Does radiotherapy of the primary rectal cancer affect prognosis after pelvic exenteration for recurrent rectal cancer?

BACKGROUND: Radiotherapy reduces local recurrence rates but is also capable of short- and long-term toxicity. It may also render treatment of local recurrence more challenging if it develops despite previous radiotherapy. OBJECTIVE: This study examined the impact of radiotherapy for the primary rectal cancer on outcomes after pelvic exenteration for local recurrence. DESIGN: We conducted a retrospective review of exenteration databases. SETTING: The study took place at a quaternary referral center that specializes in pelvic exenteration. PATIENTS: Patients referred for pelvic exenteration from October 1994 to November 2012 were reviewed. Patients who did and did not receive radiotherapy as part of their primary rectal cancer treatment were compared. MAIN OUTCOME MEASURES: The main outcomes of interest were resection margins, overall survival, disease-free survival, and surgical morbidities. RESULTS: There were 108 patients, of which 87 were eligible for analysis. Patients who received radiotherapy for their primary rectal cancer (n = 41) required more radical exenterations (68% vs 44%; p = 0.020), had lower rates of clear resection margins (63% vs 87%; p = 0.010), had increased rates of surgical complications per patient (p = 0.014), and had a lower disease-free survival (p = 0.022). Overall survival and disease-free survival in patients with clear margins were also lower in the primary irradiated patients (p = 0.049 and p < 0.0001). This difference in survival persisted in multivariate analysis that corrected for T and N stages of the primary tumor. LIMITATIONS: This study is limited by its retrospective nature and heterogeneous radiotherapy regimes among radiotherapy patients. CONCLUSIONS: Patients who previously received radiotherapy for primary rectal cancer treatment have worse oncologic outcomes than those who had not received radiotherapy after pelvic exenteration for locally recurrent rectal cancer.

Computerized segmentation and measurement of malignant pleural mesothelioma.

PURPOSE: The current linear method to track tumor progression and evaluate treatment efficacy is insufficient for malignant pleural mesothelioma (MPM). A volumetric method for tumor measurement could improve the evaluation of novel treatments, but a fully manual implementation of volume measurement is too tedious and time-consuming. This manuscript presents a computerized method for the three-dimensional segmentation and volumetric analysis of MPM. METHODS: The computerized MPM segmentation method segments the lung parenchyma and hemithoracic cavities to define the pleural space. Nonlinear diffusion and a k-means classifier are then implemented to identify MPM in the pleural space. A database of 31 computed tomography scans from 31 patients with pathologically confirmed MPM was retrospectively collected. Three observers independently outlined five randomly selected sections in each scan. The Jaccard similarity coefficient (J) between each of the observers and between the observer-defined and computer-defined segmentations was calculated. The computer-defined and the observer-defined segmentation areas (averaged over all observers) were both calculated for each axial section and compared using Bland-Altman plots. RESULTS: The median J value among observers averaged over all sections was 0.517. The median J between the computer-defined and manual segmentations was 0.484. The difference between these values was not statistically significant. The area delineated by the computerized method demonstrated variability and bias comparable to the tumor area calculated from manual delineations. CONCLUSIONS: A computerized method for segmentation and measurement of MPM was developed. This method requires minimal initialization by the user and demonstrated good agreement with manually drawn outlines and area measurements. This method will allow volumetric tracking of tumor progression and may improve the evaluation of novel MPM treatments.

The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI): a completed reference database of lung nodules on CT scans.

PURPOSE: The development of computer-aided diagnostic (CAD) methods for lung nodule detection, classification, and quantitative assessment can be facilitated through a well-characterized repository of computed tomography (CT) scans. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) completed such a database, establishing a publicly available reference for the medical imaging research community. Initiated by the National Cancer Institute (NCI), further advanced by the Foundation for the National Institutes of Health (FNIH), and accompanied by the Food and Drug Administration (FDA) through active participation, this public-private partnership demonstrates the success of a consortium founded on a consensus-based process. METHODS: Seven academic centers and eight medical imaging companies collaborated to identify, address, and resolve challenging organizational, technical, and clinical issues to provide a solid foundation for a robust database. The LIDC/IDRI Database contains 1018 cases, each of which includes images from a clinical thoracic CT scan and an associated XML file that records the results of a two-phase image annotation process performed by four experienced thoracic radiologists. In the initial blinded-read phase, each radiologist independently reviewed each CT scan and marked lesions belonging to one of three categories ("nodule > or =3 mm," "nodule <3 mm," and "non-nodule > or =3 mm"). In the subsequent unblinded-read phase, each radiologist independently reviewed their own marks along with the anonymized marks of the three other radiologists to render a final opinion. The goal of this process was to identify as completely as possible all lung nodules in each CT scan without requiring forced consensus. RESULTS: The Database contains 7371 lesions marked "nodule" by at least one radiologist. 2669 of these lesions were marked "nodule > or =3 mm" by at least one radiologist, of which 928 (34.7%) received such marks from all four radiologists. These 2669 lesions include nodule outlines and subjective nodule characteristic ratings. CONCLUSIONS: The LIDC/IDRI Database is expected to provide an essential medical imaging research resource to spur CAD development, validation, and dissemination in clinical practice.

Acceptability and face validity of two mental health screening tools for use in the routine surgical setting.

BACKGROUND: Preoperative assessment of mental health rarely occurs within routine surgery. Any screening tool selected to form part of this process must be deemed practical, acceptable and valid by clinicians and consumers alike. This study aims to assess the acceptability and face validity of two existing mental health screening tools to select one for further development and use in the routine surgical setting. METHODS: A survey of clinicians and consumers was conducted from October 2020 to March 2021 at a tertiary hospital in Sydney, Australia. Using a Likert scale (1-5, lowest to highest rating), the clinicians evaluated four domains for acceptability and two for validity (six overall) and the consumers four domains for acceptability and one for validity (five overall) on the preoperative use of the amended Kessler Psychological Distress Scale (K10) and the Somatic and Psychological Health Report-12 (SPHERE-12). Consensus was achieved through a rating of 4 or 5 being given by 70% or more of participants with domains able to remain unchanged. Free text responses were analysed into themes. RESULTS: A total of 73 participants (51 clinicians; 22 consumers) were included. The K10 received consensus scores (≥ 70%) in four out of six domains for clinicians (4/4 acceptability; 0/2 validity), and all five domains for consumers (4/4 acceptability; 1/1 validity). The SPHERE-12 received consensus scores (≥ 70%) in three domains for clinicians (3/4 acceptability; 0/2 validity), and three domains for consumers (3/4 acceptability; 0/1 validity). Six qualitative themes were described including (1) amendments to tool structure and language; (2) scale response options; (3) difficulty with somatic questions; (4) practicality and familiarity with K10; (5) challenges for specific patient cohorts and (6) timing considerations for patients. CONCLUSION: Adequate acceptability was established for the K10. However further development is required to strengthen its validity for this specific surgical cohort and purpose. Future research to determine the feasibility and acceptability of implementing and using the K10 in the routine surgical setting is now needed.

The first intestinal motility patterns in fetal mice are not mediated by neurons or interstitial cells of Cajal.

In mature animals, neurons and interstitial cells of Cajal (ICC) are essential for organized intestinal motility. We investigated motility patterns, and the roles of neurons and myenteric ICC (ICC-MP), in the duodenum and colon of developing mice in vitro. Spatiotemporal mapping revealed regular contractions that propagated in both directions from embryonic day (E)13.5 in the duodenum and E14.5 in the colon. The propagating contractions, which we termed ripples, were unaffected by tetrodotoxin and were present in the intestine of embryonic Ret null mutant mice, which lack enteric neurons. Neurally mediated motility patterns were first observed in the duodenum at E18.5. To examine the possible role of ICC-MP, three approaches were used. First, intracellular recordings from the circular muscle of the duodenum did not detect slow wave activity at E16.5, but regular slow waves were observed in some preparations of E18.5 duodenum. Second, spatiotemporal mapping revealed ripples in the duodenum of E13.5 and E16.5 W/W(v) embryos, which lack KIT+ ICC-MP and slow waves. Third, KIT-immunoreactive cells with the morphology of ICC-MP were first observed at E18.5. Hence, ripples do not appear to be mediated by ICC-MP and must be myogenic. Ripples in the duodenum and colon were abolished by cobalt chloride (1 mm). The L-type Ca(2+) channel antagonist nicardipine (2.5 microm) abolished ripples in the duodenum and reduced their frequency and size in the colon. Our findings demonstrate that prominent propagating contractions (ripples) are present in the duodenum and colon of fetal mice. Ripples are not mediated by neurons or ICC-MP, but entry of extracellular Ca(2+) through L-type Ca(2+) channels is essential. Thus, during development of the intestine, the first motor patterns to develop are myogenic.

The influence of initial outlines on manual segmentation.

PURPOSE: Initial outlines are often presented as an aid to reduce the time-cost associated with manual segmentation and measurement of structures in medical images. This study evaluated the influence of initial outlines on manual segmentation intraobserver and interobserver precision. METHODS: Three observers independently outlined all pleural mesothelioma tumors present in five computed tomography (CT) sections in each of 30 patient scans. After a lapse of time, each observer was presented with the same series of CT sections with the outlines of each observer superimposed as initial outlines. Each observer created altered outlines by altering the initial outlines to reflect their perception of the tumor boundary. Altered outlines were compared to original outlines using the Jaccard similarity coefficient (J). Intraobserver and interobserver precision of observer outlines were calculated by applying linear mixed effects analysis of variance models to the J values. The percent of minor alterations (alterations that resulted in only slight changes in the initial outline) was also recorded. RESULTS: The average J value between pairs of observer original outlines was 0.371. The average J value between pairs of observer outlines when altered from an identical initial outline was 0.796, indicating increased interobserver precision. The average difference between J values of an observer's segmentation created by altering their own initial outline and when altering a different observer's initial outline was 0.476, indicating initial outlines strongly influence intraobserver precision. Observers made minor alterations on 74.5% of initial outlines with which they were presented. CONCLUSIONS: Intraobserver and interobserver precision were strongly dependent on the initial outline. These effects are likely due to the tendency of observers to make only minor corrections to initial outlines. This finding could impact observer study design, tumor growth assessment, computer-aided diagnosis system validation, and radiation therapy target volume definition when initial outlines are used as an observer aid.

Evolving experience of operating theatre staff with the implementation of robotic-assisted surgery in the public sector.

Objectives The use of robotic-assisted surgery (RAS) remains predominantly in the private sector. In the public sector, the effect of the implementation of RAS on theatre staff is unknown. The aim of this study was to examine the knowledge and attitudes of theatre staff before and after implementation of RAS in the public sector. Methods In all, 250 theatre staff, including nursing, medical and support staff, were invited to participate in the study. A survey investigating the benefits of RAS for patients and staff, concerns towards the workplace environment and facilitators towards the implementation of new technology was administered before (June 2016) and after (February 2019) the implementation of a comprehensive RAS program. Results The survey was completed by 164 (65.6%) staff before and 200 (80.0%) staff after the implementation of RAS. With time, most nursing (P=0.002) and medical staff (P=0.003) indicated that RAS may benefit patients by reducing intraoperative complications, whereas support staff remained uncertain about this benefit (P=0.594). Before the implementation, most medical staff indicated that RAS would benefit staff, although after they were unsure about this benefit. Overall, before RAS implementation, theatre staff were mostly concerned about workplace safety, but this concern was significantly reduced after RAS implementation (P<0.010). Conclusions With time, operating theatre staff considered their RAS program to be associated with enhanced benefits to patients, and their concerns regarding workplace safety were significantly reduced. Conversely, theatre staff were unsure about the benefits of RAS to themselves. It is important for organisations to consider the evolving impact of new technology on their staff and to refine ongoing education and training programs in line with these changes. What is known about the topic? The implementation of RAS is rapidly evolving in major hospitals. Therefore, it is important to investigate the knowledge, attitudes and experiences of operating theatre staff before and after the implementation of RAS, especially in the public sector. What does this paper add? This study found that with time theatre staff considered RAS to be beneficial to patients, and their initial concerns about the effect on workplace safety were significantly reduced. What are the implications for practitioners? It is important for organisations to consider the evolving impact of the implementation of new technology on operating theatre staff and to refine ongoing education and training programs as required.

Discrete-space versus continuous-space lesion boundary and area definitions.

Measurement of the size of anatomic regions of interest in medical images is used to diagnose disease, track growth, and evaluate response to therapy. The discrete nature of medical images allows for both continuous and discrete definitions of region boundary. These definitions may, in turn, support several methods of area calculation that give substantially different quantitative values. This study investigated several boundary definitions (e.g., continuous polygon, internal discrete, and external discrete) and area calculation methods (pixel counting and Green's theorem). These methods were applied to three separate databases: A synthetic image database, the Lung Image Database Consortium database of lung nodules and a database of adrenal gland outlines. Average percent differences in area on the order of 20% were found among the different methods applied to the clinical databases. These results support the idea that inconsistent application of region boundary definition and area calculation may substantially impact measurement accuracy.

Dual energy subtraction and temporal subtraction chest radiography.

Digital radiography and display systems have revolutionized radiologic practice in recent years and have enabled clinical application of advanced image processing techniques. These include dual energy subtraction and temporal subtraction, both of which can improve diagnostic accuracy for abnormal findings in chest radiographs, especially for subtle lesions such as early lung cancer or focal pneumonia. Dual energy radiography exploits the differential attenuation of low-energy x-ray photons by calcium to produce separate images on the bones and soft tissues, which provides improved detection and characterization of both calcified and noncalcified lung lesions. Dual energy subtraction radiography is currently available from 2 of the major vendors and is in clinical use at many institutions in the United States. Temporal subtraction is a complementary technique that enhances interval change, by using a previous radiograph as a subtraction mask, so that unchanged normal anatomy is suppressed, whereas new abnormalities are enhanced. Though it is not yet a product in the United States, temporal subtraction is available for clinical use in Japan. Temporal subtraction can be combined with energy subtraction to reduce misregistration artifacts, and also has potential to improve computer-aided detection of nodules and other types of lung disease.

Effect of timing on baseline quality of life scores among surgical cancer patients.

OBJECTIVES: To investigate differences between quality of life (QoL) scores obtained preoperatively or recalled in the early postoperative period amongst patients undergoing major cancer surgery. RESULTS: Of the 283 patients included, 133 completed their baseline QoL questionnaire preoperatively and 150 postoperatively. Patient groups were broadly comparable in terms of age however the preoperative group had a lower proportion of patients from non-English speaking backgrounds. There were important and statistically significant differences between mean scores for physical health (overall physical health, physical functioning and role physical domains) and mental health (overall mental health and mental health domains) between pre- and postoperative groups. There were no differences for other domain-specific scores (bodily pain, general health, vitality, social functioning and role emotional).

The Lung Image Database Consortium (LIDC): ensuring the integrity of expert-defined "truth".

RATIONALE AND OBJECTIVES: Computer-aided diagnostic (CAD) systems fundamentally require the opinions of expert human observers to establish "truth" for algorithm development, training, and testing. The integrity of this "truth," however, must be established before investigators commit to this "gold standard" as the basis for their research. The purpose of this study was to develop a quality assurance (QA) model as an integral component of the "truth" collection process concerning the location and spatial extent of lung nodules observed on computed tomography (CT) scans to be included in the Lung Image Database Consortium (LIDC) public database. MATERIALS AND METHODS: One hundred CT scans were interpreted by four radiologists through a two-phase process. For the first of these reads (the "blinded read phase"), radiologists independently identified and annotated lesions, assigning each to one of three categories: "nodule >or=3 mm," "nodule <3 mm," or "non-nodule >or=3 mm." For the second read (the "unblinded read phase"), the same radiologists independently evaluated the same CT scans, but with all of the annotations from the previously performed blinded reads presented; each radiologist could add to, edit, or delete their own marks; change the lesion category of their own marks; or leave their marks unchanged. The post-unblinded read set of marks was grouped into discrete nodules and subjected to the QA process, which consisted of identification of potential errors introduced during the complete image annotation process and correction of those errors. Seven categories of potential error were defined; any nodule with a mark that satisfied the criterion for one of these categories was referred to the radiologist who assigned that mark for either correction or confirmation that the mark was intentional. RESULTS: A total of 105 QA issues were identified across 45 (45.0%) of the 100 CT scans. Radiologist review resulted in modifications to 101 (96.2%) of these potential errors. Twenty-one lesions erroneously marked as lung nodules after the unblinded reads had this designation removed through the QA process. CONCLUSIONS: The establishment of "truth" must incorporate a QA process to guarantee the integrity of the datasets that will provide the basis for the development, training, and testing of CAD systems.

The Lung Image Database Consortium (LIDC): an evaluation of radiologist variability in the identification of lung nodules on CT scans.

RATIONALE AND OBJECTIVES: The purpose of this study was to analyze the variability of experienced thoracic radiologists in the identification of lung nodules on computed tomography (CT) scans and thereby to investigate variability in the establishment of the "truth" against which nodule-based studies are measured. MATERIALS AND METHODS: Thirty CT scans were reviewed twice by four thoracic radiologists through a two-phase image annotation process. During the initial "blinded read" phase, radiologists independently marked lesions they identified as "nodule >or=3 mm (diameter)," "nodule <3 mm," or "non-nodule >or=3 mm." During the subsequent "unblinded read" phase, the blinded read results of all four radiologists were revealed to each radiologist, who then independently reviewed their marks along with the anonymous marks of their colleagues; a radiologist's own marks then could be deleted, added, or left unchanged. This approach was developed to identify, as completely as possible, all nodules in a scan without requiring forced consensus. RESULTS: After the initial blinded read phase, 71 lesions received "nodule >or=3 mm" marks from at least one radiologist; however, all four radiologists assigned such marks to only 24 (33.8%) of these lesions. After the unblinded reads, a total of 59 lesions were marked as "nodule >or=3 mm" by at least one radiologist. Twenty-seven (45.8%) of these lesions received such marks from all four radiologists, three (5.1%) were identified as such by three radiologists, 12 (20.3%) were identified by two radiologists, and 17 (28.8%) were identified by only a single radiologist. CONCLUSION: The two-phase image annotation process yields improved agreement among radiologists in the interpretation of nodules >or=3 mm. Nevertheless, substantial variability remains across radiologists in the task of lung nodule identification.

Use of thrombin-based haemostatic matrix in head and neck reconstructions: a potential risk factor for pulmonary embolism.

BACKGROUND: Haemostatic agents including thrombin-based haemostatic matrix are widely used in patients undergoing cardiac, vascular and spinal surgery. These agents promote local haemostasis through activation of the clotting cascade. To our knowledge, this case series is the first report of pulmonary embolization associated with FloSeal following head and neck oncology resection and free flap reconstruction. METHODS: We present five patients who were diagnosed with symptomatic pulmonary embolism after oncologic head and neck free flap reconstructions in 2014 and 2015. RESULTS: There were five patients consisting of three males and two females. The mean age was 67 years, ranging from 60 to 74 years. Pulmonary embolism occurred between 3 and 30 days with a mean of 12 days. Four out of the five reported cases showed involvement of more than one lobe, and two cases had bilateral pulmonary involvement. All but one patient underwent infratemporal fossa dissections as part of the cancer resection. Ten millilitres of FloSeal was applied to the pterygoid plexi in the four patients to achieve haemostasis. All patients received heparin infusion followed by warfarin therapy for at least 6 months with no mortality or complications relating to pulmonary embolism to date. CONCLUSION: Although inconclusive due to study design and small numbers, this series raises the possibility that there may be an association between the use of haemostatic matrix in head and neck oncologic reconstructions and pulmonary embolism. Haemostatic matrix must be used in caution when there is a direct contact with venous endolumens such as the pterygoid plexus and soleus.

Patient entry into randomized controlled trials of colorectal cancer treatment: factors influencing participation.

BACKGROUND: The objective of this study was to investigate willingness to participate in hypothetical surgical randomized controlled trials (RCTs) among patients and clinicians, who answered as if they themselves were patients. METHODS: We interviewed consecutive patients with colorectal cancer admitted for surgery at a tertiary center in Sydney, Australia. We mailed a questionnaire to all colorectal surgeons and medical oncologists in Australia. RESULTS: Overall, 42% (95% CI, 32% to 52%) of patients, 44% (95% CI, 29% to 60%) of surgeons, and 63% (95% CI, 53% to 72%) of oncologists were willing to enter a randomized clinical trial. Oncologists were significantly more likely to participate than either surgeons (P <.001) or patients (P =.001). No significant associations were seen between willingness to participate and patient characteristics. "Risk of cancer recurrence" was rated by the most patients and doctors as an important reason for refusal of trial entry, although patients additionally identified dislike of randomization and quality of life concerns as important barriers. CONCLUSION: More than 40% of patients were willing to enter into a hypothetical RCT involving surgery. Aversion to randomization and perceptions of differential impact of treatment on cancer recurrence and quality of life are likely to be major barriers to patient accrual in trials of colorectal cancer treatment.

Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages.

Motility patterns in the mature intestine require the coordinated interaction of enteric neurons, gastrointestinal smooth muscle, and interstitial cells of Cajal. In Hirschsprung's disease, the aganglionic segment causes functional obstruction, and thus the enteric nervous system (ENS) is essential for gastrointestinal motility after birth. Here we review the development of the ENS. We then focus on motility patterns in the small intestine and colon of fetal mice and larval zebrafish, where recent studies have shown that the first intestinal motility patterns are not neurally mediated. Finally, we review the development of gastrointestinal motility in humans.

Assessment of radiologist performance in the detection of lung nodules: dependence on the definition of "truth".

RATIONALE AND OBJECTIVES: Studies that evaluate the lung nodule detection performance of radiologists or computerized methods depend on an initial inventory of the nodules within the thoracic images (the "truth"). The purpose of this study was to analyze (1) variability in the "truth" defined by different combinations of experienced thoracic radiologists and (2) variability in the performance of other experienced thoracic radiologists based on these definitions of "truth" in the context of lung nodule detection in computed tomographic (CT) scans. MATERIALS AND METHODS: Twenty-five thoracic CT scans were reviewed by four thoracic radiologists, who independently marked lesions they considered to be nodules >or=3 mm in maximum diameter. Panel "truth" sets of nodules were then derived from the nodules marked by different combinations of two and three of these four radiologists. The nodule detection performance of the other radiologists was evaluated based on these panel "truth" sets. RESULTS: The number of "true" nodules in the different panel "truth" sets ranged from 15 to 89 (mean 49.8 +/- 25.6). The mean radiologist nodule detection sensitivities across radiologists and panel "truth" sets for different panel "truth" conditions ranged from 51.0 to 83.2%; mean false-positive rates ranged from 0.33 to 1.39 per case. CONCLUSIONS: Substantial variability exists across radiologists in the task of lung nodule identification in CT scans. The definition of "truth" on which lung nodule detection studies are based must be carefully considered, because even experienced thoracic radiologists may not perform well when measured against the "truth" established by other experienced thoracic radiologists.

Disturbances of colonic motility in mouse models of Hirschsprung's disease.

Mutations in genes encoding members of the GDNF and endothelin-3 (Et-3) signaling pathways can cause Hirschsprung's disease, a congenital condition associated with an absence of enteric neurons in the distal gut. GDNF signals through Ret, a receptor tyrosine kinase, and Et-3 signals through endothelin receptor B (Ednrb). The effects of Gdnf, Ret, and ET-3 haploinsufficiency and a null mutation in ET-3 on spontaneous motility patterns in adult and developing mice were investigated. Video recordings were used to construct spatiotemporal maps of spontaneous contractile patterns in colon from postnatal and adult mice in vitro. In Ret(+/-) and ET-3(+/-) mice, which have normal numbers of enteric neurons, colonic migrating motor complexes (CMMCs) displayed similar properties under control conditions and following inhibition of nitric oxide synthase (NOS) activity to wild-type mice. In the colon of Gdnf(+/-) mice and in the ganglionic region of ET-3(-/-) mice, there was a 50-60% reduction in myenteric neuron number. In Gdnf(+/-) mice, CMMCs were present, but abnormal, and the proportion of myenteric neurons containing NOS was not different from that of wild-type mice. In the ganglionic region of postnatal ET-3(-/-) mice, CMMCs were absent, and the proportion of myenteric neurons containing NOS was over 100% higher than in wild-type mice. Thus impairments in spontaneous motility patterns in the colon of Gdnf(+/-) mice and in the ganglionic region of ET-3(-/-) mice are correlated with a reduction in myenteric neuron density.

Development of colonic motility in the neonatal mouse-studies using spatiotemporal maps.

Colonic migrating motor complexes (CMMCs) are spontaneous, anally propagating constrictions, repeating every 3-5 min in mouse colon in vitro. They are regulated by the enteric nervous system and may be equivalent to mass movement contractions. We examined postnatal development of CMMCs and circular muscle innervation to gain insight into mechanisms regulating transit in the maturing colon. Video recordings of mouse colon in vitro were used to construct spatiotemporal maps of spontaneous contractile patterns. Development of nitric oxide synthase (NOS) and cholinergic nerve terminals in the circular muscle was examined immunohistochemically. In adults, CMMCs appeared regularly at 4.6 +/- 0.9-min intervals (n = 5). These intervals were reduced by inhibition of NOS (2.7 +/- 0.2 min; n = 5; P < 0.05). CMMCs were abolished by tetrodotoxin (n = 4). CMMCs at postnatal day (P)10 were indistinguishable from adult. At birth and P4, CMMCs were absent. Instead, small constrictions that propagated both orally and anally, "ripples," were seen. Ripples were unaffected by tetrodotoxin or inhibition of NOS and were present in Ret(-/-) mice (which lack enteric neurons) at embryonic day 18.5. In P6 mice, only ripples were seen in control, but NOS inhibition induced CMMCs (n = 8). NOS terminals were abundant in the circular muscle at birth; cholinergic terminals were sparse but were common by P10. In mouse, myogenic ripples are the only mechanism available to produce colonic transit at birth. At P6, neural circuits that generate CMMCs are present but are inhibited by tonic activity of nitric oxide. Adult patterns appear by P10.

Assessment of quality of life in the treatment of patients with neuropathic fecal incontinence.

INTRODUCTION: Development of quality-of-life measures has been the focus of research in colorectal disorders in recent years. The assessment of quality of life for fecal incontinence should be more important than quantitative measurement of soiling. PURPOSE: This study assesses specific patient quality-of-life objectives, categorizes objectives, and correlates these objectives with continence scores. METHODS: One hundred eighteen patients entered into a randomized, controlled trial of biofeedback were assessed using the Direct Questioning of Objectives quality-of-life measure. All objectives were documented, categorized, and correlated with continence scores and analog scales. RESULTS: In patients with neuropathic fecal incontinence, the most frequent quality-of-life group concerned the ability to get out of home, to socialize outside of home, to go shopping, and not to have to worry about the location of the nearest toilet while out of home (34 percent; 123/364). At least one of these four objectives was stated by 72 percent of patients (85/118). Only 31 percent of patients (37/118) nominated an objective related to the physical act of soiling. The ability to travel (29 percent), exercise including walking (25 percent), perform home duties (19 percent), family and relationships (22 percent), and job (13 percent) were less frequently cited by patients. CONCLUSION: Continence scores focus heavily on the physical aspects of incontinence such as soiling and hygiene, aspects which seem to be less important to the patients themselves. It is important, therefore, that assessments of fecal incontinence should include reference to quality of life, and in particular to its impact on activities relating to "getting out of the house."

Randomized, controlled trial of biofeedback with anal manometry, transanal ultrasound, or pelvic floor retraining with digital guidance alone in the treatment of mild to moderate fecal incontinence.

BACKGROUND: A prospective, three-armed, randomized, controlled trial was performed to assess whether pelvic floor exercises with biofeedback using anal manometry or transanal ultrasound are superior to pelvic floor exercises with feedback from digital examination alone in terms of continence, quality of life, physiologic sphincter strength, and compliance. Its secondary objectives were to assess whether there are any differences in these outcomes between biofeedback with transanal ultrasound vs. anal manometry and to correlate the physiologic measures with clinical outcome. METHODS: One hundred twenty patients with mild to moderate fecal incontinence were randomized into one of three treatment groups: biofeedback with anal manometry, biofeedback with transanal ultrasound, or pelvic floor exercises with feedback from digital examination alone. Commencing one week after an initial 45-minute assessment session, patients attended monthly treatments for a total of five sessions. Each session lasted 30 minutes and involved sphincter exercises with biofeedback that involved instrumentation or digital examination alone, and patients were encouraged to perform identical exercises twice per day between outpatient visits. RESULTS: One hundred two patients (85 percent) completed the four-month treatment program. Across all treatment allocations, patients experienced modest but highly significant improvements in all nine outcome measures during treatment, with 70 percent of all patients perceiving improvement in symptom severity and 69 percent of patients reporting improved quality of life. With the possible exception of isotonic fatigue time, there were no significant differences between the three treatment groups in compliance, physiologic sphincter strength, and clinical or quality-of-life measures. Correlations between physiologic measures and clinical outcomes were much stronger with ultrasound-based measures than with manometry. CONCLUSIONS: Although patients in this study who completed pelvic floor exercises with feedback from digital examination achieved no additional benefit from biofeedback and measurement with transanal ultrasound or manometry, it may be that the guidance received through digital examination alone offered patients in the pelvic floor exercise group an effective biofeedback mechanism. Contrary to our hypothesis, the use of transanal ultrasound offered no benefit over manometry, but the use of ultrasound for isotonic fatigue time and isometric fatigue contractions provided potentially important physiologic measures that require further study. This study has confirmed, through a large sample of patients, that pelvic floor retraining programs are an effective treatment for improving physiologic, clinical, and quality-of-life parameters in the short term.