[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. Differential diagnosis with cystic echinococcosis (CE) caused by E. granulosus and AE is challenging. We aimed at improving diagnosis of AE on paraffin sections of infected human tissue by immunohistochemical testing of a specific antibody. METHODOLOGY/PRINCIPAL FINDINGS: We have analysed 96 paraffin archived specimens, including 6 cutting needle biopsies and 3 fine needle aspirates, from patients with suspected AE or CE with the monoclonal antibody (mAb) Em2G11 specific for the Em2 antigen of E. multilocularis metacestodes. In human tissue, staining with mAb Em2G11 is highly specific for E. multilocularis metacestodes while no staining is detected in CE lesions. In addition, the antibody detects small particles of E. multilocularis (spems) of less than 1 µm outside the main lesion in necrotic tissue, liver sinusoids and lymphatic tissue most probably caused by shedding of parasitic material. The conventional histological diagnosis based on haematoxylin and eosin and PAS stainings were in accordance with the immunohistological diagnosis using mAb Em2G11 in 90 of 96 samples. In 6 samples conventional subtype diagnosis of echinococcosis had to be adjusted when revised by immunohistology with mAb Em2G11. CONCLUSIONS/SIGNIFICANCE: Immunohistochemistry with the mAb Em2G11 is a new, highly specific and sensitive diagnostic tool for AE. The staining of small particles of E. multilocularis (spems) outside the main lesion including immunocompetent tissue, such as lymph nodes, suggests a systemic effect on the host.
[Show abstract][Hide abstract] ABSTRACT: The present review summarizes key papers on the elimination of endotoxin in human.
Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and are involved in the pathogenesis of sepsis and septic shock. Elimination of LPS is vital; therefore, therapeutic detoxification of LPS may offer new perspectives. Multiple mechanisms eliminate LPS in human comprising molecules that bind LPS and prevent it from signaling, enzymes that degrade and detoxify LPS, processes that inactivate LPS following uptake into the reticulo-endothelial system, and mechanisms of adaptation that modify target cells responding to LPS. These mechanisms are powerful and detoxification capacity adapts as required. Results of therapeutic interventions aiming at the removal of LPS by medication (immunoglobulins) or extracorporeal means are controversial. At least in part, animal experiments revealed increased survival. Human trials confirmed the positive effects on parameters of secondary importance, but not on morbidity or survival which was attributed to the heterogeneity of patients suffering from consequences of severe infectious diseases and sepsis.
The hypothesis of LPS-driven inflammatory processes remains very attractive. However, few therapeutic yet immature options have been developed to date.
Langenbeck s Archives of Surgery 08/2010; 395(6):597-605. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present review summarizes key studies on the effects of major abdominal surgery on the host response to infection published during the last 18 months.
Surgical trauma causes stereotyped systemic proinflammatory and compensatory anti-inflammatory reactions. It is leukocyte reprogramming rather than general immune suppression. The list of recent findings is long. Preoperative infectious challenge was found to increase survival. Obesity is associated with increased production of interleukin-17A in peritonitis. Abdominal surgery alters expression of toll-like receptors (TLRs). The acute phase reaction down-regulates the transcription factor carbohydrate response element binding protein. Myosin light chain kinase activation is a final pathway of acute tight junction regulation of gut barrier and zonula occludens 1 protein is an essential effector. The brain is involved in regulating the immune and gut system. Elimination of lipopolysaccharide is challenging. Th1/Th2 ratio is lowered in patients with postoperative complications. Cholinergic anti-inflammatory pathways can inhibit tissue damage. The new substance PXL01 prevents adhesions. Postoperative infection causes incisional hernias. Hypothermia reduced human leukocyte antigen DR surface expression and delayed tumor necrosis factor clearance. Systems biology identified interferon regulatory factor 3 as the negative regulator of TLR signaling. Protective immunity could contribute defeating surgical infections.
Systemic inflammation is the usual response to trauma. All organs seem to be involved and linked up in cybernetic systems aiming at reconstitution of homeostasis. Although knowledge is still fragmentary, it is already difficult to integrate known facts and new technologies are required for information processing. Defining criteria to develop therapeutic strategies requires much more insight into molecular mechanisms and cybernetics of organ systems.
Current Opinion in Infectious Diseases 04/2010; 23(3):259-67. · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alveolar echinococcosis (AE) is life-threatening and reports on surgical procedures and results are rare, but essential.
Longitudinal surveillance and long-term follow-up of patients surgically treated for AE during the periods 1982-1999 (group A) and 2000-2006 (group B).
University hospital within an endemic area.
The median (min-max) follow-up period was 141 (5-417) months. Forty-eight surgical procedures were performed in 36 patients with AE: 63% were partial resections of the liver (additional extrahepatic resection in ten of them), 17% just extrahepatic resections, 10% biliodigestive anastomosis, and 10% exploratory laparotomies. Seventy-five percent of the operations were first-time procedures, 25% done due to a relapse. Forty-two percent of the operations were estimated to be curative (R0), whereas 58% were palliative (R1, R2). All patients had additional medical treatment and periodical follow-up. Two out of 18 (11%) patients, estimated to have had curative surgery, developed a relapse 42 and 54 months later. R0-resection rates depended on the primary, neighboring, metastasis stage of AE (S1, 100%; S2, 100%; S3a, 33%; S3b, 27%; S4, 11%). During the period 2000-2006 elective radical surgery for AE was done only if a safe distance of at least 2 cm was attainable. This concept was associated with an increased R0-resection rate of 87% for group B compared to 24% for group A. Operative procedures done to control complicated courses of AE (jaundice, cholangitis, vascular compression, bacterial superinfection) have not been curative (R2) in 82% because the disease had spread into irresectable structures. Morbidity was 19%. All patients with curative resections are alive. Fifty-six percent of the patients with palliative treatment are alive as long as 14-237 months, 28% died from AE 164-338 months after diagnosis (late lethality), and 17% died due to others diseases 96-417 months after diagnosis of AE. One out of seven (14%) patients suffering from suppurative parasitic necrosis died because it was impossible to control systemic sepsis (3% hospital lethality).
Curative surgery for AE is feasible if the parasitic mass is removable entirely. The earlier the stage, the more frequent is R0 resectability. The observance of a minimal safe distance increases the rate of R0 resections. The benefit of palliative surgery is uncertain due to favorable long-term results of medical treatment alone. However, necrotic tissue is at risk of bacterial superinfection, which can cause life-threatening sepsis. Palliative surgery is an option to treat complications, which could not be managed otherwise.
Langenbeck s Archives of Surgery 07/2009; 394(4):689-98. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this paper is to prove lymph node infestation by Echinococcus multilocularis and provide evidence for systematic lymph node dissection in curative resections for alveolar echinococcosis (AE).
Human AE is a life threatening parasitic condition, usually caused by an intrahepatic infiltrative and destructive growth of the larvae E. multilocularis. WHO guidelines provide radical hepatic resection for curative treatment. However, the current norms do not consider dissection of regional lymph nodes. No report to date has visualized concurrent lymph node infestation.
Radical excision of infested liver including regional lymph nodes with subsequent histological examination was carried out in a patient suffering from AE. The literature was reviewed and a revised state-of-the-art treatment of AE deduced.
Upon inspection the liver displayed macroscopic features of AE, in contrast to the regional lymph nodes which appeared unsuspicious. Further histological analysis confirmed regional lymph node infestation of E. multilocularis.
This is the first publication on histological evidence of E. multilocularis in regional hepatic lymph nodes, and thus, demonstrating dissemination from the liver. Since AE can spread through lymphatic drainage, even without causing macroscopic conspicuity, resection should not be resumed to the liver tissue only, but rather to consider the routine removal of regional lymph nodes as well. Omission of lymph node dissection can leave behind parasitic tissue and surgical procedures erroneously judged as curative.
Langenbeck s Archives of Surgery 05/2009; 394(4):699-704. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 42-year-old morbidly obese patient (BMI 44.1 kg/m(2)) was admitted to our emergency room with upper abdominal pain, nausea, and cholestasis. Nine years ago, a vertical banded gastroplasty had been performed (former BMI 53.5 kg/m(2)) with a subsequent weight loss to BMI 33.0 kg/m(2). After regaining weight up to a BMI of 47.6 kg/m(2), 5 years ago a conversion to a gastric bypass was realized. A computed tomography of the abdomen showed an invagination of the remaining stomach into the duodenum causing obstruction of the orifice of common bile duct. The patient underwent an open desinvagination of the intussusception and resection of the remaining stomach. Gastroduodenal intussusception is rare and mostly secondary to gastric lipoma. To prevent this rare but serious complication, the remaining stomach could be fixed at the crura of the diaphragm, tagged to the anterior abdominal wall by temporary gastrostomy tube, or resected.
Obesity Surgery 04/2009; 19(5):664-6. · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The significance of endotoxemia in man is controversial, induces cytokine release and stimulates the immune system. Exaggerated cytokine release of mononuclear cells was observed in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, repetitive administration of endotoxin can cause tolerance.
To investigate endotoxemia, plasma TNFalpha, IL-1beta, IL-6, the liberation capacity of those cytokines from mononuclear cells after LPS challenge (Delta values), and plasma antibodies to endotoxins and alpha-hemolysin of Staphylococcus aureus in ALI/ARDS.
A prospective clinical study was conducted.
The study was carried out at the University Hospital Ulm, Ulm, Germany.
The respondents were 23 patients with ALI/ARDS.
ALI/ARDS was defined according to the American-European Consensus Conference on ARDS. Blood was collected periodically. Parameters were measured by LAL or ELISA.
ARDS (P(a)O(2)/F(i)O(2) < 200) revealed higher endotoxemia (0.22-0.46 [0.06-1.15] EU/mL vs 0.05-0.14 [0.02-0.63] EU/mL) than ALI (P(a)O(2)/F(i)O(2) > 200) but lower DeltaIL-6 (124-209 [10-1214] pg/mL vs 298-746 [5-1797] pg/mL), DeltaTNFalpha (50-100 [6-660] pg/mL vs 143-243 [12-2795] pg/mL), and DeltaIL-1 (2-3 [0-26] pg/mL vs 2-14 [0-99] pg/mL). Endotoxemia correlated negative with P(a)O(2)/F(i)O(2) (r, -0.44 to -0.50). All patients presented antibodies to lipopolysaccharides and alpha-hemolysin, but the level did not correlate with P(a)O(2)/F(i)O(2).
ALI/ARDS is associated with endotoxemia. The more severe the disease, the more intense is endotoxemia but the lower is the capacity of mononuclear cells to release cytokines (tolerance). Antibodies against Gram-positive and Gram-negative bacteria are detectable in the plasma but without relation to P(a)O(2)/F(i)O(2).
Langenbeck s Archives of Surgery 08/2008; 393(4):473-8. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The World Health Organization guidelines recommend radical hepatic resection for definite treatment of alveolar echinococcosis (AE), because it can cure the patient. However, parasitic masses are not entirely removable in about 70% of patients. Even so, palliative resections are carried out, although cure cannot be achieved. As conservative treatment has improved, the role of palliative surgical procedures has to be redefined.
Critical appraisal of published reports on palliative resections for AE and estimation of the level of evidence and grade of recommendation.
Prospective randomized trials comparing palliative resections, radical resections, and conservative treatment are lacking. Most papers analyzed case series retrospectively. The number of palliative operations is significant. In the past, palliative resections were recommended in order to enhance anthelminthic drug efficacy but advances in conservative and interventional treatment improved the prognosis of AE. Prolonged survival by systematic palliative resections is not evident. However, palliative surgery is an option to treat persistent bacterial infection, fistulas, and obstructing or compressing masses. The indication is based on individual considerations and decisions.
Curative surgery for AE is feasible if parasitic tissue is entirely removable. The benefit of palliative resections is uncertain because long-term results of conservative treatment are favorable. Palliative surgery is an option for complications not being manageable otherwise.
Langenbeck s Archives of Surgery 07/2008; 394(1):199-204. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vacuum-assisted closure (vacuum sealing) is a surgical procedure for the local treatment of severe soft-tissue damage. However, systemic consequences to the host are unknown. The aim of this study was to disclose the effects of vacuum sealing on the host’s immune response and to demonstrate the early time course of endotoxin, interleukin-6 (IL-6), C-reactive protein (CRP), haptoglobin, transferrin, orosomucoid, 6-keto-prostaglandin (6KPG), α1-antitrypsin and complement C3 and C4. A total of 35 patients with closed ankle fractures were randomized into two groups and operated on within 6 h after injury. After osteosynthesis, one group was treated by vacuum sealing (VS) and the other by immediate skin closure (IS). Blood was collected immediately after admission and regularly up to 96 h after surgery. Morbidity was checked during the first year after injury. Preoperative endotoxin plasma level was increased compared with that of voluntary individuals (0.06 ± 0.02 EU/ml versus 0.021 ± 0.001 EU/ml) and peaked in patients with immediate skin suture 0.5 h after the surgical procedure at 0.11 ± 0.03 EU/ml. However, in patients with vacuum sealing, this peak was absent (0.07 ± 0.02 EU/ml). Endotoxaemia decreased to almost normal values after 24 h. Plasma IL-6 peaked 12 h postoperatively, decreasing thereafter with no difference between the groups. The plasma level of 6KPG decreased immediately after the surgical procedure in vacuum-sealed patients (before operation, 415 pg/ml; 12 h later, 251 pg/ml), but increased first in patients with immediate skin suture. CRP peaked 48 h after injury (VS, 48 ± 6 mg/l; IS, 38 ± 7 mg/l) with no difference between the groups. Transferrin decreased postoperatively (pre-op: VS, 2.49 ± 0.14 g/l; IS, 2.85 ± 0.19 g/l; 24 h: VS, 2.16 ± 0.08 g/l and IS 2.33 ± 0.11 g/l), whereas haptoglobin (pre-op: VS, 2 ± 0.21 g/l; IS, 1.7 ± 0.18 g/l; 96 h: VS, 3.4 ± 0.25 g/l, IS, 3.2 ± 0.24 g/l) and orosomucoid (pre-op: VS, 0.85 ± 0.05 g/l, IS, 0.83 ± 0.07 g/l; 96 h: VS, 0.85 ± 0.05 g/l, IS 1.14 ± 0.08 g/l) increased until day 4 with no significant difference between VS and IS. There was no relevant intergroup difference for complement C3, C4, α1-antitrypsin and morbidity (VS/IS: wound infection, 1/1; metal loosening, 1/1; prolonged healing, 1/0; prolonged pain, 3/2; and motor disturbance, 1/1). Surgery for ankle fractures is associated with temporary endotoxaemia and substantial changes in acute-phase proteins. Vacuum-assisted closure has only limited and no negative systemic immune consequences after surgery for malleolar fractures, is safe and can be used to manage severe soft-tissue damage. However, if feasible, primary skin closure is preferable.
[Show abstract][Hide abstract] ABSTRACT: Surgery can cause endotoxemia, and endotoxin aggregates to Toll-like receptors and acts proinflammatory; repetitive endotoxin application can cause tolerance. The objective of the study is to characterize early inflammatory response and expression of TLR2/4 during major abdominal surgery.
A prospective controlled study of 20 patients with elective major abdominal surgery was performed. Blood samples were collected before and at a defined time after surgery. Endotoxemia, capability of plasma to inactivate endotoxin, cytokine release of LPS-stimulated mononuclear cells, quantitative TLR mRNA expression, and plasma concentrations of TNFalpha, IL-6, C-reactive protein (CRP), alpha(1)-acid glycoprotein, transferrin, and albumin were measured.
Surgery caused endotoxemia (p = 0.053), and the capability of plasma to inactivate endotoxin was reduced (p = 0.0002). Two hours postoperatively, the plasma concentrations of TNFalpha and IL-6 peaked significantly, but the liberation capacity of mononuclear cells for cytokines (TNFalpha, IL-1beta, IL-6) was significantly reduced. The concentration of CRP and alpha(1)-acid glycoprotein peaked 48 h postoperatively, but those of transferrin and albumin were significantly decreased (p < 0.001, respectively). Median mRNA expression of TLR2 and TLR4 of mononuclear cells was not altered, and there was no obvious trend over time.
Major abdominal surgery is associated with endotoxemia, reduced capability of plasma to inactivate endotoxin, cytokine kinetics resembling those of healthy man after experimentally given LPS, and substantial acute-phase reaction. The cytokine liberation of mononuclear cells suggests a state of postoperative endotoxin tolerance. Despite these substantial changes, trends in TLR2/4 expression are not obvious.
Langenbeck s Archives of Surgery 06/2008; 394(2):293-302. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 67-year-old woman with cystic echinococcosis (CE) is presented. She had complained of upper abdominal discomfort due to large hepatic cysts. These cysts showed no typical infrastructure characteristic for CE and she had never left the rural areas of southern Germany. Most remarkably, this area is highly endemic for alveolar echinococcosis, caused by Echinococcus multilocularis, but only sporadic cases of CE have been described. Due to the discrepancy between positive Echinococcus serology, atypical morphology and residency in an area non-endemic for Echinococcus granulosus, diagnostic puncture was performed with albendazole coverage. Puncture was complicated by anaphylaxis, from which the patient recovered without sequelae. The diagnosis of CE was highly likely due to the combination of positive serology with post puncture anaphylaxis, increasing antibody titers and eosinophilia. Retrospectively, the cysts had initially corresponded to the WHO stage CE 1. The patient was treated with albendazole for 15 weeks. Under treatment, the parasitic membrane detached from the cyst wall, revealing characteristic morphology for CE, now corresponding to the WHO stage CE 3. The patient remained asymptomatic during follow-up visits.
[Show abstract][Hide abstract] ABSTRACT: Choledochal cysts are rare congenital anomalies. Their diagnosis is difficult, particulary in adults.
This case report demonstrates the diagnostic and therapeutic pitfalls.
To prevent cost-intensive and potentially life-threating complications, a choledochal cyst must be considered in the differential diagnosis whenever the rather common diagnosis of a hepatic cyst is considered.
[Show abstract][Hide abstract] ABSTRACT: A broad spectrum of hepatobiliary disorders are found in patients with inflammatory bowel diseases. The aim of the present work was to study interactions between gut and liver in experimental rat models of colitis and small bowel inflammation.
Colitis was induced either by trinitrobenzene sulphonic acid or dextran sodium sulphate. Small-bowel inflammation was induced by indomethacin. Bile acid secretion, bile acid pool, and cholesterol 7-alpha hydroxylase were studied. Cholesterol 7-alpha hydroxylase protein expression was analysed in the microsomal liver fraction. As portal mediators released form the inflamed gut we measured lipopolysaccharide, tumour necrosis factor-alpha and interleukin-1beta in portal serum. The hepatic inflammatory response was evaluated by binding activity of nuclear factor-kappaB, activator protein-1 and alpha-2-macroglobulin.
Increased bile acid secretion, total bile acid content in gut and liver (bile acid pool size), and hepatic cholesterol 7-alpha hydroxylase protein and mRNA levels were found in the two colitis models associated with only a minor hepatic acute phase and cytokine response. In contrast, during indomethacin-induced small-bowel inflammation bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase decreased in parallel to a strong hepatic cytokine and acute phase response.
Colitis without portal cytokine release and acute phase reaction shows an induction of bile acid secretion, pool size, and cholesterol 7-alpha hydroxylase. In contrast, intestinal inflammation after indomethacin treatment is associated with an acute phase response and a repression of bile acid synthesis.
European Journal of Clinical Investigation 04/2007; 37(3):222-30. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microarray expression analysis was performed in patients with major surgical trauma to identify signaling pathways which may be indicative for complicated versus uneventful reconstitution post trauma. In addition to a generalized upregulation of nonspecific stress response genes in all patients, a remarkable number of differences in gene expression patterns were found in individual patients. Some of the differing genes were associated with uncomplicated convalescence such as upregulation of both the ERK5 pathway (MAPK7 [mitogen-activated protein kinase-7]) and transcription factors which stimulate hematopoiesis and tissue reconstitution (MEF2, BMP-2, TNFRSF11A [RANK], and RUNX-1). Chemokine genes active in stem cell recruitment from the bone marrow as well as dendritic cell and natural killer (NK) cell maturation (SCYA14 [HCC-1]), and activators of the lymphoid compartment (TNFRSF7 [CD27], CD3zeta and perforin [PRF1]) were increased. In contrast, all these transcripts were downregulated in complicated reconstitution and later development of septic shock. Moreover, p38 kinase (MAPK14), S100 molecules, and members of the lipoxygenase pathway were associated with a more eventful outcome. Microarray expression studies are a promising tool for screening and then selecting differentially regulated genes in favorable as compared to complicated reconstitution post trauma.
Annals of the New York Academy of Sciences 01/2007; 1090:429-44. · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood oozing after cholecystectomy is a rare but potentially life-threatening complication. Recently, 2 patients died from this cause. The deaths resulted in criminal proceedings and medical experts were called in. The objective of this report is to describe their findings and to elucidate preoperatively unknown risk factors of bleeding.
Medical records, autopsy, and histological examination of the liver, heart, pancreas, spleen, and kidney pertaining to 2 recent cases of laparoscopic cholecystectomy were examined. Current literature on this topic was reviewed.
Preoperative risks included renal insufficiency, diabetes mellitus, and cardiopathy. The histological examination, in particular of the gallbladder bed of the liver, disclosed siderosis, inflammation, and fatty degeneration. These factors supported and perpetuated blood oozing. Postoperative ultrasonography and a hemogram might have detected and prevented death.
Inflammatory alterations, siderosis, and fatty degeneration of the liver are risk factors of postoperative hemorrhage. Autopsy and histological examination can detect those factors. Adequate postsurgical observation is mandatory, especially for patients at risk.
JSLS: Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons 01/2007; 11(1):101-5. · 0.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to evaluate the degree of endotoxin tolerance, expressed by the reduced cytokine/releasing capacity of the whole blood, data from a group of patients with trauma, severe acute pancreatitis (SAP), and diffuse peritonitis were analyzed. In SAP endotoxin levels and the tumor necrosing factor (TNF-α)–releasing capacity of the whole blood under lipopolysaccharide (LPS) stimulation were of an intermediate degree between systemic inflammatory response syndrome and severe sepsis. A mathematical model of ordinary differential equations of LPS signaling based on endotoxin kinetics and endotoxin tolerance was constructed. The mathematical model was used to reproduce the TNF-α production in trauma, SAP and peritonitis patients. The results of these numerical simulations are very similar to the determinations in real patients and argue that endotoxin tolerance may be a component of the immune dysregulation that complicates the clinical evolution of the patient with SAP.
American Journal of Surgery - AMER J SURG. 01/2007; 194(4).
[Show abstract][Hide abstract] ABSTRACT: Irinotecan alone and in combination with 5-fluorouracil (5-FU) displays potent activity in advanced colorectal cancer. The aim of this study was to estimate the potential efficacy of irinotecan for hepatic arterial infusion (HAI) chemotherapy.
We investigated the anti-proliferative effects of irinotecan alone and in combination with 5-FU in HT29 and NMG64/84 colon and COLO-357, MIA PaCa-2 and PANC-1 pancreatic cancer cell lines and in fresh tumors from patients with primary colon cancer (n=2) and colorectal liver metastases (n=11) in vitro, using the MTT growth assay and the human tumor colony-forming assay (HTCA), mimicking conditions which are achievable during HAI.
Irinotecan displayed concentration- and time-dependent cytotoxic effects in all tested cell lines. Treatment of cell lines with irinotecan followed by 5-FU did not result in synergistic anti-proliferative effects. In the HTCA, the sensitivity of each cell line varied depending on the incubation times (30, 90, 180 and 1440 min). Independent of the individual sensitivity, the IC50 concentration and time products were lowest when incubating with irinotecan for 30 min for all cell lines. The IC50 of irinotecan in HT29, NMG64/84, COLO-357, MIA PaCa-2 and PANC-1 cells at 30 min were 200, 160, 100, 400 and 150 microg/ml, respectively, in the HTCA. All isolated tumor samples displayed concentration-dependent inhibition of colony formation after exposure to irinotecan for 30 min. The IC50 of irinotecan of 5 of the 11 liver metastases was <100 microg/ml.
Irinotecan seems to be suitable for HAI therapy phase II studies. Due to the observation that several liver metastases had IC50 values that may be clinically achievable by HAI, patients with such tumors may benefit in the future from HAI using irinotecan.
Anticancer research 01/2005; 25(2A):795-804. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cystic echinococcosis (CE) is a world-wide zoonosis but is relatively rare in Western industrial countries. Surgery is the treatment of choice. However, the technical procedure varies and evidence-based knowledge is fragmentary. Cystectomy and partial resection of the liver (pericystectomy, segmental resection, hemihepatectomy) are the procedures under debate.
We present a descriptive analysis of the patients suffering from CE (anamnesis, cyst location, procedures, morbidity, lethality, hospital stay, and long-term follow-up).
A retrospective analysis was made of the medical records and questionnaires of patients surgically treated within a period of 16 years at a German university hospital.
Sixty-four patients had 101 parasitic cysts which were treated by 67 operations. The average volume of the cysts was about 400 ml (range 10 - 2200 ml). Eighty-six cysts were located within the liver and 15 in extrahepatic sites. The parasitic lesions were removed by hemihepatectomy (n = 4), segmental liver resection (n = 9), pericystectomy (n = 24), cystectomy (n = 34), and cysto-jejunostomy (n = 1). During the first half of the observation period resective procedures were preferred (81 %) whereas during the second half cystectomy predominated (82 %). Lethality was 0 %. Postoperative morbidity after resective procedures and cystectomy was 47 % and 17 %, respectively. Relapses were not observed after cystectomy, but occurred in four cases following resective procedures (twice after hemihepatectomy, 4 and 7 years later, respectively; once after segmental liver resection and once following cysto-jejunostomy, both 2 years after the respective procedure). The more extensive the surgical procedure the longer was the hospital stay.
Cystectomy should be performed as the procedure of choice because it proved to be safe, simple, effective, and meets all criteria of the surgical treatment for hydatid disease, i. e., complete elimination of the parasite, no intra-operative spillage especially by the use of Aaron's cone, and saving healthy tissue. Pericystectomy should be used for peripheral liver cysts only partially surrounded by liver tissue.
Zeitschrift für Gastroenterologie 11/2004; 42(10):1101-8. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estimation of trauma severity currently relies on clinical diagnoses and scoring systems. However, the early estimation of the severity of chest trauma and overall soft tissue trauma (STT) remains insufficient. Traditional trauma scoring systems fail to reflect the individual trauma pattern and severity, neglecting the different outcomes after injuries in different body regions. Therefore, the aim of this prospective study was to detect laboratory markers that may reflect the pattern and extent of individual trauma in the very early phase after injury.
In 107 non-selected trauma patients, blood samples were collected almost immediately and then at short intervals after the trauma. In addition to the biochemical analysis of 20 different mediators viewed as potential trauma markers, the following data were correlated with the laboratory results: injury severity score (ISS), polytrauma score (PTS), Ulmer score HTAPE (trauma pattern specific: head (H), thorax (T), abdomen (A), pelvis (P), extremities (E); 0-3 degrees each), multiple organ failure score (MOF), overall, primary and secondary lethality.
ISS and the severity of head injury were clearly higher in non-survivors (n=17) than in survivors (n=90) (median ISS: 35 versus 18; median severity of head injury (H): 3 versus 1). Whereas head injury was correlated with early death (<or=3 days: r=0.45), late death (>3 days post-trauma) was influenced by thoracic trauma (r=0.15) as well as by soft tissue trauma (STT, r=0.12). Of all investigated mediators, interleukin-6 (IL-6) displayed the highest correlations (r=0.66, P<0.00001) with the extent of chest trauma, followed by correlations with PTS, STT, fracture trauma (FT) and ISS during the first hour after trauma. There was no correlation between IL-6 and head injury. The extent of STT was correlated best to IL-8 (r=0.75), IL-6 (r=0.54), and creatine kinase (CK, r=0.49) plasma concentrations.
In the very early stage after an accident the severity of chest trauma is strongly correlated with the plasma concentration of IL-6, and the extent of overall soft tissue trauma (STT) to plasma concentrations of IL-8, IL-6, and CK.
[Show abstract][Hide abstract] ABSTRACT: Cystic echinococcosis (CE) is a worldwide zoonosis caused by larval stages of the cestode Echinococcus granulosus. Surgery, chemotherapy, and interventional procedures are the therapeutic options. Surgery can cure the patient if the parasite is removed entirely. However, the technical procedures are inconsistent and comprise partial liver resection or opening of the parasitic cyst and removal of the parasite. Laparotomy is the most common approach. In selected cases laparoscopic methods are successful. Retrospective studies outweigh prospective ones by far. However, proper management gives favorable results.
We critically review the literature and present a brief summary of current surgical strategy and focus on issues relevant for surgeons: diagnosis, indication for medical treatment, indication for surgical treatment, surgical procedures, scolicidal agents, morbidity, mortality, recurrence, perioperative medication, standards.
All surgical procedures aim at the complete removal of the parasite. Liver resection and pericystectomy are procedures that resect the closed cysts with a fairly wide safety margin. A meta-analysis shows the best results regarding lethality (1.2%), morbidity (11.7%), and recurrence rates (2%) for resective operations. However, most surgeons consider these methods as too radical for a benign disease. Procedures that remove the parasite and keep the pericyst (=cystectomy) are easier to carry out than resective ones. The meta-analysis presented revealed a lethality of 2%, morbidity of 23%, and recurrence rate of 10.4% for these operations. Omentoplasty is the option of choice for the management of the remaining cyst cavity. Despite alternative procedures surgery is the treatment of choice. Supportive measures comprise the use of scolicidal agents and postoperative benzimidazole administration. However, a critical review of the literature disclosed a lack of scientific confirmation of established treatment modalities and procedures. The results of ultrasound imaging were classified and correlated to the developmental phases of CE.
Cystectomy and omentoplasty for CE should be the standard surgical procedure because it is safe, simple, and effective and meets all criteria of surgical treatment for hydatid disease: entire elimination of the parasite, no intraoperative spillage especially by using a cone, and saving healthy tissue. Pericystectomy should be used for peripherally located liver cysts that are surrounded by parenchyma only partially. Ultrasonic classification of the parasitic lesion should be used as a guideline for therapeutic measures.
Langenbeck s Archives of Surgery 10/2003; 388(4):218-30. · 1.89 Impact Factor