Treatment Of Diarrhea In Patients Research Articles

S3514 A Case of Symptomatic Ileal Non-Secretory Neuroendocrine Tumor Successfully Treated With Octreotide

Introduction: Neuroendocrine tumor incidence is steadily increasing, likely from detection due to better imaging, routine colonoscopies, and endoscopies. Most NETs, 55%, are found in the GI tract and only 0.1-1% found on routine colonoscopy. About 40% of NETs are hormone producing leading to the clinical diagnosis of carcinoid syndrome. One of the most common symptoms of carcinoid syndrome is diarrhea occuring in 80% percent of cases, however diarrhea can be present in non-secretory NETs. Here we report a case of GNET presenting as diarrhea that responded to octreotide injections despite having normal 5-HIAA and chromogranin A levels. Case Description/Methods: Our patient is an 80 year old female with past medical history of hypertension, renal stones, and IBS with baseline diarrhea of about 2-4 pasty stools a day. In November she developed two days of severe diarrhea with 10 watery stools a day and multiple episodes of incontinence which prompted patient to go to the ED. The inpatient workup was negative for acute causes, CT showed diverticulosis, and stools returned to baseline. The patient was discharged with outpatient GI follow up. At home the severe diarrhea retuned so outpatient GI planned for colonoscopy. Results of the procedure included a 2cm submucosal non-obstructing mass in the terminal ileum. Pathology showed a G1 well differentiated neuroendocrine tumor. Patient was referred to oncology and workup revealed no metastasis on PET/CT and negative 5-HIAA and chromogranin A levels. During initial oncology visit patient was started on octreotide injections which greatly improved the diarrhea. Even with negative carcinoid workup the decision was made to continue octreotide injections and not to pursue surgical options. (Figure) Discussion: The terminal ileum is the most common GI location for NETs. Terminal ileum intubation on coloscopy is attempted 30-80% and greatly aids in diagnosis, as with our patient. Once diagnosed, there is limited guidance on treatment of diarrhea in patients with NETs and negative carcinoid workup. There are no abstracts or research on treatment of diarrhea with negative carcinoid syndrome. One treatment for carcinoid syndrome is somatostatin analogues but no guidelines with non-carcinoid NETs and therapeutic value in octreotide. However, with our patient, treatment with monthly octreotide injections resolved their symptoms. Our case emphasizes importance of ileal intubation in coloscopy and that somatostatin analogue treatment should be considered in non carcinoid NETs.Figure 1.: Small bowel (terminal ileum): well-differentiated neuroendocrine tumor (G1).

Moxibustion for diarrhea in COVID-19: A protocol for systematic review and meta-analysis.

Background:Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that is often accompanied by diarrhea, patients with symptoms such as diarrhea are more likely to develop severe pneumonia, while diarrhea is the most prominent among atypical symptoms. The incidence of diarrhea in COVID-19 patients is 2.0% to 49.5%. Moxibustion has been proven to have a therapeutic effect on diarrhea; however, there is no high-quality evidence on moxibustion for diarrhea in COVID-19 patients. This study was designed to evaluate the effectiveness and safety of moxibustion for the treatment of diarrhea in patients with COVID-19.Methods:Randomized controlled trials from December 2019 to December 2021 will be included without restrictions on language or publication date. PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases, China National Knowledge Infrastructure, Wanfang database, and VIP database will be searched. Two researchers will independently select studies, extract data and evaluate study quality. Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias of included studies. Statistical analyses will be performed using the Review Manager V.5.3 and stata 14.0.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide evidence for whether moxibustion therapy is beneficial to the treatment of diarrhea in COVID-19.Ethics and dissemination:Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations.Prospero registration number:CRD42022302933.

Fecal microbiota transplantation for TKI-induced diarrhea in patients with metastatic renal cell carcinoma.

615 Background: Diarrhea is a common adverse event of tyrosine kinase inhibitors (TKI). No standard treatment for TKI-induced diarrhea has been established, although probiotics are commonly used. In several patients TKI dose reduction is necessary. Data showing the interplay between microbiota and TKI-induced diarrhea are reported. The therapeutic modulation of gut microbiota could be useful to ameliorate TKI-related diarrhea. Our study aims to explore the efficacy and safety of fecal microbiota transplantation (FMT), compared with current clinical practice approach, for the treatment of TKI-associated diarrhea in patients with metastatic renal cell carcinoma. Methods: Patients on treatment with Pazopanib/Sunitinib as first line therapy for metastatic renal cell carcinoma and TKI-associated diarrhea (³ 4 stools per day over baseline) were randomize to receive FMT from healthy donor by colonoscopy (fresh faeces) or probiotics (L. casei DG). The primary endpoint was the resolution of TKI-related diarrhea. Baseline fecal samples were collected from all patients and donors. All patients were followed up 7, 15, 30 and 60 days after the treatment for diarrhea. Results: 21 subjects, 10 in FMT arm and 11 in control arm, have been enrolled. At 7 day-follow-up, TKI-related diarrhea disappeared in 10 patients of the FMT group and in 6 patients of the control group (100% vs 54.5%, p = 0.02). At 15-day and 30-day, 9 patients in the FMT group and 0 patients in the control group experienced resolution of diarrhea (90% vs 0%, p = 0.0001). At 60-days 8/10 patients in FMT arm did not have diarrhea. Dose reduction was necessary in 4 patients of the control group. No serious adverse events associated with any of the two treatment protocols were observed. Metagenomic analyses on collected stool samples are ongoing. Conclusions: This open-label randomised controlled trial showed the effectiveness and safety of FMT compared with probiotics in curing TKI-related diarrhea in patients with metastatic renal cell carcinoma, avoiding the necessity of dose reduction. Considering the increasing evidence, the modulation of microbiota trough FMT could also affect the efficacy of immunotherapy for metastatic renal cell carcinoma.

Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.

Two 6β- N-heterocyclic naltrexamine derivatives, NAP and NMP, have been identified as peripherally selective mu opioid receptor (MOR) antagonists. To further enhance the peripheral selectivity of both compounds, the 17-amino group and the nitrogen atom of the pyridine ring in both NAP and NMP were methylated to obtain dMNAP and dMNMP, respectively. Compared with NAP and NMP, the binding affinities of dMNAP and dMNMP shifted to MOR and KOR (kappa opioid receptor) dual selective and they acted as moderate efficacy partial agonists. The results from radioligand binding studies were further confirmed by molecular docking studies. In vivo studies demonstrated that dMNAP and dMNMP did not produce antinociception nor did they antagonize morphine's antinociceptive activity, indicating that these compounds did not act on the central nervous system. Meanwhile, both dMNAP and dMNMP significantly slowed down fecal excretion, which indicated that they were peripherally acting opioid receptor agonists. All together, these results suggested that dMNAP and dMNMP acted as peripheral mu/kappa opioid receptor modulators and may be applicable in the treatment of diarrhea in patients with bowel dysfunction.

Loperamide therapy for voluminous diarrhea in Ebola virus disease.

Loperamide therapy for voluminous diarrhea in Ebola virus disease.

Ramosetron might be useful for treating diabetic diarrhea with a rapid small bowel transit time

To the Editor, The diagnosis and treatment of diarrhea can be challenging. Diabetic diarrhea is seen mainly in patients with poorly controlled insulin-dependent diabetes who also have symptoms of diabetic peripheral and autonomic neuropathy. Typically, the diarrhea is painless, occurs during the day and night, and may be associated with fecal incontinence [1]. We used ramosetron, a selective 5-HT3 receptor antagonist, to treat diabetic diarrhea with a rapid small bowel transit time. A 49-year-old man who had developed type 2 diabetes mellitus at 42 years of age, presented with diarrhea 6 months ago. His glycemia was poorly controlled, based on a haemoglobin A1c of 17.7%. He had hypercholesterolemia, orthostatic hypotension, diabetic retinopathy, nephropathy, peripheral neuropathy, autonomic neuropathy, and gastroparesis. Current medications included insulin, losartan, atorvastatin, midodrine, metoclopramide, and domperidone. Diarrhea occurred at a frequency of > 10 bowel movements per day, with fecal urgency following meals. Steatorrhea was absent and the stool examination was unremarkable. He was prescribed conventional antidiarrheals, including a pancreatic enzyme supplement, rifaximin, probiotics, cimetropium bromide, and loperamide, but these were ineffective. He also had iron-deficiency anemia, as evidenced by a hemoglobin of 9.1 g/dL, mean corpuscular volume of 84.7 fL, 1.95% reticulocytes, and ferritin of 8.45 ng/mL. Capsule endoscopy (PillCam SB2, Given Imaging, Yokneam, Israel) was performed after upper endoscopy, colonoscopy, and abdominal computed tomography failed to explain the iron-deficiency anemia. He fasted for 12 hours before capsule ingestion. For 4 hours following ingestion of the capsule, only water was permitted, after which a liquid diet was offered. All medications except the losartan were discontinued. Capsule endoscopy identified multiple angiodysplastic lesions in the distal ileum. Interestingly, a markedly prolonged gastric emptying time (13 hours 33 minutes) with a rapid small bowel transit time (14 minutes) was noted (Fig. 1), suggesting gastroparesis and autonomic neuropathy, respectively. The diarrhea persisted, so ramosetron therapy (Irribow, Astellas Pharma Korea, Seoul, Korea) was started at 5 µg once daily before breakfast. The diarrhea and fecal urgency disappeared completely after 1 week of ramosetron treatment, with the bowel movement frequency reduced to two soft stools per day. On ceasing ramosetron, the diarrhea recurred, but was relieved once more when the medication was restarted. 5-Hydroxytrytamine (5-HT) acts on 5-HT3 parasympathetic receptors to produce smooth muscle contraction and the release of acetylcholine from nerve terminals, causing intestinal secretion to increase [2]. The 5-HT3 receptor antagonist alosetron is useful in the treatment of diarrhea in patients with irritable bowel syndrome, but must be avoided in more severe cases because of the risk of constipation [3]. The efficacy of other 5-HT3 receptor antagonists such as ondansetron [4] and ramosetron [5] in the treatment of diabetic diarrhea has been documented. Figure 1 (A) Stomach. (B) Duodenum. (C) Colon. Capsule endoscopy revealed a markedly prolonged gastric transit time with rapid small bowel transit (gastric emptying time, 13 hours 33 minutes; small bowel transit time, 14 minutes). In conclusion, given the inhibitory effects of a 5-HT3 receptor antagonist on smooth muscle contraction and secretion, ramosetron should be considered in cases of diabetic diarrhea with rapid small bowel transit. A larger study is needed to verify the efficacy of ramosetron in treating this condition.

Octreotide for the treatment of diarrhoea in patients with ileal pouch anal anastomosis: a placebo-controlled crossover study

Diarrhoea with urgency is a debilitating long-term complication of ileal pouch anal anastomosis (IPAA) after a proctocolectomy. Somatostatin analogues are used to control diarrhoea and high-output ostomies. Hence, we designed a prospective, double-blind, crossover trial to explore the efficacy and tolerability of octreotide to reduce diarrhoea in adult patients with IPAA. Patients were randomized to octreotide subcutaneously (SC), 500 μg three times daily (t.i.d.), or matching placebo SC for 7 days. Responders (a reduction in stool frequency of three or more stools per 24-h period and with a reduction in stool frequency of at least 30% after 7 days of treatment compared with baseline; the primary end-point) remained in the same group and nonresponders could cross over to the alternative treatment for 7 days. Open-label octeotide LAR 30 mg was offered to all responders on day 14. Flexible pouchoscopy with biopsies was performed at baseline in all patients and was repeated on days 7 and 14 in patients with pouchitis. Fifteen patients (11 men, median age 52 years), all with ulcerative colitis, were randomized. Three patients were withdrawn for side effects during the blinded phase. Response was achieved by two of 12 and two of 11 patients treated with octreotide or placebo, respectively (including crossover, P = 0.9). The median stool frequency remained stable in both groups [Δoctreotide: 0 (IQR, -4 to 0), Δplacebo: -1 (IQR, -1 to 1), P = 0.45]. Octreotide had no effect on the modified pouch disease activity index (mPDAI), and pouchitis persisted in five of six subjects with pouchitis at onset. One subject received open-label octreotide LAR. Octreotide has no clear beneficial effect on the stool pattern or on pouchitis severity in patients with high stool frequency after IPAA.

Nitazoxanide for the Empiric Treatment of New Onset Diarrhea in Patients with IBD and IBS

Nitazoxanide for the Empiric Treatment of New Onset Diarrhea in Patients with IBD and IBS

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.

Phase III double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea during pelvic radiation therapy: Results of North Central Cancer Treatment Group protocol N00CA

8506 Background: A randomized study (Int J Rad Oncol Biol Phys 54:195–202, 2002) demonstrated a beneficial effect for octreotide in the treatment of diarrhea in patients receiving pelvic radiation therapy. This North Central Cancer Treatment Group study was undertaken to determine the effectiveness of depot octreotide in the prevention of diarrhea during pelvic radiation therapy. Methods: Patients receiving pelvic radiation therapy, with a planned minimum dose of 45 Gy at 1.70–2.1 Gy per day, were eligible for this study. The study was designed for a Wilcoxon test, with 112 evaluable patients, to have 85% power to detect a further one grade decrease in diarrhea over and above that experienced by patients treated with placebo. Between June 13, 2002 and October 28, 2005, 120 evaluable patients were randomly allocated, in double blind fashion, to receive octreotide (62 patients) or placebo (58 patients), prior to the fourth radiation therapy fraction. Octreotide dosing: Octreotide, 100 micrograms subcutaneously on day 1 followed by depot octreotide, 20 milligrams intramuscularly on days 2 and 29. Results: Grade 0, 1, 2 and 3 diarrhea was observed in 17%, 32%, 26% and 26% of patients treated with octreotide and 18%, 34%, 22%, and 26% of patients treated with placebo (P=0.86). Grade 0, 1, 2 and 3 tenesmus was observed in 55%, 30%, 11% and 4% of patients treated with octreotide and 76%, 16%, 4%, and 4% of patients treated with placebo (P=0.04). No other statistically significant differences in toxicity were observed. Conclusions: Octreotide, as administered in this study, did not decrease diarrhea during pelvic radiation therapy. [Table: see text]

Research agenda for pediatric gastroenterology, hepatology and nutrition: secretion and diarrhea. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

Research agenda for pediatric gastroenterology, hepatology and nutrition: secretion and diarrhea. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS

OBJECTIVE: The aim of this study was to investigate the safety and effectiveness of orally administered SP-303 in patients with AIDS and diarrhea. METHODS: This is a multicenter, phase II, randomized, double blind, placebo-controlled study. HIV-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and screened for diarrhea defined as at least three abnormal ( i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg p.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up. RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 48 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h versus 150 g/24 h with placebo on day 4 of treatment ( p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 h in the placebo group ( p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight ( p = 0.008) and abnormal stool frequency ( p = 0.04) when compared to placebo-treated subjects. CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and diarrhea.

Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial

To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia. A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months. Home care. AIDS services in Lusaka and Ndola. 174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling. Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality. The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P < 0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P = 0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P = 0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted. For HIV infected Zambians with diarrhoea of more than three weeks' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.

Diarrhea and the patient receiving enteral feedings: a multifactorial problem.

Diarrhea is often considered an inevitable consequence of enteral tube feeding. The pathogenesis of diarrhea in patients receiving enteral feeding is not well understood, but it has been attributed to hypoalbuminemia, bacterial contamination of formula, characteristics of enteral feeding formula, and concomitant drug therapy. The purpose of this article is to review research regarding the etiology and treatment of diarrhea in patients receiving enteral feeding and to identify implications for nursing practice and future research.