Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning-based filter using convolutional neural network.

OBJECTIVES: To reveal the utility of motion artifact reduction with convolutional neural network (MARC) in gadoxetate disodium-enhanced multi-arterial phase MRI of the liver. METHODS: This retrospective study included 192 patients (131 men, 68.7 ± 10.3 years) receiving gadoxetate disodium-enhanced liver MRI in 2017. Datasets were submitted to a newly developed filter (MARC), consisting of 7 convolutional layers, and trained on 14,190 cropped images generated from abdominal MR images. Motion artifact for training was simulated by adding periodic k-space domain noise to the images. Original and filtered images of pre-contrast and 6 arterial phases (7 image sets per patient resulting in 1344 sets in total) were evaluated regarding motion artifacts on a 4-point scale. Lesion conspicuity in original and filtered images was ranked by side-by-side comparison. RESULTS: Of the 1344 original image sets, motion artifact score was 2 in 597, 3 in 165, and 4 in 54 sets. MARC significantly improved image quality over all phases showing an average motion artifact score of 1.97 ± 0.72 compared to 2.53 ± 0.71 in original MR images (p < 0.001). MARC improved motion scores from 2 to 1 in 177/596 (29.65%), from 3 to 2 in 119/165 (72.12%), and from 4 to 3 in 34/54 sets (62.96%). Lesion conspicuity was significantly improved (p < 0.001) without removing anatomical details. CONCLUSIONS: Motion artifacts and lesion conspicuity of gadoxetate disodium-enhanced arterial phase liver MRI were significantly improved by the MARC filter, especially in cases with substantial artifacts. This method can be of high clinical value in subjects with failing breath-hold in the scan. KEY POINTS: • This study presents a newly developed deep learning-based filter for artifact reduction using convolutional neural network (motion artifact reduction with convolutional neural network, MARC). • MARC significantly improved MR image quality after gadoxetate disodium administration by reducing motion artifacts, especially in cases with severely degraded images. • Postprocessing with MARC led to better lesion conspicuity without removing anatomical details.

Genetic variation and local differences in Pacific cod Gadus macrocephalus around Japan.

The population structure of the Pacific cod Gadus macrocephalus was examined using 15 microsatellite loci and mitochondrial DNA (ND2 region). In total, 274 individuals were sampled from 16 locations around Japan to estimate the level of genetic differentiation and effective population size (Ne ). Pairwise FST , analysis of molecular variance and Bayesian clustering analysis suggested the presence of two genetically distinct groups in waters around Japan, with a higher Ne value in the eastern group than in the western group. A possible factor that restricts gene flow between groups may be related to the water temperature differences in the south-western part of the Sea of Japan, where the Tsushima Warm Current flows around the area inhabited by the western group, which may limit migration between the west and east.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study.

BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.

Antagonistic selection factors induce a continuous population divergence in a polymorphism.

Understanding the relative importance of selection and stochastic factors in population divergence of adaptive traits is a classical topic in evolutionary biology. However, it is difficult to separate these factors and detect the effects of selection when two or more contrasting selective factors are simultaneously acting on a single locus. In the damselfly Ischnura senegalensis, females exhibit color dimorphism and morph frequencies change geographically. We here evaluated the role of selection and stochastic factors in population divergence of morph frequencies by comparing the divergences in color locus and neutral loci. Comparisons between population pairwise FST for neutral loci and for the color locus did not detect any stochastic factors affecting color locus. Although comparison between population divergence in color and neutral loci using all populations detected only divergent selection, we detected two antagonistic selective factors acting on the color locus, that is, balancing and divergent selection, when considering geographical distance between populations. Our results suggest that a combination of two antagonistic selective factors, rather than stochastic factors, establishes the geographic cline in morph frequency in this system.

Relationship between clinical factors and severity of esophageal candidiasis according to Kodsi's classification.

Severe Candida esophagitis (CE) may lead to development of strictures, hemorrhage, esophagotracheal fistula, and a consequent decrease in quality of life. Although the severity of CE has been classified based on macroscopic findings on endoscopy, the clinical significance remains unknown. The aim of the study was to elucidate the predictive clinical factors for endoscopic severity of CE. Patients who underwent upper endoscopy and answered questionnaires were prospectively enrolled. Smoking, alcohol, human immunodeficiency virus (HIV) infection, diabetes mellitus, chronic renal failure, liver cirrhosis, systemic steroids use, proton pump inhibitor use, H2 blocker use, and gastrointestinal (GI) symptoms were assessed on the same day of endoscopy. GI symptoms including epigastric pain, heartburn, reflux, hunger cramps, nausea, dysphagia, and odynophagia were assessed on a 7-point Likert scale. Endoscopic severity was classified as mild (Kodsi's grade I/II) or severe (grade III/IV). Of 1855 patients, 71 (3.8%) were diagnosed with CE (mild, n = 48; severe, n = 23). In the CE patients, 50.0% (24/48) in the mild group and 23.1% (6/23) in the severe group did not have any GI symptoms. In HIV-infected patients (n = 17), a significant correlation was found between endoscopic severity and declining CD4 cell count (Spearman's rho = -0.90; P < 0.01). Multivariate analysis revealed that GI symptoms (odds ratio [OR], 3.32) and HIV infection (OR, 3.81) were independently associated with severe CE. Patients in the severe group experienced more epigastric pain (P = 0.02), reflux symptoms (P = 0.04), dysphagia (P = 0.05), and odynophagia (P < 0.01) than those in the mild group. Of the GI symptoms, odynophagia was independently associated with severe CE (OR 9.62, P = 0.02). In conclusion, the prevalence of CE in adults who underwent endoscopy was 3.8%. Silent CE was found in both mild and severe cases. Endoscopic severity was associated with characteristic GI symptoms and comorbidity of HIV infection. A decline in immune function correlated with CE disease progression.

Urinary steroid profiling using liquid chromatography-tandem mass spectrometry for the diagnosis of canine Cushing's syndrome.

Serum cortisol measurements by chemiluminescence enzyme immunoassay (CLEIA) are widely used to diagnose hypercortisolism (HC) or Cushing's syndrome in dogs. However, they are associated with problems such as the need for multiple blood collections under stressful conditions or cross-reactivity between hormones. Therefore, a less invasive and more accurate diagnostic method is required. This study aimed to develop a urinary steroid profile analysis method using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and to evaluate its clinical usefulness. Sixty-five healthy dogs and 38 dogs with suspected HC were included in the study. Using LC/MS/MS, the levels of 11 steroid hormones in the urine were determined. We established the upper limit of the reference interval for each urinary steroid-to-creatinine ratio and evaluated their diagnostic performances. The levels of the five steroid hormones were significantly higher in the 14 dogs with HC than in the 24 dogs with mimicking HC and 65 healthy dogs. The urinary corticosterone-to-creatinine ratio showed the highest diagnostic accuracy (area under the curve, 0.96). A significant correlation was seen between urinary cortisol concentrations measured by LC/MS/MS and CLEIA (rs = 0.88, P <0.001), although the CLEIA measurements were significantly higher than the LC/MS/MS measurements (P <0.001). LC/MS/MS-based urinary steroid profiles are a promising tool for diagnosing canine HC.

Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound in a dog with trilostane-induced hypoadrenocorticism.

A 12-year-old neutered male Chihuahua dog was diagnosed with pituitary-dependent hypercortisolism and treated with trilostane. Eighty-nine days later, the dog showed lethargy accompanied by hyponatraemia and hyperkalaemia. Hypoadrenocorticism due to trilostane was suspected, but the result of the adrenocorticotropic hormone stimulation test was not conclusive. Contrast-enhanced ultrasound showed loss of adrenocortical blood flow in both adrenal glands, indicating adrenocortical hypoperfusion and isolated hypoadrenocorticism. Treatment with fludrocortisone acetate improved the condition and electrolyte abnormalities. Thirteen months later, the dog showed alopecia, and an adrenocorticotropic hormone stimulation test revealed increased cortisol concentration, indicating hypercortisolism recurrence. The dog died due to progressive deterioration 22 months after the initial presentation. Post-mortem examination revealed focally extensive necrosis with marked calcification in the parenchyma of the adrenal glands and regeneration of the cells in the zona fasciculata with severe fibrosis. Adrenocortical hypoperfusion detected by contrast-enhanced ultrasound can support the diagnosis of adrenal necrosis and hypoadrenocorticism.

In vitro susceptibility testing of Dientamoeba fragilis.

Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to evaluate the susceptibility of D. fragilis to several commonly used antiparasitic agents: diloxanide furoate, furazolidone, iodoquinol, metronidazole, nitazoxanide, ornidazole, paromomycin, secnidazole, ronidazole, tetracycline, and tinidazole. Antibiotic susceptibility testing was performed on four clinical strains of D. fragilis, designated A, E, M, and V, respectively. Molecular testing followed, and all strains were determined to be genotype 1. The activities of antiprotozoal compounds at concentrations ranging from 2 µg/ml to 500 µg/ml were determined via cell counts of D. fragilis trophozoites grown in dixenic culture. Minimum lethal concentrations (MLCs) were as follows: ornidazole, 8 to 16 µg/ml; ronidazole, 8 to 16 µg/ml; tinidazole, 31 µg/ml; metronidazole, 31 µg/ml; secnidazole, 31 to 63 µg/ml; nitazoxanide, 63 µg/ml; tetracycline, 250 µg/ml; furazolidone, 250 to 500 µg/ml; iodoquinol, 500 µg/ml; paromomycin, 500 µg/ml; and diloxanide furoate, >500 µg/ml. This is the first study to report the profiles of susceptibility to a wide range of commonly used treatments for clinical isolates of D. fragilis. Our study indicated 5-nitroimidazole derivatives to be the most active compounds in vitro against D. fragilis.

Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA.

AIMS: To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. METHODS: Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. RESULTS: All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. CONCLUSIONS: Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE.

Divergence of ovipositor length and egg shape in a brood parasitic bitterling fish through the use of different mussel hosts.

Bitterling fishes deposit their eggs on the gills of living mussels using a long ovipositor. We examined whether ovipositor length (OL) and egg shape correlated with differences in host mussel species in the family Unionidae among populations of the tabira bitterling (Acheilognathus tabira) in Japan. Bitterling populations that use mussels in the sub-family Anodontinae possessed longer ovipositors and more elongated eggs than those using mussels of Unioninae, as expected from the difference in host size between the sub-families (anodontine mussels are larger than unionine mussels). Based on a robust phylogeny of A. tabira populations, we demonstrated that the evolution of both OL and egg shape were correlated with host differences, but not with each other, suggesting that these traits have been selected for independently. Our study demonstrates how adaptive traits for brood parasitism may diverge with host shift due to different host availability and/or interspecific competition for hosts.

Predictive value of endoscopic findings in the diagnosis of active intestinal amebiasis.

Endoscopic diagnosis of amebic colitis can be difficult because its appearance may mimic other forms of colonic disease. The aim of this study was to identify predictive endoscopic findings for amebic colitis. Patients with suspected amebic colitis based on distinctive endoscopic findings such as aphthae or erosions, ulcers, exudates, or a bump, were included in the study. A total of 157 patients were selected, 50 of whom had amebic colitis. The sensitivity and specificity of endoscopic findings that were significantly associated with amebic colitis were: cecal lesions (80% and 54%), multiple number of lesions (96% and 29%), presence of aphthae or erosions (84% and 37%), and presence of exudate (88% and 74%). Multivariate analysis revealed that the best combination of findings to predict amebic colitis was the presence of cecal lesions, multiple lesions, and exudates, which corresponded to an area under the receiver operating characteristic curve of 0.89 (95% confidence interval 0.82-0.95).

Recurrence of colonic diverticular bleeding and associated risk factors.

AIM: Colonic diverticular bleeding often recurs, but the risk factors remain unclear. Our aim was to identify risk factors for recurrence in patients with diverticular bleeding. METHOD: Seventy-two hospitalized patients who were diagnosed with diverticular bleeding between 2004 and 2008 were analyzed. Rebleeding was considered as the main outcome measure, with the duration until recurrence identified from medical records. Potential risk factors for rebleeding, such as underlying pathologies, medication and smoking and drinking habits, were investigated from the medical records on initial admission. RESULTS: Of the 72 patients, 19 had a diverticular disease on the right, 16 on the left side and 37 on both sides of the colon. Recurrence was identified in 27 (38%) patients at a median interval of 1535 days. The cumulative incidence of rebleeding at 6, 12 and 24 months was 15%, 20% and 33%. Multivariate analysis revealed nonsteroid anti-inflammatory drugs (NSAIDs) (hazard ratio (HR), 2.57; 95% confidence interval (CI), 0.89-7.46; P=0.08), antiplatelet drugs (HR, 2.39; 95% CI, 1.01-5.67; P=0.05) and hypertension (HR, 4.16; 95% CI, 1.22-14.2; P=0.02) to be risk factors for rebleeding. CONCLUSION: Patients with colonic diverticular bleeding show high recurrence rates within a short period. Risk factors for recurrence have been identified as the use of NSAIDs or antiplatelet drugs and hypertension.

Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder.

The etiopathogenesis of focal and segmental glomerular sclerosis (FGS) remains unknown. Using a new animal model for FGS (FGS mouse), we demonstrate here that bone marrow transplantation from normal mice to FGS mice with a high grade of proteinuria (+ + +) ameliorates FGS, and that the transplantation of bone marrow cells or purified hemopoietic stem cells (HSCs) from FGS mice induces FGS in normal mice. These findings strongly suggest that FGS is a stem cell disorder; the abnormalities may be genetically programmed at the level of HSCs.

Studies of severe acute respiratory syndrome coronavirus pathology in human cases and animal models.

During the severe acute respiratory syndrome (SARS) outbreak of 2003, approximately 10% of SARS patients developed progressive respiratory failure and died. Since then, several animal models have been established to study SARS coronavirus, with the aim of developing new antiviral agents and vaccines. This short review describes the pathologic features of SARS in relation to their clinical presentation in human cases. It also looks at animal susceptibility after experimental infection, animal models of SARS, and the pathogenesis of this disease. It seems that adaptation of the virus within the host animal and the subsequent abnormal immune responses may be key factors in the pathogenesis of this new and fatal respiratory disease. The proteases produced in the lung during inflammation could also play an important role for exacerbation of SARS in animals.

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes.

AIM/HYPOTHESIS: Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes. METHODS: Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young non-diabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 age-matched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR. RESULTS: In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p < 0.05) lower in patients with diabetes than in non-diabetic individuals at one or more time points. Moreover, the amplitudes of mRNA expression rhythms of PER1 and PER3 genes tended to diminish in patients with diabetes. In study 2, leucocytes obtained from patients with diabetes expressed significantly (p < 0.05) lower transcript levels of BMAL1, PER1 and PER3 compared with leucocytes from control individuals, and transcript expression was inversely correlated with HbA(1c) levels (rho = -0.47 to -0.55, p < 0.05). CONCLUSIONS/INTERPRETATION: These results suggest that rhythmic mRNA expression of clock genes is dampened in peripheral leucocytes of patients with type 2 diabetes. The impairment of the circadian clock appears to be closely associated with the pathophysiology of type 2 diabetes in humans.

Multicenter phase II study of FOLFOX for metastatic colorectal cancer (mCRC) in Japan; SWIFT-1 and 2 study.

BACKGROUND/AIMS: This study assessed the efficacy and toxicity of the FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens in Japanese patients with metastatic colorectal cancer (mCRC). METHODOLOGY: Patients with mCRC were required to have ECOG performance status of 0 to 1, and to have adequate organ function. Two multicenter Phase II studies (SWIFT1/SWIFT2) were conducted in chemotherapy naive patients with mCRC. RESULTS: 112 patients were enrolled in these studies (SWIFT1: 54 patients / SWIFT2: 58 patients). The disease sites for each study were the colon in 27 patients and 28 patients, and the rectum in 27 patients and 30 patients, respectively. All patients received a median of 8 courses. After a median follow-up period of 35 months, 54 patients and 58 patients were evaluable in the respective studies, and the overall response rate was 50.0% (CR:31 PR:53). The response rate according to the sites of metastasis were as follows: liver, 54.1% (46/85); lung, 17.4% (4/23); and lymph node, 23.3% (7/30). Grade 3/4 neutropenia occurred in 14 patients (12.5%), while Grade 3/4 non-hematological toxicities were observed in 16 patients (31.0%) and Grade 3 neurotoxicity was observed in 6patients (5.4%) and 5 patients (4.5%), respectively. CONCLUSIONS: FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens complying with the international standard dosage and schedule can also be administered safely and effectively in Japan.

Epidemiology of massive hepatocellular carcinoma in dogs: A 4-year retrospective study.

Hepatocellular carcinoma (HCC) is the most common primary liver tumour in dogs. However, the clinical features and risk factors of HCC have not been confirmed. The objective of this study was to investigate the clinical features and risk factors for canine HCC. Medical records of 44 dogs diagnosed with HCC at Hokkaido University Veterinary Teaching Hospital between 2013 and 2017 were retrospectively reviewed. All dogs evaluated at the teaching hospital during the study period were used as the reference population for breed, age, sex predispositions or possible related factors for HCC, including concurrent disorders. Clinical characteristics of HCC were determined using propensity score matching analysis. The prevalence of HCC diagnosis was 0.96%. Multivariate analysis revealed that dogs diagnosed with HCC were significantly older (odds ratio [OR], 1.20; 95% confidence intervals [CI], 1.07-1.33) than the reference population. Welsh Corgis (OR, 3.68; 95% CI, 1.56-8.67) and Beagles (OR, 4.33; 95% CI, 1.58-11.90) were significantly predisposed to HCC. Twenty-seven of 44 dogs with HCC had at least one concurrent disorder. The most common concurrent disorder was hyperadrenocorticism (n = 10), and the adjusted odds of hyperadrenocorticism in dogs with HCC were 4.13 higher than those of the reference population (95% CI, 1.95-8.76). Propensity score matching analysis revealed that thrombocytosis (n = 30/43), increased alanine aminotransferase (n = 41/44), increased alkaline phosphatase (n = 42/44), and hypercalcemia (n = 13/32) were significantly associated with HCC diagnosis. The results of this study suggest that Welsh Corgis and Beagles are breeds with a predisposition for HCC and that hyperadrenocorticism might be a potential risk factor.

SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer.

BACKGROUND: Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.

Multicenter phase II trial of combination chemotherapy with weekly paclitaxel and 5-fluorouracil for the treatment of advanced or recurrent gastric carcinoma.

The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5-FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated.

Comparison of Survival Times for Dogs with Pituitary-Dependent Hyperadrenocorticism in a Primary-Care Hospital: Treated with Trilostane versus Untreated.

BACKGROUND: Although pituitary-dependent hyperadrenocorticism (PDH) is one of the most common endocrinopathies in dogs, the effects of withholding treatment on survival time in dogs with PDH remain unclear. HYPOTHESIS/OBJECTIVES: The purpose of this study was to clarify the effects of treatment in dogs with PDH by comparing survival times between dogs treated with trilostane and untreated dogs. ANIMALS: Forty-three dogs diagnosed with PDH at a primary-care hospital in Japan between June 2009 and January 2014. METHODS: Retrospective cohort study. The medical records of dogs with PDH treated with trilostane (n = 17) or left untreated (n = 26) were reviewed retrospectively. Survival analysis at 2 years after diagnosis of PDH was performed. RESULTS: Median survival time for the trilostane group was not reached (95% confidence interval [CI], 443 days-not applicable) and was significantly longer than the 506 days (95% CI, 292-564 days; P = .016) for the untreated group. Multivariate Cox proportional hazards analysis (including age at diagnosis, basal cortisol concentration at diagnosis, and treatment group) only identified assignment to the untreated group (hazard ratio, 5.01; 95% CI, 1.63-15.44) as associated with increased mortality. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this retrospective cohort study suggest that withholding treatment for dogs with PDH might be associated with a higher risk of death. This represents the largest study to date to report survival times of untreated dogs with PDH.