The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y; p = 0.023). Prolonged length of stay (>7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y ; p = 0.023). Prolonged length of stay (> 7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

Targeting the vasculature of visceral tumors: novel insights and treatment perspectives.

BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, describes a crucial process in tumor growth, disease progression, and metastasis. Therefore, the upcoming strategy of inhibiting tumor angiogenesis has generated different treatment modalities, which have been transferred into clinical practice in recent years. Currently, this concept is applied to target the vasculature of different visceral tumors and intensive clinical research has just started. MATERIALS AND METHODS: This review summarizes the modifications of systemic treatment of visceral tumors by targeting the vasculature in the past years. Moreover, novel targets and treatment strategies will be discussed to evaluate future directions. RESULTS: Leading antiangiogenic drugs combined with systemic chemotherapy have been applied with increasing success during the last years. Therefore, the concept of combining vascular targeting agents with established chemotherapeutic regimens has been increasingly adopted into the therapies of different visceral tumors. CONCLUSION: Targeting the vasculature of visceral tumors in combination with established standard tumor therapies includes major clinical potential for future therapy concepts.

Blumgart anastomosis for pancreaticojejunostomy minimizes severe complications after pancreatic head resection.

BACKGROUND: Leakage from the pancreaticojejunostomy is the major cause of septic complications after partial pancreaticoduodenectomy. This study evaluated a new transpancreatic U-suture technique (Blumgart anastomosis, BA), which aims to avoid shear forces during knot-tying. METHODS: Using a before-after study design, BA was compared with a modified Cattell-Warren anastomosis (CWA). Two patient cohorts (CWA, 90; BA, 92), which were similar with respect to primary diagnosis, age, sex and American Society of Anesthesiologists score, were compared retrospectively. Dependent variables were surgical and overall morbidity and mortality after partial pancreaticoduodenectomy. RESULTS: Duration of operation (354 versus 328 min for CWA versus BA; P = 0.002), pancreatic leakage rate (13 versus 4 per cent; P = 0.032), postoperative haemorrhage (11 versus 3 per cent; P = 0.040), total surgical complications (31 versus 15 per cent; P = 0.011), general complications (36 versus 17 per cent; P = 0.005) and length of intensive care unit stay (median 5.4 versus 2.8 days; P = 0.015) were significantly reduced after BA. These effects were not related merely to an improvement over time. CONCLUSION: BA appears to be a fast, simple and safe technique for pancreaticojejunostomy. It might reduce leakage rates and surgical complications after partial pancreaticoduodenectomy.

Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO).

BACKGROUND: Small bowel obstruction (SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment. METHODS: C57Bl6 mice were anesthetized, and a midline laparotomy was performed. A small bowel loop was ligated 5 cm proximal to ileo-cecal valve to induce SBO. Control animals received a sham midline laparotomy. SBO animals and controls were sacrificed after 3, 9, or 24 h (each n = 6). A dilated segment of small intestine located 1.5 cm oral to the ligature was prepared for multi-unit mesenteric afferent nerve recordings in vitro. Histological assessment of leukocyte infiltration was performed by myeloperoxidase (MPO). Pro-inflammatory cytokine expression was quantified by RT-PCR. Data are mean ± SEM. KEY RESULTS: Afferent firing to serosal 5-HT (500 µM) peaked at 3.9 ± 0.2 impulse/s 24 h after induction of SBO compared to 2.4 ± 0.1 impulse/s in sham controls (p < 0.05). Serosal bradykinin (0.5 µM) led to an increase in peak afferent firing of 5.3 ± 0.5 impulse/s in 24 h SBO animals compared to 3.5 ± 0.2 impulse/s in sham controls (p < 0.05). No differences in 5-HT and BK sensitivity were observed in 3 and 9 h SBO animals compared to controls. Continuous mechanical ramp distension of the intestinal loop was followed by a pressure-dependent rise in afferent nerve discharge that was reduced in 3 h SBO animals compared to sham controls (p < 0.05). MPO stains showed a rise in leukocyte infiltration of the intestine in SBO animals at 9 and 24 h (p < 0.05). Il-6 but not TNF-a gene expression was increased at 9 and 24 h in SBO animals compared to sham controls (p < 0.05). CONCLUSIONS & INFERENCES: Afferent nerve sensitivity is increased 24 h after induction of SBO. SBO led to a delayed onset intestinal inflammatory response. Inflammatory mediators released during this inflammatory response may be responsible for a later increase in afferent sensitivity. Agents with anti-inflammatory action may, therefore, have a beneficial effect during SBO and may subsequently help to prevent possible organ dysfunction.

Transplantation of H-2Kb-transgenic adrenocortical cells in the mouse having undergone an adrenalectomy: functional and morphological aspects.

BACKGROUND: A new model of cellular adrenocortical transplantation after bilateral adrenalectomy in the mouse was established. This model was used to study the effects of the expression of the transgenic MHC class I molecule H-2K(b) (Kb) on graft survival and morphologic features, corticosterone secretion, and the possibility of tolerance induction in the recipient. METHOD: A single cell suspension of purified adrenocortical cells was grafted under the kidney capsule of B10.Br (H-2k) mice having adrenalectomies. Syngeneic, fully MHC-mismatched, and MHC class I-incompatible Kb-transgenic mice served as donor strains. To analyze graft function, urinary excretion and serum levels of corticosterone were monitored over 100 days. Tolerance induction in the graft recipients of Kb-transgenic and third party skin grafts was tested on day 50 after adrenocortical transplantation. Histological sections of the adrenocortical grafts were obtained on day 100. RESULTS: Recipients of syngeneic and Kb-transgenic grafts displayed pretransplant corticosterone levels on days 20, 50, and 100 and ACTH-stimulated serum corticosterone levels similar to those of controls on day 100 after adrenocortical transplantation. In contrast, in recipients of fully MHC-mismatched grafts, corticosterone excretion was significantly reduced. In this group, 4 of 7 mice did not survive. Syngeneic skin grafts survived indefinitely in recipients of syngeneic and Kb-transgenic adrenocortical grafts, whereas Kb-transgenic and fully MHC-mismatched skin grafts were acutely rejected. Tissue sections of the adrenocortical grafts revealed vascularized cell conglomerates in syngeneic and Kb-transgenic grafts without infiltrations of mononuclear cells. Furthermore, a differentiation similar to adrenocortical organization was partly found. CONCLUSION: In conclusion, a model of cellular adrenocortical transplantation was established. The results show that syngeneic transplantation resulted in physiological corticosterone levels early after transplantation, whereas fully MHC-incompatible grafts were rejected. Recipients of Kb-transgenic grafts showed unimpaired adrenocortical function, but did not tolerize toward Kb-transgenic skin grafts. Possible mechanisms include a local immunomodulatory effect of glucocorticoids secreted by the graft and a low immunogenicity of the relatively small numbers of transplanted cells.

Behaviorally conditioned immunosuppression using cyclosporine A: central nervous system reduces IL-2 production via splenic innervation.

Bi-directional interactions between the central nervous system (CNS) and immune system are demonstrated by the modification of immune function using behavioral conditioning. However, the mechanisms by which the CNS achieves conditioned immunomodulation are still in question. Here, we report that the immunosuppressive effects of cyclosporine A (CsA) can be behaviorally conditioned in rats using saccharin as a gustatory conditioned stimulus. The conditioned effects were compared to control groups that received CsA paired with water (sham-conditioned), CsA injection on test days (CsA-treated), and unhandled rats (untreated). In conditioned animals, the mitogen-induced lymphocyte proliferation in the spleen is significantly suppressed, and the survival time of heterotopic heart allografts prolonged. These effects are paralleled by conditioned inhibition of IL-2 and IFN-gamma synthesis by splenocytes. Furthermore, the CNS-induced immunosuppression is mediated neuronally and not via the blood, since the conditioned reduction of proliferation and cytokine production is completely abrogated after surgical denervation of the spleen. Thus, during conditioning, the CNS learns to reinstate at demand a CsA-like immunosuppression via splenic innervation. This might be used as a supportive therapy for controlling immune functions.

Problems of differential diagnosis of blastomyces and Russell bodies.

The European dermato-histologist is only rarely confronted with the diagnosis of granulomatous and systemic mycosis. The proper identification in sections and smears of blastomycetes of systemic importance is rather problematic, as Russell bodies may simulate fungi in certain stains. An own observation is reported with particular emphasis on differential diagnosis.

Isolation of Listeria monocytogenes from goat cheese associated with a case of listeriosis in goat.

Listeria monocytogenes was isolated from the brain of a goat, which was euthanized due to listeriosis. A few weeks later a similar subtype of L. monocytogenes was isolated from an on-farm manufactured fresh cheese which did not contain any milk from the goat which had suffered from listeriosis. A similar subtype was also found on 1 of the shelves in the refrigerator where cheeses were stored. Prior to the onset of listeriosis, 1 fresh cheese had been made of milk from the actual goat, which may have excreted L. monocytogenes in her milk. Thus, the cheese made of this milk may have contaminated the shelves in the refrigerator which then has served as a Listeria reservoir for new cheeses during several weeks.

Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo.

PURPOSE: The close association of lymphatic and blood vessels and their coordinated development in vivo suggest that there are parallel mechanisms regulating hemangiogenesis and lymphangiogenesis. Here, we hypothesize that inhibition of the Src tyrosine kinase, apart from anti-hemangiogenic effects, results in a suppression of lymphangiogenesis. EXPERIMENTAL DESIGN: The ability of the Src kinase inhibitor PP2 to block Src in isolated lymphatic endothelial cells (LECs) was analyzed by Western Blot. The effects of PP2 on LEC proliferation, migration, and sprouting were assessed by MTT, Boyden chamber, and spheroid assays, respectively. The level of VEGF-C secreted by L3.6pl pancreatic carcinoma cells was measured by ELISA. For in vivo assessment of lymphangiogenesis, Src kinase inhibitor AZM475271 was used in mouse corneal micropocket and lymphangioma models. RESULTS: VEGF-C stimulation of isolated LECs led to an increased phosphorylation of Src kinase that was abrogated by PP2. Treatment with PP2 inhibited spheroid sprouting of LECs at even lower concentrations than suggested by the proliferation assay. Src inhibition significantly reduced the level of VEGF-C in L3.6pl supernatant. Treatment with PP2 also resulted in a significant reduction in the migratory activity of LECs. In vivo, Src inhibition reduced de novo formation of lymphangiomas and corneal neovascularization. CONCLUSIONS: Inhibition of Src kinase shows strong anti-lymphangiogenic activity in vitro and in vivo. Together with anti-angiogenic effects mediated by Src inhibition, this strategy may be attractive in the treatment of lymphatic and hematogeneous metastasis of cancer.

Inhibition of Src tyrosine kinase reverts chemoresistance toward 5-fluorouracil in human pancreatic carcinoma cells: an involvement of epidermal growth factor receptor signaling.

Resistance to chemotherapy is believed to be a major cause of treatment failure in pancreatic cancer. Thus, it is necessary to explore alternative therapeutic modalities to overcome drug resistance in pancreatic cancer treatment. We tested the hypothesis that Src tyrosine kinase inhibition could augment the chemosensitivity of 5-fluorouracil (5-FU)-resistant human pancreatic cancer cells to 5-FU. As detected by MTT proliferation assay, propidium iodide and annexin V staining, a combination of 5-FU+Src kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) reflected the chemotherapeutic sensitivity and restored the 5-FU-induced apoptosis in 5-FU-resistant cells. Furthermore, when small-interfering RNA approach to silence Src gene expression was applied, the degree of 5-FU-induced apoptosis was increased in all cell lines independently of the chemoresistance status. Western blotting and RT-PCR analysis revealed that the expression of thymidylate synthase (TS) was higher in 5-FU-resistant cells, however, decreased significantly after pretreatment with PP2. Furthermore, the combination of 5-FU+PP2 decreased the 5-FU-induced activation of epidermal growth factor receptor (EGFR)-AKT pathway. Finally, PP2 in combination with 5-FU substantially decreased the in vivo tumor growth and inhibited distant metastases. Taken together, 5-FU chemoresistance can be reversed through indirect TS regulation by inhibiting Src tyrosine kinase. A potential mechanism of action of Src kinase inhibitors on 5-FU chemosensitivity might be linked to the inhibition of 5-FU-induced EGFR-AKT activation.

[The dilemma of listeriosis control by the public health office]. / Das Dilemma der amtsärztlichen Listeriose-Bekämpfung.

The frequent occurrence of Listeria monocytogenes both superficially and in certain foods requires measures in accordance with the Federal Laws on Communicable Diseases and Safe Foods to study possible sources of the infectious agent and prevention if positive findings are reported. On the other hand, due to good defence mechanisms, the majority of the population are not at great risk. This excludes, however, immunodeficient patients, aged persons and newborn. The Federal Law on Notifiable Diseases requires only the reporting of meningitis and encephalitis as well as of listeriosis in newborn. Hence, Listeria infections with other syndromes are not registered. The some-times relatively long time of incubation and the lack of knowledge on mild and transient forms of listeriosis render the search for sources of such infections rather difficult. This results in a true dilemma. -Thus, it appears at the present to be more important to encourage strongly the producers of Listeria-endangered food, to eliminate the risk by all possible means. This, however, appears to be applicable only in a few food items. Therefore, the consumer should be more thoroughly informed, so that at least for the 'at risk' part of the population any possible danger may be minimised. Particular attention should be paid to impart good knowledge on the possibilities of preventing listeriosis by appropriately efficient methods of food preparation.