Caffeine intake enhances bowel recovery after colorectal surgery: a meta-analysis of randomized and non-randomized studies.

Postoperative ileus (POI) after colorectal surgery is a major problem that affects both patient recovery and hospital costs highlighting the importance of preventive strategies. Therefore, we aimed to perform a systematic analysis of the effects of postoperative caffeine consumption on bowel recovery and surgical morbidity after colorectal surgery. A comprehensive literature search was conducted through September 2023 for randomized and non-randomized trials comparing the effect of caffeinated versus non-caffeinated drinks on POI by evaluating bowel movement resumption, time to first flatus and solid food intake, and length of hospital stay (LOS). Secondary outcome analysis included postoperative morbidity in both groups. After data extraction and inclusion in a meta-analysis, odds ratios (ORs) for dichotomous variables and standardized mean differences (SMDs) for continuous outcomes with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed in cases of substantial heterogeneity. Six randomized and two non-randomized trials with a total of 610 patients were included in the meta-analysis. Caffeine intake significantly reduced time to first bowel movement [SMD -0.39, (95% CI -0.66 to -0.12), p = 0.005] and time to first solid food intake [SMD -0.41, (95% CI -0.79 to -0.04), p = 0.03] in elective laparoscopic colorectal surgery, while time to first flatus, LOS, and the secondary outcomes did not differ significantly. Postoperative caffeine consumption may be a reasonable strategy to prevent POI after elective colorectal surgery. However, larger randomized controlled trials (RCTs) with homogeneous study protocols, especially regarding the dosage form of caffeine and coffee, are needed.

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

Effects of fermented soymilk with Lacticaseibacillus paracasei YIT 9029 on gut microbiota and defecation habits: a randomised, double-blind, placebo-controlled study.

Previous studies have demonstrated that soymilk and Lacticaseibacillus paracasei YIT 9029 (strain Shirota: LcS) each beneficially affect the gut microbiota and defecation habits. To investigate the effects of daily consumption of fermented soymilk containing LcS (FSM), we conducted a randomised, double-blind, placebo-controlled study of 112 healthy Japanese adults with a low faecal Bifidobacterium count. They consumed 100 ml FSM or placebo (unfermented soymilk base) once daily for 4 weeks. Their gut microbiota was analysed by 16S rRNA gene amplicon sequencing and quantitative reverse transcription-polymerase chain reaction (PCR), and faecal short-chain fatty acids (SCFAs) and urinary putrefactive products were assessed during the pre- and post-consumption periods. Defecation habits were examined weekly using a subjective questionnaire. In the post-consumption period, living LcS were not detected in two subjects in the FSM group (n = 57) but were detected in one subject in the SM group (n = 55). The FSM group had a significantly higher number and relative abundance of faecal lactobacilli compared with the placebo group. The relative abundance of Bifidobacterium, alpha-diversity of microbiota, and concentrations of acetate and total SCFAs in faeces were significantly increased in the FSM group, although no significant differences were detected between the groups. The number of defecations and defecation days per week significantly increased in both groups. Subgroup analysis of 109 subjects, excluding 3 with inconsistent LcS detection (2 and 1 subjects in the FSM and SM groups, respectively), revealed that the FSM group (n = 55) had significantly greater increases in faecal acetate concentration compared with the SM group (n = 54) and significant upregulation of pathways related to energy production or glucose metabolism in the gut microbiota. These findings suggest that daily FSM consumption improves the gut microbiota and intestinal environment in healthy adults and may help to maintain health and prevent diseases. Registered at the University Hospital Medical Information Network (UMIN) clinical trials registry under: UMIN 000035612.

Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics.

BACKGROUND/OBJECTIVES: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses. METHODS: Forty-eight patients being treated with naldemedine for opioid-induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed. RESULTS: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4ß-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements. CONCLUSION: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.

Combination of Enhanced Instructions Improve Quality of Bowel Preparation: A Prospective, Colonoscopist-Blinded, Randomized, Controlled Study.

BACKGROUND: Appropriate bowel preparation is highly important for the efficacy of colonoscopy; however, up to one-third of patients do not accomplish adequate bowel preparation. OBJECTIVE: We investigated the impact of the combination of enhanced instruction on the quality of bowel preparation and its impact on clinically relevant outcomes. DESIGN: This was a colonoscopist-blinded, prospective, randomized trial. SETTINGS: All patients received regular instructions for bowel preparation. Patients were randomly assigned to the control, telephone reeducation, and combined enhanced instruction groups. PATIENTS: Outpatients aged 19 to 75 years scheduled to undergo colonoscopy were included. MAIN OUTCOME MEASURES: The main outcome was adequate bowel preparation rate. RESULTS: A total of 311 patients were randomly assigned to the combined enhanced instruction (n = 104), telephone reeducation (n = 101), and control groups (n = 106). An intention-to-treat analysis showed that the adequate bowel preparation rate was higher in the combined enhanced instruction group than in the telephone reeducation and control groups (92.3% vs 82.2% vs 76.4%, p = 0.007). The rate of compliance with the instructions was significantly higher in the combined enhanced instruction group than in the telephone reeducation and control groups. Method of education was associated with proper bowel preparation (adjusted OR 17.46; p < 0.001 for combined enhanced instruction relative to control). LIMITATIONS: This was a single-center study conducted in Korea. CONCLUSIONS: Combined enhanced instruction as an adjunct to regular instructions much improved the quality of bowel preparation and patients' adherence to the preparation instructions. The combined enhanced instruction method could be the best option for bowel preparation instruction. See Video Abstract at http://links.lww.com/DCR/B673. LA COMBINACIN DE INSTRUCCIONES MEJORADAS, INCREMENTA LA CALIDAD DE LA PREPARACIN INTESTINAL ESTUDIO PROSPECTIVO, CONTROLADO, ALEATORIO Y CIEGO PARA EL COLONOSCOPISTA: ANTECEDENTES:La preparación adecuada del intestino es muy importante para la eficacia de la colonoscopia; sin embargo, hasta un tercio de los pacientes no logran buenos resutlados.OBJETIVO:Investigar el impacto de la combinación de instrucciónes claras en la calidad de la preparación intestinal y su impacto en los resultados clínicos.DISEÑO:Trabajo aleatorio, prospectivo y ciego para el colonoscopista.AJUSTES:Los pacientes recibieron instrucciones periódicas para la preparación intestinal. Fueron asignados aleatoriamente al grupo control, educación telefónica y de instrucción mejoradas.PACIENTES:Se incluyeron pacientes ambulatorios de 19 a 75 años programados para ser sometidos a colonoscopia.PRINCIPALES MEDIDAS DE RESULTADO:El principal resultado fue una adecuada preparación intestinal.RESULTADOS:Un total de 311 pacientes fueron asignados al azar a la instrucción mejorada combinada (n = 104), reeducación telefónica (n = 101) y grupo de control (n = 106). El análisis estadístico mostró que la tasa de preparación intestinal adecuada fue mayor en el grupo combinado de instrucción mejorada que en los grupos de reeducación telefónica y control (92,3% vs 82,2% vs 76,4%, p = 0,007). La tasa de cumplimiento de las instrucciones fue significativamente mayor en el grupo de instrucción mejorada combinada que en los otros. El método de educación se asoció con una preparación intestinal adecuada (razón de posibilidades ajustada de 17,46; p <0,001 para la instrucción mejorada combinada en relación con el control.LIMITACIONES:Estudio en un solo centro realizado en Corea.CONCLUSIONES:La instrucción mejorada combinada como complemento de las instrucciones regulares mejoró mucho la calidad de la preparación intestinal y la adherencia de los pacientes a las instrucciones de preparación. El método de instrucción mejorado combinado podría ser la mejor opción para la instrucción de preparación intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B673.

7,8-Dihydroxyflavone Enhanced Colonic Cholinergic Contraction and Relieved Loperamide-Induced Constipation in Rats.

BACKGROUND: Whether 7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase receptor B (TrkB) agonist, modulates colonic smooth muscle motility and/or alleviates constipation has not yet been studied. AIMS: Here, we aimed to determine how 7,8-DHF influences carbachol (CCh)-stimulated contraction of colonic strips and the in vivo effect of 7,8-DHF on constipation. METHODS: Muscle strips were isolated from rat colons for recording contractile tension and performing western blotting. Constipation was induced in rats with loperamide. RESULTS: Although it specifically activated TrkB, 7,8-DHF applied alone neither activated PLCγ1 in the colonic strips nor induced colonic strip contraction. However, 7,8-DHF enhanced CCh-stimulated PLCγ1 activation and strip contraction. The PLCγ1 antagonist U73122 suppressed both CCh-stimulated and 7,8-DHF-enhanced/CCh-stimulated contraction. While clarifying the underlying mechanism, we revealed that 7,8-DHF augmented muscarinic M3 receptor expression in the colonic strips. The M3-selective antagonist tarafenacin specifically inhibited the 7,8-DHF-enhanced/CCh-stimulated contraction of the colonic strips. Since 7,8-DHF increased Akt phosphorylation, and LY294002 (an antagonist of PI3K upstream of Akt) dramatically inhibited both 7,8-DHF-augmented M3 expression and 7,8-DHF-enhanced/CCh-stimulated contractions, we assumed that 7,8-DHF/TrkB/Akt was associated with the modulation of M3 expression in the colonic strips. ANA-12, a specific TrkB antagonist, not only inhibited TrkB activation by 7,8-DHF but also suppressed 7,8-DHF-enhanced cholinergic contraction, 7,8-DHF/CCh-mediated activation of PLCγ1/Akt, and M3 overexpression in colonic strips. In vivo 7,8-DHF, also by promoting intestinal motility and M3 expression, significantly alleviated loperamide-induced functional constipation in rats. CONCLUSIONS: Our results suggest that 7,8-DHF regulates colonic motility possibly via a TrkB/Akt/M3 pathway and may be applicable for alleviating constipation.

Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome.

BACKGROUND: Telotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods. METHODS: First occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial. RESULTS: In TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3-4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2-3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6-11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7-11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR. CONCLUSION: The time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01677910, NCT02063659.

Diverse role of gut microbiota on reduction of ascites and intestinal injury in malignant ascites effusion rats treated with Euphorbia kansui stir-fried with vinegar.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui (EK) is the dried root of Euphorbia kansui S.L.Liou ex S.B.Ho. Clinically, processing with vinegar is for reducing toxicity of EK, and EK stir-fried with vinegar (VEK) is used to treat ascites and edema. VEK has been confirmed to reduce ascites by accelerating the promotion of intestinal contents. AIM OF THE STUDY: The study aimed to investigate whether gut microbiota could affect the expelling water retention effects and the intestinal oxidative damage of EK and VEK on malignant ascites effusion (MAE) rats. MATERIALS AND METHODS: Pseudo-germ-free (PGF) MAE rats or probiotic intervented MAE rats were treated with EK/VEK. Related indicators such as serum, ascites, urine, feces, gastrointestinal tissues were analyzed, and the structure of the gut microbiota were also studied. The relationship between gut microbiota and the expelling water retention effects of EK/VEK where then further investigated. RESULTS: VEK reduce the volume of ascites by promoting urine and feces excretion, AQP8 protein and mRNA expression, when comparing with the MAE rats, also VEK could regulate the disordered gut microbiota in MAE rats. Mixed antibiotics could diminish VEK's expelling water retention effects in MAE rats, but increased oxidative damage in intestine. While existence of gut microbiota (especially probiotics) played an important role in the protection of intestines in VEK treated MAE rats. CONCLUSION: VEK had obvious pharmacological effect on MAE and could regulate gut microbiota, but gut microbiota was not a necessary condition for its pharmacological effects. The probiotics played a synergistic role with VEK in the effects of expelling water retention and intestinal protection.

The Efficacy and Safety of Lubiprostone for Constipation in Cancer Patients Compared with Non-cancer Patients: A Retrospective Cohort Study.

Lubiprostone is an effective drug for various types of constipation in patients without cancer; however, there is no report on its efficacy and safety in patients with cancer. Our purpose was to evaluate the efficacy and safety of lubiprostone for constipation in cancer patients. We retrospectively studied 124 patients (cancer, N = 67) who were treated with lubiprostone for constipation in our hospital between June 2013 and May 2016. The number of bowel movements (BMs) increased in the both the cancer and non-cancer groups. The mean change in BM frequency did not differ between the two groups. Approximately 70% of patients in both groups had an initial BM within 24 h after administration of lubiprostone. The most common lubiprostone-related adverse events in both groups were diarrhea (38.8 vs. 14%), and nausea (22.4 vs. 8.8%). No lubiprostone-related serious adverse events occurred. Discontinuation due to the side effects of lubiprostone was more frequent in cancer patients (p = 0.023). Logistic regression analysis showed that the risk of discontinuation of lubiprostone in cancer patients was high in patients with a body-mass index (BMI) <22, and low in patients using opioids and magnesium oxide dosage ≥1000 mg/d. Our study showed that while lubiprostone was as effective in cancer patients as in non-cancer patients, in cancer patients it was associated with a high incidence of diarrhea and nausea side effects and warranted caution, especially in patients with a low BMI.

Poria ameliorates the side effects of rhubarb in pair treatment.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

Comparing the effectiveness of magnesium oxide and naldemedine in preventing opioid-induced constipation: a proof of concept, single institutional, two arm, open-label, phase II, randomized controlled trial: the MAGNET study.

BACKGROUND: Patients taking opioids are known to develop opioid-induced constipation (OIC), which reduces their quality of life. The aim of this study is to compare magnesium oxide with naldemedine and determine which is more effective in preventing OIC. METHODS: This proof-of-concept, prospective, randomized controlled trial commenced in Japan in March 2018. Initially, a questionnaire-based survey will be conducted targeting adult patients with cancer who concomitantly commenced opioid treatment and OIC prevention treatment. Patients will then be randomly allocated to a magnesium oxide group (500 mg thrice daily) or a naldemedine group (0.2 mg once daily). Each drug will be orally administered for 12 weeks. The primary endpoint is defined as any improvement in scores on the Japanese version of Patient Assessment of Constipation Quality of Life questionnaire (JPAC-QOL) from baseline to 2 weeks of treatment. DISCUSSION: The primary endpoint is change in JPAC-QOL score from baseline to 2 weeks of intervention. The key secondary endpoint will be change in spontaneous bowel movements at 2 and 12 weeks of intervention. This study will determine whether magnesium oxide or naldemedine is more effective for the prevention of OIC. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000031891. Registered March 25, 2018.

Total glucosides of paeony (TGP) alleviates constipation and intestinal inflammation in mice induced by Sjögren's syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Sjögren's syndrome (SS) is an autoimmune disease and can cause gastrointestinal disorders such as constipation and intestinal inflammation. As a kind of medicinal material, Paeonia lactiflora Pall has a variety of pharmacological effects, and it is also an indispensable component in many pharmaceutical preparations, which has been widely concerned by the medical and pharmaceutical circles. Total glucosides of paeony (TGP) is a mixture of biologically active compounds extracted from the root of Paeonia lactiflora Pall and has therapeutic effects on a variety of autoimmune diseases. AIM OF THE STUDY: To investigate the therapeutic effect of TGP on constipation and intestinal inflammation in mice modeled by SS, and to provide a basis for clinical research. MATERIALS AND METHODS: The SS model was set up by submandibular gland (SMG) immune induction method and then treated with TGP for 24 weeks. The fecal characteristics were observed and the fecal number and moisture content were measured. Colonic pathology was observed by H&E staining. The levels of serum P substance (SP), vasoactive intestinal peptide (VIP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, nitric oxide (NO), and nitric oxide synthase (NOS) were determined by enzyme linked immunosorbent assay (ELISA) and microplate method, respectively. Reverse transcription polymerase chain reaction (RT-PCR) was employed to analyze the mRNA expression of c-kit and stem cell factor (SCF) in colon. RESULTS: Compared with the model group, the dry and rough condition of the feces was improved, and the fecal gloss, number and moisture content significantly increased after the administration of TGP capsules. Meanwhile, TGP treatment improved colonic pathological damage, inhibited the serum concentrations of NO, NOS, IL-1ß, TNF-α, NF-κB and SP, increased serum VIP concentration, and up-regulated mRNA expression of SCF and c-kit in colon. CONCLUSIONS: TGP could obviously attenuate SS-mediated constipation and intestinal inflammation in mice by acting on some intestinal motility related factors and inflammatory factors.

Safety and efficacy of laxatives after major abdominal surgery: systematic review and meta-analysis.

BACKGROUND: Recovery of gastrointestinal function is often delayed after major abdominal surgery, leading to postoperative ileus (POI). Enhanced recovery protocols recommend laxatives to reduce the duration of POI, but evidence is unclear. This systematic review aimed to assess the safety and efficacy of laxative use after major abdominal surgery. METHODS: Ovid MEDLINE, Embase, Cochrane Library and PubMed databases were searched from inception to May 2019 to identify eligible RCTs focused on elective open or minimally invasive major abdominal surgery. The primary outcome was time taken to passage of stool. Secondary outcomes were time taken to tolerance of diet, time taken to flatus, length of hospital stay, postoperative complications and readmission to hospital. RESULTS: Five RCTs with a total of 416 patients were included. Laxatives reduced the time to passage of stool (mean difference (MD) -0·83 (95 per cent c.i. -1·39 to -0·26) days; P = 0·004), but there was significant heterogeneity between studies for this outcome measure. There was no difference in time to passage of flatus (MD -0·17 (-0·59 to 0·25) days; P = 0·432), time to tolerance of diet (MD -0·01 (-0·12 to 0·10) days; P = 0·865) or length of hospital stay (MD 0·01(-1·36 to 1·38) days; P = 0·992). There were insufficient data available on postoperative complications for meta-analysis. CONCLUSION: Routine postoperative laxative use after major abdominal surgery may result in earlier passage of stool but does not influence other postoperative recovery parameters. Better data are required for postoperative complications and validated outcome measures.

ANTECEDENTES: El retraso en la recuperación de la función gastrointestinal después de una cirugía abdominal mayor es frecuente y conlleva la aparición de un íleo postoperatorio (postoperative ileus, POI). Los protocolos de rehabilitación multimodal recomiendan la utilización de laxantes para reducir la duración del POI, pero su evidencia no es concluyente. Esta revisión sistemática tuvo como objetivo evaluar la seguridad y la eficacia de la utilización de laxantes tras cirugía abdominal mayor. MÉTODOS: Se realizó una búsqueda de los estudio clínicos aleatorizados (randomised controlled trials, RCTs) centrados en la cirugía abdominal mayor electiva, abierta o mínimamente invasiva, en las bases de datos Ovid MEDLINE, EMBASe, Cochrane Library y PubMed, desde el inicio hasta mayo de 2019. La variable principal fue el tiempo transcurrido hasta la primera deposición. Las variables secundarias fueron el tiempo hasta tolerar la dieta, el tiempo hasta la emisión de ventosidades, la duración de la estancia hospitalaria, las complicaciones postoperatorias y los reingresos hospitalarios. RESULTADOS: Se incluyeron cinco RCTs con un total de 416 pacientes. Los laxantes redujeron el tiempo hasta la primera deposición (diferencia media, mean difference, MD − 0,83 (i.c. del 95% −1,39 a −0,26) días; P = 0,004) pero hubo una heterogeneidad significativa entre los estudios para la medida de este resultado. No hubo diferencias en el tiempo hasta la emisión de ventosidades (DM − 0,17 (−0,59 a 0,25) días; P = 0,432), tiempo hasta la tolerancia de la dieta (DM − 0,01 (−0,12 a 0,10) días; P = 0,865) y la duración de la estancia hospitalaria (DM 0,01 (−1,36 a 1,38) días; P = 0,992). No había datos suficientes de las complicaciones postoperatorias para efectuar un metaanálisis. CONCLUSIÓN: El uso rutinario de laxantes en el postoperatorio de una cirugía abdominal mayor puede acelerar el tránsito de heces, pero no influye en otras variables de la recuperación postoperatoria. Se requieren datos de mayor calidad para evaluar las complicaciones postoperatorias y medidas de resultados validadas.

Clinical Benefits of Telotristat Ethyl in Patients With Neuroendocrine Tumors and Low Bowel Movement Frequency: An Observational Patient-Reported Outcomes Study.

OBJECTIVES: We evaluated carcinoid syndrome (CS) symptoms and the real-world effectiveness of telotristat ethyl (TE) among patients with ≤3 bowel movements (BM) per day. METHODS: Patients with CS initiating TE between March and November 2017 could participate in a nurse support program collecting demographic and CS symptom data before TE initiation (baseline) and during ≥1 monthly follow-up within 3 months. Symptoms for patients averaging ≤3 BM/d at baseline were evaluated using pre/post-Student t tests. RESULTS: Sixty-eight patients reported ≤3 BM/d at baseline. Symptom burden was high and similar to participants with higher daily BM frequency. After 3 months of TE, most patients reported stable or improved symptoms with significant improvements in urgency (88%; mean [SD], -13.2 [32.2]), stool consistency (88%; -1.3 [2.0]), BMs per day (81%; -0.2 [1.2]), abdominal pain (86%; -13.7 [25.8]), nausea (85%; -30.9 [35.7]), and daily flushing episodes (83%; -1.7 [4.4]; all except BMs per day, P < 0.05). CONCLUSIONS: This analysis illustrates high CS symptom burden among patients with relatively low daily BM frequency. After initiating TE, patients reported significant improvements in urgency, stool consistency, abdominal pain, nausea, and flushing episodes. Clinicians and population health managers should consider CS symptom burden beyond daily BM frequency when evaluating treatment selection.

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy.

INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

PEG vs. sennosides for opioid-induced constipation in cancer care.

PURPOSE: This randomized double-blind, double-dummy, 2-treatment, 2-period crossover study aimed to compare the efficacy and tolerability of polyethylene glycol (PEG) and sennosides in ambulatory cancer patients with opioid-induced constipation. METHODS: Outpatients ≥ 18 years old with cancer, at risk of or already experiencing opioid-induced constipation, were randomly assigned to begin a standard bowel protocol of escalating doses of sennosides or PEG, plus a dummy preparation. After 3 weeks, the patients switched to the alternate active product and dummy preparation. Constipation was assessed using the revised Victoria Bowel Performance Scale (rBPS) at the end of each of the 2 consecutive 21-day study periods for the number of days with a satisfactory bowel movement, the time in days to goal rBPS (G), and the treatment preference of each patient. RESULTS: Seventy patients were recruited, with 42 completing their first treatment period and 28 completing both treatment periods. For the typical patient, the expected number of days with a satisfactory bowel movement per days of treatment was found to be 1.21 times higher on PEG than on sennosides in a particular period (95% credible interval 0.96 to 1.55). Patients taking PEG were 1.47 times more likely to reach a rBPS of G before patients taking sennosides in the first period (95% confidence interval 0.74 to 2.94). There was no evidence of a difference in patient preference between laxatives. CONCLUSION: Our study found weak evidence that PEG is superior to sennosides with respect to overall effectiveness in cancer patients with opioid-induced constipation.

Effect of Caffeine Intake on Postoperative Ileus: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative ileus prolongs both hospital stay and patients' morbidity, having at the same time a great impact on health care costs. Coffee, a worldwide popular, cheap beverage might have an important effect on the motility of the postoperative bowel. METHODS: PubMed, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched. RESULTS: Four studies met the inclusion criteria of our meta-analysis. A total of 341 patients were included. The postoperative administration of coffee significantly reduces the time to first bowel movement, the time to first flatus and the time to tolerance of solid diet. Safe conclusions could not be drawn regarding the additional use of laxatives, the necessity for reinsertion of nasogastric tube or the need for reoperation as all the aforementioned outcomes did not present any statistically significance. None of the complications were attributed to the administration of coffee. CONCLUSION: The administration of coffee as a postoperative ileus prevention measure can change the way postoperative enhanced recovery is applied. Even though the mechanism of action of coffee is not fully known, currently available literature demonstrates a significant improvement in gastrointestinal motility without having any impact on postoperative morbidity. Studies with higher methodological quality can offer a more careful evaluation of the clinical use of this popular beverage.

Influence of alpha-adrenoceptor antagonists therapy on stool form in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVES: To evaluate the short-term efficacy and safety of two α1-adrenoceptor (AR) antagonists, tamsulosin and silodosin, in treating patients with untreated lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), with a focus on stool form. METHODS: This study was a non-blinded, open-label, prospective randomized comparative study. Tamsulosin or silodosin was administered to patients with untreated LUTS/BPH, and their efficacy and safety in the early stage of treatment were compared using the questionnaire of International Prostate Symptom Score (IPSS)/quality of life (QOL), the Gastrointestinal Symptom Rating Scale (GSRS), and the Bristol Stool Form Scale (BSFS). RESULTS: The per protocol set consisted of 22 patients in tamsulosin group (mean age, 70.15 ± 5.70 years) and 20 patients in silodosin group (73.00 ± 6.48 years). The total IPSS and QOL score improved within 2 weeks in both groups. Although the overall GSRS score showed no significant change in either group, "hard stools" score was significantly decreased in silodosin first at week 2, then in both groups at week 4. Furthermore, the subscale score for "constipation" was significantly decreased only in silodosin at week 4. BSFS was significantly increased at week 4 in silodosin alone. CONCLUSIONS: This study suggests that silodosin was associated with increased digestive symptoms such as diarrhea and loose stools. Therefore, oral drugs for BPH need to be selected by taking into consideration the possibility of digestive symptoms including both the state and type of stools.

Chronic, Twice-Daily Dosing of an NK2 Receptor Agonist [Lys5,MeLeu9,Nle10]-NKA(4-10), Produces Consistent Drug-Induced Micturition and Defecation in Chronic Spinal Rats.

Acute administration of [Lys5,Me,Leu9,Nle10]-NKA(4-10) (LMN-NKA) produces contractions of the detrusor and rectum with voiding in intact and acutely spinal cord injured (SCI) rats. In the current study, the ability of LMN-NKA (10 µg/kg or 100 µg/kg, subcutaneous [SC], twice a day [bid]) or vehicle to induce voiding and defecation in chronic SCI rats was examined across 30 days. After the last day of administration, voiding response rates and bladder pressure (BP) responses to LMN-NKA (intravenous [IV] and SC) were evaluated under anesthesia. In conscious rats, LMN-NKA (100 µg/kg) produced dose-dependent micturition within 5 min, with response rates >90%, and voiding efficiency >80% in males and >60% in females, which remained stable across the 1-month test period. Similarly, LMN-NKA administration rapidly induced defecation, which also remained stable. Under anesthesia, LMN-NKA increased BP, voiding efficiency, and voiding response rates, which reached 100% at 3 and 10 µg/kg IV in males and females, respectively. SC administration produced 100% response rates in males (30 µg/kg) but only 71% in females (100 µg/kg). Efficacy in rats chronically treated with LMN-NKA was similar to naïve and vehicle-treated rats, except for reduced voiding efficiency in chronically dosed female rats (100 µg/kg). No differences in bladder weights or collagen-to-smooth muscle ratios in histological sections were seen between the groups. Thus neither tolerance, nor sensitization, to LMN-NKA-induced micturition and defecation occurs with chronic administration in rats with chronic SCI. Efficacy was higher in male than in female rats.