Low anterior resection syndrome in a Scandinavian population of patients with rectal cancer: a longitudinal follow-up within the QoLiRECT study.

AIM: Low anterior resection syndrome (LARS) is common after low anterior resection. Our aim was to evaluate the prevalence and 'bother' (subjective, symptom-associated distress) of major LARS after 1 and 2 years, identify possible risk factors and relate the bowel function to a reference population. METHOD: The QoLiRECT (Quality of Life in RECTal cancer) study is a Scandinavian prospective multicentre study including 1248 patients with rectal cancer, of whom 552 had an anterior resection. Patient questionnaires were distributed at diagnosis and after 1, 2 and 5 years. Data from the baseline and at 1- and 2-year follow-up were included in this study. RESULTS: The LARS score was calculated for 309 patients at 1 year and 334 patients at 2 years. Prevalence was assessed by a generalized linear mixed effects model. Major LARS was found in 63% at 1 year and 56% at 2 years. Bother was evident in 55% at 1 year, decreasing to 46% at 2 years. Major LARS was most common among younger women (69%). Among younger patients, only marginal improvement was seen over time (63-59%), for older patients there was more improvement (62-52%). In the reference population, the highest prevalence of major LARS-like symptoms was noted in older women (12%). Preoperative radiotherapy, defunctioning stoma and tumour height were found to be associated with major LARS. CONCLUSION: Major LARS is common and possibly persistent over time. Younger patients, especially women, are more affected, and perhaps these patients should be prioritized for early stoma closure to improve the chance of a more normal bowel function.

Urinary dysfunction in patients with rectal cancer: a prospective cohort study.

AIM: Urinary dysfunction is one of many complications after treatment for rectal cancer. The aim of this study was to evaluate the prevalence of patient-reported urinary dysfunction at the time of diagnosis and at 1-year follow-up and to assess the risk factors linked to urinary incontinence. METHOD: Patients with newly diagnosed rectal cancer were included in the QoLiRECT study between 2012 and 2015. Questionnaires from the time of diagnosis and 1-year follow-up were analysed, with 1085 and 916 patients, respectively, eligible for analysis. Regression analyses were made to investigate possible risk factors for incontinence. The patient cohort was also compared with a cohort from the Swedish general population. RESULTS: At baseline, the prevalence of urinary dysfunction (14% of women, 8% of men) was similar to that in the general population. At 1-year follow-up, 20% of patients experienced urinary incontinence (29% of women, 14% of men). Emptying difficulties were experienced by 46% (41% of women, 49% of men) and urgency by 58% across both sexes. Abdominoperineal excision and urinary dysfunction at baseline were found to be independent risk factors for incontinence at 1-year follow-up. Among patients who were continent at baseline, risk factors were female sex, physical inactivity at baseline, comorbidity and abdominoperineal excision. CONCLUSION: Urinary dysfunction is frequent among patients with rectal cancer, with up to a two-fold increase in symptoms 1 year after diagnosis. Unfortunately, few factors are modifiable and these results stress the importance of informing patients of possible outcomes related to urinary dysfunction after treatment for rectal cancer.

InGaN Platelets: Synthesis and Applications toward Green and Red Light-Emitting Diodes.

In this work, we present a method to synthesize arrays of hexagonal InGaN submicrometer platelets with a top c-plane area having an extension of a few hundred nanometers by selective area metal-organic vapor-phase epitaxy. The InGaN platelets were made by in situ annealing of InGaN pyramids, whereby InGaN from the pyramid apex was thermally etched away, leaving a c-plane surface, while the inclined {101̅1} planes of the pyramids were intact. The as-formed c-planes, which are rough with islands of a few tens of nanometers, can be flattened with InGaN regrowth, showing single bilayer steps and high-quality optical properties (full width at half-maximum of photoluminescence at room temperature: 107 meV for In0.09Ga0.91N and 151 meV for In0.18Ga0.82N). Such platelets offer surfaces having relaxed lattice constants, thus enabling shifting the quantum well emission from blue (as when grown on GaN) to green and red. For single InGaN quantum wells grown on the c-plane of such InGaN platelets, a sharp interface between the quantum well and the barriers was observed. The emission energy from the quantum well, grown under the same conditions, was shifted from 2.17 eV on In0.09Ga0.91N platelets to 1.95 eV on In0.18Ga0.82N platelets as a result of a thicker quantum well and a reduced indium pulling effect on In0.18Ga0.82N platelets. On the basis of this method, prototype light-emitting diodes were demonstrated with green emission on In0.09Ga0.91N platelets and red emission on In0.18Ga0.82N platelets.

The effect of endoscopic sinus surgery on quality of life and absenteeism in patients with chronic rhinosinuitis - a multi-centre study.

BACKGROUND: Chronic rhinosinusitis with and without nasal polyps (CRSw/sNP) are common conditions decreasing health-related quality of life (HRQOL). Individual symptoms capable of predicting outcome after endoscopic sinus surgery (ESS) are poorly defined, and the indirect costs of CRS is rarely reported in Europe. METHODOLOGY: Patients with CRSw/sNP admitted for ESS were prospectively enrolled. Patients completed the 22 Sinonasal Outcome Test (SNOT-22), the short-form 36-item questionnaire (SF-36), a Visual Analogue Scale (VAS) and reported CRS-related absenteeism pre- and post-operatively. RESULTS: 181 patients were included. The SNOT-22 score diminished from 51.8 (48.7-55.0) pre-operatively to 33.0 (29.2-36.8) at 6 months. 64% achieved a clinically important improvement in the SNOT-22. SF-36 scores improved statistically significantly in all domains except Role Emotional. The VAS score halved from 68 (65-71) to 34 (29-39) at 6 months post-operatively. A pre-operative SNOT-22 score over 20 implied a greater chance of score improvement after 6 months. A multivariate model identified individual items associated with SNOT-22. Further, patients that had lees than 12 months of sinus disease derived greatest benefit. CRS-related absenteeism dropped from 8-14 days to 1-7 days 12 months after ESS. CONCLUSIONS: This prospective study showed that ESS significantly improved the HRQOL and decreased absenteeism of patients with CRSw/sNP. Shorter duration of disease and Need to blow nose and Blockage/congestion of nose of SNOT-22 were identified as predictive factors for good surgical outcome.

The association between the intake of specific dietary components and lifestyle factors and microscopic colitis.

BACKGROUND/OBJECTIVES: The incidence of microscopic colitis (MC) has increased over the previous decades. In addition to smoking and drugs, currently unidentified environmental factors may have a role. The aim of this study was to determine whether specific dietary or other lifestyle factors were associated with the development of MC. SUBJECT/METHODS: The population-based cohort Malmö Diet and Cancer Study of 28 095 individuals was examined. Information about dietary habits was collected by a modified diet history method. Data on anthropometry were measured, and socio-economic and lifestyle factors were collected by questionnaires. Cases of MC were identified in medical registers. Associations were estimated using Cox regression analysis. RESULTS: During a 22-year period, 135 patients were diagnosed with MC. Intakes of protein, carbohydrates, sucrose, saturated fat, monounsaturated fat, polyunsaturated fat, omega-3 or omega-6 fatty acids, fibre and zinc were not associated with MC. We could verify the previously reported association between MC and smoking (hazard ratio (HR): 2.29; 95% confidence interval (CI): 1.66-3.84) and the female gender (HR: 3.57; 95% CI: 2.22-5.74). High alcohol consumption was associated with an increased risk for MC (HR: 1.89 for the highest quartile; 95% CI: 0.82-4.33, P for trend=0.032). In a post hoc analysis, alcohol intake including all patients independently of consumption seemed to reduce the smoking-related risk. CONCLUSIONS: Despite a large cohort and a long follow-up period, we could not detect any dietary risk factors for MC. The aetiological mechanisms behind the positive impact of smoking and alcohol on MC risk should be investigated.

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.

A multi-centre study on quality of life and absenteeism in patients with CRS referred for endoscopic surgery.

AIMS: This study summarises the health-related quality of life (HRQOL) scores and absenteeism caused by sinus problems in patients awaiting surgery with the diagnoses recurrent acute rhinosinusitis (RARS), chronic rhinosinusitis with nasal polyps (CRS+NP) or CRS without nasal polyps (CRS-NP), in a prospective multi-centre study. METHODOLOGY: Two hundred and seven patients with RARS, CRS+NP or CRS-NP were enrolled. EP3OS definitions of CRS and NP were used. The patients completed the 22 Sinonasal Outcome Test (SNOT-22), the short-form 36-item questionnaire (SF-36), the Hospital Anxiety and Depression Scale (HAD) and a total Visual Analogue Scale (VAS) regarding rhinosinusitis symptoms. RESULTS: SNOT-22 and VAS scores indicated severe disease. Comparison of the HRQOL scores in the three rhinosinusitis subgroups showed statistical differences in nine of the SNOT-22 items and in the SF-36 subscale of bodily pain. Mean scores of SF-36 were significantly lower than that of the normal Swedish population. According to the HAD scores, 28% of the patients had probable or possible anxiety or depression disorder. Fifty-seven percent of the patients reported absenteeism from work due to sinus problems. CONCLUSIONS: RARS, CRS+NP and CRS-NP significantly decrease HRQOL. Some statistically significant differences in HRQOL were found between the three rhinosinusitis subgroups. Absenteeism due to chronic sinus conditions is considerable.

Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin-releasing hormone in serum.

BACKGROUND: The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. METHODS: Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses. KEY RESULTS: Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses. CONCLUSIONS & INFERENCES: Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.

Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis.

BACKGROUND: Assessment of gastrointestinal (GI) involvement in systemic sclerosis (SSc) is difficult. Measurement of calprotectin in faeces is a valuable tool for the assessment of inflammatory bowel diseases. Calprotectin is an intracellular protein found in leucocytes and is a potent activator of the innate immune system. OBJECTIVE: To determine whether faecal calprotectin (F-calprotectin) could serve as a biomarker of GI disease in SSc. DESIGN: In a cross-sectional study, F-calprotectin and plasma calprotectin were measured in patients with SSc using an enzyme-linked immunosorbent assay. F-calprotectin concentrations were evaluated in relation to cineradiography, medical records, laboratory measurements and patients' subjective GI symptoms. SETTING: The study was conducted at a tertiary referral centre for SSc. SUBJECTS: The study comprised 81 consecutive patients with SSc. RESULTS: A majority of the patients had pathological levels of F-calprotectin when compared to accepted clinical reference values for healthy adults. F-calprotectin did not correlate with calprotectin levels in plasma. F-calprotectin was associated with the following patient characteristics: pathological cineradiography, history of referral to another clinic because of GI disease, treatment of vitamin or mineral deficiency and use of proton pump inhibitors. We did not find any significant correlation between F-calprotectin and patient-reported GI symptoms. CONCLUSION: Faecal calprotectin is increased in a majority of patients with SSc. It correlates with objective and clinically important features of GI disease, and faecal concentrations do not vary with plasma concentrations. We suggest that F-calprotectin is a promising objective non-invasive biomarker of GI involvement in SSc.

Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects.

BACKGROUND: Oxytocin is expressed throughout the gastrointestinal tract and is released in response to a fatty meal. Administration of an oxytocin receptor antagonist prolongs the gastric emptying rate. The aim of this study was to examine the effect of oxytocin on gastric accommodation, gastric emptying time, and satiety after food intake. METHODS: Ten healthy subjects participated in a slow satiety drinking test with a liquid meal. Every 5 min the subjects scored their sensation of satiety using a visual analogue scale (VAS) until maximum satiety was reached and the amount of liquid intake was determined. Twelve subjects participated in a gastric emptying test. They were given a standardized meal containing 20 radio-opaque markers, after which fluoroscopy was performed and VAS was scored every hour. Both tests were performed four times during infusions of saline and three different oxytocin concentrations. Blood was collected for oxytocin concentration measurements. KEY RESULTS: There were no differences in the volume of nutrient intake at maximum satiety between the three doses of oxytocin and saline. However, lower satiety scores at maximum satiety were seen after oxytocin infusion (P = 0.031), with 40 mU min(-1) being the most effective dosage (P = 0.013), and this was also true 30 min after finishing the meal (P = 0.032). There was no difference in gastric emptying time between saline and oxytocin. The oxytocin concentration in plasma was increased proportional to the oxytocin infusions. CONCLUSIONS & INFERENCES: Infusion of oxytocin reduces satiety without affecting the volume of nutrient intake or gastric emptying in healthy subjects.

An association between Type 2 diabetes and alpha-antitrypsin deficiency.

AIMS: Alpha(1)-Antitrypsin (AAT) is a serine protease inhibitor which recently has been shown to prevent Type 1 diabetes development, to prolong islet allograft survival and to inhibit pancreatic B-cell apoptosis in vivo. It has also been reported that Type 1 diabetic patients have significantly lower plasma concentrations of AAT, suggesting the potential role of AAT in the pathogenesis of Type 1 diabetes. We have investigated whether plasma AAT levels are altered in Type 2 diabetes. METHODS: The study included patients with Type 2 diabetes (n = 163) and non-diabetic control subjects matched for age, sex and smoking habits (n = 158) derived from the population-based Malmö Diet and Cancer study. Plasma samples were analysed for AAT concentration and phenotype and serum glucose, insulin, C-reactive protein and lipid levels were measured. Glycated haemoglobin was also measured. RESULTS: In the diabetic group, the women had higher mean plasma AAT levels than men (P < 0.05). The mean plasma AAT levels did not differ between diabetic and control subjects. However, the number of individuals with low AAT levels (< 1.0 mg/ml) was 50% higher in the diabetic group (P < 0.05) and the frequency of AAT deficiency genotypes was 50% higher (NS) in diabetic compared with control subjects. In the group of diabetic patients with AAT < 1 mg/ml, AAT directly correlated with systolic blood pressure (P = 0.048) and inversely correlated with waist-hip ratio (P = 0.031). CONCLUSIONS: Our results provide evidence that deficiency of AAT may be associated with an increased risk of developing Type 2 diabetes.

Transients in the formation of nanowire heterostructures.

We present results on the effect of seed particle reconfiguration on the growth of short InAs and InP nanowire segments. The reconfiguration originates in two different steady state alloy compositions of the Au/In seed particle during growth of InAs and InP. From compositional analysis of the seed particle, the In content in the seed particle is determined to be 34 and 44% during InAs and InP growth, respectively. When switching between growing InAs and InP, transient effects dominate during the time period of seed particle reconfiguration. We developed a model that quantitatively explains the effect and with the added understanding we are now able to grow short period (<10 nm) nanowire superlattices.

Vasopressin receptor mRNA expression in the human gastrointestinal tract.

BACKGROUND/AIM: Vasopressin and oxytocin are closely related peptides, and both exert effects on the gastrointestinal function. In the present study, we wanted to map the expression of vasopressin receptor mRNAs (V1a, V1b/V3, and V2) in nontumorous tissue biopsy specimens of human gastrointestinal tract and surrounding tissues. METHODS: Total and polyA+ RNAs were isolated from human tissue biopsy specimens using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA. Semi-nested PCR amplifications were carried out, using gene-specific V1a, V1b/V3, and V2 receptor primers. The PCR amplicons were partially sequenced to confirm their identity. RESULTS: The present study demonstrated the expression of vasopressin receptor mRNAs in human gastrointestinal tract, pancreas, kidney, lung, brain, and ovary. The expression pattern varied between different parts of the gastrointestinal tract. In the colon ascendens, V1a receptor mRNA expression could not be detected in 3 out of 4 analyzed tissue biopsy specimens. On the other hand, all the vasopressin receptor mRNAs were expressed in all colon transversum biopsy samples. CONCLUSIONS: V1a, V1b/V3, and V2 receptor mRNAs are widely expressed throughout human gastrointestinal tract and surrounding tissues. The data obtained provide information for further mapping and determination of the physiological role of the vasopressin receptor mRNA expression in normal and tumorous tissues.

Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus.

AIMS: Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. METHODS: Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. RESULTS: Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. CONCLUSION: Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other.

Nutritional aspects in patients with functional gastrointestinal disorders and motor dysfunction in the gut. Working team report of the Swedish Motility Group (SMoG).

In reviews regarding the management of patients with functional gastrointestinal disorders and motility disturbances within the gut nutritional aspects and dietary advice is often put forward as being of great importance. However, there are relatively few high-quality, interventional studies in the literature supporting an important role for general dietary advice to improve symptoms in these patients. Nutritional supplementation to patients with malnutrition due to severe dysfunction of the gastrointestinal tract is of course less controversial, even though different views on how this should be performed exist. The content of this article is based on presentations given by the authors during the second meeting of the Swedish Motility Group held in Gothenburg in March 2005, and aims to give an overview on the role of dietary advice and nutritional supplementation to patients with gastrointestinal dysfunction of different severity.

Oesophageal dysmotility, delayed gastric emptying and autonomic neuropathy correlate to disturbed glucose homeostasis.

AIMS/HYPOTHESIS: Among diabetic patients, glucose homeostasis may be affected by abnormal gastrointestinal motility and autonomic neuropathy. This study analysed whether oesophageal dysmotility, delayed gastric emptying or autonomic neuropathy affect glucose homeostasis. MATERIALS AND METHODS: Oesophageal manometry and gastric emptying scintigraphy were performed in 20 diabetic patients. Heart-rate variation during deep breathing (expiration/inspiration [E/I] ratio) and continuous subcutaneous glucose concentrations for a period of 72 h were also monitored in the same patients. RESULTS: Oesophageal dysmotility was found in eight of 14 patients. Eleven of 20 patients had delayed gastric emptying (abnormal gastric emptying half-time [T (50)]) and nine of 18 had an abnormal E/I ratio. Complaints of abdominal fullness were predictive of delayed gastric emptying. A low peristaltic speed of the oesophagus was associated with impaired T (50) (r ( s )=-0.67; p=0.02). One hour after breakfast, subcutaneous glucose levels decreased in patients with delayed gastric emptying but continued to rise in those with normal emptying. Consequently, the median glucose level 2.5 h after breakfast was lower in the former (9.1 [4.2-12.5] vs 14.3 [11.2-17.7] mmol/l; p<0.05). Glucose fluctuations during the 72 h were significantly higher in patients with an abnormal E/I ratio than in those with a normal E/I ratio (coefficient of variation: 41 [46-49] vs 28 [27-34]%; p=0.008). CONCLUSIONS/INTERPRETATION: Abdominal fullness predicted delayed gastric emptying that was associated with diminished glucose uptake after breakfast. Low oesophageal peristaltic speed was associated with slow gastric emptying whereas parasympathetic neuropathy was associated with increased glucose variations.

Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial.

BACKGROUND: Oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract, where it affects gut function. Clinically, we have noticed an improvement of bowel habits during lactation in constipated women. The aim of this study was to examine whether oxytocin has an effect on bowel symptoms and psychological well being in women with refractory constipation. METHODS: Fifty-nine women with refractory constipation were included in a double blind, multicentre study. After a 2-week run-in period, they were randomly allocated to nasal inhalation of either placebo or oxytocin treatment twice daily for 13 weeks, followed by a 2 weeks, posttreatment period. The patients completed a questionnaire every day concerning bowel habits, abdominal pain and discomfort, and Gastrointestinal Symptoms Rating Scale (GSRS) and Psychological General Well-being (PGWB) twice during the study; namely, during the baseline period and at the end of the treatment period. RESULTS: Both oxytocin and placebo led to improvement of the constipation according to the GSRS and led to improvement in the sensation of incomplete evacuation and anorectal obstruction, without significant differences between the groups. Abdominal pain and discomfort responded weakly to oxytocin, with no effect of the placebo. In a subgroup of patients with IBS and concomitant depression, a weak improvement in depressed mood was observed after oxytocin administartion. CONCLUSION: Nasal administration of oxytocin had no significant advantage over placebo concerning an effect on constipation. However, it seems to have a positive effect on abdominal pain and discomfort and depressed mood. These findings should be further explored.