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Aim: The high incidence of lymphatic and peri-neural invasion in pancreatic cancer results in poor loco-regional control. Radical pancreatico-duodenectomy may achieve better loco-regional control, but is accompanied by increasing morbidity. Our hypothesis was that if intra-operative mapping of pathological lymph nodes (LN) is technically feasible in pancreatic cancer, it would allow for selective radical resection., Methods: In an ethically approved and statistically powered feasibility study of 72 (stopped after 20% enrollment) patients with suspected pancreatic cancer undergoing resection, we injected methylene blue dye peri- and intra-tumorally and studied its progress to identify putative 'sentinel lymph node(s)'. The Kausch-Whipple procedure (or total pancreatectomy, if required) was carried out in addition to radical LN dissection, which was evaluated histopathologically according to the Japanese criteria., Results: Over 18 months, 14/16 patients prospectively recruited underwent lymph node mapping and a mean of 20 (range 11-37) LNs per patient were harvested. Methylene blue dye injection identified blue LN(s) in 4/14 patients, none of which were positive for malignant deposits, whilst 10/14 patients had LN metastases. The commonest stations for LN metastasis were 17A or B (9/10), 8A (2/10) and 6 (3/10). The median survival for the 13 patients with cancer was 22.3 months (IQR: 10.4-30 months)., Conclusion: Sentinel lymph node mapping is not technically feasible in pancreatic cancer.

Background: Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively., Methods: 2 groups of Wistar rats underwent sham and BPD surgery. Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken., Results: Animals in the BPD group had significant reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P<0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham., Conclusions: In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery.

Iatrogenic nerve injuries have been rarely reported following laparoscopic abdominal surgeries. These can be serious complications with the potential for long-term disability. We present a rare case of bilateral sciatic nerve palsy following laparoscopic sleeve gastrectomy on a super-super-obese male with BMI 78.04 kg/m2. The procedure was completed laparoscopically in 7 hours duration, and in spite of adequate precautions, he developed bilateral sciatic nerve palsy. Nerve conduction studies showed denervation of L5/S1 confirming the diagnosis. The patient showed gradual recovery with physiotherapy, and at 18 months follow-up he was mobilizing without any walking aids, with BMI 47.34 kg/m2. Compressive nerve injuries following prolonged laparoscopic operations should be included in the list of procedural complications, especially in morbidly obese patients where the risk is significantly higher.

Endothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a double-blind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m2) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.

We have studied sarin-induced global gene expression patterns at an early time point (2 h: 0.5 x LD50) using Affymetrix Rat Neurobiology U34 chips and male Sprague-Dawley rats. A total of 46 genes showed statistically significant alterations from control levels. Three gene categories contained more of the altered genes than any other groups: ion channel (8 genes) and calcium channel and binding proteins (6 genes). Alterations were also found in the following gene groups: ATPases and ATP-based transporters (4), growth factors (4), G-protein-coupled receptor pathway-related molecules (3), neurotransmission and neurotransmitter transporters (3), cytoskeletal and cell adhesion molecules (2), hormones (2), mitochondria-associated proteins (2), myelin proteins (2), stress-activated molecules (2), cytokine (1), caspase (1), GABAnergic (1), glutamergic (1), immediate early gene (1), prostaglandin (1), transcription factor (1), and tyrosine phosphorylation molecule (1). Persistent alteration of the following genes also were noted: Arrb1, CaMKIIa, CaMKIId, Clcn5, IL-10, c-Kit, and Plp1, suggesting altered GPCR, kinase, channel, and cytokine pathways. Selected genes from the microarray data were further validated using relative RT-PCR. Some of those genes (GFAP, NF-H, CaMKIIa, Calm, and MBP) have been shown by other laboratories and ours, to be involved in the pathogenesis of sarin-induced pathology and organophosphate-induced delayed neurotoxicity (OPIDN). Induction of both proapoptotic (Bcl2l11, Casp6) and antiapoptotic (Bcl-X) genes, besides suppression of p21, suggest complex cell death/protection-related mechanisms operating early on. Principal component analysis (PCA) of the expression data confirmed that the changes in gene expression are a function of sarin exposure, since the control and treatment groups separated clearly. Our model (based on current and previous studies) indicates that both degenerative and regenerative pathways are activated early and contribute to the level of neurodegeneration at a later time, leading to neuro-pathological alterations.

We have studied sarin-induced global gene expression patterns at an early time point (15 min; 0.5xLD50) and a later time point (3 months; 1xLD50) using Affymetrix: Rat Neurobiology U34 chips in male, Sprague-Dawley rats and have identified a total of 65 (early) and 38 (late) genes showing statistically significant alterations from control levels at 15 min and 3 months, respectively. At the early time point, those that are classified as ion channel, cytoskeletal and cell adhesion molecules, in addition to neuropeptides and their receptors predominated over all other groups. The other groups included: cholinergic signaling, calcium channel and binding proteins, transporters, chemokines, GABAnergic, glutamatergic, aspartate, catecholaminergic, nitric oxide synthase, purinergic, and serotonergic signaling molecules. At the late time point, genes that are classified as calcium channel and binding proteins, cytoskeletal and cell adhesion molecules and GABAnergic signaling molecules were most prominent. Seven molecules (Ania-9, Arrb-1, CX-3C, Gabab-1d, Nos-2a, Nrxn-1b, PDE2) were identified that showed altered persistent expression in both time points. Selected genes from each of these time points were further validated using semi quantitative RT-PCR approaches. Some of the genes that were identified in the present study have been shown to be involved in organophosphate-induced neurotoxicity by both other groups as well as ours. Principal component analysis (PCA) of the expression data from both time points was used for comparative analysis of the gene expression, which indicated that the changes in gene expression were a function of dose and time of euthanasia after the treatment. Our model also predicts that besides dose and duration of post-treatment period, age and possibly other factors may be playing important roles in the regulation of pathways, leading to the neurotoxicity.

Background: Bariatric surgery is the most effective treatment for achieving long-term weight loss in morbidly obese patients. This study investigated prospective changes in gut hormones and metabolic indices after Roux-en-Y gastric bypass (RYGB)., Methods: Six patients were seen before, and at 1, 3 and 6 months after operation. Blood was collected after a 12-h fast and at regular intervals after a mixed 420-kcal meal. Hormonal responses were determined, and comparisons between basal levels and areas under the curve were made. Visual analogue scores were used to assess satiety, hunger and nausea., Results: Mean body mass index decreased from 48.3 kg/m(2) before surgery to 36.4 kg/m(2) 6 months after RYGB. This was accompanied by a decrease in fasting leptin (P < 0.001) and insulin (P = 0.021) levels. At 1, 3 and 6 months after operation, progressively increasing peptide YY (P < 0.001), enteroglucagon (P = 0.045) and glucagon-like peptide 1 (P = 0.042) responses were observed. There was no change in fasting ghrelin levels (P = 0.144). Postprandial satiety was significantly increased by 1 month after surgery and this was maintained until the end of the study (P < 0.001)., Conclusion: RYGB resulted in substantial weight loss with enhanced postprandial satiety, a sustained weight plateau, and proportionate reduction in fasting insulin and leptin levels. Lack of the expected increase in appetite and food intake as components of a counter-regulatory response may be explained by gut adaptation and the consequent graded rise in the levels of gut hormones that promote satiety., (Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: To study the effect of bariatric surgery on the entero-hypothalamic endocrine axis of humans and rodents., Background: Bariatric surgery is the most effective obesity treatment as it achieves substantial and sustained weight loss. Glycemic control and enhanced satiation improve before substantial weight loss occurs. Gut peptides, acting both peripherally and centrally, contribute to glycemic control and regulate food intake., Methods: We examined meal-stimulated responses of insulin, ghrelin, peptide YY (PYY), glucagon-like-peptide-1 (GLP-1), and pancreatic polypeptide (PP) in humans and rodents following different bariatric surgical techniques., Results: Compared with lean and obese controls, patients following Roux-en-Y gastric bypass (RYGB) had increased postprandial plasma PYY and GLP-1 favoring enhanced satiety. Furthermore, RYGB patients had early and exaggerated insulin responses, potentially mediating improved glycemic control. None of these effects were observed in patients losing equivalent weight through gastric banding. Leptin, ghrelin, and PP were similar in both the surgical groups. Using a rodent model of jejuno-intestinal bypass (JIB), we showed elevated PYY and GLP-1 in JIB rats compared with sham-operated rats. Moreover, exogenous PYY reduced food intake and blockade of endogenous PYY increased food intake. Thus, higher plasma PYY following JIB may contribute to reduced food intake and contribute to weight loss., Conclusions: Following RYGB and JIB, a pleiotropic endocrine response may contribute to the improved glycemic control, appetite reduction, and long-term changes in body weight.

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans., Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity. A longitudinal study was performed to assess the effect of bariatric surgery induced weight loss on these parameters. 73 healthy subjects across a wide range of body mass were recruited; of these, 8 underwent bariatric surgery (median BMI 52.2 kg/m2, interquartile range 50.355.9). Endothelial dependent vasodilatation was measured using the brachial artery vasodilatory response to forearm hyperemia assessed using highresolution ultrasonography., Results: Obese subjects were characterised by a complex collection of abnormalities, with hypertension, impaired glucose homeostasis, systemic inflammation and reduced FMD. BMI < or =25 kg/m2 (median FMD 9.7%, interquartile range 6.8-12.2), BMI >30 kg/m2 (median FMD 6.7% 4.8-7.5), P=0.01 comparing FMD in lean and obese subjects. A mean reduction in weight of 23.4 (4.6) kg produced an improvement in FMD from 5.3% (3.87.0) to 10.2% (7.6-13.3), P=0.01., Conclusions: Even moderate obesity leads to endothelial dysfunction. In severely obese subjects, FMD is normalized by weight loss. This improvement in FMD is associated with a decline in inflammatory markers, blood pressure and insulin. The improvement in FMD occurred despite patients remaining significantly obese. These results suggest that an integrated approach to improving endothelial function in obese humans may be necessary.

Aim: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients., Methods: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality., Results: The operative mortality in the series was 3.95%. This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Post-operative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117) or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery., Conclusion: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.

Background: Ki-Ras is well studied in its oncogenic form in relation to pancreatic pathologies. However, the individual contribution of each of the wild-type Ras isoforms (Ha-, Ki-, and N-) in pancreatic cells in health and disease is unknown., Methods: Archival formalin-fixed, paraffin-embedded specimens of normal (n = 6) and malignant pancreas (n = 35) were used for immuno-histochemical detection of Ras isoforms using a modified polymer system. In addition, immunogold labelling for Ras isoforms was done for subcellular localisation under electron microscopy., Results: Pancreatic ductal cells expressed Ha-Ras in the cytoplasm, with Ki-Ras in the apical region and N-Ras (50% of cases) in a supranuclear distribution. Pancreatic acinar cells express all three isoforms with some nuclear expression of Ki-Ras and supranuclear expression of N-Ras. Islets show Ki- and Ha-Ras mainly with differential expression of Ha-Ras (beta cells showing less Ha-Ras and more Ki-Ras than alpha cells). Electron microscopy shows that Ha-Ras is mainly localised in the endoplasmic reticulum and Golgi apparatus of the acinar cells with some plasma membrane localisation of Ki-Ras in the ductal cells. There was no change in any of the Ras isoform expression in the ductal or acinar cells in various malignancies studied (Mann-Whitney U test, p > 0.1)., Conclusions: Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state. Understanding this distinct functional distribution patterns in detail is an essential step if mutant Ki-Ras is to be targeted in the pancreas by genetic or molecular therapeutic tools.

Objective: To evaluate the impact of spleen weight on operative and clinical outcome in a series of 108 consecutive laparoscopic splenectomies., Background: Laparoscopic splenectomy as an alternative to open splenectomy for splenomegaly is regarded as controversial., Methods: Patients underwent laparoscopic splenectomy for a range of hematological disorders between November 1992 and February 2000. Multiple linear and logistic regression analysis were used to assess the effect of massive splenomegaly (>1000 g) on perioperative mortality and morbidity, after adjusting for the joint effects of patient age, weight, pre- and postoperative full blood counts, operating time, estimated blood loss, conversion rate, reoperation rate, and duration of hospital stay., Results: Massive splenomegaly was recorded in 27 of 108 (25%) cases. In this group, splenic weight ranged from 1000 to 4750 g (median, 2500 g). Patients with splenic weight >1000 g had a significantly longer median operating time (170 vs. 102 minutes, P < 0.01), conversion rate (5/27 vs. 4/81, P < 0.05), postoperative morbidity (15/27 vs. 4/81, P < 0.01), and median postoperative stay (5 vs. 3 days, P < 0.01). Multivariate analysis found splenic weight to be the most powerful predictor of morbidity (P < 0.01). Patients with splenomegaly (>1000 g) were 14 times likely to have post operative complications. One patient died 3 days after surgery, following a pulmonary embolus (spleen weight 500 g, mortality 1/108, 0.9%)., Conclusions: Laparoscopic splenectomy is feasible in patients with giant spleens. However, it is associated with greater morbidity, and the advantages of minimal access surgery in this subgroup of patients are not so clear.

We carried out a time-course study on the effects of a single intramuscular (i.m.) dose (0.5x LD(50)) of sarin (O-isopropyl methylphosphonofluoridate), also known as nerve agent GB, on the mRNA expression of acetylcholinesterase (AChE) in the brain of male Sprague-Dawley rats. Sarin inactivates the enzyme AChE which is responsible for the breakdown of the neurotransmitter acetylcholine (ACh), leading to its accumulation at ACh receptors and overstimulation of the cholinergic system. Rats were treated with 50 microg/kg of sarin (0.5x LD(50)) in 1 mL saline/kg and terminated at the following time points: 1 and 2 hr and 1, 3, and 7 days post-treatment. Control rats were treated with normal saline. Total RNA was extracted, and northern blots were hybridized with cDNA probes for AChE and 28S RNA (control). Poly-A RNA from both treated and control cortex was used for reverse transcription-polymerase chain reaction (RT-PCR)-based verification of the data from the northern blots. The results obtained indicate that a single (i.m.) dose of sarin (0.5x LD(50)) produced differential induction and persistence of AChE mRNA levels in different regions of the brain. Immediate induction of AChE transcripts was noted in the brainstem (126+/-6%), cortex (149+/-4%), midbrain (153+/-5%), and cerebellum (234+/-2%) at 1 hr. The AChE expression level, however, increased over time and remained elevated after a decline at 1 day in the previously shown more susceptible brainstem. The transcript levels remained elevated at a later time point (3 days) in the midbrain, after a dramatic decline at day 1 (110+/-2%). In the cortex, transcript levels came down to control values by day 1. The cerebellum also showed a decline of the elevated levels observed at 2 hr (275+/-2%) to control values by day 1. RT-PCR analysis of the AChE transcript at 30 min in the cortex showed an induction to 213+/-3% of the control level, confirming the expression pattern obtained by the northern blot data. The immediate induction followed by the complex pattern of the AChE mRNA time-course in the CNS may indicate that the activation of both cholinergic-related and unrelated functions of the gene plays an important role in the pathological manifestations of sarin-induced neurotoxicity.

An incidental finding of pseudomyxoma peritonei is reported in a woman with a 6-month history of postmenopausal bleeding. A transvaginal ultrasound scan revealed a poorly defined echogenic mass in the right iliac fossa above the right ovary and free fluid of mixed echogenicity in the pouch of Douglas. Laparoscopic appendicectomy and aspiration of mucinous fluid was performed without adjuvant chemotherapy. Regular postoperative follow-up scans, which are needed as the disease may have an indolent course, showed no signs of recurrence. The differential diagnosis and management of pseudomyxoma peritonei are discussed.

Objective: To evaluate the accuracy of operative assessment of the condition of the appendix during laparoscopic and open appendicectomy, and to assess whether a normal-looking appendix should be excised routinely during a laparoscopic operation., Design: Prospective study., Setting: District general hospital, UK., Subjects: 387 patients who presented with signs and symptoms of appendicitis and underwent appendicectomy., Intervention: 63 patients (16%) were operated on laparoscopically, of whom 48 were female., Main Outcome Measures: Correlation of operative with histological findings., Results: The positive predictive value of operative assessment was increased during the laparoscopic procedure in both male (94.4% to 100%) and female (78% to 88%) patients. Of 21 female patients whose appendixes looked normal at laparoscopy, 5 had other conditions (appendixes normal on histological examination) and 4 were inflamed., Conclusion: In women of childbearing age a normal-looking appendix should be resected during laparoscopic appendicectomy unless another condition is obviously the cause of the signs and symptoms.

Introduction: Recent studies have highlighted the role of increased internal anal sphincter pressure and decreased anodermal blood flow in the pathogenesis of chronic anal fissures. The duration of the effect of topical 0.2% glyceryl trinitrate (GTN) ointment on anodermal blood flow in fissure and normal areas was investigated in patients with chronic anal fissures., Methods: Six patients with chronic anal fissures in the posterior midline participated in the study. Blood flow measurements were performed on the anoderm using laser Doppler flowmetry before and immediately after the topical application of 0.2% GTN ointment and subsequent readings were taken at 5, 15, 30, 45 and 60 min in all four quadrants., Results: The mean anodermal blood flow in the fissure region is significantly lower than the mean blood flow of the rest of the anoderm before 0.2% GTN ointment is applied (228.7 +/- 61.8 flux units vs 439.3 +/- 25.5 flux units, respectively; P < 0.05). Immediately after the application of local 0.2% GTN ointment there is a significant increase in anodermal blood flow over the anal fissure region (457.8 +/- 56.5 flux units; P < 0.05) compared to the rest of the anoderm (457.4 +/- 30.8 flux units). This increase is most marked at 5 min post-GTN ointment application in the fissure area (474.6 +/- 41.1 flux units) and the blood flow in the fissure region is consistently above the rest of the anoderm for most of the 60 min., Conclusion: There is clearly reduced blood flow to the chronic anal fissure region compared to the rest of the anoderm. Topical application of glyceryl trinitrate ointment seems to significantly improve the blood flow to the fissured area in the first hour. This may therefore help in the healing of chronic anal fissures.

A novel technique to retrieve spilled gallstones in an abscess cavity with the use of minimally invasive techniques is described.

Objectives: ischaemia of the colon is an important complication of abdominal aortic aneurysm (AAA) repair. The aim of this animal study was to investigate the effect of sequential ischaemia and reperfusion on sigmoid mucosal pO2 and its association with local ET-1 release., Material and Methods: twelve pigs underwent colonic ischaemia followed by complete reperfusion. Six other animals were sham controls. A Clark-type microcatheter was used for continuous mucosal pO2 measurements. Serial systemic and inferior mesenteric vein blood samples were obtained for determination of ET-1 concentration. Neutrophil extravasation was assessed by tissue myeloperoxidase (MPO) activity., Results: arterial occlusion was associated with a gradual decrease of mucosal pO2 and local release of ET-1. After restoration of blood flow, mucosal pO2 returned to near baseline values, whereas ET-1 reached its maximum concentration during the reperfusion period. MPO activity was significantly increased., Conclusions: colonic ischaemia and reperfusion causes neutrophil extravasation and local ET-1., (Copyright 2001 Harcourt Publishers Limited.)

With the increase of long-term survivors following renal transplantation, aorto-iliac aneurysms requiring surgical management may be encountered more often. Our experience with temporary shunts for renal transplant protection during aorto-iliac aneurysm repair is presented along with a literature review of all cases on the subject. Three male patients with a median age of 56 (range 50-61) years were operated on for a dissecting aneurysm of the common iliac artery in one, respectively abdominal aortic aneurysm in the two remaining patients. All patients had impaired transplant function preoperatively with a median serum creatinine level of 167 (range 134-202) micromol/L and a median blood urea nitrogen concentration of 15 (range 9-23) pmol/L. The intra- and postoperative course was uneventful in all patients. Median postoperative serum creatinine level and blood urea nitrogen concentration were 135 (range 123-151) micromol/L and 10 (range 9-11) pmol/L, respectively. Aorto-iliac surgery in renal transplant recipients can be performed without transplant protection. However, in patients with a deteriorated transplant function or if a prolonged aortic cross-clamp time is anticipated, renal allograft protection measures may be beneficial to prevent possible ischemic damage.

Purpose: Arterial thromboembolism in patients with an unknown source of embolization is still associated with significant morbidity and mortality. The advent of transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) and the more frequent use of computed tomography (CT) have led to the identification of mural aortic thrombi (MAT) as a source of distal embolization in a much higher proportion of patients than previously appreciated. The incidence, diagnosis, and treatment of patients with MAT is reported., Methods: In a prospective study, from January 1996 to December 1998, 89 patients with acute embolic events underwent an extensive diagnostic workup, consisting of TEE, CT, or MRI, to detect the source of embolization. Patients in whom the heart (n = 51), occlusive aortoiliac disease (n = 16), or aortic aneurysms (n = 12) was identified as the source of embolization were excluded., Results: Five female and three male patients, with a median age of 63 years (range, 35 to 76 years), with bilateral or repetitive embolic events resulting from MAT were identified, representing 9% of all patients with arterial thrombembolism. All patients had several risk factors for atherosclerosis, but only one young patient had a single risk factor that promoted thrombosis. Successful percutaneous catheter aspiration embolectomy was performed in six patients. The remaining two patients underwent surgical thromboembolectomy. A below-knee amputation had to be performed in two patients, thus representing a morbidity of the primary treatment of 25%. MAT of equal value were detected in the ascending (n = 1) and thoracic aorta (n = 3) by means of TEE, CT, or MRI. MAT in the abdominal aorta (n = 4) were identified by means of CT and MRI. Surgical removal of MAT was performed in seven patients by means of graft replacement of the ascending aorta (n = 1), open thrombectomy of the descending aorta (n = 2), and thrombendarterectomy of the abdominal aorta (n = 4), without intraoperative or postoperative complications. No recurrence of MAT occurred during a median follow-up period of 13 months (range, 4 to 24 months)., Conclusion: MAT represent an important source of arterial thrombembolism. A diagnostic workup of the aorta, preferably by means of CT or MRI, should be performed in all patients in whom other sources of embolization have been ruled out. The ideal therapeutic approach to these patients still awaits prospective evaluation. However, based on our experience, MAT can be successfully treated with a definitive surgical procedure in selected patients, with low mortality and morbidity.

Objective: To study the relation between fibrosis, pancreatic blood flow (PMBF), interstitial pH (pHi), and the effects of pancreaticojejunostomy (PJ) in chronic pancreatitis., Background: Chronic pancreatitis is associated with low PMBF and pHi, suggesting the existence of underlying ischemia., Methods: In cats, the main pancreatic duct was partially obstructed and the animals were studied 2, 4, 6, and 8 weeks later. PJ was performed after 2 and 4 weeks of ductal obstruction and studied 4 weeks later. PMBF and pH were measured before and after stimulation with secretin and cholecystokinin. pHi was measured with microelectrodes, PMBF by hydrogen gas clearance. Histologic analysis of the pancreas with Sirius red (collagen stain) and fast green FCF (noncollagen protein) stains allowed semiquantitative analysis of the ratio between collagen and total protein (C/TP)., Results: With the evolution of chronic pancreatitis, there is a progressive increase in the collagen content and C/TP ratio, a reduction in basal PMBF and pHi, and loss of the normal response to stimulation. Early PJ restores collagen content, C/TP ratio, and basal and stimulated PMBF and pHi to normal. PJ performed in established CP returns the C/TP ratio to normal, improves basal PMBF, and restores the normal hyperemic response to secretion. Basal pHi is improved and the "acid tide" associated with secretin returns, but there is still no response to cholecystokinin., Conclusions: Pancreaticojejunostomy restores the elevated collagen and C/TP ratio to normal and reverses the ischemia present in CP. The authors speculate that restoration of PMBF and its normal response to stimulation allows "regeneration" and restoration of secretory function.

Background: Combined vascular and skeletal injuries are associated with a high limb loss rate. One of the major factors resulting in amputation is frequently because the allowable warm ischemia time for skeletal muscle is exceeded before adequate revascularization., Methods: Temporary vascular shunting has been used in selected patients with complete ischemia to minimize the ischemic time of the injured limb, allowing identification of vital structures, thorough debridement, and rigid internal fixation before definitive vascular repair., Results: Five male and two female patients with a median age of 46 years (range, 27-76 years) admitted with combined orthopedic and vascular injuries of the upper limbs in four and the lower limbs in three patients underwent primary vascular shunting. The median ischemic time for all patients was 180 minutes (range, 120-210 minutes). Shunt insertion was accomplished in all cases within 30 minutes. Median dwell time for the shunt was 185 minutes (range, 90-390 minutes). No shunt-related complications or limb loss occurred. During follow-up ranging from 2 to 24 months, all vascular repairs remained patent. All fractures healed primarily, except for one patient in whom a necrosis of the humeral head occurred. Five patients had an excellent and two patients a good result., Conclusion: Initial temporary vascular shunting in selected patients with combined skeletal and vascular injury of the upper or lower limb may reduce the complications resulting from prolonged ischemia and permits an unhurried and reasonable sequence of treatment.

Acute hemorrhage in the course of chronic pancreatitis is the most serious and challenging complication, and its treatment has been the subject of controversy for years. We relate our experience in the management of this complication by superselective microcoil embolization. Five patients with acute hemorrhage resulting from chronic pancreatitis between 1994 and 1997 were included in this study. All patients were men with a median age of 44 years (range, 29-59 years). The bleeding occurred into a pseudocyst in all patients, with the splenic artery as feeding vessel. In all instances, the bleeding was successfully controlled by superselective microcoil embolization. Two patients underwent subsequent uneventful elective pseudocystojejunostomy. There was no mortality or morbidity, and no rebleeding occurred during a median follow-up of 22 months (range, 8-36 months). In appropriate patients, diagnostic angiography and superselective microcoil embolization may obviate the need for emergency surgery and should be considered as treatment alternative.

Background: The mechanism by which duct decompression (DD) relieves pain in patients with chronic pancreatitis (CP) is unknown. CP is associated with increased tissue pressure (IP), low pancreatic microvascular blood flow (PMBF), and interstitial pH (pH(I)). The aims of this study were to examine the effects of acute DD on PMBF, increased IP, and pH(I) in cats with CP., Methods: The main pancreatic duct was partially obstructed. At 6 weeks PMBF (ml/min/100g H2 gas clearance), IP (mmHg needle electrode), and pH(I) (microelectrode) were measured before and after secretin stimulation. The duct was then opened, and the studies were repeated., Results: PMBF normally increased with secretin stimulation (118 +/- 20 versus 271 +/- 52, P < 0.05). IP was unaltered, and pH(I) decreased as hydrogen ions produced during bicarbonate secretion were dissipated (7.41 +/- 0.01 versus 7.38 +/- 0.01, P < 0.05). In CP, basal PMBF was lower than normal (51 +/- 6 versus 118 +/- 20, P < 0.05) and decreased with stimulation (51 +/- 3.5 versus 31 +/- 3.5, P < 0.05). Basal pancreatic IP was increased (3.47 +/- 0.7 versus 0.05 +/- 0.3, P < 0.05) and increased further with secretory stimulation (3.47 +/- 0.7 versus 4.41 +/- 0.7, P < 0.05) (a compartment syndrome). The low basal pancreatic pH(I) (7.23 +/- 0.02) did not change with secretin stimulation, since bicarbonate secretion was minimal. DD decreased IP (3.66 +/- 0.5 versus 2.81 +/- 0.5, P < 0.05) and increased PMBF (50 +/- 6 versus 79 +/- 6, P < 0.05) and pH(I) (7.24 +/- 0.02 versus 7.34 +/- 0.02, P < 0.05). The normal increase in PMBF after stimulation was restored (79 +/- 6 versus 218 +/- 54, P < 0.05). pH(I) now increased with stimulation (7.34 +/- 0.002 versus 7.37 +/- 0.002, P < 0.05), perhaps due to the marked hyperaemic response., Conclusions: DD acutely restored basal and stimulated PMBF and IP towards normal. Basal pancreatic pH(I) also improved and reflects the underlying ischaemia.

Ethanol is a common cause of both acute and chronic pancreatitis. Studies in other organs suggest that polymorphonuclear neutrophils activated by ethanol may cause tissue injury in a variety of conditions. The aim of this study was to investigate the effects of ethanol on neutrophil extravasation in the feline pancreas. Pancreata were isolated and perfused at different flow rates with varying concentrations of ethanol in either a physiological or neutrophil depleted perfusate. Neutrophil extravasation was assessed by measuring pancreatic tissue myeloperoxidase (MPO) activity. Ethanol at 2.5% (54.25 mmol/liter) was the lowest concentration that still caused significant neutrophil extravasation (3.1+/-0.8 vs 1.9+/-0.2 units, P<0.05) and was accompanied by an increase in vascular resistance of 15%. Reduction of pancreatic perfusion by 15% did not significantly increase neutrophil extravasation. (1.1+/-0.3 vs 1.6+/-0.2 units, NS) Perfusion of the pancreas with neutrophil-depleted blood containing either ethanol or saline, followed by perfusion with an ethanol-free perfusate, showed an increase in neutrophil extravasation in the ethanol group compared to the control group (3.2+/-0.9 vs 1.9+/-0.2 units, P<0.05). In conclusion, ethanol causes neutrophil extravasation in the feline pancreas independent of blood flow changes and occurs despite the absence of direct neutrophil exposure to ethanol.

Laparoscopic cholecystectomy is considered as the new gold standard operation for removal of the gallbladder, and has several advantages over the traditional open cholecystectomy. However, in the last few years there is an increasing number of case reports of port site metastases following laparoscopic cholecystectomy for unsuspected carcinoma of the gallbladder. Two case reports of trocar site metastases are presented, and they further highlight the concern of the role of minimal invasive surgery in the presence of unsuspected carcinoma of the gallbladder. In this review we speculate on the mechanisms which may be responsible for metastatic deposits during laparoscopic cholecystectomy and suggest certain recommendations.

Background: In humans with chronic pancreatitis (CP), pancreatic interstitial pressure (IP) is elevated and pancreatic blood flow (PBF) is reduced. The efficacy of surgical decompression (SD) of the pancreatic duct (ie, pancreaticojejunostomy) is believed to be due to its ability to decrease IP and pancreatic vascular resistance (Rp), which increases PBF. Pancreatic duct stenting (STE) also probably reduces IP and Rp, which may explain its efficacy. The purpose of this study was to compare the efficacy of SD with STE., Methods: CP in cats was created by narrowing the main pancreatic duct. Six weeks later, CP and normal pancreata were isolated and perfused ex vivo under basal conditions and after secretin stimulation. In normal and CP glands, IP and perfusion pressure were measured and Rp (U) was calculated. In two additional groups, the pancreatic duct was decompressed, either by stenting or by complete transection of the duct with a longitudinal capsulotomy., Results: In CP glands, IP and Rp were increased and secretory output was markedly reduced compared with the normal (0.65 +/- 0.30 mm Hg and 0.46 +/- 0.04 U vs 3.90 +/- 0.80 mm Hg and 1.68 +/- 0.05 U; P < .05). Secretin administration (2 units) increased IP and Rp in CP glands (6.60 +/- 1.10 mm Hg and 2.87 +/- 0.07 U; P < .05), but these values did not chang in normal glands (0.81 +/- 0.20 and 0.53 +/- 0.03 U; NS). STE and SD decreased IP and Rp in CP glands (2.20 +/- 0.20 to 1.0 +/- 0.40 mm Hg and 1.20 +/- 0.015 to 0.90 +/- 0.01 U, respectively; P < .05). Both methods prevented an increase of IP and Rp after secretin administration. IP and Rp decreased to a greater degree following SD, compared with STE (P < .05)., Conclusions: Both STE and SD decreased IP and Rp in this experimental model of CP. However, SD was significantly more effective than STE.

Background: Only a few isolated case reports of extrahepatic pseudoaneurysms of the hepatic arteries have been published. We present the first documented series of patients with extrahepatic pseudoaneurysms treated at a single institution, and discuss the etiology and management of this condition., Study Design: A retrospective review of all cases of extrahepatic pseudoaneurysms of the hepatic arteries between 1989 and 1997., Results: A total of seven patients with extrahepatic pseudoaneurysms of the hepatic arteries all had upper abdominal pain; five patients were also in shock secondary to a gastrointestinal bleeding from ruptured pseudoaneurysms. The most common factor of the pseudoaneurysms was previous pancreatobiliary surgery in five patients with blunt truncal trauma and chronic pancreatitis in the remaining two patients. Initial endoscopy and ultrasonography were unrevealing, whereas dynamic computed tomography (CT) scan and angiography were diagnostic. The median size of the pseudoaneurysms was 3.6 cm (range 2.1-5.7). Treatment consisted of superselective transcatheter microcoil embolization in five hemodynamically unstable patients and surgical resection of the pseudoaneurysms with vascular reconstruction in the two stable patients. Mortality and morbidity were 0% and 43%, respectively. In a median followup of 35 months (range 2-96), no recurrence of pseudoaneurysm has been found., Conclusions: A high index of suspicion combined with appropriate diagnostic modalities are required for the diagnosis of extrahepatic pseudoaneurysms. In high-risk patients, superselective transcatheter microcoil embolization should be considered the treatment of choice.

Tophaceous gout is commonly encountered and is amenable to effective medical management. A rare case of tophaceous gout in a tripartite medial sesamoid bone of the great toe is presented. Clinical presentation, differential diagnosis, and treatment of hallucal sesamoid pain are discussed.

Objective: The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis., Background: Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia., Methods: In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively., Results: In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05)., Conclusions: This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

A very large number of therapeutic trials of antidepressant drugs have been reported in the scientific literature. Until now, the comparison of one drug with another, or with placebo, has been performed typically by comparing the scores on depression rating scales of the two groups of patients at fixed points of time after the beginning of therapy. It was postulated in 1989 that the curves of the recovery scores followed an exponential curve of the formula y = ae-bx + c. This hypothesis was tested in a double-blind controlled trial of the antidepressant minaprine, with the use of the scores on the Hamilton Rating Scale for Depression (HAM-D). We found that the correlation coefficient, Pearson's r, between the log of the HAM-D value and the week number of the study was -0.99. This gives a coefficient of determination of 0.98, which makes it clear that the model adequately fits the data. We conclude that the use of the formula gives a method of testing the statistical significance of the difference between treatments as a valuable alternative to traditional tests. We believe that this would give a much more sensitive discrimination between treatments because all of the data points are used to calculate a single parameter--the slope of the curve.

Background: Although laparoscopy reveals undetected metastases in many patients with pancreatic cancer, most surgeons have chosen to proceed directly with laparotomy in an attempt at resection or for palliation of biliary and gastric outlet obstruction. In an effort to overcome this limitation, this study attempted to determine the feasibility of laparoscopic cholecystojejunostomy and gastrojejunostomy., Methods: Under general anesthesia, seven pigs underwent laparoscopic cholecystojejunostomy and gastrojejunostomy using either a hand-sutured or the stapled/sutured technique., Results: Mean operating time was less with the stapled/sutured vs hand-sutured technique (150 +/- 21 vs 230 +/- 13 min, P < 0.05). All animals recovered completely and there was no change in their weight or liver function tests as a result of the procedure. At sacrifice, all anastomoses were patent, although some were significantly narrowed in these unobstructed animals., Conclusions: These results suggest that simultaneous laparoscopic palliation of biliary and gastric outlet obstruction is feasible. We believe these results warrant further study in the clinical setting.

Priapism, a rare, potentially dangerous but largely preventable condition, remains associated with the use of drugs, many of which are of the psychotropic variety. This article reviews various aspects of this condition, with a view to increasing awareness and understanding of the condition among clinicians.

We report a case of post-traumatic osteolysis of the distal clavicle of a 25-year-old man. The diagnosis was missed for several months, and the patient continued to have pain in his right shoulder. The pain continued in spite of intensive physiotherapy. When he was seen for the first time in our clinic 6 months after the accident, the radiographs showed an osteolysis of the distal clavicle.

Background & Aims: Advanced chronic pancreatitis is associated with a reduction in pancreatic blood flow. To determine the physiological significance of this decrease, pancreatic interstitial pH was measured in a model of obstructive chronic pancreatitis in cats and in patients with chronic pancreatitis., Methods: In cats, pancreatic interstitial pH and blood flow were measured serially under basal conditions and after secretory stimulation as chronic pancreatitis evolved. Basal pancreatic interstitial pH was also measured in patients undergoing an operation for chronic pancreatitis or periampullary cancer (controls)., Results: In normal cats, pancreatic interstitial pH was 7.41 +/- 0.01 and blood flow was 124 mL.min-1.(100 g pancreas-1). With the evolution of chronic pancreatitis, interstitial pH and blood flow progressively decreased to 7.21 +/- 0.04 (P < 0.007) and 75 +/- 11 (P < 0.007), respectively. From 1 to 2 weeks, secretory stimulation reduced pancreatic interstitial pH and blood flow further, but as secretory function was lost, this effect disappeared. In patients with chronic pancreatitis, the interstitial pH was lower (7.02 +/- 0.06) than in controls (7.25 +/- 0.04; P < 0.05)., Conclusions: These observations are consistent with the hypothesis that, in chronic pancreatitis, acidic metabolites associated with pancreatic secretion accumulate within the pancreas, probably because of impaired blood flow.

Objective: To compare the short- and long-term morbidity and mortality rates of the standard Whipple pancreatoduodenectomy (SW) and its pylorus-preserving modification (PPW) in patients with malignant periampullary disease., Design: Retrospective medical record review and quality of life assessment by telephone interview., Setting: University medical center., Study Participants: Sixty-seven patients who underwent pancreatoduodenectomy (52 SW and 15 PPW) from June 1988 to January 1994., Intervention: The SW and PPW., Main Outcome Measures: Operative features and short- and long-term complications were analyzed with respect to the type and stage of cancer and the kind of pancreatic resection. Mean follow-up was 32 months (range, 1 to 5 years)., Results: The operative mortality rate for all patients who had a pancreatic resection was 1.5%. The diagnoses in the PPW vs SW groups were pancreatic cancer (four vs 27 patients), ampullary cancer (six vs seven patients), duodenal cancer (zero vs six patients), and bile duct cancer (five vs one patient). Operative mortality rates (0% vs 1.55%) and operative times (2 minutes longer for SW) were similar. Delayed gastric emptying (61% vs 41%) was more common in the PPW group, resulting in a longer hospitalization (24 vs 18 days) and a greater cost in the PPW group (P = .04). In the PPW group, a mean of five lymph nodes was removed compared with 10 in the SW group (P = .04)., Conclusions: The data provided no evidence of any advantage for the PPW in patients with malignant periampullary tumors. We continue to advocate the SW for pancreatic cancer.

Background/aims: Recent studies have suggested that, in the gastrointestinal tract, nitric oxide is an important mediator of alterations in blood flow and, in some organs, a second messenger involved in secretion. This study examined the role of NO in changes in pancreatic blood flow associated with basal and stimulated pancreatic exocrine secretion., Methods: In anesthetized cats, we determined the effects of the NO synthase inhibitor NG-monomethyl-L-arginine (10 mg/kg) and the NO donor sodium nitroprusside (10 micrograms.kg-1.min-1) on pancreatic secretion and blood flow (hydrogen gas clearance)., Results: NG-monomethyl-L-arginine had no effect on the increase in blood flow associated with secretin stimulation (271 +/- 52 vs. 290 +/- 50 mL.min-1.100 g-1) but reduced that associated with cholecystokinin stimulation (189 +/- 17 vs. 53 +/- 15 mL.min-1.100 g-1; P < 0.001). In contrast, NG-monomethyl-L-arginine significantly reduced both secretin- and cholecystokinin-stimulated secretion. Sodium nitroprusside had no effect on basal blood flow but significantly increased secretion., Conclusions: NO has a selective role in mediating changes in pancreatic perfusion and secretion. It seems to be important in stimulus-secretion coupling with both secretin and cholecystokinin but is only responsible for the accompanying increase in pancreatic blood flow with cholecystokinin.