Rectal Distension Research Articles

Diagnostic Performance of Rectal CT for Staging Rectal Cancer: Comparison with Rectal MRI and Histopathology.

To compare the diagnostic performance of rectal CT with that of high-resolution rectal MRI and histopathology in assessing rectal cancer. Sixty-seven patients with rectal cancer who underwent rectal CT with rectal distension using sonographic gel and high-resolution MRI were enrolled in this study. The distance from the anal verge/anorectal junction, distance to the mesorectal fascia (MRF), extramural depth (EMD), extramesorectal lymph node (LN) involvement, extramural venous invasion (EMVI), and T/N stages in rectal CT/MRI were analyzed by two gastrointestinal radiologists. The CT findings of 20 patients who underwent radical surgery without concurrent chemoradiotherapy were compared using histopathology. Interclass correlations and kappa statistics were used. The distance from the anal verge/anorectal junction showed an excellent intraclass correlation between CT and MRI for both reviewers. For EMD, the distance to the MRF, presence of LNs, extramesorectal LN metastasis, EMVI, T stage, and intermodality kappa or weighted kappa values between CT and MRI showed excellent agreement. Among the 20 patients who underwent radical surgery, T staging, circumferential resection margin involvement, EMVI, and LN metastasis on rectal CT showed acceptable concordance rates with histopathology. Dedicated rectal CT may be on par with rectal MRI in providing critical information to patients with rectal cancer.

Reducing PTV Margins with Daily Adaptive Radiotherapy to the Prostatic Fossa

<h3>Purpose/Objective(s)</h3> In modern trials, traditional planning target volume (PTV) margins for postoperative prostate radiotherapy have been large (7-10 mm) to account both for daily changes in patient positioning / motion and target deformation (from changes in adjacent bladder fill and/or rectal distension). With daily adaptive radiotherapy, these inter-fractional changes could be minimized, potentially reducing the margins required for treatment and improving adjacent normal tissue dosimetry. <h3>Materials/Methods</h3> A single-center retrospective study was conducted from 03/2021 to 11/2021. Patients receiving conventionally fractionated radiotherapy to their prostatic fossa +/- elective nodes with pre- and post-treatment CBCT imaging (CBCTpre and CBCTpost, respectively) were included. Clinical target volumes (CTV) were contoured by a single observer on all CBCTs (only the prostatic fossa CTV was analyzed in this study). CBCTpre and CBCTpost images were registered using the same shifts used on the day of treatment. Motion was calculated from the center of mass of CBCTpre to that of CBCTpost, which was used to determine predicted margins with Van Herk's formula. Adequate coverage with the proposed margins was verified by performing a symmetric expansion on all CBCTpre scans (PTVpre) and evaluating the overlap with CBCTpost. <h3>Results</h3> Twenty patients were included with 263 image sets available and with 248 image sets included after exclusion. The average time between scans was 10.7 ± 3.0 minutes. The estimated margins predicted to achieve ≥95% coverage for 90% of the population were 1.6 mm, 2.0 mm, and 2.2 mm (x, y, and z axes, respectively). After symmetrically expanding all CBCTpre's CTVs by 1mm, 2mm, 3mm, and 4mm, the percent of image sets achieving ≥95% coverage were 73.6%, 92.2%, 97.1%, and 98.8%. <h3>Conclusion</h3> Using daily adaptive radiotherapy could significantly decrease the required PTV margin expansions for postoperative prostate radiotherapy, as a symmetric expansion of 3 mm achieved excellent coverage in this cohort which compared favorably to historical data. Given these results were obtained from CBCTpre and CBCTpost scans in the non-adaptive setting, these results will need to be validated in a prospective cohort.

Sensory brain activation during rectal balloon distention: a pilot study in healthy volunteers to assess safety and feasibility at 1.5T

ObjectiveAlthough increasing evidence suggests a central mechanism of action for sacral neuromodulation, the exact mechanism remains unclear. We set up a scanning paradigm to measure brain activation related to various stages of rectal filling using rectal balloon distention.Materials and MethodsSix healthy volunteers underwent rectal balloon distention during MRI scanning at a 1.5T scanner with a Tx/Rx head coil. MR images were collected at four levels of distention: empty balloon (EB), first sensation volume (FSV), desire to defecate volume (DDV), maximum tolerable volume (MTV). Data were analyzed using BrainVoyager 20.4. Whole brain and ROI-based fixed-effects general linear model analyses were performed on the fMRI time-course data from all participants.ResultsRectal filling until FSV evoked the most blood-oxygen-level-dependent responses in several clusters throughout the cortex, followed by the responses evoked by rectal filling until DDV. Interestingly, rectal filling until MTV evoked negative responses compared to baseline throughout the cortex. No negative side effects were found.DiscussionThis study shows that a standardized paradigm for functional MRI combined with rectal filling is feasible and safe in healthy volunteers and is ready to be used in fecal incontinent patients to assess whether their brain activity differs from healthy controls.

Disengaging spinal afferent nerve communication with the brain in live mice

Our understanding of how abdominal organs (like the gut) communicate with the brain, via sensory nerves, has been limited by a lack of techniques to selectively activate or inhibit populations of spinal primary afferent neurons within dorsal root ganglia (DRG), of live animals. We report a survival surgery technique in mice, where select DRG are surgically removed (unilaterally or bilaterally), without interfering with other sensory or motor nerves. Using this approach, pain responses evoked by rectal distension were abolished by bilateral lumbosacral L5-S1 DRG removal, but not thoracolumbar T13-L1 DRG removal. However, animals lacking T13-L1 or L5-S1 DRG both showed reduced pain sensitivity to distal colonic distension. Removal of DRG led to selective loss of peripheral CGRP-expressing spinal afferent axons innervating visceral organs, arising from discrete spinal segments. This method thus allows spinal segment-specific determination of sensory pathway functions in conscious, free-to-move animals, without genetic modification.

Regional brain activation during rectal distention and attenuation with alosetron in a nonhuman primate model of irritable bowel syndrome.

Greater understanding of the mechanism that mediates visceral pain and hypersensitivity associated with irritable bowel syndrome (IBS) would facilitate the development of effective therapeutics to manage these symptoms. An objective marker associated with the underlying mechanisms of visceral pain and hypersensitivity could be used to guide therapeutic development. The current study examined brain activation evoked by rectal distention with functional magnetic resonance imaging (fMRI) in a cynomolgus macaque model of visceral hypersensitivity. Male, cynomolgus macaques underwent five four-week treatments of dextran sodium sulfate (DSS)-distilled water (DW), which induced mild-moderate colitis with remission during each treatment cycle. Balloon rectal distention (RD) was performed under anesthesia 14 weeks after the final DSS-DW treatment. Colonoscopy confirmed the absence of colitis prior to the start of RD. In naïve, untreated macaques, 10, 20 and 30 ml RD did not evoke brain activation. However, insular cortex/somatosensory II cortex and cerebellum were significantly activated in DSS-treated macaques at 20 and 30 ml rectal distention. Intra-rectal pressure after DSS treatment was not significantly different from that of naïve, untreated macaques, indicating lack of alteration of rectal functioning following DSS-treatment. Treatment with 5-HT3 receptor antagonist alosetron (p.o.) reduced distension-evoked brain activation and decreased intra-rectal pressure. The current findings demonstrated activation of brain regions to RD following DSS treatments which was not present in naïve macaques, suggesting visceral hypersensitivity. Brain activation in turn was reduced by alosetron, which could underlie the analgesic effect alosetron in IBS patients.

Normal Values of High-resolution Anorectal Manometry of Healthy Indians

Background/AimsHigh-resolution anorectal manometry (HRAM) measures anal sphincter function and anorectal co-ordination. This study aims to provide normal data for HRAM and evaluate the effect of gender, age, and body mass index (BMI) on anorectal functions in healthy Indian subjects.MethodsHRAM was performed on 93 healthy volunteers using a 20-channel, water-perfused catheter. We evaluated anorectal pressures, rectal sensation, and balloon expulsion time. Measurements were recorded during rest, squeeze, and simulated defecation (push).ResultsMedian anal resting pressure (88 mmHg vs 94 mmHg, P = NS), anal squeeze pressure (165 mmHg vs 147 mmHg, P = NS) were not significantly different between males and females. Rectal pressure (70 mmHg vs 54 mmHg, P = 0.024) and anal pressure (82 mmHg vs 63 mmHg, P = 0.008) during simulated evacuation without rectal distention, were higher in males. The threshold for the first sensation was lower in females (40 mL vs 30 mL, P = 0.021) but desire to defecate (105 mL vs 90 mL, P = NS) and maximum tolerable volume (160 mL vs 140 mL, P = NS) were not significantly different in males and females. Anal residual pressure (median mmHg 83 vs 71 mmHg, P = 0.025) was higher in subjects < 40 years of age. Maximum anal squeeze pressure (185 mmHg vs 165 mmHg, P = 0.024) and maximum rectal pressure (75 mmHg vs 62 mmHg, P = 0.032) during push higher in BMI < 23 kg/m2.ConclusionsThe present study provides normal data for the Indian population that can be used for comparison and further work. Age, gender, and BMI affect anorectal parameters in HRAM and should be considered while reporting.

Read-out Segmented Echo Planar Imaging with Two-Dimensional Navigator Correction (RESOLVE): An Alternative Sequence to Improve Image Quality on Diffusion-Weighted Imaging of Prostate.

We aimed to investigate if the use of read-out segmented echoplanar imaging with additional two-dimensional navigator correction (Readout Segmentation of Long Variable Echo, RESOLVE) for acquiring prostate diffusion-weighted imaging (DWI) improves image quality, compared to single-shot echoplanar imaging (ss-EPI). This single-center prospective study cohort included 162 males with suspected prostate cancer, who underwent 3 Tesla multiparametric MRI (3T-mpMRI). Two abdominal radiologists, blinded to the clinical information, separately reviewed each 3T-mpMRI study to rank geometrical distortion, degree of rectal distention, lesion conspicuity, and anatomic details delineation first on ss-EPI-DWI and later on RESOLVE-DWI using 5-point scales (1 = excellent, 5 = poor). The average of the ranking scores given by two readers was generated and used as the final score. There was good-to-excellent interreader agreement for scoring image quality parameters on both ss-EPI and RESOLVE. Geometrical distortion scores > 3 was seen in 12.3% (20/162) of ss-EPI images, with all having geometrical distortion score <3 on RESOLVE (p < .001). The mean image distortion score was significantly less on RESOLVE than ss-EPI (1.16 vs 1.61, p < .01 regardless of rectal gas, p< .05 when stratified by the degree of rectal distention ). RESOLVE was superior to ss-EPI for lesion conspicuity (mean 1.35 vs 1.53, p< .002) and anatomic delineation (2.60 vs 2.68, p< .001) of prostate on DWI. Compared to conventional ss-EPI, the use of RESOLVE for acquisition of prostate DWI resulted in significantly enhanced image quality and reduced geometrical distortion. RESOLVE could be an alternative or replacement of ss-EPI for acquiring prostate DWI with significantly less geometrical distortion and significantly improved lesion conspicuity and anatomic delineation.

Greater interruption of visual processing and memory encoding by visceral than somatic pain in healthy volunteers – An fMRI study

Visceral pain is regarded as more salient than somatic pain. It has greater affective and emotional components, i.e., it elicits higher levels of pain-related fear and is perceived as more unpleasant than somatic pain. In this fMRI study, we examined the neural effects of painful visceral as compared to painful somatic stimulation on visual processing and memory encoding in a visual categorization and surprise recognition task in healthy volunteers. During the categorization task, participants received either rectal distensions or heat stimuli applied to the forearm, with stimuli being individually matched for unpleasantness. Behaviorally, visceral pain reduced memory encoding as compared to somatic pain (Kleine-Borgmann et al., 2021). Imaging analyses now revealed that visceral pain was associated with reduced activity (i.e., greater pain-related interruption) in neural areas typically involved in visual processing and memory encoding. These include the parahippocampal gyrus, fusiform gyrus, striatum, occipital cortex, insula, and the amygdala. Moreover, reduced engagement of the lateral occipital complex during visual categorization under visceral pain was associated with higher visceral pain-related fear. These findings obtained in healthy volunteers shed light on the neural circuitry underlying the interruptive effect of visceral pain and pave the way for future studies in patient samples.

GUCY2C‐Enriched Intestinal Neuropod Cells Modulate Visceral Pain

Chronic visceral pain (CVP) is a prevalent and debilitating syndrome with limited treatments. Guanylyl cyclase C (GUCY2C) is the receptor for uroguanylin (GUCA2B) in small intestine and guanylin (GUCA2A) in colorectum. This hormone‐receptor axis produces cyclic (c)GMP accumulation, inducing intestinal fluid secretion. This forms the basis for use of GUCY2C agonists linaclotide and plecanatide to treat constipation‐type irritable bowel syndrome (IBS‐C) and chronic idiopathic constipation (CIC). Unexpectedly, GUCY2C agonists relieve CVP in these patients, and in mouse models of visceral pain. Interestingly, these patients are deficient in uroguanylin, suggesting that constipation and CVP may reflect hormone insufficiency silencing GUCY2C. Indeed, eliminating GUCY2C in mice (GUCY2C‐/‐) produced CVP, evoked by cyclic rectal distension, quantified by the abdominal withdrawal reflex and by phospho‐ERK signaling in the spinal cord dorsal horn. CVP severity in GUCY2C‐/‐ mice recapitulated TNBS‐induced inflammatory bowel disease in wild type (GUCY2+/+) mice. Oral linaclotide relieved TNBS‐induced CVP in wild type mice, but was without effect on CVP in GUCY2C‐/‐ mice. The mechanistic basis of GUCY2C‐dependent visceral analgesia remains obscure. While GUCY2C is expressed by all epithelial cells in intestine, a GUCY2C promoter‐driven GFP reporter revealed a novel rare population of cells enriched in GUCY2C mRNA, protein, and activity. GUCY2CHigh cells, concentrated in duodenum but rare in rectum, morphologically resemble enteroendocrine cells with a basal neuropod potentially synapsing on visceral afferents in the lamina propria, offering a cellular substrate for GUCY2C visceral nociceptive signaling. RNAseq analysis revealed that GUCY2CHigh neuropod cells were deficient in gene products canonically associated with GUCY2C‐driven secretion, including GUCA2A, GUCA2B, CFTR and NHE3. Rather, these cells were enriched in gene sets characteristic of neurons. Importantly, dorsal root ganglia (DRG) cells formed functional connections with GUCY2CHigh neuropod cells in co‐culture. Thus, DRG cells with GUCY2CHigh neuropod cells alone (GUCA2B‐deficient, GUCY2C silenced) were hyperexcitable following current injection, with a reduced rheobase and repetitive action potentials (APs). In contrast, adding linaclotide (hormone replete, GUCY2C activated) silenced DRG neuron excitability, raising the rheobase and eliminating repetitive APs. DRG neuron excitability was not affected by linaclotide in co‐cultures with neuropod cells from GUCY2C‐/‐ mice. Moreover, the effects of linaclotide on DRG neuron excitability was not recapitulated by extracellular cGMP. These observations suggest that GUCY2CHigh neuropod cells synapse with DRG visceral afferents and modulate their excitability. They support a model in which GUCA2B sufficiency activates GUCY2C to suppress DRG neuron excitability, while GUCA2B insufficiency silences GUCY2C to produce DRG hyperexcitability and CVP. Finally, they suggest that linaclotide relieves CVP by stimulating GUCY2CHigh neuropod cells to inhibit DRG excitability and nociceptive signaling.

Positive Treatment Expectations Shape Perceived Medication Efficacy in a Translational Placebo Paradigm for the Gut-Brain Axis.

Placebo research has established the pivotal role of treatment expectations in shaping symptom experience and patient-reported treatment outcomes. Perceived treatment efficacy constitutes a relevant yet understudied aspect, especially in the context of the gut-brain axis with visceral pain as key symptom. Using a clinically relevant experimental model of visceral pain, we elucidated effects of pre-treatment expectations on post-treatment perceived treatment efficacy as an indicator of treatment satisfaction in a translational placebo intervention. We implemented positive suggestions regarding intravenous treatment with a spasmolytic drug (in reality saline), herein applied in combination with two series of individually calibrated rectal distensions in healthy volunteers. The first series used distension pressures inducing pain (pain phase). In the second series, pressures were surreptitiously reduced, modeling pain relief (pain relief phase). Using visual analog scales (VAS), expected and perceived treatment efficacy were assessed, along with perceived pain intensity. Manipulation checks supported that the induction of positive pre-treatment expectations and the modeling of pain relief were successful. Generalized Linear Models (GLM) were implemented to assess the role of inter-individual variability in positive pre-treatment expectations in perceived treatment efficacy and pain perception. GLM indicated no association between pre-treatment expectations and perceived treatment efficacy or perceived pain for the pain phase. For the relief phase, pre-treatment expectations (p = 0.024) as well as efficacy ratings assessed after the preceding pain phase (p < 0.001) were significantly associated with treatment efficacy assessed after the relief phase, together explaining 54% of the variance in perceived treatment efficacy. The association between pre-treatment expectations and perceived pain approached significance (p = 0.057) in the relief phase. Our data from an experimental translational placebo intervention in visceral pain support that reported post-treatment medication efficacy is shaped by pre-treatment expectations. The observation that individuals with higher positive expectations reported less pain and higher treatment satisfaction after pain relief may provide first evidence that perceived symptom improvement may facilitate treatment satisfaction. The immediate experience of symptoms within a given psychosocial treatment context may dynamically change perceptions about treatment, with implications for treatment satisfaction, compliance and adherence of patients with conditions of the gut-brain axis.

Excessive sacral sweating caused by autonomic dysreflexia after traumatic brainstem injury

Abstract Rationale: Autonomic dysreflexia is a release phenomenon of spinal sympathetic preganglionic neurons from supraspinal inhibition, possibly of the lower brainstem origin. It is most frequently observed in patients with severe spinal lesions above the mid-thoracic cord. Theoretically, brainstem lesions may cause autonomic dysreflexia; however, such reports are rare. The author reports a case of autonomic dysreflexia restricted to the sacral area that appeared after brainstem lesions due to a traffic accident. Patient concerns: A 36-year-old man suffered from traumatic subarachnoid hemorrhage and hematomas in the lower brainstem. After he became alert and ambulant, he presented with neurological deficits suggestive of right-sided brainstem lesions, which were visualized on magnetic resonance images. He also complained of excessive sweating in the sacral area whenever he had a desire to void. Diagnoses: On the basis of neurological and radiological findings, and results of the thermal sweating test and sweating induced by bladder or rectal distension, his sacral hyperhidrosis was attributed to autonomic dysreflexia. Interventions: Baclofen (15 mg per day) was administered for more than three months, and the sacral hyperhidrosis gradually subsided. Outcomes: After three months, the patient returned home with minor gait disturbances and sacral sweating. Lessons: This may be the first report of excessive sweating due to autonomic dysreflexia caused by traumatic brainstem lesions restricted to the sacral territory. These observations suggest possible somatotopic arrangements, even in the supraspinal inhibitory pathways. Baclofen may be one of the choices for similar cases.

A Pilot Study of Clinical Evaluation and Formation Mechanism of Irritable Bowel Syndrome-like Symptoms in Inflammatory Bowel Disease Patients in Remission.

Background/AimsSome inflammatory bowel disease (IBD) patients in remission suffer from irritable bowel syndrome (IBS)-like symptoms (IBD-IBS). The pathogenesis has not yet been elucidated. The study aim is to evaluate relationships among quality of life (QOL), psychological status, and visceral sensitivity, and explore the formation mechanism of IBD-IBS.MethodsForty-seven patients with Crohn’s disease in remission, 24 ulcerative colitis in remission, 26 IBS, and 20 healthy controls were included in the study. The abdominal pain, QOL, anxiety, and depression were evaluated through questionnaires. Visceral sensitivity was measured by rectal balloon distension. The serum levels of 5-hydroxytryptamine (5-HT) and nerve growth factor (NGF) were measured by enzyme-linked immunosorbent assay. The expressions of tryptase, 5-HT, NGF, and related receptors in colonic tissues were detected by immunohistochemistry and western blot.ResultsPrevalence of IBS-like symptoms in Crohn’s disease and ulcerative colitis patients in clinical remission was 29.8% and 50.0%, respectively. The QOL was lower, the anxiety/depression scores were higher in IBD-IBS patients than those without IBS-like symptoms. Additionally, patients with IBD-IBS existed visceral hypersensitivity. Besides, abdominal pain was associated with poor QOL, visceral hypersensitivity, anxiety, and depression in IBD-IBS patients. The number of mast cells (MCs) and expressions of 5-HT, NGF, and related receptors were higher in IBD-IBS patients than those with no such symptoms. The serum levels of 5-HT and NGF positively correlated with abdominal pain and visceral hypersensitivity.ConclusionIBD-IBS patients may have low QOL and psychological abnormalities, as wells as visceral hypersensitivity which may be related to increased 5-HT and NGF levels released from activated mast cells.

Barostat or syringe-assisted sensory biofeedback training for constipation with rectal hyposensitivity: A randomized controlled trial.

Rectal hyposensitivity (RH) is a well-known pathophysiological dysfunction in chronic constipation. Whether biofeedback training improves RH and restores bowel function is unknown. To investigate the efficacy of barostat-assisted sensory training (BAST) with syringe-assisted sensory training (SAST) in patients with RH in a randomized controlled trial. Patients with RH and chronic constipation (Rome III) were randomized to receive 6 biweekly sessions of BAST or SAST. Verbal/visual feedback was provided during repeated rectal distensions to improve defecation desire/urge and first sensations with either 10-cm balloon connected to barostat (BAST) or 4-cm balloon connected to syringe and manometry probe (SAST). Sensory thresholds, bowel symptoms, and therapist and patient's rating of treatments were compared. The primary outcome (responders) was the improvement in ≥2sensory thresholds. Sixty-six patients were enrolled: 32 received BAST, 34 received SAST, and 56 completed study. There were significantly more responders in BAST group than SAST (78% vs. 53%, p=0.0320). Rectal sensation normalized in 81% with BAST compared to 56% with SAST (p=0.0270). When compared to baseline, desire and urge to defecate thresholds and bowel satisfaction improved with BAST (p=0.0013; p=0.0002; p=0.0001) and SAST (p=0.0012; p=0.0001; p<0.0001) and number of complete spontaneous bowel movements with BAST (p=0.0029) but without inter-group differences. Therapists rated BAST as superior to SAST (p<0.0001), but patients rated both equally. Sensory biofeedback training was effective and significantly improved rectal sensation and constipation symptoms. Although both techniques were useful, the novel BAST was more efficacious and easier to administer for treating RH.

Optimized Tibial Nerve Stimulation Partially Reduces Visceral Hypersensitivity in Rats Mediated via Autonomic and Opioid Mechanisms

The aim of this study was to investigate the therapeutic effect and possible mechanisms of tibial nerve stimulation (TNS) on visceral hypersensitivity in rats. 1) The effects of TNS with five sets of parameters on visceral sensitivity in normal rats were evaluated by the assessment of abdominal electromyogram (EMG) and abdominal withdrawal reflex (AWR). 2) The effects and mechanisms of TNS with a special set of parameters (14Hz, 330 μsec, and 40% motor threshold) were evaluated in acute visceral hypersensitivity rats induced by restraint stress and colonic hypersensitized rats induced by acetic acid during the neonatal stage assessed by the EMG, AWR, and the spectral analysis of heart rate variability derived from the electrocardiogram. 1) In normal rats, TNS did not show any effect on the visceromotor reflex. 2) In rats with restraint stress-induced hypersensitivity, TNS with the special set of parameters reduced AWR scores and EMG responses to rectal distention at a pressure of 20-60 mmHg (p < 0.05, vs. baseline for both AWR and EMG). Concurrently, TNS increased vagal activity and decreased sympathetic activity (p < 0.03 for both). 3) Similar effects were noted on the EMG (p < 0.05, vs. baseline) and AWR (p < 0.05 vs. baseline) with acute and chronic TNS in rats with chronic colonic hypersensitivity and the effects were blocked by naloxone. TNS with parameters of 14Hz, 330 μsec, and 40% motor threshold is effective in improving visceral hypersensitivity in rodent models of colonic hypersensitivity via the modulation of autonomic and opioid mechanisms.

Does pain modality play a role in the interruptive function of acute visceral compared with somatic pain?

Acute pain captures attentional resources and interferes with ongoing cognitive processes, including memory encoding. Despite broad clinical implications of this interruptive function of pain for the pathophysiology and treatment of chronic pain conditions, existing knowledge exclusively relies on studies using somatic pain models. Visceral pain is highly prevalent and seems to be more salient and threatening, suggesting that the interruptive function of pain may be higher in acute visceral compared with somatic pain. Implementing rectal distensions as a clinically relevant experimental model of visceral pain along with thermal cutaneous pain for the somatic modality, we herein examined the impact of pain modality on visual processing and memory performance in a visual encoding and recognition task and explored the modulatory role of pain-related fear and expectation in 30 healthy participants. Despite careful and dynamically adjusted matching of stimulus intensities to perceived pain unpleasantness over the course of trials, we observed greater impairment of cognition performance for the visceral modality with a medium effect size. Task performance was not modulated by expectations or by pain-related fear. Hence, even at matched unpleasantness levels, acute visceral pain is capable of interfering with memory encoding, and this impact seems to be relatively independent of pain-related cognitions or emotions, at least in healthy individuals. These results likely underestimate the detrimental effect of chronic pain on cognitive performance, which may be particularly pronounced in acute and chronic visceral pain.

Duodenal and proximal jejunal motility inhibition associated with bisacodyl-induced colonic high-amplitude propagating contractions.

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high-amplitude propagating contractions (HAPCs). Whereas the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility. Twenty-seven children (9.3 ± 1.2 yr) undergoing simultaneous high-resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed before and after colonic infusion of bisacodyl. Patients were divided into two groups: responders and nonresponders based on the presence of high-amplitude propagating contractions (HAPCs) after bisacodyl infusion. Nineteen patients were responders. A total of 188 postbisacodyl HAPCs was identified with a mean count of 10.4 ± 5.5 (range, 3-22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg. No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the nonresponders, there was no detectable change in small bowel motility after bisacodyl infusion. Bisacodyl-induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content.NEW & NOTEWORTHY The present study has shown, for the first time, that the presence of high-amplitude propagating contractions induced by bisacodyl is associated with a significant reduction in small bowel motility. These findings support of possible existence of a reflex pathway that causes inhibition of small bowel motility in response to rectal distension.

Optimization of Field Design in the Treatment of Rectal Cancer with Intensity Modulated Proton Beam Radiation Therapy: How Many Fields Are Needed to Account for Rectal Distension Uncertainty?

PurposePreoperative chemoradiation represents the standard of care in patients with locally advanced rectal cancer. Robustness is often compromised in the setting of proton beam therapy owing to the sensitivity of proton particles to tissue heterogeneity, such as with intestinal gas. The ideal beam arrangement to mitigate the anatomic uncertainty caused by intestinal gas is not well defined. Methods and MaterialsWe developed pencil beam scanning plans using (1) 1-beam posteroanterior (PA) plans, (2) 2-beam with right and left posterior oblique (RPO and LPO) plans, (3) 3-beam with PA and opposed lateral plans, and (4) 5-beam with PA, RPO, LPO, and opposed lateral plans. We created 12 plans with robustness optimization and ran a total of 60 plan evaluations for varying degrees of intestinal gas distension to evaluate which plans would maintain clinical goals to the greatest degree. ResultsA single PA beam resulted in considerable loss of target coverage to the clinical target volume prescribed 50 Gy (volume receiving 100% of the prescribed dose [V100%] < 90%) with rectal distension ≥3 cm in diameter in the short axis. In contrast, the other field designs maintained coverage with up to 5 cm of distension. On plans generated based on a 5-cm distended rectum with air medium, the 1-beam, 3-beam, and 5-beam arrangements resulted in loss of target coverage (V100% < 90%) with rectal contraction ≤3 cm, whereas the 2-beam arrangement maintained coverage to as low as 2 cm. On plans generated based on a 3-cm distension of the rectum, both the 2-beam and 3-beam arrangements maintained V100% > 90% even with collapsed rectum to as low as 1 cm, simulating a patient treatment scenario without any rectal gas. ConclusionsA single PA beam should be avoided when using proton beam therapy for rectal cancer. RPO/LPO and PA/opposed lateral arrangements may both be considered; RPO/LPO is favored to reduce integral dose and avoid beams traversing the hips. In patients for whom the plan CT has rectal distension of ≥3 cm, resimulation or strategies to reduce intestinal gas should be strongly considered.

Long-term anorectal function in rectal cancer patients treated with chemoradiotherapy and endorectal brachytherapy.

The aim was to study anorectal function in long-term survivors after combined, curatively intended, chemoradiotherapy and endorectal brachytherapy for low rectal cancer. This was a case-control design. We compared anorectal function by anal manometry, anal functional lumen imaging probe (EndoFLIP) and rectal bag distension in rectal cancer patients (RCPs) and healthy, normal subjects (NSs). Symptoms were assessed by the low anterior resection syndrome (LARS) and Wexner faecal incontinence scores. Thirteen RCPs (12 men, median age 68years, range 52-92) after 60Gy radiotherapy, 5Gy endorectal brachytherapy and oral tegafur-uracil with complete clinical response (median time since treatment 2.8years, range 2.2-5.6) were compared to 15 NSs (14 men, median age 64years, range 47-75). RCPs had lower than normal anal resting pressure, 38.6 mmHg (range 8.8-67.7) versus 58.8mmHg (25.7-105.2) (P<0.003), and squeeze pressure, 117 mmHg (55.2-203) versus 188mmHg (103-248) (P<0.01). Squeeze-induced pressure increase recorded by EndoFLIP was also lower in RCPs (q>7.56, P<0.001) as was the anal canal resistance to increasing distension (q=3.13, P<0.05). No differences in median rectal volume at first sensation (72 [22-158] vs. 82 [36-190] ml, P=0.4) or at urge to defaecate (107 [42-227] vs. 132 [59-334] ml, P=0.2) were found. However, maximum tolerable rectal volume was lower in RCPs (145 [59-319] vs. 222 [106-447] ml, P<0.02). The median (range) low anterior resection syndrome score was 27 (0-39) for RCPs and 7 (0-23) for NSs (P<0.001), while the Wexner score was 0 (0-5) versus 0 (0-4) (P=0.56). Radiotherapy combined with endorectal brachytherapy for rectal cancer causes long-term anorectal symptoms, impaired anal sphincter function and reduced rectal capacity.

Spinal Cord Perfusion Pressure Correlates with Anal Sphincter Function in a Cohort of Patients with Acute, Severe Traumatic Spinal Cord Injuries

BackgroundAcute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site.MethodsWe recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A–C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures.ResultsData were collected from 14 patients with consecutive traumatic spinal cord injury aged 22–67 years. The mean resting anal pressure was 44 cmH2O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH2O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (Ȓ2 = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH2O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH2O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70–90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry.ConclusionsOur data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence.

When gut feelings teach the brain to fear pain: Context-dependent activation of the central fear network in a novel interoceptive conditioning paradigm

The relevance of contextual factors in shaping neural mechanisms underlying visceral pain-related fear learning remains elusive. However, benign interoceptive sensations, which shape patients’ clinical reality, may context-dependently become conditioned predictors of impending visceral pain. In a novel context-dependent interoceptive conditioning paradigm, we elucidated the putative role of the central fear network in the acquisition and extinction of pain-related fear induced by interoceptive cues and pain-predictive contexts.In this fMRI study involving rectal distensions as a clinically-relevant model of visceroception, N = 27 healthy men and women underwent differential conditioning. During acquisition training, visceral sensations of low intensity as conditioned stimuli (CS) predicted visceral pain as unconditioned stimulus (US) in one context (Con+), or safety from pain in another context (Con–). During extinction training, interoceptive CS remained unpaired in both contexts, which were operationalized as images of different rooms presented in the MRI scanner.Successful contextual conditioning was supported by increased negative valence of Con+ compared to Con– after acquisition training, which resolved after extinction training. Although interoceptive CS were perceived as comparatively pleasant, they induced significantly greater neural activation of the amygdala, ventromedial PFC, and hippocampus when presented in Con+, while contexts alone did not elicit differential responses. During extinction training, a shift from CS to context differentiation was observed, with enhanced responses in the amygdala, ventromedial, and ventrolateral PFC to Con+ relative to Con–, whereas no CS-induced differential activation emerged.Context-dependent interoceptive conditioning can turn benign interoceptive cues into predictors of visceral pain that recruit key regions of the fear network. This first evidence expands knowledge about learning and memory mechanisms underlying interoceptive hypervigilance and maladaptive avoidance behavior, with implications for disorders of the gut-brain axis.