ERCP for the initial management of malignant biliary obstruction - real world data on 596 procedures.

AIMS: To evaluate outcomes of ERCP as first-line management in patients with malignant biliary obstruction (MBO) of all causes and stages, reflecting a real-life setting. METHODS: Retrospective observational study of patients with ERCP as the first-line management of MBO at Oslo University Hospital between 2015 and 2021. Primary outcome measure was a ≥ 50% decrease from the pre-procedural bilirubin within 30 days after ERCP. Secondary outcome measures were technical success of ERCP, complications and overall mortality. RESULTS: A total of 596 patients were included, median age 70 years. ASA score was ≥ III in 67% of patients. The most common cancers causing MBO were pancreatic cancer (52%), metastatic lesions (20%) and cholangiocarcinoma (16%). The primary outcome measure was achieved in 62% of patients. With endoscopic access, overall technical success was 80% with 85% for the distal extrahepatic group, 71% for the perihilar, 40% for the intrahepatic and 53% for multiple level MBOs. Reinterventions were performed in 27% of the patients. Complications occurred in 15% of the patients, including post-ERCP pancreatitis in 9%. Most complications were of minor/moderate severity (81%). Overall mortality was 33% within the first 90 days. Patients deceased by the end of the study period (83%) had median survival of 146 days (range 1-2,582 days). CONCLUSIONS: ERCP has a high rate of clinical effect and technical success in the management of both distal extrahepatic and perihilar MBO. Our data indicate that ERCP is a valid option in the first-line management of MBO.

Does the Introduction of Biosimilars Change Our Understanding about Treatment Modalities for Inflammatory Bowel Disease?

BACKGROUND: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use. CONCLUSIONS: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics.

Preoperative liquid gastric emptying rate does not predict outcome after fundoplication.

AIM OF THE STUDY: Preoperative gastric emptying (GE) rate in patients with gastrointestinal reflux disease (GERD) was evaluated as a predictor of outcome after antireflux surgery. METHODS AND PATIENTS: GE was assessed using radionuclide scintigraphy and a standardized meal with cow's milk. GE half time (T1/2), patient demographics and GERD symptoms including vomiting (>4days/week), retching (>4days/week), prolonged feeding time (>3h/day), and discomfort after meals were recorded pre- and postoperatively. A standardized follow-up included a 24-h pH-monitoring and an upper gastrointestinal contrast study. Of 74 patients undergoing Nissen fundoplication between 2003 and 2009, 35 underwent a preoperative GE study. The remaining 39 patients were not examined owing to volume intolerance, cow's milk intolerance or allergy, inability to lie still, or parents refusing participation. MAIN RESULTS: Median age at fundoplication was 4.9 [range 1.1-15.4] years, and follow-up time was median 4.3 [1.9-8.9] years. GERD recurred in 7 (20%) patients. Preoperative T1/2 in the seven patients with recurrent GERD was median 45 [21-87] min compared to 44 [16-121] min in the 28 patients without recurrent GERD (p=0.92). There was no significant difference between the one third of patients with the slowest GE [T1/2 54-121min] and the remaining patients [T1/2 16-49min] regarding GERD recurrence or postoperative vomiting, retching, prolonged feeding time, or discomfort after meals. CONCLUSION: Preoperative GE rate did not predict outcome after antireflux surgery, as slow GE was not associated with recurrent GERD or postoperative troublesome symptoms such as vomiting, retching, or meal discomfort.

Local and national electronic databases in Norway demonstrate a varying degree of validity.

OBJECTIVE: The aim of the present study was to examine the validity of local and national electronic databases using medical records as gold Standard. STUDY DESIGN AND SETTING: All hospital admissions with ICD 9-code 820.X (hip fracture) in a 1-year period were identified in the electronic discharge registers of the hospitals in Oslo and in the national electronic database (The Norwegian Patient Register). Medical records for all patients identified by the discharge registers and the logbooks of the operating theater of the hospitals were retrieved, and the diagnosis was verified. RESULTS: Compared with the total number of fractures confirmed in medical records, the electronic discharge register of one of the hospitals underestimated the number of fractures by 46%, whereas the two other overestimated the number by 17% and 19%. For the national electronic database, an overall overestimation of 19% was found. CONCLUSION: The present findings question the validity of electronic databases and thus have implications for epidemiologic studies.

Low-dose intravenous erythromycin: effects on postprandial and fasting motility of the small bowel.

BACKGROUND: Erythromycin is a motilin agonist and its effects on gastrointestinal motility are dependent on both dose and whether it is administered during the postprandial or fasting state. AIM: To study the motility response of the small bowel to a low dose of intravenous erythromycin after meal intake and during fasting. METHODS: Eighteen healthy subjects with mean age of 25 years were studied by small bowel manometry. Erythromycin was administered intravenously (0.75 mg per kg body weight) during 20 min in the postprandial (n=9) and the fasting state (n=9), and the motility response was recorded. RESULTS: Erythromycin significantly reduced the frequency of propagated contractions (P < 0.001) and the amplitude of contractions (P < 0.02) in the small bowel during established postprandial motility. During the fasting state, erythromycin invariably initiated a phase III-like activity, which was similar to the spontaneous nocturnal phase III and migrated significantly more slowly than the diurnal phase III (P < 0.01). CONCLUSIONS: A low dose of erythromycin administered intravenously during the postprandial state significantly inhibits small bowel motility, whereas administration during the fasting state initiates a phase III resembling the nocturnal rather than the diurnal phase III. These effects of erythromycin may indicate interference with vagal pathways. Due to its inhibitory effects, the clinical use of erythromycin in patients with hypomotility should be reconsidered, and the potential usefulness of these effects in patients with exaggerated intestinal motility deserves further attention.

Delay of gastric emptying by duodenal intubation: sensitive measurement of gastric emptying by the paracetamol absorption test.

AIMS: To examine the influence of duodenal intubation on gastric emptying measured by the paracetamol absorption test using a new algorithm developed to estimate emptying parameters, and to determine the sensitivity of this test. METHODS: A caloric liquid meal with paracetamol as marker of emptying was administered orally to eight healthy volunteers during phase I and phase II of the migrating motor complex (MMC) and without intubation on 3 separate days, and to 10 patients with partial gastrectomy. RESULTS: Healthy subjects: With duodenal tube, time until 25% of the meal had emptied (t25%) was 24+/-7 (phase I, P<0.02) and 21+/-6 min (phase II, P<0.02) compared with 14+/-4 min for meal intake without intubation. Time until 50% of the meal had emptied (t50%) was 45+/-8 (phase I, P<0.001) and 35+/-8 min (phase II, P<0.02) compared with 26+/-9 min for meal intake without intubation. Intraduodenal instillation of 10-20 mL of the liquid meal was reliably detected. PATIENTS: In 9 out of 10 patients with partial gastrectomy t25% was below the lower limit of the range for healthy controls, and t25% detected accelerated emptying with a higher degree of sensitivity than the commonly applied pharmacokinetic parameters Cmax and Tmax. CONCLUSIONS: A duodenal tube delays gastric emptying of a caloric liquid meal. The paracetamol absorption test emerges as a sensitive method suitable for detecting both delayed and accelerated gastric emptying of caloric liquid meals.

Are patients with Hirschsprung's disease prediabetic?

Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P <.05) and insulin (P <.02) were significantly higher in patients compared with healthy controls. Peak concentration of insulin following meal intake was significantly higher in the patient group (P <.05), and peak concentration of glucose tended to be higher in patients compared with controls (P =.06). There was no correlation between body mass index and serum levels of glucose or insulin. The present study shows that adult patients treated for HD during childhood have an impaired glucose and insulin homeostasis, indicating a mild degree of insulin resistance. This may imply susceptibility towards development of non-insulin-dependent diabetes mellitus.

Gastric emptying: the validity of the paracetamol absorption test adjusted for individual pharmacokinetics.

An algorithm for the paracetamol absorption test for gastric emptying, adjusting for individual pharmacokinetics, was recently developed. The aim of the present study was to validate the use of this algorithm. Furthermore, the algorithm was applied to elucidate whether a gastric tube interferes with the rate of gastric emptying. A caloric liquid meal with paracetamol was administered orally to nine healthy volunteers on two separate days. On one occasion, the subjects were intubated with a nasogastric tube and the meal was aspirated from the stomach 45 min after meal intake. The percentage of the meal retained in the stomach at the time of aspiration was determined by analyses of paracetamol in the aspirate and compared with calculations by the algorithm. On the other examination day, the same meal was ingested without tube and aspiration. The median percentage of the meal retained in the stomach at aspiration was 47% (range 33-70%) calculated by the algorithm and 48% (range 23-61%) based on the aspiration data. The correlation between the emptying parameters was r=0.97 (P < 0.001). The median of gastric emptying parameters was similar when the number of samples included in the calculation by the algorithm was reduced, but the range tended to increase. The gastric tube moderately inhibited gastric emptying during the period 20-40 min after meal intake (P < 0.05), but for the period from meal intake until start of aspiration, no inhibition was found. The present study demonstrates that the novel algorithm for the paracetamol absorption test provides valid estimates for gastric emptying.

Motility of the oesophagus and small bowel in adults treated for Hirschsprung's disease during early childhood.

BACKGROUND: Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung's disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.] METHODS: Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull-through technique. KEY RESULTS: The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P < 0.001). The patients had normal oesophageal motility. CONCLUSIONS & INFERENCES: This study demonstrates that adult patients with HD have preserved essential patterns of oesophageal and small bowel motility. However, abnormalities mainly characterized by increased contractile activity of the small bowel during fasting and postprandially are evident. These findings indicate alterations in neuronal control of motility and persistent involvement of the upper GI tract in this disease.

Stimulation of the small intestine by nutrients in relation to phase of the migrating motor complex.

BACKGROUND: The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied. METHODS: In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose. RESULTS: After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P < 0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC. CONCLUSIONS: The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.

The influence of the migrating motor complex on the postprandial endocrine response.

BACKGROUND: The phase of the migrating motor complex (MMC) in the proximal small intestine at meal intake modulates gastric emptying, which is accelerated after intake during phase II. In the present study the relationship between phase of the MMC at meal intake and the postprandial endocrine response was studied. METHODS: Eight healthy subjects ingested a caloric liquid meal of 2020 kJ during phase I and late phase II of the intestinal MMC, respectively, in a randomized order. Blood samples were drawn at regular intervals after meal intake and analysed for insulin, gastrin, neurotensin, cholecystokinin, motilin, and somatostatin by radioimmunoassays. RESULTS: The area under the curve (AUC) until 15 min for serum insulin (P<0.05) and plasma neurotensin (P<0.02) and AUC until 120 min for serum gastrin (P<0.05) were higher after intake during late phase II than after phase I. Plasma cholecystokinin increased earlier (P<0.05) after intake during late phase II than after phase I. Plasma motilin and somatostatin were not influenced by preceding phase of the MMC. CONCLUSIONS: This study shows that the phase of intestinal MMC at meal intake modulates the postprandial endocrine response, which may be explained by the prior entry of nutrients to the small intestine after intake during phase II.