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Objectives: Endoscopic ultrasonography (EUS) plays an important role in the diagnosis of pancreatobiliary diseases. However, an appropriate sedation method for EUS has not been established. Therefore, this study aimed to examine the safety and complications of sedation with pentazocine or pethidine hydrochloride for outpatient diagnostic EUS., Methods: We retrospectively reviewed 1302 consecutive cases in our department that underwent outpatient diagnostic EUS between April 2019 and September 2021. Until June 2020, EUS was performed under sedation with midazolam and pentazocine (pentazocine group) in principle; after June 2020, sedation with midazolam and pethidine hydrochloride (pethidine hydrochloride group) was used. A cohort of patients with comparable backgrounds was identified using propensity score matching., Results: A total of 486 cases were included in this study. Sedation-related adverse events during the endoscopic procedures were not significantly different between the groups. The median time spent in the recovery room after EUS was significantly shorter in the pethidine hydrochloride group than in the pentazocine group (69 versus vs. 77 min; p  < 0.001). The frequency of nausea or vomiting after EUS was significantly lower in the pethidine hydrochloride group than in the pentazocine group (0% [0/486] vs. 6.2% [29/486]; p  < 0.001). The frequency of readmission to the recovery room after discharge was significantly lower in the pethidine group than in the pentazocine group (0 [0%] vs. 18 [3.7%], respectively; p  < 0.001)., Conclusions: The combination of midazolam and pethidine hydrochloride is a more favorable anesthetic than the combination of midazolam and pentazocine for diagnostic EUS in outpatients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

There is little evidence regarding radiation dose perturbation caused by the self-expandable metallic stents (SEMSs) used for transpapillary biliary decompression. We aimed to compare SEMSs with plastic stents (PSs) and clarify their dosimetric characteristics. Fifteen SEMSs (10 braided and 5 lasercut type) and six PSs (diameter: 2.3-3.3 mm) were inserted into a water-equivalent solid phantom. In total, 13 SEMSs had radiopaque markers, whereas the other two did not. Using radiochromic films, the dose difference adjacent to the stents at locations proximal, distal, and arc delivery to the radiation source was evaluated based on comparison to measurement of the dose delivery in phantom without any stent in place. The median values of the dose difference for each stent were used to compare the SEMS and PS groups.Results: The dose difference (median (minimum/maximum)) was as follows: proximal, SEMSs + 2.1% (1.8 / 4.7) / PSs + 5.4% (4.1 / 6.3) (p < 0.001); distal, SEMSs -1.0% (-1.6 /-0.4) / PSs -8.9% (-11.7 / -7.4) (p < 0.001); arc delivery, SEMSs 1.2% (0.9 / 2.3) / PSs 2.2% (1.6 / 3.6) (p = 0.005). These results demonstrated that the dose differences of SEMSs were significantly smaller than those of PSs. On the other hand, the dose difference was large at surface of the radiopaque markers for SEMSs: proximal, 10.3% (7.2 / 20.9); distal, -8.4% (-16.3 / -4.2); arc delivery, 5.5% (4.2 / 9.2). SEMSs for biliary decompression can be safely used in patients undergoing radiotherapy, by focusing on the dose distribution around the stents and by paying attention to local changes in the dose distribution of radiopaque markers., Competing Interests: Declarations. Ethics approval: This study did not require an Institutional Review Board (IRB) approval and written consent because this study does not include any investigations or experiments with human participants or animals performed by any of the authors. Consent to participate: This study did not require a written consent. Consent to publish: None. Competing interests: Dr. Yoshihiro Ueda reports patent planned with Zeon Medical. Dr. Kenji Ikezawa reports provision of the stents used in this study from Boston Scientific, Olympus Medical Systems, Century Medical, Zeon Medical and Medicos Hirata; grants from ASKA Pharmaceutical; consulting fee from Medicos Hirata, honoraria for lecture from Boston Scientific, Zeon Medical, Kaneka and Medicos Hirata; patent planned with Zeon Medical. Dr. Ryoji Takada reports honoraria for manuscript writing from Medicos Hirata. Drs. Tomohiro Sagawa, Masaru Isono, Shingo Ohira, Masayoshi Miyazaki, Takuo Yamai, Kazuyoshi Ohkawa, Teruki Teshima, and Koji Konishi have no conflicts of interest or financial ties to disclose., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Background: Gemcitabine (GEM) and cisplatin (CDDP) combination therapy (GC therapy) is the standard 1st-line regimen for incurable biliary tract cancers (BTCs). However, the correlation between dynamic changes in renal function and the outcomes of GC therapy remains unclear. This study aimed to clarify the association between renal function alterations and treatment outcomes after GC therapy., Methods: We retrospectively examined 44 patients with incurable BTC who underwent GC therapy (January 2015 to December 2022). The patients were stratified according to their baseline estimated glomerular filtration rate (eGFR). Changes in eGFR, overall survival (OS), and progression-free survival (PFS)., Results: The median baseline eGFRs were 65.0 mL/min/1.73 m 2 (low group, n=22) and 90.7 mL/min/1.73 m 2 (high group, n=22). No significant background differences were observed between the groups. During the 1st course, 86.4% and 54.5% of patients in the low and high groups underwent dose adjustments and/or administration postponement, which was found to be significantly greater in the low group. In the high group, eGFR decreased with an increase in the CDDP dose (100 mg =-12.0, 200 mg =-12.7, 300 mg =-25.9, and 400 mg =-25.7 mL/min/1.73 m 2 ). In the low group, eGFR remained stable (100 mg =0.8, 200 mg =7.5, 300 mg =4.5, and 400 mg =-0.3 mL/min/1.73 m 2 ). The decrease in the eGFR in the high group was significantly greater at each CDDP dose. However, the median OS and PFS were longer in the low group (OS: 16.3 vs. 9.2 months, P=0.02; PFS: 5.4 vs. 3.6 months, P=0.02). No significant differences in adverse events were observed between the groups., Conclusions: Adjusting GC therapy based on baseline estimated glomerular eGFR may be pivotal for therapeutic benefits and renal function protection in patients with incurable BTC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-330/coif). Dr. Takuo Yamai reports honoraria for lectures from Boston Scientific and MSD, and for manuscript writing from Kaneka. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP's therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP., (© 2024. The Author(s).)

Background: Germline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy., Methods: We retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records., Results: The median patient age was 64 y (29-85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8-87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1-30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months., Conclusions: The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer., (© 2024. The Author(s).)

Background: Although patients with advanced pancreatic cancer (PC) often experience dysgeusia with zinc deficiency during chemotherapy, data on zinc supplementation for dysgeusia and its effects on nutritional status are scarce. We aimed to examine the efficacy of zinc supplementation in patients with advanced PC., Methods: Thirty-three patients with unresectable PC who presented with dysgeusia and zinc deficiency during chemotherapy and received zinc acetate hydrate between January 2018 and December 2022 were included. We evaluated the changes in serum zinc levels and the improvement in dysgeusia. Among the 26 patients who received zinc supplementation for 12 weeks, we also compared patient characteristics and changes in serum zinc and albumin levels between patients who showed improvement in dysgeusia (effective group) and those who did not (non-effective group)., Results: The serum zinc level increased significantly after zinc supplementation (median: 60 µg/dL at baseline, 99.5 µg/dL at 4 weeks, 101 µg/dL at 8 weeks and 101 µg/dL at 12 weeks). The rate of improvement in dysgeusia increased over time (18.2% at 4 weeks, 33.3% at 8 weeks, and 42.4% at 12 weeks). Comparing the effective group and non-effective group revealed that while the median serum albumin level of the effective group did not change, the non-effective group showed a significant decrease from baseline to 12 weeks (3.2 g/dL to 3.0 g/dL, p = 0.03)., Conclusion: Zinc supplementation significantly increased serum zinc levels, improving dysgeusia. Zinc supplementation might also contribute to maintaining nutritional status in patients with unresectable PC., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is used for pathological diagnosis and obtaining samples for molecular testing, facilitating the initiation of targeted therapies in patients with pancreatic cancer. However, samples obtained via EUS-TA are often insufficient, requiring more efforts to improve sampling adequacy for molecular testing. Therefore, this study investigated the use of oil blotting paper for formalin fixation of samples obtained via EUS-TA., Methods: This prospective study enrolled 42 patients who underwent EUS-TA for pancreatic cancer between September 2020 and February 2022 at the Osaka International Cancer Institute. After a portion of each sample obtained via EUS-TA was separated for routine histological evaluation, the residual samples were divided into filter paper and oil blotting paper groups for analysis. Accordingly, filter paper and oil blotting paper were used for the formalin fixation process. The total tissue, nuclear, and cytoplasm areas of each sample were quantitatively evaluated using virtual slides, and the specimen volume and histological diagnosis of each sample were evaluated by an expert pathologist., Results: All cases were cytologically diagnosed as adenocarcinoma. The area ratios of the total tissue, nuclear, and cytoplasmic portions were significantly larger in the oil blotting paper group than in the filter paper group. The frequency of cases with large amount of tumor cells was significantly higher in the oil blotting paper group (33.3%) than in the filter paper group (11.9%) (p = 0.035)., Conclusions: Oil blotting paper can increase the sample volume obtained via EUS-TA on glass slides and improve sampling adequacy for molecular testing., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Portal vein aneurysm (PVA) is a rare saccular or fusiform portal vein dilatation. The management and optimal treatment of PVA remain unknown., Case Presentation: A 53-year-old man with hepatitis C virus (HCV) infection was diagnosed with PVA measuring 28 mm in diameter. Under observation, his liver fibrosis progressed, and the PVA diameter gradually increased to 52 mm. The patient was treated with elbasvir-grazoprevir for 12 weeks, and HCV disappeared. After achieving sustained virological response, liver fibrosis improved and the PVA progression ceased., Conclusion: HCV clearance by direct-acting antiviral treatment not only regressed liver fibrosis but may have also restrained the progression of PVA in a patient with cirrhosis type C and PVA., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aim: To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis., Methods: Ninety-two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty-six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively., Results: The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size., Conclusions: Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Aims: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO., Methods: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses., Results: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth., Conclusions: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs., Competing Interests: Disclosure The following author disclosed financial relationships: M. Kitano: Speaker for Olympus Corporation; research support from Boston Scientific, Zeon Medical Inc, and Medico’s Hirata Inc. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: Pancreatic cancer (PC) has one of the worst prognoses among all solid cancers. Hospital volume has been shown to be significantly associated with outcomes in patients with PC undergoing surgery. Nonetheless, the association between hospital volume and prognosis in patients with metastatic PC remains unclear. This study aimed to examine the association between hospital volume and prognosis in patients with metastatic PC using large-scale population-based cancer registry data., Methods: This retrospective observational study was conducted using data from the Osaka Cancer Registry database. Data of patients with metastatic PC over 10 years (2009-2018) were obtained. Hospitals were categorized into high-volume hospitals (HVHs; ≥ 240 patients diagnosed with PC for 10 years), middle-volume hospitals (MVHs; 120-239 patients diagnosed with PC for 10 years), and low-volume hospitals (LVHs; < 120 patients diagnosed with PC for 10 years). Multivariate analysis was performed to identify factors associated with overall survival (OS)., Results: The analysis included 8,929 patients with metastatic PC. Median OS was significantly more favorable in HVHs than in MVHs and LVHs. Multivariate analysis adjusted for hospital volume, age, primary tumor site, year of diagnosis, chemotherapy, and radiotherapy revealed that hospital volume was an independent factor associated with OS (HVHs vs. MVHs: hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.16; P = 0.003, HVHs vs. LVHs: HR, 1.20; 95% CI, 1.13-1.27; P < 0.001)., Conclusion: Hospital volume is an independent prognostic factor in patients with metastatic PC, suggesting an association between hospital volume and treatment outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Adequate biliary decompression is important in treating bile leaks, and endoscopic transpapillary drainage is widely used for this purpose. As an indicator to evaluate the usefulness of endoscopic drainage for postoperative biliary leakage, we focused on external drain removability, which affects quality of life, after endoscopic treatment. Our aim was to clarify the success rate of external tube removal after endoscopic drainage for postoperative biliary leakage and to examine associated factors., Methods: This was a multicenter retrospective study; 99 patients with biliary leakage at 13 institutions were enrolled between April 2014 and March 2019. Among these patients, 66 who were initially treated with endoscopic interventions for biliary leakage after cholecystectomy ( n = 17) or hepatectomy ( n = 49) were reviewed., Results: In post-cholecystectomy biliary leakage, the external-drain-free rate at first endoscopic intervention was 100%, and the drains, including transpapillary stents, were successfully removed in almost all cases (16/17). In contrast, in post-hepatectomy biliary leakage, the external-drain-free rate was 44.9% (22/49), with all 22 of those patients eventually becoming entirely drain-free. A lower body mass index was the only significant factor associated with freedom from external drainage in post-hepatectomy biliary leakage (odds ratio 0.18, 95% confidence interval 0.05-0.65)., Conclusions: Initial endoscopic treatment was effective for post-cholecystectomy biliary leakage, while approximately half of the patients with post-hepatectomy biliary leakage required multidisciplinary management. Achieving freedom from external drainage contributes to patients' quality of life and may be a predictor of treatment response after endoscopic therapy for postoperative biliary leakage., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: The effectiveness of chemotherapy in older adult patients with biliary tract cancer (BTC) remains to be established, despite the fact that the majority of patients diagnosed with BTC tend to be aged ≥ 70 years. In this study, we used three databases to examine the effectiveness of chemotherapy in a large patient population aged ≥ 70 years with metastatic BTC., Methods: Using a large Japanese database that combined three data sources (Osaka Cancer Registry, Japan's Diagnosis Procedure Combination, the hospital-based cancer registry database), we extracted the data from patients pathologically diagnosed with metastatic BTC, between January 1, 2013, and December 31, 2015, in 30 designated cancer care hospitals (DCCHs). A cohort of patients with comparable backgrounds was identified using propensity score matching. The log-rank test was used to examine how chemotherapy affected overall survival (OS)., Results: Among 2,622 registered patients with BTC in 30 DCCHs, 207 older adult patients aged > 70 years with metastatic BTC were selected. Chemotherapy significantly improved the prognosis of older adult patients, according to propensity score matching (chemotherapy, 6.4 months vs. best supportive care, 1.8 months, P value < 0.001). The number of patients receiving chemotherapy tends to decrease with age. Gemcitabine plus cisplatin (GC) and gemcitabine plus S-1 (oral fluoropyrimidine) (GS) combination therapy were frequently performed in the chemotherapy group for patients under 80 years of age (70-74 years, 61.7%; 75-79 years, 62.8%). In contrast, monotherapy including GEM and S-1 was more frequently performed in age groups over 80 years (80-84 years, 56.2%; 85-89 years, 77.7%; ≥90 years, 100%). In the chemotherapy group among older adult patients aged < 85 years, the median OS was significantly longer according to age-group analysis of the 5-year age range following propensity score matching., Conclusions: In older adult patients with metastatic BTC who received chemotherapy, prolonged survival was observed. Chemotherapy may be a viable option for patients with metastatic BTC who are aged < 85 years., (© 2023. The Author(s).)

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee., Methods: We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods., Results: The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method., Conclusion: The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time., (© 2023. The Author(s).)

This study aimed to examine occupational radiation exposure to the lens of the eyes during endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, prospective, observational cohort study, we collected data regarding occupational radiation exposure to the lens of the eyes during ERCP. We measured radiation exposure of patients and examined its correlation with occupational exposure. In dosimetrically-measured ERCPs (n = 631), the median air kerma at the patient entrance reference point, air kerma-area product, and fluoroscopy time were 49.6 mGy, 13.5 Gycm 2 , and 10.9 min, respectively. The median estimated annual radiation dose to the lens of the eyes was 3.7, 2.2, and 2.4 mSv for operators, assistants, and nurses, respectively. Glass badge over lead aprons and eye dosimeter results were similar in operators but differed in assistants and nurses. A strong correlation was shown between eye dosimeter measurements and patients' radiation exposure. The shielding rates of the lead glasses were 44.6%, 66.3%, and 51.7% for operators, assistants, and nurses, respectively. This study revealed the actual occupational exposure dose for the lens of the eyes during ERCP and the efficacy of lead glass. Values of radiation exposure to patients can help estimate exposure to the lens of the eyes of medical staff., (© 2023. The Author(s).)

This report highlights the importance of considering multiple myeloma in the differential diagnosis of a pancreatic tumor with bone lesions. sampling not only from the pancreatic lesion but also from bone lesions may reach an accurate diagnosis., Competing Interests: The authors disclose no conflicts of interest., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (-) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search.

Introduction: Although older adults aged ≥75 years comprise a substantial proportion of patients diagnosed with pancreatic cancer (PC), the effectiveness of chemotherapy in older adults with PC remains to be established., Materials and Methods: This retrospective study examined the effectiveness of chemotherapy according to age in older adult patients with metastatic PC. We used a large database that combined three data sources (the hospital-based cancer registry database, Osaka Cancer Registry, and Japan's Diagnosis Procedure Combination) and extracted data from patients pathologically diagnosed with metastatic PC between 2013 and 2015 in 31 designated cancer care hospitals in Japan. Propensity score matching (PSM) was used to identify a cohort of patients with similar backgrounds. The effect of chemotherapy on overall survival (OS) was analyzed using the log-rank test., Results: Compared with 687 younger patients (<75 years old), 276 older adult patients had significant impairments in activities of daily living and poorer prognoses (6.8 vs. 4.1 months, p < 0.001), with a lower frequency of chemotherapy (81.5% vs. 55.1%; p < 0.001). PSM of older adult patients showed that chemotherapy significantly contributed to a better prognosis (best supportive care, 2.6 months vs. chemotherapy, 5.8 months, p < 0.001). Age group analysis with PSM of five-year age ranges revealed that the median OS was significantly longer in the chemotherapy group among older adult patients aged <85 years., Discussion: Chemotherapy provides a survival benefit in older adult patients with metastatic PC, and patients aged <85 years could be promising candidates for chemotherapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The usefulness of comprehensive genomic profiling (CGP) panels for thoracic malignancies after completion of the standard treatment is unclear., Methods: The results of CGP panels for malignant thoracic diseases performed at our hospital between December 2019 and June 2022 were collected. We examined whether CGP panel results led to new treatment, correlated with the effectiveness of immune checkpoint inhibitors (ICIs), or revealed secondary findings related to hereditary tumors., Results: A total of 60 patients were enrolled, of which 52 (86.6%) had lung cancer. In six (10%) patients, the panel results led to treatment with insurance-listed molecular-targeted agents; four patients had EGFR mutations not detected by the real-time polymerase chain reaction assay and two had MET ex.14 skipping mutations. In small-cell lung cancer, the tumor mutation burden was high in 4/6 (66.7%) patients and pembrolizumab was available. Another MET ex.14 skipping mutation was detected in two cases with EGFR-tyrosine kinase inhibitor resistance. ICI efficacy was ≤1 year in patients with STK-11, KEAP1, and NEF2L2 mutations. A BRCA2 mutation with a high probability of germline mutation was detected in one patient. A thymic carcinoma with no detectable oncogenic mutation responded to second-line treatment with Tegafur-Gimeracil-Oteracil Potassium (TS-1) for ≥9 years., Conclusions: CGP panels are useful in thoracic malignancies, especially lung cancer, because they can detect overlooked driver mutations and genetic alterations. We believe that the significance of conducting a CGP panel prior to treatment may also exist, as it may lead to the prediction of ICI treatment efficacy., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background and Aim: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events in the liver. The risk of exacerbating liver injury is of concern in patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), as immunotherapy can damage liver function because of the immune response against viral antigens. We assessed the feasibility of immunotherapy in HBV- or HCV-infected patients., Methods: This retrospective study included 266 patients with persistent or past HBV infection, 26 patients seropositive for anti-HCV, and 820 patients with negative viral markers for HBV and HCV, who were treated with ICIs. ICI-induced liver injury and changes in virological markers were analyzed., Results: The occurrence rates of ICI-induced liver injury in the HBsAg-positive, anti-HBc-positive/anti-HBs-positive, and anti-HBc-positive/anti-HBs-negative groups were 12.5, 21.6, and 19.1%, respectively, which were comparable with those of the negative for HBV- and HCV-related markers group (20.9%). The frequency of any grade ICI-induced liver injury was different among the HCV RNA-positive (3/5; 60.0%), anti-HCV-positive/HCV RNA-negative (2/21; 9.5%), and negative for HBV- and HCV-related markers (171/820; 20.9%) groups ( P  = 0.045), with no significant difference in grade ≥2 ICI-induced liver injury. In patients with persistent infection, neither serum HBV DNA, HBsAg, nor HCV RNA level changed significantly during ICI treatment. One of five treatment-naïve HCV-infected patients required interruption of ICI treatment due to virus-related liver injury., Conclusion: Immunotherapy is feasible for most cancer patients with chronic HBV or HCV infection; however, liver function and virological markers should be carefully monitored in treatment-naïve patients, especially those with HCV infection, during ICI treatment., (© 2022 Osaka International Cancer Institute. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Salvage chemotherapy for patients with unresectable pancreatic cancer (UR-PC) who have been treated with gemcitabine and nab-paclitaxel (GnP), and 5-fluorouracil (5-FU)/l-leucovorin (LV) plus nanoliposomal irinotecan (nal-IRI), has not been fully established. We retrospectively reviewed data from 17 patients with UR-PC who initiated 5-FU/l-LV plus oxaliplatin (FOLFOX) as salvage chemotherapy at our hospital between June 2020 and August 2021, after treatment with GnP and 5-FU/LV plus nal-IRI. The primary endpoint was tumor response. The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). The response and disease control rates were 5.9% (1/17) and 17.6% (3/17), respectively. The median PFS was 1.8 months (range: 0.4-5.2 months). Eight patients (47.1%) experienced grade 3 nonhematologic AEs, while none experienced grade 3 hematologic AEs. Two patients with controlled disease had homologous recombination deficiency (HRD)-associated gene mutations in cancer panel testing. The FOLFOX regimen benefit for UR-PC patients treated with GnP and 5-FU/LV plus nal-IRI may be limited to patients with HRD-associated gene mutations.

Background: Pancreatic cancer is associated with a high thromboembolism risk. We investigated the significance of early venous thromboembolism (VTE) detection in patients with unresectable metastatic pancreatic cancer (UR-MPC) who received first-line chemotherapy with gemcitabine plus nab-paclitaxel (GnP)., Methods: This single-center retrospective study enrolled 174 patients with UR-MPC who underwent GnP as a first-line chemotherapy from April 2017 to March 2020. The early detection of VTE (deep venous thrombosis and pulmonary thromboembolism) was defined as diagnosis by the first follow-up CT scan after the initiation of chemotherapy. We compared the patients with early detection of VTE (VTE (+) group) with the others (VTE (-) group). We examined overall survival (OS), progress free survival (PFS), severe adverse events, and predictors associated with OS using the Cox proportional hazards model., Results: Early detection of VTE was observed in 17 patients (9.8%). Thirteen patients were diagnosed with VTE at treatment initiation, and four patients were diagnosed after treatment initiation. The median time to diagnosis after treatment initiation was 55 days (range: 31-71 days). Only 3 patients were symptomatic. The VTE (+) group exhibited worse OS and PFS than the VTE (-) group (OS: 259 days vs. 400 days, P < 0.001; PFS: 120 days vs. 162 days, P = 0.008). The frequency of grade 3-4 adverse events was not significantly different. Although the performance status was poorer in the VTE (+) group, VTE was identified as a statistically significant independent predictor for OS in multivariate analyses (HR, 1.87; 95% CI, 1.02-3.44; P = 0.041)., Conclusions: Early VTE detection is a predictor of a poor prognosis in UR-MPC patients who receive GnP as first-line chemotherapy, suggesting that screening VTE for patients with UR-MPC is crucial, even if patients are asymptomatic., Competing Interests: All authors have declared that no competing interests exist.

Background and Aims: The International Consensus Guidelines updated in 2017 recommended surgery to all main duct intraductal papillary mucinous neoplasms (MD-IPMNs) with the main pancreatic duct (MPD) of 10 mm or more and those with mural nodules regardless of size. The aim of the present study was to identify predictors of malignancy in MD-IPMN among preoperative factors including MPD and mural nodule size., Methods: Twenty-six benign MD-IPMNs (7 resected and 19 nonresected) and 32 malignant MD-IPMNs (31 resected and 1 nonresected) were included in the study. MRCP, CT, EUS, and cytology were performed using pancreatic juice collected by endoscopic retrograde pancrestography (ERP). Resected IPMNs were classified as benign or malignant by histologic examination and nonresected MD-IPMNs by imaging, cytology, and observation. Cutoff values of candidate parameters were determined by receiver operating characteristic curves. Univariate and multivariate analyses by regression model were performed., Results: MPD and mural nodule size and cytology results differed significantly between benign and malignant groups. Cutoff values of MPD and mural nodule sizes were 15 mm and 10 mm with areas under the curve of .66 and .86, respectively. Mural nodules of 10 mm or more (odds ratio, 8.32; 95% confidence interval, 1.13-61.2; P = .038) and positive cytology (odds ratio, 42.5; 95% confidence interval, 4.10-439; P = .002) were shown to be independent predictors of malignancy by multivariate analysis. When MD-IPMNs with either predictor were diagnosed to be malignant, sensitivities, specificities, and overall accuracy for malignancy were 94%, 85%, and 90%, respectively., Conclusions: Mural nodules of 10 mm or more and positive cytology were independent predictors of malignancy in MD-IPMN., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Capsid allosteric modulators (CAMs) inhibit the encapsidation of hepatitis B virus (HBV) pregenomic RNA (pgRNA), which contains a pathogen-associated molecular pattern motif. However, the effect of CAMs on the innate immune response of HBV-infected hepatocytes remains unclear, and we examined this effect in this study. Administration of a CAM compound, BAY41-4109 (BAY41), to HBV-infected primary human hepatocytes (PHHs) did not change the total cytoplasmic pgRNA levels but significantly reduced intracapsid pgRNA levels, suggesting that BAY41 increased extracapsid pgRNA levels in the cytoplasm. BAY41 alone did not change the intracellular interferon (IFN)-stimulated gene (ISG) expression levels. However, BAY41 enhanced antiviral ISG induction by IFN-α in HBV-infected PHHs but did not change ISG induction by IFN-α in uninfected PHHs. Compared with BAY41 or IFN-α alone, coadministration of BAY41 and IFN-α significantly suppressed extracellular HBV-DNA levels. HBV-infected human liver-chimeric mice were treated with vehicle, BAY41, pegylated IFN-α (pegIFN-α), or BAY41 and pegIFN-α together. Compared with the vehicle control, pegIFN-α highly up-regulated intrahepatic ISG expression levels, but BAY41 alone did not change these levels. The combination of BAY41 and pegIFN-α further enhanced intrahepatic antiviral ISG expression, which was up-regulated by pegIFNα. The serum HBV-DNA levels in mice treated with the combination of BAY41 and pegIFN-α were the lowest observed in all the groups. Conclusion: CAMs enhance the host IFN response when combined with exogenous IFN-α, likely due to increased cytoplasmic extracapsid pgRNA., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background and study aims  In patients with pancreatic cancer (PC), patient-derived organoid cultures can be useful tools for personalized drug selection and preclinical evaluation of novel therapies. To establish a less invasive method of creating organoids from a patient's tumor, we examined whether PC organoids can be established using residual samples from saline flushes (RSSFs) during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Methods  Five patients with PC who underwent EUS-FNA were enrolled in a prospective study conducted at our institution. RSSFs obtained during EUS-FNA procedures were collected. An organoid culture was considered as established when ≥ 5 passages were successful. Organoid-derived xenografts were created using established organoids. Results  EUS-FNA was performed using a 22- or 25-gauge lancet needle without complications. Patient-derived organoids were successfully established in four patients (80.0 %) with the complete medium and medium for the selection of KRAS mutants. Organoid-derived xenografts were successfully created and histologically similar to EUS-FNA samples. Conclusions  Patient-derived PC organoids were successfully established using EUS-FNA RSSFs, which are produced as a byproduct of standard manipulations, but are usually not used for diagnosis. This method can be applied to all patients with PC, without additional invasive procedures, and can contribute to the development of personalized medicine and molecular research., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

An optimal therapeutic strategy for unresectable locally advanced pancreatic cancer (UR-LAPC) has not been established. This study investigated the therapeutic efficacy of chemoradiotherapy (CRT) following induction chemotherapy with gemcitabine plus nab-paclitaxel (GnP) (CRT group) compared with systemic chemotherapy alone (CTx group) in patients with UR-LAPC. This was a retrospective study of 63 consecutive patients with UR-LAPC treated at our department in a Japanese cancer referral center between February 2015 and July 2018. We excluded patients who underwent other regimens and those enrolled in another prospective study. The CRT group ( n = 25) exhibited significantly better progression-free survival (PFS) and overall survival (OS) than the CTx group ( n = 20, PFS 17.9 vs. 7.6 months, p = 0.044; OS 29.2 vs. 17.4 months, p < 0.001). In the multivariate analyses, CRT following induction chemotherapy was identified as an independent prognostic factor for OS. Seven (15.6%) patients underwent conversion surgery, all of whom were in the CRT group. The R0 resection rate was 85.7% (6/7). In summary, patients with UR-LAPC experienced favorable treatment outcomes after receiving GnP as the first-line chemotherapy, especially when receiving additional CRT. Thus, this treatment strategy represents a promising treatment option for selected patients with UR-LAPC.

Although patients with ampullary cancers frequently experience obstructive jaundice and tumor bleeding, there have been few reports on efficient management of refractory hemorrhage after conservative treatment. In this report, we describe a case of refractory bleeding from a 15-mm ampullary adenocarcinoma. A Japanese woman in her 60s was urgently hospitalized for cholangitis, pancreatitis, and sepsis treatment. Investigation with a side-viewing duodenoscope revealed an ulcerated ampullary adenocarcinoma. After the patient underwent anticoagulation therapy for pulmonary thromboembolism, the tumor bleeding gradually increased, resulting in severe anemia. Because the anemia did not improve with fasting or discontinuation of the anticoagulation therapy, the patient underwent repeated red blood cell transfusions. As no hemobilia was observed in the bile juice aspirated during endoscopic retrograde cholangiography, we supposed that the bleeding originated from the ulcerative cancer surface. We did not perform thermal therapy because we considered that it would worsen the bleeding. Abdominal angiography showed no pseudoaneurysms or extravasation. Ultimately, we performed transpapillary placement of a fully covered self-expandable metallic stent (SEMS) with an anchoring double pigtail plastic stent that resulted in successful hemostasis. In this case, the mechanism of hemostasis was not presumably explained by direct compression of the bleeding point but by indirect compression. When tumor volume is small, the radial force of the SEMS may cause compression of the tumor volume, leading to shrinkage of the bleeding blood vessels. In conclusion, covered SEMS placement could be an efficient treatment for refractory ampullary cancer bleeding, even from an ulcerated cancer surface., Competing Interests: The authors declare no conflict of interest for this article., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Primary pancreatic lymphomas (PPLs) are rare, and the histological classification of these tumors is difficult. To accurately diagnose and determine the appropriate treatment for PPLs, sufficient sample amounts are necessary. Here, we report a 73-year-old man with a primary pancreatic mantle cell lymphoma. Histological samples were obtained via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The tumor cells predominantly composed of atypical small to medium round cells, with diffuse immunoreactivity of CD20 and cyclin D1. In addition, immunoglobulin gene H chain rearrangement was detected. The patient underwent chemotherapy, resulting in complete remission. Eight years after the initiation of chemotherapy, the patient was still alive. EUS-FNA could be a useful and safe diagnostic modality for PPLs by providing enough samples for testing., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Background and Aim: The success rate of microsatellite instability (MSI) examination in biliary tract cancer (BTC) and the treatment outcomes of pembrolizumab in patients with MSI-high (MSI-H) BTC have not been fully investigated. We examined the success rate of MSI examination and the rate of MSI-H status in patients with BTC as well as the treatment outcomes of patients with MSI-H status who underwent pembrolizumab treatment., Methods: We retrospectively reviewed 60 consecutive patients with unresectable or postoperative recurrent BTC who underwent MSI examination in a Japanese cancer referral center between January 2019 and September 2020., Results: The study included 24 intrahepatic cholangiocarcinomas, 12 hilar cholangiocarcinomas, 4 distal cholangiocarcinomas, 16 gallbladder carcinomas, and 4 ampullary carcinomas. The methods of cancer tissue sampling were percutaneous liver tumor biopsy in 26 cases, surgery in 15 cases, endoscopic ultrasound fine-needle aspiration in 12 cases, transpapillary bile duct biopsy in 5 cases, and others in 2 cases. The success rate of MSI examination was 98.3% (59 of 60). MSI examination failed in only one case using a surgical specimen due to time-dependent degradation of DNA. The frequency of MSI-H BTC was 3.3% (2 of 60 cases). One patient with MSI-H intrahepatic cholangiocarcinoma achieved a complete response with pembrolizumab treatment., Conclusions: MSI examinations in BTC were successful in almost all cases, regardless of tissue sampling methods. We experienced a case in which pembrolizumab resulted in a complete response to MSI-H BTC. Since pembrolizumab for MSI-H BTC could prolong survival time, MSI examination should be performed proactively to increase treatment options., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The optimal standard second-line chemotherapy for metastatic pancreatic cancer (MPC) remains unclear. Here, we evaluated the efficacy and safety of modified fluorouracil/leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) compared with oral fluoropyrimidine S-1 as a second-line chemotherapy in patients with MPC., Methods: We retrospectively reviewed 76 consecutive patients with metastatic pancreatic adenocarcinoma who underwent mFOLFIRINOX or S-1 treatment as a second-line chemotherapy after gemcitabine plus nab-paclitaxel (GnP) failure at our department between December 2014 and February 2019., Results: Patients who underwent mFOLFIRINOX treatment exhibited significantly better objective response rates (ORRs) and progression-free survival (PFS) than S-1 (ORR, 20.0% vs 0%, P  = 0.003; PFS, 3.7 vs 2.1 months, P  = 0.010). Although baseline patient characteristics of age, performance status, and serum albumin levels differed significantly between the two groups, mFOLFIRINOX was identified as an independent factor of favorable PFS on multivariate analyses. Grade 3-4 neutropenia and peripheral sensory neuropathy occurred more frequently in the mFOLFIRINOX group. The median overall survival from the initiation of second-line chemotherapy was not significantly longer in the mFOLFIRINOX group than in the S1 group (8.5 vs 5.8 months, respectively; P  = 0.213); however, the 8-month survival rate was significantly higher in the mFOLFIRINOX group (56.0% vs 27.5%, respectively; P  = 0.030)., Conclusions: mFOLFIRINOX as a second-line regimen contributed to favorable treatment outcomes, but induced more frequent adverse events than S-1. On multivariate analyses, mFOLFIRINOX was identified as an independent factor with favorable PFS, suggesting that mFOLFIRINOX could be a promising treatment option for patients with GnP failure., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) are established as efficient and safe diagnostic modalities. However, the risk of cholangitis after EUS/EUS-FNA (post-EUS cholangitis) in patients who have biliary strictures has not been fully examined., Methods: We retrospectively reviewed 136 consecutive inpatients with biliary strictures who received EUS/EUS-FNA at our hospital from April 2012 to September 2017 and evaluated complications that occurred by the next day after EUS/EUS-FNA. Patients with percutaneous biliary drainage, those in whom it was difficult to reach the duodenum, and those receiving concurrent endoscopic retrograde cholangiopancreatography were excluded., Results: We included 121 patients (147 cases); 90 patients were malignant. Endoscopic biliary stenting (EBS) with plastic stents had already been performed in 86 cases. Post-EUS cholangitis was observed in 4.1% (6/147). No other EUS-related complications were observed. The incidence of cholangitis with EBS was significantly higher than that in the cases without EBS (7.0% [6/86] vs 0% [0/61], P = 0.042). Biliary enzyme elevation was also identified as a risk factor of cholangitis., Conclusion: Endoscopic biliary stenting was identified as a risk factor associated with post-EUS cholangitis in patients with biliary strictures. Endoscopists should pay attention to post-EUS cholangitis, especially in cases with EBS and biliary enzyme elevation., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)