Diarrhoea is a common and debilitating symptom of Carcinoid syndrome. Effective control of symptoms is achieved with somatostatin analogues (SSAs) and additional loperamide and/or codeine phosphate. Symptom control is lost with time and disease progression. There is, therefore, a strong need for additional and more effective therapies. Telotristat-ethyl is a peripheral tryptophan-hydroxylase inhibitor approved for treatment of diarrhoea. Here, we present our experience of Telotristat for treating carcinoid diarrhoea in a large cohort of patients outside of clinical trials. The primary outcome was reduction in stool frequency of >30%, as defined in most studies.
Patients were identified from a prospective database and information collected retrospectively from the hospital's electronic patient records. We included 31 patients (25 males, 6 females; Median age 69 years) on Telotristat and 10 patients on fortnightly high-dose SSA (6 males, 4 females; Median age 67 years).
The mean (range) duration of treatment in telotristat and 2 weekly SSA groups was 258 (15-479) and 689 (219-1446) days respectively. Primary endpoint was achieved in 82% (23/28) patients on Telotristat with median percentage reduction in stool frequency of 60% (IQR 50-69), compared to 28% (2/7) (22 (−30 to 55) %) in the control group. Odds ratio for reduction in stool frequency >30% was −11, (95% CI 1.71-77.1).
This real world experience supports the effectiveness and safety of Telotristat to treat carcinoid diarrhoea not adequately controlled by standard treatment with SSA.
Chronic atrophic gastritis (CAG) is a precancerous lesion of gastric cancer. This study investigated the diagnostic accuracy of serum pepsinogens in Myanmar to diagnose CAG as non-invasive makers.
A cross-sectional study of 70 dyspeptic patients without red flag signs was recruited and performed endoscopy with mucosal biopsies. Histologic severity was assessed by Operative Link for Gastritis Assessment (OLGA) staging. Serum pepsinogens (PG I and PG II) were measured by ELISA Gastro Panel, Biohit Healthcare (Finland). Serum pepsinogens I/II ratio (PGR) was calculated.
The mean (±SD) age of the study population was 52.57 (±16.33) years. The CAG was diagnosed in 61.4% of dyspeptic patients. The median values of PG I, PG II and PGR in dyspeptic patients were 114.5 ng/mL, 12.7 ng/mL and 9.5, respectively. The median values of PG I and PG II were significantly lower in patients with CAG (P = 0.006 and 0.029) but that of PGR was not significantly changed. Both PG I and PGR were reversely correlated with OLGA stages (P = 0.013 and 0.048). For the best discrimination of CAG, the cut-off values of PG I in Myanmar was ≤114 ng/mL (Sensitivity 55.8%, specificity 63%, accuracy 58.6% and AUC 0.59) and that of PGR was ≤9.5 (Sensitivity 55.8%, specificity 55.6%, accuracy 55.7% and AUC 0.56).
Either PG I or PGR is useful as a non-invasive biomarker for screening of CAG with moderate diagnostic accuracy.
The pathophysiological mechanisms of bile acid diarrhoea after cholecystectomy are unknown. Therefore, we aimed to explore the effects of cholecystectomy on the plasma biomarkers of bile acid diarrhoea: fibroblast growth factor 19 and 7α-hydroxy-4-cholesten-3-one.
Patients were examined prospectively before and after cholecystectomy. Diary registration of bowel habits with the Bristol stool scale was done for 7 days before each visit. Blood was collected at fasting and after ingestion of a solid study meal with 1250 mg unconjugated chenodeoxycholic acid. Plasma fibroblast growth factor 19 was measured with enzyme-linked immunosorbent assay and the complete bile acid profile including 7α-hydroxy-4-cholesten-3-one with high-performance liquid chromatography–tandem mass spectrometry.
Eighteen patients completed the study. The median postoperative follow-up time was 4.6 months (interquartile range [IQR] 3.9-5.8). Diary-registered bowel movement frequency and stool consistency were unchanged; none developed diarrhoea. Before cholecystectomy, mean fibroblast growth factor 19 was 102 pg/mL (95% CI 74-141) vs 92 pg/mL (67-125) after (P = .29; paired t test). Following the meal, the median 150-minute increment from fasting in fibroblast growth factor 19 was 81 pg/mL (IQR: −20 to 274) before and 186 pg/mL (111-382) after cholecystectomy (P = .03; Wilcoxon-test). Mean fasting 7α-hydroxy-4-cholesten-3-one was unchanged 6.0 ng/mL (4.1-8.7) vs 7.5 ng/mL (5.5-10.0) (P = .63; paired t test).
The stimulated postprandial response in fibroblast growth factor 19 increased after cholecystectomy, whereas fasting plasma biomarkers and bowel habits did not change significantly 3-6 months after cholecystectomy. ClinicalTrials.gov: NCT03168555.
Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are implicated in the pathogenesis of gastric adenocarcinoma (GCA), but have not been investigated together, in the South African context of low GCA incidence and high H pylori prevalence.
To determine, based on these factors, the potential for developing GCA in a local cohort with H pylori-associated dyspepsia.
Seventy-nine patients underwent gastroscopy and biopsy. Helicobacter pylori-positive biopsies were analysed for virulence factors; cytotoxin-associated antigen (CagA) and vacuolating toxin (VacA) and mosaics (Vac A m1/m2, Vac A s1/s2 or combinations). Host DNA was analysed for targeted regions in IL-1B and IL-1RN genes, to determine polymorphisms of IL-1B-511*T and IL-1RN (variable number tandem repeat [VNTR]).
The mean age was 43 years (SD ±11.7), 66% were female. Forty-eight patients (60%) were H pylori positive, 50% (24/48) demonstrated a virulent organism and 42% (20/48) of these demonstrated the most virulent carcinogenic combination; VacA m1/s1 and CagA. IL-1RN VNTR was sequenced in 25 specimens and IL-1B511 polymorphisms in 48 patients; the high-risk IL-1B511 TT allele was present in 52% (25/48) and TC allele in 33% (16/48). Overall, 85% (41/48) of patients demonstrated high-risk genetic polymorphisms. The highest risk associated with GCA, a combination of H pylori VacAm1/s1 virulence factor and IL-1B511 TT or TC allele, was demonstrated in 42% (20/48).
Almost half the patients have a combination of virulent H pylori and carcinogenic IL polymorphism. The implication of these observations on the risk of developing GCA requires further elucidation.
To avoid the late complications of endoscopic sphincterotomy (EST) such as cholangitis, liver abscess and recurrent common bile duct stones (CBDS), alternative methods should be considered in the management of CBDS, especially in younger patients.
To study the effect of biliary stent placement without EST in patients with CBDS.
Forty-nine patients with CBDS underwent biliary stent placement without EST and complications were evaluated. The rate of stone disappearance, the change in number, size and indices of stones and common bile duct (CBD) diameter were evaluated at the second endoscopic retrograde cholangiopancreatography (ERCP) 3 months later.
CBDS(s) disappeared in 11 (22.45%) of 49 patients. Almost all of the stones which disappeared after stenting without EST were <14 mm and CBD diameter <18 mm. Average diameter of the largest CBDS, mean number of CBDS, stone index and CBD diameter markedly reduced (P < 0.001, P < 0.001, P < 0.001 and P = 0.001 respectively). The size of the largest stone, stone indices and diameter of CBD in the stone disappearance cases were significantly smaller than those of the stone persistence cases (P = 0.003, P = 0.006, P = 0.004 respectively). Complications such as mild post-ERCP pancreatitis (6.12%), stent migration (10.2%) and cholangitis (4.08%) were observed.
Temporary stent placement without EST is effective for clearance of CBDS while preserving the duodenal papilla function, especially in small CBDS and less dilated CBD to avoid EST related complications.
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