[Significance of Colorectal Cancer Resection for the Elderly].

INTRODUCTION: Elderly patients requiring surgical treatment is increasing in Japan, and while surgical treatment is expected to be effective even in the very elderly, there is a lack of evidence for the safety and efficacy of surgical resection due to problems with perioperative management and operative tolerance. We therefore retrospectively examined the short-term and long-term outcomes of colorectal cancer surgery for the very elderly at our hospital. SUBJECTS: The study included 14 cases of colorectal cancer in the very elderly who underwent radical resection at our hospital between January 2010 and March 2020. RESULTS: The mean age was 92 years, PS; 1/2=8/6, ASA-PS; 2/3/4=8/4/2, primary site was C/A/T/S/R= 2/5/2/2/3, pStage; 1/2/3=1/9/4, and only 1 case of decompression with ileus tube due to obstructive symptoms was treated before surgery. All patients underwent radical surgery. Median blood loss was 61 mL, median operation time was 190.5 min, and median postoperative hospital stay was 16 days. 5 patients had CD≥2 complications. All patients did not receive adjuvant chemotherapy, and recurrence in was observed 3 patients. CONCLUSION: Surgical treatment of very elderly patients seems to be acceptable under appropriate patient selection.

Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes.

INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,259 patients with local resection alone [group A], 1,508 patients with additional surgery after local resection [group B], and 1,952 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,801 patients. The LNM incidence was 10.3% (95% confidence interval 9.3-11.4) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.2) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.2%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

How Does Omitting Additional Surgery After Local Excision Affect the Prognostic Outcome of Patients With High-risk T1 Colorectal Cancer?

OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.

A case of premortem diagnosis of cardiac tamponade due to pericardial metastasis of rectal cancer.

Colorectal cancer rarely develops pericardial metastasis, and it is an extremely rare case that cardiac tamponade due to the metastasis of colorectal cancer during life. Our case is of a 50-year-old woman who underwent laparoscopic lower anterior resection for the rectal cancer with lung metastasis 4 years ago developed cardiac tamponade due to pericardial metastasis of rectal cancer. We performed pericardiocentesis as a temporary life-saving procedure, but pericardial fluid re-accumulated within a few days. She died 23 days after admission. When a patient with advanced colorectal cancer complains dyspnea, we should consider the pericardial metastasis, and perform the proper treatment as this case.

[Migration of Internal Pancreaticojejunostomy Stents into the Bile Ducts in Patients Undergoing Pancreaticoduodenectomy].

The patient was a 68-year-old male. Pancreaticoduodenectomy(PD)for papillary carcinoma was performed. Computed tomography(CT)3 months after surgery revealed the migration of a lost Pit-stent into the bile duct. However, there were no symptoms. On CT 2 years after surgery, the lost stent had spontaneously fallen off. However, hepaticolithiasis was observed, and lithotripsy was performed using endoscopic retrograde cholangiopancreatography(ERCP). A pancreatic fistula after PD is an important complication. To prevent pancreatic fistulae, pancreatic stenting at the site of PD is performed in many cases. The postoperative in vivo kinetics of a lost stent remains to be clarified. Several case reports on complications have been published. In this study, we report a patient in whom the migration of a lost Pit-stent into the intrahepatic bile duct after PD led to hepaticolithiasis, and review the literature.

[Short-Term and Long-Term Results of Robot-Assisted Rectal Resections Performed in Our Department].

BACKGROUND: We introduced the da Vinci robotic surgical system in 2006 for the first time in Japan, and have been performing robot-assisted rectal cancer surgeries since 2010, after receiving approval from the hospital's Ethics Review Committee in 2009. Here we report the long-term and short-term outcomes of robot-assisted rectal cancer surgeries performed in our department. METHODS: Target patients were those who underwent robot-assisted radical rectal resection for rectal cancer; 165 patients in the short term(2010-2021), and 49 patients in the long term(2010-2016). Data were retrospectively analyzed, and Kaplan-Meier curves were used for the survival analysis. RESULTS: The short-term results are summarized in Table 1. The long-term results were as follows: 5-year overall survival rate, 90.8%; 5-year recurrence-free survival rate, 90.6%; 5-year cumulative local recurrence rate, 7.3%; 5-year cumulative distant metastasis rate, 9.4%. CONCLUSION: In our department, 11 years have passed since we began performing robotic rectal surgeries, and the short- and long-term results have generally been acceptable.

[Preoperative Prognostic Factors in CRS plus HIPEC for Patients with Peritoneal Dissemination of Colorectal Cancer].

Peritoneal dissemination of colorectal cancer has the poorest prognosis among metastatic sites, with an average overall survival of less than 6 months. Various treatment methods have been reported for these patients, and recently there have been several reports showing the usefulness of cytoreductive surgery(CRS)combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the studies on this treatment are limited. In this study, we retrospectively reviewed cases of CRS plus HIPEC. Twenty-one patients who underwent CRS plus HIPEC at Tokyo Medical University Hospital and Toda Central General Hospital between August 2014 and December 2017 were included in this study. The long-term and short-term survival groups were analyzed separately, and predictors of preoperative treatment efficacy were examined. The surgical approach was open in 16 cases and laparoscopic in 5 cases. Complete resection was achieved in 10 of these patients. Postoperative complications occurred in 6 patients. There were no deaths within 90 days of surgery. The median overall survival was 17.0 months, and the 1-year survival rate was 65%. Median progression-free survival was 11.0 months. In a multivariate analysis predicting long-term versus short-term survival groups, sex, primary tumor location, and P factor were independent predictors of treatment response. CRS plus HIPEC therapy is considered an effective treatment option. The predictors of preoperative treatment response include sex, primary tumor location, and P factor.

[A Case of Rectal Cancer with Solitary Lymph Node Metastasis in the Stomach after Hepatectomy for Liver Metastasis].

A 44-year-old woman had undergone a laparoscopic low anterior resection and lymph node dissection for rectal cancer (pT4aN2aH0P0M0, pStage Ⅲc)in 20XX. Six months postoperatively, a CT scan revealed recurrent liver metastasis. She underwent surgery and adjuvant chemotherapy. Three years after the initial surgery, her liver metastasis recurred again, and the patient underwent another cycle of surgical treatment and adjuvant chemotherapy. Five years after the initial surgery, a lesion was found in a gastric lesser curvature lymph node. Gastric kyphosis lymph node dissection was performed under the suspicion of a solitary lymph node metastasis. The resected lymph node was diagnosed as a medium-differentiated adenocarcinoma, with findings consistent with a lymph node metastasis from the initial rectal cancer. Postoperative adjuvant chemotherapy was administered. No recurrence was noted 6 years and 6 months after the initial surgery. Rectal cancer rarely metastasizes to the gastric lymph nodes in a solitary fashion. We describe a case of a solitary gastric regional lymph node metastasis observed after the resolution of previous liver metastases.

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study.

BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a novel nomogram was developed and validated by usirge-scale, real-world data, including the Japanese Society for Cancer of the Colon and Rectum risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4673 patients with T1 CRC treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathologic findings were extracted from the medical records of each participating institution. The discrimination ability was measured by using the concordance index, and the variability in each prediction was evaluated by using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was .784 for the clinical calculator in the development cohort and .790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathologic diagnosis based on data from a nationwide multi-institutional study. This nomogram, developed with real-world data, should improve decision-making for an appropriate treatment strategy for T1 CRC.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Retroperitoneal hibernoma resected via laparoscopic surgery.

Hibernomas are extremely rare, benign tumors of brown fat origin with no specific symptoms. Surgery is the only treatment option, and because a definitive preoperative diagnosis is often not obtained, open surgery is usually chosen. In this case, we performed laparoscopic surgery on a 33-year-old woman with retroperitoneal hibernoma. As in most cases, a definitive diagnosis had not been preoperatively made; therefore, we laparoscopically removed the retroperitoneal tumor of unknown pathology as a diagnostic treatment. We chose laparoscopic surgery because of the magnifying effect of the laparoscope and to minimize scarring. The surgery was uneventful, with a procedure time of 280 minutes and a blood loss of 20 mL. The postoperative course was uneventful with no complications or recurrence. We conclude that laparoscopic surgery may be a viable option for hibernomas.

Clinicopathological Features of Remnant Gastric Cancer After Gastrectomy.

BACKGROUND: Remnant gastric cancer (RGC) encompasses all cancers arising from the remnant stomach. Various studies have reported on RGC and its prognosis, but no consensus on its surgical treatment and postoperative management has been reached. Moreover, the correlation between the clinicopathological characteristics and long-term outcomes of RGC remains unclear. This study investigated the clinicopathological factors associated with the long-term survival of RGC patients. METHODS: The medical records (March 1993-September 2020) of 104 RGC patients from Tokyo Medical University Hospital database were analyzed. Of these 104 patients, the medical records of 63 patients who underwent surgical curative resection were analyzed using R. Kaplan-Meier plots of cumulative incidence of RGC were made. Differences in survival rates were compared using the log-rank test. Prognostic factors were analyzed using multivariate Cox regression analysis (P < .05). RESULTS: Of the 104 RGC patients, 63 underwent total remnant stomach excision. The median time from the first surgery to the total excision was 10 years. The 5-year survival rate of the 63 RGC patients was .55 ((95% CI); .417-.671). The clinicopathological factors that were significantly associated with the long-term outcome of the RGC patients were tumor diameter (≥3.5 cm), presence or absence of combined resection of multiple organs, tumor invasion (deeper than T2), TNM stage, and postoperative morbidity. The multivariate Cox regression analysis showed that tumor invasion depth was the only independent prognostic factor for RGC patients [HR (95% CI): 5.49 (2.629-11.5), P ≤ .005]. CONCLUSIONS: Among prognostic factors, tumor invasion depth was the only independent factor affecting RGC's long-term outcome.

[A Patient with Small Intestinal Leiomyosarcoma and Intussusception Who Underwent Single Port Surgery].

The patient was a 33-year-old female. She was referred to our hospital from a previous clinic with abdominal pain and vomiting. Contrast-enhanced abdominal CT revealed intussusception, leading to a diagnosis of intussusception with a small intestinal tumor as an advanced part. Intestinal obstruction symptoms were observed, and emergency surgery was performed on the same day. As a technique, single port surgery was selected, and laparoscopic reduction was attempted. However, it was ineffective. The site of intussusception was induced outside the body through a small laparotomy wound, and reduction was performed using Hutchinson's procedure. As an adjacent lymph node was markedly swollen, the mesentery involving this lymph node was dissected in a fan shape, and the tumor was extirpated. The tumor measured 40 mm in long diameter, being a hemicircular, protruding lesion. Histologically, disarray of short spindle tumor cells was observed. Immunostaining showed Kit- and DOG1-negtive reactions and partially α-SMA and desmin-positive reactions, suggesting leiomyosarcoma. With the establishment of an immunostaining-test-based classification, leiomyosarcoma is currently rare. In this study, we report a patient in whom single port surgery for intussusception related to small intestinal leiomyosarcoma was successful.

[Multiple Intestinal Perforations Caused by Diffuse Large B-Cell Lymphoma-A Case Report].

A 83-year-old man was diagnosed with diffuse large B-cell lymphoma and scheduled for treatment. However, he developed abdominal pain, and computed tomography revealed a gastrointestinal perforation. Emergency surgery was performed, upon which we identified perforations in the small intestine, and we therefore performed resection of the small intestine. R-CHOP therapy was performed postoperatively, resulting in successful tumor shrinkage. Malignant lymphoma of the small intestine often causes intestinal perforations, and the prognosis of patients with perforations is unfavorable. We report a case of a patient with multiple intestinal perforations owing to malignant lymphoma of the small intestine, in whom minimal surgery was performed and intervention in the early postoperative period was successful.

Artificial intelligence predicts lymph node metastasis or risk of lymph node metastasis in T1 colorectal cancer.

BACKGROUND: The treatment strategies for colorectal cancer (CRC) must ensure a radical cure of cancer and prevent over/under treatment. Biopsy specimens used for the definitive diagnosis of T1 CRC were analyzed using artificial intelligence (AI) to construct a risk index for lymph node metastasis. METHODS: A total of 146 T1 CRC cases were analyzed. The specimens for analysis were mainly biopsy specimens, and in the absence of biopsy specimens, the mucosal layer of the surgical specimens was analyzed. The pathology slides for each case were digitally imaged, and the morphological features of cancer cell nuclei were extracted from the tissue images. First, statistical methods were used to analyze how well these features could predict lymph node metastasis risk. A lymph node metastasis risk model using AI was created based on these morphological features, and accuracy in test cases was verified. RESULTS: Each developed model could predict lymph node metastasis risk with a > 90% accuracy in each region of interest of the training cases. Lymph node metastasis risk was predicted with 81.8-86.3% accuracy for randomly validated cases, using a learning model with biopsy data. Moreover, no case with lymph node metastasis or lymph node risk was judged to have no risk using the same model. CONCLUSIONS: AI models suggest an association between biopsy specimens and lymph node metastases in T1 CRC and may contribute to increased accuracy of preoperative diagnosis.

Effectiveness of a new triple-row circular stapler in reducing the risk of colorectal anastomotic leakage: A historical control and propensity score-matched study.

Anastomotic leakage (AL) after colorectal surgery is a serious complication. This study aimed to evaluate the effectiveness of the EEA™ circular stapler, a new triple-row circular stapler (TCS), relative to a conventional, double-row circular stapler (DCS). A total of 285 patients who underwent anastomosis with the double stapling technique at the Tokyo Medical University Hospital between 2017 and 2021 were included in this nonrandomized clinical trial with historical controls using a propensity score (PS) analysis. The primary endpoint was the risk of AL. We performed a 1:2 PS matching analysis. Before case matching, AL occurred in 15 (7.4%) and 2 (2.4%) patients in the DCS and TCS groups, respectively, with no significant difference (P = .17). After case matching, AL occurred in 13 patients (11.6%) and 1 patient (1.8%) in the DCS and TCS groups, respectively, revealing a significant difference (P = .04). Cox models were created by applying PS to adjust for group differences via regression adjustment. Odds ratios for AL in the DCS group versus the TCS group were 0.31 (95% confidence interval [CI]: 0.07-1.38) in the entire cohort, 0.15 (95% CI: 0.02-0.64) in the regression adjustment cohort, and 0.14 (95% CI: 0.02-1.09) in the 1:2 PS-matched cohort. PS analysis of clinical data suggested that the use of TCS contributes to a reduced risk of AL after colorectal anastomosis CTwith the double stapling technique.

Comparison of pressure resistance of double-rows and triple-rows circular stapler in rectal double stapling technique: In vitro study.

BACKGROUND: Anastomotic leak after gastrointestinal anastomosis is a serious complication. Anastomotic failure depends on various parameters. The aim of our study was to evaluate the pressure resistance of a new device, EEA™ circular stapler with Tri-Staple™ technology 28 mm Medium/Thick (Triple-rows circular stapler; TCS) compared with EEA™ circular stapler with DST series™ technology 28 mm, 4.8 mm staples (double-rows circular stapler; DCS). PATIENTS AND METHODS: We performed 30 anastomoses (DSC: 15, TCS: 15) of DST with porcine colon model in vitro. We performed following 3 comparative experiences; Experiment 1: observation of staple shape with a colonoscopy, Experiment 2: comparison of the pressure resistance, Experiment 3: comparison of leakage points. RESULTS: There was no hypoplasia of staples and the shapes were well-formed by colonoscopy. The leakage pressure of DCS was 19.6 ±â€…4.4 mm Hg (mean ±â€…standard deviation) and that of TCS was 38.6 ±â€…10.2 mm Hg (mean ±â€…standard deviation). There was a significantly difference between 2 groups (P < .001). 12 cases of DCS (80%) and 10 cases of TCS (66.7%) had leakages from Circular stapler point. 2 cases of DCS (13.3%) and 5 cases of TCS (33.3%) had leakages from Crossing points. Only 1 case of DCS had leakages from Dog ear point (6.7%). There was no significantly difference in leakage site between 2 groups (P = .195). CONCLUSIONS: TSC showed high pressure resistance during DST compared with that of DCS. It was suggested that TCS may contribute to the reduction of anastomotic leakage rate.

Salivary metabolomics with machine learning for colorectal cancer detection.

As the worldwide prevalence of colorectal cancer (CRC) increases, it is vital to reduce its morbidity and mortality through early detection. Saliva-based tests are an ideal noninvasive tool for CRC detection. Here, we explored and validated salivary biomarkers to distinguish patients with CRC from those with adenoma (AD) and healthy controls (HC). Saliva samples were collected from patients with CRC, AD, and HC. Untargeted salivary hydrophilic metabolite profiling was conducted using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry. An alternative decision tree (ADTree)-based machine learning (ML) method was used to assess the discrimination abilities of the quantified metabolites. A total of 2602 unstimulated saliva samples were collected from subjects with CRC (n = 235), AD (n = 50), and HC (n = 2317). Data were randomly divided into training (n = 1301) and validation datasets (n = 1301). The clustering analysis showed a clear consistency of aberrant metabolites between the two groups. The ADTree model was optimized through cross-validation (CV) using the training dataset, and the developed model was validated using the validation dataset. The model discriminating CRC + AD from HC showed area under the receiver-operating characteristic curves (AUC) of 0.860 (95% confidence interval [CI]: 0.828-0.891) for CV and 0.870 (95% CI: 0.837-0.903) for the validation dataset. The other model discriminating CRC from AD + HC showed an AUC of 0.879 (95% CI: 0.851-0.907) and 0.870 (95% CI: 0.838-0.902), respectively. Salivary metabolomics combined with ML demonstrated high accuracy and versatility in detecting CRC.