Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas.

Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral T-cell neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity is a hallmark of ATLL pathogenesis. However, the mechanisms by which ATLL cells evade natural killer (NK)-cell-mediated immunity have been poorly understood. Here we show that CD48 expression in ATLL cells determines the sensitivity for NK-cell-mediated cytotoxicity against ATLL cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening using 2 ATLL-derived cell lines and discovered CD48 as one of the best-enriched genes whose knockout conferred resistance to YT1-NK cell line-mediated cytotoxicity. The ability of CD48-knockout ATLL cells to evade NK-cell effector function was confirmed using human primary NK cells with reduced interferon-γ (IFNγ) induction and degranulation. We found that primary ATLL cells had reduced CD48 expression along with disease progression. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCLs) also expressed lower concentrations of CD48 than normal T cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK-cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK-cell-mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK-cell-associated immunotherapies.

Is Prophylactic Splenectomy Necessary for Proximal Advanced Gastric Cancer Invading the Greater Curvature with Clinically Negative Splenic Hilar Lymph Node Metastasis? A Multi-Institutional Cohort Study (YCOG2003).

BACKGROUND: Prophylactic splenectomy for hilar lymph node (#10) dissection has shown no survival benefit for patients with proximal advanced gastric cancer that does not invade the greater curvature. However, the survival benefit of prophylactic splenectomy for proximal advanced gastric cancer invading the greater curvature side, particularly for clinically negative #10 lymph node metastasis (#10[-]) cases remains controversial. METHODS: This multi-institutional retrospective study enrolled 146 consecutive patients with proximal advanced gastric cancers invading the greater curvature side with clinical #10(-) who underwent R0 total gastrectomy. For 33 of these patients, splenectomy was performed, and the remaining 113 underwent spleen-preservation gastrectomy. Short- and long-term results were compared between the splenectomy and spleen-preservation groups, with the incidence of #10 metastasis in the splenectomy group and recurrence in the spleen-preservation group compared. RESULTS: In the splenectomy group, longer operative time, greater blood loss, more frequent postoperative abdominal infection, and longer hospital stay were observed than in the spleen-preservation group. The two groups exhibited no differences in median relapse-free survival time (31.1 vs 59.8 months; P = 0.684) or median overall survival time (64.9 vs 65.1 months; P = 0.765). The pathologic #10 lymph node metastasis rate was 3% in the splenectomy group, and the #10 lymph node recurrence rate was 2.7% in the spleen-preservation group. CONCLUSIONS: Prophylactic splenectomy showed more frequent postoperative morbidities and a longer hospital stay than spleen preservation, without any long-term survival benefits.

High postoperative neutrophil-lymphocyte ratio and low preoperative lymphocyte-monocyte ratio predict poor prognosis in gastric cancer patients receiving gastrectomy with positive lavage cytology: a retrospective cohort study.

BACKGROUND: Long-term outcomes in gastric cancer patients with positive lavage cytology (CY1) are generally poor. This multi-institutional retrospective cohort study aims to evaluate the clinical significance of the neutrophil-lymphocyte ratio (NLR) and the lymphocyte-monocyte ratio (LMR) in CY1 gastric cancer patients. METHODS: A total of 121 CY1 gastric cancer patients without other non-curative factors, who underwent macroscopically curative resection, were enrolled in this study. The cutoff values of preoperative NLR (pre-NLR), postoperative NLR (post-NLR), preoperative LMR (pre-LMR), and postoperative LMR (post-LMR) were defined by the Contal and O'Quigley method as 2.3, 3.0, 2.5, and 3.2, respectively. A Cox proportional hazard model was used to identify the independent prognostic factors among NLR, LMR, and other clinicopathological factors. RESULTS: There were significant differences in the overall survival (OS) between the two groups: high post-NLR groups vs. low post-NLR group (median survival time, months) (10.9 vs. 22.8, P = 0.006) and high pre-LMR group vs. low pre-LMR group (21.3 vs. 11.0, P = 0.001). The LMR value elevated significantly after gastrectomy (P = 0.020), although not in the NLR value (P = 0.733). On multivariate analysis, high post-NLR (hazard ratio = 1.506; 95% confidence interval = 1.047-2.167; P = 0.027), low pre-LMR (1.773; 1.135-2.769, 0.012), and no postoperative chemotherapy (1.558; 1.053-2.305, 0.027) were found to be independent prognostic factors for adverse OS. CONCLUSIONS: Because a combination of high post-NLR and low pre-LMR may be an adverse prognostic marker in resectable CY1 gastric cancer patients, it is necessary to conduct a prospective trial to confirm a useful perioperative chemotherapeutic regimen for these patients.

Real-World Therapeutic Outcomes of S-1 Adjuvant Chemotherapy for pStage II/III Gastric Cancer in the Elderly.

BACKGROUND: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. METHODS: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. RESULTS: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1-100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141-0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. CONCLUSION: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

[Nutritional Status after Laparoscopic-Assisted Pylorus-Preserving Gastrectomy].

PATIENTS AND METHODS: Patients with gastric cancer who underwent laparoscopic-assisted pylorus-preserving gastrectomy (LAPPG group)or laparoscopic-assisted distal gastrectomy(LADG group)between January 2010 and December 2019 were reviewed and their postoperative nutritional status and long-term outcomes retrospectively evaluated. RESULTS: In total, 83 patients(LAPPG group, n=23; LADG group, n=60)were included. Weight loss rates 1, 6, 12, and 24 months postoperatively in the LAPPG and LADG groups were 5.7% and 7.1%, 6.6% and 9.6%, 5.8% and 10.1%, and 5.2% and 8.7%, respectively. The LADG group exhibited a significantly higher weight loss than the LAPPG group at 6, 12, and 24 months (p=0.007, 0.002, and 0.022, respectively). No recurrence was observed in either group within 5 years of surgery. The 5- year overall survival rate of patients with pathological Stage Ⅰ cancer( LAPPG group, n=23, LADG group, n=51) was higher in the LAPPG group than in the LADG group(100% vs 82.9%, p=0.027). There were 6 cases of death from other diseases in the LADG group(pneumonia, n=2, other cancer, n=2, postoperative bleeding, n=1, and heart failure, n=1)but none in the LAPPG group. CONCLUSION: The weight loss after LAPPG was significantly lower than that after LADG. Furthermore, the former showed a good prognosis without death from other diseases, such as pneumonia.

Immaturity of Bile Canalicular-Ductule Networks in the Future Liver Remnant While Associating Liver Partition and Portal Vein Occlusion for Staged Hepatectomy (ALPPS).

BACKGROUND: We studied histologic changes of bile canalicular-ductule networks in the future liver remnant (FLR) while associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS), since little is known about regeneration of these networks during the relatively short interval between procedures in ALPPS. METHODS: Bile canalicular-ductule networks were examined in specimens from eight patients treated with ALPPS and six patients undergoing hepatectomy following portal vein embolization (PVE). Expression of multidrug resistance-1 (MDR1), a membrane transporter in bile canaliculi (BC), was analyzed immunohistochemistcally. Morphologic changes of BC and tight junctions (TJs) adjoining BC were also assessed electron microscopically. RESULTS: Extrapolated kinetic growth of the FLR was greater during ALPPS (17.2 ± 6.8 mL/day) than after PVE (6.3 ± 3.4 mL/day; p = 0.005), and continuity of the MDR1-positive bile canalicular networks was less evident in ALPPS than PVE (p < 0.001). Electron microscopically, no significant difference was evident in numbers of BC or BC lumen size between the two groups; however, development of microvilli in BC was poorer in the ALPPS group than in the PVE group (p < 0.001). TJ/desmosome complexes were shorter in the ALPPS group (0.69 ± 0.52 µm) than in the PVE group (1.09 ± 0.50 µm; p < 0.001), and leaky TJs were seen more frequently in the ALPPS group (64.9 vs. 23.6%; p = 0.001). CONCLUSIONS: Regeneration of bile canalicular-ductule networks in the FLR was poorer in ALPPS than PVE, which may be associated with prolonged cholestasis following final hepatectomy in ALPPS.

[A Case of Rectal Metastasis from Breast Cancer Diagnosed Two Years after Surgery].

We report a case of rectal metastasis from breast cancer.Colorectal metastasis from breast cancer is sometimes difficult to diagnose before surgery.A transanal needle biopsy was thought to be useful for a diagnosis and selection of treatment method.

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

BACKGROUND: Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. METHODS: We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30 %, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. RESULTS: FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P > .001 and P > .001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P = .357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P = .005; OR 36.5; 95 % CI 3.0-446.3) and steatohepatitis (P = .012; OR, 29.1; 95 % CI 2.1-400.1). CONCLUSIONS: FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.

Primary Bone Lymphoma: A Clinical Analysis of 17 Patients in a Single Institution.

Primary bone lymphoma (PBL) comprises less than 1% of all malignant lymphomas. Because few studies of PBL have been conducted in Japan, the characteristics of Japanese patients with PBL have not been fully elucidated. We retrospectively analyzed 17 patients diagnosed with PBL at our institution between 2001 and 2011. Median patient age was 60 years. Eleven patients had diffuse large B-cell lymphoma and 2 patients had T-cell lymphoma histology. The spine was the most frequently involved site at the time of presentation. There were 11 patients with stage IV disease and 11 patients with high or high-intermediate risk according to the International Prognostic Index (IPI). Thirteen patients achieved complete response (CR) after initial treatment. At a median follow-up of 31 months, the 3-year overall survival (OS) and progression free survival were 63.5 and 49.9%, respectively. Localized disease, low or low-intermediate IPI, and CR after initial treatment were associated with a good outcome in patients with PBL and significantly associated with a better OS. Spine involvement and T/NK-cell phenotype are more frequent in Japanese than in Caucasian patients with PBL.

[Successful treatment of an HIV-positive multiple myeloma patient with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and maintenance therapy with lenalidomide].

A 45-year-old HIV positive male who had previously been administered anti-retrovirus therapy (ART) resulting in a good virological response and with a CD4 count of more than 1,000/µl, complained of general fatigue during a periodic examination. Laboratory data showed decreased Hb (10.8 g/dl) and increased T.P (12.0 g/dl) and IgG (9,077 mg/dl). Monoclonal gammopathy (IgG-λ) was identified and bone marrow aspiration revealed 37.6% atypical plasma cells, leading to the diagnosis of symptomatic multiple myeloma (MM) (ISS clinical staging III).Four courses of VD (bortezomib+dexamethasone) therapy were administered with concurrent ART resulting in VGPR (very good partial response), followed by peripheral blood stem cell collection (the mobilizing chemotherapy was cyclophosphamide). Then, together with ART, high-dose chemotherapy (Mel-200; L-PAM) was administered with autologous peripheral blood stem cell transplantation (PBSCT). Reconstitution of white blood cells was achieved at 10 days after PBSCT. There were no adverse effects of ART and the viral load of HIV was well controlled during the period of these treatments. The final assessment was VGPR and 10 mg/day of lenalidomide has since been administered as maintenance therapy. Standard treatment combined with PBSCT for juvenile-onset MM is also effective and safe for HIV-positive patients receiving ART.

Ramucirumab Plus Paclitaxel as a Second-line Chemotherapy in Older Adults With Advanced Gastric Cancer (YCOG1601).

BACKGROUND/AIM: Ramucirumab plus paclitaxel has been widely used as a second-line chemotherapy for treating advanced gastric cancer. However, the real-world data of this regimen for older patients with gastric cancer (GC) remains unrevealed. The aim of this study was to clarify the feasibility and efficacy of this regimen for older patients with GC in a single-arm, phase II study. PATIENTS AND METHODS: Patients aged ≥70 years having unresectable or recurrent GC who met the eligible criteria were enrolled. Paclitaxel was administered at a dose of 80 mg/m2 on days 1, 8, and 15, and ramucirumab was administered at a dose of 8 mg/kg on day 1 and day 15 of a 4-week cycle. Primary endpoint was the incidence of adverse events and secondary endpoints were response rate, progression-free survival, and overall survival. A total of 25 patients were enrolled in the full-set analysis. RESULTS: Grade 3 or more adverse events were observed in 21 patients (84.0%). Neutropenia was most frequently observed (68.0%), followed by peripheral sensory neuropathy (12.0%), and febrile neutropenia (12.0%). Median progression-free survival and overall survival were 6.9 months and 13.4 months, respectively. Disease control rate was 88.0%, and response rate of patients with measurable lesions was 52.9%. Notably, no treatment-related deaths occurred. CONCLUSION: Ramucirumab plus paclitaxel as a second-line chemotherapy demonstrated acceptable oncological outcomes, despite the occurrence of frequent adverse events. It is necessary to carefully select patients and adjust treatment regimens in older patients with GC to safely administer chemotherapy and subsequently achieve satisfactory long-term outcomes.

Long-term Outcomes of Neoadjuvant Chemotherapy With Docetaxel, Cisplatin and S-1 for Stage III Gastric Cancer.

BACKGROUND/AIM: In the previous phase I/II study, we established neoadjuvant chemotherapy (NAC) using bi-weekly docetaxel, cisplatin, and S-1 (DCS) for clinical stage III gastric cancer. This study aimed to clarify long-term outcomes of this treatment. PATIENTS AND METHODS: Relapse-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method and prognostic factors for RFS and OS were identified by univariate analysis. RESULTS: A total of 47 patients with clinical stage III gastric cancer were enrolled in this study. The 5-year RFS and OS rates were 69.8% and 74.3%, respectively, in all registered patients. Moreover, the 5-year OS and RFS rates in patients receiving R0 gastrectomy were 68.0% and 79.4%, respectively. Neutrophil-lymphocyte ratio (NLR) before NAC ≥2.41, prognostic nutritional index (PNI) before NAC ≤50.4, Glasgow prognostic score before NAC classification 2, NLR after NAC ≥1.43, PNI after NAC <48.0, and Grade 1a/1b pathological response significantly worsened RFS. NLR after NAC ≥1.43, PNI before NAC ≤50.4, NLR after NAC ≥1.43, and body weight loss >5 kg after NAC significantly worsened OS. CONCLUSION: Although bi-weekly DCS therapy as neoadjuvant setting showed acceptable long-term outcomes, poor immune-nutritional status before and after NAC caused worse long-term survival in stage III gastric cancer patients. It is warranted to conduct a well-designed prospective randomized control study to compare long-term outcomes using the bi-weekly DCS regimen between patients with and without immune-nutritional support during peri-NAC.

Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.

Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/insulin-like growth factor-I receptor tyrosine kinases.

Insulin receptor substrates (IRSs) are phosphorylated by activated insulin/insulin-like growth factor (IGF)-I receptor tyrosine kinases. Phosphotyrosyl IRSs are recognized by signaling molecules possessing src homology region 2 (SH2) domains, which mediate various insulin/IGF bioactivities. However, we have shown that IRSs are also associated with other proteins by a phosphotyrosine-independent mechanism. Here, we demonstrated that IRSs form high-molecular-mass complexes (we named these complexes IRSomes) with various proteins and we elucidated their possible roles. Blue native-polyacrylamide gel electrophoresis of cell lysates revealed IRSome formation. Some proteins associated with IRSs in IRS-isoform-, cell-type-, or stimulus-specific manners. Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-α. Also, tyrosine phosphorylation of IRS-2 by IGF-I receptor was increased when IRS-2 was contained in IRSomes prepared from FRTL-5 thyrocytes treated with dibutyryl cAMP. These results demonstrated that cytokine/hormone-induced formation of IRSomes modulates availability of IRSs to receptor tyrosine kinases.

Prognostic impact of dimensional factors in pT1 gastric cancer.

BACKGROUND: The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer. OBJECTIVES: This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer. METHODS: We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve. RESULTS: Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. CONCLUSIONS: The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

Systemic Review and Meta-analysis of Impact of Splenectomy for Advanced Gastric Cancer.

BACKGROUND/AIM: Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen. RESULTS: Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature.

Nivolumab-induced immune thrombocytopenia in a patient with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive tumor. Nivolumab showed durable antitumor effect in patients with recurrent MPM and was approved for those patients in Japan in 2018. Immune related adverse event (irAE) is occurred in various organs and is suggestive to be related to better outcome of nivolumab. Frequency of hematological irAE is low and there are few reports about hematological irAE and association between irAE and outcome of nivolumab in patients with MPM. We present a case of recurrent MPM who responded to nivolumab treatment and experienced nivolumab-induced immune thrombocytopenia (ITP). Although high dose dexamethasone was administered and platelet count increased transiently, re-administration of dexamethasone was required to maintain normal count of platelet. The careful and intensive management of ITP treatment is necessary in cases who show no response or relapse to initial glucocorticoids treatment. This is the first report about nivolumab-induced ITP and association with response to nivolumab in MPM.

Impact of associating liver partition and portal vein occlusion for staged hepatectomy on tumor growth in a mouse model of liver metastasis.

BACKGROUND: The impact of associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) on tumor growth activity was investigated. METHODS: A BALB/c mouse model (male, 8-10 weeks old) of liver metastasis labeled by red fluorescent protein was established. Changes in future liver remnant (FLR) volumes, tumor growth activity, and levels of cytokines and growth factors in liver tissues during the treatment period were compared among the models involving ALPPS, portal vein ligation (PVL), or sham operation. RESULTS: The ratio of the FLR volume to body weight at 24 h after the procedure was greater for ALPPS (4.45 ± 0.12 × 10-2) than for PVL (3.79 ± 0.12 × 10-2; P = 0.003) and sham operation (3.18 ± 0.16 × 10-2; P < 0.001). No differences in tumor progression in the FLR were observed at any time point after the procedures. Within the deportalized liver (DL), although tumor progression was observed during a later period after ALPPS (9 days postoperative) and PVL (12 days postoperative), no acceleration of tumor growth after ALPPS was observed in an early period similar to PVL. CONCLUSION: ALPPS induces a rapid increase in FLR volume and avoids remnant tumor progression during the early postoperative period.

Effect of Lactobacillus casei strain Shirota-fermented milk on metabolic abnormalities in obese prediabetic Japanese men: a randomised, double-blind, placebo-controlled trial.

An obesity-related prediabetic state is characterised by metabolic abnormalities such as post-glucose load hyperglycaemia and dyslipidaemia and consequently increases the risk for type 2 diabetes and cardiovascular disease. This study aimed to investigate the effects of Lactobacillus casei strain Shirota (LcS) on metabolic abnormalities in obese prediabetic subjects in a randomised, double-blind, placebo-controlled trial. Herein, 100 obese subjects (body mass index ≥25), who had moderate post-load hyperglycaemia (1-hr post-load plasma glucose (PG) levels ≥180 mg/dl during the oral glucose tolerance test), consumed LcS-fermented milk or placebo milk daily for 8 weeks. The post-load PG and fasting blood markers were evaluated. Although post-load PG levels were not significantly different between the groups, 1-hr post-load PG, glycoalbumin, and HbA1c levels decreased at 8 weeks compared with the baseline levels only in the LcS group (p=0.036, p=0.002, and p=0.006, respectively). The reduction in glycoalbumin levels was statistically significantly greater in the LcS group than in the placebo group (p=0.030). Stratified analyses revealed significantly improved 1-hr post-load PG and glycoalbumin levels in the LcS group compared with the placebo group among subjects with severe glucose intolerance (2-hr post-load PG levels higher than the median at baseline; p=0.036 and p=0.034, respectively). In terms of lipidic outcomes, total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels were significantly lower in the LcS group than in the placebo group (p=0.023, p=0.022, and p=0.008, respectively). These findings suggest that LcS may favourably affect metabolic abnormalities in obese prediabetic subjects, though the effects on glycaemic control may be limited.