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ABSTRACT: Laparoscopic lavage has shown promising results in nonfeculent perforated diverticulitis. It is an appealing strategy; it avoids the complications associated with resection. However, there has been some reluctance to widespread uptake because of the scarcity of large-scale studies.
This study investigated national trends in management of perforated diverticulitis.
This retrospective population study used an Irish national database to identify patients acutely admitted with diverticulitis, as defined by the International Classification of Diseases. Demographics, procedures, comorbidities, and outcomes were obtained for the years 1995 to 2008.
The study was conducted in Ireland.
Patients with International Classification of Diseases codes corresponding to diverticulitis who underwent operative intervention were included.
The primary outcome was mortality, and secondary outcomes were length of stay and postoperative complications.
Two thousand four hundred fifty-five patients underwent surgery for diverticulitis, of whom 427 underwent laparoscopic lavage. Patients selected for laparoscopic lavage had lower mortality (4.0% vs 10.4%, p < 0.001), complications (14.1% vs 25.0%, p < 0.001), and length of stay (10 days vs 20 days, p < 0.001) than those requiring laparotomy/resection. Patients older than 65 years were more likely to die (OR 4.1, p < 0.001), as were those with connective tissue disease (OR 7.3, p < 0.05) or chronic kidney disease (OR 8.0, p < 0.001).
This retrospective study is limited by the quality of data obtained and is subject to selection bias. Furthermore, the lack of disease stratification means it is not possible to identify the extent of peritonitis; feculent peritonitis has worse outcomes and is not likely to be included in the lavage group.
The number of patients selected for laparoscopic lavage in perforated diverticulitis is increasing, and the outcomes in this study are comparable to other reports. Those patients in whom laparoscopic lavage alone was suitable had lower mortality and morbidity than those in whom resection was considered necessary.
Diseases of the Colon & Rectum 09/2012; 55(9):932-8. · 3.13 Impact Factor
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ABSTRACT: Zinc is a useful addition to oral rehydration therapy for acute diarrhoea. We have assessed the mechanism of its epithelial antisecretory action when intestinal epithelial tight junctions were pharmacologically opened.
Rat isolated ileal and colonic mucosae were mounted in Ussing chambers and exposed to ZnSO(4) (Zn(2+) ) in the presence of secretagogues and inhibition of short circuit current (I(sc) ) was measured.
Pre-incubation with basolateral but not apical Zn(2+) reduced I(sc) stimulated by forskolin, carbachol and A23187. In the presence of the tight junction-opener, cytochalasin D, antisecretory effects of apically-applied Zn(2+) were enabled in colon and ileum. The apparent permeability coefficient (P(app) ) of Zn(2+) was increased 1.4- and 2.4-fold across rat ileum and colon, respectively, by cytochalasin D. Basolateral addition of Zn(2+) also reduced the I(sc) stimulated by nystatin in rat colon, confirming K channel inhibition. In comparison with other inhibitors, Zn(2+) was a relatively weak blocker of basolateral K(ATP) and K (Ca2+) channels. Exposure of ileum and colon to Zn(2+) for 60 min had minimal effects on epithelial histology.
Antisecretory effects of Zn(2+) on intestinal epithelia arose in part through nonselective blockade of basolateral K channels, which was enabled when tight junctions were open.
The Journal of pharmacy and pharmacology. 05/2012; 64(5):644-53.
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ABSTRACT: Local excision is an alternative to anterior or abdomino-perineal resection in patients with early rectal cancer. In more advanced disease, neo-adjuvant therapy (CRXT) can result in significant disease regression such that local excision may be considered. The primary aim was to assess oncological outcome in patients with T3 rectal cancer treated with CRXT and local excision due to unsuitability for or aversion to anterior resection and stoma. The secondary aim was to examine oncological outcomes in patients treated in a similar way in the published literature.
Between July 2006 and July 2009, patients with rectal cancer staged T3, N0/N1, M0 who were deemed unfit for or who refused anterior resection were offered long-course CRXT. Patients were restaged 8 weeks following completion. If there was a good response (regression grade 2 or 3 clinically and radiologically), full thickness transanal excision was performed. All patients were followed regularly (monthly CT abdomen/pelvis and annual endoscopy) to assess for recurrence of disease. A literature search of PubMed was performed to identify all prospective data available of T3 rectal cancers managed with CRXT and local excision.
Ten patients were treated over 3 years. Six patients had complete pathological response, while four patients had a partial response. The resection margins following local excision were clear in all. There was no local recurrence (median follow-up 24 months, range 9-42 months).
Neo-adjuvant chemoradiotherapy and local excision is an option in patients unfit for or averse to major surgical resection if there is a good response to CRXT.
International Journal of Colorectal Disease 12/2011; 27(6):759-64. · 2.38 Impact Factor
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ABSTRACT: Mast cells are largely found at interfaces between the environment and the internal milieu. Early knowledge of the mast cell suggested a role predominantly associated with allergy and pathologic response to antigens, but more recent research has shown a myriad of functions is likely. Wound healing is a complex process of lysis and reconstitution controlled by a series of cell signalling proteins. Mast cells have been shown to play a significant role in the early inflammatory stage of wound healing and also influence proliferation and tissue remodelling in skin. Emerging work implicates the mast cell as a modulator of intestinal healing particularly following surgical anastomosis. The study of mast cells and wound healing involves the use of cell studies and animal models through the use of mast cell inhibitors, promoters and mast cell deficient rodent strains. This review addresses wound healing in skin and the gastrointestinal tract and specifically identifies data pertaining to the role of the mast cell in the process of cell breakdown, repair and regeneration.
Current pharmaceutical design 11/2011; 17(34):3772-5. · 4.41 Impact Factor
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Annals of surgery 10/2011; 254(4):664. · 7.90 Impact Factor
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Annals of surgery 10/2011; 254(4):668. · 7.90 Impact Factor
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ABSTRACT: Adhesive small-bowel obstruction (SBO) contributes significantly to emergency surgical workload. Laparotomy remains the standard approach. Despite published reports with high success rates and low morbidity, acute SBO is still considered by many a relative contraindication to laparoscopy. Our aim was to review the available literature and define important outcomes such as feasibility, safety, iatrogenic bowel injury, and benefits to patients with acute SBO who are approached laparoscopically.
A systematic literature search was carried out using the Medline database and the search terms "laparoscopy" or "laparoscopic approach" and "bowel obstruction." Only adult studies published in English between 1990 and 2010 were included. Studies were excluded if data specific to outcomes for laparoscopic management of acute SBO could not be extracted.
Twenty-nine studies were identified. A laparoscopic approach was attempted in 2,005 patients with acute SBO. Adhesions were the most common etiology (84.9%). Laparoscopy was completed in 1,284 cases (64%), 6.7% were lap-assisted, and 0.3% were converted to hernia repair. The overall conversion rate to midline laparotomy was 29% (580/2,005). Dense adhesions, bowel resection, unidentified pathology, and iatrogenic injury accounted for the majority of conversions. When the etiology of SBO was a single-band adhesion, the success rate was 73.4%. Morbidity was 14.8% (283/1,906) and mortality was 1.5% (29/1,951). The enterotomy rate was 6.6% (110/1,673). The majority were recognized and converted to laparotomy. Laparoscopy was associated with reduced morbidity and length of stay.
Laparoscopy is a feasible and effective treatment for acute SBO with acceptable morbidity. Further studies are required to determine its impact on recurrent SBO.
Surgical Endoscopy 09/2011; 26(1):12-7. · 4.01 Impact Factor
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ABSTRACT: A variety of approaches are available for division of major vascular structures during laparoscopic colorectal resection. Ultrasonic coagulating shears (UCS), vascular staplers, plastic or titanium clips and electrothermal bipolar vessel sealing (EBVS) are currently available. We report our experience with an EBVS device, LigaSure™ (Covidien AG), used in division of the ileocolic, middle colic and inferior mesenteric arteries during laparoscopic colorectal resection.
We report the immediate outcome of 802 consecutive unselected patients who underwent elective laparoscopic colorectal cancer resection performed with use of the LigaSure™ (5 and 10 mm) at our institution over a 5-year period. Operative procedures included right hemicolectomy (n = 180), left hemicolectomy (n = 96), sigmoid colectomy (n = 347) and anterior resection (n = 179). Data were collected from a prospectively maintained cancer database and operative records. The procedures were performed primarily by three consultant surgeons with an interest in laparoscopic colorectal resection.
Of 802 cases in which the LigaSure™ device was employed to divide major vascular structures, immediate effective vessel sealing was achieved in 99.8% (n = 800). Two patients experienced related adverse events both following division of the inferior mesenteric artery with a 5 mm LigaSure™. Both patients had immediate uncontrolled haemorrhage that required laparotomy.
Use of the LigaSure™ device to seal and divide the major mesenteric vessels during laparoscopic colorectal resection is very effective, with a high success rate of 99.8%. Caution should be exercised in elderly atherosclerotic patients, particularly when using the 5-mm LigaSure™ device.
Techniques in Coloproctology 09/2011; 15(3):285-9. · 1.29 Impact Factor
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ABSTRACT: Studies investigating the activating and inhibitory actions of bioflavonoids on colonic function have yielded conflicting results. At low concentrations, flavonoids may stimulate chloride secretion while at higher concentrations they may have antisecretory actions in the colon. Naringenin (4',5,7-trihydroxyflavanone), found predominantly in citrus fruits, confers a protective effect against colorectal cancer and is purported to modulate secretory function in colonic cell lines. The aim of this study was to investigate the effects of naringenin on ion transport in rat and human colonic mucosae. Naringenin inhibited basal and stimulated chloride secretion in rat and human colonic mucosae mounted in Ussing chambers (IC(50) 330 μMol/L and 360 μMol/L respectively) and did not alter intracellular cAMP generation. Naringenin inhibited chloride secretion in MQAE (N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide) loaded crypts stimulated with forskolin. In BCECF (2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein acetoxymethyl ester) loaded crypts, naringenin caused an intracellular acidification (ΔpH/min=0.05 ± 0.004) which was sensitive to the Na-K-Cl co-transporter (NKCC) inhibitor bumetanide. In addition, the antisecretory effect of naringenin was not inhibited by blockade of barium sensitive basolateral K(+) transporters or by inhibition of Na+/H(+) exchange by amiloride. We propose that the antisecretory action of naringenin is due to inhibition of basolateral NKCC1 in rat and human colon.
European journal of pharmacology 07/2011; 668(1-2):271-7. · 2.59 Impact Factor
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Desmond C Winter
Archives of surgery (Chicago, Ill.: 1960) 07/2011; 146(7):835. · 4.32 Impact Factor
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ABSTRACT: The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.
Clinical Colorectal Cancer 06/2011; 11(1):24-30. · 1.68 Impact Factor
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ABSTRACT: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport.
The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport.
This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion.
We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.
Annals of surgery 05/2011; 254(6):957-63. · 7.90 Impact Factor
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ABSTRACT: Hypoperfusion of the bowel is a risk factor for anastomotic failure. Electrical field stimulation has been shown to improve repair in ischemic tissue, but its influence in hypoperfused colon has not been investigated. The hypothesis of this experimental animal study was that electrical field stimulation improves anastomotic healing in ischemic bowel.
Thirty rats were divided evenly into three groups: control, ischemia/placebo, and ischemia/test group. Ischemia was induced by ligation of the arterial supply to the proximal colon. The watershed area was identified and transected. Field stimulation was achieved by application of negatively charged diethylaminoethyl Sephadex beads in methylcellulose gel to the colonic epithelium prior to anastomosis. The placebo group had methylcellulose gel only applied and control animals had anastomosis only. Anastomotic strength was measured using anastomotic bursting pressure and hydroxyproline content. Systemic effect was investigated via interleukin-6 and vascular endothelial growth factor assay.
The ischemia/electrical field stimulation (EFS) group had significantly increased bursting pressure and hydroxyproline content in comparison with the placebo group (P < 0.001). Serum cytokine levels were unaffected.
Negatively charged EFS improves anastomotic healing in hypoperfused colon without induction of systemic cytokines and has potential as a local treatment in high-risk bowel anastomosis.
International Journal of Colorectal Disease 03/2011; 26(3):339-44. · 2.38 Impact Factor
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ABSTRACT: Mast cell degranulation is an important step in early wound healing in the skin however the role of the mast cell in anastomotic healing is less clear. The aim of this study was to investigate the importance of mast cell degranulation in anastomotic healing and to assess whether a promoter of mast cell degranulation could increase anastomotic healing in poorly perfused bowel.
Fifty Wistar rats were divided into five groups: control, normally perfused bowel with mast cell stabilisation, normally perfused bowel with mast cell degranulation, hypoperfused bowel, and hypoperfused bowel with mast cell degranulation. A colo-colonic anastomosis was formed in each animal. Four d later, following sacrifice, the strength of the anastomosis was assessed in each animal.
Mast cell stabilisation reduced anastomotic healing in normally perfused bowel (P < 0.001). Hypoperfused bowel resulted in reduced anastomotic strength (P < 0.001) however the addition of a mast cell degranulating agent increased healing in hypoperfused bowel to levels comparable with control.
Mast cell degranulation is essential for early anastomotic healing. Healing is reduced in hypoperfused bowel but the administration of a mast cell degranulation agent can compensate for the adverse effects of a poor blood supply on anastomotic healing.
Journal of Surgical Research 11/2010; 164(1):e73-6. · 2.25 Impact Factor
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ABSTRACT: This study aims to describe recent experience with rectal carcinoids in European and North American centers.
While considered indolent, the propensity of carcinoids to metastasize can be significant.
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).
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%.
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.
Annals of surgery 11/2010; 252(5):750-5. · 7.90 Impact Factor
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ABSTRACT: The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.
The lancet oncology 11/2010; 12(5):504-12. · 14.47 Impact Factor
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Archives of surgery (Chicago, Ill.: 1960) 10/2010; 145(10):1023-4; author reply 1024. · 4.32 Impact Factor
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ABSTRACT: Surgical site infection (SSI) is an infection occurring in an incisional wound within 30 days of surgery and significantly effects patient recovery and hospital resources.
This study sought to determine the relationship between preoperative serum albumin and SSI.
A study of 524 patients who underwent gastrointestinal surgery in 4 institutions was performed. Patients were identified using a prospective SSI database and hospital records. Serum albumin was determined preoperatively in all patients. Hypoalbuminemia was defined as albumin <30 mg/dL. Data are presented as median (interquartile range) and a difference between groups was examined using Mann-Whitney U and Fisher exact test and multiple logistic regression analysis.
A total of 105 patients developed a SSI (20%). The median time to the development of SSI was 7 (5-10) days. Having an emergency procedure (P = 0.003), having a procedure over 3 hours in duration (P = 0.047), being American Society of Anaesthetics grade 3 (P = 0.03) and not receiving preoperative antibiotics (P = 0.007) were associated with SSI while having a laparoscopic procedure reduced the likelihood of SSI (P = 0.004). Patients who developed a SSI had a lower preoperative serum albumin (30 [25-34.5] vs. 36 [32-39], P < 0.001). On multivariate analysis, hypoalbuminemia was an independent risk factor for SSI development (relative risk, RR = 5.68, 95% confidence interval: 3.45-9.35, P < 0.001). Albumin <30 mg/dL was associated with an increased rate of deep versus superficial SSI (P = 0.002). The duration of inpatient stay was negatively correlated with preoperative albumin (R = -0.319, P < 0.001).
Hypoalbuminemia is an independent risk factor for the development of SSI following gastrointestinal surgery and is associated with deeper SSI and prolonged inpatient stay.
Annals of surgery 08/2010; 252(2):325-9. · 7.90 Impact Factor
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Annals of surgery 06/2010; 251(6):1190-1; author reply 1191. · 7.90 Impact Factor
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Desmond C Winter
Colorectal Disease 03/2010; 12(3):186-7. · 2.93 Impact Factor
