Effect of X-ray tube on image quality and pancreatic ductal adenocarcinoma conspicuity in pancreatic protocol dual-energy CT.

AIM: To compare the radiation dose, image quality, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic protocol dual-energy computed tomography (CT) between two X-ray tubes mounted in the same CT machine. MATERIAL AND METHODS: This retrospective study comprised 80 patients (median age, 73 years; 45 men) who underwent pancreatic protocol dual-energy CT from January 2019 to March 2022 using either old (Group A, n=41) or new (Group B, n=39) X-ray tubes mounted in the same CT machine. The imaging parameters were completely matched between the two groups, and CT data were reconstructed at 70 and 40 keV. The CT dose-index volume (CTDIvol); CT attenuation of the abdominal aorta, pancreas, and PDAC; background noise; and qualitative scores for the image noise, overall image quality, and PDAC conspicuity were compared between the two groups. RESULTS: The CTDIvol was lower in Group B than Group A (7.9 versus 9.2 mGy; p<0.001). The CT attenuation of all anatomical structures at 70 and 40 keV was comparable between the two groups (p=0.06-0.78). The background noise was lower in Group B than Group A (12 versus 14 HU at 70 keV, p=0.046; and 26 versus 30 HU at 40 keV, p<0.001). Qualitative scores for image noise and overall image quality at 70 and 40 keV and PDAC conspicuity at 40 keV were higher in Group B than Group A (p<0.001-0.045). CONCLUSION: The latest X-ray tube could reduce the radiation dose and improve image quality in pancreatic protocol dual-energy CT.

Computed Tomography and 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Imaging Biomarkers of Lung Invasive Non-mucinous Adenocarcinoma: Prediction of Grade 3 Tumour Based on World Health Organization Grading System.

AIMS: To evaluate computed tomography (CT) and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) findings of invasive non-mucinous adenocarcinoma (INMA) of the lung as a predictor of histological tumour grade according to 2021 World Health Organization (WHO) classification. MATERIALS AND METHODS: This retrospective study included consecutive patients with surgically resected INMA who underwent both preoperative CT and 18F-FDG-PET/CT. A three-tiered tumour grade was performed based on the fifth edition of the WHO classification of lung tumours. CT imaging features and the maximum standardised uptake value (SUVmax) were compared among the three tumour grades. RESULTS: In total, 214 patients with INMA (median age 70 years; interquartile range 65-76 years; 123 men) were histologically categorised: 36 (17%) as grade 1, 102 (48%) as grade 2 and 76 (35%) as grade 3. Pure solid appearance was more frequent in grade 3 (83%) than in grades 1 (0%) and 2 (26%) (P < 0.001). The SUVmax of the entire tumour was higher in grade 3 than in grades 1 and 2 (P < 0.001). Multivariable analysis revealed that pure solid appearance (odds ratio = 94.0; P < 0.001), round/oval shape (odds ratio = 4.01; P = 0.001), spiculation (odds ratio = 2.13; P = 0.04), air bronchogram (odds ratio = 0.40; P = 0.03) and SUVmax (odds ratio = 1.45; P < 0.001) were significant predictors for grade 3 INMAs. CONCLUSION: Pure solid appearance, round/oval shape, spiculation, absence of air bronchogram and high SUVmax were associated with grade 3 INMAs. CT and 18F-FDG-PET/CT were potentially useful non-invasive imaging methods to predict the histological grade of INMAs.

Deep-learning-based image reconstruction in dynamic contrast-enhanced abdominal CT: image quality and lesion detection among reconstruction strength levels.

AIM: To evaluate the use of deep-learning-based image reconstruction (DLIR) algorithms in dynamic contrast-enhanced computed tomography (CT) of the abdomen, and to compare the image quality and lesion conspicuity among the reconstruction strength levels. MATERIALS AND METHODS: This prospective study included 59 patients with 373 hepatic lesions who underwent dynamic contrast-enhanced CT of the abdomen. All images were reconstructed using four reconstruction algorithms, including 40% adaptive statistical iterative reconstruction-Veo (ASiR-V) and DLIR at low, medium, and high-strength levels (DLIR-L, DLIR-M, and DLIR-H, respectively). The signal-to-noise ratio (SNR) of the abdominal aorta, portal vein, liver, pancreas, and spleen and the lesion-to-liver contrast-to-noise ratio (CNR) were calculated and compared among the four reconstruction algorithms. The diagnostic acceptability was qualitatively assessed and compared among the four reconstruction algorithms and the conspicuity of hepatic lesions was compared between <5 and ≥5 mm lesions. RESULTS: The SNR of each anatomical structure (p<0.0001) and CNR (p<0.0001) were significantly higher in DLIR-H than the other reconstruction algorithms. Diagnostic acceptability was significantly better in DLIR-M than the other reconstruction algorithms (p<0.0001). The conspicuity of hepatic lesions was highest when using 40% ASiR-V and tended to lessen as the reconstruction strength level was getting higher in DLIR, especially in <5 mm lesions; however, all hepatic lesions could be detected. CONCLUSIONS: DLIR improved the SNR, CNR, and image quality compared with 40% ASiR-V, while making it possible to decrease lesion conspicuity using higher reconstruction strength.

Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies.

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non-human primates.

BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non-human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans. EXPERIMENTAL APPROACH: Intrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail-withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses. KEY RESULTS: Intracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal µ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses. CONCLUSIONS AND IMPLICATIONS: Taken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ-NOP receptor system in pain processing but also supports the therapeutic potential of NOP-related ligands as analgesics.

Long-term effect of epidural injection with sustained-release lidocaine particles in a rat model of postoperative pain.

BACKGROUND: Single applications of sustained-release local anaesthetics may provide prolonged pain relief without requiring indwelling catheters, but have not yet been investigated for epidural postoperative pain management. We synthesized injectable sustained-release lidocaine particles (SRLPs) from biodegradable polymers and examined their effect in a rat model of postoperative pain. METHODS: Two types of polylactic acid particles, SRLP-10 and SRLP-25, containing 10% or 25% lidocaine, respectively, were generated and the lidocaine release was evaluated in vitro for 14 days. The SRLPs were then injected epidurally in the male Sprague-Dawley rats immediately before they received a hindpaw incision (the postoperative pain model), and hindpaw hypersensitivity was evaluated with the von Frey test. Motor paralysis and coordination were also assessed using a paralysis score and rota-rod test. Neurotoxicity and inflammation of the spinal cord, cauda equina, and tissue surrounding the injection site were histologically evaluated. RESULTS: In vitro, SRLP-10 and SRLP-25 released lidocaine over 7 and 3 days, respectively. The in vivo injection of SRLP-10 (80 mg) produced anti-hypersensitivity with no evidence of motor paralysis for 7 days after the paw incision, and SRLP-25 (60 mg) inhibited postoperative hypersensitivity for 7 days. Temporary motor paralysis (15 min) was observed after the injection of SRLP-25 (even with 40 mg). Foreign body reactions were observed around the SRLP injection site at 1 and 4 weeks after injection. No histopathological changes were observed at 1 or 4 weeks. CONCLUSIONS: The epidural injection of SRLPs produced prolonged anti-hypersensitivity in a rat model of postoperative pain with no major complications.

[Thymic carcinoid tumor with Cushing syndrome].

A case of a 71-year-old male with ectopic adrenocorticotropic polypeptide (ACTH)-producing thymic carcinoid tumor presenting Cushing's syndrome was reported. This patient had symptoms of fatigue and a polyposia for 2 years before a mediastinal tumor was detected. Chest computed tomography (CT) scan demonstrated an anterior mediastinal mass, and serum ACTH and cortisol level revealed very high. Secretion of cortisol was not inhibited in an 8-mg dexamethazone suppression test. We diagnosed ectopic ACTH-producing tumor, and performed complete excision of the thymus including thymic tumor. Histologically, the tumor demonstrated typical carcinoid with the positivity of ACTH immunostaining. After the operation, ACTH and cortisol levels were reduced and the clinical symptoms were improved rapidly. We have concluded that it is important to control serum perioperative cortisol level for the prevension of morbidity.

Cerebral blood volume changes in patients with eating disorders during word fluency: a preliminary study using multi-channel near infrared spectroscopy.

OBJECTIVE: This study investigated the characteristics of cerebral oxygenation changes in eating disorders patients (ED) and normal controls during the cognitive tasks, using a highly time-resolved, and non-invasive instrument. METHOD: Eleven female patients with anorexia nervosa or bulimia nervosa were recruited, and 11 healthy females participated. The relative concentrations of oxy-hemoglobin [o-Hb] and deoxy-hemoglobin [d-Hb] were measured during word fluency task using multichannel near infrared spectroscopy (NIRS). RESULTS: The increases of o-Hb and d-Hb during the task were compared between the groups. ED patients showed lower activation and a gradual increase in o-HB during the task. In the frontal, d-HB concentrations decreased during the task in ED patients. CONCLUSION: These specific patterns of oxygenation changes may indicate less supply and less demand of cerebral blood volume. Bedside measurements of cerebral oxygenation changes using NIRS are useful on understanding of neurophysiological features of ED.

Prognostic significance of lymph node involvement in middle and distal bile duct cancer.

BACKGROUND: Although lymph node involvement is considered an important prognostic factor, a detailed analysis has not been conducted in middle (Bm) and distal (Bi) bile duct cancer. METHODS: The histopathology of resections taken from 59 patients with Bm and Bi disease (Bm, 33 patients; Bi, 26 patients) was examined. The prevalence of lymph node involvement and its relationship to recurrence and prognosis were investigated. Survival rates were investigated according to the number of metastatic lymph nodes found, the TNM nodal stages, and the nodal stage classifications of The General Rules of the Japanese Society of Biliary Surgery. RESULTS: The frequency of nodal involvement in Bm and Bi was 45.5% and 30.8%, respectively. A significant correlation existed between a patient's prognosis and his TNM nodal stage, Japanese Society of Biliary Surgery nodal stage, and the number of metastatic lymph nodes found (P <.0001, respectively). Among 8 sites of postoperative recurrence, metastasis occurred most frequently in the liver (16/23). Patients with nodal involvement had a significantly higher rate of liver metastasis (10/23) than those without it (6/36) (P =.024). CONCLUSIONS: The number of metastatic lymph nodes found in patients with Bm or Bi cancer, and the nodal stage of their nodes, are significant prognostic indicators. Patients with nodal involvement are at high risk for liver metastasis in Bm and Bi disease.

Infrequent microsatellite instability in biliary tract cancer.

BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been reported in several tumors. However, few reports are available concerning MSI in biliary tract cancers. We investigated MSI and allelic loss at the hMLH1 and hMSH2 gene loci in biliary tract cancers. METHODS: We analyzed microsatellite alterations using 7 microsatellite markers in 38 cases of extrahepatic bile duct (EHBD) cancer and 16 cases of ampullary cancer using polymerase chain reaction and an automated fluorescent DNA sequencer. RESULTS: A MSI prevalence of 13.2% (5/38) was observed for EHBD cancer and a prevalence of 12.5% (2/16) was observed for ampullary cancer. Loss of heterozygosity at the hMLH1 and hMSH2 gene loci were observed in 4% (1/25 informative cases) and 6.1% (2/33) of EHBD cancer cases, respectively; and in 11.1% (1/9) and 8.3% (1/12) of ampullary cancer cases, respectively. The cumulative survival rate of patients with MSI was significantly better than that of patients without MSI in EHBD cancer. However, MSI was not an independent prognostic factor. CONCLUSIONS: Our results suggest that genetic defects in the DNA mismatch repair system and MSI do not play an important role in the majority of biliary tract cancers.

DNA mapping of gastric cancers using flow cytometric analysis.

Although numerous studies of gastric cancers on DNA ploidy have been reported, differences in the degree of aneuploidy (DNA index, DI) during progression have not been identified. We attempted to chart the differences in DIs during progression to clarify the role of aneuploidy in gastric cancers. We classified the gastric cancers examined into intestinal (n = 88) and diffuse (n = 48) types, and then analyzed 136 gastric cancers (intramucosal cancer, 42; submucosal cancer, 39; advanced cancer, 55) by flow cytometry using multiple sampling. In addition, we examined the DNA ploidy pattern of mucosal and submucosal lesions using the same submucosal cancers to study the tumor progression in individual cancers. Intratumoral DNA differences in DNA ploidy were observed in both types of gastric cancers. In intestinal-type cancers, multiple subclones indicated by a different DI occurred during the early stage of gastric cancers, whereas in diffuse-type cancers, multiple subclones were found primarily in advanced cancers. Although the DI varied widely in early intestinal-type cancers between 1.0 and 2.0, in early diffuse-type cancers, the DI tended to be less than 1.2. However, in advanced stage gastric cancers, the DI distribution was similar for both histological types. In intestinal-type cancers, high DI (>1.3) aneuploidy was frequently found in mucosal lesions. In contrast, only low DI (<1.2) aneuploid clones were observed in mucosal lesions of diffuse-type cancers. The present results suggest that high DI aneuploid tumor clones in intramucosal cancers acquire invasive ability when they progress to submucosal cancers, whereas DNA aneuploidy itself plays an important role in submucosal invasion of diffuse-type cancers.

Clarithromycin-resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Japan.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin is mostly due to the point mutations in the 23S rRNA. In Japan, however, the frequency of these mutations has not been fully investigated. Furthermore, no study has used gastric biopsy specimens to detect these point mutations. METHODS: The frequency of primary clarithromycin-resistant H. pylori was examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Eighty-two strains (42 isolated from patients with gastric cancer and 40 isolated from patients with chronic gastritis) were examined. Two biopsy specimens obtained from patients in whom eradication therapy including clarithromycin had failed were also studied. RESULTS: Either A2143G or A2144G point mutation was detected in 90% of clarithromycin-resistant H. pylori strains. Eight out of 82 strains (9.8%) had either A2143G or A2144G point mutation. Only one out of 42 strains in patients with gastric cancer had A2143G mutation, whereas five strains had A2144G and two had A2143G mutations in 40 strains isolated from control subjects. The proportion was significantly lower in patients with early gastric cancer (P < 0.05). This PCR-RFLP was also applicable for DNA samples extracted from biopsy specimens and infection of clarithromycin-resistant H. pylori was observed. CONCLUSION: The results suggest that the point mutation in the 23S rRNA gene is commonly seen in clarithromycin-resistant H. pylori and it contributes to the treatment failure in Japan. The PCR-RFLP system is a sensitive method by which to diagnose H. pylori infection as well as a simple method for detecting clarithromycin resistance without bacterial culture.

An automated prediction of MHC class I-binding peptides based on positional scanning with peptide libraries.

Specificities of three mouse major histocompatibility complex (MHC) class I molecules, Kb, Db, and Ld, were analyzed by positional scanning using combinatorial peptide libraries. The result of the analysis was used to create a scoring program to predict MHC-binding peptides in proteins. The capacity of the scoring was then challenged with a number of peptides by comparing the prediction with the experimental binding. The score and the experimental binding exhibited a linear correlation but with substantial deviations of data points. Statistically, for approximately 80% of randomly chosen peptides, MHC-binding capacity could be predicted within one log concentration of peptides for a half-maximal binding. Known cytotoxic T-lymphocyte epitope peptides could be predicted, with a few exceptions. In addition, frequent findings of MHC-binding peptides with incomplete or no anchor amino acid(s) suggested a substantial bias introduced by natural antigen processing in peptide selection by MHC class I molecules.

Aberrations of the K-ras, p53, and APC genes in extrahepatic bile duct cancer.

BACKGROUND AND OBJECTIVES: The genetic alterations involved in extrahepatic bile duct (EHBD) cancer are poorly understood. Our aim was to identify aberrations of the K-ras, p53, and APC genes in EHBD cancer. METHODS: We investigated aberrations of these genes in 52 EHBD cancers using polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, followed by direct sequence determination and a PCR restriction fragment length polymorphism assay. RESULTS: The K-ras, p53, and APC genes were mutated in 9.6%, 32.7%, and 0% of EHBD cancers, respectively. Loss of heterozygosity at the p53 and APC gene loci was identified in 15.6% and 38.5% of EHBD cancers, respectively. CONCLUSIONS: Our results suggest that an unknown suppressor gene on 5q other than the APC gene may be responsible for EHBD cancer.

Biological properties of opioid peptides replacing Tyr at position 1 by 2,6-dimethyl-Tyr.

To understand the effect of the replacement of Tyr residue at position 1 in opioid peptides by 2,6-dimethyl-Tyr (Dmt) on the biological property, chiral (D or L) Dmt1 analogs of Leu-enkephalin (Enk) and Tyr-D-Arg-Phe-beta Ala-NH2 (YRFB) were synthesized and their enzymatic stabilities, in vitro bioactivities and receptor binding affinities compared with those of parent peptides. [L-Dmt1]Enk (1) exhibited 4-fold higher stability against aminopeptidase-M and possessed dramatically increased activities in guinea pig ilium (GPI) (187-fold) and mouse vas deferens (MVD) (131-fold) assays, and in rat brain receptor binding assays (356-fold at mu receptor and 46-fold at delta receptor) as compared to Enk. [L-Dmt1]YRFB (3) also exhibited increased activities in GPI (46-fold) and MVD (177-fold) assays, and in the binding assays (69-fold at mu receptro and 341-fold at delta receptor) as compared to the parent peptide. [D-Dmt1]Enk (2) and [D-Dmt1]YRFB (4) exhibited activities with diminished or lesser potency than the parent peptide in all assays. These results indicate that there is a tendency for mu affinity to be enhanced more than delta affinity with introduction of L-Dmt into delta ligand peptide (Enk), and for delta affinity to be enhanced more than mu affinity in case of mu ligand peptide (YRFB), resulting in reduced receptor selectivities at the receptors.

High-dose natural interferon-alpha therapy for chronic hepatitis C with a high viral load: predictors of efficacy. The Aomori, Akita and Iwate Areas Viral Hepatitis Research Group.

BACKGROUND: The effectiveness of interferon against hepatitis C has been found to be greatly affected by viral factors. However, few controlled interferon trials have involved seemingly intractable cases of chronic hepatitis C. METHODS: In 44 patients with high hepatitis C virus RNA levels (> or = 10(5) copies/mL), we carried out a prospective, controlled study of two natural interferon-alpha regimens, seeking predictors of therapeutic efficacy. Total natural interferon-alpha doses over 6 months in two groups were 780 and 840 million units, respectively. RESULTS: High therapeutic efficacy was achieved with no significant outcome difference between the regimens. The virus eradication rate was 35% and the rate of sustained biochemical response was 45% for both regimens. Multivariate logistic regression analysis identified viral genotype as the only significant predictor of success in viral eradication. CONCLUSIONS: Hepatitis C virus genotype 2 showed high sensitivity to interferon-alpha and this therapy can be recommended even for patients with a high viral load of this genotype. In contrast, with genotype 1b, cure was extremely difficult in cases with 10(7) or more copies/mL with a single 6-month course of interferon-alpha.

Role of DNA aneuploidy, overexpression of p53 gene product, and cellular proliferation in the progression of gastric cancer.

DNA aneuploidy, p53 overexpression, and high cell proliferation frequently occur in gastric cancer. However, little is known about the time of their appearance throughout cancer progression. Therefore, the objective of the present study was to determine when such abnormalities occur during gastric cancer progression. We classified the gastric cancers examined into intestinal (n = 65) and diffuse (n = 34) types. DNA ploidy was examined using flow cytometry and expression of MIB-1 and p53 immunoreactivity were studied using the avidin-biotin complex method in three stages of gastric cancer (mucosal, submucosal, deeply invasive cancer, i.e., advanced cancer). The incidence of DNA aneuploidy in intestinal-type mucosal cancers (15/27, 55.6%) was lower than that of submucosal invasive cancers (14/16, 87.5%) or advanced cancers (19/22, 86.4%), while a low incidence of DNA aneuploidy was observed in each diffuse-type cancer group (mucosal, 1/12, 8.3%; submucosal invasive, 3/9, 33.3%; advanced, 8/14, 57.1%). Although overexpression of the p53 gene in intestinal-type cancer was found in early stage, that in diffuse-type cancer was observed in advanced stage. Among the intestinal-type mucosal cancers, the MIB-1 percent positive was higher in aneuploid tumors than diploid ones. DNA aneuploidy and overexpression of the p53 gene may play an important role in the early tumorigenesis of intestinal-type gastric cancer and in the late event of tumorigenesis of diffuse-type gastric cancer.