Pulmonary mediastinal actinomycosis with "pound cake sign" on magnetic resonance imaging mimicking an infiltrative malignant tumor: A case report.

Actinomycosis is a rare chronic suppurative granulomatous disease. Surgical biopsy is often performed in patients with chest actinomycosis because malignancy is suspected in most cases. A 62-year-old man presented to our hospital with fever and exertional dyspnea that had persisted for several months. Contrast-enhanced computed tomography showed an irregularly shaped mass with contrast enhancement in the anterior mediastinum and consolidation in the left upper lung lobe contiguous with this mass, as well as multiple nodules in both lungs. The pulmonary artery trunk was stenotic and surrounded by the mass, and the right heart system was enlarged. Thoracoscopic biopsy was performed but failed to yield a diagnosis. Contrast-enhanced computed tomography after one month revealed an increased mass and worsening right heart strain. 18F-FDG (fluorodeoxyglucose) positron emission tomography/computed tomography and contrast-enhanced magnetic resonance imaging also suggested a malignant tumor, and an open chest biopsy was performed. No malignant cells were identified and actinomycetes were detected by histopathology and bacterial culture. The patient was treated with antibiotics, following which his contrast-enhanced computed tomography findings and general condition improved.

TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Efficacy of Amamorelin in Advanced Pancreatic Cancer Patients with a Poor Performance Status.

Objective The efficacy of anamorelin in pancreatic cancer (PC) patients with a poor performance status (PS) is uncertain, as previous trials have excluded such patients. This study evaluated the efficacy of anamorelin in PC patients with a poor PS (2) compared with those with a good PS (0-1). Methods We retrospectively reviewed consecutive PC patients with cachexia who received anamorelin at our institution. The primary outcome was the proportion of responders, defined as those who maintained or gained body weight and appetite over 12 weeks. The secondary outcomes included anamorelin treatment duration, proportion of patients who discontinued anamorelin within 4 weeks (early discontinuation), and the overall survival. Results Forty-five patients (35/10) were included in this study. The proportion of responders was significantly lower in patients with a poor PS than in those with a good PS (0% vs. 37%, p=0.042). Moderate weight loss (5%-10%) and administration of pancreatic enzyme replacement therapy were associated with a response to anamorelin. A poor PS was significantly associated with a shorter treatment duration of anamorelin (14 vs. 93 days, p <0.001), a higher proportion of patients who discontinued anamorelin within 4 weeks (70% vs. 17%, p=0.003), and a reduced survival (62 vs. 188 days, p <0.001). A poor PS was associated with early discontinuation of anamorelin. Conclusions The efficacy of anamorelin is extremely limited in PC patients with a poor PS. Patients with PC with a poor PS may not be good candidates for anamorelin compared to those with a good PS.

Outcomes of partially covered self-expandable metal stents with different uncovered lengths in endoscopic ultrasound-guided hepaticogastrostomy: a Japanese retrospective study.

Background/Aims: The optimal length of the uncovered portion of partially covered self-expandable metal stents (PCSEMSs) used in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) remains unclear. This study investigated the safety and efficacy of PCSEMSs with different uncovered lengths, with a focus on stent migration and time to recurrent biliary obstruction (RBO). Methods: Outcomes of patients undergoing EUS-HGS using PCSEMSs with 5-mm and 20-mm uncovered portions at our institution from January 2016 to December 2021 were compared. Results: Sixty-two patients underwent EUS-HGS using PCSEMS (5/20-mm uncovered portions: 32/30). Stent migration occurred only in the 5-mm group. There were no differences in RBO rates (28.1% vs. 40.0%) or median time to RBO (6.8 vs. 7.1 months) between the two groups. Median overall survival (OS) was longer in the 20-mm group (3.1 vs. 4.9 months, p=0.037) due to the higher number of patients that resumed chemotherapy after EUS-HGS (56.7 vs. 28.1%, p=0.029). Good performance status, absence of hepatic metastases, and chemotherapy after EUS-HGS were independent predictors of longer OS. Conclusions: No migration was observed in patients treated with PCSEMS with 20-mm uncovered portions. Patients treated with PCSEMS with 20-mm uncovered portions performed at least as well as those treated with 5-mm uncovered portions in all material respects.

Drainage for fluid collections post pancreatic surgery and acute pancreatitis: similar but different?

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

Outcomes of 6-mm diameter fully covered self-expandable metal stents for preoperative biliary drainage in pancreatic cancer.

Background: 10-mm self-expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent-related adverse events (AEs). Methods: We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent-related non-event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent-related AEs). Secondary outcomes included stent-related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results: A total of 76 patients were included (6-mm group: 23; 10-mm group: 53). Stent-related NER (57% vs. 64%, p = 0.610), stent-related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95-5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk-reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions: Stent-related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6-mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis.

Porokeratosis is a clonal keratinization disorder characterized by solitary, linearly arranged, or generally distributed multiple skin lesions. Previous studies showed that genetic alterations in MVK, PMVK, MVD, or FDPS-genes in the mevalonate pathway-cause hereditary porokeratosis, with skin lesions harboring germline and lesion-specific somatic variants on opposite alleles. Here, we identified non-hereditary porokeratosis associated with epigenetic silencing of FDFT1, another gene in the mevalonate pathway. Skin lesions of the generalized form had germline and lesion-specific somatic variants on opposite alleles in FDFT1, representing FDFT1-associated hereditary porokeratosis identified in this study. Conversely, lesions of the solitary or linearly arranged localized form had somatic bi-allelic promoter hypermethylation or mono-allelic promoter hypermethylation with somatic genetic alterations on opposite alleles in FDFT1, indicating non-hereditary porokeratosis. FDFT1 localization was uniformly diminished within the lesions, and lesion-derived keratinocytes showed cholesterol dependence for cell growth and altered expression of genes related to cell-cycle and epidermal development, confirming that lesions form by clonal expansion of FDFT1-deficient keratinocytes. In some individuals with the localized form, gene-specific promoter hypermethylation of FDFT1 was detected in morphologically normal epidermis adjacent to methylation-related lesions but not distal to these lesions, suggesting that asymptomatic somatic epigenetic mosaicism of FDFT1 predisposes certain skin areas to the disease. Finally, consistent with its genetic etiology, topical statin treatment ameliorated lesions in FDFT1-deficient porokeratosis. In conclusion, we identified bi-allelic genetic and/or epigenetic alterations of FDFT1 as a cause of porokeratosis and shed light on the pathogenesis of skin mosaicism involving clonal expansion of epigenetically altered cells.

Association of polydoctoring and mortality among very old persons with multimorbidity: a prospective cohort study in Japan.

BACKGROUND: Polydoctoring is a crucial aspect of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear. AIM: To determine the effects of polydoctoring, as measured by the Regularly Visited Facility (RVF) indicator, on patient outcomes among older individuals with multimorbidity. DESIGN & SETTING: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilized in this study. Among the 1,026 KAWP participants aged 85-89 years, those with two or more chronic conditions were enrolled in this study. METHOD: Care fragmentation or polydoctoring, was evaluated using the RVF, a new indicator that measures the number of medical facilities consistently involved in a patient's care. Based on RVF, mortality was analysed using the Cox-hazards model, with adjustments for age, sex, frailty, and number of comorbidities. RESULTS: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2-4 comorbidities (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.18-0.99). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI 1.05-6.84). CONCLUSIONS: In older patients with multimorbidity, polydoctoring reduces mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision-making in managing older patients with multimorbidity.

Current Status of Targeted Therapy for Biliary Tract Cancer in the Era of Precision Medicine.

First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently available options in precision medicine and clinical trials for patients with advanced BTC.

Bone loss over time and risk of osteoporosis in advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a high risk of developing osteoporosis. However, the impact of osteoporosis has not been well-studied. This study aimed to evaluate bone loss over time and risk of osteoporosis in patients with advanced pancreatic cancer. METHODS: We retrospectively examined consecutive patients with unresectable pancreatic cancer who had evaluable computed tomography before treatment and at 1-year follow-up. Bone mineral density at the first lumbar vertebra was measured on computed tomography, and osteoporosis was defined as bone mineral density < 135 Hounsfield units. The prevalence and risk factors for osteoporosis, changes in bone mineral density over time and incidence of bone fractures were analyzed. RESULTS: Three hundred eighty patients were included. Osteoporosis was associated with older age, female sex, low body mass index and poor performance status at baseline. A consistent decrease in bone mineral density was observed over time regardless of age, sex or disease status, resulting in an increase in the prevalence of osteoporosis over time (47% at baseline, 79% at 1 year, 88% at 2 years, 89% at 3 years, 95% at 4 years and 100% at 5 years). Changes in bone mineral density from baseline were greater in patients with locally-advanced pancreatic cancer, in those who received modified FOLFIRINOX or S-IROX for more than 3 months, and in those who received radiation therapy. Incident fractures developed in 45 patients (12%) during follow-up. CONCLUSIONS: Osteoporosis and osteoporotic fractures were highly prevalent in patients with advanced pancreatic cancer. This study highlights the importance of screening for osteoporosis in such patients.

Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition.

IL-17-producing helper T (Th17) cells are long-lived and serve as central effector cells in chronic autoimmune diseases. The underlying mechanisms of Th17 persistence remain unclear. We demonstrated that abatacept, a CD28 antagonist, effectively prevented the development of skin disease in a Th17-dependent experimental autoimmune dermatitis model. Abatacept selectively inhibited the emergence of IL-7R-negative effector-phenotype T cells while allowing the survival and proliferation of IL-7R+ memory-phenotype cells. The surviving IL-7R+ Th17 cells expressed genes associated with alcohol/aldehyde detoxification and showed potential to transdifferentiate into IL-7R-negative effector cells. Inhibiting aldehyde dehydrogenase reduced IL-7R+ Th17 cells in vivo, independently of CD28, and exhibited additive effects when combined with abatacept. Our findings suggest that CD28 blockade prevents inflammation without eliminating persistent memory cells. These remaining memory cells can be targeted by other drugs, such as aldehyde dehydrogenase inhibitors, to limit their survival, thereby facilitating the treatment of chronic autoimmune diseases.

Risk factors for recurrent stenosis after balloon dilation for benign hepaticojejunostomy anastomotic stricture.

BACKGROUND/AIMS: Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. METHODS: We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy-endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. RESULTS: Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01-7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85-6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. CONCLUSION: Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Rotatable sphincterotome as a rescue device for endoscopic retrograde cholangiopancreatography cannulation: a single-center experience.

BACKGROUND/AIMS: Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. METHODS: We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. RESULTS: TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. CONCLUSION: The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Early versus delayed EUS-guided drainage for postoperative pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Postoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage. METHODS: Using PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model. RESULTS: From 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40-1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20-1.83, P = 0.37). CONCLUSION: POPFCs can be managed by early EUS-guided drainage without an increase in AEs.

Splenic Hilar Involvement and Sinistral Portal Hypertension in Unresectable Pancreatic Tail Cancer.

BACKGROUND: Pancreatic tail cancer (PTC) frequently displays splenic hilar involvement (SHI), but its impact on clinical outcomes remains unclear. We investigated the clinical impact of SHI in patients with unresectable PTC. METHODS: We retrospectively reviewed all patients with unresectable PTC who received first-line therapy at our institution from 2016 to 2020. RESULTS: Of the 111 included patients, 48 had SHI at diagnosis. SHI was significantly associated with younger age, liver metastasis, peritoneal dissemination, larger tumor size, modified Glasgow prognostic score of 1 or more, splenic artery involvement, gastric varices, and splenomegaly. Shorter median overall survival (OS; 9.3 vs. 11.6 months, p = 0.003) and progression-free survival (PFS; 4.3 vs. 6.3 months, p = 0.013) were observed in SHI patients. Poor performance status of 1 or 2, tumor size > 50 mm, hepatic metastasis, mGPS of 1 or 2, and SHI (hazard ratio: 1.65, 95% confidence interval: 1.08-2.52, p = 0.020) were independent predictors of shorter OS. Splenic artery pseudoaneurysm rupture and variceal rupture were rare and only observed in cases with SHI. CONCLUSIONS: Splenic hilar involvement is associated with worse outcomes in pancreatic tail cancer.

Measurement of polydoctoring as a crucial component of fragmentation of care among patients with multimorbidity: Cross-sectional study in Japan.

Background: Care fragmentation, characterized by the uncoordinated involvement of multiple healthcare providers, leads to inefficient and ineffective healthcare, posing a significant challenge in managing patients with multimorbidity. In this context, "polydoctoring," where patients see multiple specialists, emerges as a crucial aspect of care fragmentation. This study seeks to develop an indicator to assess polydoctoring, which can subsequently enhance the management of multimorbidity. Methods: Baseline survey data from the Kawasaki Aging and Wellbeing Project (KAWP) involving independent community-dwelling older adults aged 85-89 were utilized in this cross-sectional study. Polydoctoring measure was defined as the number of regularly visited facilities (RVFs). The association of RVF with the Fragmentation of Care Index (FCI) and the outcome measures of polypharmacy and ambulatory care costs were examined as indicators of care fragmentation. Results: The analysis comprised 968 participants, with an average of 4.70 comorbid chronic conditions; 65.3% of the participants had two or more RVFs, indicating polydoctoring. A significant correlation between RVF and FCI was observed. Modified Poisson regression analyses revealed associations between higher RVF and increased prevalence ratio of polypharmacy. Likewise, a higher RVF was associated with higher outpatient medical costs. Conclusions: RVF was significantly correlated with FCI, polypharmacy, and higher outpatient medical costs. Unlike complex indices, RVF is simple and intuitively comprehensible. Further research is needed to evaluate the impact of care fragmentation on patient outcomes, considering factors such as RVF thresholds, patient multimorbidity, and social support. Understanding the influence of polydoctoring can enhance care quality and efficiency for patients with multimorbidity.