitro models, knock-out/transgenic animals and high-through put analytical methodologies have resulted in a deeper understanding of cellular pathophysiology and diseases. The daily clinical management has benefited by the introduction of biomarkers and targeted therapies. This development has been accompanied by increasing specialisation across all fields of research and medicine. Therefore, clinical-translational research requires a team of competent partners nowadays. The visceral surgeon can contribute significantly to these projects. The present review highlights several aspects of translational research and put chances and potential pitfalls into perspective in context with the work of the visceral surgeon.

[Influence of mucinous and signet-ring cell differentiation on epidemiological, histological, molecular biological features, and outcome in patients with colorectal carcinoma]. / Einfluss des muzinösen und siegelringzelligen Subtyps auf epidemiologische, histologische und molekularbiologische Eigenschaften sowie auf die Prognose des kolorektalen Karzinoms.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies in the Western world. Histopathologically, adenocarcinomas are mostly diagnosed. Mucinous and signet-ring cell subtypes occur with a very low incidence. However, these subtypes differ remarkably in terms of clinical, histological and molecular biological characteristics. The aim of this review is to present a detailed analysis of current knowledge regarding differences between classical adenocarcinoma and mucinous, and signet-ring cell CRC along with potential consequences for daily practice. METHODS: For this report all articles with relevant information on differences between classical adenocarcinoma and mucinous, and signet-ring cell CRC found via Pubmed searches were analysed. Furthermore, findings of our previous study were included. RESULTS: Mucinous CRC occur with a reported incidence of 10 - 20 % in Western countries and are predominantly found in younger patients and females. They are more often diagnosed in the proximal colon and present with a higher stage at diagnosis. Furthermore, there is a higher rate of lymph node-positive tumours and peritoneal carcinomatosis. Results of molecular biological studies confirm that they may represent a different tumour entity. The response to well established chemotherapy regimens is poorer which may be attributed to the higher rate of microsatellite-instable tumours and an increased mucin secretion. The poorer outcome is likely related to the higher stage at the time of diagnosis. Signet-ring cell type CRC are rare with an incidence ranging between 0,9 % to 4 %. They are also more common in the right colon and are associated with a poorer outcome compared to adenocarcinoma and mucinous CRC. CONCLUSIONS: However, it should be noted that most of the results come from studies with a very low number of patients which can be attributed to the low incidence of mucinous and signet-ring cell CRC. Based on the findings of the present analysis, a more radical surgical approach should be considered providing that the exact preoperative histology is available. Furthermore, the histological subtype should be taken into account in future chemotherapy trials to avoid unnecessary therapy. A closer follow-up, especially for patients with signet-ring cell CRC should be discussed. In the near future, a more tailored therapy in patients with colorectal cancer would be highly desirable.

Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome.

BACKGROUND: Colon cancer predisposition is associated with mutations in BRCA1. BRCA1 protein stability depends on binding to BARD1. In different cancers, expression of differentially spliced BARD1 isoforms is correlated with poor prognosis and decreased patient survival. We therefore suspected a role of BARD1 isoforms in colon cancer. METHODS: We performed immunohistochemistry in 168 colorectal cancers, using four antibodies directed against differentially expressed regions of BARD1. We determined structure and relative expression of BARD1 mRNA isoforms in 40 tumour and paired normal peri-tumour tissues. BARD1 expression was correlated with clinical outcome. RESULTS: BARD1 isoforms were expressed in 98% of cases and not correlated with BRCA1. BARD1 mRNA isoforms were upregulated in all tumours as compared with paired normal peri-tumour tissues. Non-correlated expression and localisation of different epitopes suggested insignificant expression of full-length (FL) BARD1. Expression of N- and C-terminal epitopes correlated with increased survival, but expression of epitopes mapping to the middle of BARD1 correlated with decreased survival. Middle epitopes are present in oncogenic BARD1 isoforms, which have pro-proliferative functions. Correlated upregulation of only N- and C-terminal epitopes reflects the expression of isoforms BARD1δ and BARD1φ. CONCLUSION: Our results suggest that BARD1 isoforms, but not FL BARD1, are expressed in colon cancer and affect its progression and clinical outcome.

Inflammation and Barrett's carcinogenesis.

Barrett's esophagus (BE) is one of the most common premalignant lesions in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. Esophageal adenocarcinoma (EA) develops through progression from BE to low- and high-grade dysplasia (LGD/HGD) and to adenocarcinoma. It is widely accepted that inflammation can increase cancer risk, promoting tumor progression. Therefore, inflammation is regarded as the seventh hallmark of cancer. In recent years, the inflammation-cancer connection of Barrett's carcinogenesis has been intensively studied, unraveling genetic abnormalities. Besides genetic alterations, inflammation is also epigenetically linked to loss of protein expression through transcriptional silencing via promoter methylation. Key mediators linking inflammation and Barrett's carcinogenesis include reactive oxygen species (ROS), NFκB, inflammatory cytokines, prostaglandins, and specific microRNAs (miRNAs). Therefore, the decipherment of molecular pathways that contain these and novel inflammatory key mediators is of major importance for diagnosis, therapy, and prognosis. The detailed elucidation of the signaling molecules involved in Barrett's carcinogenesis will be important for the development of pharmaceutical inhibitors. We herein give an overview of the current knowledge of the inflammation-mediated genetic and epigenetic alterations involved in Barrett's carcinogenesis. We highlight the role of oxidative stress and deregulated DNA damage checkpoints besides the NFκB pathway.

[Acute abdomen in a patient with ANCA-associated vasculitis]. / Akutes Abdomen bei ANCA-Assoziierter Vaskulitis.

HISTORY AND FINDINGS: A 49-year-old man complained of increasing pain in the lower left abdomen. Three weeks previously joint pain had developed, and in the last 7 days the patient had noted a cutaneous rash at the lower legs. Within three days after admission a paralytic ileus developed, progressed and culminated in a small bowel perforation. In the 60 cm ileum specimen as well as in the skin lesions there was marked intra- und perivascular infiltration with neutrophil granulocytes and focal necrosis, but no granuloma. DIAGNOSIS, TREATMENT AND COURSE: As the proteinase 3 subtype of antineutrophil cytoplasmic antibodies (ANCA) was positive ANCA-associated vasculitis with gastrointestinal, cutaneous and kidney involvement was diagnosed. After initiation of cytostatic treatment with methylprednisolone boli und cyclophosphamide the patient's condition improved. The post-operative course was uneventful. CONCLUSION: ANCA-associated vasculitis rarely presents with severe gastrointestinal complications. The disease represents an interdisciplinary challenge because of its variable clinical presentation and the possibly lethal outcome if not adequately treated.

[Colorectal polyposis syndrome: a guide to diagnosis]. / Kolorektale Polyposen: Eine Anleitung zur Diagnostik.

Biopsies and resection specimens of the gastrointestinal tract are a major part of the routine workload in many histopathology departments, whereby polypoid lesions are generally the main focus. In addition to distinguishing non-neoplastic from neoplastic polyps and evaluating the grade of dysplasia of the latter, the pathologist should always consider the possibility of an underlying polyposis syndrome. Not only have additional hereditary polyposis syndromes been identified in recent years due to a better understanding of their genetic and epigenetic alterations but also knowledge on well known polyposes has improved, leading to subtyping of various forms according to their different genotype. It is essential for the histopathologist to understand that the conventional histomorphology of individual polyps combined with information on the number and distribution of these lesions and clinical data can provide clues regarding a possible hereditary background. Therefore, the correct histological assessment of polyps is not just about getting the diagnosis right, it might also lead to genetic screening of family members and spouses.

[Peritoneal splenosis 26 years after traumatic splenic rupture--rare differential diagnosis of a subepithelial gastric mass--case report and review of the literature]. / Peritoneale Splenose 26 Jahre nach traumatischer Milzruptur--seltene Differenzialdiagnose eines submukösen Magentumors--Fallbericht und Literaturübersicht.

Differential diagnoses of subepithelial gastric masses include benign (leiomyoma, lipoma, haemangioma, lymphangioma, neurogenic tumours, glomus tumour) and malignant (leiomyosarcoma, gastric Kaposi's sarcoma, metastases) neoplastic lesions, gastrointestinal stromal tumours (GIST) and lesions of non-neoplastic origin (heterotopic pancreatic tissue, intramural pseudocysts, intramural haematoma). Occasionally, however, suspected gastric wall tumours are caused by extragastral lesions that are not always easily distinguished from genuine gastric wall lesions by endoscopy or radiological imaging. We report the case of a 77-year-old patient undergoing laparoscopy for suspected gastric GIST in our institution in whom splenectomy had been performed 26 years prior to presentation due to traumatic splenic rupture. The tumour revealed to be ectopic splenic tissue located at the parietal peritoneum of the ventral abdominal wall, thereby fulfilling the definition of splenosis. Epidemiology, pathogenesis, diagnostics and therapy of splenosis are discussed in the context of a review of the relevant literature.

[Splenic granulomas - rare extraintestinal manifestation of Crohn's disease]. / Milzbefall - seltene extraintestinale Manifestation bei Morbus Crohn.

Extraintestinal manifestations of inflammatory bowel disease occur frequently in parallel to the inflammation in the bowel. The activity of extraintestinal manifestations is often divergent to the activity of intestinal inflammation. We here present the case of a rare extraintestinal manifestation of Crohn's disease and report on a 52-year-old patient with known Crohn's disease and primary sclerosing cholangitis (PSC) in clinical remission. Multiple lesions of the spleen were observed in routine MR tomography. The histological examination of a specimen obtained by MR-guided fine needle biopsy showed non-caseating epitheloid cell granulomas. The splenic granulomas regressed completely and spontaneously without specific immunmodulatory therapy.

IL-17A and IL-17F gene expression is strongly induced in the mucosa of H. pylori-infected subjects from Kenya and Germany.

Helicobacter pylori infection is the major cause of gastritis. Immunologically, H. pylori gastritis is associated with an infiltration of immune cells into gastric mucosa and the upregulation of various cytokines. Here, we analysed the gene expression of IL-1- and IL-17-related cytokines in regard to H. pylori infection in 85 German and 51 Kenyan patients with reflux-related or dyspeptic symptoms, respectively. Degree of gastritis and density of colonization were assessed histologically in accordance with the updated Sydney classification. Gene expression levels of cytokines IL-1ß, IL-8, IL-18, IL-33, IL-17A, IL-17F and IL-23 as well as IL-23R were analysed by real-time RT-PCR. In both populations, H. pylori-infected individuals had significant higher inflammatory scores for activity and chronicity than H. pylori-negative subjects (P values between 0.006 and <0.0001). IL-8 mRNA was induced up to 6-fold in H. pylori-infected patients (P < 0.05), while the expression levels of IL-1ß, IL-18, IL-23, IL-33 and IL-23R did not differ with respect to the H. pylori status in both groups. Most strikingly, a significant induction of both IL-17A and IL-17F was noted in H. pylori-infected individuals of both ethnic groups. Almost all IL-17F-positive samples revealed co-expression of IL-17A (40/42, 95.2%). Analysing IL-17A and IL-17F transcript levels of these 40 'double-positive' samples, a highly significant positive correlation between both genes was identified (P < 0.001). Taken together, H. pylori infection leads to a strong upregulation of both IL-17A and IL-17F in the gastric mucosa suggesting a regulatory link between both genes.

[Exceptional bilocular inflammatory myofibroblastic pseudotumour (IMT) characterized by recurrent thoracic tumour growth and a rare (adult) second manifestation within the mesenteric tissue of the small intestine]. / Ungewöhnlicher bilokulärer inflammatorischer myofibroblastärer Pseudotumor (IMT), charakterisiert durch thorakales Rezidiv und seltene, da adulte, Zweitmanifestation im Dünndarmmesenterium.

BACKGROUND: Despite its rare occurrence, inflammatory myofibroblastic pseudotumour (IMT) is relevant in the differential diagnosis of intestinal lesions. By the mean of an extraordinary case report, tumour site and specific characteristics, finding of the correct diagnosis, therapeutic management, and outcome of extrapulmonary IMT is decribed based also on relevant references from the literature. CASE REPORT: A 39-year old man experienced a multifocal thoracic recurrence and abdominal metastasis of IMT 12 years after successful primary resection of pulmonary IMT. The intra-abdominal lesion localised in the jejunal mesenteric tissue was removed surgically (resection status, R 0) by segmental resection of the mid-jejunum (length: 80 cm) followed by jejunojejunostomy. Histology evaluation confirmed IMT. Thoracic surgeons advised against a surgical approach to the pulmonary and thoracic lesions because of their number and proximity to the superior vena cava as well as mediastinal infiltration. Despite receiving repeated advice from his physicians, the patient has not agreed to combined immunosuppressive treatment with cyclophosphamide and steroids, because of his desire for children. He underwent 5 months of systemic steroid treatment, starting in the third postoperative month, which he then chose to stop because of Cushing symptomatology. He agreed to a computed tomography (CT) scan follow-up 12 months after surgery, which revealed slight local progression of the remaining pulmonary lesion. Administration of a second steroid medication was initiated at a lower dose. No further CT scans were obtained. At present, he is consulting with an alternative medicine practitioner. CONCLUSION: This report documents a rarely described case of IMT at a jejunal mesenteric tumour site, interpreted as an uncommon late and extraordinary, metastatic, multifocal recurrence found 12 years (!) after surgical resection of the primary pulmonary tumour.

Oxaliplatin for chemotherapeutic treatment and prevention of experimental peritoneal carcinomatosis in rats comparing the intraperitoneal and intravenous application mode.

BACKGROUND: The occurrence of peritoneal carcinomatosis after resection of colorectal carcinoma is still a major concern. In this study, we tested the cytostatic agent oxaliplatin delivered intraperitoneally and intravenously to prove whether it can significantly reduce intraperitoneal tumor growth. METHODS: Peritoneal tumor growth was experimentally induced with transfer of CC-531 colon cancer cells (5 x 10(6)) to the peritoneal surface of rats via laparotomy. Oxaliplatin was delivered either intraperitoneally or intravenously. In group A, oxaliplatin was administered directly after tumor cell transfer. While oxaliplatin was applied in group B on days 5, 10, and 15 after tumor cell implantation, in group C, it was administered on days 10, 15 and 20. The rats were sacrificed on day 30 after tumor cell transfer. Tumor weight, relative increase in tumor mass, volume of malignant ascites and the number of tumor nodes were determined. RESULTS: Oxaliplatin significantly inhibited tumor growth after direct (group A) and early postoperative application (group B) via the intraperitoneal route. The late postoperative administration of oxaliplatin (group C) did not cause a significant effect on peritoneal tumor growth as it did with the intravenous application mode in groups A, B, and C. CONCLUSIONS: In this experimental model, oxaliplatin was highly effective against intraperitoneal tumor spread but only with the intraperitoneal application route. Other cytostatic agents with different effector mechanisms should be combined with oxaliplatin to further increase the therapeutic efficacy of the favorable intraperitoneal treatment in subsequent studies testing, in addition, the effects on wound and anastomosis healing.

The combined presence of H pylori infection and gastro-oesophageal reflux disease leads to an up-regulation of CDX2 gene expression in antrum and cardia.

BACKGROUND: CDX2 is an epithelial transcription factor that regulates intestinal differentiation and is involved in the development of intestinal metaplasia (IM). AIM: To analyse the expression of CDX2 in the gastric mucosa in various locations and its relationship to Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD). METHODS: 69 patients with upper gastrointestinal symptoms were stratified into four groups according to their H pylori and GORD status. Patients without infection and without GORD were the reference group (H pylori(-)/GORD(-)). Biopsies from the antrum, corpus and cardia were assessed by histopathology according to the updated Sydney System. CDX2 transcription levels were determined by quantitative RT-PCR and immunohistochemistry. RESULTS: CDX2 gene expression was significantly up-regulated in antral and cardia mucosa of patients with both H pylori infection and GORD (26- and 100-fold, respectively; p<0.05), but remained unchanged in corpus mucosa. If only H pylori infection or GORD was present, CDX2 expression levels were 6- to 11-fold increased in the antrum, but without reaching statistical significance. CDX2 expression correlated positively with the degree of IM (p<0.01) and the degree of H pylori induced inflammation (p<0.05). Gene expression data were confirmed immunohistochemically by the detection of CDX2 in areas of IM and in focally distributed CDX2-expressing cells in non-metaplastic gastric mucosa. CONCLUSIONS: The combined presence of H pylori infection and GORD leads to an up-regulation of CDX2 gene expression in cardia and antral mucosa, but not in the corpus.

Small bowel polyps and tumours: endoscopic detection and treatment by double-balloon enteroscopy.

BACKGROUND: Double-balloon enteroscopy has allowed us not only to inspect deeply the small bowel but also to carry out interventions for diseases of the small bowel. AIM: To evaluate the utility of double-balloon enteroscopy for the diagnosis and therapy of these lesions. METHODS: All patients undergoing double-balloon enteroscopy for evaluation of small bowel polyps and tumours during a 3.75-year period at a university referral hospital were studied. The types of polyps and tumours as well as endoscopic technique of removal, surgery and complications were documented. RESULTS: The incidence of small bowel polyps and tumours in-patients undergoing DBE was 9.6%. A total of 40 double-balloon enteroscopy procedures were performed in 29 patients [13 female (44.8%), mean age 51 years, range 22-74]. The following lesions were found most frequently: adenomas in familial adenomatous polyposis syndrome, n = 8; hamartomas, n = 4 (Peutz-Jeghers and Cronkhite Canada syndromes), jejunal adenocarcinoma n = 5, neuroendocrine tumour n = 4 and others n = 6. CONCLUSIONS: The incidence of small bowel tumours in those in-patients who were undergoing double-balloon enteroscopy was 10%. Double-balloon enteroscopy is useful for the diagnosis and treatment of small bowel polyps and tumours.

Oxidative stress in ulcerative colitis-associated carcinogenesis.

Oxidative stress is defined as an imbalance between generation of reactive oxygen species (ROS) and decreased antioxidant defense systems. Oxidative stress develops particularly in inflammatory reactions because the inflammatory cells, neutrophils, and macrophages produce large amounts of ROS. It has been known for a long time that oxidative stress in inflamed tissue can pave the way for malignant tumors, and that it is a major pathogenetic factor for the well-established correlation between inflammatory diseases and cancer. Oxidative stress has long been associated with the pathogenesis of chronic inflammatory bowel disease (IBD)-related colorectal cancer. This article provides an overview of the pathology of ROS and presents recent advances concerning the role of ROS in IBD-related colorectal carcinogenesis (Fig. 1).

Low prevalence of Helicobacteraceae in gall-stone disease and gall-bladder carcinoma in the German population.

Colonisation of the hepatobiliary system with bile-resistant Helicobacter spp. has been proposed as a novel risk-factor in the pathogenesis of gall-bladder carcinoma (GBC). There are reports that biliary Helicobacter colonisation is frequent in countries with a high incidence of gall-bladder carcinoma. However, the prevalence of Helicobacteraceae in the gall-bladders of patients with GBC in Germany, a region with a low incidence of GBC, is unknown. Therefore, gall-bladder tissue from 99 patients who had undergone cholecystectomy was tested, including 57 cases of gall-stone disease (GSD), 20 cases of GBC, and 22 control patients. The presence of Helicobacter spp. was investigated by culture, immunohistochemistry and a group-specific PCR targeting the 16S rRNA gene of all currently known Helicobacteraceae. Of the 99 cases investigated, only one patient with GSD was PCR-positive for Helicobacteraceae. For this individual, sequence analysis of the 16S rRNA gene showed that it had homology closest to the 16S rRNA sequence of Helicobacter ganmani. Helicobacteraceae were not detected by culture or immunohistochemistry. The low prevalence of Helicobacteraceae in the gall-bladders investigated suggests that Helicobacteraceae do not play a predominant role in the pathogenesis of GSD and GBC in the German population. The low prevalence could be a possible explanation for a relatively low incidence of GBC in the German population, despite the fact that GSD, the major risk-factor for GBC, is highly prevalent.

Effects of low-dose aspirin on gastric erosions, cyclooxygenase expression and mucosal prostaglandin-E2 do not depend on Helicobacter pylori infection.

BACKGROUND: The mechanisms by which Helicobacter pylori and low-dose aspirin induce gastric damage are not completely elucidated. AIM: To evaluate the effects of low-dose aspirin on gastric damage, mucosal prostaglandin-E(2) levels and cyclooxygenase-enzyme expression in relation to the H. pylori status. METHODS: Twenty healthy volunteers (H. pylori positive, n = 10; H. pylori negative, n = 10) received aspirin 100 mg/die for 1 week. At days 0, 1, 3 and 7, gastric mucosal lesions were studied by oesophagogastroduodenoscopy and histology. COX-1 and COX-2 were determined by immunohistochemistry and reverse-transcriptase polymerase chain reaction, and mucosal prostaglandin-E(2) levels by enzyme-linked immunosorbent assay. Nine H. pylori-positive subjects repeated the protocol after H. pylori eradication. RESULTS: All groups developed a similar number of erosions. COX-1 and COX-2 expression, as well as mucosal prostaglandin-E(2) levels were not influenced by H. pylori status and aspirin medication. Helicobacter pylori-negative and H. pylori-eradicated subjects who developed aspirin-induced erosions had significant lower pre-treatment antral prostaglandin-E(2) levels than those without erosions (3.6 ng/microg vs. 6.3 ng/microg protein and 3.6 ng/microg vs. 6.0 ng/microg protein, respectively, P < 0.01 Mann-Whitney U-test). CONCLUSIONS: In healthy subjects, low-dose aspirin for 1 week does neither affect cyclooxygenase expression nor mucosal prostaglandin-E(2) levels. Antral prostaglandin-E(2)-basal levels appear to be critical for development of aspirin-induced gastric damage in subjects without H. pylori infection.

Close localization of DAP-kinase positive tumour-associated macrophages and apoptotic colorectal cancer cells.

The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated protein crucially involved in the induction of early apoptotic pathways. Aberrant hypermethylation of the DAP-kinase promoter plays a major role in tumorigenesis. We aimed to investigate the inactivation of DAP-kinase and its association with apoptotic cell death in 94 colorectal carcinomas. DAP-kinase promoter hypermethylation and mRNA expression were investigated using methylation-specific PCR and real-time RT-PCR, respectively. The expression of DAP-kinase, Fas, and Fas-ligand (FasL) proteins was studied by immunohistochemistry and immunofluorescence. Apoptosis of tumour cells was investigated using the TUNEL assay. DAP-kinase was expressed in tumour cells and tumour-invading macrophages and was closely associated with high numbers of apoptotic tumour cells. DAP-kinase expression co-localized with FasL overexpression in tumour-associated macrophages, and aberrant promoter hypermethylation was verified in more than 50% of carcinomas. There was a tendency for proximal tumours to show DAP-kinase promoter methylation more frequently (p = 0.07). Promoter methylation resulted in a decrease or loss of DAP-kinase protein expression in tumour cells and tumour-associated macrophages. Simultaneously, a decreased apoptotic count and loss of Fas/FasL expression was observed in tumour cells. Our study is the first to demonstrate DAP-kinase expression in invading tumour-associated macrophages in colorectal cancer. The presence of similar expression levels of DAP-kinase in tumour cells and associated macrophages, and their dependence on the promoter methylation status of the tumour cells, suggests cross talk between these cell types during apoptotic cell death.

Expression of cathepsin K in chordoma.

Invasive growth of chordoma is accompanied by severe destruction of adjacent bone tissue, a fact that requires high proteolytic activity at the tumor invasion fronts. In this context, cathepsin K is a candidate molecule. It is a protease with high collagenolytic and elastinolytic activity and previously thought to be restricted to osteoclasts and osteoclast-mediated bone resorption. In this study, 44 cases of chordoma of sphenooccipital localization, and 10 embryo-fetal specimens including chorda dorsalis were studied immunohistochemically for their expression of cathepsin K. In 4 additional snap-frozen chordoma cases, the enzyme expression was investigated by reverse transcription polymerase chain reaction and enzyme histochemistry. Ten chondrosarcomas of the skull base served as controls. Various concentrations of cathepsin K mRNA could be seen in all snap-frozen chordoma specimens. The protease was immunohistochemically expressed by the tumor cells. The immunoreactions were accentuated at the tumor invasion fronts. Enzyme histochemistry indicated a strong tumor cell-associated cathepsin K activity in invasive tumor components. In contrast to chordoma, cathepsin K was not significantly expressed in chorda dorsalis and chondrosarcoma of the skull base. In chondrosarcoma, protease expression was limited to osteoclastic cells localized between infiltrative tumor components and regular bone trabeculae. This study shows the significant expression and activity of cathepsin K in chordoma and implicates an important and direct role of this protease in the infiltrative growth of this tumor. This protease expression occurred during neoplastic transformation and did not appear in chorda dorsalis.

Fibular head autograft. A salvage technique for severely comminuted lateral fractures of the tibial plateau: report of five cases.

Severely comminuted fractures of the lateral tibial plateau with central defects of the articular cartilage have traditionally been treated with iliac crest or patellar autograft, with varying success. Arthrodesis or arthroplasty for late deformity or instability are not suitable for young, active patients. The use of the fibular head as a replacement for the tibial plateau obtained excellent or good functional results in five patients with these difficult fractures.