Hepatopancreatoduodenectomy with delayed division of the pancreatic parenchyma when utilizing a right lateral approach to the superior mesenteric artery.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is a high-risk surgical procedure. Delayed division of the pancreatic parenchyma (DDPP) was reported as a novel technique in HPD for reducing postoperative pancreatic fistula. However, it is often difficult to dissect the pancreatic head nerve plexus while leaving the pancreatic parenchyma intact, particularly in patients with a bulky tumor with vascular invasion. Of the various reported approaches to the superior mesenteric artery, the right lateral approach can provide a useful surgical field to conduct DDPP in HPD. CASE PRESENTATION: A 78-year-old man visited a local clinic with itching and jaundice. Laboratory tests revealed elevated hepatobiliary enzyme, total bilirubin, and tumor markers. Enhanced computed tomography, endoscopic retrograde cholangiopancreatography, and intraductal ultrasonography of the bile duct were performed, and he was diagnosed with perihilar cholangiocarcinoma with invasion to the right hepatic artery (40 × 15 mm, Bismuth IIIa, cT3N0M0 cStage III). After neoadjuvant chemotherapy, he underwent left hepatectomy with caudate lobectomy, pancreatoduodenectomy, and combined resection of right hepatic artery using DDPP with a right lateral approach to the superior mesenteric artery. The pathological diagnosis was perihilar cholangiocarcinoma ypT3N1M0 ypStage IIIC, R0 resection. He was discharged on postoperative day 57 in good health and has been doing well for 6 months since the surgery. CONCLUSIONS: We present an effective application of the right lateral approach to the superior mesenteric artery in DDPP during HPD. This procedure can provide a clear surgical field to easily divide the pancreatic head nerve plexus before transection of the pancreatic parenchyma.

Correlation Between the Social Network Structure and Well-Being of Health Care Workers in Intensive Care Units: Prospective Observational Study.

BACKGROUND: Effective communication strategies are becoming increasingly important in intensive care units (ICUs) where patients at high risk are treated. Distributed leadership promotes effective communication among health care professionals (HCPs). Moreover, beyond facilitating patient care, it may improve well-being among HCPs by fostering teamwork. However, the impact of distributed leadership on the communication structure and well-being of HCPs remains unclear. OBJECTIVE: We performed a social network analysis (SNA) to assess the characteristics of each HCP in the network, identify the number of HCP connections, analyze 4 centralities that can measure an HCP's importance, and evaluate the impact of distributed leadership structure on the well-being and communication structure of the medical staff. METHODS: Wearable sensors were used to obtain face-to-face interaction data from the ICU medical staff at Mie University Hospital, Japan. Participants wore a badge on the front of their clothing during working hours to measure the total frequency of face-to-face interactions. We collected data about the well-being of medical staff using the Center for Epidemiological Studies-Depression (CES-D) questionnaire and measured 4 centralities using SNA analysis. A CES-D questionnaire was administered during the study to measure the well-being of the HCPs. RESULTS: Overall, 247 ICU workers participated in this clinical study for 4 weeks yearly in February 2016, 2017, and 2018. The distributed leadership structure was established within the ICU in 2017 and 2018. We compared these results with those of the traditional leadership structure used in 2016. Most face-to-face interactions in the ICU were among nurses or between nurses and other professionals. In 2016, overall, 10 nurses could perform leadership tasks, which significantly increased to 24 in 2017 (P=.046) and 20 in 2018 (P=.046). Considering the increased number of nurses who could perform leadership duties and the collaboration created within the organization, SNA in 2018 showed that the betweenness (P=.001), degree (P<.001), and closeness (P<.001) centralities significantly increased compared with those in 2016. However, the eigenvector centrality significantly decreased in 2018 compared with that in 2016 (P=.01). The CES-D scores in 2018 also significantly decreased compared with those in 2016 (P=.01). The betweenness (r=0.269; P=.02), degree (r=0.262; P=.03), and eigenvector (r=0.261; P=.03) centralities and CES-D scores were positively correlated in 2016, whereas the closeness centrality and CES-D scores were negatively correlated (r=-0.318; P=.01). In 2018, the degree (r=-0.280; P=.01) and eigenvector (r=-0.284; P=.01) centralities were negatively correlated with CES-D scores. CONCLUSIONS: Face-to-face interactions of HCPs in the ICU were measured using wearable sensors, and nurses were found to be centrally located. However, the introduction of distributed leadership created collaboration and informal leadership in the organization, altering the social network structure of HCPs and increasing organizational well-being. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) UMIN000037046; https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000042211.

Extrapancreatic extension is a better adverse prognostic factor than tumor size in patients with localized pancreatic ductal adenocarcinoma treated with chemoradiotherapy - comparison of T category between the American Joint Committee on Cancer and Japan Pancreas Society.

BACKGROUND: T category classification for pancreatic ductal adenocarcinoma (PDAC) in the Classification of Pancreatic Cancer by the Japan Pancreas Society (JPS) is quite different from that of the American Joint Committee on Cancer (AJCC). The JPS classification focuses on extrapancreatic extension, while the AJCC focuses mainly on tumor size. This study aimed at identifying prognostic factors in PDAC patients undergoing chemoradiotherapy (CRT) by comparing the differences of T categories in these two classifications. METHODS: This retrospective study involved 344 PDAC patients who underwent CRT from 2005 to 2019 and their T-category variables were re-evaluated on computed tomography (CT) images. Disease-specific survival (DSS) was compared based on the JPS and AJCC T categories, while multivariate analysis was performed to identify prognostic factors. RESULTS: Based on the AJCC, 5-year DSS of T3 was better than those of T1 and T2 (57.1% vs. 47.7% and 37.4%). In multivariate analysis, performance status, CEA, the involvement of superior mesenteric vein and superior mesenteric artery, the JPS stage before CRT, and regimen of chemotherapy were identified as independent prognostic factors. CONCLUSIONS: In localized PDAC patients treated with chemoradiotherapy, extrapancreatic extension, as while as biological, conditional and therapeutic factors, is a better prognostic factor than tumor size.

Anterior versus posterior radical antegrade modular pancreatosplenectomy for pancreatic body and tail cancer: an inverse probability of treatment weighting with survival analysis.

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) is a standard procedure for patients with pancreatic body and tail cancer. There are two types of RAMPS: anterior and posterior, but their indications and surgical outcomes remain unclear. We compared the surgical outcomes, postoperative course, and prognosis between anterior and posterior RAMPS. METHODS: Between 2007 and 2020, 105 consecutive patients who underwent RAMPS for pancreatic body and tail cancers were divided into an anterior RAMPS group (n = 30) and a posterior RAMPS group (n = 75). To adjust for differences in preoperative characteristics and intraoperative procedures, an inverse probability of treatment weighting (IPTW) analysis was done, using propensity scores. RESULTS: After IPTW adjustment, the postoperative body temperature of the posterior RAMPS group and the amount of drain discharge in the anterior RAMPS group were significantly lower, from postoperative days (PODs) 1 to 3, but there were no differences in postoperative complications, recurrence patterns, or prognosis between the two groups. Regarding the diagnostic ability of multidetector-row computed tomography (MD-CT) for direct tumor involvement of the left adrenal gland, the sensitivity and specificity were 100% and 90.0%, respectively. CONCLUSION: Pancreatic body and tail cancer without apparent preoperative direct tumor involvement of the left adrenal gland on MD-CT may be sufficient indication for anterior RAMPS.

Clinical Significance of Plasma Tenascin-C Levels in Recipients With Prolonged Jaundice After Living Donor Liver Transplantation.

BACKGROUND: Focusing on tenascin-C (TNC), whose expression is enhanced during the tissue remodeling process, the present study aimed to clarify whether plasma TNC levels after living donor liver transplantation (LDLT) could be a predictor of irreversible liver damage in the recipients with prolonged jaundice (PJ). METHODS: Among 123 adult recipients who underwent LDLT between March 2002 and December 2016, the subjects were 79 recipients in whom we could measure plasma TNC levels preoperatively (pre-) and on postoperative days 1 to 14 (POD1 to POD14). Prolonged jaundice was defined as serum total bilirubin level >10 mg/dL on POD14, and 79 recipients were divided into 2 groups: 56 in the non-PJ (NJ) group and 23 in the PJ group. RESULTS: The PJ group had significantly increased pre-TNC; smaller grafts; decreased platelet counts POD14; increased TB-POD1, -POD7, and -POD14; increased prothrombin time-international normalized ratio on POD7 and POD14; and higher 90-day mortality than the NJ group. As for the risk factors for 90-day mortality, multivariate analysis identified TNC-POD14 as a single significant independent prognostic factor (P = .015). The best cut-off value of TNC-POD14 for 90-day survival was determined to be 193.7 ng/mL. In the PJ group, the patients with low TNC-POD14 (<193.7 ng/mL) had satisfactory survival, with 100.0 % at 90 days, while the patients with high TNC-POD14 (≥193.7 ng/mL) had significantly poor survival, with 38.5 % at 90 days (P = .004). CONCLUSIONS: In PJ after LDLT, plasma TNC-POD14 is very useful for diagnosing postoperative irreversible liver damage early.

Surgical outcomes of the Frey procedure for chronic pancreatitis: correlation between preoperative characteristics and the histological severity of pancreatic fibrosis.

PURPOSE: To evaluate the efficacy of the Frey procedure and clarify the relationship between preoperative characteristics and the histological severity of chronic pancreatitis (CP). METHODS: Thirty patients who underwent the Frey procedure for CP between January, 2002 and December, 2020, at our hospital, were enrolled in this study. The specimen cored out of the pancreatic head was assessed for CP severity. We evaluated preoperative status and surgical outcomes according to CP severity. RESULTS: Long-term pain relief was achieved in all 26 patients with sustained long-term follow-up, with complete pain relief attained in 19 (63%). Albumin levels were significantly higher 1 year postoperatively than preoperatively (p = 0.038). Histological fibrosis was assessed in the 26 patients as follows: normal (n = 4; 15%), mild (n = 8; 31%), moderate (n = 2; 8%), and severe (n = 12; 46%). These patients were divided into two groups according to the severity of fibrosis: normal/mild (n = 12) and moderate/severe (n = 14). The rates of diffuse calcification on preoperative computed tomography (CT) (71% vs. 17%, p = 0.008) and islet atrophy on insulin immunohistochemistry (100% vs. 33%, p < 0.001) were significantly higher in the moderate/severe group than in the normal/mild group. CONCLUSION: The Frey procedure can achieve good pain relief and improve nutritional status. The severity of fibrosis can be predicted based on the extent of calcification on preoperative imaging studies.

Resection type is a predictor of postoperative complications in laparoscopic partial liver resection.

BACKGROUND: Partial laparoscopic liver resection (LLR) is a procedure that can have varying levels of surgical difficulty depending on the tumor status and procedure. Therefore, we aimed to evaluate the surgical outcomes of partial LLR using a new resection classification system. METHODS: From January 2009 to May 2021, 156 patients underwent LLR; of them, 87 patients who underwent pure partial LLR were included in this study. They were classified according to the IWATE criteria as the low (n = 56) and intermediate (n = 31) difficulty groups and reclassified according to the resection type as the edge (ER, n = 45), bowl-shaped (BSR, n = 27), and dome-shaped resection (DSR, n = 15) groups. The following surgical outcomes were comparatively analyzed among the groups: intraoperative blood loss, the operation time, and complication rates. Preoperative risk factors for intraoperative blood transfusion and complications were evaluated. RESULTS: In the IWATE criteria-based analysis, the intermediate-difficulty group had significantly higher intraoperative blood loss (p = 0.005), operation time (p = 0.005), and Clavien-Dindo (CD) grade-based complication rates (CD grade 2 or higher, p = 0.03) than the low-difficulty group. When analyzing the resection type, the CD grade-based complication rate (p = 0.013) and surgical site infection (SSI, p = 0.005) were significantly higher and the postoperative hospitalization was significantly longer (p = 0.028) in the bowl-shaped resection (BSR) group than in the edge- (ER) and dome-shaped resection (DSR) groups. The tumor size (p = 0.011) and IWATE criteria score (p = 0.006) were independent risk factors for intraoperative blood transfusion in the multivariate analysis. The tumor depth (p = 0.011) and BSR (p = 0.002) were independent risk factors for complications of CD grade 2 or higher in the multivariate analysis. BSR was an independent risk factor for SSI in the multivariate analysis (p = 0.017). CONCLUSIONS: Resection type could predict the rate of postoperative complications, while the IWATE criteria could predict the intraoperative surgical difficulty.

Postoperative Donor Liver Damage Can Predict Recipient Short-Term Survival in Living Donor Liver Transplantation.

BACKGROUND: In living donor liver transplantation, surgical damage is a risk for graft dysfunction. We hypothesized that postoperative donor laboratory data reflect both donor liver damage and graft damage. Therefore, we evaluated how donor surgical factors affected recipient graft function and prognosis. PATIENTS AND METHODS: From March 2002 to December 2020, 130 consecutive recipients and donors who underwent adult-to-adult living donor liver transplantation were analyzed. Donor perioperative surgical factors were evaluated to assess risk factors for recipient 90-day mortality by univariate analysis. RESULTS: Donor postoperative maximum levels of aspartate aminotransferase (AST; P = .016), alanine transaminase (P = .048), and prothrombin time-international normalized ratio (P = .034) were risk factors. Receiver operating characteristic analysis identified 214 U/L as the most appropriate cutoff value of donor postoperative AST. After excluding 22 pairs of patients without donor data, the 108 pairs were divided into 2 groups based on donor maximum AST (D-mAST) level: the low D-mAST group (D-mAST < 241 U/L, n = 39) and the high D-mAST group (D-mAST ≥ 241 U/L, n = 69). Donor age was significantly higher in recipients in the high D-mAST group than in the low D-mAST group (P = .033). Postoperative recipient maximum AST and alanine transaminase levels and 90-day mortality were significantly higher in the high D-mAST group than in the low D-mAST group (P = .001, P = .006, and P = .009, respectively). There were no significant differences in long-term survival, although 5-year survival was slightly lower in the high D-mAST group. CONCLUSIONS: Surgical liver damage to grafts, as assessed by postoperative donor AST levels, affected recipient short-term survival.

The usefulness of modified splenic hilum hanging maneuver in laparoscopic splenectomy, especially for patients with huge spleen: a case-control study with propensity score matching.

BACKGROUND: Although Laparoscopic splenectomy (LS) have been proven to the standard operation for removal of spleen, the rate of conversion to open surgery is still higher than those of other laparoscopic surgeries, especially for huge spleen. In order to reduce the rate of conversion to open surgery, we had developed LS using modified splenic hilum hanging (MSHH) maneuver: the splenic pedicle was transected en bloc using a surgical stapler after hanging splenic hilum with an atraumatic penrose drain tube. METHODS: Between January 2005 and December 2019, we retrospectively assessed 94 patients who underwent LS. MSHH maneuver was performed in 37 patients (39.4%). We compared the intra- and postoperative outcomes between patients with or without MSHH maneuver. To adjust for differences in preoperative characteristics and blood examination, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 29 patients per group. Predictive factors of conversion from LS to open surgery were elucidated using the uni- and multi-variate analyses. RESULTS: After the propensity score matching, blood loss (268 ml vs. 50 ml), the rate of conversion to open surgery (27.6% vs. 0%), and postoperative hospital stays (15 days vs. 10 days) were significantly decreased in patients with MSHH maneuver, respectively. Among 94 patients, 19 patients (20.2%) underwent conversion to open surgery. In multivariate analysis, spleen volume (SV) and LS without MSHH maneuver were independent predictive factors of conversion to open surgery, respectively. Additionally, cut-off value of SV for conversion to open surgery was 802 ml (sensitivity: 0.684, specificity: 0.827, p < 0.001). CONCLUSIONS: LS using MSHH maneuver seems to be useful surgical technique to improve intraoperative outcomes and reduce the rate of conversion from LS to open surgery resulting in shorten postoperative hospital stay.

Phase I Study of Preoperative Chemoradiotherapy Using Gemcitabine Plus Nab-Paclitaxel for Patients Who Have Localized Pancreatic Ductal Adenocarcinoma With Contact or Invasion to Major Arteries.

OBJECTIVES: This study aimed to assess the feasibility of preoperative chemoradiotherapy using gemcitabine plus nab-paclitaxel (GnP) and to determine the recommended dose (RD) of nab-paclitaxel for patients with localized pancreatic ductal adenocarcinoma (PDAC). METHODS: The participants had localized PDAC with contact or invasion to major arteries. They received GnP on days 1, 15, 29, and 43. The dose of gemcitabine was fixed at 600 mg/m2, whereas that of nab-paclitaxel was at 3 dose levels in accordance with a standard 3 + 3 dose escalation scheme. Three-dimensional radiotherapy was administered concurrently to a total dose of 50.4 Gy per 28 fractions. RESULTS: The study cohort comprised 15 patients. Grade 3 or 4 neutropenia was observed in 4 (26.7%), leukopenia in 1 (6.7%), biliary infection in 2 (13.3%), appetite loss and nausea in 1 (6.7%), and anaphylaxis in 1 (6.7%). The RD was determined as level 2 (gemcitabine, 600 mg/m2; nab-paclitaxel, 100 mg/m2). Three patients underwent pancreatectomy after additional chemotherapy and achieved R0 resection. CONCLUSIONS: The RD of nab-paclitaxel in our chemoradiotherapy protocol using GnP was 100 mg/m2 with gemcitabine 600 mg/m2 and 3-dimensional conformal radiotherapy to a total dose of 50.4 Gy per 28 fractions for patients with localized PDAC.

Elevated Plasma Soluble PD-L1 Levels in Out-of-Hospital Cardiac Arrest Patients.

Background: A deregulated immune system has been implicated in the pathogenesis of post-cardiac arrest syndrome (PCAS). A soluble form of programmed cell death-1 (PD-1) ligand (sPD-L1) has been found at increased levels in cancer and sustained inflammation, thereby deregulating immune functions. Here, we aim to study the possible involvement of sPD-L1 in PCAS. Methods: Thirty out-of-hospital cardiac arrest (OHCA) patients consecutively admitted to the ER of Mie University Hospital were prospectively enrolled. Plasma concentrations of sPD-L1 were measured by an enzyme-linked immunosorbent assay in blood samples of all 30 OHCA patients obtained during cardiopulmonary resuscitation (CPR). In 13 patients who achieved return-of-spontaneous-circulation (ROSC), sPD-L1 levels were also measured daily in the ICU. Results: The plasma concentrations of sPD-L1 in OHCA were significantly increased; in fact, to levels as high as those observed in sepsis. sPD-L1 levels during CPR correlated with reduced peripheral lymphocyte counts and increased C-reactive protein levels. Of 13 ROSC patients, 7 cases survived in the ICU for more than 4 days. A longitudinal analysis of sPD-L1 levels in the 7 ROSC cases revealed that sPD-L1 levels occurred in parallel with organ failure. Conclusions: This study suggests that ischemia- reperfusion during CPR may aberrantly activate immune and endothelial cells to release sPD-L1 into circulation, which may play a role in the pathogenesis of immune exhaustion and organ failures associated with PCAS.

Identification of a small pericardial effusion on contrast-enhanced computed tomography indicating cardiac perforation and pericardial injury following blunt trauma: A case report.

Blunt trauma may cause cardiac perforation requiring emergency surgical repair. Cardiac perforations are usually diagnosed by the presence of a pericardial effusion on echocardiography. However, cardiac perforations and pericardial effusions are sometimes too small to detect, resulting in underdiagnosis. In this case report, we describe a 22-year-old man who was involved in a traffic accident, admitted in a state of shock, and was initially treated for tension pneumothorax and liver and spleen injuries. His initial computed tomography scans revealed a small region of enhancement, corresponding to a small pericardial effusion, indicative of a cardiac perforation. Thus, an emergency median sternotomy was performed. He was diagnosed with perforation of the left atrial ear and right atrium, which were repaired surgically. His liver and spleen injuries were also treated, and the patient was discharged 44 days after admission. The detection of a small pericardial effusion on enhanced computed tomography enabled rapid diagnosis of a cardiac perforation and ensured emergency surgical repair could be performed as soon as possible. LEARNING OBJECTIVES: •To acknowledge the difficulty of diagnosing cardiac perforation in patients with pericardial injury, based on conventional signs of blunt cardiac injury, such as sternal fracture, serum cardiac enzymes, and hemothorax.•To recognize that a small pericardial effusion on enhanced computed tomography scans is an important finding that should raise suspicion of cardiac perforation and pericardial injury.

Evaluation of hemostatic abnormalities in patients who underwent major hepatobiliary pancreatic surgery using activated partial thromboplastin time-clot waveform analysis.

INTRODUCTION: Bleeding after major hepatobiliary pancreatic (HBP) surgery may be serious. Although postoperative abnormality of the hemostatic system are important elements that affect bleeding, routine activated partial thromboplastin time (APTT) assessment is considered inadequate to predict massive bleeding (MB). Recently, APTT-clot waveform analysis (CWA) was reported to be useful for detecting coagulation disorders. METHODS: APTT-CWA was performed using the ACL-TOP analyzer in 188 patients who underwent four major HBP surgeries (distal pancreatectomy, hepatectomy, subtotal stomach-preserving pancreatoduodenectomy (SSPPD), and SSPPD with combined resection and reconstruction of the portal vein) to analyze its usefulness in predicting the risk of bleeding. RESULTS: Seventy (37.2%) patients developed MB and the incidence of MB was highest among patients who underwent hepatectomy. There were no significant differences in routine APTT, the first derivative peak (DP) time and 1/2 fibrin formation peak time between patients with MB and those without MB, throughout the postoperative course. On the other hand, the first and second DP heights were significantly lower in patients with MB than in those without MB and lowest in patients who underwent hepatectomy. CONCLUSION: APTT-CWA was able to detect the detailed changes in the hemostatic system after major HBP surgery. The patterns of APTT-CWA after major HBP surgery differed among various surgical procedures according to invasiveness. The lower first and the second DP height, which were frequently observed in hepatectomy patients, may be useful for predicting the risk of MB.

Impact of Combined Vascular Resection and Reconstruction in Patients with Advanced Perihilar Cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma often involves the adjacent vasculature, including the portal vein and hepatic artery. Combined vascular resection and reconstruction of the portal vein is more common than vascular resection and reconstruction of the hepatic artery. Herein, we aimed to elucidate the long-term outcomes in patients who underwent vascular resection and reconstruction for perihilar cholangiocarcinoma. METHODS: Between January 2004 and December 2020, 106 patients with perihilar cholangiocarcinoma were grouped into the no resection (n = 58), resection-portal vein (n = 31), and resection-hepatic artery with or without that of portal vein (n = 17) groups. RESULTS: There were no significant differences in morbidity and mortality between the three groups. The resection-portal vein and resection-hepatic artery groups had a significantly higher number of advanced tumors than the no resection group, but no significant differences were detected in the rates of lymph node metastasis and R0 resection between the three groups. The 5-year disease-specific survival in the resection-portal vein (37.6%) and resection-hepatic artery (26.9%) groups were poorer than that in the no resection group (47.8%), although the former groups had a significantly better prognosis than the latter group (7.0%). Multivariate analysis identified high preoperative carcinoembryonic antigen level (>5.7 ng/mL), intrahepatic metastasis, and non-R0 resection as independent poor prognostic factors. CONCLUSION: Although the perioperative course in the resection-portal vein and hepatic artery groups was similar to that in the no resection group, the long-term prognoses were poor in the resection-portal vein and hepatic artery groups. Pre- and postoperative multidisciplinary therapy is required for patients with vascular resection and reconstruction.

The prognostic impact of lymphocyte-to-C-reactive protein score in patients undergoing surgical resection for intrahepatic cholangiocarcinoma: A comparative study of major representative inflammatory / immunonutritional markers.

BACKGROUND: In many malignancies including intrahepatic cholangiocarcinoma (iCCA), prognostic significance of host-related inflammatory / immunonutritional markers have attracted a lot of attention. However, it is unclear which is the strongest prognostic indicator for iCCA among these markers. The aim of this study was to firstly evaluate the prognostic utility of inflammatory / immunonutritional markers in resected iCCA patients using a multiple comparison in addition to a new marker, lymphocyte-to-C-reactive protein (CRP) score. METHODS: A total of sixty iCCA patients, who underwent surgical resection between October 2004 and April 2019, were enrolled in this study. Their clinical and pathological data were retrospectively assessed using univariate and multivariate analysis to determine prognostic predictors for disease specific survival (DSS). Moreover, these patients, who were divided into high and low groups based on lymphocyte-to-CRP score, were compared these survival outcomes using Kaplan-Meier analysis with a log-rank test. RESULTS: In multivariate analysis, the significant prognostic factors were preoperative lymphocyte-to-CRP score (p = 0.008), preoperative CRP-to-albumin ratio (CAR; p = 0.017), pathological T category (p = 0.003), and pathological vascular invasion (p < 0.001). Resected iCCA patients with a low lymphocyte-to-CRP score (score 0) had significant better prognosis than patients with a high score (score 1 or 2) (p = 0.016). Notably, the mortality of the high lymphocyte-to-CRP score group did not show statistically difference from the poor mortality of unresected iCCA patients (p = 0.204). CONCLUSIONS: Preoperative lymphocyte-to-CRP score was the strongest prognostic indicator in iCCA patients with surgical resection. In these patients, early intervention with nutritional support should be considered prior to operation.

The Impact of Dabigatran Treatment on Sinusoidal Protection Against Hepatic Ischemia/Reperfusion Injury in Mice.

Thrombin is a key player in the coagulation cascade, and it is attracting much attention as a promotor of cellular injured signaling. In ischemia/reperfusion injury (IRI), which is a severe complication of liver transplantation, thrombin may also promote tissue damage. The aim of this study is to reveal whether dabigatran, a direct thrombin inhibitor, can attenuate hepatic IRI with focusing on a protection of sinusoidal endothelial cells (SECs). Both clinical patients who underwent hepatectomy and in vivo mice model of 60-minute hepatic partial-warm IRII, thrombin generation was evaluated before and after IRI. In next study, IRI mice were treated with or without dabigatran. In addition, hepatic SECs and hepatocytes pretreated with or without dabigatran were incubated in hypoxia/reoxygenation (H-R) environment in vitro. Thrombin generation evaluated by thrombin-antithrombin complex (TAT) was significantly enhanced after IRI in the clinical study and in vivo study. Thrombin exacerbated lactate dehydrogenase cytotoxicity levels in a dose-dependent manner in vitro. In an IRI model of mice, dabigatran treatment significantly improved liver histological damage, induced sinusoidal protection, and provided both antiapoptotic and anti-inflammatory effects. Furthermore, dabigatran not only enhanced endogenous thrombomodulin (TM) but also reduced excessive serum high-mobility group box-1 (HMGB-1). In H-R models of SECs, not hepatocytes, pretreatment with dabigatran markedly attenuated H-R damage, enhanced TM expression in cell lysate, and decreased extracellular HMGB-1. The supernatant of SECs pretreated with dabigatran protected hepatocytes from H-R damage and cellular death. Thrombin exacerbated hepatic IRI, and excessive extracellular HMGB-1 caused severe inflammation-induced and apoptosis-induced liver damage. In this situation, dabigatran treatment improved vascular integrity via sinusoidal protection and degraded HMGB-1 by endogenous TM enhancement on SECs, greatly ameliorating hepatic IRI.