Safety and effectiveness of avelumab in patients with Merkel cell carcinoma in general clinical practice in Japan: Post-marketing surveillance.

Avelumab, a programmed cell death ligand 1 blocking antibody, was approved for its first indication in Japan in September 2017 to treat unresectable Merkel cell carcinoma (MCC). Given that the pivotal JAVELIN Merkel 200 study only included a few Japanese patients, this post-marketing surveillance (PMS) evaluated the safety and effectiveness outcomes of patients with MCC who received avelumab in general clinical practice in Japan. This prospective, non-comparative, multicenter PMS included data from all patients with unresectable MCC who received avelumab between November 22, 2017 (avelumab launch date) and October 31, 2019. The primary objective was to evaluate avelumab safety (i.e., adverse events [AEs], adverse drug reactions [ADRs], and ADRs of safety specifications). The secondary objective was to evaluate avelumab effectiveness (i.e., objective response rate and overall survival [OS] rate). Seventy-five evaluable patients were included, of whom 81.3% experienced AEs of any grade (57.3% experienced AEs of grade ≥ 3; 41.3% experienced AEs of grade 5) and 61.3% experienced ADRs (14.7% experienced ADRs of grade ≥ 3; no grade 5 ADRs were observed). The most common ADRs were pyrexia (18.7%), infusion related reaction (10.7%), and chills (6.7%). The most common ADRs of safety specifications were infusion reactions (any grade: n = 21 [28.0%]; grade 3 or 4: n = 3 [4.0%]), thyroid dysfunction (n = 7 [9.3%]), and hepatic function disorders (n = 4 [5.3%]). The median observation period was 51 weeks. An objective response was achieved by 34/75 patients (45.3%; complete response, 24.0%; partial response, 21.3%) and 6- and 12-month OS rates were 77.7% and 59.6%, respectively. This PMS confirmed the clinical tolerability and effectiveness of avelumab in patients with MCC, with no new safety concerns. The risk-benefit profile of avelumab was comparable with that observed in clinical trials and remains favorable for use in general clinical practice in Japan.

[A case of rectal cancer with immune thrombocytopenic purpura that achieved a complete response to continued chemotherapy with eltrombopag].

A 73-year-old male patient with postoperative recurrent rectal cancer developed thrombocytopenia after XELOX therapy. Thrombocytopenia persisted despite chemotherapy discontinuation;therefore, he was referred to our department for further evaluation. Bone marrow specimen examination revealed increased immature megakaryocytes and blood test results revealed elevated platelet-associated immunoglobulin G (PA-IgG) levels, leading to immune thrombocytopenic purpura diagnosis. His platelet count recovered after prednisolone therapy. Eltrombopag treatment was introduced considering thrombocytopenia secondary to chemotherapy resumption for rectal cancer. FOLFIRI therapy was continued without platelet count reduction, and PA-IgG levels decreased over time. The patient continued chemotherapy with eltrombopag and achieved a complete treatment response.

Risk Factors for Failure of Endoscopic Management of Stone-related Ureteral Strictures.

PURPOSE: To investigate factors determining the outcomes of endoscopic management for stone-related ureteral stricture. MATERIALS AND METHODS: Data of patients who underwent endoscopic surgery for ureteral stricture due to stones from January 2016 to April 2020 were retrospectively analyzed. We compared cases successfully treated with endoscopic surgery with cases that resulted in failure. We focused on factors associated with treatment success, including cause and length of stricture, methods of stricture treatment, surgical time, and duration of hydronephrosis before the treatment. Treatment success was defined as improvement in hydronephrosis status. RESULTS: Nineteen patients were treated for stone-related ureteral stricture. Hydronephrosis was successfully improved in 12 patients (63.2%). Seven patients with failed endoscopic management had ureteroscopic lithotripsy- related stricture, whereas 3/12 (25.0%) patients with ureteroscopic lithotripsy-related stricture and 7/12 (58.3%) patients with impacted stone-related stricture were successfully treated by endoscopic management (P = .004). The prevalence of stricture length > 15 mm was significantly higher in the patients with failed management than in the patients with successful management (71.4 vs 16.6%, P = .046). Intraoperative endoscopic observation demonstrated that the mucosa of the ureteroscopic lithotripsy-related stricture had ischemic appearance with relatively long stricture length (P = 0.13) compared to the impacted stone-related stricture. No association was observed between treatment outcome and method of endoscopic management, including laser incision, balloon dilation, or both. CONCLUSION: Ureteroscopic lithotripsy as a cause and stricture length > 15 mm could affect the success rate of endoscopic management of ureteral stricture. In such cases, reconstructive management should probably be considered in the early stages.

A novel approach in creating nephrostomy using a double-lumen access sheath during endoscopic combined intrarenal surgery.

BACKGROUND: This study aimed to evaluate the safety and efficacy of an inner ureteral access sheath (i-UAS) with a double-lumen channel used in ureteroscopic lithotripsy (URS) as a dilator for the percutaneous tract in endoscopic combined intrarenal surgery (ECIRS). METHODS: This was a single-center cohort study conducted from January 2016 to April 2020. We used an i-UAS as a dilator and a double-lumen catheter to insert a safety guidewire during the creation of the nephrostomy tract in ECIRS. Univariate and multivariate analyses were performed to assess the association between the perioperative parameters and the use of i-UAS. The primary endpoint was perioperative complications, and secondary endpoints were stone-free rate (SFR), operative time, fluoroscopy time, and duration of hospitalization. RESULTS: In total, 221 patients were enrolled during the study period. Patients were divided into an i-UAS dilation group (n=108) and a one-shot dilation group (n=113). No differences were observed between the two groups in terms of patient history. Univariate analyses indicated that, in the i-UAS dilation group, the operative time was shorter [105.50 (83.75-143.25) vs. 121.00 (90.00-155.00) min; P=0.02] and the modified Valdivia position was more frequently selected. Multivariate analyses showed no significant differences in the frequency of complications, such as urinary injury or postoperative pyelonephritis, but it showed a significantly shorter operative time as well as fewer tract creation troubles in the i-UAS dilation group. CONCLUSIONS: Using an i-UAS as a dilator and a double-lumen catheter to insert a safety guidewire during ECIRS is a convenient and safe technical method for creating a nephrostomy tract that can reduce the operative time.

Robot-Assisted Fluoroscopy Versus Ultrasound-Guided Renal Access for Nephrolithotomy: A Phantom Model Benchtop Study.

Objectives: To evaluate the feasibility of robot-assisted fluoroscopy-guided (RAG) puncture and to compare RAG puncture, utilizing a novel robot system for percutaneous renal access, with ultrasound-guided (USG) puncture. Materials and Methods: We conducted a benchtop study with a renal phantom model using the automated needle targeting with an X-ray system. Seventeen urologists participated in this study and performed RAG and USG phantom punctures. The number of needle punctures, device setup time, and fluoroscopic exposure duration were recorded for the analyses. Results: The single puncture success rates of the RAG and USG punctures were 100% and 70.6%, respectively (p = 0.021). The median needle puncture time of RAG puncture was 24% shorter than that of USG puncture (35.0 vs 46.0 seconds; p < 0.001), and the median device setup time of RAG puncture was a minute longer than that of USG puncture (93.0 vs 30.5 seconds; p < 0.001). The median duration of fluoroscopic exposure of RAG puncture was longer than that of USG puncture (38.0 vs 6.5 seconds; p < 0.001). The surgeon's self-assessment results demonstrated that the participating urologists found RAG puncture to be safer and have better visibility than USG puncture; they were also more satisfied with RAG puncture. Subanalysis revealed that, in the RAG group, the attending surgeons had shorter total procedural time than the residents (p = 0.045). Conclusion: RAG puncture showed comparable results and accuracy rates with USG puncture for renal access.

Evaluation of the Dwell-Time and Dose Difference in Intravesical Bacillus Calmette-Guèrin Therapy

Objective: Bacillus Calmette-Guèrin (BCG) intravesical therapy is currently established using a low dose because of the high incidence of side-effects. Moreover, shortening the dwell time of BCG is conducted in some facilities owing to the complications associated with a long dwell time after injection. The method of BCG administration varies in each facility and even with each doctor. We evaluated whether the dwell-time and dose differences in patients who underwent intravesical BCG therapy is related to completion rates, adverse effects, and nonrecurrence rates. Methods: From November 2006 to April 2016, a total of 173 patients who received intravesical BCG therapy after transurethral resection of bladder tumor or transurethral biopsy were evaluated retrospectively. We allocated them into 4 groups based on the dose (40 or 80 mg BCG) and the dwell time (1 or 2 hours). Completion rate, side effects, and nonrecurrence rates were evaluated. Results: No significant improvement in the completion rate or reduction in side-effects was observed in any of the regimens. Although nonrecurrence rates for the 1-hour dwell time tended to be lower than the 2-hour dwell time, the difference was not significant. Conclusion: Our study suggests that reducing the BCG dose or shortening the dwell time does not reduce adverse effects or affect the nonrecurrence rate.

Hemothorax during miniaturized endoscopic combined intrarenal surgery under ureteroscope-assisted ultrasound-guided access.

INTRODUCTION: Hemothorax is a rare but life-threatening complication following mini-endoscopic combined intrarenal surgery. Herein, we describe a patient with left staghorn kidney stone who presented with hemothorax following mini-endoscopic combined intrarenal surgery under ureteroscope-assisted ultrasound-guided access. CASE PRESENTATION: A 47-year-old woman with left staghorn kidney stone underwent mini-endoscopic combined intrarenal surgery, after which she developed shortness of breath. Chest radiography and computed tomography confirmed left hemothorax. Conservative management and left intercostal chest drainage were performed without improvement. Subsequently, video-assisted thoracoscopic debridement was performed. CONCLUSION: Hemothorax is a severe complication of mini-endoscopic combined intrarenal surgery, which, regardless of accurate access through an ideal renal calyx under ureteroscope-assisted ultrasound-guided access, may lead to pleural injury. Refinement of the surgical technique and management after percutaneous nephrolithotomy is the key to avoiding life-threatening situations.

Outcomes and Complications of Simultaneous Laparoscopic Cystectomy and Laparoscopic Nephroureterectomy with Umbilical Reduced Port Surgery

Objective: In recent years, although reduced port surgeries (RPS) have been reported for many urological diseases, there have been no reports regarding simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Therefore, the aim of this study was to evaluate outcomes and complications of simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS. Methods: We performed a preliminary case series of 4 patients with synchronous upper urinary tract (UUT) tumor and invasive bladder cancer who underwent simultaneous laparoscopic cystectomy and unilateral or bilateral nephroureterectomy with umbilical RPS between 2014 and 2017 at our hospital. Demographic data, pathologic features, the surgical technique, and outcomes were retrospectively analyzed. Result: All 4 patients were men whose median age was 79 years (range 65-85 years) and median body mass index was 24.2 kg/m2 (range 21.5-27.3 kg/m2). The laparoscopic approach was technically successful in all 4 patients without the need for open conversion. The median total operative time was 434 minutes (range 372-481 minutes). The median estimated blood loss was 773 ml (range 153-923 ml), median interval to resuming oral intake was 2 days (range 1-7 days), and median hospital stay was 16 days (range 13-20 days). Conclusion: The reduced port approach is technically feasible in terms of many outcome measures, with significant cosmetic advantages. This method can be performed safely and recommended as a viable option for patients with concomitant UUT and bladder cancer.

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis.

BACKGROUND: The objective of this study was to evaluate the efficacy of a combination of gemcitabine and docetaxel (GD) as a second-line treatment for elderly patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS: A total of 122 patients with mUC who were previously treated with platinum-based chemotherapy received second-line GD therapy from July 2010 to June 2016. This consisted of 800 mg/m2 gemcitabine and 40 mg/m2 docetaxel on days 1 and 8 in each 21-day cycle. Using pooled cumulative data, we divided patients into the following three groups based on age: <65 years (Group A), from 65 to 74 years (Group B), and ≥75 years (Group C), and then the data were retrospectively analyzed. All patients were evaluated for treatment-related toxicities and assessed at every cycle by imaging studies. Kaplan-Meier curves were used for survival and recurrence analyses. Furthermore, potential prognostic factors for progression-free survival (PFS) and overall survival (OS) were assessed via univariate and multivariate Cox regression analyses. RESULTS: The median follow-up period was 8.2 months (range: 2.1-100). The median number of treatment cycles was three (range: 1-16) in Group A, three (1-15) in Group B, and two (1-11) in Group C. The objective response rate was not significantly different between the three groups. In addition, PFS and OS from the start of second-line GD therapy were also not significantly different. According to univariate and multivariate analyses of the second-line GD-treated cohort, a good performance status was the only prognostic factor for PFS and OS. In Group C, myelosuppression including predominant neutropenia and anemia, fatigue, and nausea were the main common adverse events. However, the incidence of neutropenia and a reduction in platelets were not significantly different between the three groups. Treatment-related deaths did not occur in this study. CONCLUSION: In this study, GD combination therapy as a second-line treatment for mUC resulted in favorable tumor responses and few treatment-related toxicities, even among elderly patients.

Primary diffuse large B-cell lymphoma of the ileal conduit created after radical cystectomy.

INTRODUCTION: Creation of an ileal conduit is associated with complications. A few cases have been reported on tumor development in an ileal conduit; diffuse large B-cell lymphoma originating from an ileal conduit is extremely rare. CASE PRESENTATION: A 62-year-old Japanese man who had undergone radical cystectomy and ileal conduit diversion 6 years previously presented with a whitish bulge that had developed on the surface of the ileal conduit during follow-up visit. Mass biopsy was performed and the histological diagnosis was diffuse large B-cell lymphoma. Positron emission tomography showed no metastatic lesions. We attempted chemotherapy because the tumor cells tested positive for CD20; after six courses of a regimen involving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; diffuse large B-cell lymphoma of the ileal conduit resolved gradually. The patient is alive and remains free from the diagnosed diffuse large B-cell lymphoma. CONCLUSION: We reported an extremely rare case of diffuse large B-cell lymphoma originating from the ileal conduit created after radical cystectomy.

Control of polarization and tumoricidal activity of macrophages by multicellular spheroid formation.

Immune cell-based therapy is a promising approach for cancer immunotherapy. Macrophages can be used for this purpose if their tumoricidal activity and viability are properly controlled. In the present study, we aimed to enhance these properties of macrophages by constructing uniformly sized multicellular spheroids. Mouse macrophage-like J774.1 cells were selected as model macrophages, and poly(N-isopropylacrylamide)-coated polydimethylsiloxane-based microwell plates with an approximate diameter of 750µm were used to prepare J774.1 spheroids. J774.1 spheroids were successfully generated, and the viability of cells in the spheroids was over 95%. J774.1 spheroids showed higher mRNA expression of induced nitric oxide synthase, a marker of M1-type activated macrophages, than monolayered J774.1 cells. The production of reactive oxygen species was also high in J774.1 spheroids, suggesting the existence of hypoxic regions in the spheroids. J774.1 spheroids released more tumor necrosis factor-α than monolayered cells upon stimulation with lipopolysaccharide. Moreover, J774.1 spheroids in the upper compartment of the Transwell system more efficiently inhibited the proliferation of mouse adenocarcinoma colon 26 cells in its lower compartment than monolayered J774.1 cells did. These results indicate that spheroid formation can be used to increase the tumoricidal activity of macrophages for use in cell-based cancer immunotherapy.

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma.

Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful. Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m2) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m2) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient's quality of life. Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2-9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly. Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.

A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy.

OBJECTIVES: Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. METHODS: We examined 6 patients (median age: 25 years, range: 19-27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8-84 months). RESULTS: Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP)). One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. CONCLUSIONS: Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

Using size-controlled multicellular spheroids of murine adenocarcinoma cells to efficiently establish pulmonary tumors in mice.

Previous studies demonstrated that multicellular spheroids developed using polydimethylsiloxane-based microwells exhibited superior functions, such as insulin secretion from pancreatic cells, over suspended cells. To successfully apply these spheroids, the effect of spheroid size on cellular functions must be determined. In this study, using murine adenocarcinoma colon26 cells, the authors examined whether such spheroids were useful for developing tumor-bearing animal models, which requires the efficient and stable engraftment of cancer cells at implanted sites and/or metastatic sites. The authors prepared microwells with widths of 360, 450, 560, and 770 µm through a micromolding technique, and obtained colon26 spheroids with average diameters of 169, 240, 272, and 341 µm, respectively. Small and medium spheroids were subsequently used. mRNA levels of integrin ß1, CD44, and fibronectin, molecules involved in cell adhesion, increased with increasing colon26 spheroid size. Approximately 1.5 × 104 colon26 cells in suspension or in spheroids were intravenously inoculated into BALB/c mice. At 21 days after inoculation, the lung weight of both colon26 spheroid groups, especially the group injected with small spheroids, was significantly higher than that of mice in the suspended colon26 cell group. These results indicate that controlling cancer cell spheroid size is crucial for tumor development in tumor-bearing mouse models.

Optimization of Albumin Secretion and Metabolic Activity of Cytochrome P450 1A1 of Human Hepatoblastoma HepG2 Cells in Multicellular Spheroids by Controlling Spheroid Size.

Multicellular spheroids are useful as three-dimensional cell culture systems and for cell-based therapies. Their successful application requires an understanding of the consequences of spheroid size for cellular functions. In the present study, we prepared multicellular spheroids of different sizes using the human hepatoblastoma HepG2 cells, as hepatocytes are frequently used for in vitro drug screening and cell-based therapy. Precise polydimethylsiloxane-based microwells with widths of 360, 450, 560, and 770 µm were fabricated using a micromolding technique. Incubation of HepG2 cells in cell culture plates containing the microwells resulted in the formation of HepG2 spheroids with average diameters of 195, 320, 493, and 548 µm. The cell number per spheroid positively correlated with its diameter, and the viability of HepG2 cells was 94% or above for all samples. The smallest HepG2 spheroids showed the highest albumin secretion. On the other hand, the metabolic activity of 7-ethoxyresorufin, a fluorometric substrate for CYP1A1, increased with increasing spheroid size. These results indicate that controlling spheroid size is important when preparing HepG2 spheroids and that the size of HepG2 spheroids greatly influences the cellular function of HepG2 cells in the spheroids.

Extramedullary plasmacytoma of the ureter in an HIV-positive patient.

A 45-year-old Japanese man, who was undergoing HIV infection treatment, was aware that he had gross hematuria, and he was diagnosed as having a ureteral tumor by radiographic examination. Therefore, he was referred to our department for further examination and treatment. We considered that the ureteral tumor was a urothelial carcinoma (cT2N0M0) because of the left ureteral tumor and urine cytology results, and thus, laparoscopic ureteronephrectomy was performed. The pathological diagnosis was a solitary extramedullary plasmacytoma (EMP) of the ureter. Currently, he is alive and free of disease at 7 months postoperatively. EMP develops in the nasal cavity, paranasal cavity, gastrointestinal tract, lung, thyroid, eye socket, lymph node, and various organs, but the ureter is an extremely rare site of EMP. In addition, the patient had an HIV infection. To the best of our knowledge, this is the first case of EMP of the ureter in an HIV-positive patient.

Therapeutic results in elderly patients with prostate cancer: chronological comparison in a single community hospital.

Objective: There are few reports of the long-term outcomes of elderly patients with prostate cancer. We analyzed data from our institution from the past 12 years, including the patient history, treatment methods, and prognosis of patients with prostate cancer aged 80 years or more. Patients and Methods: A total of 179 cases of prostate cancer in patients aged 80 years or more were retrospectively evaluated. We divided them chronologically into groups A, B, C, and D: Group A included 40 cases from 2002-2004; Group B, 48 cases from 2005-2007; Group C, 46 cases from 2008-2010; and Group D, 45 cases from 2011-2013. Results: Sixty-one (30%) patients changed treatment course. Interestingly, no cancer deaths occurred in the patients who changed treatment course. Although 14 (7.8%) cancer deaths occurred (A: B: C: D = 4: 4: 6: 0, respectively), all occurred in 2011 or later. Conclusion: In our study, over 50 patients who underwent treatment survived for 5 years or more. By treating prostate cancer in elderly patients when appropriate, we can lower the mortality rate due to prostate cancer. Our results support the active treatment of prostate cancer in elderly patients.

Development of a drug-coated microneedle array and its application for transdermal delivery of interferon alpha.

Interferon alpha (IFNα) is one of the most famous drugs for the treatment of chronic hepatitis C and various types of human malignancy. Protein drugs, including IFNα, are generally administered by subcutaneous or intramuscular injection due to their poor permeability and low stability in the bloodstream or gastrointestinal tract. Therefore, in the present study, novel IFNα-coated polyvinyl alcohol-based microneedle arrays (IFNα-MNs) were fabricated for the transdermal delivery of IFNα without the painful injection. IFNα was rapidly released from MNs in phosphate buffered solution and these MNs presented piercing ability in the rat skin. Slight erythema and irritation were observed when MNs were applied to the rat skin, but these skin damages completely disappeared within 24 h after removing the IFNα-MNs. Furthermore, the pharmacokinetic parameters of IFNα-MNs were similar to those of IFNα subcutaneous administration. Finally, IFNα-MNs showed a significant antitumor effect in tumor bearing mice similar to that of IFNα subcutaneous administration. These results indicate that IFNα-MNs are a useful biomaterial tool for protein drug therapy and can improve the quality of life in patients by avoidance of painful injections.

Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the α-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the experimental period. Miglitol-treated rats had lower nonfasting blood glucose levels and higher 1,5-anhydroglucitol levels, a marker for glucose fluctuations, at week 40 than control rats. The gene expression of inflammatory cytokines including interleukin-6, tumor necrosis factor-α, and interferon-γ in peripheral leukocytes gradually increased during the development of diabetes in control rats, but not in miglitol-treated rats. Our results suggest that dietary supplementation with miglitol from the preonset stage in OLETF rats improves glycemic control and reduces gene expression of cytokines related to inflammation in peripheral leukocytes.