Human papillomavirus type 16-associated primary squamous cell carcinoma of the rectum.

Primary squamous cell carcinoma (SCC) of the colorectum is an extremely rare malignancy of unknown etiology and pathogenesis. We describe an 87-year-old man with primary SCC of the rectum. Routine histology demonstrated a squamous metaplasia-dysplasia sequence of the rectal mucosa with subsequent malignant transformation. Molecular biologic analysis using polymerase chain reaction (PCR) and in situ hybridization revealed the presence of human papillomavirus type 16 (HPV-16) DNA within metaplastic, dysplastic, and SCC lesions and in tumor-free rectal mucosa. Moreover, nested reverse-transcription PCR showed transcriptional activity of the viral E6/E7 oncogenes in tumor tissue and tumor-free rectal mucosa. By contrast, 4 typical adenocarcinomas of the rectum and their adjacent normal mucosa were found to be negative for HPV by nested PCR. In line with the well-established concept of HPV-associated anogenital carcinogenesis, our results strongly suggest an etiologic role of HPV-16 in the pathogenesis of the metaplasia-dysplasia-SCC sequence in the case described.

[Network of surgical wound centers using a new electronic data processing documentation system]. / Die Vernetzung chirurgischer Wundzentren mit Hilfe eines neuen EDV-Dokumentationssystems.

UNLABELLED: Care of chronic wounds is of enormous medical, social and economic importance. Nevertheless there is a lack of epidemiological and economical data. A network of ten wound care centers was created and data were documented in a new computerized wound documentation system. METHODS: Treatment was performed according to a comprehensive and standardized wound care protocol. The new documentation system is a network-capable solution. Digital images and planimetry as well as patient and wound related data are recorded. RESULTS: During the first year the ten centers treated and documented already 3281 wounds. There is a wide spectrum of different chronic wounds treated in the participating centers. Despite of long wound duration of several wounds with a median of 5 weeks (range 0-62 years), the healing rate was 80% within 455 days. CONCLUSION: Large amounts of data can be collected and scientifically evaluated in the wound net. This is realized by a new computerized documentation system, which was integrated into the clinical routine and enables clear and standardized documentation. Therefore even large multicenter therapy studies may be performed easily in the wound net and economical data could be collected.

Growth factors in clinical practice.

Wound repair consists of a complex interaction of cellular and biochemical events. Several growth factors have been identified as regulatory polypeptides co-ordinating the healing process. Although it is not known precisely why chronic wounds do not follow the normal pattern of healing, diminished growth factor content and accelerated growth factor degradation may contribute to poor healing. Topical application of different factors exert stimulatory effects on wounds in animal models. Human data are limited but the most investigated compound is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). PDGF-BB enhances granulation tissue formation and facilitates epithelialisation. Clinical trials in patients with 'hard to heal' diabetic foot ulcers demonstrated significant improvement in the 'healing rate' and the 'time to healing' compared with controls. Refinement of therapeutic strategies with growth factors will take place in the future.

[The wound care center in surgery: an interdisciplinary concept for diagnostic and treatment of chronic wounds]. / Die chirurgische Wundsprechstunde. Ein interdisziplinäres, diagnostisches und therapeutisches Konzept für chronische Wunden.

In Germany there is no standardized wound care for patients with chronic wounds in specialized centers. We have established a wound care unit for the past 6 years. The principal concept of therapy was characterized by standardized local surgery, moist wound dressings and concomitant treatment of the underlying disease. We performed local therapy, coordinated the interdisciplinary treatment and developed a new wound documentation system for quality control. We established a close network, integrating general practitioners and home care organizations to realize a mainly outpatient treatment supported by short hospital therapy. Exclusive outpatient treatment was performed in 42% of all patients. According to our prospective data, we achieved an improvement in wound care: 69% of the wounds resistant to therapy for a mean of 30 months healed within 12 months after therapy according to our protocol. Our data strongly supported the importance of local surgery: neither wound depth nor wound infection had any influence on the healing rate, presumably due to radical excisional debridement of necrotic tissue. The presented data justify on medical and economic grounds the establishment of such wound care centers in Germany.

Polyurethane vascular prostheses decreases neointimal formation compared with expanded polytetrafluoroethylene.

PURPOSE: Synthetic grafts have been increasingly used for complex vascular reconstructions in patients with limited autologous vein availability. Materials currently in use induce increased stenosis and graft thrombosis compared with autologous vein, especially in smaller vessels. We examined whether grafts constructed of a porous biodegradation-resistant polycarbonate polyurethane (PU) exert better biocompatibility in terms of faster endothelialization and decreased chronic proliferation of intimal cells compared with expanded polytetrafluoroethylene (ePTFE). METHODS: PU or ePTFE interposition grafts were implanted into the abdominal aortas of male Sprague-Dawley rats (PU, n = 37; ePTFE, n = 32). Grafts were removed at days 1, 7, 14, 28, and 56 and 6 months and were evaluated by immunohistochemical, electron microscopic, and morphometric techniques. Bromodeoxyuridine (BrdU) was injected at 1 and 24 hours before death to determine cellular proliferation. Endothelial cells and smooth muscle cells were identified with antibodies to von Willebrand factor and alpha-actin, respectively. RESULTS: The luminal surface of PU grafts took 4 weeks to completely endothelialize, whereas ePTFE grafts took 24 weeks (P <.05). Neointimal cell proliferation was lower in PU grafts compared with ePTFE at 56 days (1.4 +/- 0.1 versus 8.6 +/- 1.5, P <.001) and at 6 months (0.15 +/- 0.002 versus 3.4 +/- 0.5, p <.001). Neointimal thickness at 6 months after implantation was 3.2 +/- 0.8 micrometer for PU compared with 10.3 +/- 3.1 micrometer for ePTFE (P <.05). CONCLUSION: Polycarbonate polyurethane small vascular prostheses promoted faster luminal endothelialization, induced less chronic intimal proliferation, and produced a significantly thinner neointima than ePTFE grafts. These findings suggest that aliphatic-polycarbonate urethanes may offer advantages over standard materials such as ePTFE for vascular graft construction.

Growth factors in distraction osteogenesis. Immuno-histological pattern of TGF-beta1 and IGF-I in human callus induced by distraction osteogenesis.

Although growth factors have been demonstrated during bone healing, their presence has not yet been confirmed in callus distraction. Therefore, in 3 patients we searched for cytokines during callus distraction. Bone biopsies were immuno-histochemically stained for TGF-beta1, IGF-I, TGF-beta type II receptor, IGF receptor, and proliferating cell nuclear antigen (PCNA). Histologically we found immature woven bone in the middle of the callus zone and increasing calcification and lamellar bone in the re-modelling zone. Osteoblasts and fibroblast-like cells in the middle zone, and osteoblasts in all zones stained for TGF-beta and its receptor. The number of positive staining cells related to proliferous activity as assessed both by PCNA, and by bone density in radiographs. IGF-I could be detected everywhere. In conclusion, growth factors are present in bone formation and in areas of re-modelling during callotasis. Their relation to proliferous activity and radiographic density supports their involvement in osteogenesis.

The mast cell-nerve axis in wound healing: a hypothesis.

Beyond their classic roles in allergic reactions and defence against parasites, mast cells can now be viewed as key players in regulating connective tissue homeostasis. There is good evidence that mast cells are in close morphological and functional contact with the peripheral nervous system. Although substantial differences exist between mast cells of different tissues and different species, they produce a wide range of agents, including cytokines, growth factors, and other regulatory molecules, and they respond to an equally wide range of substances, including neuropeptides. At our current level of understanding wound healing, inflammation plays a central role in this process, with macrophages being central protagonists at the cellular level. There is now increasing evidence that mast cells are also involved in wound healing, in health and disease. They produce and secrete histamine, heparin, and multifunctional cytokines and growth factors, which represent important agents in the wound-healing process. Reviewing the recent literature supporting this hypothesis, we also outline the clinical importance of this work to help close the gap between basic research and clinical application.

Diagnosis and management of metastatic gastrinoma by multimodality treatment including liver transplantation: report of a case.

Neuroendocrine tumors of the pancreas are being recognized with increasing frequency, not because the incidence has increased, but as a result of improvements in diagnostic tools such as radioimmunoassays for a variety of circulating peptides, and imaging methods that include positron emission tomography (PET) and immunoscintigraphy. Nevertheless, establishing the diagnosis of a neuroendocrine tumor is always a challenge to the clinician from both diagnostic and therapeutic perspectives. Liver transplantation as the ultimate therapeutic, or at least palliative, option for hepatic metastases has produced contradictory results over the past decade. We report herein the case of a 23-year-old woman who, after being diagnosed with gastrinoma in 1989, underwent the complete therapeutic array including liver transplantation for hepatic metastases in 1991. Although an extrahepatic tumor recurred 2 years later, for which double chemotherapy with 5-FU and streptozotocin was given, she is currently leading a normal life with a full-time job. This case prompted a critical review of the current literature on diagnosis and medical and surgical treatment.

Recombinant human transforming growth factor beta 3 accelerates gastric ulcer healing in rats.

BACKGROUND: Gastric ulcer healing is mediated by various endogenous growth factors. In this experimental study effect of locally and systemically applied recombinant human transforming growth factor beta 3 (rhTGF-beta 3) on gastric ulcer healing was investigated in the rat. METHODS AND RESULTS: Gastric ulcers were induced with a cryoprobe, and ulcer healing was evaluated 7 days after local infiltration (0.5 micrograms, 1.0 microgram, 2.5 micrograms, and 50 micrograms) or systemic (intravenous) application of TGF-beta 3 (500 micrograms/kg body weight). Compared with controls, a dose-dependent stimulation of ulcer healing (as evidenced by a reduction in ulcer size) was observed 7 days after local infiltration of TGF-beta 3 (1.0 microgram, 2.5 micrograms, and 50 micrograms). Corresponding increases in the levels of proliferating cell nuclear antigen (PCNA) and intracellular TGF-beta 3 expression and a downregulation of the TGF-beta type-II receptor expression were also observed in the granulation tissue of the ulcer margins. Systemic application of TGF-beta 3 produced effects similar to those observed after local treatment with 50 micrograms of the compound. CONCLUSION: Local and systemic TGF-beta 3 treatment accelerates gastric ulcer healing in rats.

Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.

BACKGROUND: The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitaxel on proliferation and migration of human arterial smooth muscle cells (haSMCs) in vitro and on neointima formation in an in vivo experimental rabbit model. METHODS AND RESULTS: Both monocultures of haSMCs and cocultures with human arterial endothelial cells (haECs) were used. Cell growth after 4, 8, and 14 days was determined in the absence or presence of platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor (bFGF), or thrombin. Nonstop paclitaxel exposure, as well as single-dose applications of paclitaxel for 24 hours or even 20 minutes (0.1 to 10.0 micromol/L), caused a complete and prolonged inhibition of haSMC growth up to day 14, with an IC50 of 2.0 nmol/L. Mitogens or cocultures with stimulating haECs did not significantly attenuate paclitaxel-induced effects. Immunohistochemistry showed characteristic cytoskeletal changes predominantly in the microtubule network. Additionally, in 20 male New Zealand White rabbits, intimal plaques were produced by electrical stimulation. In 10 animals, paclitaxel was locally applied by use of microporous balloons. Histologically, the intima wall area, wall thickness, and degree of stenosis were reduced significantly in paclitaxel-treated animals compared with controls. CONCLUSIONS: Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.

[Prognostic factors in treatment of diabetic foot ulcers]. / Prognosefaktoren in der Behandlung diabetischer Fussulzera.

138 patients with nonhealing diabetic foot ulcers were treated between 1994 and 1996. Sixty-nine percent of these foot ulcers healed within 17 weeks. Heel ulcers had a significantly lower healing rate, probably because of the difficulty of taking weight-bearing off this zone. Ischemia also correlated well with low healing rates, underlining the importance of vascular diagnosis and surgery. Since compliance is the most significant factor for success, it is mandatory to educate the patient about his disease and prevent further complications.

Growth factor expression of human arterial smooth muscle cells and endothelial cells in a transfilter coculture system.

By releasing growth factors, vascular cells can modulate proliferation and migration of neighboring cells in the arterial wall. Previous histological studies in transfilter cocultures, a culture model aimed to simulate vessel wall architecture, indicated that human arterial endothelial cells (haEC) can influence human arterial smooth muscle cell (haSMC) growth significantly. The aim of this study was to investigate the expression and secretion of various growth factors in order to better define the functional interactions between haEC and haSMC. Protein levels of platelet-derived-growth factor-AB (PDGF-AB), transforming-growth factor-beta1 (TGF-beta1), and tumor-necrosis factor-alpha (TNF-alpha) in mono- and cocultures were determined by ELISA 6, 12, 24, 48, 72 h after serum reduction. Highest PDGF-AB levels were found in monocultures with proliferative haEC, showing a peak after 24 h. In cocultures of haEC and haSMC, PDGF-AB levels were significantly lower. In contrast, neither proliferative, nor confluent haSMC released PDGF-AB significantly. Highest TGF-beta1 concentrations were detected in cocultures, followed by monocultures of haSMC and monocultures of haEC. In all cultures, TGF-beta1 levels increased in parallel with cultivation time and cell numbers, showing a maximum after 72 h. TNF-alpha could not be detected in any culture. Northern blots demonstrated a strong expression of PDGF-B chain-mRNA in haEC, but not in haSMC. PDGF-A chain and TGF-beta1-mRNA were expressed by haSMC and haEC. Addition of PDGF-AB to haSMC resulted in a potent growth stimulation, whereas TGF-beta1 and TNF-alpha exerted only moderate, divergent effects on haSMC. Histological observations in transfilter cocultures demonstrated that proliferative haEC induce the formation of fibromuscular plaques. These results suggest that proliferative haEC act as potent growth stimulators for haSMC, predominantly by PDGF-AB or -BB release.

Induction of cell-rich and lipid-rich plaques in a transfilter coculture system with human vascular cells.

Cell-to-cell interactions are mainly involved in the control of the proliferation, migration, differentiation and function of different cell types in a wide range of tissues. In the arterial vessel wall, human arterial endothelial cells (haEC) and smooth muscle cells (haSMC) coexist in close contact with each other. In atherogenesis, haSMC can migrate from the media to the subintimal space to form fibromuscular and atheromatous plaques. In the present study, a transfilter coculture system is described, in which the interface between haSMC and confluent or proliferative haEC can be studied in detail. Cells were cocultured on the opposite sides of a porous filter which separates both cell types like the internal elastic lamina in vivo. In cocultures containing proliferative haEC, haSMC growth was significantly stimulated (33.4 +/- 5.7 cells/section, p < 0.05) compared to haSMC monocultures (22.9 +/- 2.5 cells/section) and cocultures containing confluent haEC (15.6 +/- 2.9 cells/section). If confluent haEC were injured mechanically, haSMC growth increased highly significantly (71.3 +/- 16.8 cells/section, p < 0.001). Thus, cell-rich proliferates containing 5-7 layers of haSMC embedded in extracellular matrix were formed after 14 days. On the other hand, after haSMC migration to the endothelial side had occurred, the addition of LDL and monocytes to cocultures with arterial media explants and haEC resulted in the formation of lipid-rich, low-cellular structures. After 28 days, characteristic in vitro plaque growth was induced; the plaque contained a lipid core with predominantly necrotic cells, extracellular lipid accumulations, atypically shaped lipid-loaded haSMC and macrophages, similar to in vivo foam cells, as well as an increased amount of extracellular matrix (collagen I, III and IV). These areas were surrounded by typical fibromuscular caps consisting of smooth muscle alpha-actin-positive haSMC. Finally, the formation of capillaries by haEC could also be observed within these structures.

[Recurrent hematemesis and hemobilia in ruptured hepatic artery aneurysm--differential diagnostic aspects of acute, upper gastrointestinal hemorrhage]. / Rezidivierende Hämatemesis und Hämobilie bei perforiertem Leberarterien-aneurysma--ein differentialdiagnostischer Aspekt der akuten, oberen GIB.

Aneurysms of the hepatic artery are mostly localized extra hepatic (80%). Today atherosclerosis is the most prevalent etiology (32%), followed by trauma (22%) and inflammatory lesions (10%). Rupture or perforation of the aneurysm is the initial clinical manifestation (60-80%), and occurs with nearly equal frequency into the peritoneal cavity and into the hepatobiliary tract. Rupture into bile ducts is often responsible for characteristic findings of upper gastrointestinal bleedings with hematemesis. The case of a 38 year-old man is presented and the clinical manifestation, the diagnostic and therapeutic procedures are demonstrated.

[Does piggy-back liver transplantation have a detrimental effect on venous drainage?--A comparative duplex ultrasound study]. / Hat die Piggy-back Lebertransplantation einen nachteiligen Einfluss auf den venösen Abfluss?--Eine duplexsonographische Vergleichsstudie.

Venous drainage in "Piggy-back" Liver Transplantation "Piggy-back" orthotopic liver transplant (OLT) may offer some advantages (hemodynamic stability without veno-venous bypass) over standard OLT, but there is concern about the risk of venous outflow obstruction associated with this technique. In this study (n = 19 piggy-back, n = 12 standard OLT) it was possible to show, by means of duplex scanning, that flow velocity, resistance and flow of hepatic veins do not differ significantly.

[Ulcus cruris venosum: surgical debridement, antibiotic therapy and stimulation with thrombocytic growth factors]. / Ulcus Cruris Venosum: Chirurgisches Debridement, antibiotische Therapie und Stimulation mit thrombozytären Wachstumsfaktoren.

Despite the availability of various topical agents and of new technics for surgical correction, venous stasis ulcers are still characterized by high recurrent rates. Experimental data from wound healing studies demonstrate stimulation of wound healing after topical application of various growth factors (TGF beta, PDGF, EGF). The results of clinical studies suggest that topical use of an autologous platelet releasate (PDWHF) containing various growth factors accelerates healing. In this prospective study the stimulating effect of autologous PDWHF on epithelialization of small ulcers (group A, < 5000 mm2) and granulation of large ulcers before mesh grafting (> 5000 mm2) will be demonstrated. Inclusion criteria were the venous aetiology of the ulcer and the failure of conventional therapy for 6 month. Exclusion criteria were arterial occlusive disease, diabetes mellitus, acute wound infection, thrombocytopenia and pregnancy. There were 24 patients with 36 ulcers, caused by postthrombotic syndrome in one-third of cases and in two-thirds by severe insufficiency of the perforating veins. The ulcer had been present for more than in 10 years in 38% of cases, while there were 6 circumferential ulcers. The overall ulcer healing rate was 77% after a mean of 14 weeks. In group A 78% of the patients were healed after a mean of 16 weeks. In group B the mesh graft procedure was successful in 90% of the patients after a mean of 13 weeks. Compared with other conventional therapy studies, we achieved a higher healing rate. PDWHF seems to create ideal granulation tissue for mesh graft, indicated by a high uptake of the skin grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

[Standardized combined pancreas and liver explantation]. / Standardisierung der kombinierten Pankreas- und Leberexplantation.

Maximum use of organs from a single donor is mandatory as a result of the current organ shortage. In combined liver and pancreas allograft retrieval, it is vital that one remember the variability in the anatomy of vessels. Based on our experience, we describe a new technique of dividing the celiac trunk horizontally with subsequent arterial reconstruction, depending on the anatomical situation. Vascular division of the grafts can be performed either in situ or in an ex situ fashion in cases where cardiovascular function has deteriorated.