Simple Scoring System for Esophagogastric Varices Prediction in Hepatocellular Carcinoma Patients without Liver Stiffness Evaluation.

INTRODUCTION: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. MATERIALS AND METHODS: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence. RESULTS: Logistic multivariate analysis showed platelet count (≤12 × 104/µL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/µL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001). CONCLUSION: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.

Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Usefulness of aMAP Risk Score for Predicting Recurrence after Curative Treatment for Hepatocellular Carcinoma within Milan Criteria.

INTRODUCTION: The aMAP score is a prediction model for hepatocellular carcinoma (HCC) risk in chronic hepatitis patients. This study was conducted to elucidate the utility of this model for predicting initial recurrence of HCC in patients within the Milan criteria after undergoing curative treatment. METHODS: Patients with naïve HCC within the Milan criteria (n = 1,020) and treated from January 2000 to August 2022 were enrolled. The cohort was divided into two groups according to the aMAP score (high ≥60, low <60) and then compared for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Comparisons between the high and low groups showed that etiology (HBV:HCV:HBV+HCV:NBNC = 41:79:2:37 vs. 65:589:11:196, p < 0.001), AST (36 vs. 46 IU/L, p < 0.001), and multiple HCC occurrence (15% vs. 22%, p = 0.026) were significantly different. Additionally, median RFS (59.8 vs. 30.9 months; p < 0.001) and median OS (154.1 vs. 83.4 months, p < 0.01) were greater in the low group. As for patients with HCC due to chronic viral hepatitis, there was a significant difference in median RFS between the groups (59.8 vs. 30.6 months, p < 0.001), especially for HCV-positive patients (53.1 vs. 27.2 months, p = 0.002). In patients with HCC due to a nonviral cause, the difference in median RFS between the low (70.9 months) and high (32.0 months) groups was not significant. DISCUSSION: Findings of this retrospective study indicate a significant association of elevated aMAP with worse RFS in patients with HCC caused by chronic viral hepatitis, especially those with HCV. The aMAP score is considered useful to predict not only HCC-carcinogenesis risk but also risk of recurrence following curative treatment.

Pancreas stiffness in liver cirrhosis is an indicator of insulin secretion caused by portal hypertension and pancreatic congestion.

AIM: Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. METHODS: Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples. RESULTS: Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. CONCLUSIONS: In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.

Endoscopic stent placement above the sphincter of Oddi for biliary strictures after living donor liver transplantation.

BACKGROUND: Endoscopic balloon dilation and/or plastic stent placement has been a standard method for treating biliary strictures complicated post living donor liver transplantation (LDLT). The strictures may be refractory to endoscopic treatment and require long-term stent placement. However, consensus on the optimal period of the stent indwelling and usefulness of the inside stent does not exist. METHODS: We evaluated the long-term efficacy of stent treatment in patients with biliary stricture post LDLT. In addition, we compared the stent patency between inside stent and conventional outside stent. RESULTS: A total of 98 ERC sessions (median 6: range 1-14) performed on 16 patients receiving endoscopic treatment for biliary strictures post LDLT with duct-to-duct biliary reconstruction were analyzed. Biliary strictures successfully treated in 14 patients (88%) included 7 patients (44%) showing improvement of biliary strictures with repeated endoscopic stent placement. Stent replacement was carried out every 6 to 12 months for the remainder 7 patients (44%). Biliary stents were placed in 87 sessions (77 inside sessions and 10 outside sessions). Stent migration occurred 13 times (16%) and none of the inside stent sessions and the outside stent sessions, respectively. Median patency of inside stent and outside stent were 222 days (range; 8-1736) and 99 days (range; 7-356), respectively. The stent occlusion was significantly less in inside stent than in outside stent (p < 0.001). Stone formation was observed in 14 (18%) of the inside stent and 3 (30%) of the outside stent. Biliary stones were small and successfully removed endoscopically. CONCLUSIONS: The endoscopic treatment using inside stent was useful in the management of biliary strictures after LDLT.

Multicenter prospective evaluation study of endoscopic ultrasound-guided hepaticogastrostomy combined with antegrade stenting (with video).

BACKGROUND AND AIM: Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) is often indicated for advanced stage patients. Therefore it is important to prevent adverse events associated with EUS-HGS procedures and obtain long stent patency. EUS-guided antegrade stenting (AS) has been developed as an advanced technique. Thus, to prevent adverse events and achieve long stent patency, EUS-AS combined with EUS-HGS (EUS-HGAS) has been reported. The aim of the present study was to evaluate the technical feasibility and efficacy of EUS-HGAS in a multicenter, prospective study. METHODS: This prospective study was carried out at each hospital of the Therapeutic Endoscopic Ultrasound Group. Primary endpoint of this multicenter prospective study was stent patency of EUS-HGAS. RESULTS: A total of 49 patients were enrolled. Technical success rate of EUS-HGS was 95.9% (47/49). EUS-AS failed in five patients because the guidewire could not be advanced into the intestine across the bile duct obstruction site. Therefore, EUS-HGAS was successfully carried out in 40 patients (technical success rate: 85.7%). Median overall survival was 114 days. Median stent patency including stent dysfunction and patient death was 114 days. In contrast, mean stent patency was 320 days. Adverse events were seen in 10.2% (5/49) of cases. Hyperamylasemia was seen in four patients, and bleeding was seen in one patient. CONCLUSIONS: The present study is the first to evaluate EUS-HGAS. EUS-HGAS has clinical benefit for obtaining long stent patency and avoiding adverse events, although the possibility of acute pancreatitis as a result of obstruction of the orifice of the pancreatic duct must be considered.

Efficacy of chemotherapy in elderly patients with unresectable pancreatic cancer: a multicenter review of 895 patients.

BACKGROUND: The efficacy of chemotherapy for unresectable pancreatic cancer has improved. However, it is occasionally difficult to make treatment decisions for elderly patients. We reviewed the outcomes of elderly patients with unresectable pancreatic cancer by using a large cohort and evaluated whether they had received chemotherapy and the reason why. METHODS: Data for 895 pancreatic cancer patients who were treated using chemotherapy or best supportive care were analyzed considering demographics, clinical stage, treatment, and outcome. Data were analyzed using the chi-square test, Student t-test, or Mann-Whitney U-test, as appropriate. Outcomes were analyzed using the Kaplan-Meier method. Differences in survival were analyzed using the log-rank test. RESULTS: The median survival time was significantly shorter in elderly patients (≥65 years) than in younger patients (<65 years) (181 vs. 263 days, P = 0.0001). The median survival time of patients treated with chemotherapy was not significantly different between the elderly and the younger group (274 days vs. 333 days, P = 0.09), and nor was that of patients choosing best supportive care (84 days vs. 78 days, P = 0.83). These results held true even when the age cut-off between younger and elder patients was increased to 70, 75, and 80 years. Elderly patients treated with chemotherapy had a significantly longer median survival time than those choosing best supportive care (274 vs. 86 days, P < 0.0001); a significantly greater proportion of elderly patients chose best supportive care compared to younger patients (47.8 vs. 25.8%, P < 0.0001). The reason for choosing best supportive care was established in 261 elderly patients (82.9%); 133 (51.0%) met the eligibility criteria for chemotherapy, but of these, 78 (58.6%) were not informed about their disease. The treatment preferences of elderly patients were not always considered; they often received only best supportive care per family members preference (N = 65, 48.8%) or because the physician based their treatment decision only on the patient's age (N = 68, 51.1%). CONCLUSIONS: Chemotherapy appears effective for elderly pancreatic cancer patients with unresectable disease, but treatment needs to be optimized to improve prognosis.

Renal Cell Carcinoma and Hepatocellular Carcinoma in a Patient with Wilson's Disease.

No reports of renal cancer in patients with Wilson's disease (WD) exist. We herein report a 37-year-old Japanese man diagnosed with WD who had been treated with d-penicillamine 9 years prior. Hepatocellular carcinoma had been diagnosed at 36 years old and treated with radiofrequency ablation therapy. One year later, renal cancer and recurrent hepatocellular carcinoma had developed. The hepatocellular carcinoma was treated after renal cancer surgical resection of a clear-cell-type renal cell carcinoma, with iron, rather than copper, deposited on the renal cancer cells. This patient harbored a novel mutation, p. Leu1395Terfs in ATP7B.

Clinical features of patients with hepatocellular carcinoma treated with radiofrequency ablation therapy: developing a simple score to determine the need for immune-adjuvant therapy.

BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.

Improvement of long-term outcomes in pancreatic cancer and its associated factors within the gemcitabine era: a collaborative retrospective multicenter clinical review of 1,082 patients.

BACKGROUND: Although the outcomes of pancreatic cancer have been improved by gemcitabine, the changes in its characteristics and long-term outcomes within the gemcitabine era remain unclear. This study was conducted to identify clinical characteristics of pancreatic cancer patients within the gemcitabine era. METHODS: A retrospective chart review was performed at 10 centers for 1,248 consecutive patients who were ever considered to have a diagnosis of pancreatic cancer between 2001 and 2010. Data collected included demographics, diagnosis date, clinical stage, treatment, and outcome 1,082 patients met the inclusion criteria and were analyzed further. The chi-square test, Student's t-test, and Mann-Whitney U-test were used for statistical analysis. Outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Differences in survival analyses were determined using the log-rank test. RESULTS: The distribution of clinical stages was: I, 2.2% II, 3.4% III, 13% IVa, 27% and IVb, 55%. Chemotherapy alone was administered to 42% of patients and 17% underwent resection. The 1-, 3-, and 5-year survival rates were 39%, 13%, and 6.9%, respectively. The median survival time was 257 days, but differed considerably among treatments and clinical stages. Demographics, distribution of clinical stage, and cause of death did not differ between groups A (2001-2005, n=406) and B (2006-2010, n=676). However, group B included more patients who underwent chemotherapy (P<0.0001) and fewer treated with best supportive care (P=0.0004), mirroring improvements in this group's long-term outcomes (P=0.0063). Finally, factors associated with long-term outcomes derived from multivariate analysis were clinical stage (P<0.0001), location of the tumor (P=0.0294) and treatments (surgery, chemotherapy) (<0.0001). CONCLUSIONS: Long-term outcomes in pancreatic cancer has improved even within the gemcitabine era, suggesting the importance of offering chemotherapy to patients previously only considered for best supportive care. Most patients are still diagnosed at an advanced stage, making clinical strategy development for diagnosing pancreatic cancer at earlier stages essential.

Patients with Chronic Liver Disease under Surveillance for Hepatocellular Carcinoma Have a Favorable Long-Term Outcome for Pancreatic Cancer Due to Early Diagnosis and High Resection Rate.

Patients with viral hepatitis-related chronic liver disease (CLD) under surveillance for hepatocellular carcinoma (HCC) are often diagnosed with pancreatic cancer (PC) at an early stage. However, the long-term outcomes of these patients are unclear. We aimed to clarify the long-term outcomes of patients with PC with viral hepatitis-related CLD using a chart review. Data collection included the Union for International Cancer Control (UICC) stage at PC diagnosis, hepatitis B virus and hepatitis C virus status, and long-term outcomes. The distribution of the entire cohort (N = 552) was as follows: early stage (UICC 0-IB; n = 52, 9.5%) and non-early stages (UICC IIA-IV; n = 500, 90.5%). At diagnosis, the HCC surveillance group (n = 18) had more patients in the early stages than the non-surveillance group (n = 534) (50% vs. 8.0%), leading to a higher indication rate for surgical resection (72.2% vs. 29.8%) and a longer median survival time (19.0 months vs. 9.9 months). We confirmed that patients with viral hepatitis-related CLD under HCC surveillance were diagnosed with PC at an early stage. Because of the higher indication rate for surgical resection in these patients, they had favorable long-term outcomes for PC.

Clinical impact of recombinant thrombomodulin administration on disseminated intravascular coagulation due to severe acute cholangitis (Recover-AC study).

BACKGROUND AND AIM: Recombinant thrombomodulin (rhTM) is potentially effective in the treatment of disseminated intravascular coagulation (DIC). Several studies related to drugs for the treatment of acute cholangitis have shown negative results in improvement of overall survival (OS) with rhTM. The aim of this multicenter study was to evaluate the clinical effectiveness of rhTM in patients with acute cholangitis and sepsis-induced DIC who underwent biliary drainage. METHODS: A total of 284 consecutive patients, who were complicated with sepsis-induced DIC due to severe acute cholangitis, were included (rhTM group, n = 173; non-rhTM, n = 111) in this study. The primary outcome was the DIC resolution rate at 7 days after starting treatment. The 28-day survival rate was secondarily evaluated. RESULTS: DIC scores in the rhTM group improved significantly compared with the non-rhTM group on day 7 (P = .020). According to multivariate analysis, etiology of cholangitis (malignant, HR 2.28), rhTM (non-administration, HR 4.13), and DIC score (≥5, HR 2.46) were significant factors associated with failed DIC resolution on day 7. Propensity score matching created 103 matched pairs. Survival rate at day 28 was significantly higher in rhTM group (94.3%) compared with non-rhTM group (82.6%; P = .048) after propensity score matching. rhTM (non-administration, HR 2.870), DIC score (≥5, HR 2.751), and APACHE II score (≥20, HR 9.310) were significant factors associated with decreasing survival rate at day 28. CONCLUSION: In conclusion, rhTM seemed to improve patient survival, but future studies should only include patients with benign or malignant disease and should be performed according to APACHE II scores.

Comparison of Surgical Resection and Percutaneous Ultrasonographic Guided Radiofrequency Ablation for Initial Recurrence of Hepatocellular Carcinoma in Early Stage following Curative Treatment.

Background/Aim: The SURF trial showed that surgical resection (SR) and percutaneous ultrasonographic guided radiofrequency ablation (RFA) had equal therapeutic effects for small hepatocellular carcinoma (HCC). However, consensus regarding which treatment is appropriate for initial recurrent early-stage HCC remains lacking. This study aimed to elucidate therapeutic efficacy differences between SR and RFA for initial recurrent early-stage HCC. Materials/Methods: From 2000 to 2021, 371 patients with recurrent early-stage HCC (≤3 cm, ≤3 nodules) after undergoing initial curative treatment with SR or RFA were enrolled (median age 72 years; males 269; Child−Pugh A:B, n = 328:43; SR:RFA, n = 36:335). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated. Results: Although the median albumin−bilirubin (ALBI) score was better in the SR than the RFA group (−2.90 vs. −2.50, p < 0.01), there were no significant differences between them in regard to RFS (median 28.1 months, 95% CI 23.4−50.0 vs. 22.1 months, 95% CI 19.3−26.2; p = 0.34), OS (78.9 months, 95% CI 49.3­not applicable vs. 71.2 months 95% CI, 61.8−84.7; p = 0.337), or complications (8.3% vs. 9.3%; p = 1.0). In sub-analysis for RFS and OS according to ALBI grade revealed no significant differences between the SR and RFA groups (ALBI 1/2 = 28.2/17.5 vs. 24.0/23.4 months; p = 0.881/0684 and ALBI 1/2 = 78.9/58.9 vs. 115.3/52.6 months, p = 0.651/0.578, respectively). Conclusion: This retrospective study found no significant differences in regard to RFS or OS between patients in the SR and the RFA groups for initial recurrence of early-stage HCC after undergoing curative treatment. These results showing equal therapeutic efficacy of SR and RFA confirm the findings of the SURF trial.

Clinical Usefulness of Surgical Resection Including the Complementary Use of Radiofrequency Ablation for Intermediate-Stage Hepatocellular Carcinoma.

Background/Aim: For intermediate-stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC]-B) cases, transarterial chemoembolization (TACE) is recognized as the standard treatment, while systemic therapy is recommended for TACE-unsuitable HCC. However, because the curative potential is not high, this study was conducted to elucidate the potential outcomes of surgical resection (SR) for BCLC-B HCC cases. Materials/Methods: From January 2000 to July 2022, 70 patients with BCLC-B HCC treated with surgery as the initial treatment were enrolled (median age 67.5 years, beyond up-to-7 criteria 44). Forty-five were treated with SR only (SR group), while twenty-five underwent that with complemental radiofrequency ablation (RFA) (Comb group). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated in both groups. Results: The median albumin−bilirubin (ALBI) score was better in the SR as compared with the Comb group (−2.74 vs. −2.52, p = 0.02), while there were no significant differences between them for median RFS (17.7 vs. 13.1 months; p = 0.70) or median OS (66.6 vs. 72.0 months p = 0.54). As for those beyond up-to-7 criteria, there were no significant differences for median RFS (18.2 vs. 13.0 months; p = 0.36) or median OS (66.5 vs. 72.0 months; p = 0.57). An acceptable five-year cumulative survival rate (>50%) was obtained in both groups (54% vs. 64%). Conclusion: This retrospective study found no significant differences for RFS or OS between the present SR and Comb groups with BCLC-B HCC. When possible to perform, the outcome of SR for BCLC-B is favorable, with a five-year survival rate greater than 50%.

Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer.

ABSTRACT: Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients' background data and overall survival were analyzed using the Cox proportional hazard regression model.In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43-91) and 78 (53-90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58-3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs ≤4.5; HR 3.45, 95% CI 2.22-5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02-2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20-5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51-7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0-16.9), 9.4 (95% CI 7.9-10.1), 6.6 (95% CI 4.9-7.8), and 2.5 (95% CI 1.7-4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5-3.9), and 1.3 (95% CI 0.6-1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.

Easy clinical predictor for low BCAA to tyrosine ratio in chronic liver disease patients with hepatocellular carcinoma: Usefulness of ALBI score as nutritional prognostic marker.

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

Factors Related to Sleeping Disorder Due to Pruritus in Patients with Chronic Liver Disease.

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.

Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction with surgically altered anatomy: a multicenter prospective registration study.

BACKGROUND: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population. METHODS: This study involved 10 referral centers in Japan. Patients with SAA who were scheduled to receive EUS-BD for unresectable MBO between May 2016 and September 2018 were prospectively registered. The primary endpoint was technical success and the secondary outcomes were clinical success, procedure time, procedure-related adverse events (AEs), stent patency, and overall survival. RESULTS: In total, 40 patients were prospectively enrolled. The surgical reconstruction methods were gastrectomy with Roux-en-Y reconstruction (47.5%), gastrectomy with Billroth-II reconstruction (15%), pancreaticoduodenectomy (27.5%), and hepaticojejunostomy with Roux-en-Y reconstruction (10%). EUS-BD was performed for primary biliary drainage in 31 patients and for rescue biliary drainage in nine patients. Transmural stenting alone (60%), antegrade stenting alone (5%), and a combination of the two techniques (35%) were selected for patients treated with EUS-BD. Technical and clinical success rates were 100% (95% confidence interval, 91.2-100.0%) and 95% (95% confidence interval, 83.1-99.4%), respectively. Mean procedure time was 36.5 min. Early AEs were noted in six patients (15%): three self-limited bile leak, one bile peritonitis, and two pneumoperitonea. Late AEs occurred in six patients (15%): one jejunal ulcer and five stent occlusions. Stent patency rate after 3 months of survival was 95.7% (22/23). Median overall survival was 96 days. CONCLUSION: EUS-BD for MBO in patients with SAA appears to be effective and safe not only as a rescue drainage technique after failed endoscopic retrograde cholangiography but also as a primary drainage technique. CLINICAL TRIAL REGISTRATION: UMIN000022101.

ABO Blood Type and the Long-term Outcomes of Pancreatic Cancer.

Objective The long-term effect of the ABO blood type on the clinical course of patients with pancreatic cancer (PC) is inconclusive. This study aimed to determine whether or not the ABO blood type influences the long-term outcomes of PC in Japanese patients. Methods The medical records of Japanese patients with PC were reviewed. Data, including the age, sex, and outcomes, from the Ehime Pancreato-Cholangiology Study Group were analyzed. Results The mean age of the 406 patients was 71.0±10.5 years, and 220 (54.2%) were men. A total of 44.6%, 20.7%, 22.4%, and 12.3% had blood type A, B, O, and AB, respectively. The median survival time (MST) of patients with A alleles was shorter than that of patients with non-A alleles (p=0.048), especially among those who underwent resection (p=0.031). In contrast, no marked difference in the MST was noted among those who underwent chemotherapy and palliative care. Finally, a multivariate analysis confirmed A alleles as an independent factor associated with the long-term outcome of PC (p<0.05 in 2 different models). Conclusion The ABO blood type influenced the long-term outcomes of Japanese patients with PC, presumably due to its impact on disease onset and tumor behavior.

Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance.

OBJECTIVE: To evaluate whether patients with hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ2 test. RESULTS: The UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease. CONCLUSION: Patients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.