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Background: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. Methods: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. Results: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19–2.63], p = 0.005 and 1.97 [1.02–3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14–0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. Conclusions: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO. [ABSTRACT FROM AUTHOR]

A considerable number of patients with mild traumatic brain injury have been known to "talk and die." Serial neurological examinations, however, have been the only method of determining the necessity of repeat computed tomography (CT), and no validated method has been available to predict early deterioration of minor head injury. This study aimed to evaluate the association between hypertension and bradycardia, a classic sign of raised intracranial pressure (Cushing reflex) on hospital arrival and determine the clinical consequences of minor head injury after blunt trauma. We created a new Cushing Index (CI) by dividing the systolic blood pressure by the heart rate (equaling the inverse number of the Shock Index, a score for hemodynamic stability) and hypothesized that a high CI would predict surgical intervention for deterioration and in-hospital death among patients with minor head injury. To test our hypothesis, a retrospective observational study was conducted using a nationwide trauma database. Accordingly, adult blunt trauma with minor head injury (defined as a Glasgow Coma Scale of 13–15 and Abbreviated Injury Scale score of ≥2 in the head) who were transported directly from the scene by ambulances were included. Among the 338,744 trauma patients identified in the database, 38,844 were eligible for inclusion. A restricted cubic spline regression curve for risks of in-hospital death was created using the CI. Thereafter, the thresholds were determined based on inflection points of the curve, and patients were divided into low-, intermediate-, and high-CI groups. Patients with high CI showed significantly higher in-hospital mortality rates compared with those with intermediate CI (351 [3.0%] vs. 373 [2.3%]; odds ratio [OR] = 1.32 [1.14–1.53]; p < 0.001). Patients with high index also had a higher incidence of emergency cranial surgery within 24h after arrival than those with an intermediate CI (746 [6.4%] vs. 879 [5.4%]; OR = 1.20 [1.08–1.33]; p < 0.001). In addition, patients with low CI (equal to high Shock Index, meaning hemodynamically unstable) showed higher in-hospital death compared with those with intermediate CI (360 [3.3%] vs. 373 [2.3%]; p < 0.001). In conclusion, a high CI (high systolic blood pressure and low heart rate) on hospital arrival would be helpful in identifying patients with minor head injury who might experience deterioration and need close observation. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma is a lethal cancer with high metastatic properties. While surgical treatment is considered the first choice, the difficulty associated with early diagnosis reduces the success rates of these interventions. Therefore, early diagnosis, and thus treatment, of pancreatic ductal adenocarcinoma is extremely important. Past studies have shown that most patients with pancreatic ductal adenocarcinoma have impaired glucose tolerance, while hyperglycemia also reportedly promotes various malignant behaviors in pancreatic cancer cells. This review summarizes the clinical and molecular impacts of glycolysis on pancreatic ductal adenocarcinoma, with the aim of providing an invaluable reference for, and novel insights regarding, pancreatic ductal adenocarcinoma research and treatment. Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type as it is prone to metastases and is difficult to diagnose at an early stage. Despite advances in molecular detection, its clinical prognosis remains poor and it is expected to become the second leading cause of cancer-related deaths. Approximately 85% of patients develop glucose metabolism disorders, most commonly diabetes mellitus, within three years prior to their pancreatic cancer diagnosis. Diabetes, or glucose metabolism disorders related to PDAC, are typically associated with insulin resistance, and beta cell damage, among other factors. From the perspective of molecular regulatory mechanisms, glucose metabolism disorders are closely related to PDAC initiation and development and to late invasion and metastasis. In particular, abnormal glucose metabolism impacts the nutritional status and prognosis of patients with PDAC. Meanwhile, preliminary research has shown that metformin and statins are effective for the prevention or treatment of malignancies; however, no such effect has been shown in clinical trials. Hence, the causes underlying these conflicting results require further exploration. This review focuses on the clinical significance of glucose metabolism disorders in PDAC and the mechanisms behind this relationship, while also summarizing therapeutic approaches that target glycolysis. [ABSTRACT FROM AUTHOR]

Background: Rapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h. Methods: A single-center retrospective cohort study using data between January 2020 and January 2021was conducted. Data were retrieved from the hospital data warehouse. Adult patients diagnosed with COVID-19 with a positive polymerase chain reaction (PCR) who needed oxygen during admission were included. Hourly increments in oxygen demand were calculated using two consecutive oxygen values. Covariates were selected from measurements at the closest time points of oxygen data. Prediction of MV use within 12 h by required oxygen changes was evaluated with the area under the receiver operating curves (AUCs). A threshold for increased MV use risk was obtained from restricted cubic spline curves. Results: Among 66 eligible patients, 1835 oxygen data were analyzed. The AUC was 0.756 for predicting MV by oxygen demand changes, 0.888 by both amounts and changes in oxygen, and 0.933 by the model adjusted with respiratory rate, PCR quantification cycle (Ct), and days from PCR. The threshold of increments of required oxygen was identified as 0.44 L/min/h and the probability of MV use linearly increased afterward. In subgroup analyses, the threshold was lower (0.25 L/min/h) when tachypnea or frequent respiratory distress existed, whereas it was higher (1.00 L/min/h) when viral load is low (Ct ≥20 or days from PCR >7 days). Conclusions: Hourly changes in oxygen demand predicted MV use within 12 h, with a threshold of 0.44 L/min/h. This threshold was lower with an unstable respiratory condition and higher with a low viral load. [ABSTRACT FROM AUTHOR]

Pump-controlled retrograde trial off (PCRTO) is described as an effective weaning strategy for veno-arterial extracorporeal membrane oxygenation (ECMO) in the guidelines. Contrastingly, there is no established weaning strategy for veno-arteriovenous (V-AV) ECMO. We report a novel application of PCRTO in a patient undergoing V-AV ECMO.A 49-year-old man had pneumonia and a history of kidney transplantation. Two days after intubation, respiratory failure progressed and veno-venous (V-V) ECMO was introduced. On day 7 after ECMO, the configuration was changed to V-AV ECMO owing to septic cardiomyopathy due to suspected cholangitis. On day 15, with partial haemodynamic improvement and persistent respiratory failure, PCRTO was performed; the patient was safely returned to V-V ECMO.In patients undergoing V-AV ECMO, PCRTO could have the potential to accurately simulate decannulation of the arterial cannula.This novel weaning strategy could be considered in patients undergoing V-AV ECMO. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer. Despite major advances in defining the molecular mutations driving PDAC, this disease remains universally lethal with an overall 5-year survival rate of only about 7–8%. Genetic alterations in PDAC are exemplified by four critical genes (KRAS , TP53 , CDKN2A , and SMAD4) that are frequently mutated. Among these, KRAS mutation ranges from 88% to 100% in several studies. Hippo signaling is an evolutionarily conserved network that plays a key role in normal organ development and tissue regeneration. Its core consists of the serine/threonine kinases mammalian sterile 20-like kinase 1 and 2 (MST1/2) and large tumor suppressor 1 and 2. Interestingly, pancreas-specific MST1/2 double knockout mice have been reported to display a decreased pancreas mass. Many of the genes involved in the Hippo signaling pathway are recognized as tumor suppressors, while the Hippo transducers Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are identified as oncogenes. By dephosphorylation, YAP and TAZ accumulate in the nucleus and interact with transcription factors such as TEA domain transcription factor-1, 2, 3, and 4. Dysregulation of Hippo signaling and activation of YAP/TAZ have been recognized in a variety of human solid cancers, including PDAC. Recent studies have elucidated that YAP/TAZ play a crucial role in the induction of acinar-to-ductal metaplasia, an initial step in the progression to PDAC, in genetically engineered mouse models. YAP and TAZ also play a key role in the development of PDAC by both KRAS-dependent and KRAS-independent bypass mechanisms. YAP/TAZ have become extensively studied in PDAC and their biological importance during the development and progression of PDAC has been uncovered. In this review, we summarize the biological significance of a dysregulated Hippo signaling pathway or activated YAP/TAZ in PDAC and propose a role for YAP/TAZ as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Strategies to predict delayed airway obstruction in patients with inhalation injury have not been extensively studied. This study aimed to develop a novel scale, predicting the need for Delayed Intubation after inhalation injury (PDI) score.Methods: We retrospectively identified patients with inhalation injury at four tertiary care centers in Japan between 2012 and 2018. We included patients aged 15 or older and excluded those intubated within 30 min after hospital arrival. Predictors for delayed intubation were identified with univariate analyses and scored on the basis of odds ratios. The PDI score was evaluated with the area under the receiver operating characteristic (AUROC) curve and compared with other scaling systems for burn injuries.Results: Data from 158 patients were analyzed; of these patients, 18 (11.4%) were intubated during the delayed phase. Signs of respiratory distress, facial burn, and pharyngolaryngeal swelling observed on laryngoscopy, were identified as predictors for delayed intubation. The discriminatory power of the PDI (AUROC curve = 0.90; 95% confidence interval, 0.83 to 0.97; p < 0.01) was higher than that of the other scaling systems.Conclusions: We developed a novel scale for predicting delayed intubation in inhalation injury. The score should be further validated with other population. [ABSTRACT FROM AUTHOR]

2D porous carbon nanosheets (PCNs) occupy the foreground in the field of electric double-layer capacitors (EDLCs). However, the mass production of PCNs with ultrathin thicknesses is still a serious challenge. Herein, PCNs constructed of few-layer graphene sheets were synthesized from a sulfonated pitch (SP) carbon precursor and soft-template F127 by a “medium-up” strategy. SP serves as a “medium material”, while F127 acts as a “string” and “spacer”, which plays the leading role of structure directing and prevents the self-restacking of small graphene layers. After activation, sample PCN6 with high carbon yield is constructed with a thickness of only 1.3 nm, sufficient specific surface area of 3006 m2 g−1 and high e-conductivity of 135 S m−1. By virtue of its unique architecture, the PCN6-based EDLC exhibits excellent energy storage properties. In EMIMBF4 electrolyte, it demonstrates an ultrahigh Cg of 157.8 F g−1 (57.4 F cm−3) at 20 A g−1, possessing a top-level rate capacity C20/0.05 of 86.7%. Simultaneously, its energy density can retain up to 67.1 W h kg−1 at a high power density of 17.5 kW kg−1. The ingenious structural design of PCNs can afford inspiration for constructing other 2D architecture carbon materials. [ABSTRACT FROM AUTHOR]

Among all of the requirements for carbon materials used in electric double-layer capacitors (EDLCs), specific surface area (SSA) and electrical conductivity is a pair of mutual competing demands. In this paper, a series of frame-filling structural nanoporous carbons were prepared using an amphiphilic mixture of graphite oxide and a coal tar pitch-based carbonaceous material as precursor ensuring a high carbon yield. In the final porous composites, the few-layer graphene microsheets derived from graphite oxide contribute to the conductive frame construction by randomly cross-stacking during exfoliation and thermal reduction, while nanoparticles derived from coal tar pitch-based carbonaceous material fill into the frame and chemically bind on the surface of graphene microsheets of about 2 nm in thickness. The SSA is up to 2441 m 2 g −1 and the electrical conductivity is 179 S/m. It has energy storage superiorities over an ordinary nanoporous carbon, rendering a shortened relaxation time constant (5.34 s), improved gravimetric capacitance (115.4 F/g) as well as cyclic stability in 10,000 cycles with 87.8% capacity retention in 1 M TEABF 4 /PC electrolyte. The frame-filling structural nanoporous carbon shows great potential for blocks or high-capacity energy storage system by complex serial-parallel. [ABSTRACT FROM AUTHOR]

A coordination network composed of a mannose-based organic ligand and a sodium ion, ‘sugar sponge’, was synthesized for the crystalline sponge analysis of hydrophilic compounds. Owing to multiple hydrogen-bonding interactions, hydrophilic guests are firmly trapped in the 1-dimensional channel. The sugar sponge was utilized to analyze the structures of flexible alcohol and absolute configurations of chiral epoxides. [ABSTRACT FROM AUTHOR]

Achieving multiple physical properties from a single material through three-dimensional (3D) printing is important for manufacturing applications. In addition, industrial-level durability and reliability is necessary for realizing individualized manufacturing of devices using 3D printers. We investigated the properties of architected materials composed of ultraviolet (UV)-cured urethane elastomers for use as insoles. The durability and reliability of microlattice and metafoam architected materials were compared with those composed of various foamed materials currently used in medical insoles. The hardness of the architected materials was able to be continuously adjusted by controlling the design parameters, and the combination of the two materials was effective in controlling rebound resilience. In particular, the features of the architected materials were helpful for customizing the insole properties, such as hardness, propulsive force, and shock absorption, according to the user's needs. Further, using elastomer as a component led to better results in fatigue testing and UV resistance compared with the plastic foam currently used for medical purposes. Specifically, polyethylene and ethylene vinyl acetate were deformed in the fatigue test, and polyurethane was mechanically deteriorated by UV rays. Therefore, these architected materials are expected to be reliable for long-term use in insoles. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year-old woman who underwent right hepatectomy and resection of extra hepatic bile duct followed by hepatojejunostomy for hilar bile duct cancer, and mentions that percutaneous transhepatic portal vein approach to stenosis.

A new crystalline sponge, which can absorb and orient guest compounds to enable single ‐ crystal X ‐ ray analysis of them, was found from a crystallographic database by adopting empirical searching conditions. In the initial search using the Cambridge Structural Database, more than 2,800 crystal structures with void spaces were found as promising candidates. After the optimization of solvent and guest ‐ soaking conditions, a coordination network crystal with 1 ‐ dimensional channels (cross section: 10 × 10 Å2) was used for the crystallographic analysis of a liquid compound. More information can be found in the Communication by Yasuhide Inokuma, Makoto Fujita et al. on page   208 in Issue 2, 2017 (DOI: 10.1002/asia.201601551). [ABSTRACT FROM AUTHOR]

Purpose: The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients.Method: The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed.Results: Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814.Conclusions: Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients. [ABSTRACT FROM AUTHOR]

A 74-year-old man with no overt symptoms was referred for a chest computed tomography (CT) that revealed multiple bilaterally pulmonary ground-glass nodules (GGNs) with subtle changes in size over eight months. Surgical lung biopsies were performed in the left upper lobe. A pathologic study confirmed the intravascular large B-cell lymphoma (IVLBCL). This lesion was a nodule-like cluster of atypical cells, meaning that it had been localized for several months. Pulmonary IVLBCL may form focal lesions presenting as GGN on chest CT and progress slowly without apparent symptoms.

Objective Chronic pulmonary aspergillosis (CPA) is an important complication of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnosis is challenging, as both CPA and NTM-PD present as chronic cavitary disease. The present study evaluated the impact of CPA on the survival of patients with NTM-PD and revealed the key computed tomography findings for a prompt diagnosis. Methods We retrospectively reviewed patients newly diagnosed with NTM-PD in Tenri Hospital (Tenri City, Nara Prefecture, Japan) between January 2009 and March 2018; the patients were followed up until May 2021. Clinical and radiological characteristics were assessed, and patients with CPA were identified. Results A total of 611 patients were diagnosed with NTM-PD. Among them, 38 (6.2%), 102 (17%), and 471 (77%) patients were diagnosed with NTM-PD with CPA, cavitary NTM-PD without CPA, and non-cavitary NTM-PD without CPA, respectively. The 5-year survival rate of the NTM-PD with CPA group (42.8%; 95% confidence interval: 28.7-64.0%) was lower than that of the cavitary NTM-PD without CPA group (74.4%; 95% confidence interval: 65.4-84.6%). A multivariate analysis revealed that fungal balls and cavities with adjacent extrapleural fat were significant predictive factors for NTM-PD with CPA. Conclusion NTM-PD with CPA patients exhibited a worse prognosis than cavitary NTM-PD without CPA patients. Therefore, an unerring diagnosis of CPA is essential for managing patients with NTM-PD. Computed tomography findings, such as fungal balls and cavities with adjacent extrapleural fat, may be valuable diagnostic clues when CPA is suspected in patients with NTM-PD.

Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.

Introduction: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH 2 O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting., Methods and Analysis: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH 2 O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH 2 O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay., Ethics and Dissemination: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals., Trial Registration Number: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022., Protocol Version: 28 March 2023, version 4.0., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Statins are cholesterol-lowering agents that act as inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzymeA (HMG CoA) reductase. Recently, statins have received a lot of attention, especially regarding how statins act on the immune system. Here, the clinical impact of statin intake was examined in patients with resected pancreatic cancer, and the underlying mechanisms were investigated in vitro and in vivo . We found that statin intake was associated with favorable prognostic outcomes in patients with resectable pancreatic cancer. Statins, especially lipophilic statins, exert anti-proliferative effects on pancreatic cancer cells in vitro (simvastatin > fluvastatin > atorvastatin > rosuvastatin > pravastatin). Simvastatin had an anti-proliferative effect on pancreatic cancer cells with decreased the yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression by activating the JNK pathway, and simvastatin treatment with oxaliplatin revealed additive anti-growth effects. Furthermore, lipophilic and hydrophilic statins suppressed programmed cell death ligand 1 (PD-L1) expression by downregulating TAZ. Simvastatin treatment with an anti-PD-1 drug (BP0273) provided immediate anti-growth effects compared to controls, such as anti-PD-1 only and simvastatin only, and suppressed progressive disease during the early period of anti-PD-1 treatment in vivo . In conclusion, Statins display two distinct anti-cancer effects (direct anti-growth effect and elimination of immune suppression by downregulating PD-L1 expression) by targeting YAP/TAZ expression., Competing Interests: None., (AJCR Copyright © 2023.)

Background/aim: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported., Case Report: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation., Conclusion: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma and cancer-associated fibroblasts (CAFs) provide a favorable tumor microenvironment. Smad4 is known as tumor suppressor in several types of cancers including PDAC, and loss of Smad4 triggers accelerated cell invasiveness and metastatic potential. The thrombospondin-1 (TSP-1) can act as a major activator of latent transforming growth factor-β (TGF-β) in vivo. However, the roles of TSP-1 and the mediator of Smad4 loss and TGF-β signal activation during PDAC progression have not yet been addressed. The aim is to elucidate the biological role of TSP-1 in PDAC progression., Methods and Results: High substrate stiffness stimulated TSP-1 expression in CAFs, and TSP-1 knockdown inhibited cell proliferation with suppressed profibrogenic and activated stroma-related gene expressions in CAFs. Paracrine TSP-1 treatment for PDAC cells promoted cell proliferation and epithelial mesenchymal transition (EMT) with activated TGF-β signals such as phosphorylated Akt and Smad2/3 expressions. Surprisingly, knockdown of DPC4 (Smad4 gene) induced TSP-1 overexpression with TGF-β signal activation in PDAC cells. Interestingly, TSP-1 overexpression also induced downregulation of Smad4 expression and enhanced cell proliferation in vitro and in vivo. Treatment with LSKL peptide, which antagonizes TSP-1-mediated latent TGF-β activation, attenuated cell proliferation, migration and chemoresistance with enhanced apoptosis in PDAC cells., Conclusions: TSP-1 derived from CAFs stimulates loss of Smad4 expression in cancer cells and accelerates malignant behavior by TGF-β signal activation in PDAC. TSP-1 could be a novel therapeutic target, not only for CAFs in stiff stroma, but also for cancer cells in the PDAC microenvironment., Competing Interests: Declaration of Competing Interest No conflicts of interest, financial or otherwise, have been declared by the authors., (Copyright © 2022. Published by Elsevier Inc.)

Background/aim: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is highly malignant; therefore, continual, multidisciplinary treatments are essential., Case Report: In this study, two 78- and 81-year-old men were treated with the Vater papilla-preserving strategy. Case 1 had advanced HCC with BDTT expanding to the common bile duct (B4) and portal vein tumor thrombus (PVTT) of the umbilical portion. He showed triple-positive tumor markers. He underwent an extended left hepatectomy without bile duct resection following percutaneous transhepatic biliary drainage and transarterial chemoembolization (TACE). Later, TACE in combination with percutaneous microwave ablation was performed to treat four intrahepatic recurrent HCCs. Case 2 had diffuse-type HCCs accompanied by BDTT (B4) and PVTT to the right portal vein. He underwent liver partition associated with portal vein ligation for staged hepatectomy without bile duct resection. Six months later, he developed a solitary recurrent BDTT with obstructive jaundice. After percutaneous transhepatic biliary drainage, he was treated with two TACE from the various feeding arteries. Both patients achieved complete responses and are doing well without viable tumors approximately 2 years after the initial treatment., Conclusion: The Vater papilla-preserving strategy is essential for obtaining long-term survival and recurrent-free status for patients with HCC with highly extended BDTT., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)