Gino T. P. Saccone

Prospective trial of pelvic floor retraining in patients with fecal incontinence

PURPOSE: Our aim was to prospectively evaluate pelvic floor retraining (PFR) in improving symptomatic fecal incontinence. METHODS: PFR was used to treat 30 patients with fecal incontinence (28 women; age range, 29–85 (median, 68) years). PFR was performed by a physiotherapist in the outpatient department according to a strict protocol and included biofeedback using an anal plug electromyometer. Manometry (24 patients), pudendal nerve terminal motor latency (PNTML, 16 patients), and anal ultrasound (14 patients) were done before commencing therapy. Independent assessment of symptoms was done at the commencement of therapy, at 6 weeks, and at 6 and 12 months posttherapy. RESULTS: Twenty patients (67 percent) had improved incontinence scores, with eight patients (27 percent) being completely or nearly free of symptoms. Of 28 patients followed up longer than six months, 14 achieved a 25 percent or greater improvement at six weeks, which was sustained in all cases. Fourteen had an initial improvement of less than 25 percent, with only four (29 percent) showing later improvement (P<0.0001). There was no relationship between results of the therapy and patient age, initial severity of symptoms, etiology of incontinence, and results of anal manometry, PNTML, and anal ultrasound. CONCLUSIONS: PFR is a physical therapy that should be considered as the initial treatment in patients with fecal incontinence. An improvement can be expected in up to 67 percent of patients. Initial good results can predict overall outcome.

Endosonographic imaging of anal sphincter injury: does the size of the tear correlate with the degree of dysfunction?

AbstractPURPOSE: This study was designed to test the hypothesis that the extent of anal sphincter muscle injury as graded at endosonography correlates with the degree of functional impairment. METHODS: Three hundred and thirty adults presenting for evaluation of fecal incontinence were recruited. Ultrasound was performed with a 7.5-MHz radial rotating axial endoprobe in the left lateral position. Anal sphincter muscle tears were graded on the basis of the degree of circumferential involvement (< or >25 percent) and by an assessment of the superoinferior longitudinal extent of an external anal sphincter tear. Muscles that demonstrated multiple tears, poor visualization, or fragmentation were classed as fragmented. Sphincter injuries were correlated with basal and squeeze pressures at manometry, pudendal nerve terminal latencies, and the severity of symptoms using the Parks-Browning clinical score. RESULTS: Patients with an intact external anal sphincter had a higher squeeze pressure (mean, 162.6 cm H2O) than those with a partial- (mean, 125.7 cm H2O) or full-length tear (mean, 124.9 cm H2O; P < 0.0001). There was no significant difference in squeeze pressure between those with partial- vs. full-length external anal sphincter tears nor between circumference tears < or >25 percent. Basal pressure was significantly lower in those with a full-length external anal sphincter tear (47.8 cm H2O) vs. an intact external anal sphincter (65.7 cm H2O; P < 0.001). The basal pressure in those with an intact internal anal sphincter was not significantly different from those with clearly defined internal anal sphincter tears, and the degree of circumferential involvement was also not important in this regard. However, those with a fragmented internal anal sphincter had a significantly lower basal pressure than other subgroups of internal anal sphincter injuries (P < 0.001). There was no association between external or internal anal sphincter status and the mean pudendal nerve terminal motor latency, suggesting the patient groups were neurologically similar. There was no significant association between external or internal anal sphincter status and the severity of reported symptoms. CONCLUSION: Correlations between the presence or absence of muscle tears and reduced manometric function have been identified. Further grading of tears was of less importance. No relationship between muscle injuries and the severity of clinical symptoms could be elicited.

The islet-acinar axis of the pancreas: more than just insulin

Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding. The interrelationship between the endocrine and exocrine pancreas is mediated by islet-derived hormones such as insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and also neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) released by the nerves innervating the pancreas. Although considerable progress has been achieved, further work is required to fully delineate the complex interplay of the numerous mechanisms involved. This review aims to provide a comprehensive update of the current literature available, bringing together data gleaned from studies addressing the actions of individual hormones, humoral factors, and neurotransmitters on the regulation of amylase secretion from the acinar cell. This comprehensive view of the islet-acinar axis of the pancreas while acknowledging the dominant role played by insulin and somatostatin on exocrine secretion sheds light on the influence of the various neuropeptides on amylase secretion.

Intramural neural pathways between the duodenum and sphincter of Oddi in the Australian brush‐tailed possum in vivo.

1. Balloon distension of the duodenum 2 cm oral or anal to the sphincter of Oddi‐duodenal junction elevated the amplitude of spontaneous sphincter of Oddi phasic contractions by 37.7 +/‐ 8.5 or 120.1 +/‐ 79.8%, respectively (mean +/‐ S.E.M., both n = 6, P < 0.05, Wilcoxon test). To further investigate this response, this study aimed to determine if: (i) electrical field stimulation (EFS) of the duodenum influences sphincter of Oddi activity; (ii) intramural nerves mediate the response; and (iii) nicotinic and/or muscarinic receptors are involved. 2. Electrical field stimulation (70 V, 0.5 ms; 5‐60 Hz, 10‐20 s) of the duodenal anterior serosal surface 2‐4 cm oral or anal to the sphincter of Oddi‐duodenal junction, produced excitatory responses in the sphincter of Oddi in anaesthetized Australian brush‐tailed possums (n = 45). 3. These responses were frequency dependent, maximal at 30 Hz (n = 4) and abolished by tetrodotoxin (9 micrograms kg‐1 I.A.; n = 6), or by crushing the duodenum (n = 3). Hexamethonium bromide (30 mg kg‐1 I.V.) did not significantly alter the response to duodenal EFS either oral (n = 6) or anal (n = 8) to the sphincter of Oddi‐duodenal junction. Atropine sulphate (30 micrograms kg‐1 I.V.) reduced the response to duodenal EFS oral and anal to the sphincter of Oddi‐duodenal junction to 11.2 +/‐ 5.8 (n = 6) and 45.0 +/‐ 26.8% (n = 8), respectively (both P < 0.05). 4. Bilateral cervical vagotomy and guanethidine infusion (10 mg kg‐1 over 15 min I.V.) did not significantly alter the responses to duodenal EFS (n = 7). 5. Excitatory intramural neural pathways between the sphincter of Oddi and the segment of duodenum 4 cm oral and anal to the sphincter of Oddi‐duodenal junction have been demonstrated. These postganglionic pathways may involve muscarinic receptors.

Nitric oxide mediates nonadrenergic, noncholinergic neural relaxation in the Australian possum

BACKGROUND Nitric oxide has been shown to play an important role in neurally mediated relaxations of gastrointestinal smooth muscle. The aim of this study was to determine whether NO may be the inhibitory transmitter to circular smooth muscle from the sphincter of Oddi of the Australian brush-tailed possum (Trichosurus vulpecula). METHODS The effects of drugs on relaxations evoked by electrical-field stimulation of circular muscle strips precontracted with either erythromycin or carbachol were studied. Preparations were also processed histochemically to determine the presence of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivity in the tissue. RESULTS NG-nitro-L-arginine methyl ester reduced the amplitude of relaxations; this effect could be partially reversed by millimolar concentrations of L-arginine but not by D-arginine. Oxyhemoglobin also reduced the amplitude of the relaxations, and sodium nitroprusside mimicked the relaxations in precontracted strips. Histochemical processing revealed the presence of nerve cell bodies and nerve fibers associated with the circular muscle layer, which are reactive for NADPH-diaphorase and are thus likely to contain NO synthase. CONCLUSIONS These results are all consistent with NO released from nerve cells mediating a significant part of the nonadrenergic, noncholinergic relaxation of the circular muscle layer of the sphincter of Oddi.

Changes in gallbladder motility and gallstone formation following laparoscopic gastric banding for morbid obesity

UNLABELLED Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown. METHOD Twenty-six normal-weight volunteers (body mass index [BMI] less than 30) were compared with 14 morbidly obese patients (BMI greater than 40). Gallbladder volumes were measured ultrasonographically, after fasting and following stimulation with intravenous cholecystokinin-octapeptide (CCK-8) RESULTS Preoperatively, fasting gallbladder volume and residual volume after CCK stimulation were both two times greater in the obese group (P<0.02 versus controls). Per cent gallbladder emptying was not different. Gallbladder refilling was four times higher in the obese patients (P<0.01). By six weeks postoperatively, the obese patients lost 1.4+/-0.1% body weight per week. Gallbladder emptying decreased 18.4% (80.3+/-3.9% to 65.5+/-6.9%; P<0.05); residual volume rose one-third (not significant), and refilling fell 60.5% (0.43+/-0.09 to 0.26+/-0.04 mL/min; P=0.07). Three patients with weight losses of greater than 1.7% per week developed gallstones; gallbladder emptying fell outside the 95 percentile. By six months, weight loss slowed to 0.5+/-0.1% per week; gallbladder motility improved modestly. No further stones developed. CONCLUSION Rapid weight loss following laparoscopic gastric banding impairs gallbladder emptying and when pronounced, gallstones form by six weeks postoperatively. The accompanying reduction in gallbladder emptying, increased gallbladder residual volume and decreased refilling promote gallbladder stasis and hence stone formation.

Lung injury in acute pancreatitis: Mechanisms underlying augmented secondary injury

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are common complications of acute pancreatitis (AP). ALI/ARDS contribute to the majority of AP-associated deaths, particularly in the setting of secondary infection. Following secondary pulmonary infection there can be an exacerbation of AP-associated lung injury, greater than the sum of the individual injuries alone. The precise mechanisms underlying this synergism, however, are not known. In this review we discuss the main factors contributing to the development of augmented lung injury following secondary infection during AP and review the established models of AP in regard to the development of associated ALI.

The sphincter of Oddi: understanding its control and function.

Abstract  The most common functional disorders of the biliary tract and pancreas are associated with disordered motility of the sphincter of Oddi (SO). The SO is a neuromuscular structure located at the junction of the bile and pancreatic ducts with the duodenum. The primary functions of the SO are to regulate the delivery of bile and pancreatic juice into the duodenum, and to prevent the reflux of duodenal contents into the biliary and pancreatic systems. Disordered motility of the SO leads to the common and painful clinical conditions of SO dysfunction and acute pancreatitis. In order to understand normal SO motility, studies have been performed addressing SO function, control of spontaneous SO activity, responses to bioactive agents, SO innervation, and reflexes with other gastrointestinal organs. These studies have led to the current understanding of how the SO functions and may permit the development of targeted therapy for SO dysfunction and acute pancreatitis. This review summarizes the current knowledge regarding the control and regulation of SO motility, highlighting laboratory based and clinical research performed over the last 5 years.

Acute pancreatitis due to diabetes: the role of hyperglycaemia and insulin resistance.

BACKGROUND The co-existence of diabetes mellitus (DM) in patients with acute pancreatitis (AP) is linked to poor outcomes. Four large epidemiological studies have suggested an aetiological role for DM in AP. The exact nature of this role is poorly understood. OBJECTIVE To analyse the available clinical and experimental literature to determine if DM may play a causative role in AP. METHODS A systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965-2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses exploring the mechanisms of pathogenesis of AP in patients with DM. RESULTS No clinical studies could be identified directly providing pathogenetic mechanisms of DM in the causation of AP. The available data on DM and its associated metabolic changes and therapy indicate that hyperglycaemia coupled with the factors influencing insulin resistance (tumour necrosis-α, NFκB, amylin) cause an increase in reactive oxygen species generation in acinar cells. CONCLUSIONS Complex pathogenetic connections exist between AP and factors involved in the development and therapy of DM. Insulin resistance and hyperglycaemia, hallmarks of DM, are important factors linked to the susceptibility of diabetics to AP. Given the high morbidity associated with an attack of AP in a diabetic patient, targeting these two aspects by therapy may help not only to reduce the risk of development of AP, but may also help reduce the severity of an established attack in a diabetic patient.

How safe is endoscopic sphincter of Oddi manometry

Abstract The safety of endoscopic manometry of the sphincter of Oddi was evaluated in a prospective survey of 158 consecutive procedures in 126 patients with either unexplained pain after cholecystectomy or idiopathic recurrent pancreatitis. The only complication was that of pancreatitis which was defined as the development of abdominal pain in association with a plasma amylase above the reference range. This occurred in 13 patients (8%) and was more frequent (P= 0.001) when the indication for the procedure was idiopathic recurrent pancreatitis (29%) than unexplained pain (6%). Pancreatitis was also more frequent (P= 0.02) in patients with abnormal manometry (14%) than in those with normal manometry (3%) and occurred at highest frequency (50%) in a subgroup of patients with idiopathic recurrent pancreatitis and sphincter stenosis (high sphincter basal pressure). All episodes of pancreatitis were mild with a median increase in hospital stay of 2 days; no patients died. The risk of pancreatitis after endoscopic manometry is relatively low but increases in patients with abnormal sphincter manometry, particularly those with idiopathic recurrent pancreatitis.