A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope.

Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual's change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, -30.8% (95% confidence interval -42.6 to -16.8). The between-group difference (canagliflozin group - control group) of change in eGFR slope (chronic - pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD.

Clinical and genomic characteristics of IMP-producing Enterobacter cloacae complex and Klebsiella pneumoniae.

Carbapenemase-producing Enterobacterales (CPEs) are one of the top priority antimicrobial-resistant pathogens. Among CPEs, those producing acquired metallo-ß-lactamases (MBLs) are considered particularly problematic as few agents are active against them. Imipenemase (IMP) is the most frequently encountered acquired MBL in Japan, but comprehensive assessment of clinical and microbiological features of IMP-producing Enterobacterales infection remains scarce. Here, we retrospectively evaluated 62 patients who were hospitalized at a university hospital in Japan and had IMP-producing Enterobacterales from a clinical culture. The isolates were either Enterobacter cloacae complex or Klebsiella pneumoniae, and most of them were isolated from sputum. The majority of K. pneumoniae, but not E. cloacae complex isolates, were susceptible to aztreonam. Sequence type (ST) 78 and ST517 were prevalent for E. cloacae complex and K. pneumoniae, respectively, and all isolates carried blaIMP-1. Twenty-four of the patients were deemed infected with IMP-producing Enterobacterales. Among the infected patients, therapy varied and largely consisted of conventional ß-lactam agents, fluoroquinolones, or combinations. Three (13%), five (21%), and nine (38%) of them died by days 14, 30, and 90, respectively. While incremental mortality over 90 days was observed in association with underlying comorbidities, active conventional treatment options were available for most patients with IMP-producing Enterobacterales infections, distinguishing them from more multidrug-resistant CPE infections associated with globally common MBLs, such as New Delhi metallo-ß-lactamase (NDM) and Verona integron-encoded metallo-ß-lactamase (VIM).

Preoperative Prediction of Long-Term Survival After Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

Serum elastase-1 predicts malignancy in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: The indication for surgical resection of intraductal papillary mucinous neoplasms (IPMNs) is defined by imaging features, such as mural nodules. Although carbohydrate antigen (CA) 19-9 was selected as a parameter for worrisome features, no serum biomarkers were considered when deciding on surgical indications in the latest international consensus guideline. In this study, we assessed whether clinical factors, imaging findings, and serum biomarkers are useful in predicting malignant IPMNs. METHODS: A total of 234 resected IPMN cases in Chiba University Hospital from July 2005 to December 2021 were retrospectively analyzed. RESULTS: Among the 234 patients with resected IPMNs diagnosed by preoperative imaging, 117 were diagnosed with malignant pathologies (high-grade dysplasia and invasive IPMNs) according to the histological classification. In the multivariate analysis, cyst diameter ≥30 mm; p = 0.035), enhancing mural nodules on multidetector computed tomography (≥5 mm; p = 0.018), and high serum elastase-1 (≥230 ng/dl; p = 0.0007) were identified as independent malignant predictors, while CA19-9 was not. Furthermore, based on the receiver operator characteristic curve analyses, elastase-1 was superior to CA19-9 for predicting malignant IPMNs. Additionally, high serum elastase-1 levels (≥230 ng/dl; p = 0.0093) were identified as independent predictors of malignant IPMNs in patients without mural nodules on multidetector computed tomography (MDCT) in multivariate analysis. CONCLUSION: The serum elastase-1 level was found to be a potentially useful biomarker for predicting malignant IPMNs.

Nanoscale Structures of Tough Microparticle-Based Films Investigated by Synchrotron X-Ray Scattering and All-Atom Molecular-Dynamics Simulation.

In this study, the nanoscale structures of microparticle-based films are revealed by synchrotron small-angle X-ray scattering (SAXS) and all-atom molecular-dynamics (AA-MD) simulations. The microparticle-based films consisting of the simplest acrylate polymer microparticles are applied as a model because the films are formed without additives and organic solvents and exhibit high toughness properties. The characteristic interfacial thickness (tinter) obtained from the SAXS analysis reflects the mixing degree of polymer chains on the microparticle surface in the film. The cross-linking density of inner microparticles is found to be strongly correlated to not only several properties of individual microparticles, such as swelling ratio and radius of gyration, but also the tinter and toughness of the corresponding films. Therefore, the tinter and toughness values follow a linear relationship because the cross-linking restricts the mixing of polymer chains between their surfaces in the film, which is a unique feature of microparticle-based films. This characteristic also affects their deformation behavior observed by in situ SAXS during tensile testing and their density profiles calculated by AA-MD simulations. This work provides a general strategy for material design to control the physical properties and structures of their films for advanced applications, including volatile organic compound-free sustainable coatings and adhesives.

Effect of preceding drug therapy on the renal and cardiovascular outcomes of combined sodium-glucose cotransporter-2 inhibitor and glucagon-like peptide-1 receptor agonist treatment in patients with type 2 diabetes and chronic kidney disease.

AIM: To conduct a post hoc subgroup analysis of patients with type 2 diabetes (T2D) from the RECAP study, who were treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor and glucagon-like peptide 1 receptor agonist (GLP-1RA) combination therapy, focusing only on those patients who had chronic kidney disease (CKD), to examine whether the composite renal outcome differed between those who received SGLT2 inhibitor treatment first and those who received a GLP-1RA first. METHODS: We included 438 patients with CKD (GLP-1RA-first group, n = 223; SGLT2 inhibitor-first group, n = 215) from the 643 T2D patients in the RECAP study. The incidence of the composite renal outcome, defined as progression to macroalbuminuria and/or a ≥50% decrease in estimated glomerular filtration rate (eGFR), was analysed using a propensity score (PS)-matched model. Furthermore, we calculated the win ratio for these composite renal outcomes, which were weighted in the following order: (1) both a ≥50% decrease in eGFR and progression to macroalbuminuria; (2) a decrease in eGFR of ≥50% only; and (3) progression to macroalbuminuria only. RESULTS: Using the PS-matched model, 132 patients from each group were paired. The incidence of renal composite outcomes did not differ between the two groups (GLP-1RA-first group, 10%; SGLT2 inhibitor-first group, 17%; odds ratio 1.80; 95% confidence interval [CI] 0.85 to 4.26; p = 0.12). The win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was 1.83 (95% CI 1.71 to 1.95; p < 0.001). CONCLUSION: Although the renal composite outcome did not differ between the two groups, the win ratio of the GLP-1RA-first group versus the SGLT2 inhibitor-first group was significant. These results suggest that, in GLP-1RA and SGLT2 inhibitor combination therapy, the addition of an SGLT2 inhibitor to baseline GLP-1RA treatment may lead to more favourable renal outcomes.

Relationship between π-A isotherms and single microgel/microgel array structures revealed via the direct visualization of microgels at the air/water interface.

The structures of single microgels and microgel arrays formed at the air/water interface were visualized directly, and their structures correlated with π-A isotherms in order to understand the compression behavior of soft and deformable microgels at this interface. Large microgels (ca. 4 µm) were synthesized so that these can be clearly visualized at the air/water interface, even under high compression, and a series of microgel compression experiments were directly evaluated using a Langmuir trough equipped with a fluorescence microscope. The experiments revealed that upon compressing the microgel arrays at the interface voids disappeared and colloidal crystallinity increased. However, the colloidal crystallinity decreased when the microgel arrays were strongly compressed. In addition, when the structures were observed at higher magnification, it became clear that the single microgel structures, when visualized from above, changed from circular to polygonal upon compressing the microgel array. The results of this study can be expected to improve the understanding of the compression behavior of microgel arrays adsorbed at the air/water interface and will thus be useful for the creation of new functional microgel stabilizers with potential applications in e.g., bubbles and emulsions.

Elastomer Particle Monolayers Formed by the Compression of Poly(methyl acrylate) Microparticles at an Air/Water Interface.

In the previous study (Green Chem., 2023, 25, 3418), highly stretchable and mechanically tough poly(methyl acrylate) (pMA) microparticle-based elastomers can be formed by drying a microparticle-containing aqueous dispersion. This discovery has the potential to overcome the mechanical weakness of industrially produced aqueous latex films. However, in 3D-arranged particle films, structural complexity, such as the existence of defects, makes it difficult to clearly understand the relationship between the particle film structure and its mechanical properties. In this study, 2D-ordered pMA particle monolayers at the air/water interface of a Langmuir trough are prepared. Under high compression at the air/water interface, the microparticles contact their neighboring particles, and the resulting monolayers can be successfully transferred onto a solid substrate. The compression of the monolayer films is linked to an increase in the elastic modulus of the monolayer film on the solid substrate as evident from the local Young's modulus mapping using atomic force microscopy. Thus, pMA particle films with different mechanical properties can be created using a Langmuir trough.

Analysis of bacteremia at first-line antibiotic treatment for febrile neutropenia in children and adolescents: A retrospective, single-center analysis.

BACKGROUND: Control of bacterial and fungal infections is critical to improving outcomes in hematological neoplastic diseases of children and adolescents. In this study, a retrospective analysis of our previous studies on febrile neutropenia was performed to investigate bacteremia. PROCEDURE: From August 2008 to December 2023, five antibiotic studies were performed for febrile and neutropenic pediatric patients who had been treated with chemotherapy, immunosuppressive therapy, or had received stem cell transplantation in the pediatric unit at Sapporo Hokuyu Hospital. The rate of positive blood culture, detected bacteria, and susceptibility of several types of antibiotics in febrile episodes were investigated. RESULTS: Blood culture was positive in 133 of 1604 febrile episodes of 329 patients. Detected bacteria were Gram-positive cocci (61.2 %), Gram-negative bacilli (27.6 %), Gram-negative cocci (0.7 %), and Gram-positive bacilli (10.4 %). The incidence of bacteremia over time showed a decreasing trend with each passing year. In particular, the incidence of bacteremia was around 10 % in 2008-2013, whereas it was often below 5 % after 2020; this decrease was statistically significant. Although almost all detected bacteria and their susceptibilities to antibiotics (piperacillin/tazobactam, meropenem, ceftazidime, and cefozopran) did not change over time, all Escherichia coli detected after 2014 were extended-spectrum ß-lactamase-producing bacteria.

Association between heart failure in asymptomatic stages and skeletal muscle function assessed by ultrasonography in community-dwelling older adults.

BACKGROUND: Symptomatic heart failure (HF) negatively affects the quantity and quality of skeletal muscles. However, the association between asymptomatic HF and skeletal muscle function remains unclear. We aimed to use ultrasonography to elucidate the association between asymptomatic HF and skeletal muscle function in community-dwelling older adults. METHODS: This cross-sectional study comprised community-dwelling older adults aged ≥ 60 years who could perform activities of daily living independently and had never had symptomatic HF (n = 52, 76.3 ± 6.1 years). The participants were classified into three groups namely, non-HF (n = 26), stage A (n = 19), and stage B (n = 7) according to the HF stage criteria of the American Heart Association /American College of Cardiology /Heart Failure Society of America guideline. Skeletal muscle quantity and quality were assessed using ultrasonography (thickness and echo intensity) of the rectus femoris (RF) and vastus intermedius (VI) muscles. The group effects on muscle thickness and echo intensity in each group were assessed using a multivariate analysis. RESULTS: Both muscles consistently demonstrated significant group effects on the thickness and echo intensity. Thicknesses of the RF (p = 0.020) and VI (p = 0.035) were lower in the stage B group than that in the non-HF group. The echo intensities in the RF (p = 0.006) and VI (p = 0.009) were higher in the stage B group than that in the non-HF group. CONCLUSION: Asymptomatic HF negatively associated with the characteristics of skeletal muscle function, as assessed by ultrasonography in community-dwelling older adults. The stage B HF contributes to reduced skeletal muscle function as well as symptomatic HF.

Humanized mouse models with endogenously developed human natural killer cells for in vivo immunogenicity testing of HLA class I-edited iPSC-derived cells.

Human induced pluripotent stem cells (hiPSCs) genetically depleted of human leucocyte antigen (HLA) class I expression can bypass T cell alloimmunity and thus serve as a one-for-all source for cell therapies. However, these same therapies may elicit rejection by natural killer (NK) cells, since HLA class I molecules serve as inhibitory ligands of NK cells. Here, we focused on testing the capacity of endogenously developed human NK cells in humanized mice (hu-mice) using MTSRG and NSG-SGM3 strains to assay the tolerance of HLA-edited iPSC-derived cells. High NK cell reconstitution was achieved with the engraftment of cord blood-derived human hematopoietic stem cells (hHSCs) followed by the administration of human interleukin-15 (hIL-15) and IL-15 receptor alpha (hIL-15Rα). Such "hu-NK mice" rejected HLA class I-null hiPSC-derived hematopoietic progenitor cells (HPCs), megakaryocytes and T cells, but not HLA-A/B-knockout, HLA-C expressing HPCs. To our knowledge, this study is the first to recapitulate the potent endogenous NK cell response to non-tumor HLA class I-downregulated cells in vivo. Our hu-NK mouse models are suitable for the non-clinical evaluation of HLA-edited cells and will contribute to the development of universal off-the-shelf regenerative medicine.

Nanogel/Microgel Science and Beyond.

Since the first report in 1986, tremendous effort has been devoted to developing a deeper understanding of hydrogel colloidal particles (i.e., nanogels/microgels), including their synthesis, characterization, assembly, computer simulation, and various applications. At present, many researchers from diverse scientific backgrounds are using nanogels/microgels for their own research purposes, and thus, there seem to be several miscommunications. Here, in order to further accelerate the development of the nanogel/microgel research field, a personal viewpoint on this research topic is presented.

Nanoparticle-Based Tough Polymers with Crack-Propagation Resistance.

Although thin elastomer films of polymer nanoparticles are regarded as environmentally friendly materials, the low mechanical strength of the films limits their use in various applications. In the present study, we investigated the fracture resistance of latex films composed of acrylic nanoparticles where a small quantity of a rotaxane crosslinker was introduced. In contrast to conventional nanoparticle-based elastomers, the latex films composed of the rotaxane-crosslinked nanoparticles exhibited unusual crack propagation behavior; the direction of crack propagation changed from a direction parallel to the crack to one perpendicular to the crack, resulting in an increase in tear resistance. These findings will help to broaden the scope of design of new types of tough polymers composed of environmentally friendly polymer nanoparticles.

Stress-independent delay time in yielding of dilute colloidal gels.

We investigate the yielding under shear for dilute poly(N-isopropyl acrylamide-co-fumaric acid) (PNIPAM-FAc) colloidal gels obtained above the volume phase transition temperature. In this temperature range, the microgel suspensions form colloidal gels due to hydrophobic interparticle interactions under appropriate pH and ionic strength conditions. Step-strain tests revealed that yielding occurs when the applied strain exceeds a specific threshold, requiring a finite, stress-independent delay time (tD). This is distinct from previous findings on delayed yielding in other colloidal gels, where tD decreases with increasing stress. In the start-up shear tests, yield strain (γy) at a higher strain rate () increases with escalating , while γy at lower  remains constant. This characteristic γy- relationship is successfully explained by a simple model using the stress-independent tD value without an adjustable fitting parameter. The distinctive yielding behavior, underscored by a stress-independent tD, is expected to originate from strain-induced macroscopic phase separation into a dense colloidal gel and water, observable separately from rheological measurements.

Single microgel degradation governed by heterogeneous nanostructures.

Although the degradation of colloidal particles is one of the most attractive phenomena in the field of biological and environmental science, the degradation mechanism of single particles remains to be elucidated. In this study, in order to clarify the impact of the structure of a single particle on the oxidative degradation processes, thermoresponsive colloidal particles with chemical cleavage points were synthesized as a model, and their degradation behavior was evaluated using high-speed atomic force microscopy (HS-AFM) as well as conventional scattering techniques. The real-time observation of single-particle degradation revealed that the degradation behavior of microgels is governed by their inhomogeneous nanostructure, which originates from the polymerization method and their hydrophilicity. Our findings can be expected to advance the design of carriers for drug-delivery and the understanding of the formation processes of micro (nano)plastics.

Validity of claims-based diagnoses for infectious diseases common among immunocompromised patients in Japan.

BACKGROUND: To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP). METHODS: VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases. RESULTS: Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4-70.5% (HZ), 67.0-90.0% (MTB), 18.3-63.4% (NTM), and 20.0-45.0% (PJP) for prevalent cases, and 69.1-70.9% (HZ), 58.6-87.9% (MTB), 10.0-56.0% (NTM), and 22.6-51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM. CONCLUSIONS: VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.

Clinical benefits of pulmonary resection for lung metastases from pancreatic cancer.

PURPOSE: Systemic chemotherapy is generally used for metastatic pancreatic cancer; however, pulmonary resection may be a treatment option for lung oligometastases from pancreatic cancer. The current study aimed to clarify the oncological outcomes and clinical benefits of pulmonary resection for lung metastases. METHODS: Of 510 patients who underwent pancreatic resection for pancreatic cancer, 44 patients with recurrence of isolated lung metastases and one patient with simultaneous lung metastases were evaluated. RESULTS: Of the 45 patients, 20 patients were selected as candidates for pulmonary resection based on clinical factors such as recurrence-free interval (RFI) from pancreatectomy to lung metastases, number of lung metastases, and serum CA19-9 level. The post-recurrent survival of patients with pulmonary resection was significantly better than that of patients without pulmonary resection. Fourteen of the 20 patients with pulmonary resection developed tumor recurrence with a median disease-free survival (DFS) of 15 months. Univariate analyses revealed that an RFI from pancreatectomy to lung metastases of ≥28 months was associated with better DFS after pulmonary resection. Of the 14 patients with an RFI of ≥28 months, pulmonary resection resulted in prolonged chemotherapy-free interval in 12 patients. Furthermore, repeat pulmonary resection for recurrent tumors after pulmonary resection led to further cancer-free interval in some cases. CONCLUSIONS: Although many patients had tumor recurrence after pulmonary resection, pulmonary resection for lung metastases from pancreatic cancer may provide prolonged cancer-free interval without the need for chemotherapy. Pulmonary resection should be performed for the patients with a long RFI from pancreatectomy to lung metastases.

[Intraoperative Blood Flow Assessment of Gastric Tube Using Indocyanine Green fluorography during Pancreaticoduodenectomy Following Esophagectomy-Case Reports].

Case 1: A 73-year-old male, who had an intraductal papillary mucinous adenocarcinoma or resectable pancreatic cancer at the uncinate process of the pancreas five years after subtotal esophagectomy for esophageal cancer, underwent pylorus preserving pancreaticoduodenectomy(PPPD). Case 2: A 68-year-old male, who also had a resectable pancreatic cancer at the uncinate process of the pancreas 3 years after subtotal esophagectomy for esophageal cancer, underwent PPPD following neoadjuvant chemotherapy. In both cases, right gastroepiploic artery and vein were preserved to maintain the perfusion of the gastric tube during surgery. Indocyanine Green(ICG)fluorography was performed just before duodenal-jejunal anastomosis, which visually showed the well-perfused gastric tube. Both patients had no necrosis of the gastric tube, nor gastrointestinal obstruction after surgery. Intraoperative ICG fluorography was useful to evaluate the blood flow of the remaining gastric tube visually during PPPD for post-esophagectomy patients.

[Conversion Surgery Following Systemic Chemotherapy for Advanced Gallbladder Cancer with Peritoneal Dissemination-A Case Report].

A 73-year-old female was diagnosed with gallbladder cancer, but the future liver remnant volume was deemed insufficient for curative resection. Consequently, transileocolic portal vein embolization was performed. During laparotomy, multiple nodules were palpable on the peritoneal surface of the pelvic floor. Subsequently, staging laparoscopy confirmed the pathological diagnosis of adenocarcinoma in the resected nodules, indicating peritoneal dissemination of gall bladder cancer. Due to this peritoneal dissemination, surgical resection was deemed inappropriate, and the patient was initiated on systemic chemotherapy consisting of gemcitabine and cisplatin. Following 22 courses of chemotherapy, contrast-enhanced computed tomography demonstrated no significant changes in the size of the primary tumor or its location relative to the main vessels, although a small metastatic lesion was identified in the gallbladder bed. At the second staging laparoscopy, any nodules suggesting peritoneal dissemination were observed. Based on these findings, we decided to perform curative resection. The surgical procedure involved right hepatectomy plus segment 4a resection, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological examination revealed ypT3bN0M1(HEP), ypStage ⅣB, with the achievement of R0 resection. The patient survived with no recurrences for 40 months after surgery. These results suggest that aggressive therapeutic strategies, including conversion surgery following systemic chemotherapy, may be beneficial for patients initially deemed unresectable due to gallbladder cancer.

[Retrospective Study of Preoperative Serial Pancreatic Juice Aspiration Cytological Examination(SPACE)for Early Preoperative Detection of Pancreatic Cancer].

Serial pancreatic juice aspiration cytological examination(SPACE)has been reported as a reliable preoperative diagnostic method for early pancreatic cancer, when combined with imaging findings suspecting early pancreatic cancer. Among 259 patients with suspected pancreatic cancer who underwent pancreatic resection at our hospital, SPACE was preoperatively performed in 14 cases(5.4%). Of these 14 cases, final pathological diagnosis was pancreatic cancer in 12 patients (86%), including 5 patients with Stage ⅠA pancreatic cancer(35.7%), all of whom had a mass on preoperative CT or EUS. On the other hand, in the other 2 cases(14.3%), CT/EUS detected no mass but focal pancreatic parenchymal atrophy and main pancreatic duct stenosis which were the imaging findings suspecting very early pancreatic cancer such as cancer in situ. Although preoperative SPACE results of these 2 cases were class Ⅳ, final pathological results of resected specimen were low-grade PanIN in both cases. SPACE was considered useful for preoperative diagnosis of pancreatic cancer in our study, however further study is needed to examine its diagnostic accuracy for early pancreatic cancer which does not appear as a mass in any imaging modality.