Objective:In palliative medicine, accurate prognosis of patients with terminal cancer is crucial. Serum albumin (Alb), transthyretin (TTR), and C-reactive protein (CRP) have been reported to be associated with prognosis. Pancreatic cancer is generally a rapidly progressing disease with an extremely poor prognosis. In the present study, we focused on identifying prognostic factors in patients with terminal pancreatic cancer. Methods:Overall, 756 patients with terminal cancer were admitted for palliative care and died during the 3-year period from April 2018; of these, 72 patients with pancreatic cancer (9.5%; excluding those who died within 7 days of admission) were included in the study. In addition to assessing clinical symptoms at admission, blood tests were performed to measure serum Alb (g/dL), TTR (mg/dL), CRP (mg/dL), and tumor markers. Body composition was analyzed using bioelectrical impedance analysis (BIA; InBody S10) to determine skeletal muscle mass index (SMI, kg/m2), extracellular water to total body water ratio (ECW/TBW), and phase angle (°). Prognostic factors were then evaluated. Results:The median age was 75 years (range: 33-91 years), with a male-to-female ratio of 37:35. The median survival time was 24 days (range: 7-99 days). After adjusting for age, sex, and performance status as potential confounders, multivariate analysis revealed that CRP (hazard ratio [HR]: 1.0998; 95% confidence interval [CI]: 1.0248-1.1781; p=0.0072), ECW/TBW (HR: 1.4391; 95% CI: 1.1429-1.8080; p=0.0018), and depressed mood (HR: 1.155; 95% CI: 1.036-1.281; p=0.0074) were significantly associated with prognosis. The cutoff values for 4-week survival (approximately 1-month survival) were CRP ≥2.0 mg/dL and ECW/TBW ≥0.430. Conclusion:Patients with terminal pancreatic cancer presented with advanced chronic inflammation at admission in addition to cachexia. Multivariate analysis revealed that serum CRP level and ECW/TBW ratio are independent prognostic factors, suggesting that prognosis in terminal pancreatic cancer is associated with the severity of chronic inflammation and edema. Among clinical symptoms, the degree of depression may also be related to prognosis, indicating that psychological distress should be considered in palliative care assessments.

Abstract Background This study aimed to clarify the effectiveness of nutrition support team (NST) facilities for preventing central line-associated bloodstream infection (CLABSI). Methods We retrospectively analyzed the incidence of CLABSI as well as the presence or absence of additional medical fees for NST activity between 2019 and 2021, including the period before and after the COVID-19 pandemic. Subsequently, we performed between-group comparisons of the CLABSI incidence. CLABSI rates were compared based on cumulative per 1000 catheter uses during the relevant period. Results Among 47 facilities that were registered for participation, there were 34 and 13 facilities with and without additional medical fees for NST activity (NST and non-NST groups, respectively). The CLABSI incidence rate was significantly lower in the NST group 0.96 [0.28–1.73] than in the non-NST group 1.25 [075–6.10] (p < 0.05). Before the pandemic, the NST group had a lower CLABSI rate per 1000 catheter uses than the non-NST group 2019: 0.70 [0.12–1.26] vs 2.10 [0.62–5.97]. During the pandemic, the CLABSI incidence showed no significant between-group difference 2020: 0.99 [0.51–1.61] vs 1.01 [0.80–4.16]; 2021: 1.24 [0.44–2.35] vs 1.96 [1.23–5.31]; however, the CLABSI rates in the NST group remained low. Conclusion During the COVID-19 pandemic, the incidence of CLABSI was lower in the NST group than in the non-NST group, indicating the effectiveness of NST in preventing the occurrence of CLABSI.

Objectives:Patients with terminal cancer tend to have an increased frequency of a variety of clinical symptoms, including anorexia, at 1 month of life expectancy. This study examined clinical symptoms affecting anorexia in patients with terminal cancer. Methods:Of 1068 patients with terminal cancer who died and were discharged from our hospital between April 2014 and March 2016, we included 471 patients whose clinical symptoms could be subjectively assessed within 4 weeks before death.Patients were evaluated subjectively on a scale of 0 to 10 (11-point scale) using the Numerical Rating Scale (NRS) once a week for nine major clinical symptoms: (1) pain, (2) general fatigue, (3) dyspnea, (4) depressed mood, (5) anorexia, (6) insomnia, (7) nausea, (8) constipation, and (9) dry mouth. Primary data within 4 weeks prior to death were used for analysis, and Spearman's rank correlation was used to examine clinical symptoms affecting anorexia. Results:Spearman's rank correlation coefficients between anorexia and the following clinical symptoms were: pain, 0.186; general fatigue, 0.414; dyspnea, 0.15; depressed mood, 0.287; insomnia, 0.327; nausea, 0.297; constipation, 0.215; and dry mouth, 0.204. General fatigue was positively correlated with anorexia. Conclusions:General fatigue may influence anorexia in patients with terminal cancer.

Background/Aim: Catheter-related bloodstream infections (CRBSI) are frequently life-threatening. Several factors have been reported to be related to CRBSI development; however, the factors associated with CRBSI mortality are unclear as they have rarely been studied. This study investigated the factors associated with mortality in patients with CRBSI, specifically focusing on nutritional factors. Patients and Methods: This retrospective, multicenter study included in-patients with acute conditions and convalescent patients diagnosed with a CRBSI between January 2019 and December 2021 at 33 hospitals (23 general hospitals, two mixed-care hospitals, and eight convalescent hospitals). The primary outcome was death. Unadjusted and multivariable logistic regression analysis was performed to identify factors associated with mortality. Results: A total of 453 patients with CRBSI were enrolled. The causes of death were analyzed for 382 (84.3%) who survived CRBSI and 71 (15.7%) who died. Multivariable analysis revealed that Candida detected in blood culture [adjusted odds ratio (aOR)=2.72, 95% confidence interval (CI)=1.15-6.41; p=0.025)], CRBSI onset within 30 days of catheter insertion (aOR=2.28, 95% CI=1.27-4.09; p=0.005), concurrent infection (aOR=2.07, 95% CI=1.19-3.60; p=0.009), low serum albumin level (aOR=1.64, 95% CI=1.02-2.63; p=0.044), and elevated C-reactive protein level (aOR=1.05, 95% CI=1.01-1.10; p=0.028) were risk factors for mortality, whereas the use of a peripherally inserted central catheter was associated with a reduced risk of CRBSI mortality (aOR=0.30, 95% CI=0.13-0.69; p=0.004). Conclusion: Enhanced monitoring of factors, such as candida detected in blood culture, CRBSI onset within 30 days of catheter insertion, concurrent infection, low serum albumin level, elevated C-reactive protein (CRP) level and the use of a peripherally inserted central catheter (PICC), is crucial for mitigating CRBSI severity and risk of death.

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 recipi-ents 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-interna-tional 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 (& GE;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 postopera-tive irreversible liver damage early.

Objectives: Antiemetics have been widely recommended for treating opioid-induced nausea and vomiting (OINV). According to a previous study, the use of prophylactic prochlorperazine at the initiation of treatment with oral oxycodone was ineffective in preventing OINV. This study examined whether prochlorperazine injection prevents OINV and induces drowsiness in patients with end-stage cancer (a different patient population from the previous study). Methods: Patients with end-stage cancer who received opioid injections for more than 5 days between April 2017 and March 2020 were classified into two groups: the opioid and prochlorperazine injection group and opioid alone group. Their systemic conditions were evaluated on the basis of the performance status and the palliative performance scale, a prognostic indicator. Results: Of 325 patients who received opioid treatment during the study period, 156 patients met the inclusion criteria. Of these, 103 patients and 53 patients were classified into the opioid and prochlorperazine injection group (prochlorperazine) and opioid alone groups (placebo) , respectively. There was no significant difference in characteristics, age, gender, performance status, or palliative performance scale results between the 2 groups. OINV developed in 4 patients in the opioid and prochlorperazine injection groups and in 1 patient in the opioid alone group. Given that sleep disturbance develops in many patients with end-stage cancer who had a specific condition, it is difficult to conclude regarding the relationship between prochlorperazine injection and drowsiness, although this study examined this relationship. Conclusions: As with the previous study, prophylactic prochlorperazine injection was ineffective in preventing OINV in patients who received opioid injections.

BACKGROUND:Many studies have shown deterioration of the oral health environment in palliative care patients; however, most of these studies are cross-sectional. In this longitudinal observational study, we aimed to determine the oral symptoms and how they change in palliative care patients.METHODS:The participants were 82 patients (37 men, 45 women) admitted to two palliative care units in Japan between January 2018 and December 2021. The oral condition was evaluated once a week from the time of admission using the Oral Health Assessment Tool (OHAT) and performance status (PS). Friedman tests were performed on the OHAT and PS scores at 1, 2, and 3 weeks before the week of death. In addition, the Bonferroni method was used to determine how many weeks before death the changes occurred.RESULTS:PS continuously deteriorated from three weeks before death. The total OHAT score 2 weeks before death (3.44±2.10) was significantly different compared to that in the week of death (4.37±2.45). In terms of oral conditions, the properties of the saliva changed, and dry mouth became obvious.CONCLUSIONS:The results of this study revealed that the oral environment of palliative care patients became significantly dry 2 weeks before death, suggesting that it may be useful for predicting the stage of death.

Objective: Tolvaptan, a vasopressin V2 receptor antagonist, is an oral diuretic. Patients with terminal cancer develop marked fluid retention, and oral diuretics other than tolvaptan have been used as treatments without clear therapeutic effects. Herein, we aimed to study the efficacy and safety of tolvaptan in patients with terminal cancer. Methods: Tolvaptan was administered at a dose of 7.5 mg/day to 29 patients (median, 72 years) between August 2017 and February 2020. The duration of tolvaptan treatment ranged from 1 to 85 days (mean, 18.5 days). Results: Median albumin (Alb) and transthyretin (TTR) levels on admission were 2.3 g/dL (1.2–4.2 g/dL) and 8.9 mg/dL (2.1–38.2 g/dL), respectively. Median Alb and TTR levels 1 month after treatment initiation remained at 2.3 g/dL (0.8–2.9 g/dL) and 8.6 mg/dL (0.8–23.7 mg/dL), respectively. Regarding renal function indicators, median blood urea nitrogen (BUN) and creatinine levels on admission were 19.9 mg/dL (8.6–49.3 mg/dL) and 0.81 mg/dL (0.38–2.25 mg/dL), respectively. Median BUN and creatinine levels 1 month after treatment initiation were 23.4 mg/dL (13.5–34.0 mg/dL) and 0.91 mg/dL (0.39–2.41 mg/dL), respectively. No patients had hypernatremia on admission, and no effects of tolvaptan on the blood sodium level were found 1 month after treatment initiation. The median potassium level on admission was 4.2 mEq/dL (2.9–5.0 mEq/dL); tolvaptan treatment had no effects on blood potassium level. Conclusions: Tolvaptan is effective and safe for treating fluid retention refractory to conventional diuretics in patients with terminal cancer.

Objectives: Patients with cancer, especially those with lung cancer, are at high risk of developing thrombosis. Intralipos® infusion 20% is contraindicated for thrombosis, and there is no consensus on whether it can be safely used in cases of advanced cancer. We conducted a retrospective observational study to elucidate the impact of fat emulsion administration on blood coagulation in patients with terminal lung cancer. Methods: The subjects were patients with terminal lung cancer in the Department of Surgery and Palliative Medicine, Fujita Health University Nanakuri Memorial Hospital between January 2016 and December 2019. We compared changes in their blood coagulation profile before hospitalization and one month later. Results: There were a total of 213 patients with lung cancer—139 who were administered fat emulsion and 74 who were not—with no significant differences in baseline characteristics. In the fat emulsion administration group (n=27), the prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (APTT), respectively, were 1.17±0.26 (mean±standard deviation) and 30.5±5.0 s at hospitalization and 1.16±0.12 and 31.2±4.2 s one month later with no significant differences. In the non-administration group (n=6), the PT-INR and APTT, respectively, were 1.44±0.43 and 30.6±5.2 s before hospitalization and 1.28±0.18 and 33.0±7.5 s one month later with no significant differences. Conclusions: We did not identify any changes in PT-INR and APTT after fat emulsion administration in patients with terminal lung cancer. There were also no new cases of thrombosis, suggesting that fat emulsions were administered safely in patients with terminal lung cancer.

Background Our aim is to elucidate the true preoperative risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), making it possible to select POPF high-risk patients preoperatively regardless of intraoperative pancreatic consistency judged by the surgeon’s hand. Methods Among the 298 patients who underwent PD with pancreaticojejunostomy from 2007 to 2016, 262 patients had preoperative CT configurations that could be precisely evaluated. Risk factor analyses were conducted using various perioperative factors, including preoperative CT findings, such as CT values of the pancreas, pancreas-visceral fat CT value ratio and pancreatic outer contour. Pancreatic outer contour was further divided into smooth- (smooth interlobular) and serrated-type contours (feathery, irregular interlobular) by preoperative CT. Results In terms of the incidence of POPF, among the 262 patients, POPF grade B/C was found in 27 (10.3%): grade B in 23 (8.8%) and grade C in 4 (1.5%). According to multivariate analysis, a high pancreas-visceral fat CT value ratio ( p = 0.002), serrated-type contour ( p = 0.02) and no history of chemoradiotherapy ( p = 0.019) were identified as independent risk factors for POPF grade B/C. Even in patients with soft pancreas, the incidence of POPF grade B/C was 0% (0/57) in patients with a pancreas-visceral fat CT value ratio of less than − 0.4 and smooth-type contour, whereas the incidence was markedly high (45.0%, 9/20) in patients with a pancreas-visceral fat CT value ratio of − 0.4 or greater and serrated-type contour, indicating that patients with soft pancreas should be categorized into POPF high-risk and low-risk groups according to preoperative CT scan results. Conclusions The pancreas-visceral fat CT value ratio and serrated-type pancreas are useful markers to preoperatively identify true POPF high-risk groups in patients undergoing PD, regardless of the pancreatic texture judged intraoperatively.

OBJECTIVE:The aim of the study was to identify the prognostic factors before neoadjuvant chemoradiotherapy (NCRT) in the patients with localized PDAC. Furthermore, to identify the post-surgical survival predictors of patients with LAPC.SUMMARY OF BACKGROUND DATA:Surgical resection may occupy an important position in multimodal therapy for patients with LAPC; however, its indication and who obtains the true benefits, is still uncovered.MATERIALS AND METHOD:From 2005 to 2017, 319 patients with localized PDAC who underwent NCRT were reviewed. Only 159 patients were diagnosed with LAPC, of these 72 patients underwent surgical resection. We examined the pre-NCRT prognostic factors in the entire cohort and conducted further subgroup analysis for evaluating the post-surgical prognostic factors in LAPC patients under the pretext of favorable local tumor control.RESULTS:In the entire cohort, pre-NCRT CEA value was recognized as the most significant prognostic indicator by multivariate analysis. In the 72 LAPC patients who underwent surgical resection, only high CEA level was identified as an independent dismal prognostic factor before surgery. At the cut-off value: 7.2ng/mL, survival of the 15 patients whose CEA value >7.2 ng/mL was significantly unfavorable compared to those of 57 patients with <7.2 ng/mL: Median disease-specific survival time: 8.0 versus 24.0 months (P < 0.00001). Moreover, the median recurrence-free survival time of the high CEA group was only 5.4 months and there was no 1-year recurrence-free survivor.CONCLUSIONS:CEA before NCRT is a crucial prognostic indicator for localized PDAC. Moreover, LAPC with a high CEA level, especially more than 7.2 ng/mL, should still be recognized as a systemic disease, and we should be careful to decide the indication of surgery even if tumor local control seems to be durable.

Aim High-level hepatobiliary pancreatic (HBP) surgeries are highly associated with surgical site infections (SSIs), in which microorganisms have a significant role. In the present study, we investigated whether gastric Candida colonization had a significant role in SSIs after high-level HBP surgeries. Methods Between May 2016 and February 2017, the 66 patients who underwent high-level HBP surgeries were enrolled in the present study. The gastric juice was prospectively collected through nasogastric tube after general anesthesia induction and was incubated onto the CHROMagar Candida plate for the cultivation of various Candida species. First of all, we compared the incidence of SSIs according to the presence or absence of Candida species in gastric juice. Secondly, we evaluated the variables contributing to the development of SSIs by multivariate analysis. The protocol was approved by the medical ethics committee of Mie University Hospital (No.2987). Results Gastric Candida colonization was identified in 21 patients (group GC) and was not identified in the other 45 patients (group NGC). There were no differences in preoperative variables including compromised status, such as age, nutritional markers, complications of diabetes mellitus, and types of primary disease between the two groups. SSIs occurred in 57.1% (12/21) of group GC and in 17.8% (8/45) of group NGC, showing a significant difference ( p = 0.001). Multivariate analysis revealed gastric Candida colonization as a significant risk factor of SSIs (OR 6.17, p = 0.002). Conclusion Gastric Candida colonization, which is not a result of immunocompromised status, is highly associated with SSIs after high-level HBP surgeries. Trial registration Japan Primary Registries Network; UMIN-CTR ID: UMIN000040486 (retrospectively registered on 22nd May, 2020).

BACKGROUND:Arterial pseudoaneurysm is a rare but potentially fatal complication after pancreaticoduodenectomy (PD). This study aimed to evaluate the incidence and predictors associated with pseudoaneurysm formation and patient death caused by its rupture. PATIENTS AND METHOD:We retrospectively reviewed the data of 453 patients who underwent PD from April 2007 to February 2019. Uni- and multivariate analysis and receiver operating characteristic (ROC) curve analysis were performed to identify risk factors and optimal cutoff values. RESULTS:Among the 453 patients, 22 (4.9%) developed pseudoaneurysm after PD. Median duration from surgery to detection of pseudoaneurysm was 17.0 (1-51) days. The locations of pseudoaneurysms were hepatic artery in 8, splenic artery in 3, gastroduodenal artery in 4, gastric artery in 2 and others in 5 patients, and 72.7% (16/22) of patients presented with hemorrhage. All pseudoaneurysms were treated using angioembolization. Lower age (<65.5 years, p = 0.004), prolonged operation time (Cutoff ˃610 min, p = 0.026) and postoperative pancreatic fistula (POPF) (p = 0.013) were the independent risk factors for development of pseudoaneurysm. 6 (27.3%) patients died due to rupture of pseudoaneurysm and prolonged operation time (Cutoff ˃657 min, p = 0.043) was a significant risk factor for death related to pseudoaneurysm. CONCLUSION:Prolonged operating time was identified as a risk factor for both pseudoaneurysm formation and patient death following pseudoaneurysm bleeding. Interventional radiology treatment offered a central role in the treatment of pseudoaneurysms after PD. Therefore, it is important to have a high index of suspicion in high risk patients of the possibility of pseudoaneurysm formation and bleeding.

Despite the development of several therapeutic options, the prognosis of pancreatic cancer remains poor. One reason for this is the difficulty of diagnosing the disease at an early stage. For example, carbohydrate antigen (CA) 19-9, which is the most widely used biomarker for pancreatic cancer, cannot be used to detect the disease at early stages. Some studies have attempted to find novel biomarkers for pancreatic cancer. The aim of the present study was to find a novel diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC) in urine exosomes. Exosomes were isolated from urine and serum samples of patients with PDAC and control subjects, or culture media of cancer cell lines. MicroRNAs (miRNAs) were purified from exosomes. Novel biomarker candidates for PDCA were identisfied from urine exosome miRNA using expression profiling, and validated in a larger number of samples using 3D digital PCR. The results of a preliminary analysis of nine PDAC and seven control subjects revealed that the miR-3940-5p/miR-8069 ratio in urine exosomes was elevated in the patients with PDAC. Experiments using cultured cancer cell lines revealed that the elevation of the miR-3940-5p/miR-8069 ratio was specific for PDAC. Furthermore, the elevation of the miR-3940-5p/miR-8069 ratio in exosomes tended to be higher in the urine than in the serum of patients with PDAC. Validation experiments on 43 PDAC, 12 chronic pancreatitis and 25 control subjects demonstrated that the miR-3940-5p/miR-8069 ratio in urine exosomes was elevated in PDAC at a relatively early stage of the disease. When this ratio was used in combination with CA19-9 for the diagnosis of PDAC, the sensitivity and positive predictive value improved to 93.0 and 78.4%, respectively, when either of them was positive. Additionally, the positive predictive value reached 100% when both were positive. The negative predictive value also improved to 89.7% when both were negative. The miR-3940-5p/miR-8069 ratio in urine exosomes may be useful as a tool for the diagnosis of PDAC, particularly when used in combination with CA19-9.

Background The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy. Methods Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1. Results Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection. Conclusion Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.

Background Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. Methods Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). Results In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). Conclusion This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

Background After splenectomy in patients with chronic liver disease, a large spleen was reported to be not only a risk factor of portal/splenic vein thrombosis (PSVT), but also a prediction for favorable improvement of liver function. This study aimed to evaluate the risk of PSVT and the improvement of liver function after splenectomy, with special attention to spleen volume (SV). Methods This studied included 50 patients who underwent splenectomy with diagnosed chronic liver disease between January 2005 and December 2017. After evaluation of risk factors for PSVT the cut-off value of SV for predicting PSVT was determined. According to the cut-off value of SV, 50 patients were divided into 2 groups: small-volume group (SVG) and large-volume group (LVG). Postoperative liver functions were compared between the 2 groups. Results Twenty-eight patients developed PSVT. Larger SV was the most significant independent risk factor for PSVT. The cut-off value of SV was 520 mL. Preoperatively, LVG had significantly higher total bilirubin, and MELD (model for end-stage liver disease) score, and had significantly higher rates of pancytopenia than SVG. Postoperatively, compared to SVG, platelet count, choline esterase, and total cholesterol in LVG were significantly increased. Conclusion After splenectomy in the patients with chronic liver disease, large SV is an independent risk factor for PSVT, with a clear benefit in improving liver function, if PSVT is properly diagnosed and managed.

Much evidence has demonstrated the influence of Hepatitis B virus (HBV) mutations on the clinical course of HBV infection. As large (L) protein plays a crucial role for viral entry, we hypothesized that mutations in the pre-S1 promoter region might affect the expression of L protein and subsequently change the biological characters of virus. Patients infected with genotype C HBV were enrolled for analysis. HBV DNA sequences were inserted into a TA cloning vector and analyzed. To evaluate the effects of mutations in the pre-S1 promoter region, promoter activity and the expression of mRNA and L protein were analyzed using HepG2 cells. In total, 35 patients were enrolled and 13 patients (37.1%) had a single base substitution in the pre-S1 promoter region; the most frequent substitution was a G-to-A substitution at the 2765th base (G2765A) in the Sp1 region. The HBV viral load showed a negative correlation with the substitution ratio of the Sp1 region or G2765A (r = − 0.493 and − 0.473, respectively). Among those with a viral load ≤5.0 log IU/ml, patients with the G2765A substitution showed a significantly lower HBV viral load than those with the wild-type sequence. HepG2 cells transfected with the G2765A substitution vector showed reduced luciferase activity of the pre-S1 promoter, as well as reduced expression of pre-S1 mRNA and L protein. Furthermore, the G2765A substitution greatly reduced the L protein expression level of vector-produced virus particles. G2765A substitution in the pre-S1 promoter reduced the expression of L protein and resulted in a low viral load and less severe disease in chronic HBV infections.

Objectives To evaluate clinical/histological response and prognosis between preoperative gemcitabine-based chemoradiation therapy (G-CRT) and gemcitabine plus S1–based CRT (GS-CRT) for localized pancreatic ductal adenocarcinoma patients according to the 3 resectability groups. Methods Among 199 patients who had 90% or more relative dose intensity of chemotherapy and completion of radiotherapy preoperatively (G-CRT: 98 and GS-CRT: 101), the subjects were 113 patients (G-CRT: 60 and GS-CRT: 53) who underwent curative-intent resection, and we compared clinical and histological effects between the 2 regimens. Results There is a significant improvement in clinical and histological responses as assessed by reduction rate in tumor size, post-CRT serum level of carbohydrate antigen 19-9, and the ratio of histological high responder according to the Evans grading system in GS-CRT, as compared with G-CRT, which in turn significantly increased R0 resection rate (P = 0.013). These effects of GS-CRT resulted in significant improvement of disease-specific survival (median survival time, 36.0 vs 27.2 months; P = 0.042), especially in patients with unresectable locally advanced disease (36.0 vs 18.1 months, P = 0.014). Conclusions For localized pancreatic ductal adenocarcinoma patients, GS-CRT, as compared with G-CRT, provides significant improvement in clinical and histological response as well as long-time survival, especially in patients with unresectable locally advanced disease.