Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Combining electrokinetic transport and bioremediation for enhanced removal of crude oil from contaminated marine sediments: Results of a long-term, mesocosm-scale experiment.

Marine sediments represent an important sink of harmful petroleum hydrocarbons after an accidental oil spill. Electrobioremediation techniques, which combine electrokinetic transport and biodegradation processes, represent an emerging technological platform for a sustainable remediation of contaminated sediments. Here, we describe the results of a long-term mesocosm-scale electrobioremediation experiment for the treatment of marine sediments contaminated by crude oil. A dimensionally stable anode and a stainless-steel mesh cathode were employed to drive seawater electrolysis at a fixed current density of 11 A/m2. This approach allowed establishing conditions conducive to contaminants biodegradation, as confirmed by the enrichment of Alcanivorax borkumensis cells harboring the alkB-gene and other aerobic hydrocarbonoclastic bacteria. Oil chemistry analyses indicated that aromatic hydrocarbons were primarily removed from the sediment via electroosmosis and low molecular weight alkanes (nC6 to nC10) via biodegradation.

An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. PURPOSE: To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. MATERIALS AND METHODS: Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). RESULTS: The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). CONCLUSIONS: PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Relación entre el transporte y las características nutricionales de la carne porcina para consumo humano en el valle de aburrá (colombia) / Relationship between transport and nutritional characteristics of pork meat for human consumption in the valle de aburrá (colombia)

RESUMEN La carne de cerdo se considera fuente de alto valor nutritivo por su alto contenido de proteína; sin embargo, su transporte representa un eslabón crítico, por cuanto genera pérdidas económicas, cuando se producen alteraciones en el bienestar animal que repercuten en los parámetros nutricionales, disminuyen la capacidad de retención de agua y ocasionan pérdidas de proteína. El objetivo de este estudio fue relacionar las características de los transportes con las características nutricionales de la carne porcina destinada a consumo humano en el Valle de Aburrá (Antioquia, Colombia) en 2017. Se visitaron tres plantas de sacrificio del Valle de Aburrá con muestreo probabilístico estratificado por planta y afijación igual, obteniendo información de 338 animales. Se analizaron los parámetros nutricionales de las muestras cárnicas, así como variables sociodemográficas, de infraestructura, bienestar animal y prácticas de conducción de los transportistas. Se realizaron pruebas de ji-cuadrado (χ 2) para variables cualitativas dicotómicas, regresión logística para variables cualitativas politómicas y U de Mann-Whitney para variables cuantitativas. Se encontró asociación entre varios de los parámetros indagados con valores p estadísticamente significativos (p = 0,000; así, no tener suministro de agua permanente para los animales incrementa en 46,55 veces (IC 18,08 - 120,07) la posibilidad de presentar carnes nutricionalmente inadecuadas. Se concluye que factores como la falta de suministro de agua a los cerdos, el mal estado de pisos y separadores, la deficiente capacitación de los transportistas, la falta de supervisión a los animales, no tener el certificado técnico-mecánico y la velocidad promedio de 80 km/h, se asocian con la generación de productos cárnicos nutricionalmente inadecuados.

ABTRACT Pork meat is considered a source of high nutritional value due to its high protein content, however, transport is a critical link to generate economic losses by producing alterations in animal welfare, which have an impact on nutritional parameters, decreasing the capacity of water retention, and generating protein losses. The objective of this study was to relate the characteristics of transport, with the nutritional characteristics of pork for human consumption in the Valle de Aburrá (Antioquia, Colombia) in 2017. In this location, three slaughterhouses were visited with probabilistic sampling stratified by plant and equal affixation, obtaining information from 338 animals. The nutritional parameters of the meat samples and sociodemographic variables, infrastructure, animal welfare and driving practices of the transporters were analyzed. ji-square (χ 2) tests were performed for dichotomous qualitative variables, logistic regression for qualitative polytomous variables and Mann-Whitney U test for quantitative variables. An association was found between several of the parameters investigated with statistically significant p values (p = 0,000), where, having no permanent water supply for the animals increases in 46.55 times (IC 18.08 - 120.07) the possibility of presenting nutritionally inadequate meats. It was concluded that factors such as lack of water supply to pigs, poor condition of the floors and separators, lack of training in transporters, lack of supervision of animals, lack of mechanical technical certification and average speed of 80 km/h are associated with the generation of nutritionally inadequate meat products.

Translational research in neuroendocrine tumors: pitfalls and opportunities.

Interest in research on neuroendocrine tumors (NETs) has grown in the past 10 years, coinciding with improvements in our understanding of the molecular pathogenesis of NETs. In addition, NETs have become one of the most exciting settings for drug development. Two targeted agents for the management of advanced pancreatic NETs have been approved, but the development of targeted agents for NETs is limited by problems with both patient selection and demonstration of activity. In this review, we analyze these limitations and discuss ways to increase the predictive value of preclinical models for target discovery and drug development. The role of translational research and 'omics' methodologies is emphasized, with the final aim of developing personalized medicine. Because NETs usually grow slowly and metastatic tumors are found at easily accessible locations, and owing to improvements in techniques for liquid biopsies, NETs provide a unique opportunity to obtain tumor samples at all stages of the evolution of the disease and to adapt treatment to changes in tumor biology. Combining clinical and translational research is essential to achieve progress in the NET field. Slow growth and genetic stability limit and challenge both the availability and further development of preclinical models of NETs, one of the most crucial unmet research needs in the field. Finally, we suggest some useful approaches for improving clinical drug development for NETs: moving from classical RECIST-based response end points to survival parameters; searching for different criteria to define response rates (for example, antiangiogenic effects and metabolic responses); implementing randomized phase II studies to avoid single-arm phase II studies that produce limited data on drug efficacy; and using predictive biomarkers for patient selection.

[Selective biopsy of the sentinel lymph node in patients with breast cancer and previous excisional biopsy: is there a change in the reliability of the technique according to time from surgery?]. / Biopsia selectiva del ganglio centinela en pacientes con cáncer de mama y biopsia escisional previa: ¿cambia la fiabilidad de la técnica según el tiempo transcurrido desde la cirugía?

AIM: To assess the influence of time on the reliability of sentinel lymph node biopsy (SLNB) in breast cancer patients with previous excisional biopsy (EB), analyzing both the sentinel lymph node detection and the lymph node recurrence rate. MATERIAL AND METHODS: Thirty-six patients with cT1/T2 N0 breast cancer and previous EB of the lesion underwent a lymphoscintigraphy after subdermal periareolar administration of radiocolloid, the day before SLNB. Patients were classified into two groups, one including 12 patients with up to 29 days elapsed between EB and SLNB (group A), and another with the remaining 24 in which time between both procedures was of 30 days or more (group B). Scintigraphic and surgical detection of the sentinel lymph node, histological status of the sentinel lymph node and of the axillary lymph node dissection, if performed, and lymphatic recurrences during follow-up, were analyzed. RESULTS: Sentinel lymph node visualization at the lymphoscintigraphy and surgical detection were 100% in both groups. Histologically, three patients showed macrometastasis in the sentinel lymph node, one from group A and two from group B. None of the patients, not even those with malignancy of the sentinel lymph node, relapsed after a medium follow-up of 49.5 months (24-75). CONCLUSION: Time elapsed between EB and SLNB does not influence the reliability of this latter technique as long as a superficial injection of the radiopharmaceutical is performed, proving a very high detection rate of the sentinel lymph node without evidence of lymphatic relapse during follow-up.

Fatal cardiac and renal allograft rejection with lenalidomide therapy for light-chain amyloidosis.

We describe a patient who underwent a successful heart and kidney transplant for light-chain amyloidosis. She had an excellent hematologic response to bortezomib/dexamethasone therapy. Follow-up therapy with lenalidomide was started, and the patient quickly had a fatal allograft rejection of the heart and kidney. We present evidence to support the theory that lenalidomide, a known immunomodulator, may have stimulated the immune system and precipitated the fatal rejection episode.

Bacteriological, biochemical, and immunological modifications in human colostrum after Holder pasteurisation.

OBJECTIVE: The objective of this work was to evaluate the effect of Holder pasteurisation of human colostrum on a variety of microbiological, biochemical, and immunological parameters. METHODS: Colostrum samples from 10 donors, and 8 samples of mature milk used as controls, were heated at 62.5°C for 30 minutes. Bacterial counts and the concentration of furosine, lactose, myoinositol, glucose, lactulose, cytokines, and immunoglobulins were determined before and after the heat treatment. RESULTS: Mean bacterial counts in nonpasteurised colostrum samples oscillated between 2.72 and 4.13 log10 colony-forming units per millilitre in the agar media tested. Holder pasteurisation led to the destruction of the bacteria originally present in the samples. Furosine was detected in all samples before pasteurisation and increased significantly after the heat treatment (from 6.60 to 20.59 mg/100 g protein). Lactulose content was below the detection limit in nonpasteurised colostrum, but it was detected in all samples and quantified in 7 of them (from 10.68 to 38.02 mg/L) after Holder pasteurisation. Lactose, glucose, and myoinositol concentrations did not change after Holder pasteurisation. The concentrations of most cytokines and immunoglobulins were significantly higher in colostrum than in mature milk samples. Immunoglobulin content, both in colostrum and in milk samples, was reduced during pasteurisation, whereas, among cytokines, only macrophage inflammatory protein-1ß, interleukin-7, and granulocyte-macrophage-colony-stimulating factor concentrations were affected by this heat treatment. CONCLUSIONS: Lactulose and furosine content could be used as heat treatment indicators in colostrum samples. Holder pasteurisation modified the immunological profile of both colostrum and mature milk.

Caprine luteinizing hormone isoforms during the follicular phase and anestrus.

The relative proportion of the circulating luteinizing hormone isoforms in goats during follicular phase (pre-ovulatory peak; F) and anestrus (A) was investigated. Estrus was synchronized in six goats with a prostaglandin analogue. After estrus was detected, blood samples were taken at 1 h intervals for 24 h. Four anestrous goats received 100 microg i.v. of GnRH and blood samples were collected every 15 min for 5 h. Samples with the greatest LH concentration in follicular phase and after GnRH administration (anestrus) were analyzed by chromatofocusing and eluted with a pH gradient from 10.5 to 3.5. For quantification purposes eluted LH was grouped into basic (pH> or =7.5), neutral (pH 7.4-6.5) and acidic isoforms (pH< or =6.4) as well as by pH unit. In both physiological conditions (PC), basic and acidic isoforms were greater than the neutral. With this grouping criteria, there was an interaction between PC and pH group, with the proportion of neutral isoforms being greater (p<0.05) in A (12.0+/-0.8%) as compared with F (5+/-2%). Analysis by pH unit showed a very basic group of eluted isoforms (pH> or =10), which amounted to a percentage of 6.0+/-0.4% of the total observed during A, and 3+/-1% during F (p<0.05). Predominant isoforms in A eluted in the pH range 9.99-9.0 (42+/-3%) as compared to 7+/-3% (p<0.01) in that pH range in F. In contrast, the predominant isoforms in F eluted in the pH range 8.99-8.0, representing 55+/-8%, while in A the proportion was 11+/-2% (p<0.01). Isoforms eluted at the pH range 7.9-7 represented a significantly greater proportion during A (5.0+/-0.6%) as compared with F (3+/-1%). This is the first report on goat LH circulating isoforms. During A the LH isoforms secreted by the pituitary are more basic than during F.

Association of genetic markers within the KIT and KITLG genes with human male infertility.

BACKGROUND: There is much evidence involving the KIT tyrosine kinase receptor and its ligand KITLG in the survival and proliferation of germ cells. Animal models and functional studies in humans suggest that this signalling pathway plays a role in male infertility. METHODS: We studied three and two single-nucleotide polymorphisms (SNPs) (rs3819392, rs3134885, rs2237012, rs10506957 and rs995030) located within the genomic region of the KIT and KITLG genes, respectively. A total of 167 idiopathic infertile men (sperm counts <5 million spz/ml) and 465 unrelated healthy controls from the same geographical region were genotyped for these SNPs. RESULTS: We found a statistically significant association of the rs3819392 polymorphism, which is located within the KIT gene, with idiopathic male infertility. In addition, a deviation from the Hardy-Weinberg equilibrium (HWE) law was observed for rs10506957 polymorphism within the KITLG gene only in the infertile group. CONCLUSIONS: Our data indicate that the KIT/KITLG system may be involved in a low sperm count trait in humans.

[Lymphoscintigraphy and sentinel node biopsy in non-palpable breast cancer]. / Linfogammagrafía y biopsia del ganglio centinela en el carcinoma no palpable de mama.

OBJECTIVE: The aim of the study was to evaluate the efficacy of lymphatic mapping and sentinel node biopsy in non-palpable breast cancer (NPBC) patients in comparison with palpable breast cancer (PBC) patients. MATERIAL AND METHODS: 199 breast cancer patients were studied. Patients were classified into two groups: NPBC and PBC. Following sentinel node biopsy all patients underwent axillary lymphadenectomy. Surgery was performed at 4-24 h after peritumoral injection of 111MBq 99mTc-nanocolloid. Histological sentinel node analysis was performed by cytological imprinting and delayed study. The following parameters were analyzed in both groups: scintigraphic and surgical detection rates, true positives (TP), true negatives (TN), sensitivity (S), predictive negative value (PNV), false negative rate (FNR) and global precision (GP) of the technique. RESULTS: No significant differences were observed (p > 0.05) in either the lymphoscintigraphy or surgical sentinel node detection, or drainage to internal mammary chain (p = 0.211) in both groups. Metastatic axillary prevalence was lower in NPBC group (p = 0.019). Similar S, NPV and GP values (>90 %) and FNR (< or = 6 %) were found in both groups. CONCLUSIONS: The reliability of the technique is similar in both groups. Drainage is predominantly axilar. Drainage to internal mammary chain was more frequently seen in medial tumours and in NPBC. Metastatic axillary prevalence was lower in the NPBC group.

Depresión y calidad de vida en el alcoholismo / Depression and life quality in alcoholism

This paper intends to compare quality of life and its relationships with depressive symptomatology in alcoholic patients. We selected two groups the first, patients assisting a recovery center for alcoholics, and the second, patients that had attended this center in the past. Both groups received the SF-36 and the Beck Depression Inventory. Comparing the results from both groups, we could not find a significant direct relationship between patient’s appreciation about quality of life, measured by SF-36, and presence of depression, measured in the Beck Inventory.

El objetivo del presente estudio es comprar el nivel de calidad de vida y su vinculación con la sintomatología depresiva en sujetos alcohólicos. Para estos fines se han considerado dos muestras de sujetos, aquellos que están en tratamiento en un club de recuperados alcohólicos en el momento del estudio y aquellos que han pertenecido a esta institución y se encontraban en sus hogares sin asistir a las actividades de este centro. Ambas muestras se aplicaron los instrumentos de evaluación de calidad de vida (SF-36) y de presencia de síntomas depresivos (Inventario de Depresión de Beck). Al comparar ambos grupos y al efectuar las pruebas estadísticas, no se logró establecer una directa relación entre las apreciaciones acerca de la calidad de vida y la presencia de síntomas depresivos en el conjunto de la población estudiada.

Lymphoproliferative disease after lung and heart-lung transplantation: first description in Spain.

Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx).

Farmacovigilancia en nosocomios de la ciudad de Córdoba. Dos años de experiencia del Departamento de Farmacología como efector periférico de ANMAT / Drug monitoring in hospitals of Cordoba City (Argentina). 2-year-experience of the Pharmacological Department as a peripheric effect of ANMAT

Se diseñó un estudio de Farmacovigilancia (FVG), centrado en tres Hospitales Públicos de Córdoba, buscando detectar Reacciones Adversas por medicamentos. A tal fin se realizaron cursos formadores de recursos humanos en FVG. Se distribuyeron fichas de FVG., de diseño propio, recuperadas luego. Para cálculo estadístico se aplicó el INFO 4. Se recuperaron 84 fichas informadas Los grupos de medicamentos involucrados: fueron: Antibióticos (22%), cardiovasculares (16%), antiulcerosos (10%), ansiolíticos (8.75%), AINEs (8%), oncológicos (6%), anticonvulsivantes (3.75%), hipolipemiantes (3.5%), hormonas sexuales (2.5%), hipoglucemiantes (2.5%), expansores plasmáticos (2.5%). Los órganos afectados por RAM fueron: SNC (25%), piel (25%), gastrointestinal (17.5%), Sangre (7.5%), cardiovascular (7.5%), respiratorio (7%), inmunes (6%), renal (4%). El análisis de imputabilidad indicó: RAM Definidas: 10% - RAM Probables: 90%.

There were designed Monitorings study (FVG), centred on three Public Hospitals of C6rdoba, seeking to detect Adverse Reactions for medicines. To such purpose there were realized forming courses of human resources in FVG. FVG's cards were distributed, of own design, recovered then. For statistical calculation there was applied the INFO 4. 84 informed cards were recovered. The groups of involved medicines: they were: Antibiotics (22%), cardiovascular (16%), antiulcerous (10%), anxiolytics (8.75%), nonsteroidal anti-inflammatory (8%), onchologics (6%), anticonvulsants (3.75%), hypolypemics (3.5%), sexual hormones (2.5%), hypoglycemics (2.5%), plasmatic expansors (2.5%). The organs affected by RAM were: Central Nervous System (25%), skin (25%), gastrointestinal (17.5%), Bleeds (7.5%), cardiovascular (7.5%), respiratory (7%), immune (6%), renal (4%). The analysis of imputability indicated: Definite RAM: 10 % Probable RAM: 90%.

Central nervous system metastases of a pulmonary epitheloid haemangioendothelioma.

The case of a 55-yr-old male with a right pleural effusion and multiple bilateral nodules is reported. A diagnostic thoracothomy was necessary to obtain a definitive histological diagnosis. During the postoperative course, the subject's neurological condition deteriorated and multiple cerebral mass lesions were discovered. The pathological analysis of both lung and cerebral tumours revealed an atypical endothelial cell proliferation; vascular immunohistochemical markers, such as factor VIII and CD34, were strongly positive. His general condition remained poor and the patient died 18 months after the initial diagnosis. The final diagnosis was pulmonary epitheloid haemangioendothelioma with synchronous central nervous system dissemination, the first time the authors believe that association has been reported. Little is known of the prognosis and treatment of these tumours, due to their rarity. Negative prognostic factors appear to be the presence of symptoms, pleural effusion or multifocal presentations. Treatment should include surgical resection if possible; chemotherapy appears to have little effect. Watchful waiting is an acceptable option, especially in asymptomatic patients.

Lethal toxicity after 5-fluorouracil chemotherapy and its possible relationship to dihydropyrimidine dehydrogenase deficiency: a case report and review of the literature.

5-fluorouracil (5-FU) is a chemotherapeutic agent widely used in the treatment of solid malignancies, especially in colorectal cancer. A characteristic note seen with its use is the considerable interindividual variation in the incidence and severity of the toxicities seen among patients. We report the case of a 55-year old woman who presented with severe, lethal toxicity to standard doses of 5-fluorouracil (5-FU) and folinic acid. We discuss the known clinical determinants of toxicity. We also discuss the possible molecular factors implicated in the variable toxicity seen to 5-FU, especially in regards to dihiyropyrimidine dehydrogenase, a pivotal enzyme in the metabolism of 5-FU.