Tumor cell dissemination in a human colon cancer animal model: orthotopic implantation or intraportal injection?

BACKGROUND: The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination of tumor cells. METHODS: To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 x 10(6) HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow. RESULTS: Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 x 10(6) HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 x 10(6) cells also generated MRD in the bone marrow in 63% of animals. CONCLUSIONS: The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.

[Blunt trauma with bullet-proof vests. Skin lesions are no reliable predictor of injury severity]. / Stumpfes Körperstammtrauma mit ballistischer Schutzweste. Prellmarken geben keine zuverlässigen Hinweise auf innere Verletzungen.

It is well known that so-called bullet-proof vests offer protection against a wide range of penetrating trauma, but their protection against blunt trauma is less well understood. Fast projectiles may result in hematomas and contusions behind the armour. We report a traffic accident involving a young soldier wearing a ballistic protection vest resulting in a right thoracoabdominal blunt trauma leading to a confined liver compression rupture. As nearly no skin marks were detectable, we point out that every emergency department surgeon should be very suspicious if a patient wore a ballistic vest at the time of the accident--there may be no skin marks despite severe intra-abdominal trauma. Our patient recovered following hypotensive ICU treatment, thrombocyte mobilization, and factor VIIa substitution.

[Antibody treatment in colorectal cancer--what the surgeon needs to know]. / Antikörpertherapie beim metastasierten kolorektalen Karzinom--was der Chirurg wissen sollte.

Advances in the medical treatment of colorectal cancer patients have resulted in considerable improvements through the introduction of new cytotoxic drugs. The significant progress in molecular and tumour biology has produced a great number of targeted, tumour-specific, monoclonal antibodies that are now in various stages of clinical development. Two of these antibodies, cetuximab (Erbitux) und bevacizumab (Avastin), directed against the epidermal growth factor receptor (EGFR) and the vascular epithelial growth factor (VEGF), respectively, have recently been approved for use in metastatic colorectal cancer. The combination of well-known and newly developed cytotoxic agents with monoclonal antibodies makes the medical treatment of colorectal cancer patients considerably more complex, but also provides additional therapeutic strategies for patients in advanced stages of disease.

[Phlegmonous gastritis in a 44-year-old woman on immunosuppressive therapy]. / Phlegmonöse Gastritis bei einer 44-jährigen Patientin unter immunsuppressiver Therapie.

HISTORY AND ADMISSION FINDINGS: A 44-year-old woman was on long-term immunosuppressive therapy with leflunomide and adalimumab for rheumatoid arthritis. She was admitted to the emergency room with diffuse abdominal pain of sudden onset. On physical examination she had rebound tenderness in all four abdominal quadrants. INVESTIGATIONS: The white blood cell count was 3300/l, C-reactive protein 25 mg/dl and serum lactate 10 mmol/l. Abdominal computed tomography revealed a diffusely thickened gastric wall and ascites. At explorative laparotomy 1000 ml of a cloudy peritoneal fluid were aspirated and found to be negative for bacteria. But a culture of a mesenterial smear grew streptococci group A. Intra-operative endoscopy showed extensive hemorrhagic gastritis. Because there was no perforation or transmural necrosis gastric resection was not performed. DIAGNOSIS, TREATMENT AND COURSE: Diffuse thickening of the gastric wall, extended mucosal necrosis and the peritoneal finding of streptococci in an immunocompromised patient suggested the diagnosis of phlegmonous gastritis. On treatment with antibiotics and proton pump inhibitor the patient made a slow recovery over the following eight weeks. Nine months after the event an asymptomatic antral stricture was noticed at follow-up gastroscopy. CONCLUSION: Phlegmonous gastritis is a rare but life-threatening complication in immunosuppressed patients.

[New concepts in treatment of gastric carcinoma]. / Neue Konzepte in der Behandlung des Magenkarzinoms.

Despite interdisciplinary approach to gastric cancer the outcome of patients remains poor. Even after curative resection most patients suffer from progression of disease and metastasizing course. Adjuvant treatment like chemotherapy or radiation can not improve survival substantialy. This is discussed to be due to dissemination of tumor cells, which are not affected by most treatment options. The new concept of tumor specific antibody therapy with a monoclonal antibody is discussed as an effective treatment especially to fight disseminated tumor cells and thus might help to improve the outcome in stomach cancer.

Giant fold gastritis with consecutive gastric carcinoma in a patient with peutz-jeghers syndrome.

We describe the case of a 36-year-old patient with Peutz-Jeghers syndrome and a very unusual gastric morphology resembling giant fold gastritis. The latter lacked additional features of Menetrier's syndrome, was not influenced by eradication of Helicobacter pylori and persisted for more than ten years under regular endoscopic surveillance. Histologically, foveolar hyperplasia was found in the enlarged folds. Endoscopic ultrasound documented a hyperechoic widening of the gastric mucosa without involvement of the deeper layers. However, despite annual control gastroscopies, an adenocarcinoma developed between the folds and was in an already advanced stage at diagnosis (UICC III). We suggest that a variant of Peutz-Jeghers syndrome may be characterised by marked foveolar hyperplasia similar to Menetrier disease, and that not conventional endoscopy alone, but rather endoscopic ultrasound may be considered in such patients.

[Solid-pseudopapillary tumor of the pancreas as differential diagnosis in pancreatic tumors of the young]. / Der solid-pseudopapilläre Tumor des Pankreas als Differenzialdiagnose bei Pankreasraumforderungen junger Patienten.

AIM: The presentation of solid pseudopapillary tumors of the pancreas (SPTP) with examples of our own surgical department. SPTP occur typically in young women or in children and are for most of benign behavior. In about 5 % a malignant course with occurrence of metastases can develop. METHODS: Diagnosis, morphological and histological findings and therapeutic approach are described in three cases. The differential diagnosis of other tumors of the pancreas is discussed. FINDINGS: Three women (age 21, 33 and 43) with SPTP have been treated in the Department of Surgery at the University of Würzburg between 1997-1999. All tumors were resected curatively. No adjuvant treatment was performed. The follow up ranged from 31-56 months. No relapse of disease or occurrence of metastases were observed. All resected specimen revealed the typical character of SPTP with areas of solid parts and hemorrhage within the tumor. A panel of immunohistological markers (Vimentin, N-Cam, NSE, Chromogranin, Synaptophysin, Ck7, Ck19, Ck20, EMA) and expression of receptors were investigated. CONCLUSION: The diagnosis of this rare tumor can be made clinically and intraoperatively according to its typical morphology and occurrence, predominantly in young women or in children thus helping to perform adequate surgical therapy.

[Induction of apoptosis by preoperative passive immunotherapy in resectable stomach carcinoma]. / Apoptoseinduktion durch präoperative passive Immuntherapie beim resektablen Magenkarzinom.

The antibody SC-1 is a human IGM molecule, which binds to a tumor specific receptor. This SC-1 receptor is detectable on biopsies, it is present in about 50% of gastric cancers. After binding of the antibody to the receptor the tumor cells go into apoptosis. 50 patients expressing the SC-1 receptor on their tumors have been treated with SC-1 prior to gastrectomy. In 80% of cases apoptosis induction could be demonstrated in the tumors. The only side effect of the SC-1 therapy was a reversible episode of fever during antibody infusion in 8% of our patients.

Success in treatment of complicated diverticular disease is stage related.

The clinical stage of disease is one of the many factors affecting outcome after treatment for complicated diverticular disease. We retrospectively assessed surgical results during the period 1994-1999 in 406 patients with complicated diverticular disease, according to the stage of disease, surgical technique, postoperative complications, and mortality. Single-stage resection and primary anastomosis were performed safely in most patients with stage I or II disease. Severe complications were rare in stage I but increased in incidence with higher stages. Patients with stage III are a high-risk group. This stage often requires a two-stage procedure (primary anastomosis and protective ileostoma or the Hartmann procedure). Despite these measures, many severe complications occurred in stage III.

[Adjuvant immunotherapy of stomach carcinoma with antibody-induced apoptosis]. / Additive Immuntherapie des Magenkarzinoms durch antikörpervermittelte Apoptose.

The human monoclonal antibody SC-1 was isolated from a patient with a diffuse-type adenocarcinoma of the stomach and induces apoptosis of stomach carcinoma cells by binding a stomach-carcinoma-associated isoform of CD55/DAF-B. In a first clinical trial with 20 patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 and 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In 90% of the cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in 50% of the patients a significant regression of tumor mass could even be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients. These data show, that the human monoclonal antibody SC-1, which induces tumorspecific apoptosis, can be successfully used for adjuvant therapy.

Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human monoclonal antibody SC-1: first clinical and histopathological results.

In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight patients with poorly differentiated stomach adenocarcinoma of diffuse-type received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h later by gastrectomy and lymphadenectomy. In seven cases a significant induction of apoptotic activity was measured in primary tumors as compared with earlier biopsy material and in five patients a significant regression of tumor mass could be determined histopathologically. No toxic crossreactivity was observed with normal tissue or organs of patients.

[Primary extragenital manifestation of a malignant mixed Mullerian tumor of the major omentum]. / Primär extragenitale Manifestation eines malignen Müller-Mischtumors im Omentum majus.

Malignant mixed Müllerian tumours (MMMT) are tumours of the female genital tract which rarely occur in extragenital sites. We report a case of a 46-year-old female with MMMT with primary occurrence in the greater omentum. Only 19 cases of primary extragenital manifestations of this tumour are described in literature. The clinical appearance, diagnosis, therapy, histological evaluation and histogenesis are discussed.