Minimally Invasive Esophagectomy Provides Better Short- and Long-Term Outcomes Than Open Esophagectomy in Locally Advanced Esophageal Cancer.

BACKGROUND: Minimally invasive esophagectomy (MIE) has been increasingly performed for locally advanced esophageal cancer in place of open transthoracic esophagectomy (OE). This study explored the significance of MIE for esophageal squamous cell carcinoma (ESCC), focusing mainly on the depth of primary esophageal tumors. METHODS: This study retrospectively assessed short- and long-term outcomes of patients who underwent esophagectomy for ESCC from 2005 through 2021. The inverse probability of the treatment-weighting (IPTW) method was used to compare the outcomes between OE and MIE. The outcomes also were evaluated in the subgroups stratified by cT category. RESULTS: Among 1117 patients, 447 (40%) underwent OE and 670 (60%) underwent MIE. After IPTW adjustment, the incidence of any postoperative complications was significantly higher in the OE group than in the MIE group (60.8% vs 53.7%; p = 0.032), whereas the R0 resection rate was significantly higher in the MIE group (98.6% vs 92.7%; p < 0.001). The MIE group showed better 3 year overall and cancer-specific survival than the OE group (p < 0.001). The incidence of locoregional recurrence within the surgical field was significantly more frequent in the OE group (p < 0.001). In the subgroup analysis stratified by cT category, the R0 resection rate was significantly higher and the incidence of locoregional recurrence was lower in the MIE group among the patients with cT3-4 tumors. In the patients with cT1-2 tumors, MIE showed no significant benefit over OE. CONCLUSIONS: For the patients with cT3-4 tumors, MIE showed fewer postoperative complications, better locoregional control, and better prognosis than OE. Compared with OE, MIE is beneficial, especially for locally advanced ESCC.

Anatomical factor associated with thoracic procedural difficulty in robot-assisted minimally invasive esophagectomy.

BACKGROUND: Robotic surgical systems with full articulation of instruments, tremor filtering, and motion scaling can potentially overcome the procedural difficulties in endoscopic surgeries. However, whether robot-assisted minimally invasive esophagectomy (RAMIE) can overcome anatomical difficulties during thoracoscopic esophagectomy remains unclear. This study aimed to clarify the anatomical and clinical factors that influence the difficulty of RAMIE in the thoracic region. METHODS: Forty-five patients who underwent curative-intent RAMIE with upper mediastinal lymph node dissection for esophageal cancer were included. Using preoperative computed tomography images, we calculated previously reported anatomical indices to assess the upper mediastinal narrowness and vertebral body projections in the middle thoracic region. The factors influencing thoracic operative time were then investigated. RESULTS: During the thoracic procedure, the median operative time was 215 (124-367) min and the median blood loss was 20 (5-190) mL. Postoperatively, pneumonia, anastomotic leakage, and recurrent laryngeal nerve palsy occurred in 17.8%, 2.2%, and 6.7% of the patients, respectively. The multiple linear regression model revealed that a narrow upper mediastinum and greater blood loss during the thoracic procedure were significant factors associated with a prolonged thoracic operative time (P = 0.025 and P < 0.001, respectively). Upper mediastinal narrowing was not associated with postoperative complications. CONCLUSIONS: A narrow upper mediastinum was significantly associated with a prolonged thoracic operative time in patients with RAMIE.

Fully robotic side-to-side stapled anastomosis provides less anastomotic leakage than conventional minimally invasive approach in Ivor Lewis esophagectomy.

INTRODUCTION: This study evaluates surgical outcomes of minimally invasive Ivor Lewis esophagectomy (ILE) for esophageal and esophagogastric cancer, with the comparison of the robotic approach (RA) and the conventional minimally invasive approach (CA). METHODS: Selected patients who underwent minimally invasive ILE for esophageal cancer were included between January 2017 and December 2023. We retrospectively investigated the patients' background characteristics and the short-term surgical outcomes. RESULTS: In this period, among a total of 840 esophagectomies, 81 patients (9.6%) underwent minimally invasive ILE, consisting of 24 cases with RA and 57 with CA. The major indications for ILE were adenocarcinoma of the distal esophagus or esophagogastric junction and patients with prior head and neck cancer treatment. Among these thoracic approaches, there were no significant differences in the patients' indications and characteristics, including age, histology, tumor location, clinical TNM stage, and preoperative therapy. Compared with the CA group, no anastomotic leakage was observed in the RA group (17.5% vs. 0, p = .035). Rates of total postoperative complications and length of hospital stay also tended to be reduced in the RA group but did not reach significance. CONCLUSION: In the Ivor Lewis esophagectomy with a side-to-side linear-stapled anastomosis, the fully robotic approach has the potential to powerfully reduce anastomotic leakage compared to the conventional minimally invasive approach.

Gastric conduit reconstruction after esophagectomy.

A high risk of complications still accompanies gastric conduit reconstruction after esophagectomy. In this narrative review, we summarize the technological progress and the problems of gastric conduit reconstruction after esophagectomy. Several types of gastric conduits exist, including the whole stomach and the narrow gastric tube. The clinical outcomes are similar between the two types of conduits. Sufficient blood supply to the conduit is mandatory for a successful esophageal reconstruction. Recently, due to the availability of equipment and its convenience, indocyanine green angiography has been rapidly spreading. When the blood perfusion of the planning anastomotic site is insufficient, several techniques, such as the Kocher maneuver, pedunculated gastric tube with duodenal transection, and additional microvascular anastomosis, exist to decrease the risk of anastomotic failure. There are two different anastomotic sites, cervical and thoracic, and mainly two reconstructive routes, retrosternal and posterior mediastinal routes. Meta-analyses showed no significant difference in outcomes between the anastomotic sites as well as the reconstructive routes. Anastomotic techniques include hand-sewn, circular, and linear stapling. Anastomoses using linear stapling is advantageous in decreasing anastomosis-related complications. Arteriosclerosis and poorly controlled diabetes are the risk factors for anastomotic leakage, while a narrow upper mediastinal space and a damaged stomach predict leakage. Although standardization among the institutional team members is essential to decrease anastomotic complications, surgeons should learn several technical options for predictable or unpredictable intraoperative situations.

Comparison of chemotherapy outcomes between normal and high serum cortisol concentration in dogs with lymphoma.

BACKGROUND: Increased serum cortisol (COR) concentrations may induce glucocorticoid resistance by down-regulation of glucocorticoid receptor (GCR), resulting in decreased chemotherapy efficacy in dogs with lymphoma. HYPOTHESIS: Investigate the relationship between serum COR concentrations and chemotherapy outcomes in dogs with lymphoma. ANIMALS: Thirty client-owned dogs with lymphoma, with serum COR concentration measured using serum samples collected at diagnosis. METHODS: Retrospective study. Dogs were divided into 2 groups based on serum COR concentrations: a normal group (n = 16) with COR concentrations <6 µg/dL and a high group (14) with COR concentrations ≥6 µg/dL. We compared signalment, clinical signs, stage, type of lymphoma, adrenal gland size, alkaline phosphatase (ALP) activity, response to chemotherapy, progression-free survival (PFS), overall survival (OS), and rate of P-glycoprotein (P-gp)- and GCR-positive cells between the 2 groups. RESULTS: No significant differences were found in the demographic characteristics between the 2 groups. However, the high COR group exhibited a significantly lower response to chemotherapy, PFS, and OS compared with the normal COR group. Serum ALP activity was significantly higher in the high COR group than in the normal COR group. Adrenal gland size was also significantly larger in the high COR group. Although no significant differences were found in the rate of P-gp-positive cells between the 2 groups, the rate of GCR-positive cells was significantly lower in the high COR group. CONCLUSIONS AND CLINICAL IMPORTANCE: Our data suggests that measurement of serum COR concentrations may serve as a potential prognostic factor and evaluation index.

Influence of the Hypoxia-Activated Prodrug Evofosfamide (TH-302) on Glycolytic Metabolism of Canine Glioma: A Potential Improvement in Cancer Metabolism.

The transcription factor hypoxia-inducible factor 1α (HIF-1α) drives metabolic reprogramming in gliomas (GLs) under hypoxic conditions, promoting glycolysis for tumor development. Evofosfamide (EVO) releases a DNA-alkylating agent within hypoxic regions, indicating that it may serve as a hypoxia-targeted therapy. The aim of this study was to investigate the glycolytic metabolism and antitumor effects of EVO in a canine GL model. Our clinical data showed that overall survival was significantly decreased in GL dog patients with higher HIF-1α expression compared to that of those with lower HIF-1α expression, and there was a positive correlation between HIF-1α and pyruvate dehydrogenase kinase 1 (PDK1) expression, suggesting that glycolytic activity under hypoxia conditions may contribute to poor outcomes in canine GL. Our glycolysis assay tests showed that the glycolytic ATP level was higher than the mitochondrial ATP level in three types of canine GL cell lines by activating the HIF-1 signal pathway under hypoxia conditions, resulting in an overall increase in total cellular ATP production. However, treatment with EVO inhibited the glycolytic ATP level in the GL cell lines under hypoxia conditions by targeting HIF-1α-positive cells, leading to decrease in total cellular ATP production. Our in vivo tests showed that EVO significantly reduced tumor development compared to controls and temozolomide in murine GL models. A metabolic analysis demonstrated that EVO effectively suppressed glycolytic metabolism by eliminating HIF-1α-positive cells, suggesting that it may restore metabolism in canine GLs. The evidence presented here supports the favorable preclinical evaluation of EVO as a potential improvement in cancer metabolism.

Effectiveness of 2-dimensional shear wave elastography for noninvasive and reliable estimation of right atrial pressure in dogs with induced volume overload.

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) provides information on hepatic elastic modulus as shear wave velocity (SWV). HYPOTHESIS/OBJECTIVES: To assess SWV using 2D-SWE in dogs with induced volume overload, investigate the relationship between this information and right atrial pressure (RAP) measured by invasive right heart catheterization, and also evaluate the difference in SWV before and after diuretic administration. ANIMALS: Six healthy beagles. METHODS: Prospective experimental study. Right heart catheterization and 2D-SWE were performed in 6 anesthetized beagles at baseline and after the induction of volume overload. Volume overload was induced by IV hydroxyethyl starch 70/0.5 infusion (100 mL/kg/h). Furosemide (4-6 mg/kg, IV) was administered, and the SWVs were measured. RESULTS: Shear wave velocity showed a significant gradual increase during acute volume overload compared to baseline. SWV was significantly positively correlated with RAP (P < .0001, ρ = 0.9729). The area under the curve of SWV to predict RAP at >10, >15, and >20 mm Hg was 0.9896 (95% confidence interval [95% CI], 0.9690-1.000), 0.9907 (95% CI, 0.9701-1.000), and 0.9722 (95% CI, 0.9280-1.000), respectively. The SWV after diuretic use decreased significantly. CONCLUSIONS AND CLINICAL IMPORTANCE: Two-dimensional shear wave elastography might be useful for noninvasive and reliable estimation of RAP in dogs with acute volume overload and has potential as a quantitative biomarker for evaluating therapeutic response in dogs with right sided congestive heart failure.

Prevalence and risk factors of poor subjective sleep quality in elite judo athletes.

This study aimed to determine the prevalence and risk factors of poor subjective sleep quality in elite judo athletes. A subjective cross-sectional questionnaire survey was conducted with 106 elite judo athletes who participated in the training camp of the Japanese national team. Eighty-six respondents (men: 52.3%; average age: 22.9 ± 3.1 years) with complete responses were included in the analysis (valid response rate: 81.1%). Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The prevalence of poor sleep quality (PSQI score ≥ 5.5), the mean PSQI score, and subscale scores were investigated. Relationships between poor sleep quality and attributes, lifestyle habits, competition-based activities, and psychological distress were explored using Fisher's exact tests and multivariate logistic regression analysis. Thirty-five respondents (40.7%) reported poor sleep quality. The percentage and subscale scores of the respondents for sleep latency, sleep duration, and daytime dysfunction were higher than those of the population of Japanese national-level athletes. The mean PSQI score of the respondents was similar to that of some elite athlete populations but higher than those of others. Multivariate logistic regression analysis revealed that psychological distress was associated with poor sleep quality. In conclusion, the prevalence of poor subjective sleep quality in elite judo athletes was suggested to be similar or higher among elite athlete population. Sleep latency, sleep duration, and daytime dysfunction status were worse in elite judo athletes than in Japanese national-level athletes. Psychological distress was a risk factor for poor subjective sleep quality in elite judo athletes. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00444-6.

Case Report: Usefulness of Drip Infusion Cholangiography With Computed Tomography for the Diagnosis of Biloma in a Dog.

Bilomas are encapsulated collections of bile outside or inside the biliary tract within the abdominal cavity. For diagnostic and therapeutic approaches, it is important to identify the origin of bile leaks from the biliary tract. This case report describes the usefulness of drip infusion cholangiography with computed tomography (DIC-CT) for detecting the site of bile leakage in a dog with biloma. A 10-year-old, castrated male Pomeranian dog was referred to our department for gastrointestinal signs. Abdominal ultrasonography detected gallbladder mucocele without evidence of defect on the wall and well-defined anechoic localized fluid accumulation around the right division of the liver. On the other hand, there was only a small amount of ascites in the abdominal cavity. The accumulated fluid collected through abdominocentesis had a bilirubin concentration of 11.4 mg/dl, which was more than twice as high as that in serum (0.4 mg/dl), but had absence of pyogenic bacteria. The DIC-CT with meglumine iotroxate showed two well-defined large fluid collections: one between right medial and lateral lobe and the other between the right lateral lobe and caudate process of caudate lobe. Three-dimensional DIC-CT views that the former was enhanced by the contrast agent and that it communicated with an intrahepatic bile duct of the right lateral lobe. Moreover, the DIC-CT images confirmed communication with each fluid collections. After 6 days of hospitalization, a decrease in the amount of accumulated fluid was confirmed, after which cholecystectomy was performed. The dog was discharged from the hospital without complications. No signs of bile leakage were observed on follow-up imaging on postoperative day 10. According to authors knowledge, this has been the first report to show that DIC-CT can be useful for determining the origin of bile leakage in dogs with bilomas.

Extrahepatic biliary obstruction can interfere with hepatic fibrosis prediction using two-dimensional shear wave elastography in dogs.

Two-dimensional shear wave elastography (2D-SWE) can be used to quantitatively evaluate the elastic modulus of the liver as shear wave velocity (SWV), which can noninvasively predict clinically relevant hepatic fibrosis in both dogs and humans. However, extrahepatic biliary obstruction (EHBO), regardless of the presence of clinically relevant hepatic fibrosis, can influence SWVs in humans and thus may interfere with hepatic fibrosis prediction using 2D-SWE in dogs. The aim of this prospective, observational, and one-group pretest-posttest study is to investigate whether SWV measured by 2D-SWE displays a difference between dogs with and without EHBO. A total of 20 dogs were included (7 with EHBO and 13 with gallbladder pathology but no EHBO) that underwent preoperative SWV measurement using 2D-SWE. In all dogs, stages of hepatic fibrosis were evaluated histopathologically using a scoring scheme. In addition, postoperative SWVs in dogs with EHBO relieved via laparotomy were also evaluated. The median (range) SWVs in the dogs with and without EHBO were 1.91 (1.81-2.54) m/s and 1.57 (1.37-1.64) m/s, respectively. Although there was no significant difference in the histopathological hepatic fibrosis stages between the dogs with and without EHBO, the preoperative SWVs in the dogs with EHBO were significantly higher than in dogs without EHBO (P = .0004), and SWVs were found to decrease significantly after surgery (P = .0097). This study demonstrates that EHBO can increase the SWV of dogs without clinically relevant hepatic fibrosis and can interfere with the prediction of noninvasive hepatic fibrosis using 2D-SWE.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24-month interim analysis of a long-term post-marketing study (J-STEP/LT).

AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor, and is currently used to treat patients with type 2 diabetes mellitus. We designed a 3-year study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3- and 12-month interim analysis showed tofogliflozin was well-tolerated, safe and clinically effective. Here, we report the results of the 24-month interim analysis. MATERIALS AND METHODS: This is a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term). RESULTS: Of the 6,897 patients enrolled, 6,712 and 6,461 patients were analyzed for the safety and effectiveness of tofogliflozin, respectively. During the 24-month observation period, the incidence rates of adverse drug reactions (ADRs) and serious adverse drug reactions were 11.25 and 1.21%, respectively. As to adverse drug reactions of special interest, the incidence rates of hypoglycemia, polyuria/pollakiuria, volume depletion-related events, urinary tract infections and genital infection were 0.83, 1.28, 1.46, 1.18 and 1.62%, respectively. Renal disorders, and cardiovascular and cerebrovascular disorders occurred in 0.63 and 0.76% of the patients, respectively. Glycated hemoglobin A1c and bodyweight decreased significantly by -0.70% (P < 0.0001) and -2.95 kg (P < 0.0001), respectively, from baseline to week 104 (last observation carried forward). CONCLUSIONS: Significant safety concerns have not been observed, and clinical benefit including a long-term reduction in glycated hemoglobin A1c over a 104-week (24 months) observation period with weight loss was suggested in this 24-month interim analysis of the 3-year Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term in routine clinical practice.

Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus in real-world practice: Results of 12-month interim analysis of a long-term post-marketing surveillance study (J-STEP/LT).

AIMS/INTRODUCTION: Due to the paucity of tofogliflozin data, we assessed the safety and effectiveness of tofogliflozin among Japanese patients with type 2 diabetes mellitus in the clinical setting, stratifying the patients by age, sex, estimated glomerular filtration (eGFR) rate and body mass index. We report the results of a 12-month interim analysis. MATERIALS AND METHODS: This was a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of tofogliflozin with type 2 diabetes mellitus Patients/Long Term). RESULTS: Out of 6,897 patients enrolled, the safety and effectiveness analysis populations consisted of 6,712 and 6,449 patients, respectively. During 12 months, adverse drug reactions and their incidence were 9.12 and 0.88%, respectively. The incidence of hypoglycemia was 0.67%. Polyuria/pollakiuria occurred more frequently in patients aged ≥65 years than in patients aged <65 years. Women experienced higher rates of urinary tract and genital infection than men. The lowest eGFR subgroup experienced maximum volume depletion-related events. Cardiovascular and cerebrovascular disorders occurred in 0.55% of the patients. Glycated hemoglobin (HbA1c) and bodyweight significantly decreased by -0.76% and -2.73 kg, respectively, from baseline to the last observation carried forward (P < 0.0001). Except for the lowest eGFR subgroup, other eGFR subgroups showed significantly decreased HbA1c values. All eGFR subgroups showed significantly decreased bodyweight, and all body mass index subgroups showed significantly decreased HbA1c and bodyweight. CONCLUSIONS: Our interim 12-month data suggest that tofogliflozin could be used safely and effectively in Japanese patients with type 2 diabetes mellitus, as tofogliflozin was well tolerated with low hypoglycemia risk, and significantly improved HbA1c and bodyweight.

Hemolysis Is Responsible for Elevation of Serum Iron Concentration After Regular Exercises in Judo Athletes.

Serum iron concentration increases in marathon athletes after running due to mechanical destruction of red blood cells (hemolysis). This study was performed to examine whether serum iron concentration increases after regular Judo exercise, and if so, whether such post-exercise iron increase is caused by hemolysis. We examined biochemical parameters related to red blood cell and iron metabolism in 16 male competitive Judo athletes before and after traditional exercise training composed of basic movements and freestyle matchup. The parameters were adjusted for changes in plasma volume based on simultaneously measured albumin concentration. The red blood cell count, hemoglobin concentration, and hematocrit levels decreased significantly, by 6.0-8.4%, after Judo exercise. The serum iron concentration and transferrin saturation increased significantly, from 87 ± 34 µg/dL to 98 ± 29 µg/dL and from 27.1 ± 9.7% to 31.2 ± 9.0%, respectively. Furthermore, the serum free hemoglobin level increased by 33.9% (p < 0.05), and haptoglobin concentration decreased by 19.2% (p < 0.001). A significant negative correlation was observed between Δ haptoglobin concentration and Δ serum iron concentration (r = - 0.551, p = 0.027). The results of this study indicate that serum iron concentration increases significantly after Judo exercise due to hemolysis.

Usefulness of noninvasive shear wave elastography for the assessment of hepatic fibrosis in dogs with hepatic disease.

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (≥F2) in dogs with hepatic disease. OBJECTIVES: To investigate whether SWV measured by 2D-SWE can differentiate between dogs with (≥F2) and without (F0-1) clinically relevant hepatic fibrosis. ANIMALS: Twenty-eight client-owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled. METHODS: In this cross-sectional prospective study, SWVs were measured using 2D-SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine. RESULTS: Median SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81-2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44-1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37-1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal-Wallis test, P = .12). CONCLUSIONS AND CLINICAL IMPORTANCE: The 2D-SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.

Impact of sleep disordered breathing on performance in judo players.

OBJECTIVE: Previous studies have suggested that young sports players may suffer from sleep disordered breathing (SDB). It was hypothesised that SDB in heavy-class judo players was far more prevalent than expected and that it could reduce judo performance, which could be improved by appropriate therapies. To address this, the present study estimated the percentage of heavy-class judo players with SDB and investigated the effect of SDB treatment on judo performance. METHODS: We enrolled 19 young judo players from a university judo team with body weight >100 kg and/or body mass index >30 kg/m2. Both excessive daytime sleepiness (EDS) and respiratory disturbance index (RDI) were evaluated using the Epworth Sleepiness Scale (ESS) and an overnight type 3 sleep monitor. RESULTS: The percentages of young heavyweight-class judo players with EDS (ESS ≥11) and those with SDB (RDI ≥5) were both 63%, which was unexpectedly high for the age class. Seven of the participants underwent continuous positive airway pressure therapy, which improved both RDI and ESS scores (p<0.05 for each) and subsequently the sleep quality and judo performance of the participants. CONCLUSIONS: Our study indicates that young judo players might silently suffer from SDB, leading to poorer judo performance and to future cardiovascular diseases. Clinicians should be aware of the possible presence of SDB in young sports players and consider the application of diagnostic and therapeutic remedies.

Findings of contrast-enhanced ultrasonography with Sonazoid for cholangiocellular adenoma in three dogs.

Contrast-enhanced ultrasonography (CEUS) is useful to distinguish benign and malignant focal liver lesions in dogs. Cholangiocellular adenoma is an extremely rare benign tumor in dogs and has not been examined using CEUS with Sonazoid. The aim of this study was to describe findings of CEUS with Sonazoid in three dogs with cholangiocellular adenoma. All three dogs showed contrast defects in the Kupffer phase and these findings mimicked malignant neoplasia during the Kupffer phase. Moreover, all dogs showed early washout and hypoechoic lesions relative to the surrounding normal liver parenchyma in the portal phase. To our knowledge, this is the first study to report that CEUS findings of cholangiocellular adenoma with Sonazoid mimicked malignancy in three dogs.

Plasma-free amino acid profiles in dogs with hepatocellular carcinoma.

BACKGROUND: Metabolomic analysis using blood samples has been suggested to be useful for the early detection of cancer. Among metabolites, plasma-free amino acid (PFAA) profiles are potential diagnostic biomarkers for several diseases including cancer. However, the relationship between PFAA concentrations and liver tumors in dogs remains unknown. OBJECTIVE: To determine the characteristics of PFAA profiles of dogs with hepatocellular carcinoma (HCC) and correlated clinical features. ANIMALS: Thirty-four client-owned dogs diagnosed with HCC (n = 26) and benign liver diseases (n = 8) and 11 age-matched healthy dogs. METHODS: Prospective study using heparinized blood samples from fasted dogs. Plasma was deproteinized, and the concentrations of 21 amino acids were measured using an automated high-performance liquid chromatography amino acid analyzer. RESULTS: Plasma glutamic acid concentrations were significantly different among groups (P < .0024 after Bonferroni correction). Compared to healthy dogs, dogs with HCC and benign liver diseases had significantly higher concentrations of glutamic acid by post hoc analysis. However, no significant difference in the PFAA profiles of HCC and benign liver diseases were detected. In addition, preoperative and postoperative PFAA profiles of dogs with HCC were not significantly different. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased glutamic acid concentrations might play a role in the development or be a consequence of liver tumor formation. However, PFAA profiles of HCC could not be differentiated from those of benign lesions. In addition, glutamic acid concentrations did not change after surgical resection. These results indicate that PFAA profiles may not be useful biomarkers for detecting HCC in dogs.

Effect of acute volume loading on left atrial strain values derived from two-dimensional speckle tracking echocardiography in dogs.

The purpose of this study was to evaluate the cardiac acute volume loading effect on left atrial (LA) strain and strain rate (SR) parameters derived from two-dimensional speckle tracking echocardiography (2D-STE) in healthy dogs. Six healthy beagles were anesthetized and subjected to increase cardiac preload by intravenous infusion with lactated Ringer solution at 150 ml/kg/hr for 90 min. A Swan-Ganz catheter was placed to directly measure the mean pulmonary capillary wedge pressure (PCWP). Echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 min after acute volume loading began. Apical 4-chamber images focused on the LA were digitally recorded for later strain and SR analysis via 2D-STE. Acute volume loading significantly increased from baseline during LA strain and SR as assessed by the speckle tracking-based technique during reservoir and conduit function at 15 to 90 min after volume load began, and strain indices representing booster pump function were enhanced at 45 to 90 min. In addition, acute volume loading resulted in a significantly greater PCWP after fluid infusion. On multiple regression analysis, quadratic regression analysis was a better fit for the relationship between PCWP and all LA functional indices. Our findings indicated that LA function analyzed by strain and SR was enhanced during cardiac acute volume loading in healthy dogs. The change in strain and SR during acute volume loading should be interpreted with caution during the diagnosis of heart diseases related to volume overload.

Predictive factors of malignancy in dogs with focal liver lesions using clinical data and ultrasonographic features.

A definitive diagnosis of focal liver lesions (FLLs) requires invasive procedures for histopathologic examination. Thus, a simpler noninvasive diagnostic method, such as conventional ultrasonography combined with clinical data, is needed for the prediction of liver malignancy. The objective of this study was to examine the diagnostic accuracy of clinical data and ultrasonographic (US) features to differentiate benign and malignant liver lesions. Medical records and US images from dogs with FLLs that underwent abdominal US and histopathologic examinations following surgery or liver biopsy were retrospectively reviewed. Clinical data, including signalment, clinical signs and laboratory findings, and the US features of liver lesions that could act as predictive factors were assessed using univariate and multivariate analyses to evaluate the associations between predictive factors and liver malignancy. Based on the histopathologic results, 55 dogs with malignant lesions and 28 dogs with benign lesions were included in the study. The results of univariate analysis showed that several US features and platelet count were significantly associated with liver malignancy. Multivariate analysis revealed that the platelet count (thrombocytosis; odds ratio [OR]: 4.13, 95% confidence intervals [CI]: 1.81-9.41), lesion size (4.1 cm or greater; OR: 23.83, 95% CI: 3.74-151.95) and echotexture of FLLs (heterogenous; OR: 8.44; 95% CI: 1.37-51.91) were independent predictors for differentiating benign and malignant liver lesions, suggesting that a combination of clinical data and US findings of FLLs could predict liver malignancy in dogs.

Long-term safety and efficacy of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, added on glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week open-label, multicenter, post-marketing clinical study.

AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor that is currently used to treat patients with type 2 diabetes mellitus. The aim of the present study was to evaluate the safety and efficacy of tofogliflozin add-on to glucagon-like peptide-1 (GLP-1) receptor agonist monotherapy. MATERIALS AND METHODS: In this 52-week, prospective, multicenter, single arm, post-marketing clinical study, Japanese patients who had already been receiving GLP-1 receptor agonist monotherapy for ≥8 weeks, glycated hemoglobin ≥7.0 and <10.5%, and body mass index ≥18.5 and <35.0 kg/m2 were enrolled. Tofogliflozin 20 mg was orally administered once daily for 52 weeks with GLP-1 receptor agonist. Primary end-points were safety and change in glycated hemoglobin from baseline to week 52. Safety was assessed on the basis of the adverse events. Changes from baseline in fasting plasma glucose, bodyweight, blood pressure, uric acid and lipid parameters were assessed as secondary efficacy end-points. RESULTS: Of the 67 patients enrolled, 63 patients completed the study. Overall, 26 adverse drug reactions occurred in 17 patients (25.4%). Adverse drug reactions with a frequency of two or more patients (3.0%) were constipation, thirst, dehydration and pollakiuria. Hypoglycemia (n = 1) was limited. With the addition of tofogliflozin to GLP-1 receptor agonist, the subsequent mean (standard deviation) reduction in glycated hemoglobin was -0.6% (1.0%; P < 0.0001). Fasting plasma glucose, bodyweight and blood pressure were significantly improved. CONCLUSIONS: Tofogliflozin add-on to GLP-1 receptor agonist monotherapy is an effective treatment option with an acceptable safety profile.