Oral feeding in necrotizing pancreatitis.

BACKGROUND: Restoration of gastrointestinal function is a crucial determinant of favorable outcome in severe acute pancreatitis (SAP). The purpose of this study was to retrospectively review our experience with early oral feeding in patients with the necrotizing form of SAP. Over the last 10 years, we have routinely gradually increased oral feeds in order to restore gastrointestinal function. METHODS: Early low volume oral (ELVO) feeds containing 248-330 kcal/daily were routinely provided for all patients to help stimulate gastrointestinal function. Patients who received ELVO feeding within 72 hours of admission were allocated to Group I; those who received ELVO feeds after 72 hours were allocated to Group II. The volume and calories of the feed, magnitude of systemic inflammation, levels of C-reactive protein (CRP) and lipase, incidence of organ dysfunction, main outcomes, and complications were analyzed. RESULTS: In total, 129 patients received ELVO feedings. The mean CRP level on day 7 was 160 +/- 77.6 mg/l in Group I compared to 200.2 +/- 103.2 mg/l in Group II, p = 0.043. Normalization of CRP below 100 mg/l was observed on day 14 in both groups. The rate of infection and the need for surgical intervention (46.8% vs. 26%) were significantly higher in Group II (p = 0.026). Group II also had longer ICU/hospital stays (p = 0.039/p = 0.002). Overall mortality was 10%. CONCLUSIONS: ELVO feeding provides physiologic stimulation and promotes recovery of bowel function, preparing the gastrointestinal tract for low-fat hospital food in patients with necrotizing SAP. The majority of patients required no additional nutritional support.

Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut in patients with severe acute pancreatitis: a prospective feasibility study.

BACKGROUND: Experience with administration of synbiotics (prebiotics/probiotics) in patients with severe acute pancreatitis (SAP) has demonstrated immunomodulatory capacity. The aim of this trial was evaluation of the feasibility and perspective of early clinical application of oral synbiotic/prebiotic supplements in patients with SAP. METHODS: 90 SAP patients were enrolled during the period from 2005-2008. Patients were stratified according to the feeding mode. CONTROL (n = 32) group received standard whole protein feeding formula. SYNBIO (n = 30) and FIBRE groups (n = 28) received early (within first 24-48 hours) synbiotic or prebiotic supplements. Oral administration of synbiotics or prebiotics was commenced when patients were able to sip water. RESULTS: Daily provided average volume and calories of synbiotic/prebiotic blends were smaller compared to the CONTROL, p = 0.001. Oral administration of synbiotic/prebiotic supplements was associated with lower infection rate (pancreatic and peripancreatic necrosis) compared to the CONTROL, (p = 0.03; p = 0.001), lower rate of surgical interventions, p = 0.005, shorter ICU (p = 0.05) and hospital stay (p = 0.03). Synbiotic supplemented enteral stimulation of the gut resulted in reduced mortality rate compared to the CONTROL, p = 0.02. CONCLUSION: Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut seems to be a potentially valuable complement to the routine treatment protocol of SAP.

Conservative approach in the management of severe acute pancreatitis: eight-year experience in a single institution.

INTRODUCTION: Recognition of severe acute pancreatitis (SAP), intensive care, shifting away from early surgical treatment, and monitoring of the intra-abdominal pressure (IAP) is important in the management of SAP. The aim of our study was retrospective evaluation and critical assessment of the experience with SAP management protocol involving new strategy in the university hospital. METHODS: Protocols of 274 SAP patients treated in our institution during the last eight years were reassessed. APACHE II, CRP and SOFA score, IAP, pulmonary complications, ventilatory support and infection rate were evaluated. The success of the conservative treatment, surgical interventions and mortality was analysed comparing period 1 from 1999 to 2002 and period 2 from 2003 to 2006. RESULTS: More patients with necrotising SAP were treated in period 2. The average CRP and SOFA score was higher in period 2, p=0.018; p=0.011. A total of 139 patients underwent continuous veno-venous haemofiltration (CVVH) as a component of fluid resuscitation and IAP control. Application of CVVH increased in period 2, p<0.005. Only 5-8% of patients were managed with ventilatory support. The overall infection rate decreased in period 2 comprising 21%, p<0.005. Success rate of the conservative therapy reached 69% in period 2, p<0.01. Surgical treatment was performed in 41% of patients in period 1 vs. 19% in period 2, p<0.001. Overall mortality was 19%, with a reduction to 12% in year 2006. CONCLUSION: The conservative protocol-based approach is a rational treatment strategy for the management of SAP and can be successfully implemented in the setting of the university hospital.

[Impact of hyperbaric oxygen therapy on the clinical course of acute pancreatitis and systemic inflammation response syndrome].

Feasibility of hyperbaric oxygen therapy (HBO) as an efficient and safe adjunct to the standardized treatment protocol and its possible immunomodulatory impact were assessed in the prospective and controlled study of 44 patients with diagnosed acute pancreatitis (AP). The course of the disease was accompanied by systemic inflammatory response syndrome (AIRS) in all the patients on admission. The impact of AP and HBO on homeostasis, the number of performed operations, mortality rates, the levels of two cytokines, intraabdominal pressure, and side effects caused by HBO were evaluated. A treatment group consisted of 22 patients receiving HBO therapy for 3 days (twice a day) using a monoplace chamber under pressures of 1.7-1.9 ATA. Patients (n = 22) in the control group were managed in accordance with the standardized treatment protocol. The authors found more stable homeostasis, decreased mortality rate, and the number of operations in the HBO group. This type of additional therapy, possibly contributed to the decrease of intraabdominal pressure within the first six days after admission. The findings suggest HBO can affect an inflammatory response, by decreasing the levels pro-inflammatory cytokines and increasing those of anti-inflammatory ones.

Overview of tigecycline efficacy and safety in the treatment of complicated skin and skin structure infections - a European perspective.

In a randomized, double-blind, multicenter, multinational, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. Three hundred eighty-five (385) were from Europe. The primary endpoint was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results and adverse event reporting. Of the patients enrolled in Europe, 376 patients were included in the c-mITT population (tigecycline group, n = 189; vancomycin/aztreonam group, n = 187), and 326 were clinically evaluable (tigecycline group, n = 167; vancomycin/aztreonam group, n = 159). The clinical responses in the tigecycline and the vancomycin/aztreonam groups in the clinically evaluable population were 89.8% versus 95.0%. Microbiologic eradication (documented or presumed) occurred in 84.8% of the European patients receiving tigecycline and 93.2% of the European patients receiving vancomycin/aztreonam. The number of European patients reporting adverse events was similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the vancomycin/aztreonam group. Current data support findings from the overall results in the Phase 3 study and suggest that tigecycline is safe and effective for the treatment of complicated skin and skin structure infections.

Continuous veno-venous haemofiltration in the treatment of severe acute pancreatitis: 6-year experience.

BACKGROUND: Continuous veno-venous haemofiltration (CVVH) could be reasonable for attenuation of systemic complications in severe acute pancreatitis (SAP). The aim of the study was implementation and feasibility assessment of the CVVH in the treatment protocol of SAP. PATIENTS AND METHODS: CVVH was applied to 111 SAP patients during 2000-2005. APACHE II, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), serum lipase, C-reactive protein (CRP), complication rate and main outcomes were analysed comparing two periods. RESULTS: Overall, 39 patients corresponded to Balthazar grade E SAP and 72 patients to necrotizing SAP (NSAP), with an average APACHE II score of 7 and 8.5, respectively, on admission. CVVH was started within 48 h in 82% of patients. Duration of CVVH was significantly augmented in NSAP patients during the routine period, comprising 92 h (p=0.006). The clinical presentation of SIRS and MODS was similar in both periods, with more initial pulmonary dysfunctions in NSAP (p=0.048). Peripancreatic infection decreased in the routine period; surgical interventions were performed in 34.8% vs 72.4% of patients. Hospital stay comprised on average 15.9 days for grade E SAP and 29.4 days for NSAP in the routine period, with overall mortality of 10.26% and 30.5%, respectively. DISCUSSION: Application of CVVH in the treatment protocol of SAP is obscure due to relative invasiveness, a poorly understood mechanism of action and scarce clinical experience. We conclude that early pre-emptive application of CVVH is safe and feasible in the treatment of SAP. Duration of the procedure seems to be essential. Randomized clinical trials are justified. Our results are in favour of clinical application of CVVH in the treatment of SAP.

Early oral feeding in acute pancreatitis: an alternative approach to tube feeding. Preliminary report.

INTRODUCTION: Jejunal feeding is accepted in the treatment of severe acute pancreatitis (AP). Early oral feeding (EOF) is deemed to be detrimental in the early phase of AP. The aim of this study was to assess the safety and effectiveness of EOF in the treatment of AP. MATERIALS AND METHODS: 29 AP patients were prospectively enrolled within 1.96 days from the onset of disease. APACHE II score, SIRS, MODS, serum CRP and lipase were evaluated. All patients received EOF when gastro-enteric transit was not severely impaired. ICU, hospital stay and main outcomes were assessed. RESULTS: APACHE II score was > or = 8 in 10 patients at the admission ranging 0-13 points for the whole group. Alcohol (62%) and gallstones (38%) were the main etiologic factors. SIRS and MODS were diagnosed in 65% and pleural effusion in 24% of patients. EOF was started on average 3.27 days after admission providing 571 ml (280.0-1115.0 ml) of enteral formula daily for 10.38 days. Median lipase activity was 690 U/l (90-10175 U/l) and CRP concentration reached 91.25 mg/dL (3.5-210 mg/dL) before EOF. Progressive decrease of lipase activity and CRP concentration was observed during the EOF course, reaching median CRP 18.6 mg/L (4.6-96.7mg/L) by discharge. Two patients underwent surgical intervention. Minor side effects of EOF were successfully managed in 4 patients. No mortality was observed. CONCLUSION: EOF could be a safe and effective alternative of nutritional support in AP patients when gastro-enteric transit is not severely impaired. For better EOF assessment further clinical trials are required.

Increased intra-abdominal pressure: is it of any consequence in severe acute pancreatitis?

BACKGROUND: Increased intra-abdominal pressure (IAP) is detrimental for the recovery of organ function in trauma and emergency patients. The aim of this study was to assess the correlation between the dynamics of IAP and organ dysfunction in severe acute pancreatitis (SAP). MATERIALS AND METHODS: Management of SAP between 2000 and 2004 was analysed. SAP was classified according to Atlanta 1992. Organ dysfunction, systemic inflammatory response syndrome (SIRS) and outcomes in relation to the IAP were assessed. IAP was measured indirectly. RESULTS: A total of 65 patients, with an average APACHE II score of 6.44, complied with the Atlanta criteria. In all, 34 patients received conservative treatment and 31 were operated. SIRS was observed in 59 cases and multiple organ dysfunction syndrome (MODS) in 61 cases. IAP was significantly higher in the 25 most complicated patients requiring renal replacement therapy (RRT), compared with 40 patients without RRT, 31.72 vs 21.4 cm/H(2)O (p=0.037). IAP interrelated positively with SOFA score (r = + 0.371, p<0.01) and organs involved (r = + 0.356, p<0.01), and negatively with platelet count and enterally provided volume (r = - 0.284, p<0.01; r = - 0.5, p<0.01, respectively). Overall mortality (9.2%) was associated with surgery and sustained increase of the IAP over 25 cm/H(2)O. Our data support the pathophysiological interrelation of elevated IAP and development of organ dysfunction. CONCLUSION: Development of organ dysfunction in SAP could be associated with increased IAP. Grade III increase of IAP should be considered as an indicator for revision of treatment modalities.

[Increased intra-abdominal pressure--an important risk factor of early organ dysfunction in severe acute pancreatitis]. / Erhöhter intraabdomineller Druck - ein wichtiger Risikofaktor für frühe Organdysfunktionen bei schwerer akuter Pankreatitis.

BACKGROUND: Sustained increase of the intra- abdominal pressure is recently recognized as a potential risk factor of early organ dysfunction in patients with severe acute pancreatitis. Assessment of the possible mutual relevance between increased intra-abdominal pressure and early organ dysfunction is important for optimisation of the treatment strategy in this category of patients. PATIENTS AND METHODS: 71 patients with severe acute pancreatitis were entered in this prospective study. Clinical routine, sequential organ failure assessment score (SOFA), and intra-abdominal pressure were registered, considering 25 cm H 2 O a critical value for the grouping in high-risk (n = 18) and low-risk (n = 53) patients according to whether they experienced the critical level during their treatment course. RESULTS: The age structure and the initial presentation of the organ dysfunction were similar between both groups. Progression of the organ dysfunction was observed in 61 % of the high-risk patients, compared to 32 % of low-risk patients, p < 0.05. Organ function improved after three to four day treatment only in survivors. Peak intra-abdominal pressure was greater in high-risk patients, p < 0.01, but declined after three to five day treatment period in all survivors, remaining critical in nonsurvivors. 78 % of high-risk and 32 % of low-risk patients were operated, p < 0.05. The overall mortality was 8.5 %, consisting of 2 % mortality in the low-risk group and 28 % mortality in the high-risk group, p < 0.01. CONCLUSION: Increased intra-abdominal pressure could be an important risk factor of early organ dysfunction in patients with severe acute pancreatitis. Critical increase of the intra-abdominal pressure and persisting organ dysfunction are an indication for reassessment of the treatment strategy.

[Importance of a clinical protocol in the treatment of severe acute pancreatitis]. / Die Bedeutung eines klinischen Protokolls bei der Behandlung der schweren akuten Pankreatitis.

BACKGROUND: Selection of the optimal treatment strategy in severe acute pancreatitis (SAP) is a serious clinical challenge largely due to difficult differential diagnosis of patients with early SAP. The aim of this study is a retrospective evaluation of the first experiences in the treatment of patients with SAP and early SAP according to a new complex clinical protocol (CCP). METHODS: A total of 210 patients complied with Atlanta recommendations for SAP and were included in the retrospective study. Patients were stratified into two groups according to the diagnostic and treatment strategy. Non-protocol (NP) group comprised 154 patients who had received their treatment based on previous clinical routine and subjective decision of physicians in charge. 56 patients who were managed according to the new CCP developed for SAP comprised the CCP group. CCP included:- Early assessment of the severity of acute pancreatitis (APACHE II score, presence of SIRS and/or organ dysfunction); - Immediate ICU monitoring including routine measurement of the intraabdominal pressure; - Conservative treatment including early enteral nutrition, colloids, antibacterial prophylaxis and early continuous venovenous hemofiltration (CVVHF) when indicated; - Surgical treatment when conservative treatment was not effective (progression of the organ dysfunction) or presence of infection was evident. Hospital, ICU stays and outcomes were analysed. Statistical comparison was done by Mann-Whitney U-test and Chi-square test. RESULTS: The age structure and severity of the disease were similar in both groups with mean of 51.3 (15.6) vs. 46.8 (15.2) years and 9.7 (5.1) vs. 9.8 (4.4) APACHE II points in groups NP and CCP, respectively. Male/female ratio was 2 : 1, and alcohol was the main etiologic factor in about 55 % of cases in both groups. Early SAP was diagnosed in 33 % to 46 % of patients according to the results of the SOFA scoring. The results of the conservative therapy considerably improved after implementation of the CCP treatment. Surgical intervention was done in 46-52 % of patients. MODS was the main cause of death in both groups. Remarkable decrease in early mortality (within the first week from admission) was a real advantage of CCP treatment comprising 1.8 % vs. 22.1 % in NP patients, p < 0.01. Mortality from early SAP was reduced by CCP treatment to 3.8 % compared to 33 % in NP group, p < 0.01. There was a considerable reduction in postoperative mortality with CCP treatment comprising 10.3 % vs. 32.7 % in patients who did not receive CCP treatment, p < 0.05. Overall mortality associated with CCP treatment ranged to 5 %, compared to 34 % mortality in the NP treatment group, p < 0.01. Due to the considerable number of early deaths among NP patients, there was statistically longer ICU and hospital stay in CP group with mean of 14.1 (14.1) vs. 9.6 (15.2) days and 37.9 (26.7) vs. 23.4 (21.8) days, compared to NP group, p < 0.01. CONCLUSIONS: Timely recognition and complex therapy of SAP including ICU monitoring, colloids, antibacterial prophylaxis, early enteral nutrition, and CVVHF is the most effective way how to manage this category of patients. Implementation of a specialised treatment protocol considerably improves outcome and reduces the number of deaths associated with surgery and early SAP.

Clinical significance of increased intraabdominal pressure in severe acute pancreatitis.

The aim of the study was to assess whether increased intra-abdominal pressure affects the clinical course and reflects on the effectiveness of the conservative treatment in patients with severe acute pancreatitis. Data on 37 consecutive patients with severe acute pancreatitis that were collected prospectively included APACHE II score, daily measurement of the intra-abdominal pressure, and clinical routine. Group A consisted of 26 patients with intra-abdominal pressure < 25 cm/H2O during their treatment period, and group B consisted of 11 patients with intraabdominal pressure > or = 25 cm/H2O. SIRS, MODS, complication rate and mortality were analysed. The age, APACHE II scores and hospital stay were similar in both groups. ICU stay was 9.1 +/- 9.6 vs. 20.7 +/- 16.8 days in groups A and B, p < 0.05. SIRS and MODS developed less frequently in group A. More pulmonary complications developed in group B, reaching 64% compared to 19% in group A, p < 0.05. Intra-abdominal pressure had negative interrelation with enterally provided volume (r = -0.45, p < 0.001) and positive interrelation with parenterally provided volume (r = +0.27, p < 0.01) in all. Mortality was zero in group A vs. 36% in group B, p < 0.01. Increase of the intra-abdominal pressure is common during the clinical course of severe acute pancreatitis and can be associated with aggressive fluid replacement therapy. Routine measurement of the intra-abdominal pressure is rational in the clinical setting of the ICU and gives additional criteria for the evaluation of the clinical course and the effectiveness of the treatment. Marked increase of the intra-abdominal pressure should be considered a serious prognostic sign in patients with severe acute pancreatitis.

[Blood purification methods for treatment of organ failure in patients with severe pancreatitis]. / Blutreinigungsmassnahmen bei Patienten mit Organversagen bei schwerer Pankreatitis.

BACKGROUND: Recent years have shown a considerable progress in the management of severe pancreatitis (SP); however, the role of extracorporeal blood purification in the treatment of progressive multiple organ dysfunction syndrome (MODS) is not well assessed. THE AIM OF THIS STUDY: The retrospective assessment of the MODS treatment results after application of extracorporeal blood purification methods in SP patients. METHODS: 50 consecutive patients with acute pancreatitis were included in the study. Atlanta classification system was applied for stratification of patients with SP. MODS was defined according to the recommendations of the Consensus Conference of American College of Chest Physicians/Society of Critical Care Medicine in 1991, and MODS score was calculated. Involvement of the organ systems, ICU, hospital stays and main outcomes were analyzed. RESULTS: Totally, 45 patients met SP criteria. Necrotizing pancreatitis was found in 35 patients. In 19 cases the clinical course was complicated with peritonitis, in two with jaundice. Infection was present in four patients. MODS were observed in 34 patients, with average of 3.3-organ involvement. In total, 21 patients underwent surgery. Hemodialysis was necessary in 5 of the 21 patients with necrotizing pancreatitis. Hemofiltration was applied in 5, hemadsorption in 28 and plasmapheresis in 23 patients. The overall mortality in association with hemodialysis and hemofiltration reached 20 % in necrotizing pancreatitis patients. Hemadsorption was associated with 3.8 % mortality, and plasmapheresis with 25 % mortality rate in all SP patients. CONCLUSION: Combined derangement of the renal and hepatic function is highly associated with unfavorable outcome in patients with severe pancreatitis. Timely application of the extracorporeal blood purification methods may revert progression of MODS and can be successfully combined with surgery if it is needed in this category of patients.

Jejunal feeding, even when instituted late, improves outcomes in patients with severe pancreatitis and peritonitis.

This study assessed the feasibility and effectiveness of jejunal feeding (JF) after surgery due to secondary peritonitis or failed conservative therapy of severe pancreatitis. Of 60 patients, 30 were randomly assigned to receive postoperative JF and the remaining 30 constituted the control group. Acute Physiology and Chronic Health Evaluation II, nutritional intake, systemic inflammatory response syndrome, and outcomes were measured. Patients in JF group received the daily mean of 1294.6 (362.6) kcal including 830.6 (372.7.0) kcal enterally, versus 472.8 (155.8) kcal daily in the control group (P < 0.0001). There were fewer complications in the JF patients, with no significant difference; length of stay in the intensive care unit and in the hospital did not differ. The frequency of systemic inflammatory response syndrome was similar in both groups, but outcomes differed. The first surgical intervention resulted in 3.3% of relaparotomies in JF patients, caused by unresolved peritonitis, versus 26.7% in the control subjects (P = 0.03). Recovery of bowel transit took significantly less time in the JF patients (mean: 54.6 h versus 76.8 h in control subjects, P = 0.01). JF resulted in 3.3% mortality as opposed to 23.3% in the control group (P = 0.05). In conclusion, JF is feasible and effective in postoperative treatment of patients due to secondary peritonitis or severe pancreatitis. Improved bowel and peritoneal function could be the main impact of JF.

Randomised trial of safety and efficacy of postoperative enteral feeding in patients with severe pancreatitis: preliminary report.

OBJECTIVE: To find out whether postoperative enteral feeding is safe and effective in patients with severe pancreatitis. DESIGN: Prospective randomised trial. SETTING: Teaching hospital, Latvia. SUBJECTS: 29 patients who had been operated on for severe pancreatitis. INTERVENTIONS: They were randomised to have either enteral nutrition and conventional intravenous fluids postoperatively (n = 11), or conventional intravenous fluids only (n = 18). 17 additional patients who had had major abdominal operations for other conditions were also given enteral nutrition and intravenous fluids and comprised the control group. MAIN OUTCOME MEASURES: Nutritional intake, duration of stay in intensive care (ICU) and hospital morbidity, mortality, and outcome. RESULTS: 1 patient died of the 11 given enteral nutrition combined with conventional intravenous fluids, compared with 5/18 given fluids only. The pattern of bowel transit in the fed group did not differ from that in the control group. CONCLUSION: Postoperative enteral nutrition seems to be safe and effective in patients with severe pancreatitis and may improve survival. Our results suggest that enteral and parenteral nutrition may complement each other in seriously ill patients.

Renal failure in acute pancreatitis. Timing of dialysis and surgery.

Despite the progress in intensive care treatment the ongoing systemic inflammatory response syndrome (SIRS) in patients with severe pancreatitis (SP) and renal failure (RF) is associated with high mortality. The aim of this lecture is to outline the knowledge drawn from literature and personal experience and to re-evaluate the management strategy of SP patients whose clinical course is complicated with impairment of the renal function. INCIDENCE, RISK FACTORS AND OUTCOME: Impaired renal function can be observed in 14-43% of patients with SP mostly in combination with other organ system failure. SIRS is the main culprit in the pathologic process. Extent of necrosis does not correlate with derangement of the renal function, however, infection is a serious risk factor. Mortality reaches 71-84% in patients with SP and RF, which requires dialysis. Risk factors highly associated with RF and detrimental outcomes in SP patients are advancing age, prior chronic disease, cardiovascular and pulmonary failure, mechanical ventilation, hypotension, oliguria, coma, and jaundice. SP is associated with increased bowel permeability, impaired visceral perfusion, retroperitoneal oedema and increased intraabdominal pressure, which can directly affect the renal function as consequence of the acute abdominal compartment syndrome (AACS). TREATMENT: Early aggressive resuscitation including isovolemic hemodilution with dextran 60, venovenouse hemofiltration, early enteral nutrition and antibiotic prophylaxis are of extreme importance. Surgery is indicated in SP with evidence of the RF when clinical course deteriorates despite intensive care, especially if infection is present and/or AACS develops. CONCLUSION: RF in the patients with SP reflects the severity of SIRS. Improvement of the visceral perfusion is the goal of resuscitation. Surgery is indicated in case of failed conservative treatment and may be successfully combined with hemodialysis.

Shear stress induces changes in the morphology and cytoskeleton organisation of arterial endothelial cells.

OBJECTIVES: The aim of this study was to determine the changes in the morphology and cytoskeleton organisation of endothelial cells (EC) determined by exposure to a laminar flow. Cultured EC were exposed to a wall shear stress of 6 dyne/cm2 for 24 hours. CHIEF OUTCOME MEASURES: The morphology of EC was analysed by light and scanning electron microscopy. The organisation of the cytoskeleton was determined by double fluorescence labeling with antibody anti-vimentin, anti-vinculin, anti-tubulin, and with rhodamine-labeled phalloidin. RESULTS: EC exposed to laminar flow become round-shaped with decreased area of adhesion to the substrate. There was a clear reorganisation of the cytoskeleton after exposure to shear stress; the distribution of actin changed from a stress fibre pattern to a more diffuse membrane-associated distribution. These changes in shape and cytoskeleton organisation were reversible after a 48-hour resting period. CONCLUSIONS: EC respond to laminar flow in a predictable manner and these findings may be correlated to the functional changes of EC observed after exposure to shear stress.

Systemic specific active immunotherapy for solid tumors. An overview about cancer vaccinetherapy.

Augmentation of specific immunity is one of the most promising immunotherapeutical approaches against solid tumors. Protocols using autologous tumor cells or tumor associated antigens are easily performed and not charged by severe side effects. Recently some clinical trials suggested good results from immunotherapeutical protocols applied as an adjuvant to surgery in terms of disease free interval, survival and progression time in different stages. In this review the authors report the results of the most important clinical trials of vaccinetherapy in solid tumors. Little is known about the possibility of this new approach to oncology since we are at the real beginning of a new clinical treatment but in the considered trial its effectiveness seems to suggest a future wider application.