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1.
Colorectal Dis ; 23(8): 1998-2006, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33905599

ABSTRACT

AIM: Patients with locally advanced and locally recurrent rectal cancer (LARC/LRRC) experience higher rates of local recurrence (LR) and poorer overall survival than patients with primary rectal cancer restricted to the mesorectum despite improved neoadjuvant treatment regimens and radical surgical procedures. Intraoperative radiotherapy (IORT) has been suggested as an adjunctive tool in the surgical management of these challenging cases. However, clear evidence regarding the oncological benefit of IORT is sparse. The aim of this review was to update this evidence in the era of standardized neoadjuvant radiotherapy administration. METHOD: A systematic review of patients who received IORT as part of multimodal treatment for advanced rectal cancer from 2000 to 2020 and an analysis of IORT and surgery/external beam radiotherapy (EBRT) groups was performed. The primary endpoint was the rate of LR between the two groups. RESULTS: Seven papers met the predefined criteria. LR was reduced by the addition of IORT when compared with the surgery/EBRT alone group (14.7% vs. 21.4%; OR 0.55, 95% CI 0.27-1.14; p = 0.11). There was no increase in reported genitourinary morbidity, wound issues, pelvic collections or anastomotic leak in those patients who received IORT. Notably, there was no survival difference between the two groups. CONCLUSION: The addition of IORT to current treatment strategies in the management of patients with LARC/LRRC is associated with a lower rate of locoregional recurrence without increased morbidity. However, this marks a highly selective group of patients, with heterogeneity regarding indications, prior neoadjuvant treatments and/or IORT dosing.


Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms , Combined Modality Therapy , Humans , Neoadjuvant Therapy , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery
2.
World J Surg Oncol ; 19(1): 74, 2021 Mar 13.
Article in English | MEDLINE | ID: mdl-33714275

ABSTRACT

BACKGROUND: Inflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied. AIM: The aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery. METHODS: This is a retrospective study which catalogs 218 patients undergoing elective, potentially curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics. RESULTS: Elevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6, and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC = 0.871), and values above 17.5 mg/L predicted severe complications (AUC = 0.934). CONCLUSIONS: Elevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.


Subject(s)
C-Reactive Protein , Colorectal Neoplasms , C-Reactive Protein/analysis , Colorectal Neoplasms/surgery , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies
3.
Surg Infect (Larchmt) ; 20(6): 465-471, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31013189

ABSTRACT

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line sepsis is one of a number of potential morbidities. The aim of this study was to calculate the incidence of catheter-related infection (CRI) in a CRS and HIPEC patient population and to assess its influence on length of hospital stay. Methods: Data were collected on consecutive patients who underwent CRS HIPEC between August 2013 and October 2017. Data included patient demographics, timing of CVC insertion/removal, time spent in critical care, and CVC tip/blood culture results. Charts were reviewed for patients with both positive CVC culture and positive blood cultures to assess for evidence of catheter related infection and systemic inflammatory response syndrome (SIRS). Results: Data on 100 consecutive CRS HIPEC operations performed between August 2013 and October 2017 was analyzed. There were 11 CRIs in 100 CVCs, resulting in a CRI rate of 16.2 per 1,000 CVC days. Patients within the CRI group had a longer high-dependency unit (HDU) stay compared with the non-septic group (6 days vs. 4.07 days, p < 0.05). The CVC duration for the CRI and non-CRI group was 8.4 and 7.6 days, respectively (p = 0.12). The CRI group also had an increased total hospital length of stay (LOS; 20.8 days vs. 15.4 days, p < 0.05). On average, CRIs occurred eight days post-operative and four days post-HDU discharge. There was no association identified with longer CVC duration (p = 0.34). There has been an annual decline in CRI rates in CRS and HIPEC patients over the duration of the study period from 19.1 per 1,000 CVC days in 2016 to 8.2 per 1,000 CVC days in 2017. Conclusion: This is the first study to report on CRI rates in patients undergoing CRS and HIPEC. The CRI rate of 16.2 per 1,000 CVC days is higher than the overall national figure of 5.2 per 1,000 for CVC lines inserted in the operating room. Patients who developed line sepsis had longer HDU and longer overall hospital stay. Catheter-related infection was noted post-HDU discharge in all cases. Implementation of a CVC care bundle in the later years of the study period coincided with a reduction in CRI rates.


Subject(s)
Catheter-Related Infections/epidemiology , Catheterization, Central Venous/adverse effects , Cytoreduction Surgical Procedures/adverse effects , Hyperthermia, Induced/adverse effects , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies
4.
J Gastrointest Cancer ; 50(3): 660-664, 2019 09.
Article in English | MEDLINE | ID: mdl-29663116
5.
Med Mycol Case Rep ; 21: 30-33, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30023164

ABSTRACT

Invasive fungal infections in immunosuppressed transplant patients are associated with significant morbidity and mortality. We present a case of splenic mucormycosis post-double lung transplant, presenting as uncontrolled near-fatal upper gastrointestinal haemorrhage, to remind clinicians of the need to consider pre-transplant invasive fungal infection risk factors if an unexpected fungal infection arises in the post-transplant period. This case also highlights the valuable contribution of molecular technology for fungal identification but also the need for clinical correlation.

6.
AJR Am J Roentgenol ; 208(3): 531-543, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28075611

ABSTRACT

OBJECTIVE: The purpose of this article is to discuss the role of the radiologist in the treatment of peritoneal cancer, with focus placed on advanced treatment options and selection of patients with resectable disease for whom complete cytoreduction can be achieved. CONCLUSION: Peritoneal cancers traditionally have been associated with significant morbidity and universal mortality; however, the management of such cancers has evolved substantially. Advanced treatment options, including cytoreductive surgery and intraperitoneal chemotherapy, are associated with significantly improved long-term patient survival. To ensure that patients benefit from aggressive multimodality treatments, the radiologist plays a pivotal role in the multidisciplinary team to ensure careful patient selection, identifying individuals with resectable disease for whom complete cytoreduction can be achieved.


Subject(s)
Image Enhancement/methods , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/therapy , Physician's Role , Diagnosis, Differential , Evidence-Based Medicine , Humans , Reproducibility of Results , Sensitivity and Specificity , Treatment Outcome , United States
7.
Ann Surg ; 252(5): 750-5, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21037430

ABSTRACT

OBJECTIVE: This study aims to describe recent experience with rectal carcinoids in European and North American centers. BACKGROUND: While considered indolent, the propensity of carcinoids to metastasize can be significant. METHODS: Rectal carcinoid patients were identified from prospective databases maintained at 9 institutions between 1999 and 2008. Demographic, clinical, and histologic data were collated. Median follow-up was 5 years (range, 0.5-10 years). RESULTS: Two hundred two patients were identified. The median age was 55 years (range, 31-81 years). The majority of tumors were an incidental finding (n = 115, 56.9%). The median tumor size was 10 mm (range, 2-120 mm). Overall, 93 (49%) tumors were limited to the mucosa or submucosa, 45 (24%) involved the muscularis propria, 29 (15%) extended into the perirectal fat, and 6 (3%) reached the visceral peritoneum. The primary treatment modalities were endoscopic resection (n = 86, 43%) and surgical extirpation (n = 102, 50%). Forty-one patients (40%) underwent a high anterior resection, whereas 45 (44%) underwent anterior resection with total mesorectal excision. Seven patients (7%) underwent Hartman's procedure, 7 (7%) underwent abdomino-perineal resection, and 6 (6%) had transanal endoscopic microsurgery, whereas 4 (4%) patients underwent a transanal excision. Multiple variable logistic regression analysis demonstrated that tumor size greater than 10 mm and lymphovascular invasion were predictors of nodal involvement (P = 0.006 and < 0.001, respectively), whereas the presence of lymph node metastases and lymphovascular invasion was associated with subsequent development of distant metastases (P = 0.033 and 0.022, respectively). The presence of nodal metastases has a profound effect upon survival, with a 5-year survival rate of 70%, and 10-year survival of 60% for node positive tumors. Patients with distant metastases have a 4-year survival of 38%. CONCLUSION: Tumor size greater than 10 mm and lymphovascular invasion are significantly associated with the presence of nodal disease, rendering mesorectal excision advisable. Transanal excision is adequate for smaller tumors.


Subject(s)
Carcinoid Tumor/surgery , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoid Tumor/pathology , Chi-Square Distribution , Endoscopy, Gastrointestinal , Europe , Female , Follow-Up Studies , Humans , Incidental Findings , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , North America , Prospective Studies , Rectal Neoplasms/pathology , Risk Factors , Survival Rate , Treatment Outcome
8.
Surg Laparosc Endosc Percutan Tech ; 19(4): e146-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19692868

ABSTRACT

The finding of heterotopic gastric mucosa in the rectum is rare, with less than 40 reported cases in the literature. A condition of unknown etiology, several hypotheses exist including infectious and congenital. We report a case of ectopic gastric tissue in the rectum of a 47-year-old female, and her subsequent clinical course. Furthermore for the first time, we present immunohistologic evidence of the presence of Helicobacter pylori in rectal ectopic gastric tissue.


Subject(s)
Choristoma/complications , Choristoma/microbiology , Gastric Mucosa/microbiology , Helicobacter Infections/complications , Helicobacter pylori , Rectal Diseases/complications , Choristoma/diagnosis , Female , Humans , Middle Aged , Rectal Diseases/diagnosis
9.
Acta Orthop ; 79(5): 703-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18839379

ABSTRACT

BACKGROUND AND PURPOSE: Pharmacological modulation of skeletal muscle reperfusion injury after traumaassociated ischemia may improve limb salvage rates and prevent the associated systemic sequelae. Resuscitation with hypertonic saline restores the circulating volume and has favorable effects on tissue perfusion and blood pressure. We evaluated the effects of treatment with a bolus of hypertonic saline on skeletal muscle ischemia reperfusion (IR) injury and the associated end-organ injury. METHODS: Adult male Sprague-Dawley rats (n = 27) were randomized into 3 groups: (1) a control group, (2) an IR group treated with normal saline, and (3) an IR group treated with hypertonic saline. Bilateral hindlimb ischemia was induced by application of a rubber band proximal to the level of the greater trochanters for 2.5 h. The treatment groups received either normal saline (4 mL/kg) or hypertonic saline (4 mL/kg) prior to tourniquet release. Following 12 h of reperfusion, the tibialis anterior muscle was dissected and muscle function was assessed electrophysiologically. The animals were then killed, and skeletal muscle and lung tissue were harvested for evaluation. RESULTS: Hypertonic saline significantly attenuated skeletal muscle reperfusion injury, as shown by reduced myeloperoxidase content, wet-to-dry ratio, and electrical properties of skeletal muscle. There was a corresponding reduction in lung injury, as demonstrated by reduced myeloperoxidase content and reduced wet-to-dry ratio. INTERPRETATION: Treatment with hypertonic saline attenuates skeletal muscle ischemia reperfusion injury and its associated systemic sequelae.


Subject(s)
Muscle, Skeletal/drug effects , Reperfusion Injury/drug therapy , Saline Solution, Hypertonic/administration & dosage , Animals , Limb Salvage/methods , Male , Muscle, Skeletal/blood supply , Muscle, Skeletal/injuries , Random Allocation , Rats , Rats, Sprague-Dawley , Reperfusion Injury/complications , Reperfusion Injury/prevention & control
10.
Ther Clin Risk Manag ; 4(2): 569-71, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18728831

ABSTRACT

Recent studies suggest that current fluid strategies may result in excessive administration of both fluids and electrolytes. Perioperative fluid administration is dictated by an algorithmic approach, taking account of pre-operative deficit, maintenance requirements, and extrapolated third space losses. Salt and water overload is associated with pulmonary edema, ileus, and delayed wound healing. Within an intensive care population, there is a strong correlation between excessive intravascular volume and subsequent mortality, morbidity, and length of stay. Increasing weight has been shown to correspond with mortality, while achieving a negative balance within the first 72 hours of ITU admission has been postulated as an independent predictor of survival. Should a "restricted" rather than a "liberal" perioperative fluid regimen be employed? It is arguable that prevailing fluid therapy is not evidence-based. Recent observations suggest that restraint in fluid administration correlates with better outcome. The development of a protocol-based fluid optimization program may help minimize the risk of perioperative fluid overload.

11.
World J Surg ; 31(10): 1921-9, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17676377

ABSTRACT

BACKGROUND: The aim of this study was to analyze the factors that influence the advancement and the career choices of doctors and medical students. METHODS: Using the combined databases of the iformix and surgent websites, 450 doctors and medical students were invited to complete an internet-based survey. Surgent (http://www.surgent.ie) and iformix (http://www.iformix.com) are two free internet services administered by the authors. Surgent is a medical educational website, while iformix facilitates the online submission of abstracts to surgical and medical conferences across Britain and Ireland. The combined database of these two websites is approximately 4500 entries. Four hundred and fifty users represented a 10% sample based on an expected 40%-45% response rate. This was anticipated to yield between 180 and 202 respondents, statistically sufficient to analyze the data. A detailed Likert scale assessed the importance of "academic," "clinical," and "lifestyle" factors in determining career choice and progression. Analysis included descriptive statistics and inferential testing. RESULTS: Fifty percent (N = 222) of surveys were returned; 142 men and 78 women. Thirty-seven percent of respondents were Irish, 28% British, and 35% non-European. Fifteen percent were undergraduates, 4% interns, 12% had 2-4 years of clinical experience, while 69% had completed more than 4 years. Fifty-six percent had decided upon a career in general surgery. Overall, the most important factors for career choice were intellectual challenge (95%), academic opportunities (61%), and research opportunities(54%). Doctors with more than 4 years of experience deemed duration of training (p = 0.002), lifestyle during training (p = 0.02), and stress (0.005) as less important factors when considering career choice. Correlation analyses demonstrated that prestige (p = 0.002), patient relationships (p = 0.006), and advice from friends or family (p = 0.01) were more important influencing factors for interns. In terms of career advancement, 66% of non-Europeans considered family contacts important as opposed to 20% of British and 45% of Irish doctors (p < 0.001). In addition, 47% of females felt gender was important for career advancement as opposed to 31% of males (p = 0.01). CONCLUSIONS: Academic and clinical factors play an important role in career choice. However, it is clear that lifestyle factors predominate in determining an individual's career decisions in surgery.


Subject(s)
Career Choice , Career Mobility , General Surgery , Adult , Female , General Surgery/economics , Humans , Income , Ireland , Life Style , Male , Physicians, Women/statistics & numerical data , United Kingdom
12.
J Membr Biol ; 211(1): 35-42, 2006 May.
Article in English | MEDLINE | ID: mdl-16988862

ABSTRACT

Hypertonic saline (HTS) suppresses tumor cell-endothelial interactions by reducing integrin expression. This translates into reduced adhesion, migration and metastatic potential. This study determined the relative contributions of hyperosmolarity and sodium-specific hypertonicity on the inhibitory effects of HTS, the intracellular pH and sodium responses to HTS and the role of cytoskeletal remodeling in these changes. Human colonic tumor cells (LS174T) were exposed to lipopolysaccharide under isotonic, hypertonic, sodium-free (N-methyl-D-glucamine), hyperosmolar (mannitol or urea), disrupted cytoskeletal (10 microg/ml cytochalasin D) conditions or in the presence of 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Beta(1) integrin expression was measured flow-cytometrically. Intracellular sodium and pH were measured with confocal laser microscopic imaging. Statistical analysis was performed with analysis of variance, and P < 0.05 was considered significant. Data are represented as mean +/- SEM. Hypertonic exposure attenuated integrin expression (62.03 +/- 4.7% of control, P < 0.04). No discernible effect was observed with sodium-free or hyperosmolar solutions. HTS evoked a cellular alkalinization (by a mean 0.2 pH units) and an increase in cytosolic sodium concentration (by a mean 12.4 mM, P < 0.001) via upregulation of sodium-hydrogen exchange. Disassembly of actin microfilaments by cytochalasin D and antiporter inhibition with EIPA abrogated the effect of hypertonicity on integrin expression and intracellular sodium and pH (P < 0.05). HTS downregulates adhesion molecule expression via a hypertonic, sodium-specific, cytoskeletally mediated mechanism that involves activation of sodium-hydrogen exchange with associated changes in intracellular pH and sodium concentrations.


Subject(s)
Cell Membrane/metabolism , Colonic Neoplasms/metabolism , Saline Solution, Hypertonic , Sodium/metabolism , Cell Line, Tumor , Humans , Integrin beta1/biosynthesis , Integrin beta1/genetics , Neoplasm Metastasis
14.
Surg Infect (Larchmt) ; 7(6): 501-11, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17233567

ABSTRACT

BACKGROUND: The immunomodulatory potential of nitric oxide provides prospective strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that inhibition of nitric oxide synthase (NOS) reduces end-organ injury in pancreatitis. METHODS: Pancreatitis was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injection of 20% L-arginine (500 mg/100 g of body weight). Animals were randomized into four groups of 45: Pancreatitis without intervention; pre-treatment with i.p. aminoguanidine (AMG) (50 mg/kg), an isoform-specific inhibitor of inducible NOS; post-treatment with AMG (50 mg/kg); and controls. Pancreatic and pulmonary pathology, neutrophil infiltration (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage, wet:dry weight ratio), NOS expression, and concentrations of pro-inflammatory cytokines (tumor necrosis factor-alpha; interleukin-6) were assessed. RESULTS: Inhibition of iNOS significantly reduced end-organ injury. Pancreatic and pulmonary injury scores were markedly attenuated in the AMG treatment groups compared with no intervention (p < 0.05). Increased endothelial permeability (2,411.1 +/- 47.9) and neutrophil sequestration (1.99 +/- 0.01) were manifest in the untreated animals compared with AMG pretreatment (1,286.8 +/- 35.1 and 1,548.0 +/- 0.1; p < 0.05). In addition, a significant reduction in inflammatory cytokine concentrations was observed (p < 0.05). CONCLUSIONS: Inhibition of inducible NOS encourages a more benign immunologic profile, minimizing the deleterious effects of unrestrained neutrophil sequestration subsequent to pancreatitis.


Subject(s)
Lung/pathology , Nitric Oxide Synthase/biosynthesis , Pancreatitis/pathology , Animals , Enzyme Induction , Lung/immunology , Male , Nitric Oxide/metabolism , Pancreas/immunology , Pancreas/pathology , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Pancreatitis/mortality , Rats , Rats, Sprague-Dawley
15.
Hepatobiliary Pancreat Dis Int ; 4(1): 126-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15730936

ABSTRACT

BACKGROUND: The exact mechanism by which cyclooxygenase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreatitis, a disease process characterized by a systemic inflammatory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group): controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung injuries were assessed histologically. Lung injury was assessed utilizing wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancreatic tissue. RESULTS: The animals treated with COX-2 inhibitors displayed significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were significantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significantly attenuates the severity of both pancreatitis and its associated systemic inflammatory response and end-organ injury.


Subject(s)
Cyclooxygenase Inhibitors/pharmacology , Lung Diseases/pathology , Lung Injury , Pancreatitis/pathology , Prostaglandin-Endoperoxide Synthases/drug effects , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Arginine , Biopsy, Needle , Blotting, Western , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Disease Models, Animal , Immunohistochemistry , Lung Diseases/complications , Male , Pancreatitis/complications , Probability , Random Allocation , Rats , Rats, Sprague-Dawley , Reference Values , Risk Factors , Sensitivity and Specificity , Statistics, Nonparametric , Up-Regulation
16.
Surgery ; 136(1): 76-83, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15232542

ABSTRACT

BACKGROUND: Hypertonic saline infusion dampens inflammatory responses and suppresses neutrophil-endothelial interaction by reducing adhesion molecule expression. This study tested the hypothesis that hypertonic saline attenuates tumor cell adhesion to the endothelium through a similar mechanism. METHODS: Human colon cancer cells (LS174T) were transfected with green fluorescent protein and exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 under hypertonic and isotonic conditions for 1 and 4 hours. Confluent human umbilical vein endothelial cells were similarly exposed. Cellular apoptosis and expression of adhesion molecules and laminin were measured by flow cytometry. Tumor cell adhesion to endothelium and laminin was assessed with fluorescence microscopy. Data are represented as mean +/- standard error of mean, and an ANOVA test was performed to gauge statistical significance, with P <.05 considered significant. RESULTS: Hypertonic exposure significantly reduced tumor cell adhesion despite the presence of the perioperative cell stressors (42 +/- 2.9 vs 172.5 +/- 12.4, P <.05), attenuated tumor cell beta-1 integrin (14.43 vs 23.84, P <.05), and endothelial cell laminin expression (22.78 +/- 2.2 vs 33.74 +/- 2.4, P <.05), but did not significantly alter cell viability. CONCLUSION: Hypertonic saline significantly attenuates tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. This may halt the metastatic behavior of tumor cells shed at surgery.


Subject(s)
Cell Adhesion/drug effects , Cell Communication/drug effects , Colonic Neoplasms/physiopathology , Endothelial Cells/drug effects , Saline Solution, Hypertonic/pharmacology , Cell Adhesion Molecules/biosynthesis , Cell Line, Tumor , Humans , Laminin/biosynthesis
17.
Ann Surg ; 238(2): 249-57, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12894019

ABSTRACT

OBJECTIVE: This study sought to determine whether hypertonic saline (HTS) infusion modulates the host response to bacterial challenge. METHODS: Sepsis was induced in 30 Balb-C mice by intraperitoneal injection of Escherichia coli (5 x 107 organisms per animal). In 10 mice, resuscitation was performed at 0 and 24 hours with a 4 mL/kg bolus of HTS (7.5% NaCl), 10 animals received 4 mL/kg of normal saline (0.9% NaCl), and the remaining animals received 30 mL/kg of normal saline. Samples of blood, spleen, and lung were cultured at 8 and 36 hours. Polymorphonucleocytes were incubated in isotonic or hypertonic medium before culture with E. coli. Phagocytosis was assessed by flow cytometry, whereas intracellular bacterial killing was measured after inhibition of phagocytosis with cytochalasin B. Intracellular formation of free radicals was assessed by the molecular probe CM-H(2)DCFDA. Mitogen-activated protein (MAP) kinase p38 and ERK-1 phosphorylation, and nuclear factor kappa B (NFkappaB) activation were determined. Data are represented as means (SEM), and an analysis of variance test was performed to gauge statistical significance. RESULTS: Significantly reduced bacterial culture was observed in the animals resuscitated with HTS when compared with their NS counterparts, in blood (51.8 +/- 4.3 vs. 82.0 +/- 3.3 and 78.4 +/- 4.8, P = 0.005), lung (40.0 +/- 4.1 vs. 93.2 +/- 2.1 and 80.9 +/- 4.7, P = 0.002), and spleen (56.4 +/- 3.8 vs. 85.4 +/- 4.2 and 90.1 +/- 5.9, P = 0.05). Intracellular killing of bacteria increased markedly (P = 0.026) and superoxide generation was enhanced upon exposure to HTS (775.78 +/- 23.6 vs. 696.57 +/- 42.2, P = 0.017) despite inhibition of MAP kinase and NFkappaB activation. CONCLUSIONS: HTS significantly enhances intracellular killing of bacteria while attenuating receptor-mediated activation of proinflammatory cascades.


Subject(s)
Escherichia coli Infections/therapy , Neutrophils/metabolism , Saline Solution, Hypertonic/therapeutic use , Superoxides/metabolism , Analysis of Variance , Animals , Computer Graphics , Disease Models, Animal , Enzyme Activation , Humans , Male , Mice , Mice, Inbred BALB C , Mitogen-Activated Protein Kinase Kinases/metabolism , NF-kappa B/metabolism , Phagocytosis/drug effects , Random Allocation , Survival Analysis
18.
Arch Surg ; 138(1): 9-14, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12511143

ABSTRACT

HYPOTHESIS: Inhibition of neutrophil-endothelial cell interactions by hypertonic saline (HTS) may confer protection against organ injury in states of immunologic disarray. This study tested the hypothesis that infusion of HTS modulates the development of end-organ injury in a model of lower-torso ischemia-reperfusion injury. DESIGN: Ischemia-reperfusion injury was induced in 30 male Sprague-Dawley rats by infrarenal aortic cross-clamp for 30 minutes, followed by reperfusion for 2 hours. At 0 and 60 minutes of reperfusion, intravenous HTS (7.5% sodium chloride, 4 mL/kg) was administered to 6 rats each, and another 12 received either 4 or 30 mL/kg of isotonic sodium chloride solution. Six rats received HTS, 4 mL/kg, before ischemia. At 2 hours, we assessed liver function, pulmonary injury, neutrophil infiltration (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage and wet-dry weight ratios), and proinflammatory cytokine levels (tumor necrosis factor alpha and interleukin 6). RESULTS: Infusion with HTS before or after ischemia significantly reduced end-organ injury. Histopathologic pulmonary injury scores were markedly attenuated in the HTS group (5.82 +/- 1.3) and the HTS pretreated group (4.91 +/- 1.6) compared with the isotonic sodium chloride solution groups (8.54 +/- 1.1) (P =.04). Pulmonary neutrophil sequestration (2.07 +/- 0.23) and increased endothelial permeability (4.68 +/- 0.44) were manifest in animals resuscitated with isotonic sodium chloride solution compared with HTS treatment (1.54 +/- 0.19 [P =.04] and 2.06 +/- 0.26 [P =.02]) and pretreatment (1.18 +/- 0.12 [P =.04] and 1.25 +/- 0.07 [P =.002]). In addition, a significant reduction in serum tumor necrosis factor alpha (P =.04) and interleukin 6 (P =.048) levels was observed, whereas HTS resuscitation attenuated the upsurge in aspartate transaminase (P =.03) and alanine transaminase levels (P =.047). CONCLUSIONS: Resuscitation with HTS attenuates the pulmonary edema and tissue injury due to lower-torso ischemia-reperfusion and maintains a more benign immunologic profile.


Subject(s)
Lung Diseases/immunology , Lung Diseases/prevention & control , Reperfusion Injury/immunology , Reperfusion Injury/prevention & control , Saline Solution, Hypertonic/administration & dosage , Animals , Aorta, Thoracic , Cell Communication/immunology , Constriction , Endothelium/physiopathology , Infusions, Intravenous , Interleukin-6/blood , Interleukin-6/immunology , Liver/physiopathology , Lung Diseases/pathology , Lung Diseases/therapy , Male , Models, Animal , Permeability/drug effects , Peroxidase/analysis , Peroxidase/immunology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/pathology , Reperfusion Injury/therapy , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/immunology
19.
Curr Opin Crit Care ; 8(2): 158-63, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12386518

ABSTRACT

Lung injury is the most pertinent manifestation of extra-abdominal organ dysfunction in pancreatitis. The propensity of this retroperitoneal inflammatory condition to engender a diffuse and life-threatening lung injury is significant. Approximately one third of patients will develop acute lung injury and acute respiratory distress syndrome, which account for 60% of all deaths within the first week. The variability in the clinical course of pancreatitis renders it a vexing entity and makes demonstration of the efficacy of any specific intervention difficult. The distinct pathologic entity of pancreatitis-associated lung injury is reviewed with a focus on etiology and potential therapeutic maneuvers.


Subject(s)
Neutrophils/physiology , Pancreatitis/complications , Respiratory Distress Syndrome/etiology , Cell Adhesion , Humans , Neutrophil Activation , Neutrophils/immunology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/therapy , Signal Transduction
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