Real-World Clinical Profile of Patients Prescribed Evolocumab in Japan.

BACKGROUND: Real-world utilization data for evolocumab, the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be introduced in Japan in 2016, to date are limited. This study aimed to clarify the current real-world patient user profiles of evolocumab based on large-scale health claims data.Methods and Results: This retrospective database study examined patients from a health administrative database (MDV database) who initiated evolocumab between April 2016 (baseline) and November 2021. Characteristics and clinical profiles of this patient population are described. In all, 4,022 patients were included in the final analysis. Most evolocumab prescriptions occurred in the outpatient setting (3,170; 78.82%), and 940 patients (23.37%) had a recent diagnosis of familial hypercholesterolemia. Common recent atherosclerotic cardiovascular disease events at baseline included myocardial infarction (1,633; 40.60%), unstable angina (561; 13.95%), and ischemic stroke (408; 10.14%). Comorbidity diseases included hypertension (2,504; 62.26%), heart failure (1,750; 43.51%), diabetes (1,199; 29.81%), and chronic kidney disease (297; 7.38%). Among the lipid-lowering regimens concomitant with evolocumab, ezetimibe+statin was used most frequently (1,281; 31.85%), followed by no concomitant lipid-lowering regimen (1,190; 29.59%), statin (950; 23.62%), and ezetimibe (601; 14.94%). The median evolocumab treatment duration for all patients was 260 days (interquartile range 57-575 days). CONCLUSIONS: This study provides real-world insights into evolocumab utilization in Japan for optimizing patient care and adherence to guideline-based therapies to better address hypercholesterolemia in Japan.

Cytokine release syndrome following durvalumab and tremelimumab in advanced hepatocellular carcinoma: A case report with cytokine and damage-associated molecular pattern analysis.

Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell hyperactivation caused by therapeutic agents, pathogens, cancers, and autoimmune diseases. In recent years, CRS has emerged as a rare, but significant, immune-related adverse event linked to immune checkpoint inhibitor therapy. Furthermore, several previous studies suggested that damage-associated molecular patterns (DAMPs) could be involved in malignancy-related CRS. In this study, we present a case of severe CRS following combination therapy with durvalumab and tremelimumab for advanced hepatocellular carcinoma, which recurred during treatment, as well as an analysis of cytokine and DAMPs trends. A 35-year-old woman diagnosed with hepatocellular carcinoma underwent a partial hepatectomy. Due to cancer recurrence, she started a combination of durvalumab and tremelimumab. Then, 29 days post-administration, she developed fever and headache, initially suspected as sepsis. Despite antibiotics, her condition worsened, leading to disseminated intravascular coagulation and hemophagocytic syndrome. The clinical course and elevated serum interleukin-6 levels led to a CRS diagnosis. Steroid pulse therapy was administered, resulting in temporary improvement. However, she relapsed with increased interleukin-6, prompting tocilizumab treatment. Her condition improved, and she was discharged on day 22. Measurements of inflammatory cytokines interferon-γ, tumor necrosis factor-α, and DAMPs, along with interleukin-6, using preserved serum samples, confirmed marked elevation at CRS onset. CRS can occur after the administration of any immune checkpoint inhibitor, with the most likely trigger being the release of DAMPs associated with tumor collapse.

Relationships between the global symptom score and electrophysiological findings after surgical release for carpal tunnel syndrome: Indications and outcomes.

PURPOSE: Regarding surgical indications for carpal tunnel syndrome (CTS), the hypothesis that the recovery processes of subjective symptoms differ among pain, sensory, and motor symptoms and correlate with recovery in objective nerve conduction studies was examined in the present study. METHODS: The global symptom score (GSS) is a method used to assess clinical outcomes and covers subjective symptoms, including pain (pain and nocturnal awakening), sensory (numbness and paresthesia), and motor (weakness/clumsiness) symptoms. The relationships between long-term changes in GSS and recovery in nerve conduction studies were investigated. RESULTS: Forty patients (40 hands) were included (mean age 65 years; 80% female; 68% with moderate CTS: sensory nerve conduction velocity < 45 m/s and motor nerve distal latency > 4.5 ms). Pain and nocturnal awakening rapidly subsided within 1 month after surgery and did not recur in the long term (median 5.6 years). Paresthesia significantly decreased 3 months after surgery and in the long term thereafter. Weakness/clumsiness significantly decreased at 1 year. Sensory nerve distal latency, conduction velocity, and amplitude significantly improved 3 months and 1 year after surgery, and correlated with nocturnal awakening in the short term (3 months) in moderate CTS cases. The patient satisfaction rate was 91%. CONCLUSION: Rapid recovery was observed in pain and nocturnal awakening, of which nocturnal awakening correlated with the recovery of sensory nerve conduction velocity. Patients with pain symptoms due to moderate CTS may benefit from surgical release.

Quantitative evaluation of hippocampal gray-white matter boundary blurring in medial temporal lobe epilepsy with hippocampal sclerosis.

INTRODUCTION: The magnetic resonance imaging (MRI) findings of hippocampal sclerosis (HS) include decreased volume, increased signal intensity, and hippocampal gray-white matter boundary blurring (HGWBB). Given that the layered structure is obscure in HS, there have been no reports on the quantitative evaluation of HGWBB and its relationship with the clinical outcome. Thus, this study aims to correlate the extent of HGWBB to its clinical manifestation of HS. METHODS: Fifty-four patients with temporal lobe epilepsy who underwent hippocampal resection were enrolled. To evaluate HGWBB quantitatively, we defined an index by calculating the standard deviation of the intrahippocampal signal on short tau inversion recovery. In addition, we created a prognostic scoring system using four criteria, including hippocampal signal intensity, size of hippocampal cross-sectional area, presence of temporal lobe lesions, and the HGWBB index. RESULTS: The HGWBB index was significantly lower on the affected side than on the unaffected side (p < 0.001). This trend was more prominent in the poor prognosis group than that in the good prognosis group. The prognostic scoring system revealed that when three or more criteria were positive, the prognostic accuracy reached 87.5% sensitivity and 71.7% specificity. CONCLUSION: The HGWBB index is useful for the diagnosis of temporal lobe epilepsy with HS and for predicting seizure outcomes when used with another index of hippocampal volume loss and increased signal intensity.

Enhancement of Acinetobacter baumannii biofilm growth by cephem antibiotics via enrichment of protein and extracellular DNA in the biofilm matrices.

AIMS: The aims were to determine the effects of subinhibitory concentrations of eight cephem and carbapenem antibiotics on the biofilm formation of Acinetobacter baumannii cells and examine their effects on pre-established biofilms. METHODS AND RESULTS: Effects of antibiotics on biofilm formation were assayed using microtitre plates with polystyrene peg-lids. Cefmetazole, ceftriaxone, ceftazidime and cefpirome increased the biomass of pre-established biofilms on pegs in the range of their sub-minimum inhibitory concentrations (MICs), whereas none increased biofilm formation by planktonic cells. Carbapenems had a negative effect. The constituents of antibiotic-induced biofilms were analysed. Ceftriaxone or ceftazidime treatment markedly increased the matrix constituent amounts in the biofilms (carbohydrate, 2.7-fold; protein, 8.9-12.7-fold; lipid, 3.3-3.6-fold; DNA, 9.1-12.2-fold; outer membrane vesicles, 2.7-3.8-fold and viable cells, 6.8-10.1-fold). The antibiotic-enhanced biofilms had increased outer membrane protein A and were resistant to the anti-biofilm effect of azithromycin. CONCLUSIONS: Some cephems increased the biomass of pre-established biofilms in the ranges of their sub-MICs. The antibiotic-enhanced biofilms possessed more virulent characteristics than normal biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Incomplete administration of certain cephems following biofilm-related Ac. baumannii infections could adversely cause exacerbated and chronic clinical results.

Delineation of prostatic calcification using quantitative susceptibility mapping: Spatial accuracy for magnetic resonance-only radiotherapy planning.

To investigate the spatial accuracy of delineating prostatic calcifications by quantitative susceptibility mapping (QSM) in comparison with computed tomography (CT), we conducted phantom and human studies. Five differently-sized spherical hydroxyapatites mimicking prostatic calcification (pseudo-calcification) were arranged in the order of their sizes at the center of a plastic container filled with gelatin. This calcification phantom underwent magnetic resonance (MR) imaging, including the multiple spoiled gradient-echo sequences (SPGR) for the QSM and CT as a reference. The volume of each pseudo-calcification and center-to-center distance between the pseudo-calcifications delineated by QSM and CT were measured. In the human study, eight patients with prostate cancer who underwent radiation therapy and had some prostatic calcifications were included. The patients underwent CT and SPGR and modified DIXON sequence for MR-only simulation. The hybrid QSM processing combined with the complex signals in the SPGR and water and fat fraction maps estimated from the modified DIXON sequence were used to reconstruct the pelvic susceptibility map in humans. The threshold of CT numbers was set at 130 HU, while the QSM images were manually segmented in the calcification phantom and human studies. In the phantom study, there was an excellent agreement in the pseudo-calcification volumes between QSM and CT (y = 1.02x - 7.38, R2  = 0.99). The signal profiles had similar trends in CT and QSM. The center-to-center distances between the pseudo-calcifications in the phantom were also identical in QSM and CT. The calcification volumes were almost identical between the QSM and CT in the human study (y = 0.95x - 9.32, R2  = 1.00). QSM can offer geometric and volumetric accuracies to delineate prostatic calcifications, similar to CT. The prostatic calcification delineated by QSM may facilitate image-guided radiotherapy in the MR-only simulation workflow.

[Successful R0 Resection of Two Metachronous Krukenberg Tumors from Gastric Cancer-A Case Report].

A 50s woman with a stomachache was referred to our hospital with diagnosed gastric cancer. Upper endoscopy showed a type 3 tumor in the lower gastric body, and CT demonstrated a pelvic tumor 10 cm in size. Laparoscopic surgery was performed; since the pelvic tumor was found to derive from the left ovary, left oophorectomy and total gastrectomy were performed. Pathological examination revealed that the ovarian tumor was a gastric cancer metastasis. Adjuvant chemotherapy with S-1 monotherapy was introduced. Four months after the operation, metastasis was suspected due to right ovary tumor edema. Due to the possibility of obtaining R0 resection and adverse events of chemotherapy, we chose right oophorectomy. Pathological examination demonstrated signet-ring cell cancer. Fourteen months after the first operation, the patient is alive with no recurrence or metastasis.

[A Case of Multiple Gastric GIST with Lymph Nodes Metastases in a Young Woman].

A 21-year-old woman with bloody stool was referred to our hospital with multiple submucosal tumors at the posterior and anterior wall of the gastric angle under upper gastrointestinal endoscopy. Both of the tumors were diagnosed with gastric gastrointestinal stromal tumor(GIST)by EUS-FNA, then laparoscopic distal gastrectomy with D1 lymph node dissection was performed. The size of those tumors were 47 mm and 15 mm respectively, and pathological examination revealed multiple lymph nodes metastases. Neither KIT nor PDGFRA mutation was found. She had received postoperative adjuvant chemotherapy with imatinib mesylate for 3 years. No sign of recurrence has been confirmed thereafter. GISTs in young adults are rare and their oncological features are considered to be different from common type of GIST.

Structural study of the recognition mechanism of tau antibody Tau2r3 with the key sequence (VQIINK) in tau aggregation.

One of the histopathological features of Alzheimer's disease (AD) is higher order neurofibrillary tangles formed by abnormally aggregated tau protein. The sequence 275VQIINK280 in the microtubule-binding domain of tau plays a key role in tau aggregation. Therefore, an aggregation inhibitor targeting the VQIINK region in tau may be an effective therapeutic agent for AD. We have previously shown that the Fab domain (Fab2r3) of a tau antibody that recognizes the VQIINK sequence can inhibit tau aggregation, and we have determined the tertiary structure of the Fab2r3-VQIINK complex. In this report, we determined the tertiary structure of apo Fab2r3 and analyzed differences in the structures of apo Fab2r3 and Fab2r3-VQIINK to examine the ligand recognition mechanism of Fab2r3. In comparison with the Fab2r3-VQIINK structure, there were large differences in the arrangement of the constant and variable domains in apo Fab2r3. Remarkable structural changes were especially observed in the H3 and L3 loop regions of the complementarity determining regions (CDRs) in apo Fab2r3 and the Fab2r3-VQIINK complex. These structural differences in CDRs suggest that formation of hydrophobic pockets suitable for the antigen is important for antigen recognition by tau antibodies.

Iron-Utilization System in Vibrio vulnificus M2799.

Vibrio vulnificus is a Gram-negative pathogenic bacterium that causes serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In the ferric-utilization system in V. vulnificus M2799, an isochorismate synthase (ICS) and an outer membrane receptor, VuuA, are required under low-iron conditions, but alternative proteins FatB and VuuB can function as a periplasmic-binding protein and a ferric-chelate reductase, respectively. The vulnibactin-export system is assembled from TolCV1 and several RND proteins, including VV1_1681. In heme acquisition, HupA and HvtA serve as specific outer membrane receptors and HupB is a sole periplasmic-binding protein, unlike FatB in the ferric-vulnibactin utilization system. We propose that ferric-siderophore periplasmic-binding proteins and ferric-chelate reductases are potential targets for drug discovery in infectious diseases.

[A Case of Remnant Gastric Cancer with Mesojejunal Lymph Node Metastasis].

A 62-year-old man underwent radical surgery for the treatment of remnant gastric cancer with mesojejunal lymph node metastasis. According to the 15th edition of the Japanese Gastric Cancer Association, a histological diagnosis of B-35-A, type 3, tub2>tub1, pT3(SS), pN3a(10/37), cM0, CY0, pStage ⅢB was made. All lymph node metastases were recognized in the mesojejunum. Adjuvant chemotherapy with S-1 plus docetaxel was initiated after 4 weeks of surgery. The patient is still alive without recurrence after 1 year of surgery. Thus, radical surgery with dissection of the mesojejunum and intensive adjuvant chemotherapy might improve the prognosis in a remnant gastric cancer patient with mesojejunal lymph node metastasis.

[Complete Response to Neoadjuvant Chemotherapy with Imatinib of a Large Gastric GIST-A Case Report].

A 54-year-old woman was presented with the intraabdominal mass to our hospital. Abdominal CT showed 22 cm tumor of the stomach with invasion to the pancreas and the spleen. Upper GI endoscopy showed submucosal tumor at the stomach body, and endoscopic US showed low echoic tumor. The tumor was diagnosed as gastric GIST by biopsy with c-kit positive cells. After 4 months of neoadjuvant therapy with imatinib, she underwent total gastrectomy, distal pancreatectomy and splenectomy. Histopathologically, there were no viable tumor cells in the resected specimen. The patient has no evidence of recurrence at 8 months post operation.

VuuB and IutB reduce ferric-vulnibactin in Vibrio vulnificus M2799.

Vibrio vulnificus, a pathogenic bacterium that causes serious infections in humans, requires iron for growth. Clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, namely, vulnibactin, to capture iron (III) from the environment. Growth experiments using a deletion mutant indicated that VuuB, a member of the FAD-containing siderophore-interacting protein family, plays a crucial role in Fe3+-vulnibactin reduction. IutB, a member of the ferric-siderophore reductase family, stands a substitute for VuuB in its absence. It remained unclear why V. vulnificus M2799 has two proteins with relevant functions. Here we biochemically characterized VuuB and IutB using purified recombinant proteins. Purified VuuB, a flavoprotein, catalyzed the reduction of Fe3+-nitrilotriacetic acid as its electron acceptor, in the presence of NADH as its electron donor and FAD as its cofactor. IutB catalyzed the reduction of Fe3+-nitrilotriacetic acid, in the presence of NADH, NADPH, or reduced glutathione as its electron donor. The optimal pH values and temperatures of VuuB and IutB were 7.0 and 37 °C, and 8.5 and 45 °C, respectively. On analyzing their ferric-chelate reductase activities, both VuuB and IutB were found to catalyze the reduction of Fe3+-aerobactin, Fe3+-vibriobactin, and Fe3+-vulnibactin. When the biologically relevant substrate, Fe3+-vulnibactin, was used, the levels of ferric-chelate reductase activities were similar between VuuB and IutB. Finally, the mRNA levels were quantified by qRT-PCR in M2799 cells cultivated under low-iron conditions. The number of vuuB mRNA was 8.5 times greater than that of iutB. The expression ratio correlated with the growth of their mutants in the presence of vulnibactin.

Identification of the heme acquisition system in Vibrio vulnificus M2799.

Vibrio vulnificus, the causative agent of serious, often fatal, infections in humans, requires iron for its pathogenesis. As such, it obtains iron via both vulnibactin and heme-mediated iron-uptake systems. In this study, we identified the heme acquisition system in V. vulnificus M2799. The nucleotide sequences of the genes encoding heme receptors HupA and HvtA and the ATP-binding cassette (ABC) transport system proteins HupB, HupC, and HupD were determined, and then used in the construction of deletion mutants developed from a Δics strain, which could not synthesize vulnibactin. Growth experiments using these mutants indicated that HupA and HvtA are major and minor heme receptors, respectively. The expressions of two proteins were analyzed by the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Furthermore, complementation analyses confirmed that the HupBCD proteins are the only ABC transport system shared by both the HupA and HvtA receptors. This is the first genetic evidence that the HupBCD proteins are essential for heme acquisition by V. vulnificus. Further investigation showed that hupA, hvtA, and hupBCD are regulated by Fur. The qRT-PCR analysis of the heme receptor genes revealed that HupR, a LysR-family positive transcriptional activator, upregulates the expression of hupA, but not hvtA. In addition, ptrB was co-transcribed with hvtA, and PtrB had no influence on growth in low-iron CM9 medium supplemented with hemin, hemoglobin, or cytochrome C.

Biological effects of hydrogen peroxide administered intratumorally with or without irradiation in murine tumors.

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H2 O2 were investigated using computed tomography. The effects of H2 O2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H2 O2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H2 O2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H2 O2 was injected before irradiation. The group irradiated immediately after H2 O2 injection showed the longest tumor growth delay. Dose-modifying factors were 1.7-2.0 when combined with single irradiation and 1.3-1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H2 O2 . H2 O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2 O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.

IutB participates in the ferric-vulnibactin utilization system in Vibrio vulnificus M2799.

Vibrio vulnificus, an opportunistic pathogen that causes a serious, often fatal, infection in humans, requires iron for its growth. This bacterium utilizes iron from the environment via the vulnibactin-mediated iron uptake system. The mechanisms of vulnibactin biosynthesis, vulnibactin export, and ferric-vulnibactin uptake systems have been reported, whereas the ferric-vulnibactin reduction mechanism in the cell remains unclear. The results of our previous study showed that VuuB, a member of the flavin adenine dinucleotide-containing siderophore-interacting protein family, is a ferric-vulnibactin reductase, but there are other reductases that can complement for the defective vuuB. The aim of this study was to identify these proteins that can complement the loss of function of VuuB. We constructed mutants of genes encoding putative reductases in V. vulnificus M2799, and analyzed their growth under low-iron conditions. Complementation analyses confirmed that IutB, which functions as a ferric-aerobactin reductase, participates in ferric-vulnibactin reduction in the absence of VuuB. This is the first genetic evidence that ferric-vulnibactin is reduced by a member of the ferric-siderophore reductase protein family. In the aerobactin-utilization system, IutB plays a major role in ferric-aerobactin reduction in V. vulnificus M2799, and VuuB and DesB can compensate for the defect of IutB. Furthermore, the expression of iutB and desB was found to be regulated by iron and a ferric uptake regulator.

[A Case of Leiomyosarcoma of the Small Intestine with Intestinal Hemorrhage Due to Intraluminal Penetration].

A 40-year-old man was referred to our hospital because of severe anemia and small intestinal tumor revealed by computed tomography. The enteroscopy exam showed the intraluminal penetration of the tumor, which was considered as a cause of anemia. Although emergency operation was performed laparoscopically, intraoperative findings indicated tumor invasion into peritoneum, and we converted from laparoscopic surgery to open surgery that included concomitant peritoneum resection. Histopathological findings showed spindle-shaped tumor cells with severe atypia. Immunohistochemical study showed tumor cells to be positive for aSMA, but negative for c-kit and CD34, then we diagnosed the tumor as leiomyosarcoma of the ileum. Since leiomyosarcoma of the small intestine is a rare entity, we have reported with literature consideration.

[Multidisciplinary Treatment for Squamous Cell Carcinoma of the Anal Canal].

Chemoradiotherapy(CRT)has been recognized as a standard treatment for locoregional squamous cell carcinoma of the anal canal in Western countries. However, surgery had historically been considered as a standard treatment and there are only a few reports on CRT for anal canal cancer in Japan. In this study, we analyzed medical records of 5 anal canal cancer patients treated with CRT in our hospital between 2005 and 2015. Patients' characteristics were as follows: median age, 70 years (range 42-80 years); male/female, 1/4; and clinical Stage I / III a/ III b, 3/1/1. The regimens of chemotherapy were MMC plus 5-FU in 4 patients and CDDP in 1 patient. The median follow-up period was 30 months(range, 6 to 100 months). After CRT, 4 patients achieved complete response. The other patient with partial response underwent salvage surgery. All patients were alive without recurrence. In conclusion, our retrospective study showed that CRT is considered to be a standard treat- ment for anal canal cancer.

The RND protein is involved in the vulnibactin export system in Vibrio vulnificus M2799.

Vibrio vulnificus, an opportunistic marine bacterium that causes a serious, often fatal, infection in humans, requires iron for its pathogenesis. This bacterium exports vulnibactin for iron acquisition from the environment. The mechanisms of vulnibactin biosynthesis and ferric-vulnibactin uptake systems have recently been reported, while the vulnibactin export system has not been reported. Mutant growth under low-iron concentration conditions and a bioassay of the culture supernatant indicate that the VV1_0612 protein plays a crucial role in the vulnibactin secretion as a component of the resistance-nodulation-division (RND)-type efflux system in V. vulnificus M2799. To identify which RND protein(s) together with VV1_0612 TolC constituted the RND efflux system for vulnibactin secretion, deletion mutants of 11 RND protein-encoding genes were constructed. The growth inhibition of a multiple mutant (Δ11) of the RND protein-encoding genes was observed 6 h after the beginning of the culture. Furthermore, ΔVV1_1681 exhibited a growth curve that was similar to that of Δ11, while the multiple mutant except ΔVV1_1681 showed the same growth as the wild-type strain. These results indicate that the VV1_1681 protein is involved in the vulnibactin export system of V. vulnificus M2799. This is the first genetic evidence that vulnibactin is secreted through the RND-type efflux systems in V. vulnificus.

[Two cases of advanced gastric cancer achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose CDDP].

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.