Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
1.
N Engl J Med ; 387(25): 2305-2316, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36342173

ABSTRACT

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).


Subject(s)
Chronic Limb-Threatening Ischemia , Limb Salvage , Vascular Surgical Procedures , Humans , Chronic Limb-Threatening Ischemia/surgery , Chronic Limb-Threatening Ischemia/therapy , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Limb Salvage/adverse effects , Limb Salvage/methods , Retrospective Studies , Risk Factors , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/methods , Saphenous Vein/transplantation
2.
Surg Clin North Am ; 98(2): 267-277, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29502771

ABSTRACT

Lower extremity deep venous thrombosis is a leading cause of morbidity and mortality. The mainstay of therapy is medical. However, anticoagulation does not remove the thrombus and restore venous patency. In select patients, early thrombus removal and anticoagulation can restore venous patency, preserve venous valve function, and may reduce the incidence of postthrombotic syndrome. Catheter-directed therapies are minimally invasive with low complication rates. However, in patients with a contraindication to thrombolytic agents who can receive anticoagulation, open thrombectomy should be considered if indications for thrombus removal are met and patients are good operative risks.


Subject(s)
Lower Extremity/blood supply , Thrombectomy/methods , Venous Thrombosis/surgery , Humans , Lower Extremity/surgery , Perioperative Care/methods , Postthrombotic Syndrome/prevention & control , Stents , Thrombectomy/instrumentation , Venous Thrombosis/diagnosis
3.
Ann Vasc Surg ; 42: 32-38, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28341502

ABSTRACT

BACKGROUND: Current guidelines recommend vascular mapping ultrasound (US) prior to arteriovenous fistula creation. Blunted venous waveforms (BVWs) suggest central venous stenosis; however, this relationship and one between BVWs and the presence of a central venous catheter (CVC) remain unclear. METHODS: All patients who received upper extremity vascular mapping US between January 2013 and October 2014 at a single institution were retrospectively reviewed. Patient demographics, comorbidities, US results, pacemaker history, and CVC status were collected. Waveforms were assessed at the proximal subclavian vein/distal axillary vein and interpreted by radiologists. Patients were determined to have central venous stenosis (CVS) if detected by venography within 6 months of US. RESULTS: There were 342 patients, of which 165 (48%) had a current CVC and 29 (8.5%) had BVW of at least 1 arm. Right-sided BVW were associated with a history of a prior ipsilateral CVC (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.6-12.6, P = 0.009). Of the 342 patients, 69 (20%) had a venogram within 6 months. Seventeen (25%) of the 69 patients had CVS, with 7 involving the left subclavian vein, 8 the right subclavian vein, and 3 the superior vena cava (one patient had tandem stenoses). A BVW on the left side was not associated with any CVS. A BVW on the right side was associated with an ipsilateral CVS (OR = 5.8, 95% CI = 1.2-27.4, P = 0.04). This association persisted in the setting of a prior CVC (relative risk = 1.3, 95% CI = 0.9-2, P = 0.01). CONCLUSIONS: There are associations between right-sided BVW and an ipsilateral subclavian vein stenosis. We recommend that hemodialysis access planning includes venography to rule out central vein stenosis in patients with BVW, especially if right-sided and in the setting of a prior CVC.


Subject(s)
Axillary Vein/diagnostic imaging , Subclavian Vein/diagnostic imaging , Ultrasonography, Doppler, Color , Upper Extremity/blood supply , Vascular Diseases/diagnostic imaging , Vascular Patency , Axillary Vein/physiopathology , Blood Flow Velocity , California , Catheterization, Central Venous/adverse effects , Chi-Square Distribution , Constriction, Pathologic , Female , Humans , Male , Middle Aged , Odds Ratio , Phlebography , Predictive Value of Tests , Prognosis , Pulsatile Flow , Regional Blood Flow , Renal Dialysis , Retrospective Studies , Risk Factors , Subclavian Vein/physiopathology , Time Factors , Vascular Diseases/etiology , Vascular Diseases/physiopathology
4.
J Vasc Surg ; 65(2): 444-451, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27986484

ABSTRACT

OBJECTIVE: The autogenous arteriovenous fistula (AVF) has been shown to be superior to the arteriovenous graft (AVG) with respect to cost, complications, and primary patency. Therefore, the National Kidney Foundation Disease Outcomes Quality Initiative guidelines recommend reserving AVGs for patients who do not have adequate superficial venous anatomy to support AVF placement. The brachial artery-brachial vein arteriovenous fistula (BVAVF) has emerged as an autologous last-effort alternative. However, there are limited data comparing BVAVFs and AVGs in patients who are otherwise not candidates for a traditional AVF. METHODS: Patients who received a BVAVF from July 2009 to July 2014 were compared with those who received an AVG during the same period. At our institution, BVAVF and AVG are only performed in patients with poor superficial venous anatomy. Patient demographic data, operative details, and subsequent follow-up were collected. BVAVFs were performed with a two-stage approach, with initial arteriovenous anastomosis, followed by delayed superficialization or transposition. Our primary outcome measure was primary functional assisted patency at 1 year. Patients lost to follow-up were excluded. A subgroup analysis was also performed for patients in whom the BVAVF or the AVG was their first hemodialysis access surgery. RESULTS: During the study period, 29 patients underwent BVAVF and 32 underwent AVG. There were no differences in age, gender, or presence of diabetes between the two groups. The median days to cannulation from the initial operation were 141 (interquartile range, 94-214) in the BVAVF group and 29 (interquartile range, 14-33) in the AVG group (P < .001). Fewer patients required interventions to maintain or re-establish patency in the BVAVF group than in the AVG group (10% v. 44%; P < .01). The 1-year primary patency was greater for BVAVF (62% vs 25%; P < .01); however, there was no difference in the functional assisted primary patency rates at 1 year (45% vs 25%; P = .1). Subgroup analysis demonstrated greater 1-year primary functional assisted primary patency (52% vs 19%; P < .05) in patients without prior access surgery. CONCLUSIONS: The BVAVF is a viable alternative to the AVG in patients with inadequate superficial venous anatomy, especially in access-naïve patients. The decision to perform BVAVF must be weighed against the delay in functional maturation expected compared with AVG.


Subject(s)
Arteriovenous Shunt, Surgical/methods , Blood Vessel Prosthesis Implantation/methods , Brachial Artery/surgery , Renal Dialysis , Upper Extremity/blood supply , Veins/surgery , Aged , Arteriovenous Shunt, Surgical/adverse effects , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Brachial Artery/diagnostic imaging , Brachial Artery/physiopathology , Female , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Graft Occlusion, Vascular/therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Polytetrafluoroethylene , Prosthesis Design , Retreatment , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Patency , Veins/diagnostic imaging , Veins/physiopathology
5.
J Vasc Surg ; 63(6): 1483-95, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26926938

ABSTRACT

OBJECTIVE: Endovascular treatment of ascending aortic lesions has been reported, but to date, no FDA-approved studies have been conducted to define feasibility and the use of endografts in this particular location or to analyze the critical factors involved. METHODS: Patients were consented for entry into an FDA-approved physician-sponsored investigational device exemption study to investigate the outcome of those with ascending aortic pathologies. These patients were suitable according to the instructions for use for endovascular repair with a Valiant Captivia (Medtronic, Inc, Minneapolis, Minn) thoracic stent graft, a device designed specifically for deployment in the ascending aorta. All patients had sequential gated-cardiac computed tomography scans, with data being entered into the VQI Complex TEVAR software (West Lebanon, NH). All procedures were performed in a hybrid room, with the capability to convert to an open repair to ensure maximal patient protection. The first five patients constituted the feasibility study, with continued enrollment based on initial results and submission of an annual report to the FDA. RESULTS: Thirty-nine patients were screened, and six patients were entered into the physician-sponsored investigational device exemption study. Although there was no early mortality, there was one late death. All patients had sequential computed tomographies and cardiac echocardiograms with no evidence of migration, one type 1a endoleak, one postoperative stroke, and regression of the aortic lesions in the excluded aortic segment. CONCLUSIONS: In this feasibility study, the preliminary evaluation of endovascular treatment for ascending aortic pathologies demonstrates uniform accuracy of deployment and secure fixation up to 17.5 months of follow-up. There is positive remodeling of the excluded aortic segments similar to surveillance studies involving the descending aorta.


Subject(s)
Aorta/surgery , Aortic Diseases/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Device Approval , Endovascular Procedures/instrumentation , Stents , United States Food and Drug Administration , Aged , Aged, 80 and over , Aorta/diagnostic imaging , Aortic Diseases/diagnostic imaging , Aortic Diseases/mortality , Aortography/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Cardiac-Gated Imaging Techniques , Computed Tomography Angiography , Echocardiography , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Feasibility Studies , Female , Humans , Male , Middle Aged , Multidetector Computed Tomography , Postoperative Complications/etiology , Prospective Studies , Prosthesis Design , Time Factors , Treatment Outcome , United States
6.
Arch Surg ; 146(4): 427-31, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21502450

ABSTRACT

HYPOTHESIS: Direct inguinal hernia repair with acellular human dermis (AHD) may offer greater symptom improvement and lower risk of hernia recurrence than anatomical repair without mesh (AWM) after mesh removal (with or without neurectomy) for postherniorrhaphy inguinodynia. DESIGN: Retrospective cohort study with long-term follow-up. SETTING: Tertiary referral center for mesh inguinodynia. PATIENTS: Patients undergoing meshectomy (with or without neurectomy) for postherniorrhaphy inguinodynia were identified. Medical records were reviewed, and patients were contacted to evaluate outcomes. Patients whose postmeshectomy hernias were repaired using AHD vs AWM were compared. MAIN OUTCOME MEASURES: Patient satisfaction and recurrence. RESULTS: Sixty-seven patients (35 in the AHD group and 32 in the AWM group) completed the follow-up. Patient demographics, duration and severity of symptoms, and time to meshectomy were similar between groups. The mean length of follow-up was 31.9 months for the AHD group and 80.2 months for the AWM group (P < .001). Fewer neurectomies were performed in the AHD group than in the AWM group (43% [15 of 35] vs 72% [23 of 32], P = .03). Eighty-three percent (29 of 35) of patients in the AHD group reported good or excellent groin pain improvement compared with 72% (23 of 32) of patients in the AWM group (P = .38). Eighty-three percent (29 of 35) of patients in the AHD group were satisfied with results compared with 81% (26 of 32) of patients in the AWM group (P = >.99). The AHD vs AWM procedures were associated with similar recovery, time to hernia recurrence, complication rates (11% [4 of 35] vs 3% [1 of 32], P = .36), and hernia recurrence rates (9% [3 of 35] vs 12% [4 of 32], P = .80). Predictors of patient dissatisfaction with meshectomy included patient smoking (odds ratio, 9.1; P = .01) and filing of workers' compensation claims (odds ratio, 12.8; P = .02). CONCLUSIONS: Meshectomy (with or without neurectomy) for postherniorrhaphy inguinodynia leads to significant symptom improvement and patient satisfaction, with acceptable morbidity and recurrence rates. The use of AHD vs AWM does not improve iatrogenic hernia recurrence.


Subject(s)
Biocompatible Materials/therapeutic use , Dermis , Device Removal , Hernia, Inguinal/surgery , Patient Satisfaction , Surgical Mesh , Adult , Analysis of Variance , Dermis/transplantation , Female , Follow-Up Studies , Hernia, Inguinal/etiology , Hernia, Inguinal/prevention & control , Humans , Male , Middle Aged , Neurosurgical Procedures , Pain, Postoperative/etiology , Pain, Postoperative/surgery , Pelvic Pain/etiology , Pelvic Pain/surgery , Retrospective Studies , Secondary Prevention , Smoking , Surgical Mesh/adverse effects , Surgical Procedures, Operative/adverse effects , Surgical Procedures, Operative/methods , Time Factors , Treatment Outcome , Workers' Compensation
7.
Ann Surg ; 253(2): 287-302, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21135697

ABSTRACT

OBJECTIVE: To examine whether feeding tube placement into high-risk patients using a team-based protocol and electromagnetic tube tracking reduces complications associated with blind tube placement and to evaluate safety of blind tube placement in alert, low-risk patients. BACKGROUND: Approximately 1·2 million feeding tubes with stylets are placed annually in the US. Serious complications during placement exceed the rates of retained sponges and wrong site surgery. Several suggested solutions to the problem have been proposed but none completely eliminate the serious complications and many are neither cost-effective nor practical. METHODS: In a retrospective, single center study, we compared complications after bedside feeding tube placement using a blind technique in 2005 to a hospital protocol mandating tube placement in high-risk patients by a Tube Team in 2007 using electromagnetic tracking. Outcome variables included airway placement, pneumothorax, death, and radiology resource utilization. RESULTS: The Tube Team protocol eliminated airway tube placement (0 of 1154 vs. 20 of 1822, P < 0.001), pneumothorax (0/715 vs. 11/1822, P = 0.009), and all mortality whereas improving placement (83.9% success vs. 60.5%, P<0.001) in high-risk patients compared to the 2005 study. The number of x-rays obtained per tube (1.07 +/− 0.01 vs. 1.49 +/− 0.026, P < 0.001) and need for fluoroscopy (2.1% vs. 10.9%, P < 0.001) significantly dropped with the Tube Team. A final comparison was made to low-risk patients considered acceptable for blind tube placement in 2007 due to their alertness and ability to cooperate and provide feedback during tube placement. Although no mortality occurred during blind placement in low risk, alert patients, blind placement resulted in significantly increased airway placement (3/143, p = 0.001) and pneumothorax (2 of 143, P = 0.01) compared to the Tube Team protocol. Most patients who would have required fluoroscopic placement of feeding tube due to failed blind technique had successful placement by the Team avoiding fluoroscopy. CONCLUSION: Feeding tube placement by a dedicated team using electromagnetic tracking eliminates the morbidity and mortality of this common hospital procedure. Blind placement is not acceptable in awake, alert patients.


Subject(s)
Electromagnetic Phenomena , Enteral Nutrition/methods , Intubation, Gastrointestinal/methods , Patient Care Team , Quality Assurance, Health Care , Enteral Nutrition/adverse effects , Enteral Nutrition/instrumentation , Female , Fluoroscopy , Humans , Intubation, Gastrointestinal/instrumentation , Male , Middle Aged , Pneumothorax/etiology , Radiography, Thoracic
8.
Am J Physiol Gastrointest Liver Physiol ; 299(6): G1222-30, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20864657

ABSTRACT

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived hormone that is a proposed treatment for human short bowel syndrome (SBS). The objective was to determine how the timing, duration, and cessation of GLP-2 administration affect intestinal adaptation and enterocyte kinetics in a rat model of human SBS that results in intestinal failure requiring total parenteral nutrition (TPN). Rats underwent 60% jejunoileal resection plus cecectomy and jugular vein cannulation and were maintained exclusively with TPN for 18 days in these treatments: TPN control (no GLP-2); sustained GLP-2 (1-18 days); early GLP-2 (1-7 days, killed at 7 or 18 days); and delayed GLP-2 (12-18 days). Body weight gain was similar across groups, and plasma bioactive GLP-2 was significantly increased with coinfusion of GLP-2 (100 µg·kg⁻¹·day⁻¹) with TPN. GLP-2-treated rats showed significant increases in duodenum and jejunum mucosal dry mass, protein, DNA, and sucrase activity compared with TPN control. The increased jejunum cellularity reflected significantly decreased apoptosis and increased crypt mitosis and crypt fission due to GLP-2. When GLP-2 infusion stopped at 7 days, these effects were reversed at 18 days. Sustained GLP-2 infusion significantly increased duodenum length and decreased 18-day mortality to 0% from 37.5% deaths in TPN control (P = 0.08). Colon proglucagon expression quantified by real-time RT-qPCR was increased in TPN controls and attenuated by GLP-2 infusion; jejunal expression of the GLP-2 receptor did not differ among groups. In summary, early, sustained GLP-2 infusion reduces mortality, induces crypt fission, and is required for intestinal adaptation, whereas cessation of GLP-2 reverses gains in mucosal cellularity in a rat model of intestinal failure.


Subject(s)
Glucagon-Like Peptide 2/administration & dosage , Glucagon-Like Peptide 2/pharmacology , Parenteral Nutrition, Total , Short Bowel Syndrome/therapy , Animals , Apoptosis , Body Weight/drug effects , Drug Administration Schedule , Enterocytes/cytology , Enterocytes/drug effects , Enterocytes/physiology , Gene Expression Regulation , Intestine, Small/cytology , Intestine, Small/pathology , Male , Mitosis , Proglucagon/genetics , Proglucagon/metabolism , Rats , Rats, Sprague-Dawley
9.
Am J Physiol Gastrointest Liver Physiol ; 299(2): G338-47, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20539007

ABSTRACT

We previously reported that rats receiving total parenteral nutrition (TPN) undergo significant pancreatic atrophy characterized by reduced total protein and digestive enzyme expression due to a lack of intestinal stimulation by nutrients (Baumler MD, Nelson DW, Ney DM, Groblewski GE. Am J Physiol Gastrointest Liver Physiol 292: G857-G866, 2007). Essentially identical results were recently reported in mice fed protein-free diets (Crozier SJ, D'Alecy LG, Ernst SA, Ginsburg LE, Williams JA. Gastroenterology 137: 1093-1101, 2009), provoking the question of whether reductions in pancreatic protein and digestive enzyme expression could be prevented by providing amino acids orally or by intravenous (IV) infusion while maintaining intestinal stimulation with fat and carbohydrate. Controlled studies were conducted in rats with IV catheters including orally fed/saline infusion or TPN-fed control rats compared with rats fed a protein-free diet, oral amino acid, or IV amino acid feeding, all with oral carbohydrate and fat. Interestingly, neither oral nor IV amino acids were sufficient to prevent the pancreatic atrophy seen for TPN controls or protein-free diets. Oral and IV amino acids partially attenuated the 75-90% reductions in pancreatic amylase and trypsinogen expression; however, values remained 50% lower than orally fed control rats. Lipase expression was more modestly reduced by a lack of dietary protein but did respond to IV amino acids. In comparison, chymotrypsinogen expression was induced nearly twofold in TPN animals but was not altered in other experimental groups compared with oral control animals. In contrast to pancreas, protein-free diets had no detectable effects on jejunal mucosal villus height, total mass, protein, DNA, or sucrase activity. These data underscore that, in the rat, intact dietary protein is essential in maintaining pancreatic growth and digestive enzyme adaptation but has surprisingly little effect on small intestinal mucosa.


Subject(s)
Amino Acids/administration & dosage , Dietary Proteins/metabolism , Pancreas/physiopathology , Protein Deficiency/physiopathology , Adaptation, Physiological/drug effects , Administration, Oral , Amylases/metabolism , Animals , Atrophy , Chymotrypsinogen/metabolism , Diet, Protein-Restricted , Growth , Injections, Intravenous , Intestinal Mucosa/drug effects , Intestine, Small/drug effects , Lipase/metabolism , Male , Pancreas/drug effects , Pancreas/pathology , Parenteral Nutrition, Total , Rats , Rats, Sprague-Dawley , Trypsinogen/metabolism
10.
Pancreas ; 39(3): 377-84, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19904225

ABSTRACT

OBJECTIVES: Our aim was to determine if total parenteral nutrition (TPN)-induced pancreatic atrophy and Hsp70 expression attenuates cerulein-induced pancreatitis in rats. METHODS: Rats were randomized to a 7-day course of saline infusion plus a semipurified diet or TPN, with or without an intravenous cerulein injection or vehicle on day 7, and killed 1 or 6 hours after the injection. Based on a pilot study, 1 hour was the primary time point. Pancreatic atrophy was determined by mass, protein, and DNA contents. Pancreatic heat shock protein 70 (Hsp70) expression was measured by Western analysis. Histological examination of the pancreas assessed for edema, inflammation, vacuolization, and apoptosis. Serum amylase activity was measured using the Phadebas assay. Pancreatic trypsinogen activation was measured using a fluorometric substrate assay. RESULTS: The saline-infused rats fed orally gained significantly more weight than TPN rats. The TPN decreased the pancreatic mass and protein content and the protein-DNA ratio and increased the pancreatic DNA content compared with the saline. The TPN increased the pancreatic Hsp70 expression by 91% compared with the saline. The TPN reduced the cerulein-induced pancreatic histological edema, the vacuolization, and the inflammation compared with the saline. The increase in the serum amylase level after cerulein injection was significantly attenuated, and trypsinogen activation was reduced in TPN animals compared with the saline group. CONCLUSIONS: Lack of luminal nutrients with a 7-day course of TPN provides moderate protection against cerulein-induced pancreatitis in rats.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , Pancreatitis/therapy , Parenteral Nutrition, Total , Amylases/blood , Animals , Ceruletide/toxicity , Male , Pancreatitis/chemically induced , Pancreatitis/metabolism , Rats , Rats, Sprague-Dawley , Trypsinogen/metabolism
11.
JPEN J Parenter Enteral Nutr ; 33(6): 629-38; discussion 638-9, 2009.
Article in English | MEDLINE | ID: mdl-19644131

ABSTRACT

BACKGROUND: Bowel resection may lead to short bowel syndrome (SBS), which often requires parenteral nutrition (PN) due to inadequate intestinal adaptation. The objective of this study was to determine the time course of adaptation and proglucagon system responses after bowel resection in a PN-dependent rat model of SBS. METHODS: Rats underwent jugular catheter placement and a 60% jejunoileal resection + cecectomy with jejunoileal anastomosis or transection control surgery. Rats were maintained exclusively with PN and killed at 4 hours to 12 days. A nonsurgical group served as baseline. Bowel growth and digestive capacity were assessed by mucosal mass, protein, DNA, histology, and sucrase activity. Plasma insulin-like growth factor I (IGF-I) and bioactive glucagon-like peptide 2 (GLP-2) were measured by radioimmunoassay. RESULTS: Jejunum cellularity changed significantly over time with resection but not transection, peaking at days 3-4 and declining by day 12. Jejunum sucrase-specific activity decreased significantly with time after resection and transection. Colon crypt depth increased over time with resection but not transection, peaking at days 7-12. Plasma bioactive GLP-2 and colon proglucagon levels peaked from days 4-7 after resection and then approached baseline. Plasma IGF-I increased with resection through day 12. Jejunum and colon GLP-2 receptor RNAs peaked by day 1 and then declined below baseline. CONCLUSIONS: After bowel resection resulting in SBS in the rat, peak proglucagon, plasma GLP-2, and GLP-2 receptor levels are insufficient to promote jejunal adaptation. The colon adapts with resection, expresses proglucagon, and should be preserved when possible in massive intestinal resection.


Subject(s)
Colon/metabolism , Glucagon-Like Peptide 2/metabolism , Jejunum/pathology , Proglucagon/metabolism , Short Bowel Syndrome/metabolism , Animals , Colon/surgery , Glucagon-Like Peptide 2/blood , Glucagon-Like Peptide-2 Receptor , Humans , Insulin-Like Growth Factor I/metabolism , Jejunum/metabolism , Jejunum/surgery , Male , Models, Animal , Parenteral Nutrition , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Glucagon/blood , Short Bowel Syndrome/pathology , Short Bowel Syndrome/physiopathology , Sucrose/metabolism
12.
Surg Clin North Am ; 88(5): 1047-72, vii, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18790154

ABSTRACT

Minimally invasive surgery for colorectal cancer is a burgeoning field of general surgery. Randomized controlled trials have assessed short-term patient-oriented and long-term oncologic outcomes for laparoscopic resection. These trials have demonstrated that the laparoscopic approach is equivalent to open surgery with a shorter hospital stay. Laparoscopic resection also may result in improved short-term patient-oriented outcomes and equivalent oncologic resections versus the open approach. Transanal excision of select rectal cancer using endoscopic microsurgery is promising and robotic-assisted laparoscopic surgery is an emerging modality. The efficacy of minimally invasive treatment for rectal cancer compared with conventional approaches will be clarified further in randomized controlled trials.


Subject(s)
Colectomy , Colorectal Neoplasms/surgery , Laparoscopy , Colectomy/methods , Colonic Neoplasms/surgery , Humans , Minimally Invasive Surgical Procedures , Neoplasm Recurrence, Local , Quality of Life , Rectal Neoplasms/surgery , Robotics
13.
JPEN J Parenter Enteral Nutr ; 32(3): 254-65, 2008.
Article in English | MEDLINE | ID: mdl-18443137

ABSTRACT

BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor expression. METHODS: Rats underwent transection or 70% jejunoileal resection +/- GLP-2 infusion (100 microg/kg body weight/d) and were fed a semipurified diet with continuous infusion of GLP-2 or saline by means of jugular catheter. After 7 days, body weight, mucosal cellularity (dry mass, protein and DNA), crypt-villus height, and crypt cell proliferation (by bromodeoxyuridine staining) were determined. Plasma bioactive GLP-2 (by radioimmunoassay), proglucagon and GLP-2 receptor mRNA expression (by Northern blot and real-time reverse transcriptase quantitative polymerase chain reaction) were measured. GLP-2 receptor was colocalized to neuroendocrine markers by immunohistochemistry. RESULTS: Low-dose exogenous GLP-2 increased mucosal cellularity and crypt-villus height in the duodenum, jejunum, and ileum; enterocyte proliferation in the jejunal crypt; and duodenal and jejunal sucrase segmental activity. Plasma bioactive GLP-2 concentration increased 70% upon resection, with an additional 54% increase upon GLP-2 infusion in resected rats (P < .05). Ileal proglucagon mRNA expression increased with resection, and exogenous ileum GLP-2 failed to blunt this response. Exogenous GLP-2 increased ileum GLP-2 receptor expression 3-fold in resected animals and was colocalized to vasoactive intestinal peptide-positive and endothelial nitric oxide synthase-expressing enteric neurons and serotonin-containing enteroendocrine cells in the jejunum and ileum of resected rats. CONCLUSIONS: Exogenous GLP-2 augments adaptive growth and digestive capacity of the residual small intestine in a rat model of mid-small bowel resection by increasing plasma GLP-2 concentrations and GLP-2 receptor expression without diminishing endogenous proglucagon expression.


Subject(s)
Adaptation, Physiological , Enteral Nutrition , Glucagon-Like Peptide 2/pharmacology , Intestinal Mucosa/drug effects , Proglucagon/metabolism , Receptors, Glucagon/metabolism , Animals , Cell Division/drug effects , Disease Models, Animal , Immunohistochemistry , Intestinal Mucosa/cytology , Intestinal Mucosa/physiology , Intestine, Small/cytology , Intestine, Small/growth & development , Intestine, Small/physiology , Intestine, Small/surgery , Male , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Weight Gain
14.
Am J Physiol Regul Integr Comp Physiol ; 294(4): R1175-84, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18256135

ABSTRACT

Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I mRNA, and ileal proglucagon mRNA. Plasma IGF-I concentration was restored to fed levels with 2 days of ad libitum refeeding but not with 4 days of intravenous or intragastric refeeding. Administration of an inhibitor of endogenous GLP-2 (rat GLP-2 3-33) during ad libitum refeeding partially attenuated mucosal growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas intravenous refeeding had no effect. Intestinal regeneration after 4 days of intragastric or 2 days of ad libitum refeeding was positively associated with increases in plasma concentrations of GLP-2 and jejunal IGF-I mRNA. These data suggest that luminal nutrients stimulate intestinal growth, in part, by increased expression of both GLP-2 and IGF-I.


Subject(s)
Eating , Fasting/blood , Glucagon-Like Peptide 2/metabolism , Ileum/metabolism , Insulin-Like Growth Factor I/metabolism , Jejunum/metabolism , Parenteral Nutrition , Regeneration , Adaptation, Physiological , Animals , Body Weight , Dose-Response Relationship, Drug , Glucagon-Like Peptide 2/antagonists & inhibitors , Glucagon-Like Peptide 2/blood , Glucagon-Like Peptide 2/pharmacology , Ileum/drug effects , Ileum/growth & development , Infusions, Intravenous , Insulin/blood , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor Binding Protein 5/metabolism , Insulin-Like Growth Factor I/genetics , Intestinal Mucosa/growth & development , Intestinal Mucosa/metabolism , Intubation, Gastrointestinal , Jejunum/drug effects , Jejunum/enzymology , Jejunum/growth & development , Male , Nitrogen/metabolism , Peptide Fragments/pharmacology , Proglucagon/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Sodium-Glucose Transporter 1/metabolism , Sucrase/metabolism , Time Factors
15.
J Biol Chem ; 277(29): 26681-8, 2002 Jul 19.
Article in English | MEDLINE | ID: mdl-11997395

ABSTRACT

Sodium channel beta subunits modulate channel kinetic properties and cell surface expression levels and function as cell adhesion molecules. beta 1 and beta 2 participate in homophilic cell adhesion resulting in ankyrin recruitment to cell contact sites. We hypothesized that a tyrosine residue in the cytoplasmic domain of beta 1 may be important for ankyrin recruitment and tested our hypothesis using beta 1 mutants replacing Tyr(181) with alanine (beta 1Y181A), phenylalanine (beta 1Y181F), or glutamate (beta 1Y181E), or a truncated construct deleting all residues beyond Tyr(181) (beta 1L182(STOP)). Ankyrin recruitment was observed in beta 1L182(STOP), showing that residues Ile(166)-Tyr(181) contain the major ankyrin recruiting activity of beta 1. Ankyrin recruitment was abolished in beta 1Y181E, suggesting that tyrosine phosphorylation of beta 1 may inhibit beta 1-ankyrin interactions. Ankyrin(G) and beta 1 associate in rat brain membranes and in transfected cells expressing beta 1 and ankyrin(G) in the absence of sodium channel alpha subunits. beta 1 subunits are recognized by anti-phosphotyrosine antibodies following treatment of these cell lines with fibroblast growth factor. beta 1 and ankryin(G) association is not detectable in cells following treatment with fibroblast growth factor. Ankyrin(G) and beta 1Y181E do not associate even in the absence of fibroblast growth factor treatment. beta 1 subunit-mediated cell adhesion and ankyrin recruitment may contribute to sodium channel placement at nodes of Ranvier. The phosphorylation state of beta 1Y181 may be a critical regulatory step in these developmental processes.


Subject(s)
Ankyrins/metabolism , Sodium Channels/physiology , Amino Acid Sequence , Animals , Cell Adhesion , Cricetinae , Cricetulus , Drosophila , Molecular Sequence Data , Phosphorylation , Protein Conformation , Rabbits , Sodium Channels/chemistry , Structure-Activity Relationship , Transfection , Tyrosine/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...