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Multidetector row computed tomography (MDCT) creates massive amounts of data, which can overload a picture archiving and communication system (PACS). To solve this problem, we designed a new data storage and image interpretation system in an existing PACS. Two MDCT image datasets, a thick- and a thin-section dataset, and a single-detector CT thick-section dataset were reconstructed. The thin-section dataset was archived in existing PACS disk space reserved for temporary storage, and the system overwrote the source data to preserve available disk space. The thick-section datasets were archived permanently. Multiplanar reformation (MPR) images were reconstructed from the stored thin-section datasets on the PACS workstation. In regular interpretations by eight radiologists during the same week, the volume of images and the times taken for interpretation of thick-section images with (246 CT examinations) or without (170 CT examinations) thin-section images were recorded, and the diagnostic usefulness of the thin-section images was evaluated. Thin-section datasets and MPR images were used in 79% and 18% of cases, respectively. The radiologists' assessments of this system were useful, though the volume of images and times taken to archive, retrieve, and interpret thick-section images together with thin-section images were significantly greater than the times taken without thin-section images. The limitations were compensated for by the usefulness of thin-section images. This data storage and image interpretation system improves the storage and availability of the thin-section datasets of MDCT and can prevent overloading problems in an existing PACS for the moment. [ABSTRACT FROM AUTHOR]

Objectives: Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC., Materials and Methods: A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS)., Results: A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy., Conclusions: This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

The assessment of programmed death-ligand 1 (PD-L1) expression in esophageal squamous cell carcinoma (ESCC) has become increasingly important with the rise of immune checkpoint inhibitors (ICIs). However, challenges persist, including subjective interpretation and the unclear significance of staining intensity, as well as contrasting roles in tumoral and stromal regions. Our study enhances the understanding of PD-L1 in ESCCs by analyzing its expression in tumors and stroma with H-scores, highlighting its distinct clinicopathological impacts. In a retrospective cohort of 194 ESCC specimens from surgical resection, we quantified PD-L1 expression in tumoral and stromal compartments using H-scores, analyzing whole slide images with digital pathology analysis software. Kaplan-Meier analysis demonstrated that higher PD-L1 expression is significantly associated with improved postoperative overall survival (OS) and recurrence-free survival (RFS) in both tumoral and stromal areas. Multivariable analysis identified high tumoral PD-L1 expression as an independent prognostic factor for prolonged OS and RFS (HR = 0.47, p = 0.007; HR = 0.54, p = 0.022, respectively). In a separate analysis, high stromal PD-L1 expression was found to correlate with less advanced pathological stages and a prolonged response to cytotoxic chemotherapy, with no similar correlation found for ICI treatment response. This study reveals PD-L1's contrasting role in the ESCC tumor immune microenvironment, impacting prognosis, tumor stage, and treatment response.

Background: Median arcuate ligament compression syndrome (MALS) causes upper abdominal pain and at times hemodynamic abnormalities in the pancreaticoduodenal region. Herein, we present a case of a 70 year-old man, initially diagnosed with splenic infarction and was successfully treated laparoscopically., Case Presentation: A 70-year-old man with abdominal pain admitted to our hospital. Abdominal-enhanced computed tomography revealed a poorly contrasted area in the spleen and stenosis at the root of the celiac artery. Arterial dilatation was observed around the pancreaticoduodenal arcade, however, no obvious aneurysm formation or arterial dissection was observed. Abdominal-enhanced magnetic resonance imaging indicated the disappearance of the flow void at the root of the celiac artery. The patient had no history of atrial fibrillation and was diagnosed with splenic infarction due to median arcuate ligament compression syndrome. We performed a laparoscopic median arcuate ligament section with five ports. Intraoperative ultrasonography showed a retrograde blood flow in the common hepatic artery and the celiac artery. After releasing the compression, the antegrade blood flow from the celiac artery to the splenic artery, and the common hepatic artery were visualized using intraoperative ultrasonography. The postoperative course of the patient was uneventful, and he was discharged on postoperative day 9. Postoperative computed tomography a month after surgery revealed no residual stenosis of the celiac artery or dilation of the pancreaticoduodenal arcade. Furthermore, the poorly contrasted area of the spleen improved., Conclusions: Reports indicate that hemodynamic changes in the abdominal visceral arteries due to median arcuate ligament compression are related to the formation of pancreaticoduodenal aneurysms. In this case, median arcuate ligament compression syndrome caused splenic infarction by reducing blood flow to the splenic artery., (© 2024. The Author(s).)

Tenascin C (TNC) is an extracellular matrix glycoprotein that is highly expressed in cancer stroma and is associated with tumor progression in pancreatic adenocarcinoma (PAAD). In this study, we aimed to investigate the potential involvement of TNC in the response to immune checkpoint inhibitors (ICI) among PAAD patients. Transcriptomic profiles were obtained from public databases and analyzed to compare TNC mRNA levels between tumor and normal tissues. Bioinformatic programs were used to predict paracrine communications between cancer cells and cancer-associated fibroblasts (CAFs), and the Tumor Immune Dysfunction and Exclusion (TIDE) score was calculated to predict response to ICI treatment in PAAD patients. An independent immunotherapeutic cohort was used to validate the clinical impact of the signatures. Results showed that TNC mRNA levels were significantly upregulated in tumors compared to normal tissues in PAAD, and patients with high TNC expression had significantly shorter overall survival than those with low TNC expression (P = 0.0125). TNC was predominantly expressed in CAFs of PAAD patients and was found to potentially enhance the epithelial-mesenchymal transition (EMT) of cancer cells via integrin receptors, contributing to resistance to ICI treatment. Patients with high TNC expression and high ITGαV or ITGB3 expression were associated with poor response to ICI therapy. In conclusion, these findings suggest that TNC -high CAFs play a crucial role in tumor progression and resistance to ICI therapy in PAAD patients, and targeting TNC and its interactions with cancer cells may provide a potential strategy for improving the efficacy of ICI therapy in PAAD., Competing Interests: None., (AJCR Copyright © 2023.)

The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment (TME) in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Here, we divide the sporadic colon cancer tissue samples with transcriptomic data into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs) and then, analyze the data using CIBERSORTx deconvolution software. EOCC tumors are more enriched in CAFs with fibroblast associated protein positive expression (FAP(+)) than LOCC tumors. EOCC patients with higher FAP mRNA levels in CAFs have shorter OS (Log-rank test, p < 0.029). Spatial transcriptomic analysis of 112 areas of interest, using NanoString GeoMx digital spatial profiling, demonstrate that FAP(+) CAFs at the EOCC tumor invasive margin show a significant upregulation of WNT signaling and higher mRNA/protein levels of fibroblast growth factor 20 (FGF20). Tumor epithelial cells at tumor invasive margin of EOCC tumors neighboring FAP(+) CAFs show significantly higher mRNA/protein levels of fibroblast growth factor receptor (FGFR2) and PI3K/Akt signaling activation. NichNET analysis show a potential interaction between FGF20 and FGFFR2. The role of FGF20 in activating FGFR2/pFGFR2 and AKT/pAKT was validated in-vitro. In conclusion, we identify a unique FAP(+) CAF population that showed WNT signaling upregulation and increased FGF20 levels; while neighbor tumor cells show the upregulation/activation of FGFR2-PI3K/Akt signaling at the tumor invasive margin of EOCC tumors., (© 2023. The Author(s).)

Background: Pseudoaneurysm (PA) rupture after pancreaticoduodenectomy (PD) is a life-threatening complication. Most PA cases originate from postoperative pancreatic fistulas (POPFs). Although several risk factors for POPF have been identified, specific risk factors for PA formation remain unclear. Therefore, we retrospectively analyzed PD cases with soft pancreas and proposed a novel strategy for early detection of PA formation., Methods: Overall, 120 patients underwent PD between 2010 and 2020 at our institution; of these, 65 patients with soft pancreas were enrolled. We evaluated the clinicopathological factors influencing PA formation and developed a risk score to predict PA formation., Results: In total, 11 of the 65 patients developed PAs (PA formation group: PAG), and 8 of these 11 PAs ruptured. The median time to PA formation was 15 days, with a minimum of 5 days. The PAG was significantly older than the non-PA formation group, were predominantly men, and had comorbid diabetes mellitus. Pre- and intra-operative findings were similar between the two groups. Importantly, no significant differences were found in postoperative drain amylase levels and total drain amylase content. Cholinesterase and C-reactive protein (CRP) levels on postoperative day (POD) 3 were significantly different between the two groups. Multivariate analysis showed that cholinesterase ≤ 112 U/L and CRP ≥ 16.0 mg/dl on POD 3 were independent predictors of PA formation., Conclusions: Decreased cholinesterase and elevated CRP on POD 3 (Cho-C score) are useful predictors of PA formation in cases with soft pancreas. In such cases, periodic computed tomography evaluations and strict drain management are necessary to prevent life-threatening hemorrhage., (© 2023. The Author(s).)

Background: The usefulness of static monitoring using central venous pressure has been reported for anesthetic management in hepatectomy. It is unclear whether intra-hepatectomy dynamic monitoring can predict the postoperative course. We aimed to investigate the association between intraoperative dynamic monitoring and post-hepatectomy complications. Furthermore, we propose a novel anesthetic management strategy to reduce postoperative complication., Methods: From 2018 to 2021, 93 patients underwent hepatectomy at our hospital. Fifty-three patients who underwent dynamic monitoring during hepatectomy were enrolled. Flo Trac system was used for dynamic monitoring. The baseline central venous oxygen saturation (ScvO 2 ) was defined as the average ScvO 2 for 30 min after anesthesia induction. ScvO 2 fluctuation (ΔScvO 2 ) was defined as the difference between the baseline and minimum ScvO 2 . Postoperative complications were evaluated using the comprehensive complication index (CCI)., Results: Patients with ΔScvO 2  ≥ 10% had significantly higher CCI scores (0 vs. 20.9: p = 0.043). In univariate analysis, patients with higher CCI scores demonstrated significantly higher preoperative C-reactive protein-to-lymphocyte ratio (7.51 vs. 24.49: p = 0.039), intraoperative bleeding (105 vs. 581 ml: p = 0.008), number of patients with major hepatectomy (4/45 vs. 3/8: p = 0.028), and number of patients with ΔScvO 2  ≥ 10% (11/45 vs. 6/8; p = 0.010). Multivariate logistic regression analysis revealed that ΔScvO 2  ≥ 10% (odds ratio: 9.53, p = 0.016) was the only independent predictor of elevated CCI., Conclusions: Central venous oxygen saturation fluctuation during hepatectomy is a predictor of postoperative complications. Anesthetic management based on intraoperative dynamic monitoring and minimizing the change in ScvO 2 is a potential strategy for decreasing the risk of post-hepatectomy complications., (© 2023. The Author(s).)

Background: Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile-derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application., Methods: Bile samples from seven patients with malignant diseases (hilar CCA = 4, distal CCA = 3) and eight patients with benign diseases (gallstones = 6, primary sclerosing cholangitis = 1, autoimmune pancreatitis = 1) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker., Results: Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98-fold higher in the malignant group than in the benign group (P = 0.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643-1.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1 μg/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620-1.000)., Conclusion: PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Glucose and lipid tolerance reportedly exhibit diurnal variations, being lower in the evening than in the morning. Therefore, the effects of exercise on glucose and blood lipid levels at different times of the day may differ. This study aimed to investigate the effects of short-term endurance exercise intervention in the morning versus late afternoon on 24-h blood glucose variability and blood lipid levels., Methods: Twelve healthy young men participated in a randomized crossover trial. The participants were assigned to morning (09:00-11:00) or late afternoon (16:00-18:00) endurance exercise for a week, consisting of supervised exercise sessions on Mondays, Wednesdays, and Fridays. In the morning and evening trials, the participants walked for 60 min on a treadmill at approximately 60% of maximal oxygen uptake (VO 2max ). Following a 2-week wash-out period, the participants performed the exercise training regimen at another time point. Continuous glucose monitoring was used to evaluate blood glucose fluctuations during each 24-h trial period. Blood samples were collected before and after each intervention to examine blood lipid and hormonal responses., Results: Examination of the area under the curve (AUC) of the glucose level changes for 24 h after the late afternoon versus morning exercise intervention revealed significantly lower values for the former versus the latter ( P < 0.01). The AUC of glucose level changes after each meal was also lower after the late afternoon versus morning intervention, and significantly lower values were observed in the late afternoon versus morning trial for breakfast and dinner ( P < 0.05, P < 0.01). In addition, a significant decrease in triglycerides (TG) and TG/high-density lipoprotein cholesterol (HDL-C) was noted after versus before the late afternoon intervention ( P < 0.05)., Conclusions: These results suggest that late afternoon endurance exercise is more effective than morning endurance exercise at improving 24-h glucose and triglyceride levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Furuhashi, Takahashi, Chijiki, Nanba, Inami, Radak, Sakamoto and Shibata.)

Background: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices., Methods: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications., Results: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881-16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096-31.825; P = 0.039)., Conclusions: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications., (© 2022. The Author(s).)

Background/objective: Pancreaticoduodenectomy (PD) is highly invasive with unsatisfactory postoperative complication rates. Nutritional and fluid management after major surgery attracts much attention with regard to the reduction in severe postoperative complications. We retrospectively analyzed PD cases and proposed a novel strategy for perioperative fluid and nutritional therapy according to the risk stratification by pancreatic fistula (PF) and delayed gastric emptying (DGE)., Methods: Between 2003 and 2018, 140 patients underwent PD at our institute of which 134 patients were enrolled. We evaluated the clinicopathological factors affecting severe (≥10%) body weight loss (BWL), factors affecting the incidence of PF and intraabdominal complications (IAC), and factors related to DGE., Results: Multivariate analysis indicated that male sex, severe PF, and DGE are significant risk factors for BWL ≥10%. PF and IAC were predominantly observed in male patients and those with non-pancreatic cancer. A fluid balance ≥6000 ml on postoperative day 2 was the sole risk factor for primary DGE. Secondary DGE significantly correlated with stomach preserving PD. Importantly, the average BWL was around 15% in grade B or C secondary DGE., Conclusion: Severe postoperative complications resulted in significant BWL. Enteral feeding is unnecessary in cases with a hard pancreas and dilated pancreatic duct if appropriate perioperative fluid management is performed. Secondary DGE followed by PF or IAC is unavoidable to some extent, especially in the case of soft pancreas with a fine pancreatic duct. In such cases, enteral feeding with tube ileostomy should be considered, and stomach preserving PD is likely to be harmful., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Chronic or acute ambient temperature change alter the gut microbiota and the metabolites, regulating metabolic functions. Short-chain fatty acids (SCFAs) produced by gut bacteria reduce the risk of disease. Feeding patterns and gut microbiota that are involved in SCFAs production are controlled by the circadian clock. Hence, the effect of environmental temperature change on SCFAs production is expected depending on the exposure timing. In addition, there is limited research on effects of habitual cold exposure on the gut microbiota and SCFAs production compared to chronic or acute exposure. Therefore, the aim was to examine the effect of cold or heat exposure timing on SCFAs production. After exposing mice to 7 or 37 °C for 3 h a day at each point for 10 days, samples were collected, and cecal pH, SCFA concentration, and BAT weight was measured. As a result, cold exposure at ZT18 increased cecal pH and decreased SCFAs. Intestinal peristalsis was suppressed due to the cold exposure at ZT18. The results reveal differing effects of intermittent cold exposure on the gut environment depending on exposure timing. In particular, ZT18 (active phase) is the timing to be the most detrimental to the gut environment of mice.

Background/aim: We sought to identify the mechanisms of perineural invasion in pancreatic ductal adenocarcinoma (PDAC)., Materials and Methods: We utilized in vitro cancer cell-nerve co-culture models comprising human PDAC cell lines (MIA Paca2 and PANC-1) and a dorsal root ganglion (DRG) isolated from neonatal mice. We compared gene expression profiles between cell lines with/without DRG conditioned medium (DRG-CM) using RNA-sequencing (RNA-seq)., Results: Migration, invasion, and neurotropism were significantly enhanced in MIA Paca2 but not in PANC-1 cells co-cultured with DRGs. Among 285 genes which showed significant differences in expression levels between cell lines in RNA-seq, we focused on Ephrin receptor A4 (EPHA4), which was upregulated in MIA Paca2 cells treated with DRG-CM. The abilities of migration, invasion, and neurotropism enhanced by DRG co-culture were abolished when EPHA4 was knocked down by siRNA in MIA Paca2 cells., Conclusion: EPHA4 can be a potential target gene to regulate perineural invasion in PDAC cells.

Background: We sought to identify the risk factors of totally implantable central venous access port (TICVAP)-related infections in patients with malignant disease., Patients and Methods: Overall, 324 consecutive patients who received a TICVAP at our institution were retrospectively analysed. We further analysed cases of TICVAP-related complications. The risk factors for TICVAP-related infection were investigated using Cox regression hazard models., Results: With a median TICVAP duration of 268 days (range=1-1,859 days), TICVAP-related complications were observed in 36 cases and infectious complications in late phase were the most common, seen in 19 cases (9.26%). A multivariate analysis showed that patients with head and neck malignancy (p<0.001) and patients who received TICVAP insertion in the upper arm (p<0.001) were independently at a higher risk for TICVAP-related infections., Conclusion: Patients with head and neck malignancy or TICVAP insertion in the upper arm have potentially increased risk for late-phase TICVAP-related infections., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: As internet use becomes more widespread, the screen time (ST) of elementary school students increases yearly. It is known that longer durations of ST can affect obesity, physical activity, dry eye disease, and learning ability. However, the effects of ST just before bedtime have not been clarified. Therefore, we examined ST duration and timing effects on elementary school children., Methods: We conducted a survey of 7419 elementary school students in Tokyo, Japan using a questionnaire on food education. ST duration and timing (just before bedtime) served as the explanatory variables, and the relationship between obesity, physical activity, dry eyes, and learning ability was analyzed using logistic regression analysis. Gender, school year, height, and weight were considered confounding factors. First, we examined whether ST duration and timing were related to each objective variable, using a univariate model to examine all variables. Thereafter, we performed multivariate logistic regression analyses for all variables showing a significant difference in the univariate models., Results: A significant association was observed between ST duration and obesity, physical activity, and academic performance, indicating that a longer ST duration may lead to obesity, decreased physical activity, and decreased academic performance. ST timing was associated with obesity, dry eyes, and academic performance, and ST immediately before bedtime contributed to obesity, dry eyes, and reduced academic performance. Furthermore, the results of investigating the combined effect of ST duration and timing (immediately before bedtime) on these factors revealed that ST timing has a greater effect on dry eyes, and ST duration has a greater effect on academic performance., Conclusion: Our findings indicate that ST in school children is related to obesity, physical activity, dry eyes, and learning ability, and they suggest that not only the duration but also the timing of ST is important.

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10 -8 ). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10 -4 ). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10 -11 ). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.

Background: Choroidal malignant melanoma is the most common primary malignant tumor of the eye in adults. Prognosis after recurrence of this disease has been dismal because of the absence of an effective therapy. However, resection of recurrent foci and a subsequent treatment with immune-checkpoint inhibitor may improve the prognosis after recurrence of this disease. This study presents a case of late-onset liver metastases of choroidal malignant melanoma, successfully treated with hepatectomy and postoperative adjuvant nivolumab., Case Presentation: A 53-year-old woman had undergone left ocular enucleation because of choroidal malignant melanoma 13 years prior to admission. She visited a nearby clinic with complaints of epigastric pain. She was referred to our hospital because a giant liver tumor was observed on abdominal ultrasonography. Enhanced computed tomography revealed multiple liver tumors in the right lobe, 49 mm in diameter with ring enhancement in subsegment (S) 5/6, and 14 and 8 mm without any enhancement in S7 and S5, respectively. On magnetic resonance imaging, the main tumor showed high intensity on T1-weighted with fat suppression, suggesting melanin deposition. Based on the diagnosis of multiple liver metastases of choroidal malignant melanoma, right hepatectomy and regional lymphadenectomy were performed. She was discharged without postoperative complications. Histological examination revealed that all tumors were metastatic malignant melanoma. She was treated with nivolumab postoperatively, and no recurrences were observed during 22 months of follow-up., Conclusions: Aggressive surgery plus adjuvant nivolumab appears to be a promising treatment for choroidal malignant melanoma with late-onset liver metastases.

Background: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy., Methods: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis., Results: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%., Conclusions: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.

Cancer development is often preceded by the appearance of preneoplastic lesions. In gastric carcinogenesis, chronic inflammation and histopathologic progression of the stomach epithelium lead to the development of metaplasia and eventually adenocarcinoma. The cell surface protein CD44, especially its variant isoforms (CD44v), has been implicated in metaplasia-carcinoma sequence progression in the stomach. We recently found that CD44v interacts with and stabilizes xCT, a subunit of the cystine transporter system xc(-), in cancer cells and thereby increases cystine uptake and confers resistance to various types of cellular stress in vivo. The functional relevance of CD44v and xCT in the development of preneoplastic lesions, however, has remained unknown. We have now examined the role of the CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) in mouse models of gastric carcinogenesis. CD44v was found to be expressed de novo in SPEM, and CD44v(+) metaplastic cells manifested upregulation of xCT expression compared with CD44v(-) cells. Genetic ablation of CD44 or treatment with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the development of SPEM and subsequent gastric tumor growth. Therapy targeted to CD44v-xCT could thus prove effective for prevention or attenuation of the CD44v-dependent development of preneoplastic lesions and cancer., (© 2013 Japanese Cancer Association.)

Solid-pseudopapillary tumors of the pancreas (SPTs) are comparatively rare and have low malignancy, with a predilection for young women. Diagnosis is difficult when a SPT develops in a boundary region with other organs. Here, we report a 42-year old woman with a SPT of the pancreas mimicking a submucosal tumor of the stomach on imaging. She was admitted to our hospital complaining of abdominal pain. We suspected a submucosal tumor of the stomach from the findings of endoscopy, endoscopic ultrasonography and abdominal computed tomography. However, angiography showed that some of the tumor vessels arose from the pancreas. Intraoperative findings revealed the tumor originated from the pancreas. Therefore, distal pancreatectomy was performed. The pathological diagnosis was SPT of the pancreas.

Nitric oxide (NO), which plays a role in the posttranslational modification of proteins, exhibits tumoricidal activity. However, the mechanism remains largely unclear. We investigated whether the regulation of insulin receptor substrate (IRS)-1 protein expression and insulin/insulin-like growth factor (IGF) signaling by NO is involved in the proliferation and invasion of pancreatic cancer cells. NO donor inhibited insulin/IGF-I-stimulated phosphorylation of insulin receptor/IGF-I receptor, IRS-1, Akt/PKB, and glycogen synthase kinase-3beta along with decreased expression of IRS-1 protein in MIAPaCa-2 cells, whereas NO donor enhanced the phosphorylation of extracellular signal-regulated kinase-1/2. In contrast, a selective inducible nitric oxide synthase inhibitor, 1400W, upregulated the expression of IRS-1 protein and the phosphorylation of IRS-1, Akt/PKB, and glycogen synthase kinase-3beta, along with enhanced proliferation and invasion of Panc-1 cells expressing inducible nitric oxide synthase protein. NO donor induced IRS-1 protein reduction through increased ubiquitination and degradation. For the detection of the site responsible for NO-induced ubiquitination, IRS-1 deletion mutant genes were transfected and overexpressed in MIAPaCa-2 cells. The results indicate that the COOH terminus of the IRS-1 protein is required for NO donor-induced ubiquitination and protein degradation. Cells stably transfected with COOH-terminal deletion mutants of IRS-1 exhibited reduced IGF signaling and cell proliferation compared with vector alone-transfected cells, with no influence of NO on IGF signaling and invasion, although stable transfectants with full-length IRS-1 protein exhibited remarkable NO-induced reduction in IGF signaling, cell proliferation, and invasion. These findings indicate that NO inhibits the proliferation and invasion of pancreatic cancer cells, at least in part, through upregulation of IRS-1 protein degradation and resultant downregulation of the insulin/IGF-I-Akt pathway.

Although accurate information on thoracolumbar bone structure is essential when computed tomography (CT) images are examined, there is no automated method of labeling all the vertebrae and ribs on a CT scan. We are developing a computer-aided diagnosis system that labels ribs and thoracolumbar vertebrae automatically and have evaluated its accuracy. A candidate bone was extracted from the CT image volume data by pixel thresholding and connectivity analysis. All non-bony anatomical structures were removed using a linear discriminate of distribution of CT values and anatomical characteristics. The vertebrae were separated from the ribs on the basis of their distances from the centers of the vertebral bodies. Finally, the thoracic cage and lumbar vertebrae were extracted, and each vertebra was labeled with its own anatomical number by histogram analysis along the craniocaudal midline. The ribs were labeled in a similar manner, based on location data. Twenty-three cases were used for accuracy comparison between our method and the radiologist's. The automated labeling of the thoracolumbar vertebrae was concordant with the judgments of the radiologist in all cases, and all but the first and second ribs were labeled correctly. These two ribs were frequently misidentified, presumably because of pericostal anatomical clutter or high densities of contrast material in the injected veins. We are confident that this system can contribute usefully as part of a picture archiving and communication system workstation, though further technical improvement is required for identification of the upper ribs.

Background: The diagnosis of acute coronary syndrome (ACS), especially non-ST-elevation myocardial infarction and unstable angina in the emergency department (ED) still remains a challenge. Multislice computed tomography (MSCT) allows assessment of not only coronary artery stenoses and occlusions, but also assessment of coronary artery plaques and myocardial perfusion status., Methods and Results: MSCT was performed in 31 patients who were admitted to the ED because of chest pain persisting at least 30 min and non-diagnostic ECG changes and normal serum enzyme concentrations. Using MSCT, ACS was defined by coronary artery stenosis > or = 75% accompanied by computed tomography (CT)-low-density plaques, and/or by the presence of myocardial perfusion defects. ACS was confirmed by coronary stenosis > or = 75% by coronary angiography and/or subsequent elevation of troponin I concentration. In total, 22 patients were diagnosed as having ACS. MSCT detected stenoses with CT-low-density plaques in 21 and non-transmural myocardial perfusion defect in 3 patients. There was 1 false-positive and 1 false-negative result. The sensitivity and specificity of MSCT to identify ACS was 95.5% and 88.9%, respectively., Conclusion: MSCT provides diagnostic operating characteristics suitable for triage of patients with ACS in the ED.

Background: Anomalous origins of the coronary artery are rare, but may cause myocardial ischemia and sudden death. Thus, their reliable identification is crucial for any imaging method that attempts coronary artery visualization and of those available multislice computed tomography (MSCT), which provides excellent spatial resolution, may be the most promising., Methods and Results: In consecutive 1,153 patients, MSCT identified 5 patients (0.43 %) with an anomalous origin of the coronary artery. The left circumflex artery (LCX) originated from the right sinus of Valsalva in 1 patient, and the right coronary artery originated from the left sinus of Valsalva and coursed between the aortic root and the pulmonary artery in 3 patients. In 1 patient, MSCT identified the absence of the LCX and high-grade atherosclerotic stenosis in the right coronary artery., Conclusion: MSCT can detect the anomalous origin and course of the coronary artery in relation to the great vessels. It is also useful for identifying atherosclerotic coronary artery disease superimposed on the anomalous vascular system.

The present study was designed to investigate the accuracy of multislice spiral computed tomography (MSCT) in detecting coronary artery disease, compared with coronary angiography (CAG), using a new retrospectively ECG-gated reconstruction method that reduced cardiac motion artifact. The study group comprised 54 consecutive patients undergoing MSCT and CAG. MSCT was performed using a SOMATOM Volume Zoom (4-detector-row, Siemens, Germany) with slice thickness 1.0 mm, pitch 1.5 (table feed: 1.5 mm per rotation) and gantry rotation time 500 ms. Metoprolol (20-60 mg) was administered orally prior to MSCT imaging. ECG-gated image reconstruction was performed with the reconstruction window (250 ms) positioned immediately before atrial contraction in order to reduce the cardiac motion artifact caused by the abrupt diastolic ventricular movement occurring during the rapid filling and atrial contraction periods. Following inspection of the volume rendering images, multiplanar reconstruction images and axial images of the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx) and right coronary artery (RCA) were obtained and evaluated for luminal narrowing. The results were compared with those obtained by CAG. Of 216 coronary arteries, 206 (95.4%) were assessable; 10 arteries were excluded from the analysis because of severe calcification (n=4), stents (n=3) or insufficient contrast enhancement (n=3). The sensitivity to detect coronary stenoses >or=50% was 93.5% and the specificity to define luminal narrowing <50% was 97.2%. The positive predictive value and the negative predictive value were 93.5% and 97.2%, respectively. The sensitivity was still satisfactory (80.6%) even when non-assessable arteries were included in the analysis. The new retrospectively ECG-gated reconstruction method for MSCT has excellent diagnostic accuracy in detecting significant coronary artery stenoses.

Although the excellent spatial resolution of multislice spiral computed tomography (MSCT) enables the coronary arteries to be visualized, its limited temporal resolution results in poor image reproducibility because of cardiac motion artifact (CMA) and hence limits its widespread clinical use. A novel retrospectively ECG-gated reconstruction method has been developed to minimize CMA. In 88 consecutive patients, the scan data were reconstructed using 2 retrospectively ECG-gated reconstruction methods. Method 1: the end of the reconstruction window (250 ms) was positioned at the peak of the P wave on ECG, which corresponded to the end of the slow filling phase during diastole immediately before atrial contraction. Method 2 (conventional method): relative retrospective gating with 50% referred to the R-R interval was performed so that the beginning of the reconstruction window (250 ms) was positioned at the halfway point between the R-R intervals of the heart cycle. The quality of the coronary artery images was evaluated according to the presence or absence of CMA. The assessment was applied to the left main coronary artery (LMCA), the left anterior descending artery (LAD, segments #6, #7 and #8), the left circumflex artery (LCx, segments #11 and #13) and the right coronary artery (RCA, segments #1, #2 and #3). The first diagonal artery (#9-1), the obtuse marginal artery (#12-1), the posterior descending artery (#4-PD), the atrioventricular node branch (#4-AV) and the first right ventricular branch (RV) were also evaluated. Of the 88 patients, 85 were eligible for image evaluation. Method 1 allowed visualization of the major coronary arteries without CMA in the majority of patients. The LCA system (segments #5-7, #11 and #13) and the proximal portion of the RCA were visualized in more than 94% of patients. Artifact-free visualization of the distal portion of the LAD (segment #8) and RCA (#4PD and #4AV), and side branches (#9-1, #12-1 and RV) was also achieved in more than 80% of patients. On the other hand, CMA occurred frequently on images obtained by Method 2. The LCx and RCA systems were the most affected by CMA, revealing only 41% artifact-free visualization of the segment #13, 39% of #1, 15% of #2 and 32% of #3. Thus, Method 1, which avoids the ventricular motion occurring during the rapid filling and atrial contraction phases, gives superior image quality over the conventional ECG-gated reconstruction method.