Harnessing Minimal Residual Disease as a Predictor for Colorectal Cancer: Promising Horizons Amidst Challenges.

Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the potential of MRD detection based on circulating tumor DNA (ctDNA) to revolutionize management for CRC patients. MRD detection represents an opportunity for risk stratification, treatment guidance, and early relapse monitoring. Here we overviewed the evolving landscape of MRD technology and its promising applications through the most up-to-date research and reviews, underscoring the transformative potential of this approach. Our primary focus is to provide a point-to-point perspective and address key challenges relating to the adoption of ctDNA-based MRD detection in the clinical setting. By identifying critical areas of interest and hurdles surrounding clinical significance, detection criteria, and potential applications of basic research, this article offers insights into the advancements needed to evaluate the role of ctDNA in CRC MRD detection, contributing to favorable clinical options and improved outcomes in the management of CRC.

Therapeutic Landscapes in Colorectal Carcinoma.

Colorectal cancer (CRC) is a disease of major public health and socioeconomic concern [...].

Retrospective study of lameness in beef cattle in northeastern Sardinia, Italy.

Lameness is one of the most prevalent diseases affecting dairy and beef cattle, resulting in decreased animal performance, decreased animal welfare, and substantial economic loss. In extensive beef cattle farming, the risk factors for this multifactorial disease are largely unexplored. This study aims to conduct a preliminary epidemiological survey of risk factors in beef cattle in extensive breeding, evaluate the farmer's perception of lameness, and determine the recurrence frequency of the pathologies under investigation in treated animals. The study was conducted in Sardinia, Italy. The population of the study consisted of 14379 cattle from 230 farms. An ad hoc questionnaire was developed to collect all the necessary data. A strong association was found between breed and the occurrence and recurrence of lameness (p < 0.0001). In addition, the Country of origin of both bulls and cows was found to be correlated with the incidence of lameness (p < 0.0001 and 0.0001, respectively). Farmers who indicated on the questionnaire that lameness was not important on their farm had more animals with recurrences (p < 0.0001) than other farmers. The veterinarian's treatment choice differed significantly by farmer concern (p = 0.007) and was associated with less disease recurrence (p < 0.0001), resulting in greater farmer satisfaction (p < 0.007). Pure cow breed, French bull origin, and farmer's age were detected as significant predictors of lameness issues, with pure cow breed and French bull origin having the strongest associations (p = 0.009). Even though the results of this study are preliminary, they indicate that breed selection is crucial in extensive beef farms to reduce lameness prevalence. In addition, it would be reasonable to train breeders to prevent and diagnose lameness early in order to collaborate with veterinarians to prevent recurrence.

Sutureless Technique for Surgical Castration in Adult Boars: A Feasibility Study.

The heterogeneity of Italian manufacturing processes results in the production of a large variety of pork products. In Sardinia, boars are raised and butchered to produce charcuterie. These animals are castrated before slaughter as androstenone would otherwise taint the meat, rendering it unfit for human consumption. However, to date, the literature concerning surgical orchiectomy in adult boars is limited. The goal of this study is to assess whether a sutureless swine orchiectomy procedure is feasible. Additionally, this study aims to determine the appropriate traction force needed to tie knots in the deferens duct of pigs of different weights and ages. Two groups were created: the first (n = 91) underwent orchiectomy by suture ligation; the second (n = 20) was castrated using the sutureless technique. Deferens ducts of animals in the first group (n = 182) were collected following castration, and their tensile strength was measured. Pearson's linear correlation was used to determine the relationship between the maximum traction force and weight and age groups. A correlation of 0.99 and 0.96 was shown between traction force and age and traction force and weight, respectively. In accordance with these results, sutureless castration was performed on 20 animals, calibrating the pulling force needed according to the age and weight of the boars. No complications were observed during the feasibility study, thus validating sutureless orchiectomy in adult boars.

Inflammatory Indexes as Predictive Biomarkers of Postoperative Complications in Oncological Thoracic Surgery.

The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = -0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.

Metaproteomic Profile of the Colonic Luminal Microbiota From Patients With Colon Cancer.

Recent studies have provided evidence of interactions among the gut microbiota (GM), local host immune cells, and intestinal tissues in colon carcinogenesis. However, little is known regarding the functions exerted by the GM in colon cancer (CC), particularly with respect to tumor clinical classification and lymphocyte infiltration. In addition, stool, usually employed as a proxy of the GM, cannot fully represent the original complexity of CC microenvironment. Here, we present a pilot study aimed at characterizing the metaproteome of CC-associated colonic luminal contents and identifying its possible associations with CC clinicopathological features. Colonic luminal contents were collected from 24 CC tissue specimens immediately after surgery. Samples were analyzed by shotgun metaproteomics. Almost 30,000 microbial peptides were quantified in the samples, enabling the achievement of the taxonomic and functional profile of the tumor-associated colonic luminal metaproteome. Upon sample aggregation based on tumor stage, grade, or tumor-infiltrating lymphocytes (TILs), peptide sets enabling discrimination of sample groups were identified through discriminant analysis (DA). As a result, Bifidobacterium and Bacteroides fragilis were significantly enriched in high-stage and high-grade CC, respectively. Among metabolic functions, formate-tetrahydrofolate ligase was significantly associated with high-stage CC. Finally, based on the results of this pilot study, we assessed the optimal sample size for differential metaproteomic studies analyzing colonic luminal contents. In conclusion, we provide a detailed picture of the microbial and host components of the colonic luminal proteome and propose promising associations between GM taxonomic/functional features and CC clinicopathological features. Future studies will be needed to verify the prognostic value of these data and to fully exploit the potential of metaproteomics in enhancing our knowledge concerning CC progression.

Current management of incidental gallbladder cancer: A review.

Early-stage gallbladder cancer (GBC) is mostly discovered incidentally by the pathologist after cholecystectomy for a presumed benign disease. It is the most common malignancy of the biliary tract with a variable incidence rate all over the World. The majority of patients with GBC remain asymptomatic for a long time and diagnosis is usually late when the disease is at an advanced stage. Radical surgery consisting in resection of the gallbladder liver bed and regional lymph nodes seems to be the best treatment option for incidental GBC. However, recurrence rates after salvage surgery are still high and the addition of neoadjuvant/adjuvant chemotherapy may improve outcomes. The aim of the present review is to evaluate current literature for advances in management of incidental GBC, with particular focus on staging techniques and surgical options.

Intrafollicular oocyte transfer (IFOT): Potential feasibility in the ovine species.

Intra-follicular oocyte transfer (IFOT) is a promising and innovative technique for in vivo embryo production previously described for equines and bovines. The aim of this study was to assess the feasibility of IFOT in the ovine species. Two preliminary in vivo and in vitro trials were performed to test the optimal procedures and timing for IFOT. In the in vivo trial, follicular growth was monitored with transrectal ultrasonography in ten adult ewes to preliminarily determine the ovulation and ideal timing for IFOT. The in vitro trial assessed i) the optimal inner diameter of the injection needle and ii) the recovery rate and integrity of injected cumulus-oocyte complexes (COCs) after follicle aspiration. For IFOT and embryo collection, five ewes were synchronized by CIDR insertion. Forty hours after CIDR removal, in ewes under sedation and general anesthesia, the ovaries were exposed by laparotomy, and the preovulatory follicle was injected with COCs previously collected from ovaries obtained from an abattoir. At 4 h after surgery, fully recovered ewes were housed in a paddock with a ram of proven fertility. Crayon marking on ram's chest was used to detect mating. Ovulation was assessed 40 h after the transfer of oocytes by transrectal ultrasonography. On day 6 after IFOT, embryo collection was performed by uterine flushing. In the in vitro testing, injection of >5 mm follicles with a 28 G needle loaded with 30 COCs in a 5 µL volume resulted in higher recovery rates and better preservation of COCs integrity. In the in vivo trial, ultrasound scanning revealed that ovulation occurred between 60 and 72 h after CIDR removal in all animals. In one ewe subjected to IFOT, 22/24 oocytes were effectively injected into the preovulatory follicle, but no embryos were collected after flushing. In the remaining four animals, 85/102 oocytes were injected, and six cleaved embryos, 12 morulae and 1 blastocyst were collected, including native embryos. This preliminary investigation indicated that IFOT in ovine species resulted in ovulation, fimbrial capture, tubal transport of heterologous oocytes and in vivo embryo production. Further studies are needed to optimize the embryo recovery rate and develop less invasive techniques for oocyte injection and uterine flushing, such as through a laparoscopic or transcervical approach.

Quantitative Metabolomics to Explore the Role of Plasma Polyamines in Colorectal Cancer.

Colorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms. These data together with an evaluation of the inflammatory indexes might represent suitable biomarkers for the identification of CRC patients. The statistical models revealed good discrimination in distinguishing CRC patients from healthy subjects. The plasma assessment of ornithine and acetylspermine, as well as lymphocyte/platelet ratio, revealed helpful information on the progression of CRC. The combined profiles of circulating polyamines and inflammatory indexes, together with the application of an innovative technology, could represent a valuable tool for discriminating patients from different clinical groups.

A Portrait of Intratumoral Genomic and Transcriptomic Heterogeneity at Single-Cell Level in Colorectal Cancer.

In the study of cancer, omics technologies are supporting the transition from traditional clinical approaches to precision medicine. Intra-tumoral heterogeneity (ITH) is detectable within a single tumor in which cancer cell subpopulations with different genome features coexist in a patient in different tumor areas or may evolve/differ over time. Colorectal carcinoma (CRC) is characterized by heterogeneous features involving genomic, epigenomic, and transcriptomic alterations. The study of ITH is a promising new frontier to lay the foundation towards successful CRC diagnosis and treatment. Genome and transcriptome sequencing together with editing technologies are revolutionizing biomedical research, representing the most promising tools for overcoming unmet clinical and research challenges. Rapid advances in both bulk and single-cell next-generation sequencing (NGS) are identifying primary and metastatic intratumoral genomic and transcriptional heterogeneity. They provide critical insight in the origin and spatiotemporal evolution of genomic clones responsible for early and late therapeutic resistance and relapse. Single-cell technologies can be used to define subpopulations within a known cell type by searching for differential gene expression within the cell population of interest and/or effectively isolating signal from rare cell populations that would not be detectable by other methods. Each single-cell sequencing analysis is driven by clustering of cells based on their differentially expressed genes. Genes that drive clustering can be used as unique markers for a specific cell population. In this review we analyzed, starting from published data, the possible achievement of a transition from clinical CRC research to precision medicine with an emphasis on new single-cell based techniques; at the same time, we focused on all approaches and issues related to this promising technology. This transition might enable noninvasive screening for early diagnosis, individualized prediction of therapeutic response, and discovery of additional novel drug targets.

Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.

Perianal mucinous adenocarcinoma with dysplastic polyps of the colon: A case report.

INTRODUCTION: Perianal mucinous adenocarcinoma is rarely encountered in the setting of anal neoplasms. The rarity of the disease and the paucity of publications on this topic are responsible for a lack of diagnostic and therapeutic guidelines. PRESENTATION OF CASE: An 80-year-old man with mucinous adenocarcinoma of the anal canal associated with dysplastic polyps of the colon was treated by multiple endoscopic polypectomies and abdomino-perineal resection of the rectum. We discuss the management of this rare case from the diagnosis up to one-year follow-up. DISCUSSION: Perianal mucinous adenocarcinoma is a very rare entity frequently combined with chronic fistulas. Inflammatory symptoms may mislead its diagnosis, which is often delayed. The unique association between perianal mucinous adenocarcinoma and dysplastic polyps of the colon, that we have reported, may suggest a secondary etiology. High clinical suspicion is important for early and correct diagnosis, which should be based on endoanal ultrasound and/or magnetic resonance imaging followed by deep tissue biopsies. CONCLUSION: We stress the importance of accumulating such cases in the literature. The understanding of the etiopathogenic mechanisms may lead to the development of novel diagnostic and therapeutic protocols.

Use of saline contrast ultrasonography in the diagnosis of complete jugular vein occlusion in a horse.

Background: Thrombophlebitis and thrombosis are the most common causes of jugular vein occlusion in horses. Medical and surgical treatments aim to recanalize the occluded vessel and reduce proximal venous congestion and edema. Case Description: The present report describes a clinical case of equine jugular vein thrombosis (JVT) with complete vein occlusion diagnosed by saline contrast ultrasonography (SCU) and confirmed by contrast venography. Conclusion: Our results demonstrated that the SCU test can be easily performed and objectively interpreted using standard ultrasound equipment; it is not expensive and it does not require x-ray exposure. The SCU test is a valid tool to assess vessel patency and presence of collateral circulation in JVT. The test could therefore be used to monitor the progression of the disease and the effectiveness of therapy against JVT in horses.

Landscape of transcriptome variations uncovering known and novel driver events in colorectal carcinoma.

We focused on an integrated view of genomic changes in Colorectal cancer (CRC) and distant normal colon tissue (NTC) to test the effectiveness of expression profiling on identification of molecular targets. We performed transcriptome on 16 primary coupled CRC and NTC tissues. We identified pathways and networks related to pathophysiology of CRC and selected potential therapeutic targets. CRC cells have multiple ways to reprogram its transcriptome: a functional enrichment analysis in 285 genes, 25% mutated, showed that they control the major cellular processes known to promote tumorigenesis. Among the genes showing alternative splicing, cell cycle related genes were upregulated (CCND1, CDC25B, MCM2, MCM3), while genes involved in fatty acid metabolism (ACAAA2, ACADS, ACAT1, ACOX, CPT1A, HMGCS2) were downregulated. Overall 148 genes showed differential splicing identifying 17 new isoforms. Most of them are involved in the pathogenesis of CRC, although the functions of these variants remain unknown. We identified 2 in-frame fusion events, KRT19-KRT18 and EEF1A1-HSP90AB1, encoding for chemical proteins in two CRC patients. We draw a functional interactome map involving integrated multiple genomic features in CRC. Finally, we underline that two functional cell programs are prevalently deregulated and absolutely crucial to determinate and sustain CRC phenotype.

Effect of Probiotic Use on Adverse Events in Adult Patients with Inflammatory Bowel Disease: a Retrospective Cohort Study.

Alterations of intestinal microflora are involved in the pathogenesis and natural history of inflammatory bowel diseases (IBDs). Manipulation of human gut microbiota with probiotics may be a therapeutic option. In this retrospective cohort study, the benefits of probiotic use in reducing adverse events were analyzed. Data from clinical charts of IBD patients followed up for at least 36 months were retrieved. The occurrence of adverse events including the need for systemic steroids, hospitalization, and surgery related to IBD was analyzed according to age, gender, body mass index, treatments, IBD phenotype, disease duration, and probiotic use. The amount of probiotic use was calculated as the ratio of time under probiotic treatment to the disease duration starting from the date of the first probiotic administration and expressed as a percentage. Patients were stratified according to the percentage of probiotic use as ≤ 24%, 25-74%, and ≥ 75%, and the number of adverse events per patient-years was calculated. Results were adjusted for Crohn's disease (CD) and ulcerative colitis (UC) by multivariate analysis including study variables. Data from 200 patients (78 CD, 122 UC; 117 females; mean age 40.6 ± 15.3 years; mean disease duration 12.1 ± 8.7 years) were available. CD patients taking probiotics for 25-74% of the disease duration experienced a 64% reduction in total adverse events. The need for systemic steroids, hospitalization, and surgery dropped to zero events per person-year in UC patients and decreased by 93% (p < 0.001) in CD patients taking probiotics for ≥ 75% of the disease duration. Our findings suggest that the use of probiotics may be an additional therapeutic tool in patients with IBD.

Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression.

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.

MicroRNA-425-5p Expression Affects BRAF/RAS/MAPK Pathways In Colorectal Cancers.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide and about 20% is metastatic at diagnosis and untreatable. The anti-EGFR therapy in metastatic patients is led by the presence of KRAS-mutations in tumor tissue. KRAS-wild-type CRC patients showed a positive response rate of about 70% to cetuximab or panitumumab combined with chemotherapy. MiRNAs are promising markers in oncology and could improve our knowledge on pathogenesis and drug resistance in CRC patients. This class of molecules represents an opportunity for the development of miRNA-based strategies to overcome the ineffectiveness of anti-EGFR therapy. We performed an integrative analysis of miRNA expression profile between KRAS-mutated CRC and KRAS-wildtype CRC and paired normal colic tissue (NCT). We revealed an overexpression of miR-425-5p in KRAS-mutated CRC compared to KRAS-wild type CRC and NCT and demonstrated that miR-425-5p exerts regulatory effects on target genes involved in cellular proliferation, migration, invasion, apoptosis molecular networks. These epigenetic mechanisms could be responsible of the strong aggressiveness of KRAS-mutated CRC compared to KRAS-wildtype CRC. We proved that some miR-425-5p targeted genes are involved in EGFR tyrosine kinase inhibitor resistance pathway, suggesting that therapies based on miR-425-5p may have strong potential in targeting KRAS-driven CRC. Moreover, we demonstrated a role in the oncogenesis of miR-31-5p, miR-625-5p and miR-579 by comparing CRC versus NCT. Our results underlined that miR-425-5p might act as an oncogene to participate in the pathogenesis of KRAS-mutated CRC and contribute to increase the aggressiveness of this subcategory of CRC, controlling a complex molecular network.

Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma.

Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong prognostic differences and responses to treatment, and 20% have incurable metastatic disease at diagnosis. We considered it essential to investigate mechanisms that control cellular regulatory networks, such as the miRNA-mRNA interaction, known to be involved in cancer pathogenesis. We conducted a human miRNome analysis by TaqMan low density array, comparing CRC to normal colon tissue (NCT, and experimentally identified gene targets of miRNAs deregulated, by anti-correlation analysis, with the CRC whole-transcriptome profile obtained from RNASeq experiments. We identified an integrated signature of 20 deregulated miRNAs in CRC. Enrichment analyses of the gene targets controlled by these miRNAs brought to light 25 genes, members of pathways known to lead to cell growth and death (CCND1, NKD1, FZD3, MAD2L1, etc.), such as cell metabolism (ACSL6, PRPS1-2). A screening of prognosis-mediated miRNAs underlined that the overexpression of miR-224 promotes CRC metastasis, and is associated with high stage and poor survival. These findings suggest that the biology and progression of CRC depend on deregulation of multiple miRNAs that cause a complex dysfunction of cellular molecular networks. Our results have further established miRNA-mRNA interactions and defined multiple pathways involved in CRC pathogenesis.

Red cell distribution width and mean platelet volume as predictors of anastomotic dehiscence in colorectal surgery A pilot multicenter case-match study.

AIM: One of the most serious complications in modern colorectal surgery is the occurrence of an anastomotic dehiscence. The aim of this study was to evaluate the role of preoperative red cell distribution width (RDW) and mean platelet volume (MPV) as predictors of anastomotic dehiscence in elective surgery for colorectal cancer. MATERIALS AND METHODS: Forty-two patients with a clinically manifested anastomotic dehiscence after oncological colorectal surgery, and 42 controls matched for age, sex, pathological stage and tumor localization were enrolled. Correlations between the preoperative RDW and MPV values and anastomotic dehiscence were investigated. RESULTS: Both the median RDW value (14.4 % vs 13.1%; p=0.007) and the median MPV value (8.0 fL vs 7.5 fL; p=0.037) were significantly higher in patients with anastomotic dehiscence than in those without. In multiple regression analysis only the RDW remained significantly associated with anastomotic dehiscence. CONCLUSIONS: The preoperative values of RDW may be useful in predicting anastomotic damage in elective oncological surgery. KEY WORDS: Anastomotic Dehiscence, MPV, RDW.

Determination of minimum alveolar concentration and cardiovascular effects of desflurane in positive-pressure ventilated sheep.

OBJECTIVE To determine the minimum alveolar concentration of desflurane (MACDES) and effects on cardiovascular variables in positive-pressure ventilated sheep. ANIMALS 13 adult female sheep. PROCEDURES Anesthesia was induced with desflurane. After a 30-minute equilibration at an end-tidal concentration of desflurane (etDES) of 10.5%, an electrical stimulus (5 Hz/ms and 50 mA) was applied for 1 minute or until gross purposeful movement occurred. The etDES was then changed by 0.5% (modified up-down method), depending on whether a positive motor response had been elicited, and stimulation was repeated. The MACDES was the etDES midway between a positive and negative response. After MACDES was determined, etDES was increased to 1.3 and 1.6 MACDES. Animals were allowed to equilibrate for 15 minutes, and cardiovascular, blood gas, acid-base, and hematologic variables were measured. Times to induction of anesthesia, extubation, attainment of sternal position, and standing and duration of anesthesia were recorded. RESULTS Mean ± SD MACDES was 9.81 ± 0.79%. Times to intubation, extubation, and standing were 4.81 ± 2.21 minutes, 14.09 ± 4.05 minutes, and 32.4 ± 12.5 minutes, respectively. Duration of anesthesia was 226 ± 22 minutes. Heart rate increased significantly at induction of anesthesia but otherwise remained at preanesthetic rates. Arterial blood pressures progressively decreased with increasing etDES; pressures increased slightly only in response to noxious stimulation. CONCLUSIONS AND CLINICAL RELEVANCE The MACDES determined here compared favorably with that determined for other sheep populations and indicated similar anesthetic potency as in other species. Desflurane caused dose-dependent arterial hypotension, which indicated the need for careful blood pressure monitoring.