[Poorly differentiated neuroendocrine small-cell carcinoma of the gallbladder]. / Schlecht differenziertes neuroendokrines kleinzelliges Karzinom der Gallenblase.

BACKGROUND: Neuroendocrine tumours of the gastroenteropancreatic system (GEP-NETs) are rare, in particular those of the gallbladder. Due to the limited therapeutic options, surgical resection is favoured. CASE REPORT AND METHODS: Described below is the case of a 69-year-old male with a lymphogenically metastasising, poorly differentiated neuroendocrine carcinoma of the gallbladder who presented with unspecific abdominal pain. RESULTS AND CLINICAL COURSE: Following complete surgical resection of the tumour and the lymph node metastases he developed a recurrence 6  weeks post-operatively. The recurrence was treated with chemotherapy. Re-staging after three courses, however, showed further tumour progression. Prior to the start of a second-line treatment the patient died 13  weeks after surgery. CONCLUSIONS: This case demonstrates the complexity of this rare disease with diagnosis in advanced tumour stage and poor prognosis.

[Adenocarcinoma of small bowel. An underdiagnosed disease]. / Adenokarzinome des Dünndarms. Eine Krankheit, an die selten gedacht wird.

BACKGROUND: Small bowel adenocarcinoma is a rare disease. The diagnosis is often disguised by nonspecific and varied presenting symptoms. Adenocarcinoma of the small bowel is typically detected at a late stage and with a poor prognosis. PATIENTS AND METHODS: The records of 42 patients with small bowel adenocarcinomas diagnosed in 2 surgical clinics between 1995 and 2009 were reviewed for patient and tumor characteristics, treatment effects and survival. RESULTS: The tumor locations were the duodenum (50%), jejunum (38%) and ileum (12%). In comparison to patients seen before 2004 the observed frequency of emergency operations or palliative procedures as well as stage distribution did not change. The median overall survival was 19 months with a 5-year overall survival of 20%. For patients with resections, reduced performance status, higher stage and residual disease after resection predicted decreased overall survival in univariate analysis. Residual disease and pT category were predictive of survival in multivariate analysis. CONCLUSION: Complete resection provides the only means of a cure. In cases where curative resection cannot be performed the prognosis remains poor. Further study on the methods for early detection and effective adjuvant chemotherapy should be investigated, however, the available data are limited.

[Symptomatic non-parasitic liver cysts: early and long-term results of surgical management]. / Früh- und Spätergebnisse nach Operation von nicht parasitären gutartigen Leberzysten.

BACKGROUND: Symptomatic congenital cysts of the liver, whether solitary or multiple in appearance, can be treated by a laparoscopic approach. Here we present our single centre experience encompassing a rather large cohort of patients. PATIENTS AND METHODS: From our prospective surgical database, introduced for quality management and surveillance, we identified 34 consecutive patients who were operated on for congenital liver cysts between 1995 and 2004. Using a questionnaire, the patients were contacted to assess actual complaints, the recurrence of operated cysts or the frequency of newly developed cysts. During follow-up two patients had died of other diseases. Of the remaining 32 patients 30 answered the questionnaire (94 %). The median postoperative follow-up was 55 months (range: 8-121). RESULTS: There were 29 women and 5 men with solitary (n = 10) or multiple (n = 20) liver cysts and polycystic liver disease (n = 4), all complained of unspecific upper abdominal pain. Due to previous operations or coexisting diseases open laparotomy was performed in 7 patients and laparoscopic unroofing was performed in 27 patients. The conversion rate to open laparotomy was 7 % (n = 2). Solitary cysts were unroofed in 25 patients and multiple cysts in 8 patients. The resected cysts had a median diameter of 10.5 cm (solitary cysts: 7-19 cm, multiple cysts: 4-23 cm). The only postoperative complications were 3 cases of bilioma (8.9 %), which required open revision in one case. There were no cysts recurrences, but persisting upper gastrointestinal pain, backache or problems arising from the scars were reported by 9 patients (30 %). CONCLUSION: In cases of symptomatic congenital liver cysts laparoscopic unroofing should be considered the treatment of choice.

Ferric iron is genotoxic in non-transformed and preneoplastic human colon cells.

Iron could be a relevant risk factor for carcinogenesis since it catalyses the formation of reactive oxygen species (ROS), which damage DNA. We previously demonstrated genotoxic effects by ferric iron using the human colon cancer cell line HT29. Here we investigated ferric iron in primary non-transformed colon cells and in a preneoplastic colon adenoma cell line (LT97), which both are suitable models to study effects of carcinogens during early stages of cell transformation. Genetic damage was determined using the Comet assay. Comet FISH (fluorescence in situ hybridization) was used to assess specific effects on TP53. Fe-NTA (0-1000 microM, 30 min, 37 degrees C) significantly induced single strand breaks in primary colon cells (500 microM Fe-NTA: Tail intensity [TI] 22.6%+/-5.0% versus RPMI control: TI 10.6%+/-3.9%, p<0.01) and in LT97 cells (1000 microM Fe-NTA: TI 26.8%+/-7.3% versus RPMI control: TI 11.1%+/-3.7%, p<0.01). With the Comet FISH protocol lower concentrations of Fe-NTA significantly increased DNA damage already at 100 and 250 microM Fe-NTA in primary colon and LT97 adenoma cells, respectively. This damage was detected as an enhanced migration of TP53 signals into the comet tail in both cell types, which indicates a high susceptibility of this tumor relevant gene towards Fe-NTA. In conclusion, Fe-NTA acts genotoxic in non-transformed and in preneoplastic human colon cells, in which it also enhances migration of TP53 at relatively low concentrations. Translated to the in vivo situation these results suggest that iron overload putatively contributes to a genotoxic risk during early stages of colorectal carcinogenesis on account of its genotoxic potential in non-tumorigenic human colon cells.

Feasibility and accuracy of TRUS in the pre-treatment staging for rectal carcinoma in general practice.

AIMS: Transrectal ultrasonography (TRUS) is the diagnostic tool of choice for local staging of rectal carcinoma. The accuracy in determining of tumour infiltration depth has been reported to reach 95% (on average, 85%). The aim of the study was to analyse the diagnostic accuracy of the TRUS in the clinical routine. PATIENTS AND METHODS: From 01/01/2000 to 12/31/2003, all patients with rectal carcinoma were enrolled in a prospective multicenter observational study. In case of complete findings of pre-operative TRUS and post-operative histological investigation of the surgical specimen on the tumour infiltration depth, overall accuracy of TRUS was determined. RESULTS: Overall, 13,610 patients with rectal carcinoma were enrolled in the study. Five thousand and fifty-six subjects (37%) underwent TRUS. In 3,501 patients, TRUS finding (uT-stage) could be compared with the result of the definitive histologic investigation (pT-stage). The accuracy of TRUS in all T-stages was 65.8%. The highest sensitivity was achieved in the T3-stage (74.9%), while in T2, T1, and T4, it was 59.6, 59.0 and 31.1%, respectively. In discriminating tumour growth limited to the rectal wall vs that through the rectal wall into the neighboring tissue, TRUS-associated accuracy was 76.5%. There were no differences between various tumour locations above the anocutaneous line. CONCLUSIONS: Diagnostic accuracy of TRUS in determining depth of tumour infiltration within or through the rectum wall in the routinuous diagnostic of rectal carcinoma does not reach the excellent published study results. A considerable improvement of the qualitative outcome in using this specific diagnostic tool appears to be recommendable to utilize its advantages such as high accuracy, efficacy, and practicability in the diagnostic process and deriving consequences for a possible neoadjuvant treatment as well as optimal planning of the surgical approach.

Effect of inappropriate initial empiric antibiotic therapy on outcome of patients with community-acquired intra-abdominal infections requiring surgery.

To assess the significance of initial empiric parenteral antibiotic therapy in patients requiring surgery for community-acquired secondary peritonitis, 425 patients hospitalized between January 1999 and September 2001 in 20 clinics across Germany were followed for a total of 6,521 patient days. Perforated appendix (38%), colon (27%), or gastroduodenum (22%) were the most common sites of infection. Escherichia coli was the most common pathogen. A total of 54 (13%) patients received inappropriate initial parenteral therapy not covering all bacteria isolated, or not covering both aerobes and anaerobes in the absence of culture results. Clinical success, predefined as the infection resolving with initial or step-down therapy after primary surgery, was achieved in 322 patients (75.7%; 95% confidence interval (CI), 70.6-81.2). Patients were more likely to have clinical success if initial antibiotic therapy was appropriate (78.6%; 95% CI, 73.6-83.9) rather than inappropriate (53.4%; 95% CI, 41.1-69.3). Patients having clinical success were estimated to stay 13.9 days in hospital (95% CI, 13.1-14.7), while those who had clinical failure stayed 19.8 days (95% CI, 17.3-22.3). In conclusion, appropriateness of initial parenteral antibiotic therapy was a predictor of clinical success, which in turn was associated with length of stay.

Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples.

This study describes a novel in vitro method in genetic toxicology that is based on detection of chemical-induced DNA damage connected with altered migration of TP53 in primary human colonocytes. Techniques were developed to isolate high numbers of human epithelial colon cells from surgical tissues. High quantities of viable cells were obtained per donor. The primary cells were treated with the endogenous risk factors trans-2-hexenal, and hydrogen peroxide. Global DNA damage and repair were measured by single-cell gel electrophoresis (Comet assay). We compared responses of primary colon cells to HT29clone19A, a differentiated human colon tumour cell line, for which the karyotype was analysed with 24-colour FISH. Both compounds were genotoxic in both cell types and most of the induced DNA damage was repaired after 30 min. Specific migration of TP53 was determined by fluorescence in situ hybridization (Comet FISH). Using primary colon cells, we quantified the migration of TP53 signals into the comet tails. In these cells TP53 was more sensitive than global DNA for genotoxicity induced by trans-2-hexenal and H(2)O(2). HT29clone19A cells cannot be used for Comet FISH because of their aberrant karyotype. The approach described allows us to obtain more knowledge of putative risk factors in colon carcinogenesis.

Secondary peritonitis: severity of disease and activation of peritoneal cells.

OBJECTIVE: To compare the degree of the inflammatory response of human peritoneum with the severity of peritonitis. DESIGN: Clinical laboratory study. SETTING: University hospital, Germany. SUBJECTS: 15 patients with diffuse secondary peritonitis and 5 having conventional cholecystectomy (controls) had peritoneal specimens taken from the site of incision. MAIN OUTCOME MEASURES: Correlation between presence of indicators of the inflammatory response: interleukin 1 (IL-1), interleukin 6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), antibacterial protein (defensin 3 reflecting the activation of granulocytes), the antibody clone HAM 56 (for detection of local macrophages), and antibodies against macrophage migration inhibiting factor (MIF)-related proteins 8 and 14 (MRP 8 and 14), and clinical state evaluated by the Mannheim Peritonitis Index (MPI), the Peritonitis Index Altona II (PIA II) and the Acute Physiology Score (APS). C-reactive protein (CRP) concentrations were measured preoperatively in the serum. RESULTS: Expression of MRP 8 and 14, HAM 56, and defensin 3 was significantly higher in patients with peritonitis than in controls (p < 0.05). Expression of IL-1 and IL-6 was almost undetectable. ICAM-1 expression correlated significantly with phagocytic activation. There was no correlation between clinical scores, CRP, and immunohistochemically detectable variables. CONCLUSION: The pattern of peritoneal inflammatory reactions is relatively uniform and does not correlate with the clinical grading of severity.

[Harmless or life threatening? Properly assessing soft tissue infections]. / Harmlos oder lebensgefährlich? So schätzen Sie Weichteilinfektionen richtig ein.

Soft tissue infections are highly diverse in presentation, and their severity is readily underestimated. Classifications in the literature are not uniform. Clinically, a recommended classification is based on the spread of the infection into deeper regions: superficial and deep soft tissue infections. Superficial infections, that is, those confined to the cutis and subcutis, include furuncles, erysipelas and phlegmons (acute suppurative inflammation). The second group--infection affecting fascia and muscle--include both classical gas gangrene and necrotizing fasciitis which, despite aggressive treatment, are associated with a high mortality rate. The present review shows the classification and differential diagnosis of these infections.

In vitro peritonitis: basic inflammatory reactions in a two-chamber coculture model of human peritoneum.

We developed an in vitro model of the peritoneum by coculturing human umbilical vein endothelial cells (HUVEC) and human peritoneal mesothelial cells (HPMC) to gather information on peritoneal physiology and to closer reflect the in vivo situation in humans. HUVEC and HPMC were seeded on collagen-coated polytetraflourethylene-insert membranes of pore size 3 microm. HUVEC were grown on the bottom of the membrane and HMPC on the top. The confluent cells were monitored by measuring transepithelial resistance and by confocal microscopy. The transmigration of PMNs as an important mechanism during secondary peritonitis was studied in this two-chamber model. PMNs were isolated by density separation. After stimulation of HMPC with the complement factor 5 split product C5a (1 ng/ml) or tumor necrosis factor-alpha (TNF-alpha; 10 or 50 microg/ml) for 1 h, 1 x 10(6) PMN were given to the lower compartment. Controls were cocultured cells without stimulation. After 1, 2, and 6 h nonadherent PMNs in the upper compartment were harvested and counted, interleukin-8 was measured in each compartment, and cells on the membrane were paraffin-embedded for immunohistochemistry. Each experiment was performed four times. Cells grew to confluence within 2-5 days and were detected on their respective seeding side by CD34 and cytokeratin 18 counterstaining. Transmigration of PMNs after C5a or TNF-alpha stimulation showed a significant time-dependent increase between 1 h and 6 h (P<0.05). PMNs were found in significantly higher numbers after stimulation with either C5a or TNF-alpha at 1, 2, and 6 h than without stimulation. After stimulation of HPMC, interleukin-8 secretion to the apical compartment increased in a time-dependent fashion, resulting in a gradient between the two chambers. Linear regression analysis revealed significant correlation between transmigrated PMN and interleukin-8 in stimulated cocultures; no correlation was found in controls. This new in vitro peritoneum consisting of cocultured mesothelial and endothelial cells may allow more detailed assessment of peritoneal pathophysiology. Generation of an interleukin-8 gradient affecting the migration of PNMs across the cocultured membrane represents a parameter which may be addressed in further studies.

Local inflammatory peritoneal response to operative trauma: studies on cell activity, cytokine expression, and adhesion molecules.

OBJECTIVE: To test the hypothesis that different surgical procedures may lead to different degrees of activation of the human peritoneal response. DESIGN: Clinical laboratory study. SETTING: University Hospital, Germany. MATERIAL: Peritoneal specimens taken from the incision or parietal resection margins at the beginning and end of laparoscopic or open cholecystectomy, or other conventional open operations (n = 5 in each group). MAIN OUTCOME MEASURES: Detection of indicators of the inflammatory response: interleukin 1 (IL-1), interleukin 6 (IL-6), intercellular adhesion molecule- (ICAM-1), antibacterial protein (defensin 3 that reflects the activation of granulocytes), the antibody clone HAM 56 (for detection of local macrophages), and antibodies against macrophage inhibiting factor (MIF)-related proteins 8 and 14 (MRP 8 and 14). RESULTS: The rise between preoperative and postoperative evaluations was significant for each variable (p < 0.05). With one single exception (IL-6 between laparoscopic cholecystectomy and other operations), the one way analysis of variance (ANOVA) showed no significant differences among the three groups in the detectable increases in staining. Linear regression analysis showed no correlation between length of operation and increases in immunohistochemically detected inflammatory variables. CONCLUSION: Minimally invasive surgery does not necessarily mean minimal peritoneal damage. The immunohistochemical evaluation of the local cellular response may provide additional objective criteria for the grading of operative trauma.

Identification of a differential expression of two cDNAs between malignant mesothelioma and normal mesothelial cells using the RNA fingerprint method.

The RNA fingerprint method was used to identify mRNAs that were differentially expressed during the development of human mesothelial cell cancer. We report the isolation of two differentially expressed clones. One clone was expressed in the metastatic mesothelioma cell line M1A and in the malignant mesothelioma cell line M1 and downregulated in normal mesothelial cells. M1 and M1A were derived from a primary and metastatic tumor of the same patient. The other clone was only expressed in normal mesothelial cells. The different expression pattern was confirmed by Northern blot analysis. One clone had a striking sequence homology to the soares pregnant uterus NbHPU homo sapiens cDNA clone. The other clone contained a high sequence homology to the human mRNA for ORF. The biological function of the corresponding genes is unknown. The specificity of expression of the two sequence tags was further examined on different cancer cell lines and normal tissues.

Early thoracoscopic debridement and drainage as definite treatment for pleural empyema.

OBJECTIVE: To report our experience with early thoracoscopic debridement and drainage in the treatment of pleural empyema in the fibrinopurulent or early organising phase. DESIGN: Prospective open study. SETTING: District hospital, Germany. SUBJECTS: 10 Patients operated on between August 1991 and April 1993. INTERVENTIONS: Double lumen intubation, followed by thoracoscopic opening of the empyema, evacuation of all pus under vision, debridement of the lung, irrigation of the thoracic cavity and insertion of a chest drain. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Cultures taken during the operation grew no pathogens in five cases; Streptococcus pneumoniae, and haemolytic streptococci (once in combination with Staphylococcus aureus), were cultured in two cases each; and Mycobacterium tuberculosis in one. Chest drains were removed a mean of 8.5 days after operation. All patients were well without signs of infection 1-21 months later, and in no case was conversion to open operation necessary. CONCLUSION: Early thoracoscopic debridement and drainage is a safe and effective alternative to open treatment of patients with pleural empyema in the fibrinopurulent or early organising phase.