Chemotherapy-induced Diarrhea Research Articles

Use of Probiotics in the Management of Chemotherapy‐Induced Diarrhea: A Case Study

Gastrointestinal disturbances (particularly diarrhea) are often induced in response to cancer treatments such as chemotherapy or radiation. Oral chemotherapeutic agents can induce diarrhea by damaging the intestinal lining. Two common oral drugs used in cancer treatment that are known to have gastrointestinal side effects are capecitabine and lapatinib. In this brief communication, the authors discuss a case study of a stage IV breast cancer patient whose chemotherapy-induced diarrhea was treated successfully with a multispecies combination of probiotics. This is a unique study in which grade 3 chemotherapy-induced diarrhea (characterized by 7-9 stools per day and associated with incontinence and abdominal cramping) was treated with only a multispecies combination of probiotics. Probiotics have been used to treat diarrhea in patients with irritable bowel syndrome, ulcerative colitis, pouchitis, and Crohn's disease. More recently, probiotics have been used to treat chemotherapy-induced diarrhea in colon cancer patients. This case study demonstrates that the probiotics can also be used to treat severe cases of chemotherapy-induced diarrhea in breast cancer patients. The use of different probiotics in gastrointestinal diseases is an increasingly important area of study, and more research into this area is needed. This study demonstrates that probiotics should be considered for advanced breast cancer patients with chemotherapy-induced diarrhea.

Chemotherapy-induced diarrhoea

Diarrhoea is a major manifestation of chemotherapy-induced mucositis that until recently has received very little attention. To date, there is no detailed understanding of the underlying mechanisms of the condition. The purpose of this review is to examine the plethora of recent studies, both in the laboratory and in the clinic, which have attempted to elucidate effective treatment options. Over recent years, there have been many new treatment options trialled for ameliorating chemotherapy-induced diarrhoea. Some of these have shown great promise in small clinical studies and now need to be investigated in larger trials. Furthermore, there have been developments in the understanding of the underlying mechanisms of chemotherapy-induced diarrhoea. These developments may also lead to effective treatment options. Here, we describe the current thinking behind the mechanisms of chemotherapy-induced diarrhoea and present current and new treatment options. This opinion article highlights the shift towards more effective research into diarrhoea caused by chemotherapy.

Intestinal Permeability and Vitamin A Absorption in Patients With Chemotherapy-Induced Diarrhea

Gastrointestinal toxicity is one of the most common side effects of anticancer therapy. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability and vitamin A absorption in patients with chemotherapy-induced diarrhea (CID). We have assessed intestinal permeability, by measuring absorption of lactulose, mannitol, xylose, and vitamin A absorption, in 11 patients with CID, 10 healthy controls, and 24 untreated patients with gastrointestinal tumors. Urinary lactulose, mannitol and xylose were measured by capillary gas chromatography and serum retinol and retinyl esters were determined by high performance liquid chromatography. The results obtained in patients and controls were compared by Mann-Whitney U test. Lactulose/mannitol and lactulose/xylose ratios were increased and retinol esters (retinyl palmitate and retinyl stearate) were decreased significantly in patients with CID. Measurements of intestinal permeability and vitamin A absorption may represent sensitive tools in the assessment of CID.

Faecal microflora and β-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats

Objectives: Chemotherapy-induced diarrhea (CID) is a well recognized side effect of cancer treatment. However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which β-glucuronidase produced by gut bacteria is thought to be involved. Methods: Rats were treated with 200mg/kg irinotecan and killed at various time points up to 72 h. Rats were monitored for diarrhea. Sections were stained for β-glucuronidase expression, and faecal DNA was analysed using real time PCR. Results: Diarrhea occurred, as expected, following irinotecan treatment. β-glucuronidase expression increased in the jejunum and colon. Faecal flora changed quantitatively after treatment also, with increases in E. coli, Staphylococcus spp., and Clostridium spp. (all β-glucuronidase producing), and decreases in Lactobacillus spp., Bifidobacterium spp. (both beneficial bacteria), and Bacteroides spp. (β-glucuronidase producing, major component of intestinal flora). Conclusions: Irinotecan-induced diarrhea may be caused by an increase in β-glucuronidase producing bacteria. However, the increase in bacteria may also be caused by irinotecan, further exaggerating the toxicity of the drug, and emphasising the need for these specific bacteria to be therapeutically targeted for successful treatment regimens to be accomplished.

ABCG2 Q141K polymorphism is associated with chemotherapy‐induced diarrhea in patients with diffuse large B‐cell lymphoma who received frontline rituximab plus cyclophosphamide/doxorubicin/ vincristine/prednisone chemotherapy

ATP-binding cassette transporter G2 (ABCG2) is the most recently described transporter of the multidrug-resistance pump and it promotes resistance to anticancer drugs such as doxorubicin, mitoxantrone, topotecan, and SN-38. Of the ABCG2 polymorphisms, V12M and Q141K alter the functional activity of the ABCG2 transporter and influence the drug response and various toxicities to chemotherapeutic agents. We therefore evaluated the impact of the ABCG2 V12M and Q141K polymorphisms on the therapeutic outcomes and toxicities of primary rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in 145 Korean patients with diffuse large B-cell lymphoma (DLBCL). ABCG2 V12M and Q141K genotyping was carried out by pyrosequencing of polymerase chain reaction products. The clinical characteristics, treatment outcomes, toxicities of the patients, and the predictive value of the polymorphisms on response, survival, and adverse events to R-CHOP for 145 patients were analyzed according to the ABCG2 V12M and Q141K polymorphisms. No differences were observed according to ABCG2 Q141K and V12M genotype in patient characteristics, disease characteristics, response, survival, or hematology toxicity profiles in patients with DLBCL who received frontline R-CHOP chemotherapy. On multivariate analysis, grade I-IV diarrhea was statistically significant according to ABCG2 Q141K polymorphism (the QQ genotype vs the QK or KK genotypes; hazard ratio 2.835; 95% confidence interval 1.432-5.613; P = 0.003). This study demonstrates that the ABCG2 Q141K polymorphism may correlate with chemotherapy-induced diarrhea in patients with DLBCL who have received frontline R-CHOP chemotherapy, and this has implications for optimizing treatment with such agents.

Irinotecan-induced mucositis is associated with changes in intestinal mucins

Mucositis is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy and radiotherapy. Irinotecan is used to treat a variety of solid tumours, through the inhibition of DNA topoisomerase I and is linked with severe mucositis and diarrhoea. Mucus production appears to be increased, which may contribute to the development of diarrhoea. Dark agouti rats were treated with irinotecan, and tissues collected at several time points up to 72 h. Goblet cells and mucin secretion were investigated, as well as mucin expression (Muc2 and Muc4) and kruppel-like factor (Klf) 4 using immunohistochemistry in the gastrointestinal tract. Both goblet cells and cells positive for Muc expression were counted, and analysed statistically using the Mann-Whitney U test with Bonferroni correction. Goblet cells decreased significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. Irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea.

Established and potential therapeutic applications of octreotide in palliative care

Octreotide acetate was developed as a pharmacologically stable, long-acting analogue of the hormone somatostatin. Mimicking the actions of somatostatin, octreotide has been used for its antisecretory effects. Randomized control trials have established the efficacy of octreotide for malignant bowel obstruction and for chemotherapy-induced diarrhea. Octreotide has proven to be an effective agent for symptoms of carcinoid syndrome. Newer uses include for bone marrow transplantation, infectious diarrheal syndromes, and management of hepatic metastases. More evidence is needed for the establishment of its efficacy for hypercalcemia, pain, pleural effusions, diarrhea after celiac plexus block, and malignant ascites.

Chemotherapy induced diarrhea

To provide a current review of the literature related to chemotherapy induced diarrhea (CID), including clinical assessment, recommended management guidelines and investigational pharmacological approaches for the prevention and treatment of CID. A search of MEDLINE, PubMed, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, and Web of Science (1996-2006) databases was conducted using terms such as: chemotherapy, diarrhea, diarrhoea, and irinotecan. Appropriate references from selected articles were also used. The search engine, Google, provided further access to information. The retrieved literature was reviewed to include all articles pertaining to the pathophysiology, assessment and management of CID. Diarrhea is a debilitating and potentially life-threatening side effect associated with many chemotherapeutic agents. Despite the high incidence and severity of CID, it is often under recognized and poorly managed. A multidisciplinary panel recently updated recommended practice guidelines for the assessment and management of CID. Prompt and aggressive intervention is important in order to minimize the negative consequences of CID, such as dehydration, which may cause interruptions in optimal clinical outcomes or may lead to life-threatening sequelae. Further investigation into the pathophysiology of CID may allow for more directed approaches in the prophylaxis and treatment of CID.

Onkologie für den Grundversorger – Stand 2007

Despite intensive efforts are malignant diseases still responsible for most of the deaths occurring in persons of middle age. This article reviews some recent recommendations and new developments in cancer prevention and screening. Moreover it lists the different new therapeutic agents that are now in increasing use in oncological treatments with a special focus on their new side effects potential. Especially the skin toxicity associated with agents targeting the epidermal growth factor receptor (EGFR) is reviewed. Treatment guidelines for chemotherapy-induced emesis, diarrhea and myelosuppression are also discussed. Another topic covered is the follow-up of cancer patients after discharge from the oncologist.

VSL#3 probiotic treatment reduces chemotherapy-induced diarrhoea and weight loss

Background: One of the most common toxicities of cancer treatment is diarrhoea. Probiotics have been shown effective at preventing diarrhoea in inflammatory bowel disease and may prove useful in the oncology setting. Aim: The primary aim of this study was to investigate the probiotic mixture, VSL#3, for amelioration of chemotherapy-induced diarrhoea (CID). Methods: This experiment was carried out in a clinically relevant model of CID. VSL#3 was administered to female DA rats in one of three schedules. Irinotecan was used to induce mucositis and diarrhoea, with rats monitored for 7 days to record incidence of weight-loss and diarrhoea. At study completion, intestines were collected to investigate histological and proliferative changes, apoptosis levels and mucin composition. Results: VSL#3 reduced weight loss following irinotecan when administered before and after chemotherapy. Moderate and severe diarrhoea was also prevented in these rats. This was associated with a significant increase in crypt proliferation combined with an inhibition of apoptosis in both the small and large intestines. VSL#3 also prevented irinotecan-induced increases in goblet cells within jejunal crypts. Conclusions: VSL#3 is effective at preventing severe diarrhoea following chemotherapy with irinotecan and therefore has potential to be used clinically by cancer patients.

Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis. The aim of this study was to evaluate systemic availability of dietary amino acids (leucine) during chemotherapy-induced mucositis. We studied eight childhood cancer patients (age 1.5-16 y) on 2 d, i.e. the day before chemotherapy and 3-5 d after. Chemotherapy-induced oral mucositis and diarrhea were scored on a World Health Organization toxicity scale. Stable isotope tracers were used to measure first-pass splanchnic leucine uptake and whole-body leucine kinetics. Patients showed increased mucositis and/or diarrhea toxicity scores (p < 0.0001) after chemotherapy. Systemic availability of enterally administered leucine was not significantly affected by chemotherapy (before 60%, after 90%, p = 0.46). Interestingly, five patients already showed a negative leucine balance before chemotherapy. In conclusion, most children receiving chemotherapy are already catabolic before start of a new cycle of chemotherapy. Amino acid transport as measured by leucine uptake in the intestine is not affected by chemotherapy-induced mucositis.

Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5‐HT signalling and metabolism in human disease

Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT(3) receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT(4) agonists such as Prucalopride and 5-HT(4) partial agonists such as Tegaserod.

RTOG 0315: A randomized, double-blind, placebo-controlled phase III study to determine the efficacy of octreotide acetate in preventing or reducing the severity of chemoradiation-induced diarrhea in patients with anal or rectal cancer

4032 Background: Diarrhea is a common side effect of chemoradiation for pelvic malignancies. Octreotide acetate has been shown to control grade 3–4 chemotherapy-induced diarrhea in &gt;90% of patients. The primary objective of this randomized placebo-controlled phase III study was to determine the efficacy of long acting octreotide acetate in preventing the onset of grade 2–4 diarrhea. Secondary objectives were to assess the impact of diarrhea on chemoradiation delivery and medical resource utilization. Methods: Eligible patients (pts) with primary anal or rectal cancer, and scheduled to receive concurrent chemoradiation to a minimum dose of 45 Gy using pelvic field sizes greater than 10x10cm, were enrolled. Pts with history of pelvic radiotherapy, chronic bowel disease, diarrhea of grade ≥2, or colostomy were excluded from the study. Pts were stratified by RT dose (&lt;50 Gy and ≥50 Gy), chemotherapy (bolus and continuous) and gender. Pts were randomized to receive two 30 mg intramuscular injections of octreotide acetate (Sandostatin LAR® Depot) or placebo. Injections were given between day -7 and day -4 and on day 22 (± 3 days) of RT. The primary endpoint was incidence of grade 2, 3, or 4 diarrhea (CTCAE v3.0). Assuming a 45% placebo incidence rate, a one-sided chi-square test (alpha 0.05) would require 226 pts to detect a 42% reduction in incidence due to octreotide acetate. Results: The study accrued 233 pts (215 analyzable), 106 pts in the placebo arm and 109 pts in the octreotide acetate arm. The majority of pts (80%) on each arm had rectal cancer. There was no statistically significant difference in incidence of grade 2+ diarrhea (p=0.21) with 52 (49%) and 48 (44%) in the placebo and octreotide acetate treatment arms, respectively. There was also no statistically significant difference between the treatment arms in chemoradiation delivery or medical resource utilization. Conclusions: Prophylactic use of octreotide acetate was not shown to significantly reduce the incidence of mild, moderate or severe diarrhea. No significant financial relationships to disclose.

Prevention and Management of Chemotherapy-Induced Diarrhea in Patients with Colorectal Cancer: A Consensus Statement by the Canadian Working Group on Chemotherapy-Induced Diarrhea

Chemotherapy-induced diarrhea (cid) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of cid and its impact on patient management are frequently under-recognized in clinical practice.A Canadian working group, consisting of medical oncologists and an oncology pharmacist, was formed in 2001 to review the optimal approach to managing cid and to identify and implement new areas of research. The recommendations that follow are the result of the group's work.Acute medical management of cid includes loperamide or diphenoxylate as first-line agents. Subcutaneous octreotide is recommended for intractable grade 2 diarrhea and may be considered for grade 1 cid that does not resolve with high-dose loperamide. Hospitalization is recommended for patients with grades 3 and 4 cid; in-hospital care includes rehydration, antibiotic therapy, and octreotide.A chemotherapy dose reduction is generally advised for patients who have experienced grade 3 or 4 diarrhea in a previous chemotherapy cycle. If a dose reduction is not desired, prophylaxis with intramuscular long-acting release octreotide may be considered.The foregoing recommendations are based on expert opinion and require validation in prospective clinical trials.

Celecoxib and Mucosal Protection: Translation from an Animal Model to a Phase I Clinical Trial of Celecoxib, Irinotecan, and 5-Fluorouracil

Chemotherapy-induced diarrhea occurs secondary to mucosal inflammation and may be cyclooxygenase-2 mediated. Cyclooxygenase-2 inhibitors may ameliorate chemotherapy-induced mucosal toxicity and enhance its antitumor effect. We investigated this hypothesis in the Ward colorectal cancer rat model and in a phase I clinical study. In the Ward rat model, irinotecan was given daily x 3 or weekly x 4 with or without celecoxib. In the phase I clinical study, we planned to escalate the dose of irinotecan in the FOLFIRI regimen (irinotecan, 5-fluorouracil, and leucovorin) with a fixed dose of celecoxib. Irinotecan was escalated in four dose levels: 180, 200, 220, and 260 mg/m2. Celecoxib was administered as 400 mg, twice daily starting on day 2 of cycle 1. Pharmacokinetics of irinotecan, SN-38, and SN-38G were obtained on days 1 and 14. A standard 3+3 dose escalation scheme was used. Plasma concentrations of irinotecan, SN-38, and SN-38G were measured using high-pressure liquid chromatography. Celecoxib ameliorated diarrhea, weight loss, and lethality and resulted in synergistic antitumor effect in the rat model. Twelve patients with advanced cancers were enrolled and evaluable for dose-limiting toxicity (DLT). Diarrhea was the cause for discontinuation in one. Grade 2 and 3 diarrhea occurred in three and two patients, respectively. One patient had DLT at dose level 2 (grade 3 diarrhea). Two had a DLT at DL3 (G3 emesis and myocardial infarct). Celecoxib had limited influence on the pharmacokinetics of irinotecan in this data set. Maximum tolerated dose of irinotecan in FOLFIRI schedule with celecoxib is 200 mg/m2.

Prevention and Management of Chemotherapy-Induced Diarrhea in Patients with Colorectal Cancer

Prevention and Management of Chemotherapy-Induced Diarrhea in Patients with Colorectal Cancer

Chemotherapy-induced diarrhea is associated with changes in the luminal environment in the DA rat.

The microflora of the gastrointestinal tract (GIT) are a complex ecosystem, performing a number of beneficial functions. Irinotecan causes both early and late diarrhea, the latter possibly caused, in part, by changes in the microflora of the GIT. Female DA rats were given atropine subcutaneously, prior to a single 200 mg/kg intraperitoneal dose of irinotecan. Animals were monitored for diarrhea and killed at 30 and 60 mins, 2, 6, 12, 24, 48, and 72 hrs after chemotherapy administration. Control rats received no treatment. Fecal samples and stomach, jejunum, and colon samples were collected and stored at -70 degrees C until required. Standard microbiological culture techniques were used to grow and isolate the flora. Biochemical tests were used to identify the bacteria. The level of growth was noted for relative comparison between time points and graded accordingly. Early diarrhea was observed in the rats from 2-6 hrs after treatment, after which time the diarrhea resolved. Late onset diarrhea was apparent 72 hrs after treatment. Changes were seen in the flora of the stomach, jejunum, colon and feces. The majority of microflora changes were seen 6, 12, and 24 hrs after treatment, with a relative increase or decrease in the presence of bacteria in comparison with control rats. In some rats bacteria were not observed at all time points, and different bacteria not seen in control animals were identified in rats treated with irinotecan. These changes were observed up to 72 hrs after treatment. In conclusion, irinotecan treatment causes changes in the flora of the stomach, jejunum, colon, and feces of rats and is associated with the development of diarrhea. These changes in flora may have systemic effects and in particular may contribute to the development of chemotherapy-induced mucositis.

Acute Enterocolitis Incidence in Patients with Hematological Malignancies Receiving Myelotoxic Therapy Requiring Hematopoietic Stem Cell Support - Palifermin Experience.

Background: Chemotherapeutic agents can cause severe oral and gastrointestinal mucositis, for which there is currently no treatment. Previous research demonstrates that palifermin - keratinocyte growth factor - is potentially antimucotoxic, reducing the duration and severity of oral mucositis after intense chemotherapy in hematological cancers. The primary aim of this study was to determine palifermin effectiveness in ameliorating chemotherapy-induced diarrhoea and oral mucositis incidence. Palifermin adverse events were also assessed.Methods: Retrospective observational study involving patients with hematological malignancies undergoing autologous hematopoietic stem-cell transplantation after myelotoxic therapy. All the patients received antibiotic, antifungal, and antiviral prophylaxis. Patients being treated with palifermin to decrease the incidence and duration of severe oral mucositis (Palifermin Group) were compared to a control group of patients who did not receive palifermin (Control Group). Palifermin was administered during 3 consecutive days, before and after myelotoxic therapy in a 60 μg/Kg daily intravenous dose.Results: Twenty-four patients were included, 8 in Palifermin Group and 16 in Control Group. Baseline malignancies were Hodgkin and non Hodgkin lymphoma, acute myeloid leukemia, and multiple myeloma. All patients underwent autologous hematopoietic stem-cell transplantation after the following conditioning regimes: BEAM, BuCy, and Mel200 respectively. In Palifermin Group, 62.5% were male, mean age 47.6±13.0 years, mean disease duration of 22.3±10.1 months (N=8). In Control Group 56.3% were male, mean age 45.8±12.1 years (N=16). Mean performance status (Karnofsky Index) was 80±14.1% and 71.3±15.1%, in each group, respectively. No statistically significant differences between Palifermin and Control Groups were found regarding the degree of diarrhoea, although in the Palifermin Group the majority of patients presented a grade 2 (N=3) and in the Control Group a grade 3 (N=6). In the Palifermin Group there was a tendency for a lower incidence of hypoalbuminemia [12.5% (Palifermin Group) vs. 50% (Control Group)], which corresponded to a significant lower difference in the needs for receiving parenteral nutrition (P=0.011). Nevertheless, these findings were not translated in less febrile episodes or less iv antibiotic therapy days. There were no significant differences between the two groups regarding the degree of oral mucositis, the number of days of analgesic opioids use, and the number of hospitalization days, most probably due to the small sample considered. The most common adverse events in the Palifermin Group were reversible erythema and edema of the face and upper trunk that have occurred only in 3 patients. Weight increase was mild and similar in both groups of patients [Median weight increase±SD: 1,0±1,7 Kg (Palifermin Group) vs 2,0±2,5 Kg (Control group)].Conclusion: Gastrointestinal and oral mucositis are common consequences of cancer therapy with a direct and significant impact on the quality of life and care costs, also affecting patient's survival. Our exploratory study shows that palifermin treatment is well tolerated, potentially reducing diarrhoea and the incidence of hypoalbuminemia, and significantly reducing the needs for parenteral nutrition. However further studies with an increased number of patients will be necessary to provide more evidence concerning palifermin efficacy in the management of these cancer therapy's debilitating side-effects.

Is there an experimental basis for the development of ischaemic colitis as a result of 5-HT3antagonist treatment?

5-HT(3) antagonists are effective treatments for chemotherapy-induced emesis and diarrhoea and urgency and pain associated with irritable bowel syndrome. Reports of ischaemic colitis led to restricted use of the approved drug, alosetron. This article briefly reviews the controversial information from epidemiology and adverse reaction reports and addresses the experimental basis for the development of ischaemic colitis as a result of 5-HT(3) antagonist treatment. The author reviews the potential factors based involved in the ischaemic colitis and ways in which this class of compound may influence those factors based on experimental evidence, including the literature on any vascular effects of these agents. Finally, the article addresses the theoretical basis for the constipation as a predisposing factor for the development of ischaemic colitis. The evidence reviewed suggests that further studies are needed to explore the principles to prove or disprove the association.

Development and validation of a liquid chromatography method for the simultaneous determination of α‐tocopherol, retinol and retinyl esters in human serum using a monolithic column for the monitoring of anticancer therapy side effects

Among other side effects, administration of anticancer agents is accompanied by manifestations of gastrointestinal toxicity and disturbances of antioxidant balance. The monitoring of these toxic effects in clinical practice is impeded by a dearth of reliable laboratory methods. Therefore, a simple and rapid reversed-phase high-performance liquid chromatography procedure for selective and sensitive determination of retinol, a-tocopherol, and retinyl esters (retinyl-palmitate and retinyl-stearate) in blood serum has been developed and presented in this study. A Series 200 LC HPLC instrument from Perkin Elmer (Norwalk, USA) with diode-array detector (DAD) was used for the analysis. Separations of retinol, alpha-tocopherol, retinyl-palmitate, and retinyl-stearate were performed using a Chromolith Performance RP-18e, 100 x 4.6 mm monolithic column from Merck (Darmstadt, Germany). Gradient elution was used at a flow rate of 3 mL/min; the mobile phase was methanol-water (95:5, v/v) for 0-2.1 min and methanol-2-propanol (60:40, v/v) for 2.1-4.9 min. The total time of analysis was 6 min. The injection volume was 20 microL and the analysis was performed at ambient temperature. Detection of retinol, alpha-tocopherol, and retinyl esters was carried out at 325, 295, and 330 nm, respectively. For practical assessment of the method, the vitamin A absorption test was performed on seven healthy controls as well as on six patients with non-small cell lung carcinoma or head and neck carcinoma previously treated by chemotherapy and/or radiotherapy, six patients with rectal carcinoma before chemoradiotherapy, four patients with gastrointestinal stromal tumor (GIST) before treatment with imatinib, and a breast cancer patient with chemotherapy-induced diarrhea. Present data demonstrate the feasibility of large scale HPLC determination of vitamin E, vitamin A, and retinyl esters in human serum using a silica monolithic column, and this method may represent a valuable aid in the laboratory monitoring of the toxicity of anticancer therapy.