Anal function after endoluminal locoregional resection by transanal endoscopic microsurgery and radiotherapy for rectal cancer.

AIM: In patients with rectal cancer, surgery and chemoradiotherapy may affect anal sphincter function. Few studies have evaluated anorectal function after neoadjuvant chemoradiotherapy (n-CRT) and/or transanal endoscopic microsurgery (TEM). The aim of this study was to evaluate the effects of n-CRT and TEM on anorectal function. METHOD: Thirty-seven patients with rectal cancer underwent anorectal manometry and Wexner scoring for faecal incontinence at baseline, after n-CRT (cT2-T3N0 cancer) and at 4 and 12 months after surgery. Water-perfused manometry measured anal tone at rest and during squeezing, rectal sensitivity and compliance. Twenty-seven and 10 patients, respectively, underwent TEM without (Group A) or with n-CRT (Group B). RESULTS: In Group A, anal resting pressure decreased from 68 ± 23 to 54 ± 26 mmHg at 4 months (P = 0.04) and improved 12 months after surgery (60 ± 30 mmHg). The Wexner score showed a significant increase in gas incontinence (59%), soiling (44%) and urgency (37%) rates at 4 months, followed by clinical improvement at 1 year (41%, 26% and 18%, respectively). In group B, anal resting pressure decreased from 65 ± 23 to 50 ± 18 mmHg at 4 months but remained stable at 12 months (44 ± 11 mmHg, P = 0.02 vs preoperative values - no significant difference compared with evaluation at 4 months). Gas incontinence, soiling and urgency were observed in 50%, 50%, 25% and in 38%, 12% and 12% of cases, respectively, 4 and 12 months after treatment. CONCLUSION: TEM does not significantly affect anal function. Instead, n-CRT does affect anal function but without causing major anal incontinence.

Constipation: an emerging risk factor for Parkinson's disease?

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α-synuclein (α-SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α-SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α-SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.

Chronic constipation in hypercalcemic patients with primary hyperparathyroidism.

BACKGROUND: Chronic constipation (C), among gastrointestinal symptoms, is commonly associated with primary hyperparathyroidism (PHPT) and probably attributable to hypercalcemia. OBJECTIVE OF THE STUDY: To evaluate in patients affected with PHPT the prevalence of C utilizing a validated questionnaire and the current prevalence of C compared to that observed in the past and to evaluate the relationship between C and the severity of PHPT. METHODS: 55 outpatients affected with PHPT, admitted to our Department of Internal Medicine and Medical Specialities in the years (2006-2009) were studied (group 1: 50 postmenopausal women and 5 men, mean age 61.9 +/- 9.4 years), together with 55 sex and age matched controls (group 2). Also considered were a group of PHPT patients observed, in the same ambulatory, during the years '70-'80 (group 3). A questionnaire, Rome II criteria, was administered and used to define C, whereas only anamneses were used to define C in group 3. RESULTS: The prevalence of C in patients with PHPT was 21.8% in group 1 vs 12.7% in group 2 (n.s.) and 32.7% in group 3. There is a decreasing trend in the prevalence of C in patients with PHPT as observed from 1970-89 to 2006-2009 (p < 0.05). The reduction of C was associated together with a significant reduction in the serum calcium level (p < 0.001). The presence of C vs its absence in patients with PHPT is characterized by higher values of calcemia (p < 0.001), ionized calcium (p < 0.001), and parathyroid hormone (p = 0.019). CONCLUSION: The actual prevalence of C in patients with PHPT is not significantly different from that found in the control group and is decreasing with respect to the past years. Moreover, C seems to be associated with the severity of the disease rather than with the diagnosis of PHPT per se.

Human muscle-derived stem cells. Effectiveness in animal models of faecal incontinence. Research scheduling.

Researchers believe that human muscle-derived cells are able to restore leak-point pressure to normal levels by differentiating into new muscle fibres that prevent anal sphincter muscle atrophy. Laboratory data are needed to identify exactly how these cells work to regenerate muscle. The objective of this study is to test whether stem cells can be employed to treat internal anal sphincter (IAS) injuries in humans; to this end, this work will use a two-step process to study: first, the effectiveness of the treatment in a sample of animals with artificial injuries to the IAS and then to verify the results in a population of selected humans affected by pathology.

[Algometric approach in the diagnostic evaluation of chest pain]. / Approccio algometrico nella valutazione diagnostica del dolore toracico.

OBJECTIVE: To contribute to a global clinical evaluation of the patients with chest pain, giving a quantitative analysis of the painful experience in the sensory, emotional, value and mixed component and searching significant differences among the different causes of the symptom. MATERIALS AND METHODS: We have administered the "Questionario Italiano del Dolore" by De Benedictis et al. to 92 patients with chest pain, who were divided into 4 diagnostic groups (acute coronary syndrome, coronary artery disease, oesophagus-gastric disease and other) and compared for the quantitative-qualitative features of the associated pain. RESULTS: PRIrcE (Global Value Component) resulted higher in the group "other" (A) compared to the patients with acute ischemic heart disease (CIA), with a statistically significant difference (test U-Mann-Whitney; p = 0.04). This group shows statistically significant differences in the emotional component (PRIrcA; p = 0.01) even compared to pain associated with oesophagus-gastric disease (G). In regard to PRIrcA, the difference between G group and the group of patients with chronic ischemic heart disease (CIC), as well as the "double" category, resulted markedly significant (p = 0.03 and p = 0.01 respectively). We extrapolated the "describers" chosen by at least 50% of patients in every category and obtained the semantics configuration of chest pain for every diagnosis. CONCLUSIONS: PRIrcE resulted lower in CIA group. PRIrcE e PR-IrcA are more represented in CIC group. The same conclusion is valid in the differentiation of pain between CIA and G group and between CIA and A group (the most representative of chronic pain). We found higher values in emotional component compared to pain of new onset as pain becomes chronic.

Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene.

Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio-pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti-inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.

Chronic constipation in hemiplegic patients.

AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed >= 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients' mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.

Chronic abdominal pain associated with intermittent compression of the celiac artery.

Recurrent abdominal pain (RAP), surely one of the most frequent causes of medical intervention, is frequently present in many gastrointestinal disease. Usually no structural and/or biochemical alterations can be demonstrated. This condition is, therefore, considered to be due to functional disorders such as irritable bowel syndrome (IBS) or functional dyspepsia. Previous observations suggest the presence of a rare alteration of celiac vessels among the possible causes of RAP. This pathological condition was known as Dunbar syndrome. We report 2 cases of chronic abdominal pain. The former reported weight loss and the latter anemia with iron deficiency. It is remarkable that patients with initial diagnosis of IBS can be affected by celiac disease (CD), which is the cause of their abdominal pain. Our patients were tested for CD; the former was negative and IBS was diagnosed, the latter was positive and a gluten free diet was prescribed. The presence of an epigastric bruit, accentuated during expiration, suggested a possible vascular alteration known as tripod celiac artery compression syndrome. Duplex Doppler sonography suggests the diagnosis of celiac arterial constriction due the diaphragmatic ligament. These cases show that tripod celiac artery compression syndrome might be a cause of RAP and that it may be evaluated and investigated when the clinical examination discloses an abdominal systolic bruit.

Neurologic disorders affecting the anorectum.

Neurologic disorders that affect the brain, spinal cord, or extrinsic innervation may present with similar symptoms and share common pathophysiology, such as rectal impaction, loss of an urge to defecate, inability to trigger a defecation sequence, obstructive defecation, or incontinence. If these symptoms are persistent or bothersome, they require treatment. The management of a patient with neurologic anorectal dysfunction depends on the underlying pathophysiologic mechanisms. Dietary advice, bowel training, pharmacotherapy, and rehabilitative treatment may be used alone or in combination.

Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation.

AIMS: To assess the long term therapeutic effectiveness, safety, and tolerability of low daily doses of isosmotic PEG electrolyte solutions (PMF-100) administered for a six month period for the treatment of functional constipation, in a double blind, placebo controlled, parallel group study. METHODS: After an initial four week run in period with PMF-100 (250 ml twice daily; PEG 14.6 g twice daily), 70 patients suffering from chronic constipation (58 females, aged 42 (15) years) with normalised bowel frequency (>3 bowel movements (bm)/week) were randomly allocated to receive either PMF-100 or placebo, contained in sachets (one sachet in 250 ml of water twice daily) for 20 weeks. Patients were assessed at four week intervals, and reported frequency and modality of evacuation, laxative use, and relevant symptoms on a diary card. At weeks 1, 12, and 24, a physical examination and laboratory tests were performed. RESULTS: Complete remission of constipation was reported by a significantly (p<0.01) higher number of patients treated with PMF-100 compared with placebo at each four week visit. At the end of the study, 77% of the PMF-100 group and 20% of the placebo group were asymptomatic. Compared with placebo, patients treated with PMF-100 reported hard/pellety stools and straining at defecation less frequently, a significantly higher bowel frequency (week 12: 7. 4 (3.1) v 4.3 (2.5) bm/week, 95% CI 1.64, 4.42; week 24: 7.4 (3.2) v 5.4 (2.1) bm/week, 95% CI 0.13,3.93), reduced consumption of laxative/four weeks (week 12: 0.7 (2.7) v 2.2 (3.3), 95% CI -2.29, 0. 03; week 24: 0.2 (0.8) v 1.4 (2), 95% CI -2.07, -0.023), reduced mean number of sachets used (week 12: 33 (13) v 43 (12), 95% CI -17. 24, 4.56; week 24: 33 (13) v 44 (12), 95% CI -19.68, -2.24), and reduced number of drop outs for therapy failure (16 v 3; p<0.005). Adverse events, physical findings, laboratory values, palatability, and overall tolerance of the solutions did not differ between groups. CONCLUSIONS: Administration of small daily doses of isosmotic PEG electrolyte balanced solutions was effective over a six month period for the treatment of functional constipation. A mean daily dose of approximately 300 ml of PEG solution (PEG 17.52 g) appeared to be safe, well tolerated, and devoid of significant side effects.

Anorectal function in multiple system atrophy and Parkinson's disease.

This study was designed to investigate anorectal function in Parkinson's disease and multiple system atrophy (MSA). After a standardized interview, 17 patients with Parkinson's disease (PD) and 16 patients with multiple system atrophy (MSA) underwent anorectal manometry with a continuously perfused multi-lumen catheter, located to record pressures from the anal canal, and a balloon for rectal distension. Data were analyzed by observers blind to the neurologic diagnosis. Disease duration was shorter in the MSA than in the PD group (6+/-4 versus 10+/-5 yrs, p<0.05). Most patients reported a bowel frequency of less than three evacuations per week and some patients had fecal incontinence. Most manometric recordings disclosed an abnormal pattern during straining (a paradoxic contraction or lack of inhibition) in 13 patients with MSA and 11 patients with PD. Mean anal pressures and rectal sensitivity threshold were not significantly higher in the MSA group, whereas the inhibitory anal reflex and rectal compliance thresholds were within the normal range in both groups. Manometric patterns did not differentiate patients with MSA from patients with PD. Most patients in both groups showed an abnormal straining pattern, decreased anal tone, or both dysfunctions. In conclusion, our findings suggest that although bowel and anorectal dysfunctions do not differentiate MSA from PD, both abnormalities occur earlier and develop faster in MSA than in PD.

Chronic neurogenic lesions of the external anal sphincter and abdomino-perineal dyssynergia in chronic constipation.

BACKGROUND: Neuropathy of the pudendal nerves which may be found in constipated patients has been considered the result of pelvic floor descent due to the repetitive acts of straining at stool. However, the relationship between abdominopelvic dyssynergia, which may lead to repetitive acts of straining and neurophysiopathologic alterations of the pelvic floor has not yet been fully elucidated. AIM: Of this study was to assess the relationship between neurophysiologic alterations of the external anal sphincter, patterns of altered evacuation and defaecographic pelvic floor physiology in 32 patients with chronic idiopathic constipation. RESULTS: At electromyography partial muscle denervation, identified as chronic neurogenic lesions of the external anal sphincter, were found in 19% and dyssynergia (co-contraction of external anal sphincter and abdominal muscles) in 34% of the investigated subjects. Patients with different electromyography patterns did not differ as far as concerns symptoms of altered evacuation, bowel frequency, use of digital manoeuvres, age, and duration of symptoms. The presence of neurophysiologic alterations was significantly associated with altered defaecographic findings: reduced ano-rectal angle at rest in chronic neurogenic lesions and abdomino-pelvic dyssynergia (p < 0.01); excessive pelvic floor descent in the presence of chronic neurogenic lesions (p < 0.05). CONCLUSIONS: In chronically constipated patients symptoms of altered defaecation do not appear to be related to abdomino-pelvic dyssynergia and/or chronic neurogenic lesion of the external anal sphincter and do not show any association with defaecographic alterations. These results suggest that straining at evacuation can be induced by additional factors other than abdomino-pelvic dyssynergia and chronic neurogenic lesions and that these two alterations have different pathogenetic mechanisms.

Use of low dose polyethylene glycol solutions in the treatment of functional constipation.

A brief review is made of trials which used low doses of polyethylene glycol (13-30 g/day) solutions (125-500 ml/day) in the treatment of chronic functional constipation. Most of these were short-term studies, and confirmed that polyethylene glycol solution increased bowel frequency, improved defaecation and decreased stool consistency. Three studies reported that polyethylene glycol electrolyte solution accelerated transit through the large bowel. One long-term study observed remission of constipation-related symptoms in more than 70% of the polyethylene glycol electrolyte solution treated patients, and the efficacy of the treatment was maintained over a 6-month period, despite progressive reduction of daily dosage.

Sequential treatment of chronic constipation in paraplegic subjects.

Chronic constipation is the main gastrointestinal complaint of spinal cord injury (SCI) patients, and has a significant effect on patients' lives, concerning nursing dependence, morbidity and complications. Many therapies have been proposed to treat chronic severe constipation, most of them with limited effect or being unpredictable in their effect or being expensive or very radical. Ten spinal cord injury patients have been submitted to a therapeutic protocol based on a high residue diet, a standardised water intake, and on the use of a sequential schedule of evacuating stimuli. After four weeks of treatment the patients showed an increased frequency of bowel movements per week, a decreased total gastrointestinal transit time, and a decreased need for oral and rectal laxatives. This treatment seems to be effective in modifying patients' bowel habits, and therefore could be considered as a standardised protocol for the management of severe constipation in those who are paraplegic.

Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation.

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42 +/- 15 years, mean +/- SD), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8 +/- 2.3 vs placebo: 2.8 +/- 1.6; P < 0.002) and a significant decrease in straining at defecation (P < 0.01), stool consistency (P < 0.02), and use of laxatives (P < 0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Effect of wheat bran in treatment of chronic nonorganic constipation. A double-blind controlled trial.

After a two-week basal period, 24 patients were randomly allocated to receive, with a crossover double-blind design, for two consecutive four-week periods, bran (20 g/24 hr) or placebo. The daily intake of water and dietary fibers was standardized. Symptomatology, oroanal transit time, bowel frequency, and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment. Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period. Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit. During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit. Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments.

Effect of endogenous cholecystokinin on postprandial gallbladder refilling. Ultrasonographic study in healthy subjects and in gallstone patients.

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB "contractor" patient with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P < 0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.

Perendoscopic manometry of the distal ileum and ileocecal junction: technique, normal patterns, and comparison with transileostomy manometry.

The technique of perendoscopic manometry was used to study the motor patterns of the ileocecal junction and distal ileum. An expert endoscopist cannulated the distal ileum of 20 unsedated subjects in 260 +/- 252 (mean +/- SD) seconds, causing no discomfort beyond that of an ordinary colonoscopic examination. No sphincter-like motor activity was detected at the ileocecal junction, and four distinct motility patterns were identified in the distal ileum: (1) tone variations, (2) slow phasic contractions, (3) regular rapid phasic contractions, and (4) prolonged rapid phasic contractions. Previous appendectomy and insertion of the colonoscope into the distal ileum to position the manometric catheter did not affect the manometric recordings. Perendoscopic manometry of the distal ileum was compared with transileostomy manometry in 9 subjects. Perendoscopic and transileostomy manometric recordings showed the same motor patterns except for a longer occurrence of tone variations with perendoscopic manometry. In conclusion, this study shows that perendoscopic manometry of the distal ileum and ileocecal junction is feasible; recorded motor patterns are not affected.

Role of body position, gender, and age on pelvic floor location and mobility.

The location and mobility of pelvic floor in different body positions and their relation to age and gender was assessed in 117 patients (19 men, 98 women, age range 10-77 years) with chronic nonorganic constipation (defined as less than three bowel movements per week for at least three years) by means of defocography. Eleven females (age range 16-69 years), without gastrointestinal symptoms, affected by noninvasive carcinoma of the cervix represented a control group. Pelvic floor location was measured as the distance in centimeters of the anorectal junction from the pubococcygeal line; pelvic floor mobility was measured during squeezing, straining, and defecation assuming the pelvic location at rest as zero reference. Pelvic floor location and mobility did not differ between controls and constipated patients. In both groups pelvic floor location at rest was significantly higher (P = 0.001) with patients lying down than sitting up, whereas pelvic floor mobility during squeezing was greater with the patients sitting up than lying down (P = 0.003). In both positions, pelvic floor location at rest was significantly lower (P = 0.01) in females than in males. Pelvic floor mobility during squeezing was significantly different between gender. Parity and hysterectomy did not appear to affect pelvic floor location. Data emerging from this study indicate that body position is one of the major determinants of the pelvic floor location.