Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have remained an unresolved issue. This study sought to investigate the clinical significance of pre- and postoperative ctDNA analyses and their impact on the prognosis of PDAC patients. METHODS: Digital droplet polymerase chain reaction detected ctDNA in pre- and postoperative plasma samples prospectively obtained from patients with resectable and borderline-resectable PDAC. Its associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. The patients were sorted according to the presence of pre- and postoperative ctDNA, and its ability to stratify prognosis was evaluated. RESULTS: The study analyzed 97 patients. Both pre- and postoperative ctDNA were detected in 9 patients, and neither was detected in 55 patients. Whereas 15 patients harbored only preoperative ctDNA, 18 patients had only postoperative ctDNA. The multivariate analysis showed that the presence of preoperative ctDNA was associated with poorer OS (P = 0.008) and that postoperative ctDNA was not associated with either RFS or OS. Survival did not differ significantly between the patients with a positive shift in ctDNA status and those without detectable pre- or postoperative ctDNA. CONCLUSIONS: For the patients with PDAC, the presence of preoperative ctDNA was significantly associated poor OS, whereas postoperative ctDNA was not associated with poor survival. A positive change in ctDNA did not affect patients' survival.

Aeromonas dhakensis is not a rare cause of Aeromonas bacteremia in Hiroshima, Japan.

Aeromonas dhakensis, a newly recognized species, is often misidentified as A. hydrophila, A. veronii, or A. caviae by commercial phenotypic tests. Limited data about A. dhakensis are available in Japan. We retrospectively analyzed the patients with monomicrobial Aeromonas bacteremia at Hiroshima University Hospital from January 2011 to December 2017, and species re-identification was conducted using rpoD and gyrB gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Of the 19 strains from blood isolates, A. caviae (n = 9, 47.4%), A. dhakensis (n = 4, 21.1%), A. hydrophila (n = 3, 15.8%), and A. veronii (n = 3, 15.8%) were re-identified. A. dhakensis was phenotypically misidentified as A. hydrophila (n = 3, 75%) or A. sobria (n = 1, 25%). A. dhakensis was also misidentified as A. caviae (n = 2, 50%), A. hydrophila (n = 1, 25%), and A. jandaei (n = 1, 25%) in MALDI-TOF MS system. Malignancies (n = 12, 63.2%) and liver cirrhosis (n = 7, 36.8%) were common comorbidities. Biliary tract infection was the most frequent source of Aeromonas bacteremia (n = 11, 57.9%). The major source of A. dhakensis bacteremia was also biliary tract infection (n = 3, 75%), and the 14-day infection-related mortality of A. dhakensis was 25%. A. dhakensis isolates showed similar clinical characteristics, antimicrobial susceptibility, and mortality with those of other Aeromonas species isolates. This study demonstrated that A. dhakensis is not a rare cause of Aeromonas bacteremia, but is often misidentified as A. hydrophila in Hiroshima, Japan. Further studies should be conducted to identify the geographical distribution and clinical impact of A. dhakensis in Japan.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement on Changes in Cardiac Sympathetic Nervous Function.

The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) on changes in cardiac sympathetic nervous (CSN) function remains unclear. Using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, we investigated the impact of PPM after TAVR on CSN activity.We enrolled 44 of 117 patients with severe aortic stenosis who underwent TAVR for analysis in the present study. We conducted 123I-MIBG scintigraphy at baseline and at about 9 months after TAVR. Differences between baseline and post-TAVR 123I-MIBG parameters were compared between cases with and without PPM.There were 17 and 27 patients with and without PPM, respectively. Those without PPM exhibited significantly decreased left ventricular mass index (122 ± 36 g/m2 versus 108 ± 30 g/m2, P < 0.001) following TAVR, whereas those with PPM did not (117 ± 21 g/m2 versus 110 ± 17 g/m2, P = 0.09). Significant improvements in delayed heart-to-mediastinum (H/M) ratio (2.8 ± 0.4 versus 3.0 ± 0.4, P = 0.004) and washout rate (WR) (33% ± 10% versus 24% ± 12%, P < 0.001) were observed after TAVR in patients without PPM but not in those with PPM. Multivariable linear regression analysis revealed PPM to be a negative predictor of improvements in delayed H/M ratio and WR.Delayed H/M ratio and WR improve significantly after TAVR in the absence of PPM, whereas these improvements are not observed in patients with PPM. Hence, the presence of PPM is a negative predictor of improvements in delayed H/M ratio and WR in patients undergoing TAVR.

Gastrectomy for invasive micropapillary carcinoma is associated with poorer disease-free and disease-specific survival.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a relatively rare subtype of gastric adenocarcinoma and has aggressive histopathologic characteristics, including lymphatic and vascular invasion. However, the associated long-term survival outcomes remain unclear. This study aimed to compare the clinicopathological characteristics and prognosis of gastric adenocarcinoma with and without IMPC using propensity score-matched (PSM) analysis. METHODS: Patients with gastric adenocarcinoma who underwent gastrectomy between 2006 and 2015 were included in the analysis. PSM analysis was performed to compensate for the background heterogeneity between the groups. The primary endpoint was disease-free survival (DFS) after gastrectomy, and the secondary endpoints were disease-specific survival (DSS) and recurrence pattern. RESULTS: Of 882 patients who underwent gastrectomy for gastric adenocarcinoma, with a follow-up duration greater than 36 months, 35 were diagnosed as having gastric adenocarcinoma with IMPC. After PSM, 70 patients, including 35 with IMPC and 35 without IMPC, were selected. Gastric adenocarcinoma with IMPC is characterized by lymphatic invasion (94% versus 69%, p = 0.012). Patients with IMPC had significantly poorer DFS than those without IMPC, with 3-year DFS rates of 62.2% and 93.4% (p = 0.003), respectively. Furthermore, a significant difference was also observed in DSS (p = 0.016); patients with IMPC more frequently developed liver metastasis (20%) than those without IMPC (3%, p = 0.006). CONCLUSIONS: Resected gastric carcinoma with IMPC was associated with poorer DFS and DSS; furthermore, an increased rate of lymphatic invasion and liver metastasis was noted than in cases without IMPC.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

BACKGROUND: Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). OBJECTIVE: The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. METHODS: Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. RESULTS: High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. CONCLUSIONS: High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone.

BACKGROUND: Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential. OBJECTIVES: To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone). METHODS: Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS. CONCLUSIONS: High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.

Prognostic impact of postoperative complication after pancreatoduodenectomy for pancreatic adenocarcinoma stratified by the resectability status.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the prognostic impact of postoperative complications after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) stratified by resectability status. METHODS: Medical records of 226 patients with pancreatic head carcinoma who underwent PD, including 115 with resectable (R) and 111 with borderline resectable/unresectable (BR/UR) PDAC, were reviewed retrospectively. Major complications were defined as grade III or IV based on the Clavien-Dindo classification system. The prognostic impact of major complications on overall survival (OS) was analyzed using univariate and multivariate analyses with stratification by resectability status. RESULTS: A multivariate analysis in the BR/UR group identified R1 resection (P = 0.03), T 3/4 stage (P = 0.03), and incidence of major complications (P = 0.03) as independent risk factors for poor survival, whereas major complications did not affect survival in the R group. Initiation of adjuvant gemcitabine plus S-1 chemotherapy occurred significantly less frequently for patients with major complications than for those without major complications in the BR/UR group (P = 0.02). CONCLUSION: A negative prognostic impact of postoperative major complications after PD was observed in patients with BR/UR PDAC, whereas the prognostic impact was unclear in patients with R PDAC.

Comparison of Transcarotid vs. Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: Recently, the carotid artery has been used as an alternative approach for transcatheter aortic valve implantation (TAVI). The aim of this study was to prove the safety and feasibility of transcarotid (TC) vs. transfemoral (TF) TAVI. Methods and Results: This retrospective study enrolled 726 consecutive patients with severe symptomatic aortic stenosis. All patients underwent TC-TAVI or TF-TAVI at Hôpital Haut-Lévèque, Bordeaux Heart University Hospital between September 2012 and October 2017. The TC-TAVI (n=83) and TF-TAVI (n=643) groups were compared statistically. The EuroSCORE II was significantly higher (8.2±6.7 vs. 6.4±5.5; P=0.007) and rates of current smoking, dyslipidemia and peripheral arterial disease were higher in the TC-TAVI than TF-TAVI group. All TC-TAVIs and 9.3% of TF-TAVIs were performed under general anesthesia. Radiation time was significantly shorter in the TC-TAVI than TF-TAVI group (14.5±6.0 vs. 23.0±10.8 min; P<0.001). Postimplant balloon valvuloplasty was performed more frequently in the TF-TAVI than TC-TAVI group (7.2% vs. 19.4%; P=0.006). Postoperative echocardiographic data were similar between the 2 groups, and there were no significant differences in 30-day mortality (8.4% vs. 5.0%; P=0.189) or stroke rate (1.2% vs. 2.6%; P=0.428) between the TF-TAVI and TC-TAVI groups. CONCLUSIONS: The feasibility and 30-day safety of TC-TAVI and TF-TAVI are similar. When TF-TAVI is not suitable anatomically for a particular patient, TC-TAVI is a preferable alternative.

Chemoradiotherapy for Initially Unresectable Locally Advanced Cholangiocarcinoma.

OBJECTIVE: Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. METHODS: Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50 Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. RESULTS: Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37 months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10 months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). CONCLUSIONS: Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas.

Association between histological features of epicardial adipose tissue and coronary plaque characteristics on computed tomography angiography.

The means by which epicardial adipose tissue (EAT) could influence coronary plaque progression biologically remain unclear. We investigated the association between the histological findings of EAT and coronary plaque characteristics assessed by coronary computed tomography angiography (CCTA). We enrolled 34 patients in whom one or more coronary plaques containing non-calcified components were detected on CCTA before cardiac surgery [coronary artery bypass graft (CABG) or non-CABG]. We evaluated visceral adipose tissue (VAT) area, EAT volume, and coronary plaque characteristics including minimum computed tomography density (CTD) and vascular Remodeling Index (RI). Lower CTD and higher RI were considered as high-risk characteristics, and coronary plaque with both CTD < 39 Hounsfield units and RI > 1.05 was defined as two-characteristic plaque (2-CP). The numbers of CD68+ macrophages and CD31+ microvessels were assessed in six random high-power fields (400×) of EAT samples obtained during cardiac surgery. The entire cohort showed a wide range of EAT volume, which were similar between patients with 2-CP and those without. Patients with 2-CP had more amounts of EAT macrophages (85 ± 38 versus 45 ± 22, p = 0.0005) and vascularity (62 ± 33 versus 37 ± 19, p = 0.013) than those without. On multivariate analyses adjusted for age, sex, coronary risk factors, statin use, type of surgery, VAT area, EAT volume, and coronary calcium score, the presence of 2-CP showed significant correlation with increased EAT macrophages (ß = 0.65, p = 0.014) and vascularity (ß = 0.74, p = 0.0053). Our findings support the hypothesis that EAT biologic activities are associated with coronary plaque vulnerability.

Spinal cord injury as a complication of thoracic endovascular aneurysm repair.

OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication of thoracic aortic aneurysm repair in the era of thoracic endovascular aneurysm repair (TEVAR). This review aims to clarify the causes of SCI during TEVAR and to propose ways that it may be prevented. METHODS AND RESULTS: We performed an extensive literature search of SCI during TEVAR. Based on the existing literature, we examined the anatomy of the anterior spinal cord artery, which supplies blood to the anterior aspect of the spinal cord, and discuss reported effective ways to prevent SCI during TEVAR, including augmentation of arterial blood pressure and drainage of cerebrospinal fluid. CONCLUSION: After reviewing the mechanism of SCI during TEVAR, we evaluated promising preventative measures.

The long-term outcomes of partial arch repair using the frozen elephant trunk technique for distal arch aortic aneurysm.

PURPOSE: The purpose of this study was to evaluate the long-term results of partial arch repair using the frozen elephant trunk (FET) technique for distal arch aortic aneurysm and to examine the late complications. METHODS: Thirty-eight patients with true distal arch aortic aneurysms were repaired with FET introduced through an incision in the proximal arch aorta. Follow-up computed tomography was performed every 6 or 12 months in 36 surviving patients. The maximum dimension of the excluded aneurysmal space was measured to determine whether the aneurysmal space had decreased or disappeared. Late complications were also evaluated during the long-term follow-up. RESULTS: There was 1 hospital death (2.6%) and 1 (2.6%) case of paraplegia. There were 2 late sudden deaths (5.2%) thought to be due to aneurysm rupture and arrhythmia. Postoperative serial-computed tomography showed shrinkage of the excluded aneurysmal space in 33 of 36 patients. Late aneurysmal formation occurred in the anastomotic site in three patients. One patient underwent thoracic endovascular stent grafting 10 years after surgery, 1 patient had total arch replacement 9 years after surgery, and 1 died due to rupture. CONCLUSION: Frozen elephant trunk was found to be a useful alternative for treating true distal arch aortic aneurysm. However, we must be alert for late aneurysmal formation at the incision site.

Abdominal organ protection strategy for aortic arch aneurysm surgery.

INTRODUCTION: Body temperature maintained during open distal anastomosis in patients who undergo aortic surgery has been showing an upward trend; however, a higher temperature may increase visceral organ and spinal cord injury. Distal perfusion may reduce abdominal organ injury, especially acute kidney injury (AKI). METHODS: From 2009 to 2016, 56 patients who underwent ascending aortic and/or aortic arch surgery were enrolled. Open distal anastomosis was performed using one of three protection strategies: 1) systemic temperature of 25°C followed by selective cerebral perfusion (SCP) with lower body circulatory arrest (Group CA25, n=27); 2) systemic temperature of 28°C followed by SCP with lower body circulatory arrest (Group CA28, n=4); and 3) systemic temperature of 28°C followed by SCP with distal aortic perfusion (Group DP, n=25). RESULTS: During the postoperative course, levels of blood urea nitrogen, creatinine, liver enzymes, lactate dehydrogenase and lactate in Groups CA28 and CA25 were significantly higher than those in Group DP. AKI defined by the AKI Network occurred in 28 cases (50%) and 3 cases required permanent hemodialysis. AKI was significantly higher in Groups CA25 and CA28 than in Group DP (p=0.026). Mid-term follow-up showed that patients who developed postoperative AKI were more likely to suffer from cardiovascular events. CONCLUSIONS: Distal perfusion during open distal anastomosis reduced kidney and liver injury after thoracic aortic surgery despite an increased body temperature of up to 28°C. This strategy may be useful to prevent AKI, liver dysfunction, the need for hemodialysis and multiple organ failure and could improve mid-term results.

H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.

BACKGROUND: A common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves sodium channel activity in mutated channels and known to be a genetic modifier of Brugada syndrome patients (BrS). We investigated clinical manifestations and underlying mechanisms of H558R in BrS. METHODS AND RESULTS: We genotyped H558R in 100 BrS (mean age 45 ± 14 years; 91 men) and 1875 controls (mean age 54 ± 18 years; 1546 men). We compared clinical parameters in BrS with and without H558R (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections from 30 patients during aortic aneurysm operations and compared SCN5A expression and methylation with or without H558R. H558R was less frequent in BrS than controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level was significantly higher and the methylation rate was significantly lower in sections with H558R (N = 10) than those without (0.98 ± 0.14 vs. 0.83 ± 0.19, P = 0.04; 0.7 ± 0.2% vs. 1.6 ± 0.1%, P = 0.004, respectively). In BrS with heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G allele expression. CONCLUSION: The SCN5A polymorphism H558R may be a modifier that protects against VF occurrence in BrS. The H558R decreased the SCN5A promoter methylation and increased the expression level in cardiac tissue. An allelic expression imbalance in BrS with a heterozygous H558R may also contribute to the protective effects in heterozygous mutations.

Comparison of the prognostic impact of pre- and post-operative CA19-9, SPan-1, and DUPAN-II levels in patients with pancreatic carcinoma.

BACKGROUND: Although serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. METHODS: Pre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available. RESULTS: Elevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS. CONCLUSION: When the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period.

Sarcopenia is closely associated with pancreatic exocrine insufficiency in patients with pancreatic disease.

BACKGROUND/OBJECTIVES: The loss of skeletal muscle mass (sarcopenia) is associated with the poor prognosis of pancreatic cancer. It has been reported pancreatic exocrine insufficiency (PEI) is associated with serum nutritional markers in chronic pancreatitis. However, there has been no report about the relationship between sarcopenia and PEI. The aim of this study is to determine whether body composition, including skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue content (IMAC), and serum nutritional markers are associated with pancreatic exocrine function in patients with pancreatic disease. METHODS: Data were collected prospectively on 132 patients with pancreatic disease. SM, SAT, VAT and IMAC were assessed by computed tomography. Patients underwent a 13C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. Serum nutritional markers were measured at the same time of 13C-labeled mixed triglyceride breath test. Patients were stratified by quartiles according to each body component, and for each component the lowest group was defined as the lowest quartile, treating men and women separately. The lowest group for SM was defined as sarcopenia. PEI was defined as a percentage 13CO2 cumulative dose at 7 h below 5%. RESULTS: Sarcopenia was associated with PEI in both men (P < 0.001) and women (P = 0.012). Serum albumin was associated with PEI in men only (P = 0.005). Among all patients, sarcopenia (P = 0.001) and serum albumin (P = 0.058) were associated with PEI. On multivariate analysis, only sarcopenia remained independently associated with PEI (P < 0.001). CONCLUSIONS: Sarcopenia is independently associated with PEI in patients with pancreatic disease.

A Novel Blood Viscosity Estimation Method Based on Pressure-Flow Characteristics of an Oxygenator During Cardiopulmonary Bypass.

During cardiopulmonary bypass (CPB), blood viscosity conspicuously increases and decreases due to changes in hematocrit and blood temperature. Nevertheless, blood viscosity is typically not evaluated, because there is no technology that can provide simple, continuous, noncontact monitoring. We modeled the pressure-flow characteristics of an oxygenator in a previous study, and in that study we quantified the influence of viscosity on oxygenator function. The pressure-flow monitoring information in the oxygenator is derived from our model and enables the estimation of viscosity. The viscosity estimation method was proposed and investigated in an in vitro experiment. Three samples of whole bovine blood with different hematocrit levels (21.8, 31.0, and 39.8%) were prepared and perfused into the oxygenator. As the temperature changed from 37°C to 27°C, the mean inlet pressure (Pin ) and outlet pressure (Pout ) of the oxygenator and the flow (Q) and viscosity of the blood were measured. The estimated viscosity was calculated from the pressure gradient (ΔP = Pin - Pout ) and Q and was compared to the measured blood viscosity. A strong correlation was found between the two methods for all samples. Bland-Altman analysis revealed a mean bias of -0.0263 mPa.s, a standard deviation of 0.071 mPa.s, limits of agreement of -0.114-0.166 mPa.s, and a percent error of 5%. Therefore, this method is considered compatible with the torsional oscillation viscometer that has plus or minus 5% measurement accuracy. Our study offers the possibility of continuously estimating blood viscosity during CPB.

A Case of Anterolateral Papillary Muscle Rupture Caused by Isolated First Diagonal Branch Occlusion.

A 74-year-old man hospitalized due to acute myocardial infarction (AMI) of the first diagonal branch developed cardiogenic shock. Ultrasonography showed anterolateral papillary muscle rupture (PMR) which caused anterior mitral leaflet prolapse and severe mitral valve regurgitation, and he successfully underwent mitral valve replacement. Anterolateral PMR causing anterior mitral leaflet prolapse due to obstruction of the first diagonal branch is rare and should be considered in such an AMI case.

[Prevention of Spinal Cord Ischemia During Thoracic Endovascular Aortic Repair].

Spinal cord ischemia(SCI) has been devastating complication of endovascular thoracic and thoracoabdominal aortic repair. Spinal cord blood supply arises from not only segmental artery, subclavian artery, hypogastric artery and these branches, but also perivertebral vasculature and paravertebral muscle and small arterial network, and risk factors of SCI were multifactorial. There are several adjuncts/strategies which are utilized to minimize the incidence of SCI: cerebrospinal fluid drainage, perioperative management of high mean arterial pressure, intraoperative evoked potential monitoring, and staged thoracoabdominal aortic repair. Recent developments including near-infrared spectroscopy, minimally invasive segmental artery coil embolization, and temporary aneurysm sac perfusion should be evaluated to prevent SCI.

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. METHODS: We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA. RESULTS: Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001). CONCLUSIONS: Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.