Colorectal motor and sensory function after hysterectomy.

PURPOSE: Women may develop constipation after hysterectomy. The pathophysiology and underlying mechanisms are poorly understood. They may originate from either neural damage of rectum and colon or changes in anatomical constellation of the remaining pelvic organs. The aim of this study is to evaluate sensory and motor functions of rectum and colon in women with newly developed constipation after hysterectomy in comparison with women without constipation and healthy controls after hysterectomy . METHODS: Barostat measurements were performed in posthysterectomy women with constipation (PH-C), without constipation (PH-NC), and healthy controls (n = 10, every group). Outcome measures were rectal and colonic compliance (millilitre per millimetre of mercury), rectocolonic perception in reaction to mechanical distension (millimetre; VAS scores) and rectocolonic reflex (millilitre per millimetre of mercury). RESULTS: No differences in rectal or colonic compliance were observed. Urge perception due to rectal distension increased significantly in controls (from 7 ± 5 to 41 ± 10 mm; p < 0.05) and PH-NC group (from 3 ± 1 to 24 ± 9 mm; p < 0.05), but not in PH-C patients (1 ± 1 to 11 ± 5 mm; ns). In healthy controls and the PN-NC group, respectively, 100 and 70 % of subjects reached the minimal threshold value for urge of 10 mm during the isobaric distension sequence. In the PH-C group, only two subjects (20 %) reached this threshold (p < 0.05). Rectal pain perception, phasic colonic motility and the rectocolonic reflex were intact in all three groups. CONCLUSIONS: Colorectal motor and sensory function is generally well preserved in women with constipation after hysterectomy. It is unlikely that the symptom of constipation after hysterectomy has been caused by iatrogenic neuronal damage in these patients.

Two patients with extremely elevated tumor markers: where is the malignancy?

Serum tumor markers are useful to evaluate a cancer's response to treatment, for early detection of cancer relapse, and, in some cases, to diagnose malignancy. In this paper, we present two patients with significantly elevated serum tumor markers without evidence of malignant disease. An 18-year-old patient suffering from autoimmune hepatitis had markedly increased alpha-fetoprotein (aFP) levels (2,002 µg/L; normal <10 ug/L). Extensive imaging showed no signs of hepatocellular carcinoma or other cancer, and treatment with Prednisone led to rapid normalization of both liver enzymes and aFP. The second patient, a 60-year-old female with painless jaundice due to biliary stone disease, had very high serum levels of CA19-9 (18,000 kU/L, normal <27 kU/L). Liver biochemistry and serum CA19-9 concentration decreased to almost normal values (45 kU/L) after biliary stenting. These cases demonstrate that serum tumor markers can be elevated in benign disease and are therefore not appropriate to diagnose cancer.

Symptoms in patients with ulcerative colitis in remission are associated with visceral hypersensitivity and mast cell activity.

OBJECTIVE: Patients with ulcerative colitis in remission (UCR) frequently report irritable bowel syndrome (IBS)-like symptoms. Recent studies have pointed to the role of mast cells in mediating visceral hypersensitivity in IBS. We hypothesized that visceral hypersensitivity is frequently present in patients with UCR and is related to the quantity and activity of mast cells in the sigmoid mucosa. MATERIAL AND METHODS: A group of 17 controls and 19 patients with UCR were studied. Rectal compliance and perception were measured by electronic barostat. Sigmoid biopsies were taken to quantify the amount of mast cells, degranulating mast cells and mast cells in close proximity to mucosal nerve endings. RESULTS: Visceroperception significantly increased in UCR (p < 0.05) versus controls. Rectal perception correlated positively with IBS-like symptoms in UCR (r = 0.969; p < 0.05). The amount of mucosal mast cells (per 100 crypts) was significantly increased in UCR versus controls: 228 ± 20 versus 163 ± 18 (p < 0.05). In the UCR patients a higher percentage of mucosal mast cells was in close proximity to nerve endings (58 ± 4 vs. 38 ± 3% in controls; p < 0.05) or was degranulating (40 ± 7 vs. 16 ± 4% in controls; p < 0.05). There was a significant but weak correlation between quantity of mucosal mast cells and pain perception (r = 0.32; p < 0.05). CONCLUSION: Rectal hypersensitivity is associated with mucosal presence and activation of mast cells and with IBS-like symptoms in patients with UCR.

Dysfunctional cognitions, anxiety and depression in irritable bowel syndrome.

GOALS AND BACKGROUND: Patients with irritable bowel syndrome (IBS) have significantly impaired quality of life (QoL). We investigated the presence of dysfunctional cognitions, anxiety, and depression symptoms and their impact on daily symptoms and QoL in a large IBS cohort. STUDY: A total of 268 IBS patients (Rome II criteria, age 18 to 65 y) were included. Patients completed a 2-week daily symptom diary. The Short Form-36 was used to score QoL. The 31-items Cognitive Scale for Functional Bowel Disorders (CSFBD) and the Hospital Anxiety and Depression Scale (HADS) were used to analyze the psychological factors. RESULTS: Possible anxiety and depression disorders were present in 30% and 22% of IBS patients, respectively. Patients with anxiety and depression had significantly higher mean symptom scores, impaired QoL, and higher CSFBD scores (P<0.01). Physical and mental QoL were both affected by depression (HADS-D) and dysfunctional cognitions (P<0.01). Only physical QoL, not mental QoL, was affected by referral type (hospital setting vs. community based; P<0.01). Only mental QoL was affected by anxiety (HADS-A) (P<0.01). Dysfunctional cognitions independently of anxiety and depression influenced QoL and IBS symptoms. CONCLUSIONS: In this IBS cohort, dysfunctional cognitions independently influence physical and mental QoL and symptom severity. Presence of possible anxiety and depression disorders resulted in higher symptoms, lower QoL, and higher CSFBD scores. The results point toward an important role of psychological factors, especially dysfunctional cognitions on QoL and symptom scores in IBS patients.

Testing a biobehavioral model of irritable bowel syndrome.

OBJECTIVE: The pathogenesis of irritable bowel syndrome (IBS) is probably multifactorial with dysfunction at different levels of the brain-gut axis. The aim of this study was to evaluate an existing biobehavioral model of IBS symptom generation in a large group of patients. MATERIAL AND METHODS: In 104 IBS patients, we assessed symptom severity by a symptom diary, visceral hypersensitivity using a barostat, autonomic function by measuring arterial baroreflex sensitivity and psychological functioning using questionnaires. Structural equation modeling was used to calculate the reciprocal and chronological relationships between the model variables. RESULTS: Analysis of the adjusted original model indicated poor fit [Satorra-Bentler chi=28.47; degrees of freedom (df)=11, P<0.01; comparative fit index (CFI)=0.78], which was caused by omission of two paths (illness behavior-IBS symptoms and trauma-IBS symptoms). The revised model yielded a reasonable fit (chi=13.88, df=9, P=0.13; CFI=0.94). The model explained 18.7% of the variance in IBS symptoms. Illness behavior completely mediated the effect of cognitions on IBS symptoms and partly mediated the effect of trauma on IBS symptoms. The fit of this alternative model was good (chi=9.85, df=8, P=0.28; CFI=0.98). The alternative model explained 20.0% of the variance in IBS symptoms. CONCLUSION: The proposed biobehavioral model could not be validated. Although visceral hypersensitivity and IBS symptom severity significantly correlate, autonomic function and IBS symptoms do not. Cognitive-behavioral aspects are important in the clinical expression of IBS, with illness behavior playing an intermediate and central role.

Symptom severity but not psychopathology predicts visceral hypersensitivity in irritable bowel syndrome.

BACKGROUND & AIMS: Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS), but the relationship with clinical symptoms and psychological factors has not been fully established. We aimed to (1) evaluate these variables in a large cohort of IBS patients, recruited from both hospital and general practice, and in healthy controls and (2) assess which of these factors predicts the occurrence of visceral hypersensitivity in IBS. METHODS: Rectal compliance and perception (intensity, perception thresholds; visual analogue scale, 0-100 mm) were assessed by a rectal barostat study (ramp distention) in 101 IBS patients and 40 healthy volunteers. IBS symptom severity was scored by using a 14-day 5-item diary. Anxiety, depression, somatization, vigilance, pain coping, dysfunctional cognitions, psychoneuroticism, and quality of life were assessed with psychometric questionnaires. RESULTS: Rectal compliance was significantly reduced in IBS patients compared with controls (P < .01), as were thresholds for pain (27 +/- 15 vs 35 +/- 8 mm Hg; P < .01) and urge (P < .05). Levels of anxiety, depression, neuroticism, somatization, and dysfunctional cognitions were significantly increased in IBS patients versus controls, whereas pain coping and quality of life were significantly worse. Hypersensitivity to rectal distention occurred in 33% of patients and was associated with increased symptom severity (P = .016), but not with demographic characteristics or psychological disturbances. CONCLUSIONS: Hypersensitivity to balloon distention occurs in 33% of IBS patients and is predicted by symptom severity but not by psychological or demographic characteristics.

Proximal and distal gut hormone secretion in irritable bowel syndrome.

OBJECTIVE: Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS. MATERIAL AND METHODS: We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls. RESULTS: Fasting plasma CCK levels were significantly elevated in patients (1.2+/-0.8 pM) compared with those in controls (0.8+/-0.7 pM, p=0.006), as was the incremental postprandial CCK response (72+/-73 versus 40+/-42 pM.60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215+/-135 versus 162+/-169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1+/-36.5 versus 60.8+/-25.1 versus 57.5+/-23.9 pM, one-way ANOVA p=0.003). CONCLUSIONS: IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.

Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome.

OBJECTIVES: Imbalances in the genetically controlled pro- and anti-inflammatory cytokine production may promote ongoing low-grade inflammation after an acute gastroenteritis, and subsequently, irritable bowel syndrome (IBS) (post-infectious IBS, PI-IBS). We studied gene promoter single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNF-alpha, pro-inflammatory) and interleukin-10 (IL-10, anti-inflammatory) in IBS patients and controls. METHODS: DNA was extracted from peripheral blood leucocytes of 111 IBS patients and 162 healthy controls. Genotype and allele frequencies were assessed by analyzing SNPs at position -308 (TNF-alpha) and -1082 and -819 (IL-10). RESULTS: Homozygous high producers for TNF-alpha (A/A) were rare (overall prevalence 2.6%). The heterozygous TNF-alpha genotype (G/A, high producer) was significantly more prevalent in IBS compared to controls (41%vs 26%, p= 0.02). More patients (41%) than controls (30%) were positive for the A allele (p= 0.044; odds ratio (OR) 1.68, 95% confidence interval (CI) 1.01-2.79), with a similar trend for diarrhea (54%) versus constipation and alternating subtypes (<33%, p= 0.079), but not for subgroups according to a history of acute gastroenteritis. IL-10 genotypes were similarly distributed in patients and controls for both SNPs. Possession of a high producer TNF-alpha and a low producer IL-10 genotype were significantly more prevalent in IBS (9%) versus controls (3%, p= 0.035; OR 3.11, 95% CI 1.03-9.36) and in diarrhea (20%) compared to other IBS subtypes (<4%, p= 0.026). CONCLUSIONS: Our results support the emerging hypothesis that genetically determined immune activity plays a role in the pathophysiology of IBS. Future studies in larger, clinically relevant, IBS subgroups are warranted to establish definite associations with cytokine gene polymorphisms.

Viscerosensory-cardiovascular reflexes: altered baroreflex sensitivity in irritable bowel syndrome.

Animal studies have demonstrated that visceral afferent stimulation alters autonomic cardiovascular reflexes. This mechanism might play an important role in the pathophysiology of conditions associated with visceral hypersensitivity, such as irritable bowel syndrome (IBS). As such, studies in humans are lacking, we measured viscerosensory-cardiovascular reflex interactions in IBS patients and healthy controls. Systolic blood pressure (SBP), heart rate (HR), and arterial baroreflex sensitivity (BRS) were studied in 87 IBS patients and 36 healthy controls under baseline conditions and during mild (15 mmHg) and intense (35 mmHg) visceral stimulation by rectal balloon distension. BRS was computed from continuous ECG and arterial blood pressure signals (Finapres-method) during 5-min periods of 15-min metronome respiration. Baseline SBP and HR were not different between patients and controls. In both groups, SBP increased similarly during rectal stimulation, whereas HR decreased during mild and increased intense stimulation. BRS was significantly higher in patients compared with controls at baseline (7.9 +/- 5.4 vs. 5.7 +/- 3.7 ms/mmHg, P = 0.03) and increased significantly in both groups during mild stimulation. This increase persisted in controls during intense stimulation, but BRS returned to baseline in patients. BRS was not significantly different between groups during rectal distension. This study demonstrates the presence of a viscerosensory-cardiovascular reflex in healthy individuals and in IBS patients. The increased BRS in IBS patients at baseline may either be a training-effect (frequent challenging of the reflex) or reflects altered viscerosensory processing at the nucleus tractus solitarii.

Effect of neurotensin on colorectal motor and sensory function in humans.

PURPOSE: Animal studies have shown that neurotensin stimulates colonic motility, but little is known on the effect on rectocolonic function in humans. This study was designed to investigate the effect of neurotensin on rectal and colonic motor and sensory function and colonic reflexes in humans. METHODS: Motor and sensory function of the descending colon and rectum were studied in eight healthy volunteers (5 females; age range, 20-58 years) by using a dual, computerized, rectocolonic, barostat assembly. Measurements were performed during placebo and neurotensin infusion (5 pmol/kg per minute), respectively. Compliance and reflex mechanisms were assessed in both rectum and descending colon. Symptom perception (urge and pain) was scored using Visual Analog Scales (0-10 cm). RESULTS: Neurotensin significantly (P < 0.05) increased rectal compliance (from 9 +/- 1.1 to 10.1 +/- 1.1 ml/mmHg) and colonic compliance (from 7.9 +/- 0.4 to 9 +/- 0.7 ml/mmHg) during stepwise distensions. Intensity of urge and pain perception during rectal distension was increased by neurotensin (P < 0.05). Sensations during colonic distensions were not altered by neurotensin. For colonic reflexes, during rectal distension the colonic bag volume increased significantly (P < 0.05), whereas during colonic distension rectal bag volume decreased significantly (P < 0.05). Neurotensin delayed the occurrence of these reflexes: they were present at significantly higher pressures compared to placebo (P < 0.05). CONCLUSIONS: We demonstrated the presence of both a rectocolonic inhibitory and a colorectal stimulatory reflex in healthy volunteers. Neurotensin increases compliance and modulates rectal but not colonic sensitivity. Colorectal and rectocolonic reflexes are impaired during infusion of neurotensin.