Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

In vitro feeding of Hyalomma lusitanicum ticks on artificial membranes.

In vitro feeding of ticks (Acari: Ixodidae) is an important means to study the biology of ticks and their vectorial capacity. Here, we have adapted the tick Hyalomma lusitanicum Koch to previously published silicone-based membranes for in vitro feeding. For comparison purposes data on pre-oviposition, oviposition and hatching from females engorged on animals were used. A total of 68 engorged females out of 169 were obtained; feeding duration and feeding behaviour were similar to that of ticks on live host animals, although the final weight achieved for membrane-fed ticks was lower than that of their animal-fed counterparts. Comparison of the time taken for egg production and hatching showed that pre-oviposition was faster for membrane-fed ticks (16 days) than for animal-fed ticks (36 days), whereas the duration of oviposition-hatching was the same for the two feeding methods (34 days). We also observed that seasonality has an influence on tick feeding success: the conditions in Spring/Summer accelerated the tick life cycle. It is concluded that relatively large numbers of homogeneous laboratory-raised Hyalomma ticks can be produced without feeding them on experimental animals.

The effect of excluding ungulates on the abundance of ixodid ticks on wild rabbit (Oryctolagus cuniculus).

Tick abundance depends heavily on host density, so reducing access to the host should reduce tick populations in a determined area. In this study we compared the Parasitic Index (PI = average number of ticks per rabbit) of two wild rabbit populations separated 16 years ago by a fence keeping ungulates from moving freely. Two areas were selected (closed and open) wherein 50 wild rabbits per area were sampled for ticks. The PI in the open area (PI = 989.62) was significantly higher than in the closed area (PI = 515.40). Hyalomma lusitanicum Koch was globally the most abundant species, followed by Rhipicephalus pusillus Gil Collado, Rhipicephalus bursa Canestrini and Fanzago, Haemaphysalis hispanica Gil Collado, Rhipicephalus sanguineus s.l. Latreille and Ixodes ventalloi Gil Collado. Differences between areas varied depending on the species. The number of H. hispanica, R. bursa and R. pusillus were significantly more abundant on rabbits in the closed area, whereas H. lusitanicum predominated in the open area. Ungulates in the open area may have played an important role as the main or alternative host for ticks and/or drawing some tick species away from rabbits. In the closed area other reasons such as inter-specific competition could have influenced the tick abundance. These results show a clear reduction in tick abundance for at least 16 years as well as influenced species distribution.

Influence of environmental temperature and humidity on questing ticks in central Spain.

Ticks are important ectoparasites and vectors of the pathogens that cause disease in humans and animals. At a natural reserve in Ciudad Real (Spain), an uncontrollable infestation of wild animals with Hyalomma lusitanicum (Koch) has been reported by some game reserve owners. Many questions about distribution, abundance, and phenology of this tick in this area remain unanswered. The aim of this study was to determine if temperature and relative humidity affect the questing tick's activity in four species of ticks in a meso-Mediterranean area, especially that of H. lusitanicum. Data for tick populations in six selected sampling sites every month, between January 2007 and December 2013 were used. Temperature and humidity values (ground and environmental) were recorded. The sampling effort, the similarity between sites, and the phenology of the species were analyzed. Effects of environmental variables on tick's activity were assessed by general linear models (GLM) whereas the comparative importance of variables was measured by hierarchical variance partitioning. Hyalomma lusitanicum represented 96.3% of the four species of ticks collected. Spring and summer months presented a higher activity of ticks, than autumn and winter months. In general, humidity variables were negatively related to the activity of ticks, whereas temperature variables were positively related. Our results suggest that the highest activity in the area is produced by biological characteristics of H. lusitanicum; being temperature and humidity the most important environmental factors influencing the abundance of this species in the region.

Long-Term Ecological Study of Host-Seeking Adults of Hyalomma lusitanicum (Acari: Ixodidae) in a Meso-Mediterranean Climate.

From January 2007 to December 2014, three representative meso-Mediterranean bioclimatic environment types were sampled monthly using blanket-dragging techniques to determine the tick abundance rate. Hyalomma lusitanicum Koch, 1844 was the most prevalent species (96.58%) followed by Dermacentor marginatus Sulzer, 1776; Rhipicephalus pusillus Gil Collado, 1936; and Rhipicephalus bursa Canestrini and Fanzago, 1878. H. lusitanicum adults begin questing activity around March, numbers rising quickly reaching their peak in May­June and then diminishing until the end of the year, with a small increase in September­October. This pattern was clear and constant throughout the years, irrespective of the microclimate or biotope tested.

Long term study of ixodid ticks feeding on red deer (Cervus elaphus) in a meso-Mediterranean climate.

Red deer (Cervus elaphus L.) are very valuable in trophy-hunting but also contribute to the preservation of natural areas. They are affected by many parasites and pathogens, including hard ticks that are not only important parasites themselves but can also act as vectors and/or reservoirs of pathogens. Tick phenology is complex insofar as population dynamics depend on environmental conditions, vegetation, host availability and their own intrinsic characteristic. Ticks were collected monthly from January 2007 to December 2014 from red deer on a natural reserve located in a meso-Mediterranean environment in Central Spain. A total of 8978 specimens of ixodid ticks were recovered with a mean Parasitization Index of 65.06 ticks/deer. Red deer were infected the whole year round with a summer-spring pattern and two secondary peaks in February and October. The main species was Hyalomma lusitanicum Koch followed by Rhipicephalus bursa Canestrini and Fanzago, Rhipicephalus pusillus Gil Collado, Dermacentor marginatus Sulzer and Ixodes ricinus L. Hyalomma lusitanicum has a complex life cycle in which several generations initiate their cycle at different times throughout the year, most probably lasting more than 1 year. We also describe the ability of nymphs to feed on large ungulates even though their habitual host is wild rabbit.

Seasonal dynamics of ixodid ticks on wild rabbits Oryctolagus cuniculus (Leporidae) from Central Spain.

Rabbit Hemorrhagic Disease and Myxomatosis caused a decline in the rabbit population in the second half of the last century. Despite some recovery, the risk of vector-borne disease is present and thus the importance of controlling vector populations. In the current study, we describe the ixodid tick fauna in wild rabbit in a natural reserve in Ciudad Real (Central Spain) during the course of two 3-year periods (2007-2009 and 2012-2014). Of all the ticks collected on average 72.5 % were larvae, 24.4 % nymphs and 3.1 % adults, although the percentage varied monthly. Seven tick species were identified: Hyalomma lusitanicum Koch (Parasitic indicator [PI] = number of ticks per examined rabbit = 96.47), Rhipicephalus pusillus Gil Collado (PI = 47.37), Haemaphysalis hispanica Gil Collado (PI = 12.15), Ixodes ventalloi Gil Collado (PI = 0.65), R. bursa Canestrini and Fanzago (PI = 0.18), R. sanguineus Latreille (PI = 0.11), Dermacentor marginatus Sulzer (PI = 0.01). In spring and summer, most abundant were larvae of H. lusitanicum, followed by immature stages of R. pusillus and Ha. hispanica. In autumn, the main tick species were nymphs of I. ventalloi whereas in winter adults of Ha. hispanica were more numerous. Rhipicephalus pusillus was present all year long, although not always in high percentage. PI of other species (R. bursa, R. sanguineus and D. marginatus) were too low to be representative. The seasonal dynamics of ticks on wild rabbit defined in this study could be useful to design species-specific control strategies.

Differences in questing tick species distribution between Atlantic and continental climate regions in Spain.

Climate and vegetation in Spain vary from north to south, affecting tick distribution and consequently the presence of tick-borne diseases. The aim of this study was to investigate throughout a 2-yr study the distribution of the different exophilic questing tick species present in 18 areas: eight located in central and 10 in northern Spain. The same methodology was used in both areas, sampling vegetation on a monthly basis by blanket dragging for 20- to 30-min intervals. A total of 12 species belonging to the genera Ixodes, Haemaphysalis, Rhipicephalus, Dermacentor, and Hyalomma was identified. Differences in species distribution and prevalence were dramatically different. The most frequent and abundant species in northern Spain were Ixodes ricinus (67% of adult ticks) and Haemaphysalis punctata (8%), whereas Hyalomma lusitanicum (86%) and Dermacentor marginatus (12%) were the most abundant in central Spain. There were important differences in the monthly seasonal patterns for the different tick species. These results highlight important differences in tick distribution in neighboring areas and underline the need for ongoing surveillance programs to monitor tick population dynamics and the prevalence of tick-borne pathogens.

Seasonal Dynamics of Fleas (Siphonaptera: Pulicidae, Ceratophyllidae and Leptopsyllidae) on Oryctolagus cuniculus in a Meso-Mediterranean Area of Central Spain.

Flea infestations of wild rabbits were examined monthly in central Spain in a meso-Mediterranean area for 5 yr. A total of 1,180 wild rabbits were trapped and 7,022 fleas were collected from them. Overall, the prevalence was 74.1% with a mean flea index of 5.95 fleas per rabbit. Four flea species were identified: Spilopsyllus cuniculi (Dale, 1878) was the most abundant species (accounting for 74.3% of fleas collected) followed by Xenopsylla cunicularis (Smit, 1957), Odontopsyllus quirosi (Gil Collado, 1934), and Nosopsyllus fasciatus (Bosc, 1800) (18.9, 6.7, and 0.1%, respectively). The highest prevalence was observed in S. cuniculi (48.6%) followed by X. cunicularis, O. quirosi, and N. fasciatus (34.3, 20.0, and 0.6%, respectively). Odontopsyllus quirosi and S. cuniculi were mainly collected from autumn to spring with the peak of infestation in winter, while X. cunicularis was mainly found from spring to autumn with maximum levels of infestation during the summer months. The relevance of these findings is discussed.

Urinary and fecal incontinence in patients with advanced ovarian cancer treated with CRS + HIPEC.

PURPOSE: The objective of this work was to analyze the long-term prevalence of urinary and fecal incontinence and their impact on quality of life in patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (CRS + HIPEC). METHODS: This cross-sectional study included a series of patients with advanced and recurrent ovarian cancer treated by CRS + HIPEC, with a disease-free period of at least 12 months after the procedure. Urinary incontinence was evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), fecal incontinence using the Wexner test and the Fecal Incontinence Quality of Life (FIQL) questionnaire and global quality of life using the Short Form 36 (SF-36) survey. RESULTS: A total of 64 patients were included in the study, with a median age of 55 years (range 28-78). The urinary incontinence rate was 45% and the fecal incontinence rate was 20%. Up to 14% of the patients presented both types of incontinence. The presence of urinary or fecal incontinence generated a significant negative impact on quality of life in relation to patients without incontinence. DISCUSSION: Urinary and fecal incontinence is frequent in the follow-up of ovarian cancer patients treated with CRS + HIPEC. Reconsidering the approach to the pelvis without peritoneal metastases in the peritoneum could modify the incidence of these pelvic floor dysfunctions.

Probiotic Properties of Alcaligenes faecalis Isolated from Argyrosomus regius in Experimental Peritonitis (Rat Model).

A strain of Alcaligenes faecalis A12C (A. faecalis A12C) isolated from Argyrosomus regius is a probiotic in fish. Previous experiments showed that A. faecalis A12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whether A. faecalis A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis. We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) received A. faecalis A12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after A. faecalis A12C administration was 100% in all groups. Mild eosinophilia (1.5%, p < 0.01) and increased aspartate aminotransferase (86 IU/L, p < 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significant E. coli decline in faeces, parallel to an increase in A. faecalis A12C at 7 days. E. coli had a tendency to recover initial values, while A. faecalis A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with A. faecalis A12C before E. coli intra-abdominal inoculation, and IC group inoculated with no A. faecalis A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that A. faecalis A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.

Differences in the pressures of canal anal and rectal sensitivity in patients with fecal incontinence, chronic constipation and healthy subjects.

INTRODUCTION: There exists a great variability in the manometric findings between patients with anal incontinence (AI) and healthy subjects. The correlation between the pressures of the anal canal and the AI is not exact by the wide rank of normal values. OBJECTIVES: Prospective study to evaluate differences in the pressures of the anal canal and in rectal sensitivity in patients with AI, chronic constipation (CC) and healthy subjects. MATERIAL AND METHODS: Ninety four patients with AI, 36 patients with CC and 15 healthy subjects were included. The following data were obtained: age, sex, resting pressure, anal canal length (ACL), squeeze maximum pressure (SMP), squeeze pressure duration (SPD), first sensation, urge and maximum tolerated volume (MTV). Statistical study: test of Kruskal-Wallis, test of Mann-Whitney, and multinomial logistic regression test. RESULTS: There were significant differences in the resting pressure (p < 0.001), the ACL (p < 0.001) and the SMP (p < 0.01) in the group of AI with respect to the other two groups. The volume for the first sensation was significantly lower in the healthy subjects than that in the other two groups (p < 0.05). The urge volume and the MVT were smaller in the group with AI with respect to the other groups (p < 0.001). In multivariate analysis the age, the resting pressure and the volume for the first sensation and urge increase the relative risk for AI. CONCLUSIONS: The greater age, the decrease in anal canal resting pressure and the alteration of rectal sensation increase the risk for AI.

Risk factors and management of incisional hernia after cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal surface malignancies.

BACKGROUND: The incidence of incisional hernia in patients with peritoneal surface malignancies treated by cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear, and the criteria commonly used to indicate their repair cannot be applied in these patients. The objective of this work was to analyze the incidence of incisional hernias in these patients, identify the risk factors associated with their appearance, and propose an algorithm for their management. METHODS: We analyzed a series of patients with malignant pathologies of the peritoneal surface treated by cytoreduction with peritonectomy and HIPEC procedures between January 2008 and June 2017. Only patients with a minimum postoperative follow-up period of 12 months were included. RESULTS: Our series included 282 patients, 28 (10%) of whom developed an incisional hernia during the follow-up period. Fifty-one patients, all with ovarian cancer with peritoneal dissemination, did not receive HIPEC after cytoreduction as they were part of the control arm of the CARCINOHIPEC clinical trial (NCT02328716) or because they did not provide specific informed consent. In the multivariate analysis, treatment with HIPEC (OR 2.56, 95% CI [1.57, 4.31], p = 0.032) and the administration of preoperative systemic chemotherapy (OR = 1.59, 95% CI [1.26, 3.58], p = 0.041) were found to be independent factors related to the appearance of an incisional hernia. CONCLUSIONS: The incidence of incisional hernia after cytoreduction and HIPEC is within the ranges described in the literature for other abdominal surgery procedures. The use of systemic chemotherapy and treatment with HIPEC, in particular, were identified as factors related to their occurrence.

Spirocercosis in red fox (Vulpes vulpes) in a natural reserve located in a meso-Mediterranean area.

Spirocerca lupi Rudolphi 1809 (Nematoda Spirocercidae) has an indirect cycle involving intermediate and paratenic hosts, having domestic or wild canids as the main definitive hosts. The most frequent pathology affecting dogs is a granulomatous tumor-like growth containing adults in the oesophagus and aorta. There are very few references about the presence of nodules in the stomach. There is scant information about the epidemiology of this disease in wild red foxes in meso-Mediterranean areas. In this work we report on the natural infection of wild red foxes by Spirocerca lupi and the damage produced in the stomach wall in an area where contact with other potential definitive hosts (canids) is very rare. From July 2015 to November 2016, 61 red foxes were sampled. 18.03% of the stomach walls examined had nodules containing Spirocerca lupi adults and eggs. The prevalence of infection was similar for young and adult groups (23.81 and 18.18%; χ2 = 0.25; df = 1; P = 0.6171) and it was higher in females than in males (25.81 versus 10.00%, χ2 = 2.58; df = 1; P = 0.1082). The red fox population in the area seems to be well established judging from their age distribution and the fact that they could be captured all year round. It would appear that in the absence of other main definitive host S. lupi population is able to survive just parasitizing red foxes. Pathologic effects of this parasite on red foxes seems to show some differences related to domestic dogs. These results also indicates as predator control programs can maintain suitable host populations with reduced level of infection.

Preservation of Malassezia pachydermatis using skimmed milk as cryoprotective agent.

This study evaluated the effect of skimmed milk as a cryoprotectant for the maintenance and long-term preservation of 70 Malassezia pachydermatis strains. An initial suspension of each strain was prepared in sterile distilled water with skimmed milk. The most effective method was cryopreservation that ensured 100% viability for 2years.

Control of Hyalomma lusitanicum (Acari: Ixodidade) Ticks Infesting Oryctolagus cuniculus (Lagomorpha: Leporidae) Using the Entomopathogenic Fungus Beauveria bassiana (Hyocreales: Clavicipitaceae) in Field Conditions.

Entomopathogenic fungi are widely used to control arthropods not just in agricultural settings but also in Veterinary Medicine and Public Health. These products have been employed to control tick populations and tick-borne diseases. The effectiveness of these control measures not only depends on the fungi, but also on the tick species and environmental conditions. In Mesomediterranean areas, tick species are adapted to extreme climatic conditions and it is therefore especially important to develop suitable tick control strategies. The aim of this study was to evaluate the effectiveness of a new method of tick control which entails the application of a commercial strain of Beauveria bassiana (Balsamo, Vuillemin) on wild rabbit burrows under field conditions. Aqueous solutions of the product were applied using a mist blower sprayer into 1,717 burrows. Two trials were performed, one in spring and the other in summer. The parasitic index (PI) was calculated for 10 rabbits per treatment per time point on day +30, +60, and +90 posttreatment and efficiency was calculated by comparing the PI for ticks in treated and untreated rabbits. A total of 20,234 ixodid ticks were collected. Hyalomma lusitanicum Koch, 1844 was the most abundant tick feeding on rabbits. Treatment significantly reduced the PI in spring (by 78.63% and 63.28% on day +30 and +60, respectively; P < 0.05), but appeared to be less effective in summer, with a marginally significant tick reduction of 35.72% on day +30 (P = 0.05). Results suggest that the efficacy of applications inside burrows could be temperature-dependent and that such applications could be an economic alternative to rabbit tick control during at least two months using a diluted solution of B. bassiana conidia.

Field evaluation of targeted selective treatments to control subclinical gastrointestinal nematode infections on small ruminant farms.

Targeted selective treatments (TST) are designed to identify those animals that would actually benefit from anthelmintic treatment, thus reducing the amount of drugs used and bringing down economic cost. In this study we assayed three TST programs based on GIN egg output, clinical sign and live weight criteria in a single area where only sub-clinical infections tend to occur and no anthelmintic resistance is reported. The study was carried out from February 2011 to August 2013 on four farms applying different management systems: an Ovine Extensive System, Ovine Semi-extensive Semi-irrigated System focusing on "Rubia del Molar" and Colmenareña" breeds, Ovine Semi-extensive System and Caprine Organic Semi-extensive System. The number of sheep and goats treated in all the TST strategies was lower in comparison with systematic treatments, especially when selected based on clinical signs (100%, in both years), followed by egg output (87.57% and 90.44% in the first and second year respectively) and finally by live weight (37.95% and 96.69%, in the first and second year respectively). FEC was low throughout the study for all animals and groups. Apparently, the TST applied did not influence live body weight. Preliminary results show that all three targeted selective treatments significantly reduced the number of animals treated and the cost of anthelmintic treatment on the farms, maintaining productivity in a low challenge environment. These results also seem to indicate that systematic anthelmintic treatments are unnecessary under these circumstances and traditional anthelmintic regimes should therefore be modified.

Prognostic factors for local control, regional control and survival in oropharyngeal squamous cell carcinoma.

We have performed univariate and multivariate analysis to identify the clinical and treatment-related prognostic factors in a series of 254 patients with newly diagnosed, histologically proven, oropharyngeal squamous cell carcinoma treated with radical radiation therapy. The probabilities of local control, regional control, disease-free survival (DFS) and adjusted survival (AS) were calculated using the Kaplan-Meier method and differences between curves were evaluated by the Mantel-Cox test. The obtained significant variables in the univariate analysis were analysed using the Cox proportional hazards model. In the Cox multivariate analysis, four variables significantly influenced local control probability in the following order: tumour diameter, N stage, alcohol intake and weight loss. N stage significantly influenced the probability of regional control. Five variables influenced both DFS and AS: N stage, tumour diameter, weight loss, alcohol intake and tumour origin within the posterior oropharyngeal wall.

Episcleral iridium-192 wire therapy for choroidal melanomas.

PURPOSE: To evaluate the effectivity of high-dose episcleral iridium-192 wires in the treatment of choroidal melanoma. METHODS AND MATERIALS: In 1983, the Departments of Radiation Oncology and Ophthalmology at the Clínica Puerta de Hierro, Madrid, Spain, initiated a clinical study using removable episcleral iridium-192 wires in the treatment of choroidal melanoma. Sixty-six evaluable patients were treated from January 1983 through July 1992. Two patients had a small sized tumor (3%), 28 had a medium sized tumor (42%), and 36 patients had a large tumor (54%). The mean follow-up was 40 months (6-118 months). The dose to the apex of the tumor ranged from 66 to 97 Gy (mean 76.6 Gy), and the doses at 2 mm depth ranged from 77 to 433 Gy (mean 200 Gy). RESULTS: Tumor regression or stabilization was observed in 53 of the 66 patients (90%). Visual acuity improved following treatment in 5 out of 54 patients (9%), remaining unchanged in 30 out of 54 (56%), and decreased in 19 out of 54 (35%) patients. The remaining seven patients had undergone enucleation. Late complications have been documented in 20 out of 66 patients (30%), including 6 patients in whom enucleation was required because of radiation-related complications. The probability of survival and survival free of local progression was 93% at 5 years and 79% at 10 years. The probability of retaining the treated eye is 82% after the fifth year posttreatment. CONCLUSIONS: Treatment of choroidal melanomas with episcleral iridium-192 wires is as effective as treatment with other radioactive applications. We feel that our results using iridium-192 wires are comparable to the other methods. However, we think that our technique is simple to implement, relatively inexpensive, and well tolerated.

Phase II study of radiochemotherapy with UFT and low-dose oral leucovorin in patients with unresectable rectal cancer.

PURPOSE: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer. METHODS AND MATERIALS: Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy. RESULTS: Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%). CONCLUSION: The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.