Search

Vonoprazan (VPZ), a new potassium-competitive acid blocker, has been approved and used for Helicobacter pylori eradication in Japan. To date, many studies, as well as several systematic reviews and meta-analyses (MAs), have compared VPZ-based 7-day triple therapy with proton pump inhibitor (PPI)-based therapy. An MA of randomized controlled trials (RCTs) comparing first-line VPZ- with PPI-based triple therapy, the latter featuring amoxicillin (AMPC) and clarithromycin (CAM), found that approximately 30% of patients hosted CAM-resistant H. pylori; however, the reliability was poor because of high heterogeneity and a risk of selection bias. VPZ-based triple therapy is superior to PPI-based triple therapy for patients with CAM-resistant H. pylori, but not for those with CAM-susceptible H. pylori. An MA of non-RCTs found that second-line VPZ-based triple therapies were slightly (~2.6%) better than PPI-based triple therapies (with AMPC and metronidazole). However, the reliability of that MA was also low because of selection bias, confounding variables and a risk of publication bias; in addition, it is difficult to generalize the results because of a lack of data on antibiotic resistance. VPZ-based triple therapy (involving AMPC and sitafloxacin) was more effective than PPI-based triple therapy in a third-line setting, but a confirmatory RCT is needed. Non-RCT studies indicated that VPZ-based triple therapy involving CAM and metronidazole may be promising. Any further RCTs must explore the antibiotic-resistance status when evaluating the possible superiority of a potassium-competitive acid blocker.

For an esophageal submucosal mass suspicious of granular cell tumor (GCT) based on gross appearance and endoscopic ultrasound findings, a sufficient number of biopsy specimens is required for a definite diagnosis using immunohistochemical examination. When the specimen obtained by forceps biopsy is insufficient, endoscopic ultrasound-fine needle aspiration (EUS-FNA) is believed to be an useful alternative. However, it may be difficult to obtain an adequate amount of tumor material using EUS-FNA. Mucosal incision-assisted biopsy (MIAB) is a simple method that can collect larger amounts of specimens. This procedure is helpful for physicians who encounter the problem of obtaining an adequate amount of biopsy material from esophageal tumors suspicious for GCT. We present a case of esophageal GCT that was successfully diagnosed through MIAB.

Background In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4–B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4–B1 patients. Methods From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications). Results The median follow-up duration was 31.3 months (range: 15.1–71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8–45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months’ observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin–bilirubin grade, respectively. Conclusions For patients with BCLC stage A4–B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.

Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Endoscopic ultrasonography has become a routine procedure in clinical practice and is widely accepted as a safe procedure. Previous studies have reported that severe bleeding rarely occurs even when performing fine-needle aspiration biopsy. Severe hemorrhage following non-interventional endoscopic ultrasonography has never been reported. We herein report a case of hemorrhagic shock due to hemoperitoneum caused by a ruptured right gastroepiploic artery consequent to a diagnostic endoscopic ultrasonography. The patient was administered two antithrombotic agents. An extensive diagnostic workup contributed to the correct diagnosis, which led to a successful treatment by transcatheter arterial embolization. Endoscopists should be aware of this rare, but potentially fatal, adverse event of endoscopic ultrasonography.

BACKGROUND In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years. AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously. METHODS In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US. RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US (P < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S7-8 was identified in 51.7%. CONCLUSION Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.

By analyzing possible factors contributing to imaging misevaluation of arterial phase (AP) vascularity, we aimed to provide a more proper way to detect AP hypervascularity of hepatocellular carcinomas (HCCs) using the noninvasive imaging modalities magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS). We retrospectively recruited 164 pathologically confirmed HCC lesions from 128 patients. Using CEUS with Sonazoid (SCEUS) and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid MRI (EOB-MRI), AP vascularity of the lesions was evaluated and inconsistencies in interpretation were examined. Indicators of margin, echogenicity, and halo and mosaic signs of lesions on grayscale US; depth of lesions on SCEUS; and tumoral homogeneity, signal contrast ratio of lesions to the surrounding area on precontrast and AP images on EOB-MRI, and histological grade were investigated. When precontrast images were used to adjust the AP enhancement ratio, the proportion of inconsistent interpretations of AP vascularity declined from 26.2% (43/164; 29 non-hypervascularity instances using EOB-MRI and 14 using SCEUS) to 16.5% (27/164; 7 using EOB-MRI and 20 using SCEUS). Greater lesion depth (P = 0.017), ill-defined tumoral margin (P = 0.028), absence of halo sign (P = 0.034), and histologically early HCC (P = 0.007) on SCEUS, and small size (P = 0.012) and heterogeneity (P = 0.013) of lesions and slight enhancement (low AP enhancement ratio) (P = 0.018 and 0.009 before and after adjustment) on EOB-MRI, may relate to undetectable hypervascularity. SCEUS and EOB-MRI may show discrepancies in evaluating AP vascularity in the case of deep, ill-defined, heterogeneous, slightly enhanced lesions, and histologically early HCCs. We recommend adjusting AP with precontrast images in EOB-MRI, and combining both modalities to detect hypervascularity.

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

BACKGROUND The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIM To investigate the reduction of HCC development due to ETV therapy by meta-analysis. METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019). RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log10IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log10IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment. CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

Background and Aim To assess the efficacy and safety of 7‐day Helicobacter pylori rescue treatment consisting of a vonoprazan (VPZ), metronidazole (MNZ), and sitafloxacin (STFX) regimen (VPZ‐MNZ‐STFX therapy) in patients with penicillin allergy. Methods This was a registered prospective intervention study. Patients with penicillin allergy who were diagnosed with H. pylori infection and had a history of H. pylori eradication were eligible for inclusion. Seventeen patients were prospectively treated with VPZ 20 mg bid, MNZ 250 mg bid, and STFX 100 mg bid for 7 days. Safety was evaluated using a questionnaire on adverse effects. Results The eradication rate of 7‐day VPZ‐MNZ‐SFTX therapy was 88.2% (95% confidence interval: 63.6–98.5%; n = 17) in both intention‐to‐treat and per‐protocol analyses. On the questionnaire, 25% of patients reported experiencing diarrhea, with a score of 2 or 3. All patients undergoing VPZ‐MNZ‐STFX therapy completed 100% of their medication course. Conclusion Rescue H. pylori eradication with VPZ‐MNZ‐STFX therapy is effective and well tolerated in patients with penicillin allergy (UMIN000016335, jRCTs031180133).

Superficial nonampullary duodenal epithelial tumors (SNADETs) have become frequently detected and referred for endoscopic resection (ER). However, optimal treatment methods and long-term outcomes after ER of SNADETs have not been fully elucidated. We aimed to clarify them by analyzing our large cohort of patients with SNADETs.We enrolled 190 consecutive tumors from 189 patients undergoing ER between January 2004 and September 2019. Cases were stratified into endoscopic submucosal dissection (ESD), conventional endoscopic mucosal resection, (CEMR) and underwater endoscopic mucosal resection (UEMR). Baseline characteristics and short-term outcomes were compared between the groups. Long-term outcomes were also investigated with a median follow-up of 36 months.ESD significantly exceeded CEMR (96.4% vs. 52.9%;While tumors ≤10 mm seem to be good indications for endoscopic mucosal resection, ESD should be considered for larger tumors to better achieve complete resection. Patients with submucosal invasive carcinomas have a great risk of cancer death. Therefore, a close follow-up and an additional treatment are desirable.

The Morisky Medication Adherence Scale is a clinically relevant tool used to evaluate medication adherence. In the current study, the validity and reliability of a Japanese version of the Morisky Medication Adherence Scale and factors related to low adherence were investigated in patients with ulcerative colitis. The original English version was translated into Japanese and then 3 institutions in Japan administered that Japanese version to 428 patients taking medication. Factor validity, internal consistency, and correlations between the Morisky Medication Adherence Scale and adherence were calculated on the basis of patients' own reports of skipped medication, and known group validity between clinically different groups was assessed. Logistic regression was used to assess relationships between low adherence and other factors. The Morisky Medication Adherence Scale identified 184 of 428 patients (43.0%) who exhibited low adherence. Confirmed factor analysis indicated one-dimensionality of the scale. Cronbach's α was 0.74. The Morisky Medication Adherence Scale score was significantly correlated with self-reported missed medication. Patients who were on concomitant induction therapy exhibited significantly better Morisky Medication Adherence Scale scores than those who were not. Patients with low adherence reported difficulty taking medicine, having proctitis, and ulcerative colitis duration of less than 5 years, and were of younger age. The Japanese Morisky Medication Adherence Scale yielded clinically relevant measures of adherence in patients with ulcerative colitis and may promote further international comparative studies.

BACKGROUND Postoperative delayed bleeding (PDB) after gastric endoscopic submucosal dissection (ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population; however, a consensus has yet to be reached. AIM To examine the efficacy of third-look endoscopy (TLE) for PDB prevention. METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB (E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group. RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9% (9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates (L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence (10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed (5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics’ use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents (8.7% vs 23.1% and 5.0% vs 29.4%, respectively). CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.

Katsuaki Ogushi,1,* Makoto Chuma,1,* Haruki Uojima,2 Hisashi Hidaka,2 Kazushi Numata,1 Satoshi Kobayashi,3 Shunji Hirose,4 Nobuhiro Hattori,5 Tomoaki Fujikawa,6 Takahide Nakazawa,2 Naohisa Wada,2 Shuitirou Iwasaki,2 Taito Fukushima,3 Yusuke Sano,3 Makoto Ueno,3 Kuniyuki Kawano,3 Kota Tsuruya,4 Masako Shomura,4 Tsunamasa Watanabe,5 Kotaro Matsunaga,5 Yosuke Kunishi,7 Yusuke Saigusa,8 Kuniyasu Irie,9 Shogo Iwabuchi,6 Makoto Kako,10 Manabu Morimoto,3 Tatehiro Kagawa,4 Katsuaki Tanaka,11 Shin Maeda9 1Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan; 3Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; 6Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan; 7Department of Gastroenterology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan; 8Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 9Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan; 10Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan; 11Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan*These authors contributed equally to this workCorrespondence: Makoto Chuma Gastroenterological CenterYokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa 2320024, JapanTel +81 45 261 5656Fax +81 45 253 9955Email chuma@yokohama-cu.ac.jpPurpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P < 0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥ 0.7 vs < 0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5– 7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.Keywords: lenvatinib, tyrosine kinase inhibitor, hepatocellular carcinoma, Child-Pugh, adverse events, overall survival

Introduction Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. Methods A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. Results The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child–Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5–13). The albumin–bilirubin (ALBI) score ranged from − 3.01 to − 0.45 (median − 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child–Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child–Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10−4 and 2.42 × 10−4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. Conclusion Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. Trial Registration UMIN registration no, 000038587. Electronic supplementary material The online version of this article (10.1007/s40121-020-00329-y) contains supplementary material, which is available to authorized users.

Background/Aims: Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is used to treat thrombocytopenia based on the results of a phase 3 trial, including data for single-use administration in patients with chronic liver disease (CLD) undergoing invasive procedures. We aimed to evaluate the efficacy and safety of repeated lusutrombopag use. Methods: Lusutrombopag was administered repeatedly in patients undergoing multi-cycle invasive procedures at intervals >1 month. Results: Data from 8 patients (median platelet count at baseline, 44.0 [range, 35–49] × 109/L) and 25 cycles of invasive procedures, including 2 cycles in 3 patients, 3 cycles in 4 patients, and 7 cycles in 1 patient, were retrospectively evaluated. The procedures included 18 transarterial chemoembolizations, 5 radiofrequency ablations, and 2 liver needle biopsies. Platelet counts increased significantly compared with baseline, and median changes in platelet counts were 46.0 × 109/L (p = 0.012) in cycle 1, 44.0 × 109/L (p = 0.012) in cycle 2, and 42.0 × 109/L (p = 0.008) in cycles 3–7. No severe adverse events, including portal vein thrombus or bleeding, were observed. Conclusions: Repeated use of lusutrombopag might be safe and effective against thrombocytopenia in patients with CLD undergoing multi-cycle invasive procedures, although long-term data from more patients are required.

OBJECTIVES Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. METHODS We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. RESULTS Both D-MT (41.7 vs. 92.0%; P

Background and Aim Endoscopic duodenal stenting for patients with malignant gastric outlet obstruction (GOO) has been widespread; however, clinical trials evaluating the structures of duodenal stents are lacking. Thus, we aimed to investigate the clinical outcomes of a highly flexible duodenal stent for GOO patients. Methods A prospective study of duodenal stenting for GOO patients from five hospitals between August 2017 and August 2018 was performed. WallFlex Duodenal Soft were used in all procedures. The primary endpoint was clinical success, defined as an improvement in the GOO scoring system. Results The study enrolled 31 patients (12 women, 19 men) with GOO, with a median age of 70 (range 52–90) years. Primary diseases were pancreatic cancer, gastric cancer, biliary tract cancer, and others in 14, 10, 3, and 4 patients, respectively. The technical success rate was 97%, and the clinical success rate was 87%. Simultaneous biliary drainage was performed in 19% of patients. Adverse events occurred in three patients. Chemotherapy was given in 41% of clinically successful cases, and the median overall survival time after stent placement was 82 days (range, 30–341 days), and. Stent dysfunction occurred in 30% of clinically successful cases (stent ingrowth in seven and stent overgrowth in one patient). The median time to stent dysfunction was 157 days (range, 11–183 days). Six patients were treated with additional stent placement after dysfunction. Conclusion Placement of a highly flexible duodenal stent is an effective and safe treatment for patients with GOO (UMIN‐CTR 000028783)., We evaluated the clinical outcome of a highly flexible duodenal stent for gastric outlet obstruction in this multicenter prospective study. Placement of WallFlex Duodenal Soft was an effective and safe procedure.

BACKGROUND In a phase III trial of lenvatinib as first-line treatment for advanced unresectable hepatocellular carcinoma (uHCC), the drug proved non-inferior to sorafenib in terms of the overall survival, but offered better progression-free survival. However, the effects of lenvatinib in uHCC patients with a tumor thrombus in the main portal vein and/or a high tumor burden (tumor occupancy more than 50% of the total liver volume), remain unclear, because these were set as exclusion criteria in the aforementioned trial. CASE SUMMARY A 53-year-old man (case 1) and 66-year-old woman (case 2) with uHCC presented to us with a tumor thrombus in both the main portal vein and inferior vena cava, a high tumor burden accompanied by a tumor diameter greater than > 100 mm, and distant metastasis, with the residual liver function classified as grade 2A according to the modified Albumin–Bilirubin grading. We started both patients on lenvatinib. The therapeutic effect, as evaluated by the modified Response Evaluation Criteria in Solid Tumors, was rated as partial response in both case 1 and case 2 (at 8 wk and 4 wk after the start of lenvatinib administration, respectively). The therapeutic effect was sustained for 6 mo in case 1 and 20 mo in case 2. Fever occurred as an adverse event in both case 1 and 2, and hyperthyroidism and thrombocytopenia in only case 2, neither of which, however, necessitated treatment discontinuation. CONCLUSION Even in hepatocellular carcinoma patients with poor prognostic factors, if the liver function is well-preserved, lenvatinib is effective and safe.

Objective This study compared the clinicopathological features and treatment outcomes of patients with primary early gastric cancers (EGCs) who had undergone Helicobacter pylori eradication and endoscopic submucosal dissection (ESD) with those of patients who were H. pylori-positive and had undergone ESD. Additionally, we investigated the incidence of metachronous cancer in these patients. Methods We retrospectively analyzed 1849 EGCs in 1407 patients who underwent ESD whom 201 primary EGCs were detected after H. pylori eradication (eradication group) and 1648 primary EGCs were detected in patients infected with H. pylori (infection group). We evaluated the clinicopathological features and treatment outcomes of the first ESD. We next divided 938 patients whose follow-up periods were >1 year into three groups, an eradication group (n = 61), an infection group (n = 562), and an eradication after ESD group (n = 315). The groups' cumulative metachronous occurrence rates were determined. Results The eradication group's median tumor size was significantly smaller, and the tumors were significantly more likely to be flat/depressed than those in the infection group. The groups did not differ regarding the treatment outcomes. The cumulative incidence of metachronous cancer was significantly higher in the eradication group than in the eradication after ESD group (P = 0.0454) and in the infection group than in the eradication after ESD group (P = 0.0233). Conclusion The treatment outcomes for EGC in the eradication group were favorable. The higher incidence of metachronous cancer in the eradication group suggests that careful endoscopic follow-up examinations are required.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

Direct-acting anti-virals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. In a phase III trial in Japan, treatment with the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir (G/P) resulted in a small number of patients with refractory factors. We aimed to evaluate the effectiveness and safety of G/P, especially among patients with these refractory factors, and the influence of these factors on treatment. In a prospective, multicenter study involving 33 medical institutions, 1439 patients were treated with G/P, and their efficacy, safety, and most frequent adverse effects (AEs) were analyzed. Overall SVR12 rates were 99.1% (1397/1410) in the per-protocol-analysis, and genotype sustained virologic response SVR12 rates were: genotype 1, 99.4% (707/711); genotype 2, 99.4% (670/674); genotype 3, 80.0% (16/20). DAA-naive patients (p = 0.008) with HCV genotype except 3 (genotype 1 vs. 3, p = 2.68 × 10–5; genotype 2 vs. 3, p = 3.28 × 10–5) had significantly higher SVR12 rates. No significant difference was observed between CKD stage 1–3 (99.1% [1209/1220]) and chronic kidney disease (CKD) stage 4–5 (98.9% [188/190]) patients, or between cirrhotic (99.0% [398/402]) and non-cirrhotic (99.1% [999/1008]) patients. Multiple logistic regression analysis revealed that genotype 3 [OR 33.404, 95% CI (7.512–148.550), p value (p = 4.06 × 10–5)] and past experience of IFN-free DAAs [OR 3.977, 95% CI (1.153–13.725), p value (p = 0.029)] were both significantly independent predictors of non-SVR12. AEs were reported in 28.2% of patients, and 1.6% discontinued treatment owing to drug-related AEs. AEs were significantly higher in CKD stage 4–5 (41.6% [79/190]) than CKD stage 1–3 (26.1% [319/1220]) patients (p = 2.00 × 10–5). AEs were also significantly higher in cirrhotic (38.6% [155/402]) than in non-cirrhotic (24.1% [243/1008]) (p = 2.91 × 10–18) patients. G/P regimen is highly effective and safe to treat CHC patients even with refractory factors such as CKD and advanced liver fibrosis. However, patients with past experience of IFN-free DAA treatment and genotype 3, CKD stage 4 or 5, and advanced liver fibrosis should be more closely observed.

Ultrasonography (US) has the overwhelming advantages of not entailing radiation exposure and being a noninvasive, real-time, convenient, easy-to-perform, and relatively inexpensive imaging modality. It is used as the first-line imaging modality for screening, detection, and diagnosis of focal liver lesions (FLLs) [small hepatocellular carcinomas (HCCs), in particular]. However, with the increasing demand for accurate and early diagnosis of small HCCs, newer radiologic methods need to be explored to overcome certain limitations of US. For example, the imaging is easily negatively affected by the presence of gas, rib cage, and subcutaneous fat, and is insensitive for capturing the subtle but vital information on the blood flow. It was in response to this need that new promising technologies such as contrast-enhanced ultrasound and fusion imaging were introduced for the detection of liver lesions. This paper presents an overview of the epidemiology and mechanisms of the development of HCCs, with an emphasis on the application of US in the diagnosis and treatment of FLLs. The aim of this article is to provide the state-of-the-art developments in the imaging diagnosis of FLLs and evaluation of ablation treatment of early HCCs. By keeping abreast of these recent advances, we hope that doctors and researchers working in the field of diagnosis/treatment of liver diseases will be able to discriminate benign FLLs such as regenerative nodules and focal nodular hyperplasia from HCCs, so as to avoid unnecessary repeated tumor biopsies and overtreatment. In particular, we expect that small HCCs or precancerous nodules (such as dysplastic nodules) can be accurately diagnosed and appropriately treated even at an early stage.

We evaluated the efficacy of fusion imaging combining contrast-enhanced ultrasonography (CEUS) images and arterial phase contrast-enhanced CT (CECT) or hepatobiliary phase magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) images for the early evaluation of the effectiveness of radiofrequency ablation (RFA) for small hypervascular hepatocellular carcinoma (HCC) with iso-echoic or unclear margins on conventional US. Forty HCCs (22 iso-echoic and 18 unclear margin lesions) with mean diameters of 13.7 mm were treated using RFA under the guidance of fusion imaging with CEUS. The adequacy of RFA was evaluated using fusion imaging with CEUS 1 day after RFA. CECT or EOB-MRI was performed 1 month after RFA. We reviewed the images obtained using both modalities. When the 1-month CECT or EOB-MRI scans were used as the reference standard, the sensitivity, specificity, and accuracy of the 1-day fusion imaging for the diagnosis of the adequate ablation of these HCCs were 97, 100, and 98%, respectively; the kappa value for the agreement between the findings using the two modalities was 0.655. Fusion imaging with CEUS appears to be a useful method for the early evaluation of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear margins on conventional US.

Background & Aims: E-cadherin (Cdh1) is a key molecule for adherence required for maintenance of structural homeostasis. Loss of E-cadherin leads to poor prognosis and the development of resistance to chemotherapy in pancreatic cancer. Here, we evaluated the physiological and pathologic roles of E-cadherin in the pancreas. Methods: We crossbred Ptf1a-Cre mice with Cdh1f/f mice to examine the physiological roles of E-cadherin in the pancreas. In addition, we crossbred these mice with LSL-KrasG12D/+ mice (PKC) to investigate the pathologic roles of E-cadherin. We also generated a tamoxifen-inducible system (Ptf1a-CreERT model). Organoids derived from these models using lentiviral transduction were analyzed for immunohistochemical features. Established cell lines from these organoids were analyzed for migratory and invasive activities as well as gene expression by complementary DNA microarray analyses. Results: None of the Ptf1a-Cre mice crossbred with Cdh1f/f mice survived for more than 28 days. We observed aberrant epithelial tubules that resembled the structure of acinar-to-ductal metaplasia after postnatal day 6, showing features of pancreatitis. All of the PKC mice died within 10 days. We observed tumorigenicity with increasing stroma-like aggressive tumors. Ptf1a-CreERT models showed that deletion of E-cadherin led to earlier pancreatic intraepithelial neoplasm formation. Cells established from PKC organoids had greater migratory and invasive activities, and these allograft tumors showed a poorly differentiated phenotype. Gene expression analysis indicated that Hdac1 was up-regulated in PKC cell lines and a histone deacetylase 1 inhibitor suppressed PKC cell proliferation. Conclusions: Under physiological conditions, E-cadherin is important for maintaining the tissue homeostasis of the pancreas. Under pathologic conditions with mutational Kras activation, E-cadherin plays an important role in tumor formation via the acquisition of tumorigenic activity. Keywords: Pancreas, Oncogene, Gene Regulation, Pancreatic Cancer, E-Cadherin

Purpose This study evaluated the usefulness of intraprocedural contrast-enhanced ultrasound (CEUS)/ultrasound (US) fusion imaging using a perflubutane-based contrast agent combined with preprocedural auto sweep three-dimensional US to obtain volume data for guidance and evaluation of the therapeutic efficacy of radiofrequency ablation (RFA). Methods This uncontrolled clinical trial included 50 hepatocellular carcinomas (HCCs) with a mean diameter of 15.3 mm that had been treated by RFA. The efficacy of RFA was evaluated by CEUS/US fusion imaging during the procedure. If the ablation was deemed to be inadequate, further ablation was performed until adequate ablation was achieved. Contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) was performed a month after RFA, and the images obtained using each modality were reviewed to evaluate the efficacy of RFA. Results Thirty-three of the 50 lesions were evaluated by CEUS/US fusion imaging as having been adequately ablated after the first RFA procedure. The ablation was evaluated as inadequate in the remaining 17 lesions, for which additional ablation was performed. Ninety-eight (49/50) of all HCCs were evaluated as having been eventually adequately ablated on intraprocedural CEUS/US fusion imaging. The concordance rate for evaluations between intraprocedural CEUS/US fusion imaging and CECT/CEMRI performed 1 month after RFA was 88% (44/50). The kappa value for agreement between the two methods of evaluation was 0.792. Conclusion Intraprocedural fusion imaging combining CEUS and auto sweep three-dimensional US appears to be a useful modality for RFA guidance and evaluation of therapeutic efficacy of RFA in patients with HCC.

Purpose To assess the impact of clinical factors on the safety and efficacy of atezolizumab plus bevacizumab (ATZ+BV) treatment in patients with unresectable hepatocellular carcinoma (u-HCC). Method Ninety-four u-HCC patients who were treated with ATZ+BV at multiple centers were enrolled. We defined Child-Pugh (CP)-A patients who received ATZ+BV treatment as a 1st line therapy as the 'meets the broad sense of the IMbrave150 criteria' group (B-IMbrave150-in, n=46), and patients who received ATZ+BV treatment as a later line therapy or CP-B patients (regardless of whether ATZ+BV was a 1st line or later line therapy) as the B-IMbrave150-out group (n=48). Patients were retrospectively analyzed for adverse events (AEs) and treatment outcomes according to their clinical status characteristics, including neutrophil lymphocyte ratio (NLR) at baseline. Results The overall incidence of AEs was 87.2% (82/94 patients). The frequency of interruption of ATZ+BV treatment due to fatigue was higher in CP-B than CP-A patients (P=0.030). Objective response (OR) rates of the B-IMbrave150-in group (28.3%, 39.1%) were significantly higher than those of the B-IMbrave150-out group (8.3%, 18.8%; P=0.0157, 0.0401) using Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST, respectively. In multivariate analysis, neutrophil lymphocyte ratio (NLR) (hazard ratio (HR), 4.591; P=0.0160) and B-IMbrave150 criteria (HR, 4.108; P=0.0261) were independent factors associated with the OR of ATZ+BV treatment using RECIST. Conclusion In real-world practice, ATZ+BV treatment might offer significant benefits in patients who meet B-IMbrave150 criteria or have low NLR. This article is protected by copyright. All rights reserved.

Recently, a novel clip device, SureClipWe retrospectively reviewed the medical records of 40 patients who underwent EP for ampullary neoplasms between October 2009 and March 2020. Prophylactic closure after resection was performed using the conventional clip between 2014 and 2018, and with the SureClipThe median age of the patients (25 males and 15 females) was 70 years. The en block resection rate was 82.5% and the curative resection rate was 80.0%. Histologically, 11 (27.5%) patients had malignancy. Prophylactic closure was performed in 29 (72.5%) patients (17 conventional clips, 12 SureClipIn the present study, prophylactic clipping of the mucosal break using the SureClip

Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1R132C or IDH2R172S, and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated IDH1/2 mutations.

Thrombotic microangiopathy (TMA) is a serious complication following kidney transplantation. Although intestinal TMA is a major organ injury and causes abdominal pain, diarrhea and bloody stools, the clinical and endoscopic characteristics of small intestinal TMA remain unclear. Here, we report a drug-induced small intestinal TMA, which did not meet the laboratory-defined TMA criteria but was diagnosed by balloon-assisted enteroscopy (BAE). A 32-year-old woman who underwent kidney transplantation at the age of 10 years complained of abdominal pain, diarrhea and bloody stools one month after starting everolimus (EVE) as an immunosuppressant. Although she did not meet the diagnostic criteria for TMA serologically, BAE revealed a circumferential ulcer in the jejunum, and the pathological findings of a biopsy specimen showed microvascular thrombi, compatible with intestinal TMA. Her symptoms improved upon the discontinuation of EVE, demonstrating that EVE can cause drug-induced intestinal TMA. The present case suggests that BAE should be performed when abdominal pain, diarrhea, and bloody stools occur in patients receiving immunosuppressive medication following kidney transplantation, even if there is no evidence of TMA according to the laboratory definition.

Background This study aimed to compare the value of Sonazoid contrast-enhanced ultrasound (SCEUS) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) for histological grading diagnosis, especially for early hepatocellular carcinoma (eHCC). Methods A total of 163 histopathologically confirmed HCC lesions were retrospectively collected, including 71 eHCCs (27 hypervascular, 44 non-hypervascular) and 92 advanced HCCs (adHCC) (73 hypervascular, 19 non-hypervascular). We performed SCEUS to evaluate the lesions' vascularity during the portal phase (PP) and the echogenicity during the post-vascular phase (PVP). EOB-MRI was used to determine the signal intensity between lesions and the surrounding liver parenchyma on unenhanced T1-weighted images (pre-contrast ratio) in the hepatobiliary phase (HBP) (post-contrast ratio). Results For the PP and PVP of SCEUS (for all lesions), the pre-and post-contrast ratios of EOB-MRI (for all hypervascular lesions) showed statistical differences in the diagnosis of some (but not all) histological grades. For the diagnosis of eHCC, isoechogenicity in the PVP achieved the best diagnostic efficacy [area under the receiver operating characteristic curve (AUC) =0.892]. Whether used independently or in a combination of any form, all indicators failed to produce a higher diagnostic efficacy than PVP. Post- (≥0.610) and pre-contrast ratios (≥0.981) yielded acceptable diagnostic efficacy, with, respectively, accuracy levels of 69.3% and 75.5% and AUC values of 0.719 and 0.736. For eHCC diagnosis, the post-contrast ratio (≥0.625) and combined diagnosis using pre- (≥0.907) and post-contrast ratios (≥0.609) revealed the highest sensitivity (92.6%) for hypervascular lesions and perfect specificity (100%) for non-hypervascular lesions. Conclusions Unenhanced T1-weighted images and the HBP of EOB-MRI [regardless of the vascularity in the arterial phase (AP)], and the PP and PVP of SCEUS showed their value in the histological grading diagnosis of HCC. In particular, isoechogenicity in the PVP may have promising diagnostic utility for eHCC.

Background/Aims: The aim of this study was to determine the correlation between low-dose ramosetron pretreatment and gastric emptying using a novel, non-invasive technique for measuring gastric emptying, namely, the continuous real-time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). Materials and Methods: Twelve healthy male volunteers participated in this randomized two-way crossover study. The subjects fasted overnight and were randomly assigned to receive the test meal (200 kcal per 200 mL) after an hour pre-treatment with 5 µg ramosetron or the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal with the 13C-acetic acid breath test performed continuously using the BreathID system. Using Oridion Research Software (β version), T 1/2, T lag, GEC and the regression-estimated constants (β and κ) were calculated. The differences in the parameters measured at two time-points were analyzed using Wilcoxon’s signed-rank test. Results: There was a significant difference in the calculated parameter β. No significant differences in the calculated parameters T 1/2, T lag, GEC or κ were observed between the test meal with ramosetron group and the test meal alone group. Conclusion: This study showed that ramosetron pre-treatment enhances the early gastric emptying of liquid nutrients.

Background and aim Oral 5-aminosalicylic acid (5-ASA) is recommended for the therapy of mild to moderate intestinal Behcet's disease (BD). However, the induction remission efficacy and endoscopic outcomes of 5-ASA are unknown. We investigated remission induction at 8 weeks, endoscopic outcomes until 52 weeks, and event-free survival at 52 weeks in patients with intestinal BD treated with 5-ASA. Methods Forty-one patients with intestinal BD were treated with oral 5-ASA. Clinical remission was evaluated with the Crohn's disease activity index (CDAI). The endoscopic response was evaluated using the modified global gastrointestinal endoscopic assessment scores. Rescue therapy-free survival and surgery-free survival at 52 weeks were estimated, and predictive factors for a clinical response at weeks 8 and 52 were identified. Results Seven patients (17%) withdrew 5-ASA early (≤ 8 weeks) because of adverse events. At week 8, clinical efficacy could be accurately evaluated in 28 patients, and the response and remission rates were 61% and 57%, respectively, using the CDAI. Endoscopic evaluation was achieved in 17 patients up to 52 weeks, and the endoscopic response and remission rates were 71% and 35%, respectively. The probabilities of rescue therapy-free survival and surgery-free survival were 73% and 100%, respectively, at 52 weeks in all 41 patients. The predictive factors for therapeutic effectiveness at week 8 were a higher baseline C-reactive protein level and CDAI, but they were negative predictive factors for a 52-week response. Conclusions 5-ASA is effective for clinical and endoscopic induction and maintaining a response in patients with mild to moderate intestinal BD.

AIMS Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P

Potentially curative treatments for early-stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early-stage HCC. Consecutive patients with ≤3 early-stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3-year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7-9.2; versus 12.9%, 95% CI, 9.9-16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3-year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2-77.7; and 70.4%; 95% CI, 58.5-79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well-compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.

In cancer patients, impairment of kidney function is not uncommon. Recently, the efficacy of the combination of gemcitabine and nab-paclitaxel for pancreatic ductal adenocarcinoma (PDAC) patients has been reported, however, there is no recommendation for dose and administration to patients undergoing hemodialysis (HD). A 66-year-old man began receiving HD for chronic renal failure 4 years previously. He suffered from diarrhea, back pain, and loss of appetite, and his weight gradually decreased. Abdominal dynamic computed tomography showed a 45-mm hypodense mass in the pancreatic body and a 30-mm hypodense mass in the liver. The patient was diagnosed with metastatic PDAC. He started combination chemotherapy of gemcitabine and nab-paclitaxel without dose modification. He developed pneumonia and neutropenia in the first and second courses, so we modified to a 60% dose of gemcitabine and nab-paclitaxel on day 1 every 2 weeks. After dose modification, he continued combination chemotherapy for over 7 months without severe adverse events or tumor progression. Combination chemotherapy using gemcitabine and nab-paclitaxel was effective in a PDAC patient undergoing HD. While it is possible to originally administer these drugs with no dose modification, early dose modification was needed for our patient because of severe adverse events.