Severe Diarrhea In Patients Research Articles

Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study

BackgroundChemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine.MethodsA single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea.ResultsA total of 746 patients were included. Median age was 64 years (interquartile range 57–71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54–7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85–5.87) were the only risk factors for severe diarrhea.ConclusionsFemale patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.

Prognostic factors for severe diarrhea in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation with capecitabine: A single-center cohort study.

e15176 Background: Chemoradiation with concomitant capecitabine (CRT) followed by total mesorectal excision is the standard of care for locally advanced rectal carcinoma (LARC). Grade ≥ 3 diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiotherapy. The aim of this study is to describe the risk factors of grade ≥ 3 diarrhea in patients with LARC during CRT. Methods: A single centre retrospective cohort study was conducted in our tertiary center. All patients with LARC treated with CRT from 2009 to 2015 were included. Patients with local recurrence who received CRT for the first time were also included. Univariate logistic regression analyses were used, followed by a multivariate analysis of the significant factors with backward selection at p < 0.05. Results: A total of 738 patients were included: 67% male, median age 64 years (range 17-88), 95% primary presentation. DPYD-testing was not performed upfront. In this cohort 69 patients (9%) developed ≥3 grade diarrhea. In the univariate analysis, factors significantly associated with ≥3 grade diarrhea were; female gender, age ≥65 years, body weight and decreased renal function (defined as MDRD GFR < 60 ml/min/1,73 m2). The following factors remained significantly associated with ≥3 grade diarrhea in the multivariate analysis; female gender (odds ratio (OR) 2.77, 95% confidence interval (CI) 1.54-4.99, p 0.001), age ≥65 years (OR 2.85, 95% CI 1.63-4.98, p < 0.001) and a lower bodyweight (OR 0.98, 95% CI 0.96-1.00, p 0.015). Conclusions: Female gender and age ≥65 years significantly increase the risk of grade ≥ 3 diarrhea caused by neoadjuvant CRT for LARC. So, older female patient must be closely watched during this treatment to intervene on time. The difference in toxicity between females and males might be explained by the pelvic anatomical differences between men and women. The found prognostic factors will be validated in a second cohort of patients with LARC treated with CRT. Besides, sarcopenia will be tested as a prognostic factor as well.

Traditional Chinese medicine Gegen Qinlian decoction ameliorates irinotecan chemotherapy-induced gut toxicity in mice

BackgroundGegen Qinlian decoction (GQT), is a classic traditional Chinese medicine formula chronicled in Shang Han Lun, and is widely used to treat diarrhea and inflammation symptoms in various gastrointestinal disorders. Although it has been found to inhibit delayed-onset mice diarrhea resulted from irinotecan (CPT-11) administration in preliminary experiments, the underlying mechanisms and chemical components remain elusive. MethodsThe effective fraction of GQT by macroporous resin elution was obtained and screened using a diarrhea mouse model induced by CPT-11 and quantified by UPLC analysis. The protective effect of GQT extract towards alleviating diarrhea in mice following CPT-11 administration was further investigated. The levels of inflammatory cytokines and intestinal tight junction related proteins in colonic tissues were determined. The inhibitory effect of GQT extract against hCE2 was evaluated by a fluorescence-based method. Lastly, the synergistic effect of GQT extract combined with CPT-11 against tumor growth in a colorectal tumor mouse model, induced by HT-29 colon cancer cells xenograft subcutaneously, was investigated. ResultsThe obtained GQT extract, which profoundly ameliorated the gut toxicity induced by CPT-11, contained puerarin, liquiritin, berberine, and baicalin of 27.2 mg/g, 4.6 mg/g, 491.4 mg/g, and 304.2 mg/g, respectively. After 5 days of administration of GQT extract to mice with diarrhea induced by CPT-11, aberrantly elevated levels of pro-inflammatory cytokines, including IL-1β, COX-2, ICAM-1, and TNF-α, were significantly decreased. Meanwhile, GQT extract also exhibited a remarkable anti-oxidative stress effect, involving activating the Keap1/Nrf2 pathway, and up-regulating the intestinal barrier function by enhancing the expression of tight junction proteins ZO-1, HO-1, and occludin. Additionally, a potent inhibitory effect of GQT extract against hCE2 was observedin vitro, with its IC50 value of 0.187 mg/ml, suggesting alleviating activity on hCE2-mediated severe diarrhea in patients suffered from CPT-11. Moreover, GQT extract was shown to improve inhibition of the colonic tumor growth synergistically with CPT-11. ConclusionThe present study indicates that GQT extract can ameliorate CPT-11 induced gut toxicity in mice and improve CPT-11 efficacy in colorectal cancer treatment.

UGT1A1 Gene Polymorphism Predicts Irinotecan-Induced Severe Neutropenia and Diarrhea in Chinese Cancer Patients.

Irinotecan was widely used in colon cancer and lung cancer, etc., and adverse reactions occur some times. The primary aim of this research is to investigate the association between UGT1A1 gene polymorphisms and irinotecan-related adverse effect in Chinese Han population with a novel kind of gene chip technology. UGT1A1*6/*28 gene polymorphisms were detected by PCR and gene chip as well as sequencing. The correlation between UGT1A1 gene polymorphisms and severe delayed diarrhea or neutropenia and effect on response rate and progression-free survival were analyzed. A total of 106 patients receiving irinotecan-based regimens and with detected UGT1A1 gene polymorphisms were enrolled in this research. According to our results, no significant differences of severe diarrhea were found in patients with UGT1A1*6 genotypes (p = 0.608). However, the incidence of severe diarrhea in patients with TA7/7 genotype (66.7%, 4/6) was significantly higher than that in patients with TA6/7 (31.5%, 6/19) or TA6/6 (1.28%, 1/78) genotypes (p < 0.001). The incidence of severe hematologic toxicity in patients with AA (100%, 2/2) was significantly higher than that in patients with GA (33.3%, 7/21) or GG genotype (7.23%, 6/83) (p = 0.011). In terms of irinotecan-based regimens in cancers, UGT1A1*6 plays a more vital role in hematologic toxicity (p = 0.011) whereas UGT1A1*28 get more involved in diarrhea (p < 0.001).

Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancer patients treated with adjuvant concurrent chemoradiotherapy

The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT). Four hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model. A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea. The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.

Association of a novel polymorphism G-133C of thymidylate synthase (TYMS) gene with 5-FU-related severe diarrhea in Japanese patients with colorectal cancer

14108 Background: 5-FU remains a key drug for the treatment of several cancers, including cancers of the colorectum, stomach, and breast. Increasing evidence suggests that genetic polymorphism results in increased toxicity. This prospective study intended to elucidate the relations between 5-FU-related toxicity and polymorphisms of several genes. Methods: Blood for genotyping was obtained before treatment. Blood samples were drawn at 2-week intervals for 8 weeks to assess hematologic toxicity. Adverse events were assessed according to NCI CTC, v2.0. The genes encoding TYMS and thymidine phosphorylase (ECGF1) were analyzed with leukocyte DNA obtained from patients with colorectal cancer who received 5-FU (500 or 600 mg/m2) and leucovorin (LV) (250 mg/m2) weekly for 6 weeks every 8 weeks. Results: Seventy-eight patients with colorectal cancer were enrolled and genotyped. Toxicity was evaluated in all patients. No genetic polymorphisms detected were significantly associated with 5-FU-related hematological toxicity. Only G- 133C located in the 5’-UTR region of the TYMS gene was significantly associated with 5-FU-related grade 3 diarrhea. Conclusions: The TYMS G-133C SNP may be a critical determinant of severe diarrhea in patients treated with 5-FU/LV. [Table: see text] No significant financial relationships to disclose.

Severe Diarrhea in Patients with Advanced- Stage Colorectal Cancer Receiving FOLFOX or FOLFIRI Chemotherapy: The Development of a Risk Prediction Tool

FOLFOX (oxaliplatin/leucovorin/5-fluorouracil) and FOLFIRI (irinotecan/leucovorin/5-fluorouracil) are important regimens for the treatment of advanced-stage colorectal cancer (CRC). However, both are associated with severe diarrhea, leading to hospitalization, dose reductions/delays, and even death. In this study, the development of a prediction model for severe diarrhea is described. The records of 200 patients with CRC who had received FOLFOX or FOLFIRI in 3 Canadian cancer centers were reviewed. Clinical and biochemistry parameters potentially associated with diarrhea were abstracted. Logistic regression analysis was applied to develop the final risk model. A risk scoring system, ranging from 0 to 15, was then created from the regression parameters. A receiver operative characteristic curve analysis was done to measure the accuracy of the scoring system. Important predictors for severe diarrhea included existing comorbidity, patient performance status, an increased baseline bilirubin level, resection of the primary tumor, FOLFOX chemotherapy, metastatic or advanced locoregional versus resected stage IV disease, and the initiation of treatment in the summer months. The receiver operative characteristic analysis had an area under the curve of 0.80 (95% confidence interval, 0.74-0.87). An overall risk score of > or = 7 for a given patient was identified as being the optimal cutoff to maximize the sensitivity (61.4%) and specificity (89.6%) of the prediction tool. We developed a prediction tool for severe diarrhea in patients with CRC receiving FOLFOX or FOLFIRI chemotherapy. To make the model available for easy use and access, we have incorporated it on to our risk prediction Web site: www.PredictPatientEvents.com. Prospective external validation is also being planned.

Long-acting octreotide in the treatment of diarrhea after pelvic pouch surgery

After pelvic pouch surgery (restorative proctocolectomy), periodic or continuous diarrhea is common. Distressing diarrhea may be triggered by pouchitis, cuffitis or an anastomotic stricture. Medical therapy with loperamide or diphenoxylate is often unsatisfactory even after the correction of the underlying problem. Seven patients, who earlier had undergone restorative proctocolectomy, were treated with a standard dose of 10 mg of long-acting octreotide (Sandostatin LAR) for prolonged and distressing diarrhea which had not responded to conventional medication. Five of the patients had complete relief of diarrhea. The effect lasted for at least two months after a single dose. Two patients did not respond. No sideeffects were reported. Long-acting octreotide is effective in the treatment of severe diarrhea in patients after pelvic pouch surgery.

Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis

Objective The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Methods Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Results Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15–36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Conclusions Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

Blastocystis hominis in human immunodeficiency virus-related diarrhea.

A wide variety of bacterial, viral, and parasitic pathogens can cause severe diarrhea in patients with advanced human immunodeficiency virus (HIV) infection. Conflicting evidence exists as to whether Blastocystis hominis should also be included among the infectious agents capable of causing HIV-related diarrhea. We determined the prevalence and clinical significance of B. hominis in a cohort of 262 patients with HIV infection, presenting at the infectious diseases department of a tertiary referral university hospital in northern Germany. B. hominis was detected in stool samples of 99 patients (38%). The isolation rate varied highly between the different groups. Homosexual men (43%; odds ratio (OR), 2.1; p = 0.01) had a higher detection rate than patients from other risk groups (26%), and patients with acquired immunodeficiency syndrome (46%; OR, 1.8; p = 0.03) were more likely to carry B. hominis than patients in earlier stages of their HIV infection (32%). An association with clinical symptoms was not evident. Presence of B. hominis, however, was frequently associated with the concurrent isolation of other enteric pathogens or apathogenic parasites. The data suggest that the isolation of B. hominis does not justify treatment even in symptomatic, severely immunocompromised patients. Most patients will either have spontaneous resolution of symptoms or successful identification of other infectious or noninfectious etiologies. Therapy should be limited to patients with persistent unexplained symptoms after a thorough evaluation and a complete screening for alternative etiologies, including the use of endoscopic procedures and the careful examination of multiple specimens.

Microtubule inhibitors block Cryptosporidium parvum infection of a human enterocyte cell line

No effective therapy exists for Cryptosporidium parvum, a coccidial protozoan parasite that causes severe diarrhea in patients with AIDS. The role of microtubules in parasite invasion of host cells was investigated by incubating 10(7) oocysts with a HT 29.74 cell line for 24 h in the presence of microtubule-disrupting drugs. The number of parasites per 1,000 cells was reduced by 77% (P < 0.001, n = 4) from 182 +/- 3 in untreated cells to 42 +/- 4 in cells treated with 10(-4) M colchicine. Inhibition of C. parvum infection was concentration dependent. Similar results were seen with a second microtubular depolymerization agent, vinblastine. These data suggest that microtubules are important in host cell invasion by C. parvum and may represent targets for development of new therapeutic drugs for treatment of cryptosporidiosis.

Rotavirus antigen detection in patients with HIV infection and diarrhea.

A wide variety of bacterial, viral, and parasitic pathogens can cause severe diarrhea in patients with advanced human immunodeficiency virus (HIV) infection. The role of enteric viruses, especially rotaviruses, in HIV-related diarrhea is still unclear. One hundred and six stool samples from 66 HIV-infected patients with otherwise unexplained diarrhea and 35 samples from 35 patients with advanced HIV infection but without diarrhea were tested for the presence of rotavirus antigen. Rotavirus was detected in 13 samples from 9 patients with diarrhea and in none of the samples from patients without diarrhea. Two patients had recurrence of rotavirus infection more than 6 months after the first episode. Rotavirus was associated with prolonged diarrhea, often accompanied by abdominal cramping. Symptoms were readily controlled with anti-diarrheal and pain-relieving measures. Illness was self-limited and did not require hospitalization. A seasonal variation, typical of infantile rotavirus infection, was not observed in this setting. While rotavirus infection has been infrequently detected in American HIV-infected patients, the prevalence in Australia and Europe appears to be considerably higher.

Gastroenterology: An Annotated Bibliography of Recent Literature

Gastroenterology: An Annotated Bibliography of Recent Literature

Comparison of Sucrose and Glucose in the Oral Electrolyte Therapy of Cholera and Other Severe Diarrheas

The effectiveness of sucrose and glucose electrolyte solutions as fluid replacement in cholera and severe diarrheas from other causes was compared. Subjects in this study which took place in Bangladesh were of both sexes and were aged 5 years or older. Patients were randomly assigned to 1 of the 2 oral solutions; both had concentrations of 96 mEq of sodium, 25 mEq of Potassium, 72 mEq of chloride, 24 mEq of bicarbonate, and 25 mEq of citrate, and 1 solution had 40 gm of sucrose and the other 20 gm of glucose. The solutions were coded and the test was double-blind. Of 122 patients, 69 were given sucrose and 53 the glucose solution. The total success rate was 86% from sucrose-electrolyte solution and 87% for glucose. In addition, total volumes needed for successful therapy were essentially the same. In 10 of 17 failures (7 sucrose and 3 glucose) the same therapy was used again after intravenous therapy, and only 2 cases remained failures. Thes results suggest that sucrose can effectively replace glucose in an oral electrolyte solution for severe diarrhea in patients over 5 years of age.