AI analysis and modified type classification for endocytoscopic observation of esophageal lesions.

Endocytoscopy (EC) facilitates real-time histological diagnosis of esophageal lesions in vivo. We developed a deep-learning artificial intelligence (AI) system for analysis of EC images and compared its diagnostic ability with that of an expert pathologist and nonexpert endoscopists. Our new AI was based on a vision transformer model (DeiT) and trained using 7983 EC images of the esophagus (2368 malignant and 5615 nonmalignant). The AI evaluated 114 randomly arranged EC pictures (33 ESCC and 81 nonmalignant lesions) from 38 consecutive cases. An expert pathologist and two nonexpert endoscopists also analyzed the same image set according to the modified type classification (adding four EC features of nonmalignant lesions to our previous classification). The area under the curve calculated from the receiver-operating characteristic curve for the AI analysis was 0.92. In per-image analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 91.2%, 91.2%, 85.9%, and 83.3%, respectively. The kappa value between the pathologist and the AI, and between the two endoscopists and the AI showed moderate concordance; that between the pathologist and the two endoscopists showed poor concordance. In per-patient analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 94.7%, 92.1%, 86.8%, and 89.5%, respectively. The modified type classification aided high overall diagnostic accuracy by the pathologist and nonexpert endoscopists. The diagnostic ability of the AI was equal or superior to that of the experienced pathologist. AI is expected to support endoscopists in diagnosing esophageal lesions based on EC images.

Clinical outcomes of gastric tube reconstruction following laparoscopic proximal gastrectomy for early gastric cancer in the upper third of the stomach: experience with 100 consecutive cases.

BACKGROUND: Gastric tube reconstruction is a form of esophagogastrostomy performed after laparoscopic proximal gastrectomy (LPG). It is a simple and safe technique, but it may cause reflux esophagitis (RE) and impair postsurgical QOL. For several years, we have developed the gastric tube reconstruction and performed it on more than 100 patients. This study aimed to determine whether gastric tube reconstruction can be a feasible choice after LPG in regard to surgical safety and postoperative nutritional status. METHODS: The subjects consisted of 171 patients who underwent LPG (n = 102) or laparoscopic total gastrectomy (LTG) (n = 69). We compared the two groups in terms of surgical outcomes, incidence rate of RE, and nutritional status including postoperative weight loss and hemoglobin levels. RESULTS: There were no significant differences with regard to the surgical duration and blood loss between the two groups. The incidence of RE was not significantly higher with LPG than with LTG (16.7% vs. 10.1%, respectively; P = 0.07). Later than 2 years and 6 months after surgery, the body weight percentage of preoperative body weight in the LPG group was significantly higher than that in the LTG group. Hemoglobin and ferritin levels in the LPG group were significantly higher than those in the LTG group, later than one after surgery. The overall survival rates were similar between the two groups (5-year survival rates: 97.1% vs. 94.2% in the LPG and LTG groups, respectively; P = 0.69). CONCLUSIONS: Gastric tube reconstruction after LPG is simple and had better outcomes than LTG in terms of postoperative nutritional status.

[A Case of Synchronous Gallbladder Metastasis Originating from Advanced Gastric Cancer].

Gallbladder metastasis from gastric cancer is often found accidentally during postoperative pathological examinations, and its preoperative diagnosis is very difficult. There are a few reports in diagnostic imaging, and it is well known to have a very poor prognosis. There have been 13 reports on gallbladder metastasis from gastric cancer in the Japanese literature. Among the 13 reports, 10 cases were diagnosed with gallbladder metastasis synchronously and only 1 case was diagnosed as gallbladder metastasis before surgery. One case was reported as hematogenous metastasis, and 9 cases were reported as lymphoid metastasis. In total, 7 patients died, all within the first year after surgery. We experienced a case of synchronous gallbladder metastasis from gastric cancer.

[A Case of Advanced Recurrent Colorectal Cancer with Complete Response to Pembrolizumab Chemotherapy].

The efficacy of pembrolizumab has been demonstrated for all solid tumors showing high frequency microsatellite instability- high(MSI-High). It is a possible treatment option even in cases which do not respond to other forms of chemotherapy. We report a case of a 69-year-old man with MSI-High recurrent colorectal cancer with complete response(CR)after pembrolizumab therapy. Sigmoidectomy, extensive lymph node dissection, and partial bladder resection were performed for sigmoid colon cancer at another hospital. Histopathological examination revealed a T4a, N0, M0, Stage Ⅱb tumor. Six months after the operation, Hartmann's operation and partial resection of the small intestine were performed for local recurrence. However, the tumor invading the retroperitoneum was unresectable. Postoperative SOX therapy was performed, but it was discontinued due to Grade 3 diarrhea during the first course. The laboratory test showed MSI-High during the first course. Pembrolizumab chemotherapy was introduced as second-line therapy. Computed tomography examination after 2 courses (6 weeks)revealed reduction in the major axis of the tumor by 30% or more. After 4 courses(12 weeks), the tumor was further reduced, and a partial response(PR)was diagnosed. The tumor completely disappeared after 6 courses, and a complete response was achieved after 8 courses. The CR has been maintained for about 7 months.

Chondromodulin-1 and vascular endothelial growth factor-A expression in esophageal squamous cell carcinoma: accelerator and brake theory for angiogenesis at the early stage of cancer progression.

BACKGROUND: Magnifying endoscopy has demonstrated dramatic morphologic changes in the surface microvasculature of superficial esophageal squamous cell carcinoma (ESCC) according to the depth of invasion. We investigated the mechanism of angiogenesis in early-stage ESCC by examining the expression of vascular endothelial growth factor (VEGF)-A and chondromodulin (ChM)-1. METHODS: Using 41 samples of superficial esophageal cancer (EP and LPM 19 cases, MM or deeper 22 cases) and 7 samples of regenerative squamous epithelium, the expression of VEGF-A and ChM-1 was examined in relation to the histological grade or morphology of the surface microvasculature demonstrated by magnifying endoscopy (types A, B, and C correspond to types A, B1, and B2 and B3 of the magnifying endoscopic classification of the Japan Esophageal Society, respectively). We also investigated the correlation between CD31-positive microvessel density (MVD) and VEGF-A or ChM-1 expression. RESULTS: In normal squamous epithelium, regenerative squamous epithelium, EP and LPM cancer, and MM or deeper cancer, the positivity rates for VEGF-A and ChM-1 were 0%, 85.7%, 52.6% and 90.9%, respectively, and 48.5%, 71.4%, 73.7% and 23.8%, respectively. The VEGF-A and ChM-1 positivity rates in type B or type C vasculature were 70.0% and 76.2%, respectively, and 75.0% and 19.0%, respectively. The expression of neither VEGF-A nor ChM-1 in cancer cells was correlated with MVD (P = 0.19 and 0.68, respectively), whereas that of VEGF-A in stromal mononuclear cells (SMCs) was significantly correlated with MVD (P = 0.04). CONCLUSION: Angiogenesis at the early stage of ESCC progression is configured by the balance between accelerator (angiogenic factors from both cancer cells and SMCs) and brake (angiogenic inhibitor) factors.

Novel computer-assisted diagnosis system for endoscopic disease activity in patients with ulcerative colitis.

BACKGROUND AND AIMS: Evaluation of endoscopic disease activity for patients with ulcerative colitis (UC) is important when determining the treatment of choice. However, endoscopists require a certain period of training to evaluate the activity of inflammation properly, and interobserver variability exists. Therefore, we constructed a computer-assisted diagnosis (CAD) system using a convolutional neural network (CNN) and evaluated its performance using a large dataset of endoscopic images from patients with UC. METHODS: A CNN-based CAD system was constructed based on GoogLeNet architecture. The CNN was trained using 26,304 colonoscopy images from a cumulative total of 841 patients with UC, which were tagged with anatomic locations and Mayo endoscopic scores. The performance of the CNN in identifying normal mucosa (Mayo 0) and mucosal healing state (Mayo 0-1) was evaluated in an independent test set of 3981 images from 114 patients with UC, by calculating the areas under the receiver operating characteristic curves (AUROCs). In addition, AUROCs in the right side of the colon, left side of the colon, and rectum were evaluated. RESULTS: The CNN-based CAD system showed a high level of performance with AUROCs of 0.86 and 0.98 to identify Mayo 0 and 0-1, respectively. The performance of the CNN was better for the rectum than for the right side and left side of the colon when identifying Mayo 0 (AUROC = 0.92, 0.83, and 0.83, respectively). CONCLUSIONS: The performance of the CNN-based CAD system was robust when used to identify endoscopic inflammation severity in patients with UC, highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver variability.

Diagnostic outcomes of esophageal cancer by artificial intelligence using convolutional neural networks.

BACKGROUND AND AIMS: The prognosis of esophageal cancer is relatively poor. Patients are usually diagnosed at an advanced stage when it is often too late for effective treatment. Recently, artificial intelligence (AI) using deep learning has made remarkable progress in medicine. However, there are no reports on its application for diagnosing esophageal cancer. Here, we demonstrate the diagnostic ability of AI to detect esophageal cancer including squamous cell carcinoma and adenocarcinoma. METHODS: We retrospectively collected 8428 training images of esophageal cancer from 384 patients at the Cancer Institute Hospital, Japan. Using these, we developed deep learning through convolutional neural networks (CNNs). We also prepared 1118 test images for 47 patients with 49 esophageal cancers and 50 patients without esophageal cancer to evaluate the diagnostic accuracy. RESULTS: The CNN took 27 seconds to analyze 1118 test images and correctly detected esophageal cancer cases with a sensitivity of 98%. CNN could detect all 7 small cancer lesions less than 10 mm in size. Although the positive predictive value for each image was 40%, misdiagnosing shadows and normal structures led to a negative predictive value of 95%. The CNN could distinguish superficial esophageal cancer from advanced cancer with an accuracy of 98%. CONCLUSIONS: The constructed CNN system for detecting esophageal cancer can analyze stored endoscopic images in a short time with high sensitivity. However, more training would lead to higher diagnostic accuracy. This system can facilitate early detection in practice, leading to a better prognosis in the near future.

[A Case of Peritoneal Metastasis of Appendiceal Mucinous Carcinoma Successfully Managed by Multidisciplinary Treatment].

There is no established treatment for appendiceal mucinous adenocarcinoma. When this condition is complicated by pseudomyxoma peritonei(PMP), multidisciplinary treatment is often administered. A 40-year-old woman was diagnosed with right ovarian cancer for which laparotomy was performed. At the time of laparotomy, we considered the tumor to be an appendiceal carcinoma infiltrating the right ovary and performed ileocecal resection with lymph node dissection(D3)and right salpingo-oophorectomy. The pathological diagnosis was stage pT3, pN0, pM0, pStage Ⅱ mucinous adenocarcinoma of the appendix. Fourteen months later, the patient underwent abdominal total hysterectomy and left salpingo-oophorectomy because a CT scan suggested recurrence in the uterus, left fallopian tube, and ovary. Seventeen months after the second operation, despite adjuvant chemotherapy, CT revealed a peritoneal nodule in the pelvic cavity. Therefore, we administered chemotherapy comprising 5 lines for 32 months, which resulted in failure. CT showed an enlarged tumor and ascites and the patient became terminally ill. We repeatedly performed cytoreduction surgery and intraperitoneal chemotherapy, which improved her QOL. One year after discharge, abdominal CT showing an abdominal wall and intraperitoneal mass. We performed again cytoreduction surgery and intraperitoneal chemotherapy. Her postoperative course is good and she is currently an outpatient.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm Complicated by Pseudomyxoma Peritoneri Successfully Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy].

We experienced a case of low-grade appendiceal mucinous neoplasm complicated by pseudomyxoma peritonei that was successfully treated with cytoreductive surgery and early postoperative intraperitoneal chemotherapy. The patient was a 26- year-old man with massive ascites and a swollen appendix on the computed tomography(CT). The appendix was a cystic mass of 5 cm in size. The entire parietal peritoneum, omentum, stomach, spleen, gall bladder, and entire colon were covered with numerous mucous nodules. Total colectomy, total gastrectomy, splenectomy, cholecystectomy, total omentectomy, parietal peritonectomy, ileostomy, and intraperitoneal irrigation were performed. The pathological diagnosis was low-grade appendiceal mucinous neoplasm. Postoperative intraperitoneal chemotherapy with cisplatin and mitomycin C was performed. A residual tumor was found on the dorsal side of the hepatoduodenal ligament 3 months postoperation on the CT. The residual tumor was successfully excised via a concomitant resection of the hepatic caudate lobe. Postoperative intraperitoneal chemotherapy was then performed. No recurrence was found at 8 months postoperation. The addition of early postoperative intraperitoneal chemotherapy improved the patient's quality of life in a short period. This could be one of the treatment options.

[Analysis of Palliative Stents for Colonic Stenosis Due to Extracolonic Cancers].

We retrospectively reviewed 13 patients in whom endoscopic stenting for colonic stenosis due to extracolonic cancers(non- CRC group)was attempted between July 2012 and January 2018. There were 5 men and 8 women, with a median age of 69 years. Primary malignancies causing colonic stenosis were gastric cancer(n=4), cholangiocarcinoma(n=2), pancreatic cancer(n=2), lung cancer(n=2), uterine cancer(n=2), and ovarian cancer(n=1). The non-CRC group patients demonstrated a significantly lower technical success rate than those who received palliative stents for colonic stenosis for primary colorectal cancer(n=51)(69% vs 98%, p<0.01). In addition, the non-CRC group patients(n=13)also demonstrated a significantly lower technical success rate(69% vs 99%, pp<0.01)than those who received stents aiming to subsequently undergo a bridge to surgery. Nonetheless, colorectal stenting for extracolonic malignancies appears to be a minimally invasive treatment and could offer patients rapid relief. Thus, it could be an effective alternative to some palliative therapies.

Diagnosis using deep-learning artificial intelligence based on the endocytoscopic observation of the esophagus.

BACKGROUND AND AIMS: The endocytoscopic system (ECS) helps in virtual realization of histology and can aid in confirming histological diagnosis in vivo. We propose replacing biopsy-based histology for esophageal squamous cell carcinoma (ESCC) by using the ECS. We applied deep-learning artificial intelligence (AI) to analyse ECS images of the esophagus to determine whether AI can support endoscopists for the replacement of biopsy-based histology. METHODS: A convolutional neural network-based AI was constructed based on GoogLeNet and trained using 4715 ECS images of the esophagus (1141 malignant and 3574 non-malignant images). To evaluate the diagnostic accuracy of the AI, an independent test set of 1520 ECS images, collected from 55 consecutive patients (27 ESCCs and 28 benign esophageal lesions) were examined. RESULTS: On the basis of the receiver-operating characteristic curve analysis, the areas under the curve of the total images, higher magnification pictures, and lower magnification pictures were 0.85, 0.90, and 0.72, respectively. The AI correctly diagnosed 25 of the 27 ESCC cases, with an overall sensitivity of 92.6%. Twenty-five of the 28 non-cancerous lesions were diagnosed as non-malignant, with a specificity of 89.3% and an overall accuracy of 90.9%. Two cases of malignant lesions, misdiagnosed as non-malignant by the AI, were correctly diagnosed as malignant by the endoscopist. Among the 3 cases of non-cancerous lesions diagnosed as malignant by the AI, 2 were of radiation-related esophagitis and one was of gastroesophageal reflux disease. CONCLUSION: AI is expected to support endoscopists in diagnosing ESCC based on ECS images without biopsy-based histological reference.

[Clinicopathological Study of Perforated Gastric Cancer Treated with Surgery].

This retrospective study evaluated an appropriate surgical treatment in patients with perforated gastric cancer. The clinicopathological and survival data on 17 perforated gastric cancer patients treated with surgery were analyzed. The one-stage or two-stage gastrectomy was performed in 8 and 5 patients, respectively. The omental patch repair was performed in 4 patients. In univariate analysis, non-curative(R2)resection with gross residual tumor(p<0.01)and postoperative complications( p=0.01)were found to be significant unfavorable factors for overall survival(OS). In multivariate analysis, R2 resection was identified to be an only independent significant unfavorable factor for OS. Patients who underwent curative(R0) resection had long-term survival, while patients with R2 resection and postoperative complication had limited survival times. These results suggest that R0 resection may be optimal to improve survival in patients with perforated gastric cancer, regardless of whether patients underwent a one-stage or two-stage gastrectomy based on the patient's condition.

[A Case of Giant Retroperitoneal Liposarcoma Resected after Trabectedin Chemotherapy].

The basic treatment for retroperitoneal liposarcoma is surgical therapy. Since the administration of trabectedin for soft tissue sarcoma has been approved, another option for soft tissue sarcoma treatment has been added. We report a case of radical resection after trabectedin therapy for initially unresectable retroperitoneal liposarcoma. A 61-year-old man was admitted to our hospital with an abdominal tumor. A tumor, about 50 cm in maximal diameter, that was not movable throughout the abdomen was observed. Computed tomography revealed a giant tumor almost occupying the entire abdomen, and he was diagnosed with retroperitoneal liposarcoma based on histopathological examination of a puncture specimen. Chemotherapy containing trabectedin was administered. At the end of 8 courses, he achieved stable disease. However, the movability improved, and surgery was performed. The procedure was tumor resection with right kidney, adrenal gland, and inferior vena cava resection. Histopathological examination revealed a mixed type of well differentiated type and dedifferentiated type. The patient is alive without recurrence 10 months after the surgery.

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma.

BACKGROUND: The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear. METHODS: Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs. RESULTS: On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis. CONCLUSION: TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.

A newly developed continuous zoom-focus endocytoscope.

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074. Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to × 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma. Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo. Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.

[Outcomes of Elderly Patients with Perforated Colorectal Cancer].

We retrospectively investigatedoutcomes in surgically treatedeld erly patients with perforatedcolorectal cancer. The clinicopathological andsurvival data on 54 perforatedcolorectal cancer patients treatedwith surgery were analyzed. They included 12 patients≥75 years old(elderly group)and4 2 patients<75 years old(non-elderly group). There were no significant differences in terms of clinicopathological features, the severity of peritonitis and classification of sepsis, the development of disseminatedintravascular coagulopathy, andmortality within 30days between the 2 groups. The frequency of using chemo- therapy for Stage IV disease did not differ significantly in the 2 groups. The use of adjuvant chemotherapy for Stage II / III disease was significantly less frequent in elderly group than in non-elderly group(p=0.01). The progression-free and overall survival time for Stage II / III diseases did not significantly differ between the 2 groups. In conclusion, the prognosis of elderly patients with perforated colorectal cancer seems to be equivalent to that of the non-elderly patients. The indication of (adjuvant)chemotherapy may be controversial in such elderly patients.

[The Characteristics and Treatment Outcomes for Desmoid Tumors Associated with Familial Adenomatous Polyposis].

INTRODUCTION: The characteristics of desmoid tumors(DTs)associated with familial adenomatous polyposis(FAP)and relationships between the development of DTs and the sites of APC germline mutation have not closely been examined Japan. PATIENTS AND METHODS: This retrospective study was performed to address these issues by examining patients with FAP who underwent proctocolectomy between 1981 and 2015. RESULTS: The cumulative 2-year incidence of DT development was 50%. The DTs developed in the abdominal wall only in 2, in the abdominal wall plus intra-abdominally in 4, and intra-abdominally in 2. Clinical stages according to the Church's classification included Stage I in 3, Stage II in 2, Stage III in 1, and Stage IV in 2. Among 31 patients with a confirmed pathogenic germline APC mutation, patients with mutation in 3' site of codon 1400 (n=7)tended to develop DTs more frequently than those with mutation in 5' site of codon 1400(n=24)(p=0.08). The cumulative 5-year survival rate in patients with DT development was 73.3%. Including 2 patients undergoing initial colectomy at other institutions, the therapeutic efficacy in 4 patients with severe intraabdominal DTs(Stage III /Stage IV )who were given chemotherapy comprising doxorubicin plus dacarbazine(DOX plus DTIC)revealed partial response in 3 and complete response in 1. Febrile neutropenia was recorded in 2 of these patients. CONCLUSION: The frequency of DTs development and genotype-phenotype relationship of FAP patients seems to concur with those reported from Western countries. Since the DOX plus DTIC therapy for severe DTs is valid but toxicity is high, the development of less toxic regimens are warranted.

[A Family with Peutz-Jeghers Syndrome Having Various Malignant Diseases].

We report a 27-year-old female who was diagnosed with adenocarcinoma of the uterine cervix associated with Peutz- Jeghers syndrome(PJS). She had undergone 5 surgeries for intestinal intussusception and had been diagnosed with PJS. She was referred to our hospital, complaining of watery vaginal discharge, and was diagnosed with adenocarcinoma of the uterine cervix. Following neoadjuvant chemotherapy, radical hysterectomy and small intestinal polypectomy by intraoperative endoscopy were performed. Among the third-degree relatives of her family, 10 had been diagnosed with PJS; of these 10, uterine cervical adenocarcinoma occurred in 3 relatives, pancreatic cancer in 2, cholangiocellular carcinoma in 1, and colon cancer in 1. Patients with PJS are at increased risk of developing malignant tumors in various organs. A recent review of the literature from Japan revealed that the cumulative cancer risk was estimated to be 83%by the age of 70 years, with especially high incidence rates of uterine cervical adenocarcinoma, colorectal cancer, and pancreas cancer. Surveillance for malignant neoplasms in patients with PJS is recommended, focusing on the sex and age of the patients.

[Characteristics and Outcomes of Treatment in Patients with Stage IV Colorectal Cancer with Mismatch Repair Deficiency].

Mismatch repair(MMR)protein deficiency in colorectal cancer is well correlated with high-level microsatellite instability (MSI-H). There are little data on mismatch repair deficiency(dMMR)colorectal cancers in Japan. In addition, we have no available data on the therapeutic efficacy of oxaliplatin(oxa)-based chemotherapy, one of the standard treatment regimens for metastatic colorectal cancer, for patients with dMMR colorectal cancer. The subjects were 254 patients with Stage IV colorectal cancer whose tumors were immunohistochemically stained for MMR proteins, MLH1, MSH2, MSH6, and PMS2. Patients who underwent R0 resection were excluded. Clinicopathologic factors and the efficacy of oxa-based chemotherapy were compared between patients with dMMR colorectal cancer and those with mismatch repair proficient(pMMR)colorectal cancer. There were 7(2.8%)patients with dMMR. Four patients demonstrated both MLH1 and PMS2 loss, while 3 patients demonstrated both MSH2 and MSH6 loss. Though the dMMR had a higher frequency in female patients(p=0.02) and a lower frequency in those with liver metastasis(p<0.01), the other clinicopathologic factors evaluated did not significantly differ between the dMMR group and the pMMR group. One hundred and fifty patients with unresectable disease or R1/2 resection received first-line oxa-based chemotherapy. The median overall survival was 23.2 months and 16.2 months in patients with dMMR(n=4)and those with pMMR, respectively(n=146)(p=0.33). The frequency of dMMR amongStag e IV colorectal cancers was lower than those(4-11%)reported in Western countries. Therefore, the clinical significance of universal screeningfor dMMR in all colorectal cancer samples may not be valid. Concerningsurvival benefit, oxa-based chemotherapy seems to be an effective alternative in clinical practice for metastatic colorectal cancer patients with dMMR.