Cystic fibrosis transmembrane conductance regulator modulates enteric cholinergic activities and is abnormally expressed in the enteric ganglia of patients with slow transit constipation.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) was recently found in the enteric nervous system, where its role is unclear. We aimed to identify which enteric neuronal structures express CFTR, whether CFTR modulates enteric neurotransmission and if altered CFTR expression is associated with slow transit constipation (STC). METHODS: Immunofluorescence double labeling was performed to localize CFTR with various neuronal and glial cell markers in the human colon. The immunoreactivity (IR) of CFTR and choline acetyltransferase (ChAT) on myenteric plexus of control and STC colon was quantitatively analyzed. In control colonic muscle strips, electrical field stimulation (EFS) evoked contractile responses and the release of acetylcholine (ACh) was measured in the presence of the CFTR channel inhibitor, CFTR(inh)-172. RESULTS: CFTR-IR was densely localized to myenteric ganglia, where it was co-localized with neuronal markers HuC/D and ß-tubulin, and glial marker S-100 but little with glial fibrillary acidic protein. Vesicular ACh transport was almost exclusively co-localized with CFTR, but neurons expressing nitric oxide synthase were CFTR negative. Significant reductions of CFTR-IR (P < 0.01) and ChAT-IR (P < 0.05) were observed on myenteric ganglia of STC compared to control. Pre-treatment of colonic muscle strips with CFTR(inh)-172 (10 µM) significantly inhibited EFS-evoked contractile responses (P < 0.01) and ACh release (P < 0.05). CONCLUSIONS: Co-localization of CFTR-IR with cholinergic markers, inhibition of EFS-induced colonic muscle contractility and ACh release by CFTR(inh)-172 suggest that CFTR modulates enteric cholinergic neurotransmission. The downregulation of CFTR and ChAT in myenteric ganglia of STC correlated with the impaired contractile responses to EFS.

Patient compliance with surveillance colonoscopy: patient factors and the use of a graded recall system.

BACKGROUND: Surveillance colonoscopy allows for the early detection and improved treatment outcomes in colorectal neoplasms but compliance rates and factors require further investigation. METHODS: This is a retrospective cohort study examining 816 patients recalled for surveillance colonoscopy at an Australian colorectal practice over a 6-month period. Primary outcome was compliance with colonoscopy within 12 months of recall. The secondary outcome of this study was to identify factors affecting compliance including patient factors and the practices' graded recall system. RESULTS: A total of 715 patients (87.6%) were compliant with recall requests for repeat colonoscopy. Significantly higher compliance rates were noted with a personal history of adenomatous polyps (90.9% versus 85.6%, P = 0.025). Those with private insurance or Department of Veterans Affairs were more likely to be compliant than those publicly funded (89.0% versus 93.3% versus 79.0%, P = 0.007). No statistically significant difference in compliance was shown with a personal history of colorectal cancer, diverticular disease, perianal disease, National Health and Medical Research Council risk category, gender, time associated with the practice or the clinician. There was a significant positive correlation between the number of letters sent and compliance with recall, with 61.8% being compliant after a single letter, and a final cumulative compliance after five letters of 87.6% (R = 0.882, P = 0.048). CONCLUSION: A graded recall system can achieve compliance rates as high as 87.6% compared to a single letter only achieving 61.8% compliance. A history of adenomatous polyps and insurance status were the only factors shown to result in higher recall compliance.

Sarcopenia in children with perforated appendicitis.

BACKGROUND: Decreased skeletal muscle mass, or sarcopenia, has been shown to be associated with worse postoperative recovery and a higher risk of complications in adult surgical patients. We hypothesized that pediatric patients with complicated appendicitis may experience sarcopenic changes over the course of their treatment. METHODS: The medical records and computed tomography scans of 36 pediatric complex appendicitis patients who had both preoperative and postoperative computerized tomography scans at our hospital were reviewed. Changes in psoas muscle area were examined using linear mixed models with random patient-level intercept and time effects. RESULTS: The median change in body mass index among all patients from admission to discharge was -0.8 kg/m2 (interquartile range: -1.3 to -0.2). The mean percentage change in psoas muscle area per day over the course of appendicitis-related treatment was -0.81% (95% confidence interval: -1.12 to -0.50) (P < 0.001). The relative decrease in psoas muscle area per day did not vary by initial body mass index, gender, or race (P > 0.10 for all interactions). CONCLUSIONS: Our data suggest that pediatric patients with complex appendicitis experience sarcopenic changes during their hospital admission. Given previous reports that sarcopenia is a significant predictor of worse surgical outcomes, more investigation is warranted to assess whether these changes are associated with postsurgical complications and to evaluate potential interventions that may prevent these changes.

Single visit surgery for pediatric ambulatory surgical procedures: a satisfaction and cost analysis.

BACKGROUND: Single visit surgery (SVS) consists of same-day pre-operative assessment and operation with telephone post-operative follow-up. This reduces family time commitment to 1 hospital trip rather than 2-3. We began SVS for ambulatory patients with clear surgical indications in 2013. We sought to determine family satisfaction, cost savings to families, and institutional financial feasibility of SVS. METHODS: SVS patients were compared to age/case matched conventional surgery (CS) patients. Satisfaction was assessed by post-operative telephone survey. Family costs were calculated as the sum of lost revenue (based on median income) and transportation costs ($0.50/mile). RESULTS: Satisfaction was high in both groups (98% for SVS vs. 93% for CS; p=0.27). 40% of CS families indicated that they would have preferred SVS, whereas no SVS families indicated preference for the CS option (p<0.001). Distance from the hospital did not correlate with satisfaction. Estimated cost savings for an SVS family was $188. Reimbursement, hospital and physician charges, and day-of-surgery cancellation rates were similar. CONCLUSIONS: SVS provides substantial cost savings to families while maintaining patient satisfaction and equivalent institutional reimbursement. SVS is an effective approach to low-risk ambulatory surgical procedures that is less disruptive to families, facilitates access to pediatric surgical care, and reduces resource utilization. TYPE OF STUDY: Cost Effectiveness Study. LEVEL OF EVIDENCE: Level II.

Sclerotherapy for splenic cysts in children.

BACKGROUND: Sclerotherapy has been described as a treatment option for nonparasitic pediatric splenic cysts; however, there are limited data on its long-term effectiveness. METHODS: We performed a retrospective review and prospective follow-up imaging study of children treated for nonparasitic splenic cysts at our institution during 2006-2015. Included patients had International Classification of Disease, Ninth Revision, Clinical Modification diagnosis code 289.59 or 759.0 and underwent either sclerotherapy or a partial splenic operation (partial splenectomy, cyst excision, or marsupialization). Charts were reviewed for demographics, imaging, treatments, and complications. Identified patients were contacted and asked to return for splenic ultrasonography. RESULTS: Six surgical patients and 19 sclerotherapy patients were identified. Sclerotherapy patients underwent a median of four treatments with a decrease in the size of the cyst or complete ablation in 89.5% (17/19). Of the two patients who underwent unsuccessful sclerotherapy, one patient had sclerotherapy with sotradecol and ethanol for eight treatments, developed infection, and underwent total splenectomy. The other patient did not improve with sclerotherapy and underwent partial splenectomy. Nine patients (eight patients treated with sclerotherapy and one patient treated with partial splenectomy) were successfully contacted and underwent follow-up imaging at a median follow-up of 2.4 y since last treatment. Of the eight patients treated with sclerotherapy, four patients remained cyst-free, three had small residual asymptomatic cysts stable in size, and one developed a recurrent small asymptomatic cyst; the patient treated with surgery had no recurrence. CONCLUSIONS: Sclerotherapy appears to be an effective and durable alternative treatment for children with splenic cysts.

Patients exposed to diagnostic head and neck radiation for the management of shunted hydrocephalus have a significant risk of developing thyroid nodules.

PURPOSE: External radiation to the head and neck can lead to an increased incidence of thyroid nodules. We investigated whether patients requiring repeated head and neck imaging for the management of shunted hydrocephalus had a higher incidence of ultrasound-detected thyroid nodules compared to reports of comparable age. METHODS: Patients treated at our institution for shunted hydrocephalus from 1990 to 2003 were contacted. Enroled patients underwent a thyroid ultrasound. Demographic data and radiation exposure history were obtained retrospectively. RESULTS: Thyroid nodules were identified sonographically in 15/112 patients (13.6 %). Patients with thyroid nodules were older (mean 24.3 ± 7.6 years) than those without (mean 18.4 ± 8.0 years) (p = 0.005). Those with a detectable thyroid nodule had a longer follow up time compared to those who did not (mean 21.9 ± 5.5 vs. 15.1 ± 7 years, respectively) (p = 0.018). CONCLUSION: Patients with shunted hydrocephalus are exposed to substantial head and neck radiation from diagnostic imaging and have a higher incidence of thyroid nodules detected by ultrasonography. These patients should be provided ongoing surveillance for detection of thyroid nodules and the possibility of malignancy.

A Rare Cause of Postoperative Abdominal Pain in a Spinal Fusion Patient.

We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who later developed nausea, emesis, and abdominal pain. We discuss the epidemiology, prevalence, anatomic findings, symptoms, diagnostic tests, and clinical management, including nonsurgical and surgical therapies, of superior mesenteric artery syndrome (SMAS), a rare condition. Over a 2-week period, the patient developed an uncommon type of bowel obstruction likely related to her initial thin body habitus, correction of her deformity, and weight loss after surgery. The patient returned to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric-jejunal (G-J) feeding tube. The patient had the G-J feeding tube in place for approximately 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved, and she gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure, and SMAS is a rare condition. However, in the case of an asthenic adolescent with postoperative weight loss, intestinal obstruction can develop. When planning operative spinal correction in scoliosis patients who have a low body mass index at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation.

Plasma TIMP-1 and CEA as Markers for Detection of Primary Colorectal Cancer: A Prospective Validation Study Including Symptomatic and Non-symptomatic Individuals.

BACKGROUND/AIM: The combination of plasma tissue inhibitor of metalloproteinases-1 (1) and CEA has been shown to have utility in early detection of colorectal cancer (2). A prospective study was performed to validate previous findings. PATIENTS AND METHODS: Individuals undergoing large bowel endoscopy were prospectively included (N=1965). Baseline data and co-morbidity were recorded. The primary end-point was the detection of CRC. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined using an automated analysis platform when all samples were collected. RESULTS: CRC was detected in 32 individuals, 24 with colonic cancer (CC) and 8 with rectal cancer (RC). Other findings were 265 with adenomas and 889 with non-neoplastic pathology. The biomarker levels were elevated in plasma from patients with CRC, but also from patients with various co-morbidities compared to individuals without any findings at endoscopy. Univariate analysis demonstrated that both markers were significant predictors of CRC. The odds ratios (OR) for an elevated TIMP-1 level for the detection of CRC was 6.2 [95% confidence interval (CI)=3.1-13.0, p<0.0001] and for an elevated CEA level was 2.4 (95% CI=1.9-2.9, p<0.0001). A subset analysis with CC as the end-point showed an OR for TIMP-1 of 7.0 (95% CI=3.2-15.3, p<0.0001). Multivariable analysis including TIMP-1, CEA and age resulted in an OR for TIMP-1 of 2.0 (95% CI=0.7-5.2, p=0.078) and for CEA the OR was 2.2 (95% CI=1.8-2.8, p<0.0001). CONCLUSION: This prospective study validates a previous study testing the detection of CRC based on TIMP-1 and CEA levels (3).

Prediction of symptom improvement in children with biliary dyskinesia.

BACKGROUND: Rates of cholecystectomy for biliary dyskinesia are rising. Our objective was to identify clinical determinants of symptom improvement in children undergoing cholecystectomy for biliary dyskinesia. METHODS: This retrospective cohort study included patients undergoing cholecystectomy for biliary dyskinesia from 2006-2013 who had their gallbladder ejection fraction (EF) measured by either cholecystokinin-stimulated hepatobiliary iminodiacetic acid scan and/or fatty meal ultrasound. Patients presenting from 2010-2013 were interviewed >1 y after cholecystectomy to determine symptom improvement, complete symptom resolution, and any postoperative clinical interventions related to biliary dyskinesia. Sensitivity and positive predictive values for the diagnostic tests for symptom improvement were calculated. Multivariable logistic regression models were used to identify preoperative characteristics associated with symptom improvement. RESULTS: Of the 153 included patients, 76% were female, 89% were Caucasian, and 39% were obese. At postoperative evaluation, symptom improvement was reported by 82% of the patients and complete symptom resolution in 56%. For both the hepatobiliary iminodiacetic acid and fatty meal ultrasound, the sensitivity of the test to predict symptom improvement increased with higher EF, whereas the positive predictive values remained around 80%. Of the 41 patients who participated in phone interview for long-term follow-up, 85% reported symptom improvement and 44% reported complete symptom resolution. Factors associated with symptom improvement included a shorter duration of pain, a history of vomiting, and a history of epigastric pain. CONCLUSIONS: Despite not identifying an EF level that predicted symptom improvement, over 80% of patients undergoing cholecystectomy for biliary dyskinesia reported symptom improvement. These results support continuing to offer cholecystectomy to treat biliary dyskinesia in children.

Inverse expression of prostaglandin E2-related enzymes highlights differences between diverticulitis and inflammatory bowel disease.

BACKGROUND: Prostaglandin E2 (PGE2) is the dominant prostaglandin in the colon and is associated with colonic inflammation. PGE2 levels are regulated not only by cyclooxygenases (COX-1 and COX-2) but also by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the major PGE2-degrading enzyme. Information about the involvement of 15-PGDH in colonic inflammation is sparse. AIM: We thus aimed to determine the gene expression and immunoreactivity (IR) of COX-1, COX-2, and 15-PGDH in colonic mucosa from patients with diverse inflammatory disorders: ulcerative colitis (UC), Crohn's disease (CD), and acute diverticular disease (DD). METHODS: RNA from human colonic mucosa was extracted and assessed for gene expression by real-time PCR. Intact colon sections were processed for immunohistochemistry with immunostaining of the mucosal areas quantified using ImageJ. RESULTS: In colonic mucosa of both UC and CD, COX-2 mRNA and COX-2-IR were significantly increased, whereas 15-PGDH mRNA and 15-PGDH-IR were significantly reduced. In macroscopically undamaged acute DD mucosa, the opposite findings were seen: for both gene expression and immunoreactivity, there was a significant downregulation of COX-2 and upregulation of 15-PGDH. COX-1 mRNA and COX-1-IR remained unchanged in all diseases. CONCLUSIONS: Our study for the first time demonstrated differential expression of the PGE2-related enzymes COX-2 and 15-PGDH in colonic mucosa from UC, CD, and acute DD. The reduction of 15-PGDH in IBD provides an additional mechanism for PGE2 increase in IBD. With respect to DD, alterations of PGE2-related enzymes suggest that a low PGE2 level may precede the onset of inflammation, thus providing new insight into the pathogenesis of DD.

Xanthogranulomatous appendicitis in a child: report of a case and review of the literature.

Xanthogranulomatous inflammation is a well-described inflammatory process, which may involve any organ but is most frequently encountered in the gall bladder and the kidney. There are rare reports of xanthogranulomatous appendicitis (XA) in the adult population, but only one brief mention of such a diagnosis in a child. In this report, we describe the case of an 11-year-old boy who presented with clinical signs and symptoms of acute appendicitis necessitating appendectomy. Upon microscopic examination, the appendix showed the typical features of XA. To the best of our knowledge, this is the first well-described case XA in a noninterval appendix in a child. We also reviewed the limited medical literature on the subject.

Hemokinin-1 stimulates prostaglandin E2 production in human colon through activation of cyclooxygenase-2 and inhibition of 15-hydroxyprostaglandin dehydrogenase.

Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune system rather than neurons, and may participate in the immune and inflammatory response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up-regulation of the TAC4 gene encoding HK-1 and increased production of prostaglandin E2 (PGE2) occur. Our aim was to examine the mechanistic link between human HK-1 and PGE2 production in normal human colon. Exogenous HK-1 (0.1 µM) for 4 h evoked an increased PGE2 release from colonic mucosal and muscle explants by 10- and 3.5-fold, respectively, compared with unstimulated time controls. The HK-1-stimulated PGE2 release was inhibited by the tachykinin receptor antagonists (S)1-2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl-4-phenyl-l azonia-bicyclo[2.2.2]octane (SR140333) [neurokinin-1 (NK1)] and N-[(2S)-4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide (SR48968) [neurokinin-2 (NK2)] and was also inhibited by the cyclooxygenase (COX)-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398) but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560). A parallel study with substance P showed similar results. Molecular studies with HK-1-treated explants demonstrated a stimulatory effect on COX-2 expression at both transcription and protein levels. It is noteworthy that this was coupled with HK-1-induced down-regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression. Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells, platelets, and ganglia. This finding provides an additional mechanism for HK-1-evoked PGE2 increase, in which HK-1 may interfere with the downstream metabolism of PGE2 by suppressing 15-PGDH expression. In conclusion, our results uncover a novel inflammatory role for HK-1, which signals via NK1 and NK2 receptors to regulate PGE2 release from human colonic tissue, and may further explain a pathological role for HK-1 in IBD when abnormal levels of PGE2 occur.

Factor analysis identifies subgroups of constipation.

AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging self-report questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.

Cyclooxygenase-dependent alterations in substance P-mediated contractility and tachykinin NK1 receptor expression in the colonic circular muscle of patients with slow transit constipation.

Tachykinins are important neurotransmitters regulating intestinal motility. Slow transit constipation (STC) represents an extreme colonic dysmotility with unknown etiology that predominantly affects women. We examined whether the tachykinin system is involved in the pathogenesis of STC. Isolated sigmoid colon circular muscle from female STC and control patients was studied using functional and quantitative reverse transcriptase-polymerase chain reaction methods. A possible alteration of neurotransmission was investigated by electrical field stimulation (EFS) and ganglionic stimulation by dimethylphenylpiperazinium (DMPP). Substance P (SP)-mediated contractions in circular muscle strips were significantly diminished in STC compared with age-matched control (P < 0.001). In contrast, contractile responses to neurokinin A, the selective tachykinin NK(2) receptor agonist, [Lys(5),MeLeu(9),Nle(10)]NKA(4-10), and acetylcholine were unaltered in STC. The reduced responses to SP in STC were fully restored by indomethacin, partially reversed by tetrodotoxin (TTX), but unaffected by atropine or hexamethonium. The restoration by indomethacin was blocked by the NK(1) receptor antagonist CP99994 [(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] and TTX. In STC colonic muscle, there was a significant increase of NK(1) receptor mRNA expression, but no difference in NK(2) mRNA level. DMPP generated biphasic responses, relaxation at lower and contraction at higher concentrations. Although the responses to DMPP were similar in STC and control, an altered contractile pattern in response to EFS was observed in STC circular muscle. In conclusion, we postulate that the diminished contractile response to SP in STC is due to an increased release of inhibitory prostaglandins through activation of up-regulated NK(1) receptors. Our results also indicate some malfunction of the enteric nervous system in STC.

Tachykinin NK2 receptor and functional mechanisms in human colon: changes with indomethacin and in diverticular disease and ulcerative colitis.

Neurokinin A (NKA) is an important spasmogen in human colon. We examined inflammatory disease-related changes in the tachykinin NK(2) receptor system in human sigmoid colon circular muscle, using functional, radioligand binding, and quantitative reverse transcription-polymerase chain reaction methods. In circular muscle strips, indomethacin enhanced contractile responses to NKA (p < 0.01) and to the NK(2) receptor-selective agonist [Lys(5),MeLeu(9),Nle(10)]-NKA(4-10) (p < 0.05) in both normal and acute diverticular disease (DD) specimens, indicating NK(2) receptor-mediated release of relaxant prostanoids. Contractile responses to both tachykinins were reduced in strips from DD (p < 0.001) and ulcerative colitis (UC) (p < 0.05) specimens. Responses to acetylcholine were no different in other strips from the same disease patients, demonstrating that the change in responsiveness to tachykinins in disease is specifically mediated by the NK(2) receptor. In membranes from UC specimens, receptor affinity for (125)I-NKA (median K(D) 0.91 nM, n = 16) was lower (p < 0.01) than that in age-matched control specimens (K(D) 0.55 nM, n = 40), whereas K(D) (0.65 nM, n = 28) in DD was no different from control. No disease-related changes in receptor number (B(max)) were found (mean, 2.0-2.5 fmol/mg of wet weight tissue), suggesting that the reduced contractile responses in disease are not due to a loss of receptor number. Different mechanisms may account for the reduced contractility in DD compared with UC. A gender-related difference in receptor density was seen in controls, with B(max) lower in females (1.77 fmol/mg, n = 15) than in males (2.60 fmol/mg, n = 25, p = 0.01). In contrast, no gender-related differences were seen in NK(2) receptor mRNA in control colonic muscle, indicating that the gender difference is a post-translational event.

Synchronous resection of colorectal primary cancer and liver metastases.

BACKGROUND: Patients with synchronous colorectal liver metastases are thought to have a less favorable prognosis than those with colorectal cancer alone. Surgical treatment options are controversial, be it synchronous resection or staged resection. This study compared the clinical, perioperative, disease-free survival (DFS), and overall survival (OS) results of patients undergoing synchronous resection versus staged resection. METHODS: An observational cohort study of 103 patients with synchronous colorectal liver metastases was performed. All data were collected prospectively. Clinical, perioperative, DFS, and OS results of patients undergoing synchronous resection (group I, n = 73) and staged resection (group II, n = 30) were compared. RESULTS: More patients in group I had poorly differentiated colorectal cancer, bilobar liver metastases, more than three liver metastases, < or =4 cm liver metastases, and shorter hospital stays than patients in group II. There were no significant statistically differences in DFS and OS between the two groups. The median DFS of groups I and II were 28 and 26 months, respectively (p = 0.585). The median OS of groups I and II were 37 and 36 months, respectively (p = 0.900). CONCLUSIONS: Synchronous resection achieved DFSs and OSs similar to those seen after staged resection while avoiding a second major operation.

Impaired proximal colonic motor response to rectal mechanical and chemical stimulation in obstructed defecation.

PURPOSE: Both motor and sensory dysfunction have been implicated in the pathogenesis of obstructed defecation. We have found that despite preservation of a defecatory urge, patients with obstructed defecation have lost the normal predefecatory augmentation in frequency and amplitude of colonic propagating pressure waves. This observation might be explainable by either altered rectal sensory thresholds or by dysfunction in the colonic motor apparatus. By measuring rectal sensory thresholds and proximal colonic motor responses to rectal mechanical and chemical stimuli, we tested the hypotheses that central perception of rectal stimuli is enhanced and that the proximal colonic motor response to rectal stimulation is attenuated. METHODS: In seven patients with obstructed defecation and ten healthy volunteers we measured proximal colonic motor responses and sensory thresholds in response to both rectal balloon distention and rectal instillation of chenodeoxycholic acid. RESULTS: In controls, but not in patients, rectal mechanical distention significantly reduced and chemical stimulation significantly increased the frequency of proximal colonic propagating sequences (P = 0.01). There was no significant difference in rectal sensory thresholds between patients and controls. Prior instillation of chenodeoxycholic acid significantly reduced (P < 0.03) maximum tolerated balloon volume and defecatory urge volume to comparable degree in both patients and controls. CONCLUSIONS: In obstructed defecation, 1) the normal rectocolonic pathways mediating stimulation-induced proximal colonic propagating pressure waves are nonfunctioning, and. 2) central perception of these rectal stimuli is normal.

Bowel, bladder and sexual function in women undergoing laparoscopic posterior compartment repair in the presence of apical or anterior compartment dysfunction.

OBJECTIVE: The aim of the study was to analyse the functional outcome of women undergoing a laparoscopic posterior compartment repair in the presence of anterior or apical compartment dysfunction. DESIGN: Prospective cohort study. METHODS: Forty women, median age 65 years (41-78), with symptoms of genital prolapse 31 (78%), urinary dysfunction 32 (80%) and bowel dysfunction 40 (100%), underwent laparoscopic posterior compartment repair in conjunction with an anterior compartment repair. Pre-operative and postoperative bowel and bladder function was prospectively assessed with a Wexner continence score, Vienna constipation score and a urinary dysfunction score. Twenty-eight (70%) and 24 patients (60%) had pre-operative urodynamics and anorectal manometry. Post-operatively all women were also assessed with a Watt's sexual dysfunction score and a linear analogue patient satisfaction score. Twelve women (30%) had postoperative anal manometry. RESULTS: At 20 months median follow-up, 30 (97%), 20 (62%) and 12 (31%) women reported improvement in their prolapse, urinary and bowel symptoms, respectively. Post-operatively, one woman reported denovo faecal incontinence, four worsening obstructive defecation and three denovo urinary dysfunction. Nine women (35%) reported denovo dyspareunia. The mean time to clinical deterioration following surgery was 11 months. Bowel function improvement was the only factor to significantly correlate with postoperative patient satisfaction. CONCLUSION: The functional outcome of laparoscopic posterior compartment repair in the presence of anterior compartment dysfunction is disappointing. Preoperative counselling is important to ensure that patients have reasonable and realistic expectations from repair surgery, and an understanding that anatomical improvement might not be followed by long-term functional improvement.