Gastrointestinal consequences of cancer treatment: evaluation of 10 years' experience at a tertiary UK centre.

OBJECTIVE: Up to 90% of patients treated for pelvic cancers experience chronic gastrointestinal (GI) symptoms. This study characterises this patient cohort at a single centre, addressing a paucity of publications reporting 'real-world' experiences. METHOD: Outpatient referrals, from oncology to the gastroenterology and nutrition services, at a tertiary London hospital from 2006 to 2016, were retrospectively identified. Patient characteristics, reported symptoms, investigations, diagnoses, response to therapeutics and follow-up were recorded. RESULTS: Of 269 patients referred, 81% were within the latter 5 years. A total of 260 patients had diagnoses of pelvic cancers (prostatic (52%), cervical (19%) and endometrial (19%)). Among 247 treated with radiotherapy, the median time from radiotherapy to symptom onset was 8 months. Common symptoms were rectal bleeding (51%), diarrhoea (32%), faecal urgency (19%) and pain (19%). Patients underwent a median of three investigations including lower GI endoscopy (86%), thyroid function tests (33%) and glucose hydrogen breath test (30%). Diagnoses included radiation proctopathy (39%), colonic polyps (16%), pelvic floor dysfunction (12%), bile acid malabsorption (BAM) (8%), small intestinal bacterial overgrowth (SIBO) (8%), vitamin D deficiency (7%) and iron deficiency (7%). Among 164 discharged patients, the time to discharge was 7 months, after a median of two appointments. CONCLUSIONS: This unique patient group reports a complex mix of symptoms and requires specialist review and consideration of often uninvestigated diagnoses (pelvic dysfunction, BAM, SIBO and nutritional deficiencies). Such patients are often overlooked, compared with those suffering many other chronic GI disorders. Further reports from non-dedicated centres treating patients with pelvic radiation disease will aid in understanding of secondary GI diagnoses and variation in practice.

Diagnosis of chronic anaemia in gastrointestinal disorders: A guideline by the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Italian Society of Paediatric Gastroenterology Hepatology and Nutrition (SIGENP).

Anaemia is a common pathologic condition, present in almost 5% of the adult population. Iron deficiency is the most common cause; other mechanisms can be involved, making anaemia a multi-factorial disorder in most cases. Anaemia being a frequent manifestation in the diseases of the gastrointestinal tract, patients are often referred to gastroenterologists. Furthermore, upper and lower endoscopy and enteroscopy are pivotal to the diagnostic roadmap of anaemia. In spite of its relevance in the daily clinical practice, there is a limited number of gastroenterological guidelines dedicated to the diagnosis of anaemia. For this reason, the Italian Association of Hospital Gastroenterologists and Endoscopists and the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition commissioned a panel of experts to prepare a specific guideline on anaemia and its diagnostic roadmap in the gastroenterological scenario. The panel also discussed about the potential involvement of gastroenterologists and endoscopists in the management of patients with anaemia, with particular attention to the correct use of investigations. The panel paid particular attention to practical issues with the aim to support gastroenterologists in their clinical practice when dealing with patients with anaemia.

Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis.

BACKGROUND: Gastric electric stimulation (GES) is a treatment approach to refractory gastroparesis, possibly acting centrally via afferent vagus nerve stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that could eliminate the safety risks of or identify likely responders to implantable neurostimulators. OBJECTIVE: This open-label proof-of-concept study assessed the effects of nVNS in patients with severe drug-refractory gastroparesis. METHODS: Patients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms in diaries daily for 2 weeks before treatment (baseline) and during ≥3 weeks of nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self-administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s stimulations to the vagus nerve in the neck (two stimulations to each side three times daily during weeks 1 and 2; three stimulations to each side three times daily during week 3 and beyond). Response was defined as a ≥1 point decrease from baseline in GCSI score. RESULTS: Thirty-five patients enrolled; 23 were compliant with study procedures and were included in the analysis; 7 continued treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43% (10/23) for the duration of therapy (3-6 weeks). For the entire cohort and the 10 responders, improvements from baseline were noted for mean total GCSI and GCSI subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating). No serious AEs were reported. CONCLUSIONS: These preliminary results provide a signal that nVNS may be useful for treating refractory gastroparesis. Larger controlled studies are warranted.

Impact of NS5A sequences of Hepatitis C virus genotype 1a on early viral kinetics during treatment with peginterferon- alpha 2a plus ribavirin.

UNLABELLED: BACKGROUND. Hepatitis C virus (HCV) genotype 1 is the most prevalent genotype in Western countries, and treatment with pegylated interferon (pegIFN) plus ribavirin fails in 50%-60% of patients. Genetic variability within the NS5A dsRNA-dependent protein kinase binding domain (PKRbd) of HCV-1b has been associated with responsiveness to IFN- alpha . Little is known about NS5A sequences of HCV-1a. We investigated whether genetic variability of HCV-1a NS5A correlates with the early HCV kinetics during treatment. METHODS: Twenty-four treatment-naive, HCV-1a-infected patients were treated with standard doses of pegIFN- alpha 2a plus ribavirin. HCV viremia was quantitated at days 0, 1, 2, and 3 and weeks 1, 2, 4, 8, and 12 of treatment. According to HCV kinetics, patients were classified as early rapid responders, early moderate responders, or early slow responders. The full-length HCV NS5A was sequenced at baseline and at week 1. RESULTS: At baseline, variability of the NS5A C terminus (concentrated in the PKRbd) is associated with interferon efficacy but not with the second phase of the early viral decline that has been associated with a sustained virologic response. Comparisons between baseline and week-1 full-length sequences did not show significant increases in mutations. CONCLUSIONS: Genetic variability of HCV-1a NS5A does not predict responsiveness to IFN- alpha . Differences in early kinetics during combination therapy are not due to selection of IFN-resistant HCV strains.

Individualization of antiviral treatment regimens for chronic hepatitis C.

The treatment of patients with chronic hepatitis C has rapidly evolved in the past 10 years. The introduction of ribavirin and, more recently, its combination with pegylated interferon represent two landmark changes in improving the treatment efficacy. Overall, sustained virological response at present can be expected in 43-46% of patients infected with genotype 1 and 75-80% in genotype 2 or 3 infection. In addition, factors associated with a lower or greater chance of response to treatment have now been identified, thus providing a basis for modifying current therapy according to the needs of different patient groups. Accumulating evidence demonstrates that individualized treatment regimens, according to the timing of treatment-induced viral clearance, provide a safe and cost-effective approach, as well as an improvement in treatment efficacy.

Novel type of hepatitis B virus mutation: replacement mutation involving a hepatocyte nuclear factor 1 binding site tandem repeat in chronic hepatitis B virus genotype E.

The genetic diversity of hepatitis B virus (HBV) strains has evolved through mutations such as point mutations, deletions or insertions, and recombination. We identified and characterized a novel type of mutation which is a complex of external insertion, deletion, and internal duplication in sequences from one of six patients with chronic hepatitis B virus genotype E (HBV/E). We provisionally named this mutation a "replacement mutation"; the core promoter upstream regulatory sequence/basic core promoter was replaced with a part of the S1 promoter covering the hepatocyte nuclear factor 1 (HNF1) binding site, followed by a tandem repeat of the HNF1 site. A longitudinal analysis of the HBV population over 6 years showed the clonal change from wild-type HBV/E to replacement-mutant type, resulting in a lower hepatitis B (HB) e antigen titer, a high HBV DNA level in serum, and progression of liver fibrosis. In an in vitro study using a replication model, the replacement-mutant HBV showed higher replication levels than the wild-type HBV/E replicon, probably mediated by altered transcription factor binding. Additionally, this HNF1 site replacement mutation was associated with excessive HB nucleocapsid protein expression in hepatocytes, in both in vivo and in vitro studies. This novel mutation may be specific to HBV genotype E, and its prevalence requires further investigation.