Long-term survival of metastatic small intestine neuroendocrine tumors: a meta-analysis.

This meta-analysis aims to evaluate the long-term survival and prognostic factors in patients with metastatic small intestine neuroendocrine tumors (siNETs). Patients with siNETs usually present with advanced disease, limiting curative treatment options. The overall survival seems favorable compared to other cancers, but differences in terminology, lack of consistent coding, conflicting results from smaller cohorts, and recent developments of new treatment options make (reliable) survival data difficult to achieve. Nevertheless, accurate survival data are essential for many facets of health care. A systematic literature search was performed using MEDLINE®(PubMed), EMBASE®, Web of Science, and Cochrane Library up to June 30, 2021. Studies were included if the overall survival data in patients with metastatic siNETs were reported. The results were pooled in a random-effects meta-analysis and are reported as hazard ratios and 95% CIs. Subgroup analyses and meta-regression were performed to assess the observed heterogeneity and the impact of important prognostic factors. After screening 9065 abstracts, there were 23 studies, published between 1995 and 2021, that met the inclusion criteria, with a total of 8636 patients. The weighted 5- and 10-year overall survival was 67 and 37%, respectively. Meta-regression identified younger age and primary tumor resection to be associated with better prognosis. Subgroup analyses showed similar results. This study confirms that in an advanced, metastatic setting, the weighted 5- and 10-year overall survival reveal a favorable prognosis, improving over the last few decades. Meta-regression showed that age at diagnosis is an important prognostic factor.

Impact of Specific Bowel Symptoms on Quality of Life in Patients with Midgut Neuroendocrine Tumours.

INTRODUCTION: Patients with midgut neuroendocrine tumours (NETs) suffer from decreased health-related quality of life (HRQoL), in large part due to bowel symptoms. However, it is unknown which bowel symptoms affect HRQoL the most. An enhanced understanding of this is essential to better focus treatment on this aspect of the disease. This study aimed to determine which bowel symptoms affect HRQoL the most in patients with midgut NETs. METHODS: Consenting patients with midgut NET completed the Memorial Sloan Kettering Bowel Function Instrument and the HRQoL questionnaire (EORTC QLQ-C30). The correlation between bowel symptoms and HRQoL was analysed using multiple linear regression, adjusting for age, Charlson Comorbidity Index score, presence of metastatic disease, chromogranin A, and BMI yielding ß-coefficients with 95% confidence intervals. RESULTS: Totally, 119 patients with midgut NET completed the questionnaires and were included in the study. Loose stool and bowel frequency ≥ 3/day were the most common bowel symptoms, reported by 47% and 56% of patients, respectively. However, sensitivity to certain types of food and beverages, a feeling of incomplete emptying of the bowel, and soiling were the symptoms most strongly correlated with decreased HRQoL, especially within domains concerning role and social function, with ß-coefficients for the strongest correlated symptoms of 15.0 and 14.6, respectively. DISCUSSION: While symptoms concerning stool consistency and frequency are common in patients with midgut NET, our study suggests that other, more socially stigmatising symptoms affect patients' HRQoL more. Our findings could help caregivers understand patients' perceptions of the disease and provide avenues for more directed therapies.

Irregular Dietary Habits with a High Intake of Cereals and Sweets Are Associated with More Severe Gastrointestinal Symptoms in IBS Patients.

Dietary advice constitutes one of the first choices of treatment for irritable bowel syndrome (IBS). We have recognized an increased prevalence of sucrase-isomaltase (SI) gene variants in IBS patients, possibly rendering starch- and sucrose-intolerance. The aims were to examine participants' dietary habits at baseline, to correlate habits with gastrointestinal (GI) symptoms and blood levels of minerals and vitamins, and to examine the effect of a starch- and sucrose-reduced diet (SSRD) on GI symptoms. In the study 105 IBS patients (82 women, 46.06 ± 13.11 years), irritable bowel syndrome-symptom severity scale (IBS-SSS)>175, were randomized to SSRD for 2 weeks or continued ordinary eating habits. Blood samples, visual analog scale for irritable bowel syndrome (VAS-IBS), IBS-SSS, and 4-day food diaries were collected at baseline and after 2 weeks. Patients with irregular dietary habits exhibited higher IBS-SSS than patients with regular habits (p = 0.029). Women already on a diet had lower ferritin levels than others (p = 0.029). The intervention led to 66.3% of patients being responders, with differences in the change of IBS-SSS (p < 0.001), abdominal pain (p = 0.001), diarrhea (p = 0.002), bloating and flatulence (p = 0.005), psychological well-being (p = 0.048), and intestinal symptoms' influence on daily life (p < 0.001), compared to controls. Decreased intake of cereals and sweets/soft drinks correlated with decreased scores.

Endoscopic versus Laparoscopic Full-Thickness Biopsy in the Pathological Evaluation of the Enteric Nervous System.

A full-thickness biopsy of the bowel wall is required to evaluate the enteric nervous system. A patient with aggravating gastrointestinal symptoms underwent a laparoscopic full-thickness biopsy of the ileum and, 1 year later, an endoscopic full-thickness biopsy of the sigmoid colon. Both samples showed enteric neuropathy characterized by vacuolated and enlarged neurons. The length of the myenteric plexus was greater in the endoscopic (23 mm) compared to the laparoscopic (11 mm) biopsy, with fewer tissue artefacts in the endoscopic approach [corrected]. Clinical deterioration was paralleled by enteric neuropathy with an increase in the percentage of vacuolated and enlarged enteric neurons from 24 to 35%.

Endoscopic full-thickness biopsy, a novel method in the work up of complicated abdominal symptoms.

Gastrointestinal complaints without obvious organic causes confirmed by clinical laboratory analyses, endoscopy or radiology are often referred to functional entities. Irritable bowel syndrome (IBS) is the most common functional disorder in the gut. Careful examination of these patients may reveal other diagnoses of defined etiologies, e.g., enteric neuropathy, microscopic colitis, and primary Sjögre's syndrome. The present case describes a young patient with incapacitating gastrointestinal symptoms presumed to be IBS, who underwent endoscopic full-thickness biopsy in sigmoid colon. Histopathological examination revealed degenerative enteric neuropathy, possibly secondary to chronic ischemia.

Smoking- and alcohol habits in relation to the clinical picture of women with microscopic colitis compared to controls.

BACKGROUND: Microscopic colitis (MC) induces gastrointestinal symptoms, which are partly overlapping with irritable bowel syndrome (IBS), predominately in middle-aged and elderly women. The etiology is unknown, but association with smoking has been found. The aim of this study was to examine whether the increased risk for smokers to develop MC is a true association, or rather the result of confounding factors. Therefore, patients suffering from MC and population-based controls from the same geographic area were studied regarding smoking- and alcohol habits, and other simultaneous, lifestyle factors, concerning the clinical expression of the disease. METHODS: Women at the age of 73 years or younger, who had been treated for biopsy-verified MC at any of the Departments of Gastroenterology in Skåne, between 2002 and 2010, were invited to the study (240 patients). Women (737) from the population-based prospective cohort study, Malmö Diet and Cancer Study (MDCS), served as controls. A self-administered questionnaire about lifestyle factors, gastrointestinal symptoms, medical conditions and medication at the time for the study was sent by post. RESULTS: Altogether, 131 women with MC could be included after age-matching with controls (median age 56 years) and exclusion of secondary MC. Patients were divided into persistent MC (MC1) and transient MC (MC2). Past smoking was associated with increased risk to develop MC2 (OR = 2.67, 95 CI = 1.15-6.23), whereas current smoking was associated with increased risk to develop MC1 (OR = 3.18, 95 CI = 1.57-6.42). Concomitant symptoms of IBS were associated with smoking (OR = 4.24, 95 CI = 1.92-9.32). Alcohol drinking had no association with MC or IBS. CONCLUSIONS: The results suggest that past smoking is associated with transient MC, whereas current smoking is associated with persistent MC. Smoking is associated with MC patients with concomitant IBS-like symptoms.

A cross-sectional study of subclinical and clinical thyroid disorders in women with microscopic colitis compared to controls.

BACKGROUND AND AIMS. Microscopic colitis (MC), predominantly affecting women, is associated with thyroid disorders, although purely defined of which type, or compared with controls. Its association with subclinical thyroid disorders, and related increased risk of cardiovascular diseases, has never been examined. The aim was to examine the prevalence of autoantibodies and subclinical and clinical thyroid dysfunction in female patients with MC compared with controls. METHODS. Women younger than 73 years old with biopsy-verified MC from the Department of Gastroenterology in Skåne, during 2002-2010, were invited. Out of 240 identified, 133 were finally included. A questionnaire about medical history was completed and blood samples were collected. Serum was analyzed for free thyroxin and triiodothyronine, thyroid-stimulating hormone and anti-thyroid peroxidase (anti-TPO) antibodies. A population-based group of 737 women served as controls. RESULT. The prevalence of thyroid disorders in patients was higher compared to controls [odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.78-4.99], but the prevalence of subclinical disorders was not different (OR = 1.18, 95% CI = 0.48-2.85). Anti-TPO antibodies were present in 10.6% of MC patients and 18.6% of controls. Twenty-five MC patients had hypothyroidism: 15 with Hashimoto's hypothyroidism, 6 with completed treatment of thyrotoxicosis and 4 with completed surgery after nontoxic goiter. CONCLUSION. Thyroid disorders, autoimmune hypothyroidism being most frequent, are more prevalent in patients with MC than in controls, whereas the prevalence of subclinical thyroid disorders in MC patients does not differ significantly from controls.

Auto-antibodies and their association with clinical findings in women diagnosed with microscopic colitis.

BACKGROUND: Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. METHODS AND FINDINGS: Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59-67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. CONCLUSIONS: Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC.

Mucosa-associated bacteria in two middle-aged women diagnosed with collagenous colitis.

AIM: To characterize the colon microbiota in two women histologically diagnosed with collagenous colitis using a culture-independent method. METHODS: Biopsies were taken from the ascending colon and the total DNA was extracted. Universal bacterial primers were used to amplify the bacterial 16S rRNA genes. The amplicons were then cloned into competent Escherichia coli cells. The clones were sequenced and identified by comparison to known sequences. RESULTS: The clones could be divided into 44 different phylotypes. The microbiota was dominated by Firmicutes and Bacteroidetes. Seven phylotypes were found in both patients and constituted 47.5% of the total number of clones. Of these, the most dominating were clones similar to Bacteroides cellulosilyticus, Bacteroides caccae, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides dorei within Bacteroidetes. Sequences similar to Faecalibacterium prausnitzii and Clostridium citroniae were also found in both patients. CONCLUSION: A predominance of potentially pathogenic Bacteroides spp., and the presence of clones showing similarity to Clostridium clostridioforme were found but the overall colon microbiota showed similarities to a healthy one. Etiologies for collagenous colitis other than an adverse bacterial flora must also be considered.

Esophageal dysmotility is more common than gastroparesis in diabetes mellitus and is associated with retinopathy.

OBJECTIVES: Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic and asymptomatic patients. Esophageal dysmotility has also been described, but is not as well-characterized. The etiology and effect of these complications need to be clarified. The aim of the present study was to evaluate esophageal and gastric motility, complications, gastrointestinal symptoms, and plasma biomarkers in a cross-sectional study comprising patients with diabetes mellitus. METHODS: Patients with diabetes were consecutively asked to participate, and eventually 84 volunteers were included in the study. Esophageal manometry and the gastric emptying test were performed in all patients. Type of diabetes, symptoms, diabetic complications, body mass index (BMI), and biomarkers were recorded. Patients were interviewed about gastrointestinal symptoms. RESULTS: Esophageal dysmotility was present in 63% of patients and gastroparesis in 13% of patients. There was no difference in dysmotility between patients with type 1 and type 2 diabetes or between genders. Gastrointestinal symptoms did not correlate to objective findings. Age correlated negatively with gastric emptying rate (p = 0.004). Patients with esophageal dysmotility had longer duration of diabetes compared to those without dysmotility (p = 0.043). In logistic regression analysis, retinopathy was strongly associated with esophageal dysmotility, independent of duration (p = 0.003). CONCLUSIONS: Esophageal dysmotility is more common than gastroparesis in diabetes mellitus independent of gender, symptoms, and type of diabetes. There is a strong association between retinopathy and esophageal dysmotility.

The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women.

BACKGROUND: Lactobacillus species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, Lactobacillus flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels. METHODS: Vaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing. RESULTS: Lactobacillus crispatus was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found. CONCLUSION: Lactobacillus crispatus was more prevalent in the vaginal flora of fertile women, whereas the Lactobacillus flora of rectum did not correlate to the vaginal flora nor to hormonal levels.