[Preoperative chemoradiation in esophageal cancer: experience of a single center in 102 patients]. / Präoperative Radio-Chemotherapie beim Osophaguskarzinom: Erfahrungen eines Zentrums mit 102 Patienten.

The (dis-)advantages of preoperative chemoradiation in patients with esophageal cancer (EC) are still controversial as data are lacking showing a clear cut benefit. Therefore, data of neoadjuvant therapy of our hospital have been analyzed. Since 1994 102 patients with an EC (33 % adenocarcinoma, 67 % squamous cell cancer, scc) were operated after receiving preoperative chemoradiation (36 Gy radiation, 1.8 Gy/day for 4 weeks, 500 mg/m (2) 5-FU for 4 weeks and 20 mg/m (2) Cisplatin, day 1-5, week 1 and 4). Operation was performed usually 8-10 weeks after treatment start. In 11.7 % of patients with an adenocarcinoma a complete pathological response (CR, pT0N0M0) was observed and a pT0 stage in 20.6 %. 38.2 % of these patients were staged as pN0. Postoperative morbidity was observed in 66 % (anastomotic leakage in 20 %, recurrent nerve palsy in 23 %). In-hospital mortality was 5.9 %. 5-year survival was calculated as 30.5 %, in patients wit a CR 66 %.26.5 % of patients with a scc revealed a CR. However no effect at all was observed in 32 % of these patients. 56 % were staged as pN0. Postoperative morbidity was observed in 87 % (anastomotic leakage in 16 %, recurrent nerve palsy in 32 %). In-hospital mortality was 11.8 %. 5-year survival was calculated as 19.2 %, in patients with a CR 45 %. The impact of pN stage was significant (p = 0.0052). These results underline the benefit of neoadjuvant therapy in patients with a CR. Further on, a pN0 stage is an important prognostic indicator. However, it remains open, whether neoadjuvant therapy leads to a downstaging of lymph node involvement, as histological confirmation in clinically positive lymph node is seldom performed prospectively.

[Therapy of the pilonidal sinus--Primary wound closure or open wound after excision]. / Die Therapie des Sinus pilonidalis - Primärer Wundverschluss versus offene Wundbehandlung nach Exzision.

The postoperative follow up of 177 operations in 162 patients with pilonidal sinus was investigated. After excision of the sinus a primary wound closure was performed in 80 cases; in 83 cases the wound was left open. After primary wound closure 40 % of the patients showed a primary healing of the wound. Although the remaining 60 % of the wounds healed secondarily the patients were not disabled longer and did not demonstrate more frequently recurrences than those with open wound management. As a consequence we recommend a primary wound closure after excision of a pilonidal sinus.

Predictive factors for response to neoadjuvant therapy in patients with oesophageal cancer.

BACKGROUND: Preoperative radio-chemotherapy (RCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of RCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) in samples of EC obtained by endoscopy prior to the start of the treatment. METHODS: Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, RCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables. RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patients. Eight of 56 patients who received RCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P=0.0026). None of the investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P=0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10.7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS: According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:6 or less prior to RCX will respond to this therapy.

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.

Colchicine inhibits taurodeoxycholate transport in pericentral but not in periportal hepatocytes.

Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.

[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.

Immunological surrogate parameters in a prognostic model for multi-organ failure and death.

OBJECTIVE: To assess the ability of clinical or biochemical parameters to predict outcome (survival or non-survival; severe or moderate/no complication) using multiple regression analyses. DESIGN: Prospective, descriptive cohort study with no interventions SETTING: 12 surgical intensive care units of university hospitals and large community hospitals; four medical school research laboratories in eight European countries PATIENTS: 128 surgical patients with major intra-abdominal surgery admitted for at least two days to an intensive care unit MAIN OUTCOME MEASURES: Prediction of complications or survival based on analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure Score, Acute Physiology and Chronic Health Evaluation II scores) and immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6, IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters, with comparison of predicted and actual outcomes. RESULTS: APACHE II, MODS score, MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly different between survivors and non-survivors and patients with/without severe complications by univariate analysis. By multivariate analysis only MOF, MODS score, IL-6, platelets, comorbidity predicted complications with a sensitivity of 82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE II score, plasma IL-8 and complications predicted death (sensitivity 84%; specificity 90%). CONCLUSION: Immunological surrogate parameters may predict complications and death of surgical ICU patients. The use of several parameters may add to increase sensitivity and specificity in a prognostic model.

Coverage of enterococci in community acquired secondary peritonitis: results of a randomized trial.

INTRODUCTION: The increasing number of enterococcal infections in hospitals and reports about the development of resistance of these bacteria make it necessary to review their importance as co-pathogens in secondary peritonitis. MATERIALS AND METHODS: A prospective randomized controlled trial on primary therapy of secondary peritonitis was carried out in six centers comparing cephalosporin-based antibiotic therapy to acylaminopenicillin-based therapy. RESULTS: Enterococci were only cultured in 6 of 110 cases from the abdomen and were found in only 5 cases of postoperative complications. No differences were found between penicillin-based vs. cephalosporin-based therapy. CONCLUSION: The study supports the view that these bacteria continue to play a minor role in secondary peritonitis. The point has to be emphasized, however, that the patients under study were in relatively good condition (APACHE II median 9 for cephalosporins and 10 for penicillins) and that postoperative cases of peritonitis were excluded.

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.

Ampullary hamartoma: A rare cause of biliary obstruction.

Tumors of the papilla of Vater are very rare. Despite advanced imaging techniques the distinction between benign and malignant tumors remains very difficult. Because most ampullary and periampullary tumors are malignant, primary management is surgical. Here we report the case of a 65-year-old man with biliary obstruction caused by an ampullary hamartoma simulating cancer. The correct diagnosis was not established until surgery.

Epidemiology and pathophysiology of intraabdominal infections (IAI).

Intraabdominal infection continues to be one of the major challenges in general surgery. Whilst the term "peritonitis" means an inflammation of the peritoneum regardless of its etiology, intraabdominal infections encompass all forms of bacterial peritonitis, of intraabdominal abscesses and of infections of intraabdominal organs. Several classification systems have been suggested for peritonitis and intraabdominal infections, respectively. However, neither phenomenological classifications nor classification systems with respect to the origin of bacterial contamination have a proven relevance for the clinical course of this disease. Moreover, most of the studies dealing with secondary peritonitis or intraabdominal infections are ill-comparable because of wide variations of inclusion criteria. Thus the true incidence of secondary bacterial peritonitis is difficult to assess. With respect to its etiology perforation of hollow viscus is the leading cause followed by postoperative peritonitis, ischemic damage of bowel wall, infection of intraabdominal organs and translocation in nonbacterial peritonitis. The anatomic origin of bacterial contamination and microbiological findings are no major predictors of outcome. However, the preoperative physiological derangement, the surgical clearance of the infectious focus and the response to treatment are established prognostic factors. The pathogenesis of intraabdominal infections is determined by bacterial factors which influence the transition from contamination to infection. Intraabdominal adjuvants and the local host response are additionally important. Bacterial stimuli lead to an almost uniform activation response which is triggered by reaction of mesothelial cells and interspersed peritoneal macrophages and which also involves plasmatic systems, endothelial cells and extra- and intravascular leukocytes. The local consequences of this activation are the transmigration of granulocytes from peritoneal capillaries to the mesothelial surface and a dilatation of peritoneal blood vessels resulting in enhanced permeability, peritoneal edema and lastly the formation of protein-rich peritoneal exudate.

Near-field luminescence measurements on GaInAsP/InP double heterostructures at room temperature.

Spatially resolved near-field luminescence spectroscopy was carried out on locally grown InP ridges, overgrown by a GaInAsP layer in metal organic molecular beam epitaxy. For free access to the quaternary layer the cleaved surface was investigated. Two different reflection scanning near-field microscopy setups were used. In the illumination mode we were able to estimate the charge-carrier diffusion in the InP. For improving the spatial resolution, measurements were also carried out in the collection mode. Here a shift of the center wavelength toward lower energy occurs near the side facets. This can be a result of a material composition gradient or of strained growth near the side facets. A second recombination channel at 1115 nm occurs at the growth-nongrowth transition. With the simultaneous recorded topography this recombination channel can be localized in the quaternary layer grown on the side of the InP ridge.

The in vitro synergistic inhibitory effect of human amniotic fluid and gentamicin on growth of Escherichia coli.

The activity of serum and its synergistic effect with many antibiotics against bacteria are well known. Few reports are available on similar phenomena produced by human amniotic fluid (HAF). Thus we investigated the antibacterial activity of HAF and the presence of a synergistic effect with gentamicin (GM) against Escherichia coli strains. Antimicrobial activity was evaluated as a delay of the growth curve, using a turbidimetric method. E. coli ATCC 10798 and E. coli SC 12155 were employed as test micro-organisms in nutrient broth, and GM was used at a subinhibitory concentration. HAF exerted antibacterial activity and, cooperating with GM at subinhibitory concentration, enhanced its antibiotic activity against E. coli. The presence of Schlievert's glycoprotein in HAF could explain these results.

Effects of peritonitis exudates on chemotaxis and phagocytosis of human neutrophils.

OBJECTIVE: To elucidate the in vitro effects of peritoneal exudate in patients with peritonitis on the functions of normal neutrophils (chemotaxis and phagocytosis) and to correlate these findings with constituents of the exudate, severity of disease, and clinical course. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Fifty consecutive patients with secondary peritonitis and healthy volunteers. INTERVENTIONS: Samples of peritoneal exudate were taken during operation and tested for their ability to stimulate or inhibit chemotaxis and phagocytosis of polymorphonuclear neutrophils (PMN). MAIN OUTCOME MEASURES: Correlation between chemotaxis and phagocytosis and concentrations of constituents of peritoneal exudate. RESULTS: Mean (SD) exudate-induced chemotaxis was 102.5 (22.8) microns compared with 62.3 (4) in the buffer control and 116 (17) in the 1 ng/ml C5a buffer control. The mean (SD) phagocytic index (uptake of zymosan and Candida albicans) was 68.8 (28.1) % of the respective serum control. There were correlations between chemotaxis and concentrations of C3a, endotoxin, and white cell count in the exudates; between phagocytosis and concentrations of C3a, IgG, IgM, protein and granulocyte elastase activity (GE and GE-alpha 1 proteinase inhibitor complex) in the peritoneal exudate; concentrations of endotoxin, and tumour necrosis factor alpha (TNF alpha), and granulocyte elastase activity in the exudate; and concentrations of C3a, IgG, IgM, and fibrinopeptide A in the exudate. There were no differences in chemotaxis and phagocytosis between patients who survived and those who died, and only the APACHE II score, the Sepsis Severity Score and the Mannheim Peritonitis Index correlated with mortality. CONCLUSION: It is still not clear whether other constituents of the exudate, variable conditions of resorption, inflammatory conditions within the peritoneal lining, or the individual patient's capacity to limit the systemic response, may have a critical role.

[Enema-induced hyperphosphatemia in ileus of the small and large intestine]. / Klysma-induzierte Hyperphosphatämie bei Dünn- und Dickdarmileus.

We report a case of severe hyperphosphatemia following repeated use of phosphate-containing enemas in a patient with small and large bowel ileus, who died from acute renal and cardiovascular failure. Refractory hypocalcemia presumably resulted from precipitation of calcium-phosphate. Hypocalcemia may induce alterations which seriously compromise the clinical course.

Indications for surgical treatment of acute pancreatitis.

The clinical spectrum of acute pancreatitis ranges from mild, self-limiting symptoms to fulminant illness that may rapidly lead to multiple organ failure and death. Differentiation between acute interstitial pancreatitis, necrotizing pancreatitis, pancreatic abscess and acute pseudocyst is mandatory for the choice of surgical treatment. If morphological evaluation by dynamic pancreatography reveals pancreatic or peripancreatic necrosis, bacteriological evaluation by CT-guided fine-needle aspiration is the mainstay of further decision-making, and should be performed if general signs of inflammation are not improved by conservative therapy. Basically, operative treatment may be directed against underlying pathology (e.g. cholelithiasis), or may aim to manage complications. Infected necrosis is the only clear indication for surgery. Whether the choice should be debridement and gravity drainage, continuous closed lavage of the lesser sac, staged relaparotomies, or open packing, depends on the extent of the process and the individual situation. Peripancreatic fluid collections and pancreatic pseudocysts without major ductal pathology rarely need operative treatment in the early stages, whereas abscesses resulting from infected necrosis should be dealt with by surgery rather than by percutaneous drainage.

[Diagnosis and treatment strategy of intra-abdominal abscess]. / Diagnose und Behandlungsstrategie intraabdomineller Abszesse.

Intraabdominal abscesses are life-threatening complications of inflammatory processes or major surgery. Ultrasonography, computed tomography, magnetic resonance, and scintigraphy are the diagnostic methods of choice. The sole diagnosis intraabdominal abcess" is insufficient to recommend a specific therapeutic strategy. Therapy depends upon etiology and localization of the process and the individual situation of the patient. An individualizing strategy may include both operative and percutaneous drainage. 100 patients with intraabdominal abscesses were treated in our department from 1987 through 1991. Roughly one third was diagnosed intraoperatively whereas less than one half of the pretherapeutically diagnosed abscesses were treated by percutaneous drainage.

[The value of colon contrast enema in ileus diagnosis]. / Bedeutung des Kolonkontrasteinlaufs in der Ileusdiagnostik.

In 115 patients with clinical and radiological signs of small and/or large bowel obstruction the contrast enema of the colon was evaluated prospectively to localize the site of occlusion in the colon. Contrast enema was performed in 76 patients with Gastrografin and in 39 with barium. In 22 of 24 patients with large bowel obstruction, in 7 of 11 with combined small and large bowel obstruction, in 4 of 14 with small bowel obstruction and in 19 of 66 with partial obstruction the site of obstruction was identified in the colon. In 107 of 115 patients the site of intestinal obstruction in the colon was either confirmed or excluded (sensitivity 89.2%, specificity 96.6%). In 6 patients the contrast enema failed due to incontinence, missing cooperation or insufficient preparation. In two cases with coprostasis the occlusion was missinterpreted as a carcinoma. Electrolytes and serum fluid concentration before and after the enema were not significantly influenced using the different contrast media. Contrast enema is indicated in patients with intestinal obstruction of unknown site, malignancies, after radiation therapy and recurrent partial obstruction.