Development of a novel endoscopic hemostasis-assisted navigation AI system in the standardization of post-ESD coagulation.

Background and study aims While gastric endoscopic submucosal dissection (ESD) has become a treatment with fewer complications, delayed bleeding remains a challenge. Post-ESD coagulation (PEC) is performed to prevent delayed bleeding. Therefore, we developed an artificial intelligence (AI) to detect vessels that require PEC in real time. Materials and methods Training data were extracted from 153 gastric ESD videos with sufficient images taken with a second-look endoscopy (SLE) and annotated as follows: (1) vessels that showed bleeding during SLE without PEC; (2) vessels that did not bleed during SLE with PEC; and (3) vessels that did not bleed even without PEC. The training model was created using Google Cloud Vertex AI and a program was created to display the vessels requiring PEC in real time using a bounding box. The evaluation of this AI was verified with 12 unlearned test videos, including four cases that required additional coagulation during SLE. Results The results of the test video validation indicated that 109 vessels on the ulcer required cauterization. Of these, 80 vessels (73.4%) were correctly determined as not requiring additional treatment. However, 25 vessels (22.9%), which did not require PEC, were overestimated. In the four videos that required additional coagulation in SLE, AI was able to detect all bleeding vessels. Conclusions The effectiveness and safety of this endoscopic treatment-assisted AI system that identifies visible vessels requiring PEC should be confirmed in future studies.

Artificial intelligence model for analyzing colonic endoscopy images to detect changes associated with irritable bowel syndrome.

IBS is not considered to be an organic disease and usually shows no abnormality on lower gastrointestinal endoscopy, although biofilm formation, dysbiosis, and histological microinflammation have recently been reported in patients with IBS. In this study, we investigated whether an artificial intelligence (AI) colorectal image model can identify minute endoscopic changes, which cannot typically be detected by human investigators, that are associated with IBS. Study subjects were identified based on electronic medical records and categorized as IBS (Group I; n = 11), IBS with predominant constipation (IBS-C; Group C; n = 12), and IBS with predominant diarrhea (IBS-D; Group D; n = 12). The study subjects had no other diseases. Colonoscopy images from IBS patients and from asymptomatic healthy subjects (Group N; n = 88) were obtained. Google Cloud Platform AutoML Vision (single-label classification) was used to construct AI image models to calculate sensitivity, specificity, predictive value, and AUC. A total of 2479, 382, 538, and 484 images were randomly selected for Groups N, I, C and D, respectively. The AUC of the model discriminating between Group N and I was 0.95. Sensitivity, specificity, positive predictive value, and negative predictive value of Group I detection were 30.8%, 97.6%, 66.7%, and 90.2%, respectively. The overall AUC of the model discriminating between Groups N, C, and D was 0.83; sensitivity, specificity, and positive predictive value of Group N were 87.5%, 46.2%, and 79.9%, respectively. Using the image AI model, colonoscopy images of IBS could be discriminated from healthy subjects at AUC 0.95. Prospective studies are needed to further validate whether this externally validated model has similar diagnostic capabilities at other facilities and whether it can be used to determine treatment efficacy.

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

Endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of gastric linitis plastica.

We report two cases of patients with gastric linitis plastica (GLP), in which the histopathological diagnosis was made by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen-tip needle. Esophagogastroduodenoscopy findings showed mucosal swelling and poor distensibility of the gastric antrum. Abdominal computed tomography findings showed significant thickening of the gastric wall at the antrum. Conventional endoscopic and bite-on-bite biopsy were attempted but resulted in failure to diagnose the lesions. We performed EUS-FNB to obtain histopathological samples from a deeper site, which confirmed the diagnosis. We considered this method safe and effective for the diagnosis of GLP.

A Review of Potential Role of Capsule Endoscopy in the Work-Up for Chemotherapy-Induced Diarrhea.

Chemotherapy-induced diarrhea (CID) is a common, severe side effect of chemotherapy, immunotherapy, and targeted therapy. Because patients are more prone to continuing chemotherapy if they do not suffer from CID, appropriate diagnosis and monitoring of this disease are essential. However, suitable monitoring methods are yet to be developed. To date, several studies have shown that small-bowel capsule endoscopy (SBCE) is useful in visualizing the entire small intestinal mucosa and detecting small intestinal abnormalities, including bleeding, malignant tumors, and mucosal injury, associated with the use of nonsteroidal anti-inflammatory drugs and low-dose aspirin. Currently, limited studies have evaluated the small intestinal mucosa using SBCE in patients receiving fluoropyrimidine-based chemotherapy or immune checkpoint inhibitors. These studies have reported that small intestinal mucosal injury is common in patients with severe fluoropyrimidine-induced diarrhea. SBCE might be a useful screening method for the early detection of enterocolitis induced by immune checkpoint inhibitors. SBCE may be a powerful tool for the diagnosis and monitoring of CID, and understanding its indication, contraindication, and capsule-retention risk for each patient is important for clinicians.

The potential diagnostic significance of crypt differentiation in gastric dysplasia.

AIMS: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.

Bilateral Serous Retinal Detachment Associated with a Mitogen-activated Protein KinaseKinase Inhibitor in a Patient with BRAF-mutant Colorectal Cancer.

We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.

Intensive surveillance endoscopy for multiple gastrointestinal tumors in a patient with constitutional mismatch repair deficiency: case report.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient's condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD. CASE PRESENTATION: A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1). CONCLUSIONS: Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient's condition.

Comparison of Histological Sample Volumes among Various Endoscopic Ultrasound-Guided Biopsy Needles.

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) enables easy and accurate pathological assessment. Here, we compared and assessed the area of samples on glass slides for three needle types: a 19-gauge Franseen needle (Acquire, Boston Scientific, Natick, MA, USA), a 22-gauge Franseen needle, and a 19-gauge fine-needle aspiration (FNA) needle (EZ Shot 3 Plus; Olympus, Tokyo, Japan). Among patients with suspected pancreatic cancer, with a ≥20 mm tumor located in the pancreatic body and tail, and who underwent EUS-FNA or FNB between June 2018 and March 2020, 10 were randomly selected to test each needle. The areas of histological tissue and blood clot samples were measured using the BZ-X800 imaging software (Keyence Corporation, Osaka, Japan). Baseline patient characteristics and pathological sample data showed no significant differences among the needles. The 19-gauge Franseen needle obtained significantly more histological tissue samples than the 19-gauge conventional needle (p = 0.010) and 22-gauge Franseen needle (p = 0.008). Conversely, there was no significant difference between the 19-gauge conventional needle and 22-gauge Franseen needle (p = 0.838) in this regard. The 19-gauge Franseen needle could collect more samples than the other needles, contributing to giving a more precise pathological diagnosis and more information, including genomic profiling.

Endoscopic Ultrasound-guided Fine Needle Aspiration for the Diagnosis of Duodenal Stenosis Due to Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) initially presents with hematuria and hydronephrosis. We report a case of UTUC presenting with initial findings of duodenal stenosis before the appearance of hydronephrosis. A 59-year-old man presented with upper abdominal symptoms on his initial visit. Esophagogastroduodenoscopy (EGD) revealed circumferential stenosis at the descending part of the duodenum. However, the underlying cause of duodenal stenosis was unknown as repeated histopathological examinations of endoscopic biopsy specimens showed no specific findings. We then performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the thickened duodenal wall, and successfully diagnosed duodenal metastasis of UTUC. EUS-FNA is an effective diagnostic method in cases in which the cause of duodenal stenosis is unknown.

Effectiveness of S-O Clip-Assisted Colorectal Endoscopic Submucosal Dissection.

This study aimed to assess the utility of the S-O clip during colorectal endoscopic submucosal dissection (ESD). We conducted a retrospective study on 185 patients who underwent colorectal ESD from January 2015 to January 2020. The patients were divided into two groups: before and after the introduction of the S-O clip. Forty-two patients underwent conventional ESD (CO group) and 29 patients underwent ESD using the S-O clip (SO group). We compared the surgery duration, dissection speed, en bloc resection rate, and complication rate between both groups. Compared with the CO group, the SO group had a significantly shorter surgery duration (70.7 ± 37.9 min vs. 51.2 ± 18.6 min; p = 0.017), a significantly higher dissection speed (15.1 ± 9.0 min vs. 26.3 ± 13.8 min; p < 0.001), a significantly higher en bloc resection rate (80.9% vs. 98.8%; p ≤ 0.001), and a significantly lower perforation rate (4.3% vs. 1.3%). In the right colon, the surgery duration was significantly shorter and the dissection speed was significantly higher in the SO group than in the CO group. Moreover, the rate of en bloc resection improved significantly in the right colon. S-O clip-assisted ESD reduces the procedure time and improves the treatment effects, especially in the right colon.

Diagnostic Fine-Needle Biopsy of Small Solid Pancreatic Lesions Using a Franseen Needle during Endoscopic Ultrasound Examination.

BACKGROUND AND AIM: During endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNB), Franseen needles can help collect sufficient tissue to permit histopathological assessment. However, its efficacy might be limited by the size of the targeted lesion. This study aimed to evaluate the feasibility of histopathological assessment of small solid pancreatic lesions using a 22-gauge Franseen needle during EUS-FNB. METHODS: This retrospective study evaluated data from all patients who underwent EUS-FNB using a Franseen needle for solid pancreatic lesions at the University of Toyama Hospital between June 2018 and April 2020. RESULTS: The study included 159 patients who had 152 malignant lesions and 7 benign lesions. The malignant lesions included pancreatic cancers (n = 134), neuroendocrine neoplasms (n = 15), metastatic tumors (n = 2), and a solid pseudopapillary neoplasm (n = 1). The diagnostic accuracy of EUS-FNB (combining histology and cytology) was 98.7%. However, the histopathological diagnosis was only confirmed for 64.3% of small lesions (<10 mm), relative to 97.2% for larger lesions. Multivariate analysis also revealed that lesion size of <10 mm predicted a less accurate histopathological diagnosis (odds ratio: 6.97, 95% confidence interval: 1.02-47.67; p = 0.041). Further analyses revealed a failed histological diagnosis in 4 patients with lesions of <5 mm in size and accurate diagnoses in 9 out of 10 patients with lesions of 5-10 mm in size. CONCLUSIONS: The diagnostic accuracy for small lesions (<10 mm), especially for lesions of <5 mm, based on histological examination alone, was significantly lower than that for others (>10 mm). Furthermore, multivariate analysis revealed that only lesion size was an independent predictor of histopathological diagnosis accuracy.

Assessment of a Hands-On Seminar on Gastrointestinal Ultrasound.

Transabdominal gastrointestinal (GI) ultrasound (US), despite its utility, is not a common procedure and underappreciated owing to its difficulty to perform. This study aimed to disseminate the skills of GIUS and assess the impact of our hands-on seminar. We annually held a half-day, hands-on seminar on GIUS at University of Toyama Hospital for physicians and sonographers from 2015 to 2017. Two months after the seminar, we inquired about clinical attainment by questionnaire. Out of 55 participants, 46 (83.6%) returned their questionnaires. Twenty participants (43.5%) reported that they had successfully diagnosed at least one GI disorder via GIUS since the seminar. Residual analyses stratified by the participants' background showed that the novices, those having < 2 years' experience in performing abdominal US, or no prior knowledge of GIUS, had significantly lower attainment rates (23.5% and 12.5%, respectively) than the others. Participants with 2 to 5 years' experience in performing abdominal US or with some knowledge of GIUS had much higher rates of diagnosing GI disorders (54.5% and 57.9%, respectively). Nearly half of the participants had identified GI disorders using GIUS in 2 months following the training. The hands-on seminar was beneficial in disseminating these skills among a wide range of US operators.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea.

BACKGROUND: Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID. METHODS: In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID. RESULTS: Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06-8.19). CONCLUSIONS: Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

Factors correlated with drug use for constipation: perspectives from the 2016 open Japanese National Database.

BACKGROUND: The prevalence of chronic constipation is increased in females and with age or environmental (low temperature), racial, socioeconomic, and habitual risk factors. The impact of low outside temperature on constipation drug use remains unclear. Here, we investigated risk factors for constipation drug use by evaluating data from the Japanese National Database. METHODS: This ecological study used the 2016 open Japanese National Database of health insurance claims (prescriptions) to acquire the number of health insurance prescription claims in all 47 prefectures for drugs to relieve constipation, antihypertensives, vasodilators, as well as medical check-ups and questionnaire responses. Internet survey on room temperatures in 2010 were also used. Pearson correlation coefficients (r) between the number of population-based prescriptions for each item were calculated and multiple linear regression analysis (MLR) was performed. RESULTS: Prescriptions for magnesium laxatives significantly correlated with aging (r = 0.58), vasodilators (r = 0.53), being female (r = 0.43), antihypertensives (r = 0.39), and inversely with eating ≤2 h before bedtime (r = - 0.37), total crime rate (r = - 0.33), insomnia (r = - 0.33), and population density (r = - 0.31). Stimulant laxatives (sennoside and picosulfate) were significantly correlated with antihypertensives (r = 0.79), aging (r = 0.69), vasodilators (r = 0.67), and being female (r = 0.56), and were inversely associated with average outside temperature (r = - 0.62), total crime rate (r = - 0.52), average income (r = - 0.51), and 30-min of vigorous exercise (r = - 0.44). Fecal interventions were significantly correlated with aging (r = 0.55) and female (r = 0.59), and inversely correlated with population density (r = - 0.41) and total crime rate (r = - 0.38). MLR analysis identified aging as the only significant risk factor for magnesium laxative use (partial slope [ß] = 1241.0). Female sex and antihypertensives were independent risk factors for stimulant laxative prescriptions (ß = 44,547.0 and 0.2) and average outside temperature and 30-min of vigorous exercise were independent preventive factors (ß = - 616.8 and - 219.1). CONCLUSION: We identified associations of magnesium laxatives with aging, stimulant laxatives with female sex, antihypertensives, low outside temperature and less 30 min of vigorous exercise.

Management of Remnant or Recurrent Lesions after Endoscopic Papillectomy.

Endoscopic papillectomy (EP) for ampullary adenomas achieves cure rates ranging from 76% to 90%, and recurrence rates are as high as 33%. If remnant or recurrent lesions after prior EP are endoscopically visible and are not suspected of intraductal extension into the biliary or pancreatic duct, repeated snaring and cutting can be performed until all visible lesions are completely resected. However, endoscopic ablative therapies, particularly argon plasma coagulation, can be attempted for tiny or uncertain remnant and recurrent lesions. In addition, intraductal radiofrequency ablation has recently been attempted for residual intraductal lesions after EP at several institutions. Although still under investigation, it has shown some promise. It might be offered as an alternative to surgery, particularly in patients who are unfit for surgery or those who refuse to undergo surgery.

[Severe interstitial lung disease after one cycle of nivolumab treatment in a patient with advanced gastric cancer].

Although nivolumab was previously reported to cause immune-related interstitial lung diseases (ILD), the detailed characteristics of ILD in gastric cancer are not fully understood. We herein present a rare case of a 66-year-old male with advanced gastric cancer who experienced acute-onset high-grade fever and dyspnea and diagnosed with early-onset ILD during the first cycle of nivolumab. Computed tomography revealed patchy infiltrative shadows and ground-glass opacities. No pathological bacteria were detected in the sputum or the bronchoalveolar lavage, and serous antigens for virus and beta-D-glucan were below the detection limit. These findings were consistent with nivolumab-induced organizing pneumonia. The steroid pulse therapy was effective for ILD, and the patient had complete radiological response, although he relapsed twice during the steroid tapering period.

Multiple Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum.

A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.

Neuroendocrine Carcinoma of the Stomach: A Response to Combination Chemotherapy Consisting of Ramucirumab Plus Paclitaxel.

Extrapulmonary neuroendocrine carcinoma (NEC) is a rare disease, and there is no standard chemotherapy. A 73-year-old man was diagnosed with advanced gastric NEC. He received chemotherapy of irinotecan plus cisplatin, and amrubicin monotherapy. After failure of second-line chemotherapy, he received ramucirumab plus paclitaxel; this treatment was chosen because vascular endothelial growth factor 2 was strongly expressed in the tumor endothelial cells. After two cycles, his NEC had markedly reduced in size, and he continued with this treatment for over eight months. In this case, the combination of an anti-angiogenic inhibitor and a cytotoxic agent was highly effective for gastric NEC.

Phase I/II Study of S-1 Plus Cisplatin Alternating With S-1 Plus Docetaxel in Patients With Advanced Gastric Cancer.

OBJECTIVES: To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with advanced gastric cancer, we conducted a phase I/II study to determine the maximum tolerated dose and recommended dose, and evaluate efficacy and toxicity. MATERIALS AND METHODS: Patients with histologically confirmed unresectable and recurrent gastric cancer were enrolled in this study. Cisplatin was administered on day 1 and the dose escalated by 10 mg/m from a starting dose of 40 mg/m in the phase I part. S-1 was given orally at 80 mg/m on days 1 to 14 and docetaxel at 40 mg/m on day 22 in combination with S-1 80 mg/m on days 22 to 35. The treatment was repeated every 6 weeks. The primary endpoint of the phase II analysis was the response rate. RESULTS: Nine patients entered the phase I and 24 the phase II part. Because 50% of patients (3/6) developed dose-limiting toxicities in the phase I part, the maximum tolerated dose of cisplatin was presumed to be 50 mg/m. Therefore, the estimated recommended dose of cisplatin was 40 mg/m; 27 patients received that dose. The response rate was 59.3% (95% confidence interval, 40.8-77.8) and the median follow-up 26.2 months. The median progression-free survival was 7.9 months and the median overall survival 18.6 months. The most common grade 3/4 toxicities were neutropenia (59.3%), leucopenia (37.0%), and anemia (29.6%). These toxicities were tolerable and manageable. CONCLUSION: This alternating treatment seems to have promising activity with tolerable toxicities in the first-line treatment of patients with advanced gastric cancer.